Initial commit
This commit is contained in:
Zhongwei Li
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\documentclass[10pt,letterpaper]{article}
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% Packages
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\usepackage[margin=0.5in]{geometry}
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\usepackage[utf8]{inputenc}
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\usepackage[T1]{fontenc}
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\usepackage{helvet}
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\renewcommand{\familydefault}{\sfdefault}
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\usepackage{xcolor}
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\usepackage{tcolorbox}
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\usepackage{array}
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\usepackage{tabularx}
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\usepackage{booktabs}
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\usepackage{enumitem}
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\usepackage{titlesec}
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\usepackage{fancyhdr}
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\usepackage{graphicx}
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% Color definitions
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\definecolor{headerblue}{RGB}{0,102,204}
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\definecolor{tier1green}{RGB}{0,153,76}
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\definecolor{tier2orange}{RGB}{255,152,0}
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\definecolor{tier3gray}{RGB}{158,158,158}
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\definecolor{mutationred}{RGB}{244,67,54}
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\definecolor{amplificationblue}{RGB}{33,150,243}
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\definecolor{fusionpurple}{RGB}{156,39,176}
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\definecolor{highlightgray}{RGB}{240,240,240}
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% Section formatting
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\titleformat{\section}{\normalfont\fontsize{11}{12}\bfseries\color{headerblue}}{\thesection}{0.5em}{}
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\titlespacing*{\section}{0pt}{4pt}{2pt}
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\titleformat{\subsection}{\normalfont\fontsize{10}{11}\bfseries}{\thesubsection}{0.5em}{}
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\titlespacing*{\subsection}{0pt}{3pt}{1pt}
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% List formatting
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\setlist[itemize]{leftmargin=*,itemsep=0pt,parsep=0pt,topsep=1pt}
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\setlist[enumerate]{leftmargin=*,itemsep=0pt,parsep=0pt,topsep=1pt}
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\setlength{\parindent}{0pt}
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\setlength{\parskip}{2pt}
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% Header/footer
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\pagestyle{fancy}
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\fancyhf{}
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\fancyhead[L]{\footnotesize \textbf{Genomic Profile Report: [PATIENT ID]}}
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\fancyhead[R]{\footnotesize Page \thepage}
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\renewcommand{\headrulewidth}{0.5pt}
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\fancyfoot[C]{\footnotesize Confidential Laboratory Report - CLIA/CAP Certified}
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\begin{document}
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% Title block
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\begin{center}
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{\fontsize{14}{16}\selectfont\bfseries\color{headerblue} COMPREHENSIVE GENOMIC PROFILING REPORT}\\[2pt]
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{\fontsize{10}{12}\selectfont [Laboratory Name] | CLIA \#: [Number] | CAP \#: [Number]}
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\end{center}
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\vspace{2pt}
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% Patient/Specimen Information
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\begin{tcolorbox}[colback=highlightgray,colframe=black]
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\begin{minipage}{0.48\textwidth}
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{\small
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\textbf{Patient Information}\\
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Patient ID: [De-identified ID]\\
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Date of Birth: [De-identified/Age only]\\
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Sex: [M/F]\\
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Ordering Physician: [Name, MD]
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}
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\end{minipage}
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\hfill
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\begin{minipage}{0.48\textwidth}
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{\small
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\textbf{Specimen Information}\\
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Specimen Type: [Tissue/Blood/Other]\\
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Collection Date: [Date]\\
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Received Date: [Date]\\
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Report Date: [Date]
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}
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\end{minipage}
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\end{tcolorbox}
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\vspace{2pt}
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% Diagnosis
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\textbf{Diagnosis}: [Cancer type, stage, histology]
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\textbf{Testing Performed}: [Assay name - e.g., FoundationOne CDx, NGS Panel]
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\vspace{2pt}
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% Results Summary Box
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\begin{tcolorbox}[enhanced,colback=tier1green!10,colframe=tier1green,
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title=\textbf{RESULTS SUMMARY},fonttitle=\bfseries,coltitle=black]
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{\small
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\textbf{Actionable Findings}: [X] alteration(s) detected
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\begin{itemize}
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\item \textbf{Tier 1}: [Number] FDA-approved therapy target(s)
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\item \textbf{Tier 2}: [Number] clinical trial or off-label option(s)
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\item \textbf{Tier 3}: [Number] variant(s) of uncertain significance
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\end{itemize}
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\textbf{Additional Biomarkers}:
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\begin{itemize}
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\item Tumor Mutational Burden (TMB): [X.X] mutations/Mb - [High/Intermediate/Low]
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\item Microsatellite Status: [MSI-H / MSS / Not assessed]
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\item PD-L1 Expression: [X\% TPS / Not assessed]
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\end{itemize}
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}
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\end{tcolorbox}
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\section{Tier 1: FDA-Approved Targeted Therapies}
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\begin{tcolorbox}[enhanced,colback=tier1green!5,colframe=tier1green,
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title={\colorbox{mutationred!60}{\textcolor{white}{\textbf{MUTATION}}} \textbf{[Gene Name] [Alteration]} \hfill \textbf{TIER 1 - ACTIONABLE}},
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fonttitle=\bfseries\small,coltitle=black]
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{\small
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\textbf{Alteration}: [Gene] [Specific variant - e.g., EGFR p.L858R (c.2573T>G)]\\
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\textbf{Variant Allele Frequency (VAF)}: XX\% (suggests [clonal/subclonal] mutation)\\
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\textbf{Classification}: [Pathogenic / Likely Pathogenic] (ClinVar, OncoKB)
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\textbf{Clinical Significance}: \textcolor{tier1green}{\textbf{ACTIONABLE - FDA-APPROVED THERAPY AVAILABLE}}
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\textbf{FDA-Approved Therapy}:
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\begin{itemize}
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\item \textbf{Drug}: [Drug name (brand name)] XX mg [PO/IV] [schedule]
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\item \textbf{Indication}: [Specific disease, line of therapy]
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\item \textbf{Evidence}: [Pivotal trial] - [Key results with HR, ORR, median survival]
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\item \textbf{Guideline}: NCCN Category [1/2A], [ESMO/ASCO recommendation]
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\item \textbf{Expected Outcomes}: ORR XX\%, median PFS XX months
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\end{itemize}
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\textbf{Alternative Therapies}:
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\begin{itemize}
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\item [Alternative drug] - [Indication, evidence level]
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\end{itemize}
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\textbf{Recommendation}: \textbf{STRONG} - Consider [drug name] as [first-line/second-line] therapy (GRADE 1A)
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}
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\end{tcolorbox}
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\vspace{3pt}
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\begin{tcolorbox}[enhanced,colback=tier1green!5,colframe=tier1green,
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title={\colorbox{amplificationblue!60}{\textcolor{white}{\textbf{AMPLIFICATION}}} \textbf{[Gene] Amplification} \hfill \textbf{TIER 1}},
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fonttitle=\bfseries\small,coltitle=black]
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{\small
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\textbf{Alteration}: [Gene name] amplification\\
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\textbf{Copy Number}: [X.X] copies per cell (threshold for positivity: ≥[Y])\\
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\textbf{Method}: [NGS copy number analysis / FISH]
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\textbf{Clinical Significance}: \textcolor{tier1green}{\textbf{ACTIONABLE - COMPANION DIAGNOSTIC}}
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\textbf{Therapy Options}: [Similar structure as mutation section]
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}
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\end{tcolorbox}
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\section{Tier 2: Clinical Trial or Guideline-Recommended Off-Label}
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\begin{tcolorbox}[enhanced,colback=tier2orange!5,colframe=tier2orange,
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title={\colorbox{fusionpurple!60}{\textcolor{white}{\textbf{FUSION}}} \textbf{[Gene] Rearrangement} \hfill \textbf{TIER 2 - INVESTIGATIONAL}},
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fonttitle=\bfseries\small,coltitle=black]
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{\small
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\textbf{Alteration}: [Gene A]-[Gene B] fusion detected\\
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\textbf{Method}: [RNA-seq / DNA NGS / FISH]
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\textbf{Clinical Significance}: \textcolor{tier2orange}{\textbf{INVESTIGATIONAL - CLINICAL TRIAL PREFERRED}}
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\textbf{Treatment Options}:
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\begin{itemize}
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\item \textbf{Clinical Trial}: [Specific trial or trial search guidance]
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\item \textbf{Off-Label Option}: [Drug] - NCCN Category 2A recommendation
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\item \textbf{Evidence}: [Phase 2 data, basket trial results, case series]
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\end{itemize}
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\textbf{Recommendation}: \textbf{CONDITIONAL} - Consider clinical trial enrollment or off-label use after standard therapy (GRADE 2B)
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}
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\end{tcolorbox}
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\section{Tier 3: Variants of Uncertain Significance (VUS)}
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\begin{tcolorbox}[colback=tier3gray!10,colframe=tier3gray]
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{\small
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\textbf{[Gene] [Variant]}: [Description]\\
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\textbf{Classification}: Variant of Uncertain Significance (VUS)\\
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\textbf{Clinical Actionability}: None currently - insufficient evidence\\
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\textbf{Recommendation}: No treatment change based on this finding; may be reclassified as evidence emerges
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}
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\end{tcolorbox}
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\section{Biomarkers Assessed - Negative}
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\textbf{No Alterations Detected in}:
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\begin{multicols}{3}
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\begin{itemize}
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\item [Gene 1]
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\item [Gene 2]
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\item [Gene 3]
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\item [Gene 4]
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\item [Gene 5]
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\item [Gene 6]
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\end{itemize}
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\end{multicols}
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\section{Additional Biomarkers}
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\subsection{Tumor Mutational Burden (TMB)}
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\textbf{TMB}: [X.X] mutations per megabase
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\textbf{Classification}:
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\begin{itemize}
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\item $\geq$10 mut/Mb: TMB-high (potential immunotherapy benefit)
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\item 6-9 mut/Mb: TMB-intermediate
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\item <6 mut/Mb: TMB-low
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\end{itemize}
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\textbf{Result}: [TMB-high / TMB-intermediate / TMB-low]
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\textbf{Clinical Implication}:
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\begin{itemize}
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\item TMB-high: Consider immunotherapy; pembrolizumab FDA-approved for TMB-H ($\geq$10) solid tumors
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\item TMB-intermediate/low: Standard chemotherapy or biomarker-directed therapy
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\end{itemize}
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\subsection{Microsatellite Instability (MSI)}
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\textbf{MSI Status}: [MSI-H / MSI-L / MSS]
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\textbf{Method}: [NGS-based MSI calling / PCR-based assay]
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\textbf{Clinical Implication}:
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\begin{itemize}
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\item MSI-H: Immunotherapy highly effective (ORR 30-60\%); pembrolizumab, nivolumab approved
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\item MSS: Standard therapy; MSI-H-specific therapies not indicated
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\item If MSI-H + [relevant cancer] + young age: Consider germline Lynch syndrome testing
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\end{itemize}
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\section{Integrated Treatment Recommendations}
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\begin{tcolorbox}[enhanced,colback=stronggreen!10,colframe=tier1green,
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title=\textbf{PERSONALIZED TREATMENT PLAN},fonttitle=\bfseries,coltitle=black]
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{\small
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Based on the genomic profile, the following treatment approach is recommended:
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\textbf{Primary Recommendation (GRADE 1A)}:
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\begin{itemize}
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\item \textbf{[Drug targeting identified alteration]}
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\item Dosing: [Specific dose and schedule]
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\item Evidence: [Supporting data]
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\item Expected outcomes: ORR XX\%, median PFS XX months
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\end{itemize}
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\textbf{If Primary Recommendation Contraindicated}:
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\begin{itemize}
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\item Alternative 1: [Second-line biomarker-directed option]
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\item Alternative 2: [Standard therapy if targeted therapy ineligible]
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\end{itemize}
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\textbf{At Progression}:
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\begin{itemize}
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\item Repeat molecular profiling (liquid biopsy or tissue) for resistance mechanisms
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\item Expected resistance alterations: [e.g., EGFR T790M, MET amplification]
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\item Sequential targeted therapy if secondary actionable alteration identified
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\end{itemize}
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\textbf{Clinical Trial Matching}:
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\begin{itemize}
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\item [List relevant trials based on identified alterations]
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\item ClinicalTrials.gov search terms: [Suggested keywords]
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\end{itemize}
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}
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\end{tcolorbox}
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\section{Clinical Trial Matching}
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\begin{table}[H]
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\centering
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\small
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\begin{tabular}{llll}
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\toprule
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\textbf{Trial} & \textbf{Intervention} & \textbf{Biomarker} & \textbf{Phase} \\
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\midrule
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[NCT Number] & [Drug/regimen] & [Matching biomarker] & Phase [1/2/3] \\
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[NCT Number] & [Drug/regimen] & [Matching biomarker] & Phase [1/2/3] \\
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\bottomrule
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\end{tabular}
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\caption{Potential clinical trials based on molecular profile (as of [date])}
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\end{table}
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\textit{Note: Trial availability changes frequently. Search ClinicalTrials.gov for current options.}
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\section{Methodology}
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\subsection{Assay Information}
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\textbf{Test Name}: [FoundationOne CDx / Custom NGS Panel / Other]\\
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\textbf{Methodology}: Next-generation sequencing (NGS)\\
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\textbf{Genes Analyzed}: [Number] genes for SNVs, indels, CNVs, and rearrangements\\
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\textbf{Coverage Depth}: [XXX]x median coverage\\
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\textbf{Limit of Detection}: [X\%] variant allele frequency
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\textbf{Specimen Details}:
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\begin{itemize}
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\item Specimen type: [FFPE tissue block / Blood (ctDNA)]
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\item Tumor content: [XX\%] (minimum 20\% required for optimal sensitivity)
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\item DNA quality: [Adequate / Suboptimal]
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\item DNA quantity: [XX ng] (minimum [Y ng] required)
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\end{itemize}
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\subsection{Interpretation}
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\textbf{Variant Classification}:
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\begin{itemize}
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\item Pathogenic: Disease-causing, clinically significant
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\item Likely Pathogenic: Probably disease-causing based on available evidence
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\item VUS: Uncertain significance, insufficient evidence for classification
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\item Likely Benign: Probably not disease-causing
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\item Benign: Not disease-causing
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\end{itemize}
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\textbf{Databases Referenced}:
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\begin{itemize}
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\item OncoKB (Memorial Sloan Kettering)
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\item CIViC (Clinical Interpretations of Variants in Cancer)
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\item ClinVar (NCBI)
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\item COSMIC (Catalogue of Somatic Mutations in Cancer)
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\item [Others - PMKB, CGI, etc.]
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\end{itemize}
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\section{Limitations}
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\begin{itemize}
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\item This test analyzes [somatic/germline] alterations in tumor tissue. [If somatic: Results not informative for inherited cancer risk]
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\item Negative result does not exclude presence of alterations in genes not covered by this panel
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\item Low VAF alterations (<5\%) may not be detected due to assay sensitivity limits
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\item Copy number analysis limited for small amplifications or deletions
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\item Structural variants detection depends on breakpoint location within sequenced regions
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\item TMB and MSI calculations are estimate-based; consider orthogonal testing if borderline
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\end{itemize}
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\section{Recommendations for Referring Clinician}
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\begin{enumerate}
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\item \textbf{[Action 1]}: [e.g., Initiate targeted therapy with drug X based on detected alteration]
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\item \textbf{[Action 2]}: [e.g., Consider clinical trial enrollment for Tier 2 alteration]
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\item \textbf{[Action 3]}: [e.g., Repeat molecular profiling at progression to identify resistance mechanisms]
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\item \textbf{[Action 4]}: [e.g., If MSI-H detected and patient <50 years, refer for genetic counseling for Lynch syndrome]
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\item \textbf{[Action 5]}: [e.g., Share report with molecular tumor board for complex decision-making]
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\end{enumerate}
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\section{References}
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\begin{enumerate}
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\item [FDA Label for companion diagnostic]
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\item [Key clinical trial supporting biomarker-therapy association]
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\item [NCCN Guideline reference]
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\item [OncoKB database version]
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\item [Assay validation publication]
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\end{enumerate}
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\vspace{10pt}
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\hrule
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||||
\vspace{4pt}
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||||
{\footnotesize
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||||
\textbf{Laboratory Director}: [Name, MD, PhD] | [Board certifications]\\
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\textbf{Report Authorized By}: [Name, credentials] | Date: [Date]\\
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||||
\textbf{Laboratory}: [Name, address]\\
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||||
\textbf{CLIA \#}: [Number] | \textbf{CAP \#}: [Number]\\
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\textbf{Questions}: Contact [Name] at [Phone] or [Email]
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\vspace{2pt}
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||||
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\textit{This report is intended for use by qualified healthcare professionals. The information provided is based on current scientific literature and databases. Interpretation and treatment decisions should be made by qualified physicians in consultation with the patient. This test was performed in a CLIA-certified, CAP-accredited laboratory.}
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}
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\end{document}
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@@ -0,0 +1,222 @@
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\documentclass[10pt,letterpaper,landscape]{article}
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||||
% Landscape for wider flowcharts
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||||
\usepackage[margin=0.4in]{geometry}
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||||
\usepackage[utf8]{inputenc}
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||||
\usepackage[T1]{fontenc}
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||||
\usepackage{helvet}
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||||
\renewcommand{\familydefault}{\sfdefault}
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\usepackage{xcolor}
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||||
\usepackage{tcolorbox}
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\usepackage{tikz}
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\usetikzlibrary{shapes,arrows,positioning,fit,calc}
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\usepackage{fancyhdr}
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% Color definitions
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\definecolor{headerblue}{RGB}{0,102,204}
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\definecolor{actiongreen}{RGB}{0,153,76}
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\definecolor{decisionyellow}{RGB}{255,193,7}
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\definecolor{urgentred}{RGB}{220,20,60}
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\definecolor{infobox}{RGB}{33,150,243}
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\definecolor{routineblue}{RGB}{100,181,246}
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% Header/footer
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||||
\pagestyle{fancy}
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||||
\fancyhf{}
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||||
\fancyhead[L]{\footnotesize \textbf{Clinical Pathway: [CONDITION/DISEASE]}}
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||||
\fancyhead[R]{\footnotesize Version X.X | [Date]}
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\renewcommand{\headrulewidth}{0.5pt}
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||||
\fancyfoot[C]{\footnotesize Evidence-Based Clinical Decision Pathway | For Professional Use Only | Page \thepage}
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||||
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||||
% TikZ styles
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||||
\tikzstyle{startstop} = [rectangle, rounded corners=8pt, minimum width=3cm, minimum height=1cm, text centered, draw=black, fill=headerblue!20, font=\small\bfseries]
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\tikzstyle{decision} = [diamond, minimum width=3cm, minimum height=1.2cm, text centered, draw=black, fill=decisionyellow!40, font=\small, aspect=2, inner sep=0pt]
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\tikzstyle{process} = [rectangle, rounded corners=4pt, minimum width=3.5cm, minimum height=0.9cm, text centered, draw=black, fill=actiongreen!20, font=\small]
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\tikzstyle{urgent} = [rectangle, rounded corners=4pt, minimum width=3.5cm, minimum height=0.9cm, text centered, draw=urgentred, line width=1.5pt, fill=urgentred!15, font=\small\bfseries]
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||||
\tikzstyle{routine} = [rectangle, rounded corners=4pt, minimum width=3.5cm, minimum height=0.9cm, text centered, draw=black, fill=routineblue!20, font=\small]
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||||
\tikzstyle{info} = [rectangle, rounded corners=2pt, minimum width=2.5cm, minimum height=0.7cm, text centered, draw=infobox, fill=infobox!10, font=\footnotesize]
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||||
\tikzstyle{arrow} = [thick,->,>=stealth]
|
||||
\tikzstyle{urgentarrow} = [ultra thick,->,>=stealth,color=urgentred]
|
||||
|
||||
\setlength{\parindent}{0pt}
|
||||
|
||||
\begin{document}
|
||||
|
||||
\begin{center}
|
||||
{\fontsize{16}{18}\selectfont\bfseries\color{headerblue} CLINICAL DECISION PATHWAY}\\[2pt]
|
||||
{\fontsize{13}{15}\selectfont\bfseries [Disease/Condition - e.g., Acute Chest Pain Management]}\\[2pt]
|
||||
{\fontsize{10}{12}\selectfont [Institution Name] | Version X.X | Effective Date: [Date]}
|
||||
\end{center}
|
||||
|
||||
\vspace{6pt}
|
||||
|
||||
% Legend box
|
||||
\begin{tcolorbox}[colback=white,colframe=black,width=\textwidth]
|
||||
\begin{minipage}{0.48\textwidth}
|
||||
\textbf{Pathway Symbols:}\\[2pt]
|
||||
\begin{tikzpicture}[node distance=0.5cm]
|
||||
\node[startstop, scale=0.7] (start) {Start/End};
|
||||
\node[decision, right=1cm of start, scale=0.7] (dec) {Decision\\Point};
|
||||
\node[process, right=1cm of dec, scale=0.7] (proc) {Action/Process};
|
||||
\end{tikzpicture}
|
||||
\end{minipage}
|
||||
\begin{minipage}{0.48\textwidth}
|
||||
\textbf{Urgency Color Coding:}\\[2pt]
|
||||
\begin{tikzpicture}[node distance=0.5cm]
|
||||
\node[urgent, scale=0.7] (urg) {URGENT\\<1 hour};
|
||||
\node[process, right=1cm of urg, scale=0.7] (sem) {Semi-Urgent\\<24 hours};
|
||||
\node[routine, right=1cm of sem, scale=0.7] (rout) {Routine\\>24 hours};
|
||||
\end{tikzpicture}
|
||||
\end{minipage}
|
||||
\end{tcolorbox}
|
||||
|
||||
\vspace{4pt}
|
||||
|
||||
% Main flowchart
|
||||
\begin{center}
|
||||
\begin{tikzpicture}[node distance=2.2cm and 3cm, auto]
|
||||
|
||||
% Start
|
||||
\node [startstop] (start) {Patient Presentation:\\[2pt] [Chief Complaint]};
|
||||
|
||||
% First decision
|
||||
\node [decision, below=of start] (decision1) {[Critical\\Criteria\\Present?]};
|
||||
|
||||
% Urgent pathway (left branch)
|
||||
\node [urgent, left=of decision1, below=1.8cm] (urgent1) {IMMEDIATE ACTION:\\[2pt] [Specific intervention]\\[2pt] Call Code/Transfer};
|
||||
|
||||
% Continue evaluation (right branch)
|
||||
\node [process, right=of decision1, below=1.8cm] (eval1) {Continue\\Evaluation:\\[2pt][Tests/Assessment]};
|
||||
|
||||
% Second decision
|
||||
\node [decision, below=of eval1] (decision2) {[Risk\\Score\\$\geq$X?]};
|
||||
|
||||
% High risk pathway
|
||||
\node [urgent, left=of decision2, below=1.8cm] (high) {HIGH RISK:\\[2pt] Admit ICU/Telemetry\\[2pt] [Specific management]};
|
||||
|
||||
% Moderate risk
|
||||
\node [process, below=of decision2] (moderate) {MODERATE RISK:\\[2pt] Admit for observation\\[2pt] Serial testing};
|
||||
|
||||
% Low risk pathway
|
||||
\node [routine, right=of decision2, below=1.8cm] (low) {LOW RISK:\\[2pt] Outpatient management\\[2pt] Follow-up in X days};
|
||||
|
||||
% Final outcome node
|
||||
\node [startstop, below=of moderate, node distance=2.5cm] (outcome) {Definitive Management\\Based on Results};
|
||||
|
||||
% Arrows
|
||||
\draw [urgentarrow] (start) -- (decision1);
|
||||
\draw [urgentarrow] (decision1) -| node[near start,left] {YES} (urgent1);
|
||||
\draw [arrow] (decision1) -| node[near start,right] {NO} (eval1);
|
||||
\draw [arrow] (eval1) -- (decision2);
|
||||
\draw [arrow] (decision2) -| node[near start,left] {HIGH} (high);
|
||||
\draw [arrow] (decision2) -- node[right] {MODERATE} (moderate);
|
||||
\draw [arrow] (decision2) -| node[near start,right] {LOW} (low);
|
||||
\draw [arrow] (urgent1) |- (outcome);
|
||||
\draw [arrow] (high) |- (outcome);
|
||||
\draw [arrow] (moderate) -- (outcome);
|
||||
\draw [arrow] (low) |- (outcome);
|
||||
|
||||
% Information boxes
|
||||
\node [info, right=1.5cm of eval1] (info1) {[Criteria]:\\[1pt] \footnotesize • Item 1\\• Item 2\\• Item 3};
|
||||
\node [info, right=1.5cm of decision2] (info2) {[Score]:\\[1pt] \footnotesize Calculate:\\risk score};
|
||||
|
||||
\end{tikzpicture}
|
||||
\end{center}
|
||||
|
||||
\vspace{8pt}
|
||||
|
||||
% Detailed pathway steps
|
||||
\begin{tcolorbox}[colback=highlightgray!30,colframe=headerblue,title=\textbf{Detailed Pathway Steps},fonttitle=\bfseries]
|
||||
|
||||
\textbf{STEP 1: Initial Assessment}
|
||||
\begin{itemize}
|
||||
\item Vital signs: BP, HR, RR, temp, O₂ saturation
|
||||
\item Focused history: [Key elements]
|
||||
\item Physical examination: [Key findings]
|
||||
\item Initial labs: [Specify tests]
|
||||
\item ECG (if applicable)
|
||||
\end{itemize}
|
||||
|
||||
\textbf{STEP 2: Risk Stratification}
|
||||
\begin{itemize}
|
||||
\item Calculate [Risk Score Name] (see scoring table below)
|
||||
\item Identify high-risk features requiring immediate intervention
|
||||
\item Document risk category in medical record
|
||||
\end{itemize}
|
||||
|
||||
\textbf{STEP 3: Treatment Initiation}
|
||||
\begin{itemize}
|
||||
\item Urgent: [Specific interventions within 1 hour]
|
||||
\item Semi-urgent: [Interventions within 24 hours]
|
||||
\item Routine: [Standard management approach]
|
||||
\end{itemize}
|
||||
|
||||
\textbf{STEP 4: Monitoring and Reassessment}
|
||||
\begin{itemize}
|
||||
\item Frequency: [Based on risk category]
|
||||
\item Parameters: [What to monitor]
|
||||
\item Escalation criteria: [When to intensify treatment]
|
||||
\item De-escalation criteria: [When to transition to lower intensity]
|
||||
\end{itemize}
|
||||
|
||||
\end{tcolorbox}
|
||||
|
||||
\vspace{4pt}
|
||||
|
||||
% Risk scoring table
|
||||
\begin{tcolorbox}[colback=white,colframe=headerblue,title=\textbf{[Risk Score Name] Calculation},fonttitle=\bfseries]
|
||||
{\small
|
||||
\begin{tabular}{lc}
|
||||
\toprule
|
||||
\textbf{Clinical Feature} & \textbf{Points} \\
|
||||
\midrule
|
||||
[Feature 1 - e.g., Age $\geq$65 years] & +1 \\
|
||||
[Feature 2 - e.g., Prior history] & +1 \\
|
||||
[Feature 3 - e.g., Abnormal lab value] & +2 \\
|
||||
[Feature 4 - e.g., Specific symptom] & +1 \\
|
||||
[Feature 5 - e.g., Imaging finding] & +2 \\
|
||||
\midrule
|
||||
\textbf{Total Score} & \textbf{0-X points} \\
|
||||
\bottomrule
|
||||
\end{tabular}
|
||||
|
||||
\vspace{4pt}
|
||||
|
||||
\textbf{Risk Categories}:
|
||||
\begin{itemize}
|
||||
\item \textbf{Low Risk}: 0-1 points → [Management approach, predicted outcome]
|
||||
\item \textbf{Moderate Risk}: 2-3 points → [Management approach, predicted outcome]
|
||||
\item \textbf{High Risk}: $\geq$4 points → [Management approach, predicted outcome]
|
||||
\end{itemize}
|
||||
}
|
||||
\end{tcolorbox}
|
||||
|
||||
\vspace{4pt}
|
||||
|
||||
% Evidence basis
|
||||
\begin{tcolorbox}[colback=actiongreen!5,colframe=actiongreen,title=\textbf{Evidence Basis for Pathway},fonttitle=\bfseries]
|
||||
{\small
|
||||
\textbf{Key Supporting Evidence}:
|
||||
\begin{enumerate}
|
||||
\item \textbf{[Clinical Trial/Study]}: [Key finding supporting pathway decision]
|
||||
\item \textbf{Guidelines}: NCCN/ASCO/AHA/ACC/[Relevant society] [Year] - [Recommendation level]
|
||||
\item \textbf{Meta-Analysis}: [If applicable - pooled results supporting approach]
|
||||
\end{enumerate}
|
||||
|
||||
\textbf{Validation}: Pathway validated at [institution] with [X\%] adherence rate and [outcome metrics].
|
||||
|
||||
\textbf{Last Updated}: [Date] based on [new trial, guideline update, or scheduled review]
|
||||
}
|
||||
\end{tcolorbox}
|
||||
|
||||
\vspace{8pt}
|
||||
|
||||
\hrule
|
||||
\vspace{4pt}
|
||||
{\footnotesize
|
||||
\textbf{Pathway Committee}: [Names, titles] | \textbf{Approved}: [Date] | \textbf{Next Review}: [Date]\\
|
||||
\textbf{Contact for Questions}: [Name, email, phone]
|
||||
}
|
||||
|
||||
\end{document}
|
||||
|
||||
@@ -0,0 +1,359 @@
|
||||
\documentclass[10pt,letterpaper]{article}
|
||||
|
||||
% Packages
|
||||
\usepackage[margin=0.5in]{geometry}
|
||||
\usepackage[utf8]{inputenc}
|
||||
\usepackage[T1]{fontenc}
|
||||
\usepackage{helvet}
|
||||
\renewcommand{\familydefault}{\sfdefault}
|
||||
\usepackage{xcolor}
|
||||
\usepackage{tcolorbox}
|
||||
\usepackage{array}
|
||||
\usepackage{tabularx}
|
||||
\usepackage{booktabs}
|
||||
\usepackage{enumitem}
|
||||
\usepackage{titlesec}
|
||||
\usepackage{fancyhdr}
|
||||
\usepackage{multicol}
|
||||
\usepackage{graphicx}
|
||||
\usepackage{float}
|
||||
|
||||
% Color definitions
|
||||
\definecolor{headerblue}{RGB}{0,102,204}
|
||||
\definecolor{highlightgreen}{RGB}{0,153,76}
|
||||
\definecolor{warningred}{RGB}{204,0,0}
|
||||
\definecolor{highlightgray}{RGB}{240,240,240}
|
||||
\definecolor{biomarkerblue}{RGB}{51,102,204}
|
||||
|
||||
% Section formatting - compact
|
||||
\titleformat{\section}{\normalfont\fontsize{11}{12}\bfseries\color{headerblue}}{\thesection}{0.5em}{}
|
||||
\titlespacing*{\section}{0pt}{4pt}{2pt}
|
||||
|
||||
\titleformat{\subsection}{\normalfont\fontsize{10}{11}\bfseries}{\thesubsection}{0.5em}{}
|
||||
\titlespacing*{\subsection}{0pt}{3pt}{1pt}
|
||||
|
||||
% List formatting - ultra compact
|
||||
\setlist[itemize]{leftmargin=*,itemsep=0pt,parsep=0pt,topsep=1pt}
|
||||
\setlist[enumerate]{leftmargin=*,itemsep=0pt,parsep=0pt,topsep=1pt}
|
||||
|
||||
% Remove paragraph indentation
|
||||
\setlength{\parindent}{0pt}
|
||||
\setlength{\parskip}{2pt}
|
||||
|
||||
% Header/footer
|
||||
\pagestyle{fancy}
|
||||
\fancyhf{}
|
||||
\fancyhead[L]{\footnotesize \textbf{Clinical Decision Support: [COHORT NAME]}}
|
||||
\fancyhead[R]{\footnotesize Page \thepage}
|
||||
\renewcommand{\headrulewidth}{0.5pt}
|
||||
\fancyfoot[C]{\footnotesize Confidential Medical Document - For Professional Use Only}
|
||||
|
||||
\begin{document}
|
||||
|
||||
% Title block - compact
|
||||
\begin{center}
|
||||
{\fontsize{14}{16}\selectfont\bfseries\color{headerblue} PATIENT COHORT ANALYSIS REPORT}\\[2pt]
|
||||
{\fontsize{12}{14}\selectfont\bfseries [Cohort Description - e.g., NSCLC Patients Stratified by PD-L1 Expression]}\\[2pt]
|
||||
{\fontsize{10}{12}\selectfont [Institution/Study Name]}\\[1pt]
|
||||
{\fontsize{9}{11}\selectfont Report Date: [Date]}
|
||||
\end{center}
|
||||
|
||||
\vspace{4pt}
|
||||
|
||||
% Executive Summary Box
|
||||
\begin{tcolorbox}[colback=highlightgray,colframe=headerblue,title=\textbf{Executive Summary},fonttitle=\bfseries\small,coltitle=black]
|
||||
{\small
|
||||
\textbf{Cohort}: [n=XX] patients with [disease] stratified by [biomarker/characteristic]
|
||||
|
||||
\textbf{Key Findings}:
|
||||
\begin{itemize}
|
||||
\item [Primary finding - e.g., Biomarker+ patients had significantly longer PFS]
|
||||
\item [Secondary finding - e.g., ORR 45\% vs 30\%, p=0.023]
|
||||
\item [Safety finding - e.g., Similar toxicity profiles between groups]
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Clinical Implications}: [Treatment recommendations based on findings]
|
||||
}
|
||||
\end{tcolorbox}
|
||||
|
||||
\vspace{2pt}
|
||||
|
||||
\section{Cohort Characteristics}
|
||||
|
||||
\subsection{Patient Demographics}
|
||||
|
||||
[Narrative description of cohort composition, inclusion/exclusion criteria, time period]
|
||||
|
||||
\begin{table}[H]
|
||||
\centering
|
||||
\small
|
||||
\begin{tabular}{lccc}
|
||||
\toprule
|
||||
\textbf{Characteristic} & \textbf{Group A (n=XX)} & \textbf{Group B (n=XX)} & \textbf{p-value} \\
|
||||
\midrule
|
||||
Age, years (median [IQR]) & XX [XX-XX] & XX [XX-XX] & X.XX \\
|
||||
Sex, n (\%) & & & \\
|
||||
\quad Male & XX (XX\%) & XX (XX\%) & X.XX \\
|
||||
\quad Female & XX (XX\%) & XX (XX\%) & \\
|
||||
ECOG PS, n (\%) & & & \\
|
||||
\quad 0-1 & XX (XX\%) & XX (XX\%) & X.XX \\
|
||||
\quad 2 & XX (XX\%) & XX (XX\%) & \\
|
||||
Disease Stage, n (\%) & & & \\
|
||||
\quad III & XX (XX\%) & XX (XX\%) & X.XX \\
|
||||
\quad IV & XX (XX\%) & XX (XX\%) & \\
|
||||
Prior Lines of Therapy & & & \\
|
||||
\quad 0 (treatment-naïve) & XX (XX\%) & XX (XX\%) & X.XX \\
|
||||
\quad 1-2 & XX (XX\%) & XX (XX\%) & \\
|
||||
\quad $\geq$3 & XX (XX\%) & XX (XX\%) & \\
|
||||
\bottomrule
|
||||
\end{tabular}
|
||||
\caption{Baseline patient demographics and clinical characteristics}
|
||||
\end{table}
|
||||
|
||||
\subsection{Biomarker Profile}
|
||||
|
||||
\begin{tcolorbox}[colback=biomarkerblue!10,colframe=biomarkerblue,title=\textbf{Biomarker Stratification},fonttitle=\bfseries\small]
|
||||
{\small
|
||||
\textbf{Classification Method}: [e.g., IHC for PD-L1 expression, NGS for mutations, gene expression clustering]
|
||||
|
||||
\textbf{Group Definitions}:
|
||||
\begin{itemize}
|
||||
\item \textbf{Group A (Biomarker+)}: [n=XX] - [Definition, e.g., PD-L1 TPS $\geq$50\%, or Mesenchymal-Immune-Active subtype]
|
||||
\item \textbf{Group B (Biomarker-)}: [n=XX] - [Definition, e.g., PD-L1 TPS <50\%]
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Molecular Features of Group A}:
|
||||
\begin{itemize}
|
||||
\item [Feature 1]: XX\% (n=XX) - [Clinical significance]
|
||||
\item [Feature 2]: XX\% (n=XX) - [Clinical significance]
|
||||
\item [Feature 3]: Elevated/decreased [marker] (median [value])
|
||||
\end{itemize}
|
||||
}
|
||||
\end{tcolorbox}
|
||||
|
||||
\section{Treatment Exposures}
|
||||
|
||||
\begin{table}[H]
|
||||
\centering
|
||||
\small
|
||||
\begin{tabular}{lcc}
|
||||
\toprule
|
||||
\textbf{Treatment Received} & \textbf{Group A, n (\%)} & \textbf{Group B, n (\%)} \\
|
||||
\midrule
|
||||
[Treatment regimen 1] & XX (XX\%) & XX (XX\%) \\
|
||||
[Treatment regimen 2] & XX (XX\%) & XX (XX\%) \\
|
||||
[Treatment regimen 3] & XX (XX\%) & XX (XX\%) \\
|
||||
Median cycles received (range) & X (X-X) & X (X-X) \\
|
||||
\bottomrule
|
||||
\end{tabular}
|
||||
\caption{Treatment exposures by biomarker group}
|
||||
\end{table}
|
||||
|
||||
\section{Treatment Outcomes}
|
||||
|
||||
\subsection{Response Rates}
|
||||
|
||||
\begin{table}[H]
|
||||
\centering
|
||||
\small
|
||||
\begin{tabular}{lccc}
|
||||
\toprule
|
||||
\textbf{Response Category} & \textbf{Group A (n=XX)} & \textbf{Group B (n=XX)} & \textbf{p-value} \\
|
||||
\midrule
|
||||
Objective Response Rate (ORR) & XX\% [95\% CI] & XX\% [95\% CI] & X.XXX \\
|
||||
\quad Complete Response (CR) & XX (XX\%) & XX (XX\%) & \\
|
||||
\quad Partial Response (PR) & XX (XX\%) & XX (XX\%) & \\
|
||||
Disease Control Rate (DCR) & XX\% [95\% CI] & XX\% [95\% CI] & X.XXX \\
|
||||
\quad Stable Disease (SD) & XX (XX\%) & XX (XX\%) & \\
|
||||
Progressive Disease (PD) & XX (XX\%) & XX (XX\%) & \\
|
||||
\midrule
|
||||
Median Duration of Response (months) & X.X (95\% CI X.X-X.X) & X.X (95\% CI X.X-X.X) & X.XXX \\
|
||||
\bottomrule
|
||||
\end{tabular}
|
||||
\caption{Best overall response by biomarker group (RECIST v1.1 criteria)}
|
||||
\end{table}
|
||||
|
||||
\subsection{Survival Outcomes}
|
||||
|
||||
\textbf{Progression-Free Survival (PFS)}:
|
||||
\begin{itemize}
|
||||
\item Group A: Median X.X months (95\% CI X.X-X.X), 12-month PFS rate: XX\%
|
||||
\item Group B: Median X.X months (95\% CI X.X-X.X), 12-month PFS rate: XX\%
|
||||
\item Hazard Ratio: X.XX (95\% CI X.XX-X.XX), log-rank p = X.XXX
|
||||
\item \textit{[Interpretation: Group A had XX\% reduction in risk of progression compared to Group B]}
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Overall Survival (OS)}:
|
||||
\begin{itemize}
|
||||
\item Group A: Median XX.X months (95\% CI XX.X-XX.X), 12-month OS rate: XX\%
|
||||
\item Group B: Median XX.X months (95\% CI XX.X-XX.X), 12-month OS rate: XX\%
|
||||
\item Hazard Ratio: X.XX (95\% CI X.XX-X.XX), log-rank p = X.XXX
|
||||
\item \textit{[Interpretation: XX\% reduction in risk of death for Group A]}
|
||||
\end{itemize}
|
||||
|
||||
% Note: Include Kaplan-Meier curves as figures if available
|
||||
% \begin{figure}[H]
|
||||
% \centering
|
||||
% \includegraphics[width=0.9\textwidth]{figures/pfs_by_biomarker.pdf}
|
||||
% \caption{Progression-free survival by biomarker status}
|
||||
% \end{figure}
|
||||
|
||||
\section{Safety and Tolerability}
|
||||
|
||||
\begin{table}[H]
|
||||
\centering
|
||||
\small
|
||||
\begin{tabular}{lcccc}
|
||||
\toprule
|
||||
\multirow{2}{*}{\textbf{Adverse Event}} & \multicolumn{2}{c}{\textbf{Any Grade, n (\%)}} & \multicolumn{2}{c}{\textbf{Grade 3-4, n (\%)}} \\
|
||||
\cmidrule(lr){2-3} \cmidrule(lr){4-5}
|
||||
& Group A & Group B & Group A & Group B \\
|
||||
\midrule
|
||||
[AE 1 - e.g., Fatigue] & XX (XX\%) & XX (XX\%) & X (X\%) & X (X\%) \\
|
||||
[AE 2 - e.g., Nausea] & XX (XX\%) & XX (XX\%) & X (X\%) & X (X\%) \\
|
||||
[AE 3 - e.g., Neutropenia] & XX (XX\%) & XX (XX\%) & X (X\%) & X (X\%) \\
|
||||
[AE 4 - e.g., Diarrhea] & XX (XX\%) & XX (XX\%) & X (X\%) & X (X\%) \\
|
||||
[AE 5 - immune-related] & XX (XX\%) & XX (XX\%) & X (X\%) & X (X\%) \\
|
||||
\midrule
|
||||
Treatment discontinuation & XX (XX\%) & XX (XX\%) & \multicolumn{2}{c}{-} \\
|
||||
Dose reductions & XX (XX\%) & XX (XX\%) & \multicolumn{2}{c}{-} \\
|
||||
\bottomrule
|
||||
\end{tabular}
|
||||
\caption{Treatment-emergent adverse events by biomarker group (CTCAE v5.0)}
|
||||
\end{table}
|
||||
|
||||
\section{Statistical Analysis}
|
||||
|
||||
\subsection{Methods}
|
||||
|
||||
\textbf{Study Design}: [Retrospective cohort analysis / Prospective cohort / Post-hoc analysis of clinical trial]
|
||||
|
||||
\textbf{Statistical Tests}:
|
||||
\begin{itemize}
|
||||
\item Continuous variables: [t-test / Mann-Whitney U test], reported as [mean $\pm$ SD / median [IQR]]
|
||||
\item Categorical variables: Chi-square test or Fisher's exact test (if expected count <5)
|
||||
\item Survival analysis: Kaplan-Meier method, log-rank test, Cox proportional hazards regression
|
||||
\item Significance level: Two-sided p<0.05 considered statistically significant
|
||||
\item Software: [R version X.X.X, survival package / SAS / Stata / Python lifelines]
|
||||
\end{itemize}
|
||||
|
||||
\subsection{Multivariable Analysis}
|
||||
|
||||
Cox regression model adjusting for baseline prognostic factors:
|
||||
|
||||
\begin{table}[H]
|
||||
\centering
|
||||
\small
|
||||
\begin{tabular}{lccc}
|
||||
\toprule
|
||||
\textbf{Variable} & \textbf{Hazard Ratio} & \textbf{95\% CI} & \textbf{p-value} \\
|
||||
\midrule
|
||||
Biomarker+ (vs Biomarker-) & X.XX & X.XX-X.XX & X.XXX \\
|
||||
Age (per 10 years) & X.XX & X.XX-X.XX & X.XXX \\
|
||||
ECOG PS 2 (vs 0-1) & X.XX & X.XX-X.XX & X.XXX \\
|
||||
Stage IV (vs III) & X.XX & X.XX-X.XX & X.XXX \\
|
||||
[Additional variable] & X.XX & X.XX-X.XX & X.XXX \\
|
||||
\bottomrule
|
||||
\end{tabular}
|
||||
\caption{Multivariable Cox regression for progression-free survival}
|
||||
\end{table}
|
||||
|
||||
\textbf{Interpretation}: After adjusting for age, performance status, and disease stage, [biomarker status] remained an independent predictor of [PFS/OS] (HR X.XX, 95\% CI X.XX-X.XX, p=X.XXX).
|
||||
|
||||
\section{Clinical Implications}
|
||||
|
||||
\begin{tcolorbox}[colback=highlightgreen!10,colframe=highlightgreen,title=\textbf{Treatment Recommendations},fonttitle=\bfseries\small]
|
||||
{\small
|
||||
\textbf{For Biomarker-Positive Patients (Group A)}:
|
||||
|
||||
\textbf{Preferred Regimen} (GRADE 1A):
|
||||
\begin{itemize}
|
||||
\item [Specific treatment based on biomarker]
|
||||
\item Evidence: [Trial name/data showing benefit in biomarker+ population]
|
||||
\item Expected outcomes: ORR XX\%, median PFS XX months
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Monitoring}:
|
||||
\begin{itemize}
|
||||
\item Imaging every [X weeks] for response assessment
|
||||
\item [Specific lab monitoring for biomarker+ patients]
|
||||
\item Watch for [specific toxicities more common in this group]
|
||||
\end{itemize}
|
||||
|
||||
\textbf{For Biomarker-Negative Patients (Group B)}:
|
||||
|
||||
\textbf{Standard Regimen} (GRADE 1B):
|
||||
\begin{itemize}
|
||||
\item [Standard therapy for biomarker- population]
|
||||
\item Expected outcomes: ORR XX\%, median PFS XX months
|
||||
\item Consider [alternative approaches or clinical trial enrollment]
|
||||
\end{itemize}
|
||||
}
|
||||
\end{tcolorbox}
|
||||
|
||||
\section{Subgroup Analyses}
|
||||
|
||||
\textbf{Interaction Testing}: Treatment effect by biomarker subgroup (p-interaction = X.XXX)
|
||||
|
||||
[Describe whether treatment benefit differs by biomarker status - i.e., predictive biomarker]
|
||||
|
||||
Additional exploratory subgroups:
|
||||
\begin{itemize}
|
||||
\item Age <65 vs $\geq$65 years
|
||||
\item Sex (male vs female)
|
||||
\item Prior lines of therapy (0 vs 1+ prior treatments)
|
||||
\item Disease burden (high vs low tumor burden)
|
||||
\end{itemize}
|
||||
|
||||
\section{Strengths and Limitations}
|
||||
|
||||
\subsection{Strengths}
|
||||
\begin{itemize}
|
||||
\item [e.g., Biomarker-stratified analysis with prospectively defined groups]
|
||||
\item [e.g., Adequate sample size for statistical power]
|
||||
\item [e.g., Standardized response assessment using RECIST v1.1]
|
||||
\item [e.g., Multivariable analysis adjusting for confounders]
|
||||
\end{itemize}
|
||||
|
||||
\subsection{Limitations}
|
||||
\begin{itemize}
|
||||
\item [e.g., Retrospective design with potential selection bias]
|
||||
\item [e.g., Single-institution cohort may limit generalizability]
|
||||
\item [e.g., Biomarker testing not available for all patients (XX\% tested)]
|
||||
\item [e.g., Limited follow-up for OS (median X months)]
|
||||
\item [e.g., Heterogeneous treatment regimens across cohort]
|
||||
\end{itemize}
|
||||
|
||||
\section{Conclusions}
|
||||
|
||||
[Paragraph summarizing key findings]
|
||||
|
||||
[Biomarker-positive patients demonstrated [significantly better/worse] outcomes compared to biomarker-negative patients, with [outcome metric] of [values] (HR X.XX, p=X.XXX). These findings support [biomarker-guided therapy selection / routine biomarker testing / specific treatment approach].]
|
||||
|
||||
[Future directions: Prospective validation in independent cohort, investigation of mechanisms, clinical trial design implications]
|
||||
|
||||
\section{References}
|
||||
|
||||
\begin{enumerate}
|
||||
\item [Reference 1 - Key clinical trial]
|
||||
\item [Reference 2 - Biomarker validation study]
|
||||
\item [Reference 3 - Guideline reference (NCCN, ASCO, ESMO)]
|
||||
\item [Reference 4 - Statistical methods reference]
|
||||
\item [Reference 5 - Additional supporting evidence]
|
||||
\end{enumerate}
|
||||
|
||||
\vspace{10pt}
|
||||
|
||||
\hrule
|
||||
\vspace{4pt}
|
||||
{\footnotesize
|
||||
\textbf{Report Prepared By}: [Name, Title]\\
|
||||
\textbf{Date}: [Date]\\
|
||||
\textbf{Contact}: [Email/Phone]\\
|
||||
\textbf{Institutional Review}: [IRB approval number if applicable]\\
|
||||
\textbf{Data Cut-Off Date}: [Date]\\
|
||||
\textbf{Confidentiality}: This document contains proprietary clinical data. Distribution restricted to authorized personnel only.
|
||||
}
|
||||
|
||||
\end{document}
|
||||
|
||||
149
skills/clinical-decision-support/assets/color_schemes.tex
Normal file
149
skills/clinical-decision-support/assets/color_schemes.tex
Normal file
@@ -0,0 +1,149 @@
|
||||
% Clinical Decision Support Color Schemes
|
||||
% For use in LaTeX documents
|
||||
|
||||
% ============================================================================
|
||||
% PRIMARY THEME COLORS
|
||||
% ============================================================================
|
||||
|
||||
% Header and structural elements
|
||||
\definecolor{headerblue}{RGB}{0,102,204} % Section headers, titles
|
||||
\definecolor{highlightgray}{RGB}{240,240,240} % Background boxes
|
||||
|
||||
% ============================================================================
|
||||
% RECOMMENDATION STRENGTH COLORS
|
||||
% ============================================================================
|
||||
|
||||
% Strong recommendations (benefits clearly outweigh risks)
|
||||
\definecolor{stronggreen}{RGB}{0,153,76} % Grade 1A, 1B
|
||||
\definecolor{strongdark}{RGB}{0,120,60} % Darker variant for emphasis
|
||||
|
||||
% Conditional recommendations (trade-offs exist)
|
||||
\definecolor{conditionalyellow}{RGB}{255,193,7} % Grade 2A, 2B, 2C
|
||||
\definecolor{conditionalamber}{RGB}{255,160,0} % Darker variant
|
||||
|
||||
% Research/Investigational (insufficient evidence)
|
||||
\definecolor{researchblue}{RGB}{33,150,243} % Clinical trials
|
||||
\definecolor{researchdark}{RGB}{25,118,210} % Darker variant
|
||||
|
||||
% Not recommended / Contraindicated
|
||||
\definecolor{warningred}{RGB}{204,0,0} % Strong recommendation against
|
||||
\definecolor{dangerred}{RGB}{220,20,60} % Critical warnings, urgent actions
|
||||
|
||||
% ============================================================================
|
||||
% URGENCY LEVELS (Clinical Pathways)
|
||||
% ============================================================================
|
||||
|
||||
\definecolor{urgentred}{RGB}{220,20,60} % Immediate action (<1 hour)
|
||||
\definecolor{semiurgent}{RGB}{255,152,0} % Action within 24 hours
|
||||
\definecolor{routineblue}{RGB}{100,181,246} % Routine care (>24 hours)
|
||||
\definecolor{actiongreen}{RGB}{0,153,76} % Standard interventions
|
||||
|
||||
% ============================================================================
|
||||
% BIOMARKER CATEGORIES
|
||||
% ============================================================================
|
||||
|
||||
% Alteration types
|
||||
\definecolor{mutationred}{RGB}{244,67,54} % Point mutations, SNVs
|
||||
\definecolor{amplificationblue}{RGB}{33,150,243} % Copy number gains
|
||||
\definecolor{deletionpurple}{RGB}{156,39,176} % Copy number losses
|
||||
\definecolor{fusionpurple}{RGB}{156,39,176} % Gene fusions/rearrangements
|
||||
\definecolor{expressionorange}{RGB}{255,152,0} % Expression alterations
|
||||
|
||||
% Actionability tiers
|
||||
\definecolor{tier1green}{RGB}{0,153,76} % FDA-approved therapy
|
||||
\definecolor{tier2orange}{RGB}{255,152,0} % Clinical trial/off-label
|
||||
\definecolor{tier3gray}{RGB}{158,158,158} % VUS, no action
|
||||
|
||||
% ============================================================================
|
||||
% STATISTICAL SIGNIFICANCE
|
||||
% ============================================================================
|
||||
|
||||
\definecolor{significant}{RGB}{0,153,76} % p < 0.05, statistically significant
|
||||
\definecolor{trending}{RGB}{255,193,7} % p = 0.05-0.10, trending
|
||||
\definecolor{nonsignificant}{RGB}{158,158,158} % p > 0.10, not significant
|
||||
|
||||
% ============================================================================
|
||||
% OUTCOME CATEGORIES
|
||||
% ============================================================================
|
||||
|
||||
% Response assessment (RECIST)
|
||||
\definecolor{completeresponse}{RGB}{0,153,76} % CR (complete response)
|
||||
\definecolor{partialresponse}{RGB}{76,175,80} % PR (partial response)
|
||||
\definecolor{stabledisease}{RGB}{255,193,7} % SD (stable disease)
|
||||
\definecolor{progressivedisease}{RGB}{244,67,54} % PD (progressive disease)
|
||||
|
||||
% Survival outcomes
|
||||
\definecolor{survivedgreen}{RGB}{0,153,76} % Patient alive
|
||||
\definecolor{eventred}{RGB}{244,67,54} % Event occurred (death, progression)
|
||||
\definecolor{censoredgray}{RGB}{158,158,158} % Censored observation
|
||||
|
||||
% ============================================================================
|
||||
% ADVERSE EVENT SEVERITY (CTCAE)
|
||||
% ============================================================================
|
||||
|
||||
\definecolor{grade1}{RGB}{255,235,59} % Mild
|
||||
\definecolor{grade2}{RGB}{255,193,7} % Moderate
|
||||
\definecolor{grade3}{RGB}{255,152,0} % Severe
|
||||
\definecolor{grade4}{RGB}{244,67,54} % Life-threatening
|
||||
\definecolor{grade5}{RGB}{198,40,40} % Fatal
|
||||
|
||||
% ============================================================================
|
||||
% COLORBLIND-SAFE PALETTE (Okabe-Ito)
|
||||
% ============================================================================
|
||||
% Use these for graphs/figures to ensure accessibility
|
||||
|
||||
\definecolor{okabe1}{RGB}{230,159,0} % Orange
|
||||
\definecolor{okabe2}{RGB}{86,180,233} % Sky blue
|
||||
\definecolor{okabe3}{RGB}{0,158,115} % Bluish green
|
||||
\definecolor{okabe4}{RGB}{240,228,66} % Yellow
|
||||
\definecolor{okabe5}{RGB}{0,114,178} % Blue
|
||||
\definecolor{okabe6}{RGB}{213,94,0} % Vermillion
|
||||
\definecolor{okabe7}{RGB}{204,121,167} % Reddish purple
|
||||
|
||||
% ============================================================================
|
||||
% USAGE EXAMPLES
|
||||
% ============================================================================
|
||||
|
||||
% Example 1: Strong recommendation box
|
||||
% \begin{tcolorbox}[enhanced,colback=stronggreen!10,colframe=stronggreen,
|
||||
% title={\textbf{STRONG RECOMMENDATION} \hfill \textbf{GRADE: 1A}}]
|
||||
% We recommend osimertinib for EGFR-mutated NSCLC...
|
||||
% \end{tcolorbox}
|
||||
|
||||
% Example 2: Conditional recommendation box
|
||||
% \begin{tcolorbox}[enhanced,colback=conditionalyellow!10,colframe=conditionalyellow,
|
||||
% title={\textbf{CONDITIONAL RECOMMENDATION} \hfill \textbf{GRADE: 2B}}]
|
||||
% We suggest considering maintenance therapy...
|
||||
% \end{tcolorbox}
|
||||
|
||||
% Example 3: Biomarker alteration
|
||||
% \colorbox{mutationred!60}{\textcolor{white}{\textbf{MUTATION}}}
|
||||
|
||||
% Example 4: Statistical significance in table
|
||||
% \cellcolor{significant!20} p < 0.001
|
||||
|
||||
% Example 5: Adverse event severity
|
||||
% \textcolor{grade3}{Grade 3} or \colorbox{grade3!30}{Grade 3}
|
||||
|
||||
% ============================================================================
|
||||
% ACCESSIBILITY NOTES
|
||||
% ============================================================================
|
||||
|
||||
% 1. Always use sufficient color contrast (4.5:1 ratio for normal text)
|
||||
% 2. Do not rely on color alone - use symbols/text as well
|
||||
% 3. Test in grayscale to ensure readability
|
||||
% 4. Use Okabe-Ito palette for colorblind accessibility in figures
|
||||
% 5. Add text labels to colored boxes ("STRONG", "CONDITIONAL", etc.)
|
||||
|
||||
% ============================================================================
|
||||
% STYLE CONSISTENCY
|
||||
% ============================================================================
|
||||
|
||||
% Font: Helvetica (sans-serif) for clinical documents
|
||||
% Margins: 0.5 inches for compact professional appearance
|
||||
% Font sizes: 10pt body, 11pt subsections, 12-14pt headers
|
||||
% Line spacing: Compact (minimal whitespace for dense information)
|
||||
% Boxes: tcolorbox with rounded corners, colored backgrounds at 10-20% opacity
|
||||
|
||||
% End of color scheme definitions
|
||||
|
||||
208
skills/clinical-decision-support/assets/example_gbm_cohort.md
Normal file
208
skills/clinical-decision-support/assets/example_gbm_cohort.md
Normal file
@@ -0,0 +1,208 @@
|
||||
# Example: GBM Molecular Subtype Cohort Analysis
|
||||
|
||||
## Clinical Context
|
||||
|
||||
This example demonstrates a patient cohort analysis stratified by molecular biomarkers, similar to the GBM Mesenchymal-Immune-Active cluster analysis provided as reference.
|
||||
|
||||
## Cohort Overview
|
||||
|
||||
**Disease**: Glioblastoma (GBM), IDH-wild-type
|
||||
|
||||
**Study Population**: n=60 patients with newly diagnosed GBM treated with standard Stupp protocol (temozolomide + radiation → adjuvant temozolomide)
|
||||
|
||||
**Molecular Classification**: Verhaak 2010 subtypes with immune signature refinement
|
||||
- **Group A**: Mesenchymal-Immune-Active subtype (n=18, 30%)
|
||||
- **Group B**: Other molecular subtypes (Proneural, Classical, Neural) (n=42, 70%)
|
||||
|
||||
**Study Period**: January 2019 - December 2022
|
||||
|
||||
**Data Source**: Single academic medical center, retrospective cohort analysis
|
||||
|
||||
## Biomarker Classification
|
||||
|
||||
### Mesenchymal-Immune-Active Subtype Characteristics
|
||||
|
||||
**Molecular Features**:
|
||||
- NF1 alterations (mutations or deletions): 72% (13/18)
|
||||
- High YKL-40 (CHI3L1) expression: 100% (18/18, median z-score +2.8)
|
||||
- Immune gene signature: Elevated (median ESTIMATE immune score +1250)
|
||||
- CD163+ macrophage infiltration: High density (median 195 cells/mm², range 120-340)
|
||||
- MES (mesenchymal) signature score: >0.5 (all patients)
|
||||
|
||||
**Clinical Characteristics**:
|
||||
- Median age: 64 years (range 42-76)
|
||||
- Male: 61% (11/18)
|
||||
- Tumor location: Temporal lobe predominant (55%)
|
||||
- Multifocal disease: 33% (6/18) - higher than overall cohort
|
||||
|
||||
### Comparison Groups (Other Subtypes)
|
||||
|
||||
**Molecular Features**:
|
||||
- Proneural: n=15 (25%) - PDGFRA amplification, younger age
|
||||
- Classical: n=18 (30%) - EGFR amplification, chromosome 7+/10-
|
||||
- Neural: n=9 (15%) - neuronal markers, may include normal tissue
|
||||
|
||||
## Treatment Outcomes
|
||||
|
||||
### Response Assessment (RANO Criteria)
|
||||
|
||||
**Objective Response Rate** (after chemoradiation, ~3 months):
|
||||
- Mesenchymal-Immune-Active: 6/18 (33%) - CR 0, PR 6
|
||||
- Other subtypes: 18/42 (43%) - CR 1, PR 17
|
||||
- p = 0.48 (Fisher's exact)
|
||||
|
||||
**Interpretation**: No significant difference in initial response rates
|
||||
|
||||
### Survival Outcomes
|
||||
|
||||
**Progression-Free Survival (PFS)**:
|
||||
- Mesenchymal-Immune-Active: Median 7.2 months (95% CI 5.8-9.1)
|
||||
- Other subtypes: Median 9.5 months (95% CI 8.1-11.3)
|
||||
- Hazard Ratio: 1.58 (95% CI 0.89-2.81), p = 0.12
|
||||
- 6-month PFS rate: 61% vs 74%
|
||||
|
||||
**Overall Survival (OS)**:
|
||||
- Mesenchymal-Immune-Active: Median 12.8 months (95% CI 10.2-15.4)
|
||||
- Other subtypes: Median 16.3 months (95% CI 14.7-18.9)
|
||||
- Hazard Ratio: 1.72 (95% CI 0.95-3.11), p = 0.073
|
||||
- 12-month OS rate: 55% vs 68%
|
||||
- 24-month OS rate: 17% vs 31%
|
||||
|
||||
**Interpretation**: Trend toward worse survival in mesenchymal-immune-active subtype, not reaching statistical significance in this cohort size
|
||||
|
||||
### Response to Bevacizumab at Recurrence
|
||||
|
||||
**Subset Analysis** (patients receiving bevacizumab at first recurrence, n=35):
|
||||
- Mesenchymal-Immune-Active: n=12
|
||||
- ORR: 58% (7/12)
|
||||
- Median PFS2 (from bevacizumab start): 6.8 months
|
||||
- Other subtypes: n=23
|
||||
- ORR: 35% (8/23)
|
||||
- Median PFS2: 4.2 months
|
||||
- p = 0.19 (Fisher's exact for ORR)
|
||||
- HR for PFS2: 0.62 (95% CI 0.29-1.32), p = 0.21
|
||||
|
||||
**Interpretation**: Exploratory finding suggesting enhanced benefit from bevacizumab in mesenchymal-immune-active subtype (not statistically significant with small sample)
|
||||
|
||||
## Safety Profile
|
||||
|
||||
**Treatment-Related Adverse Events** (Temozolomide):
|
||||
|
||||
No significant differences in toxicity between molecular subtypes:
|
||||
- Lymphopenia (any grade): 89% vs 86%, p = 0.77
|
||||
- Thrombocytopenia (grade 3-4): 22% vs 19%, p = 0.79
|
||||
- Fatigue (any grade): 94% vs 90%, p = 0.60
|
||||
- Treatment discontinuation: 17% vs 14%, p = 0.77
|
||||
|
||||
## Clinical Implications
|
||||
|
||||
### Treatment Recommendations
|
||||
|
||||
**For Mesenchymal-Immune-Active GBM**:
|
||||
|
||||
1. **First-Line**: Standard Stupp protocol (no change based on subtype)
|
||||
- Evidence: No proven benefit for alternative first-line strategies
|
||||
- GRADE: 1A (strong recommendation, high-quality evidence)
|
||||
|
||||
2. **At Recurrence - Consider Bevacizumab Earlier**:
|
||||
- Rationale: Exploratory data suggesting enhanced anti-angiogenic response
|
||||
- Evidence: Mesenchymal GBM has high VEGF expression, angiogenic phenotype
|
||||
- GRADE: 2C (conditional recommendation, low-quality evidence from subset)
|
||||
|
||||
3. **Clinical Trial Enrollment - Immunotherapy Combinations**:
|
||||
- Rationale: High immune cell infiltration may predict immunotherapy benefit
|
||||
- Targets: PD-1/PD-L1 blockade ± anti-CTLA-4 or anti-angiogenic agents
|
||||
- Evidence: Ongoing trials (CheckMate-498, CheckMate-548 showed negative results, but did not select for immune-active)
|
||||
- GRADE: R (research recommendation)
|
||||
|
||||
**For Other GBM Subtypes**:
|
||||
- Standard treatment per NCCN guidelines
|
||||
- Consider tumor treating fields (Optune) after radiation completion
|
||||
- Clinical trials based on specific molecular features (EGFR amplification → EGFR inhibitor trials)
|
||||
|
||||
### Prognostic Information
|
||||
|
||||
**Counseling Patients**:
|
||||
- Mesenchymal-immune-active subtype associated with trend toward shorter survival (12.8 vs 16.3 months)
|
||||
- Not definitive due to small sample size and confidence intervals overlapping
|
||||
- Prospective validation needed
|
||||
- Should not alter standard first-line treatment
|
||||
|
||||
## Study Limitations
|
||||
|
||||
1. **Small Sample Size**: n=18 in mesenchymal-immune-active group limits statistical power
|
||||
2. **Retrospective Design**: Potential selection bias, unmeasured confounders
|
||||
3. **Single Institution**: May not generalize to other populations
|
||||
4. **Heterogeneous Recurrence Treatment**: Not all patients received bevacizumab; treatment selection bias
|
||||
5. **Molecular Classification**: Based on bulk tumor RNA-seq; intratumoral heterogeneity not captured
|
||||
6. **No Central Pathology Review**: Molecular classification performed locally
|
||||
|
||||
## Future Directions
|
||||
|
||||
1. **Prospective Validation**: Confirm survival differences in independent cohort (n>100 per group for adequate power)
|
||||
2. **Biomarker Testing**: Develop clinically feasible assay for mesenchymal-immune subtype identification
|
||||
3. **Clinical Trial Design**: Immunotherapy combinations targeting mesenchymal-immune-active GBM specifically
|
||||
4. **Mechanistic Studies**: Investigate why mesenchymal-immune GBM may respond better to bevacizumab
|
||||
5. **Longitudinal Analysis**: Track molecular subtype evolution over treatment course
|
||||
|
||||
## Data Presentation Example
|
||||
|
||||
### Baseline Characteristics Table
|
||||
|
||||
```
|
||||
Characteristic Mesenchymal-IA (n=18) Other (n=42) p-value
|
||||
Age, years (median [IQR]) 64 [56-71] 61 [53-68] 0.42
|
||||
Sex, n (%)
|
||||
Male 11 (61%) 24 (57%) 0.78
|
||||
Female 7 (39%) 18 (43%)
|
||||
ECOG PS, n (%)
|
||||
0-1 15 (83%) 37 (88%) 0.63
|
||||
2 3 (17%) 5 (12%)
|
||||
Tumor location
|
||||
Frontal 4 (22%) 15 (36%) 0.35
|
||||
Temporal 10 (56%) 16 (38%)
|
||||
Parietal/Occipital 4 (22%) 11 (26%)
|
||||
Extent of resection
|
||||
Gross total 8 (44%) 22 (52%) 0.58
|
||||
Subtotal 10 (56%) 20 (48%)
|
||||
MGMT promoter methylated 5 (28%) 18 (43%) 0.27
|
||||
```
|
||||
|
||||
### Survival Outcomes Summary
|
||||
|
||||
```
|
||||
Endpoint Mesenchymal-IA Other HR (95% CI) p-value
|
||||
Median PFS, months (95% CI) 7.2 (5.8-9.1) 9.5 (8.1-11.3) 1.58 (0.89-2.81) 0.12
|
||||
6-month PFS rate 61% 74%
|
||||
Median OS, months (95% CI) 12.8 (10.2-15.4) 16.3 (14.7-18.9) 1.72 (0.95-3.11) 0.073
|
||||
12-month OS rate 55% 68%
|
||||
24-month OS rate 17% 31%
|
||||
```
|
||||
|
||||
## Key Takeaways
|
||||
|
||||
1. **Molecular heterogeneity exists** in GBM with distinct subtypes
|
||||
2. **Mesenchymal-immune-active subtype** characterized by NF1 alterations, immune infiltration
|
||||
3. **Trend toward worse prognosis** but not statistically significant (power limitations)
|
||||
4. **Potential bevacizumab benefit** hypothesis-generating, requires prospective validation
|
||||
5. **Immunotherapy target**: High immune infiltration rational for checkpoint inhibitor trials
|
||||
6. **Clinical implementation pending**: Need prospective validation before routine subtyping
|
||||
|
||||
## References
|
||||
|
||||
1. Verhaak RG, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17(1):98-110.
|
||||
2. Wang Q, et al. Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment. Cancer Cell. 2017;32(1):42-56.
|
||||
3. Stupp R, et al. Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. NEJM. 2005;352(10):987-996.
|
||||
4. Gilbert MR, et al. Bevacizumab for Newly Diagnosed Glioblastoma. NEJM. 2014;370(8):699-708.
|
||||
5. NCCN Clinical Practice Guidelines in Oncology: Central Nervous System Cancers. Version 1.2024.
|
||||
|
||||
---
|
||||
|
||||
**This example demonstrates**:
|
||||
- Biomarker-based stratification methodology
|
||||
- Outcome reporting with appropriate statistics
|
||||
- Clinical contextualization of findings
|
||||
- Evidence-based recommendations with grading
|
||||
- Transparent limitation discussion
|
||||
- Structure suitable for pharmaceutical/clinical research documentation
|
||||
|
||||
@@ -0,0 +1,328 @@
|
||||
# Recommendation Strength Guide
|
||||
|
||||
## GRADE Framework for Clinical Recommendations
|
||||
|
||||
### Components of a Recommendation
|
||||
|
||||
Every clinical recommendation should address:
|
||||
|
||||
1. **Population**: Who should receive the intervention?
|
||||
2. **Intervention**: What specific treatment/action?
|
||||
3. **Comparator**: Compared to what alternative?
|
||||
4. **Outcome**: What are the expected results?
|
||||
5. **Strength**: How strong is the recommendation?
|
||||
6. **Quality of Evidence**: How confident are we in the evidence?
|
||||
|
||||
### Recommendation Strength (Grade 1 vs Grade 2)
|
||||
|
||||
#### Strong Recommendation (Grade 1)
|
||||
|
||||
**When to Use**:
|
||||
- Desirable effects clearly outweigh undesirable effects (or vice versa)
|
||||
- High or moderate quality evidence
|
||||
- Values and preferences: Little variability expected
|
||||
- Resource implications: Cost-effective or cost considerations minor
|
||||
|
||||
**Wording**: "We recommend..." or "Clinicians should..."
|
||||
|
||||
**Implications**:
|
||||
- Most patients should receive the recommended intervention
|
||||
- Adherence to recommendation could be a quality indicator
|
||||
- Policy-makers can adapt as performance measure
|
||||
|
||||
**Examples**:
|
||||
|
||||
```
|
||||
STRONG RECOMMENDATION FOR (Grade 1):
|
||||
|
||||
"We recommend osimertinib 80 mg daily as first-line therapy for adults with
|
||||
advanced NSCLC harboring EGFR exon 19 deletion or L858R mutation (Strong
|
||||
recommendation, High-quality evidence - GRADE 1A)."
|
||||
|
||||
Rationale:
|
||||
- Large PFS benefit: 18.9 vs 10.2 months (HR 0.46, p<0.001)
|
||||
- OS benefit: 38.6 vs 31.8 months (HR 0.80, p=0.046)
|
||||
- Better tolerability: Lower grade 3-4 AEs
|
||||
- Evidence: High-quality (large RCT, low risk of bias)
|
||||
- Benefits clearly outweigh harms
|
||||
```
|
||||
|
||||
```
|
||||
STRONG RECOMMENDATION AGAINST (Grade 1):
|
||||
|
||||
"We recommend against using bevacizumab in the first-line treatment of newly
|
||||
diagnosed glioblastoma to improve overall survival (Strong recommendation against,
|
||||
High-quality evidence - GRADE 1A)."
|
||||
|
||||
Rationale:
|
||||
- No OS benefit: HR 0.88 (0.76-1.02), p=0.10 (AVAglio trial)
|
||||
- Toxicity: Increased grade ≥3 AEs (66% vs 52%)
|
||||
- Evidence: High-quality (two large phase 3 RCTs)
|
||||
- Harms outweigh lack of survival benefit
|
||||
```
|
||||
|
||||
#### Conditional/Weak Recommendation (Grade 2)
|
||||
|
||||
**When to Use**:
|
||||
- Desirable and undesirable effects closely balanced
|
||||
- Low or very low quality evidence
|
||||
- Values and preferences: Substantial variability
|
||||
- Resource implications: High cost or limited access
|
||||
|
||||
**Wording**: "We suggest..." or "Clinicians might..."
|
||||
|
||||
**Implications**:
|
||||
- Different choices will be appropriate for different patients
|
||||
- Shared decision-making essential
|
||||
- Policy-making requires substantial debate and stakeholder involvement
|
||||
|
||||
**Examples**:
|
||||
|
||||
```
|
||||
CONDITIONAL RECOMMENDATION FOR (Grade 2):
|
||||
|
||||
"We suggest considering maintenance pemetrexed after first-line platinum-pemetrexed
|
||||
chemotherapy for advanced non-squamous NSCLC in patients without disease progression
|
||||
(Conditional recommendation, Moderate-quality evidence - GRADE 2B)."
|
||||
|
||||
Rationale:
|
||||
- Modest PFS benefit: 4.0 vs 2.0 months (HR 0.62)
|
||||
- No OS benefit: 13.9 vs 11.0 months (HR 0.79, p=0.23)
|
||||
- Toxicity: Continued chemotherapy burden
|
||||
- Quality of life: Trade-off between symptom control and treatment side effects
|
||||
- Patient values: Some prioritize time off treatment, others prioritize disease control
|
||||
- Shared decision-making essential
|
||||
```
|
||||
|
||||
```
|
||||
CONDITIONAL RECOMMENDATION - EITHER OPTION ACCEPTABLE (Grade 2):
|
||||
|
||||
"We suggest either pembrolizumab monotherapy OR pembrolizumab plus platinum-doublet
|
||||
chemotherapy as first-line treatment for PD-L1 ≥50% NSCLC, based on patient
|
||||
preferences and clinical factors (Conditional recommendation, High-quality evidence -
|
||||
GRADE 2A)."
|
||||
|
||||
Rationale:
|
||||
- Both regimens NCCN Category 1 preferred
|
||||
- Monotherapy: Less toxicity, oral vs IV, better quality of life
|
||||
- Combination: Higher ORR (48% vs 39%), numerically longer PFS
|
||||
- OS: Similar between strategies
|
||||
- Patient values: Varies widely (tolerability vs response rate priority)
|
||||
```
|
||||
|
||||
### Evidence Quality (⊕⊕⊕⊕ to ⊕○○○)
|
||||
|
||||
#### High Quality (⊕⊕⊕⊕)
|
||||
|
||||
- Further research very unlikely to change confidence in effect estimate
|
||||
- Consistent results from well-designed RCTs
|
||||
- No serious limitations
|
||||
- Direct evidence (target population, intervention, outcomes)
|
||||
- Precise estimate (narrow CI)
|
||||
|
||||
**Example**: FLAURA trial for osimertinib in EGFR+ NSCLC - Large RCT, consistent results, low risk of bias, direct outcomes
|
||||
|
||||
#### Moderate Quality (⊕⊕⊕○)
|
||||
|
||||
- Further research likely to impact confidence and may change estimate
|
||||
- RCTs with some limitations OR very strong evidence from observational studies
|
||||
- Some inconsistency, indirectness, imprecision, or publication bias
|
||||
|
||||
**Example**: Single RCT with some limitations, or multiple RCTs with moderate heterogeneity
|
||||
|
||||
#### Low Quality (⊕⊕○○)
|
||||
|
||||
- Further research very likely to have important impact on confidence in estimate
|
||||
- Observational studies OR RCTs with serious limitations
|
||||
- Serious issues with consistency, directness, precision, or bias
|
||||
|
||||
**Example**: Well-conducted cohort study, or RCT with high attrition and unclear allocation concealment
|
||||
|
||||
#### Very Low Quality (⊕○○○)
|
||||
|
||||
- Estimate of effect very uncertain
|
||||
- Case series, expert opinion, mechanistic reasoning
|
||||
- Very serious limitations
|
||||
|
||||
**Example**: Retrospective case series, expert consensus without systematic review
|
||||
|
||||
## Combining Strength and Quality
|
||||
|
||||
### All Nine Possible Combinations
|
||||
|
||||
| Evidence Quality | Strong For (↑↑) | Weak For (↑) | Strong Against (↓↓) | Weak Against (↓) |
|
||||
|-----------------|----------------|--------------|---------------------|------------------|
|
||||
| **High (⊕⊕⊕⊕)** | Grade 1A | Grade 2A | Grade 1A (against) | Grade 2A (against) |
|
||||
| **Moderate (⊕⊕⊕○)** | Grade 1B | Grade 2B | Grade 1B (against) | Grade 2B (against) |
|
||||
| **Low (⊕⊕○○)** | Grade 1C* | Grade 2C | Grade 1C (against)* | Grade 2C (against) |
|
||||
| **Very Low (⊕○○○)** | Grade 1D* | Grade 2D | Grade 1D (against)* | Grade 2D (against) |
|
||||
|
||||
*Rare: Strong recommendations usually require at least moderate-quality evidence
|
||||
|
||||
### Unusual Combinations (When They Occur)
|
||||
|
||||
**Strong Recommendation with Low Quality Evidence (Grade 1C)**
|
||||
|
||||
Rare, but can occur when:
|
||||
- Large magnitude of effect from observational data (RR >5 or <0.2)
|
||||
- Low quality evidence, but clear benefit-harm balance
|
||||
- Example: Anticoagulation for atrial fibrillation (before RCTs, strong observational data)
|
||||
|
||||
**Weak Recommendation with High Quality Evidence (Grade 2A)**
|
||||
|
||||
Occurs when:
|
||||
- Benefits and harms closely balanced
|
||||
- Patient values highly variable
|
||||
- Example: Aspirin for primary prevention in low-risk individuals (benefits small, bleeding risk present, patient values vary)
|
||||
|
||||
## Wording Templates
|
||||
|
||||
### Strong Recommendations
|
||||
|
||||
**FOR (↑↑)**:
|
||||
- "We recommend [intervention] for [population]."
|
||||
- "Clinicians should [action]."
|
||||
- "[Intervention] is recommended."
|
||||
|
||||
**AGAINST (↓↓)**:
|
||||
- "We recommend against [intervention] for [population]."
|
||||
- "Clinicians should not [action]."
|
||||
- "[Intervention] is not recommended."
|
||||
|
||||
### Conditional/Weak Recommendations
|
||||
|
||||
**FOR (↑)**:
|
||||
- "We suggest [intervention] for [population]."
|
||||
- "Clinicians might consider [action]."
|
||||
- "[Intervention] may be considered for selected patients."
|
||||
|
||||
**AGAINST (↓)**:
|
||||
- "We suggest not using [intervention] for [population]."
|
||||
- "Clinicians might avoid [action]."
|
||||
- "[Intervention] is generally not recommended."
|
||||
|
||||
**EITHER ACCEPTABLE**:
|
||||
- "We suggest either [option A] or [option B] based on patient preferences."
|
||||
- "Either approach is reasonable."
|
||||
|
||||
## Color Coding for Visual Documents
|
||||
|
||||
**Strong Recommendations (Green Background)**:
|
||||
- RGB(0, 153, 76) or #009954
|
||||
- Clear visual priority
|
||||
- Use for Grade 1A, 1B
|
||||
|
||||
**Conditional Recommendations (Yellow Background)**:
|
||||
- RGB(255, 193, 7) or #FFC107
|
||||
- Indicates discussion needed
|
||||
- Use for Grade 2A, 2B, 2C
|
||||
|
||||
**Research/Investigational (Blue Background)**:
|
||||
- RGB(33, 150, 243) or #2196F3
|
||||
- Clinical trial consideration
|
||||
- Insufficient evidence for standard care
|
||||
|
||||
**Not Recommended (Red Border/Background)**:
|
||||
- RGB(220, 20, 60) or #DC143C
|
||||
- Strong recommendation against
|
||||
- Evidence of harm or no benefit
|
||||
|
||||
## Common Scenarios
|
||||
|
||||
### Scenario 1: Strong Evidence, Clear Benefit-Harm Balance
|
||||
|
||||
**Example**: Pembrolizumab for PD-L1 ≥50% NSCLC
|
||||
|
||||
- Evidence: Large phase 3 RCT (KEYNOTE-024), n=305, well-designed
|
||||
- Results: PFS HR 0.50 (0.37-0.68), OS HR 0.60 (0.41-0.89)
|
||||
- Toxicity: Lower grade 3-5 AEs than chemotherapy (27% vs 53%)
|
||||
- Patient values: Most prioritize efficacy and tolerability
|
||||
|
||||
**Recommendation**: STRONG FOR (Grade 1A)
|
||||
|
||||
### Scenario 2: Moderate Evidence, Balanced Trade-Offs
|
||||
|
||||
**Example**: Adjuvant immunotherapy for resected melanoma
|
||||
|
||||
- Evidence: RCT showing relapse-free survival benefit, OS data immature
|
||||
- Results: Recurrence risk reduced but ongoing toxicity
|
||||
- Toxicity: Immune-related AEs requiring steroids (some severe)
|
||||
- Cost: High annual cost for 12 months treatment
|
||||
- Patient values: Variable (some prioritize recurrence prevention, others avoid toxicity)
|
||||
|
||||
**Recommendation**: CONDITIONAL FOR (Grade 2B)
|
||||
|
||||
### Scenario 3: Low Evidence, but Severe Consequence
|
||||
|
||||
**Example**: Anticoagulation for prosthetic heart valve
|
||||
|
||||
- Evidence: No RCTs (would be unethical), observational data and mechanistic reasoning
|
||||
- Consequence: Very high thromboembolic risk without anticoagulation
|
||||
- Benefit-harm: Clear despite low quality evidence
|
||||
|
||||
**Recommendation**: STRONG FOR (Grade 1C)
|
||||
|
||||
### Scenario 4: High Evidence, but Patient Preferences Vary
|
||||
|
||||
**Example**: Breast reconstruction after mastectomy
|
||||
|
||||
- Evidence: High-quality data on outcomes and satisfaction
|
||||
- Trade-offs: Cosmetic benefit vs additional surgery, recovery time
|
||||
- Values: Highly personal decision, wide preference variability
|
||||
|
||||
**Recommendation**: CONDITIONAL (Grade 2A) - discuss options, patient decides
|
||||
|
||||
## Documentation Template
|
||||
|
||||
```
|
||||
RECOMMENDATION: [State recommendation clearly]
|
||||
|
||||
Strength: [STRONG / CONDITIONAL]
|
||||
Quality of Evidence: [HIGH / MODERATE / LOW / VERY LOW]
|
||||
GRADE: [1A / 1B / 2A / 2B / 2C]
|
||||
|
||||
Evidence Summary:
|
||||
- Primary study: [Citation]
|
||||
- Design: [RCT / Observational / Meta-analysis]
|
||||
- Sample size: n = [X]
|
||||
- Results: [Primary outcome with effect size, CI, p-value]
|
||||
- Quality assessment: [Strengths and limitations]
|
||||
|
||||
Benefits:
|
||||
- [Quantified benefit 1]
|
||||
- [Quantified benefit 2]
|
||||
|
||||
Harms:
|
||||
- [Quantified harm 1]
|
||||
- [Quantified harm 2]
|
||||
|
||||
Balance: [Benefits clearly outweigh harms / Close balance requiring discussion / etc.]
|
||||
|
||||
Values and Preferences: [Little variability / Substantial variability]
|
||||
|
||||
Cost Considerations: [If relevant]
|
||||
|
||||
Guideline Concordance:
|
||||
- NCCN: [Category and recommendation]
|
||||
- ASCO: [Recommendation]
|
||||
- ESMO: [Grade and recommendation]
|
||||
```
|
||||
|
||||
## Quality Checklist
|
||||
|
||||
Before finalizing recommendations, verify:
|
||||
|
||||
- [ ] Recommendation statement is clear and actionable
|
||||
- [ ] Strength is explicitly stated (strong vs conditional)
|
||||
- [ ] Quality of evidence is graded (high/moderate/low/very low)
|
||||
- [ ] GRADE notation provided (1A, 1B, 2A, 2B, 2C)
|
||||
- [ ] Evidence is cited with specific study results
|
||||
- [ ] Benefits are quantified (effect sizes with CIs)
|
||||
- [ ] Harms are quantified (AE rates)
|
||||
- [ ] Balance of benefits/harms is explained
|
||||
- [ ] Patient values consideration is addressed (if conditional)
|
||||
- [ ] Alternative options are mentioned
|
||||
- [ ] Guideline concordance is documented
|
||||
- [ ] Special populations are addressed (elderly, renal/hepatic impairment)
|
||||
- [ ] Monitoring requirements are specified
|
||||
|
||||
@@ -0,0 +1,529 @@
|
||||
\documentclass[10pt,letterpaper]{article}
|
||||
|
||||
% Packages
|
||||
\usepackage[margin=0.5in]{geometry}
|
||||
\usepackage[utf8]{inputenc}
|
||||
\usepackage[T1]{fontenc}
|
||||
\usepackage{helvet}
|
||||
\renewcommand{\familydefault}{\sfdefault}
|
||||
\usepackage{xcolor}
|
||||
\usepackage{tcolorbox}
|
||||
\usepackage{array}
|
||||
\usepackage{tabularx}
|
||||
\usepackage{booktabs}
|
||||
\usepackage{enumitem}
|
||||
\usepackage{titlesec}
|
||||
\usepackage{fancyhdr}
|
||||
\usepackage{multicol}
|
||||
\usepackage{graphicx}
|
||||
\usepackage{tikz}
|
||||
\usetikzlibrary{shapes,arrows,positioning}
|
||||
|
||||
% Color definitions
|
||||
\definecolor{headerblue}{RGB}{0,102,204}
|
||||
\definecolor{stronggreen}{RGB}{0,153,76}
|
||||
\definecolor{conditionalyellow}{RGB}{255,193,7}
|
||||
\definecolor{researchblue}{RGB}{33,150,243}
|
||||
\definecolor{warningred}{RGB}{204,0,0}
|
||||
\definecolor{highlightgray}{RGB}{240,240,240}
|
||||
|
||||
% Section formatting - compact
|
||||
\titleformat{\section}{\normalfont\fontsize{11}{12}\bfseries\color{headerblue}}{\thesection}{0.5em}{}
|
||||
\titlespacing*{\section}{0pt}{4pt}{2pt}
|
||||
|
||||
\titleformat{\subsection}{\normalfont\fontsize{10}{11}\bfseries}{\thesubsection}{0.5em}{}
|
||||
\titlespacing*{\subsection}{0pt}{3pt}{1pt}
|
||||
|
||||
% List formatting - ultra compact
|
||||
\setlist[itemize]{leftmargin=*,itemsep=0pt,parsep=0pt,topsep=1pt}
|
||||
\setlist[enumerate]{leftmargin=*,itemsep=0pt,parsep=0pt,topsep=1pt}
|
||||
|
||||
% Remove paragraph indentation
|
||||
\setlength{\parindent}{0pt}
|
||||
\setlength{\parskip}{2pt}
|
||||
|
||||
% Header/footer
|
||||
\pagestyle{fancy}
|
||||
\fancyhf{}
|
||||
\fancyhead[L]{\footnotesize \textbf{Treatment Recommendations: [CONDITION]}}
|
||||
\fancyhead[R]{\footnotesize Page \thepage}
|
||||
\renewcommand{\headrulewidth}{0.5pt}
|
||||
\fancyfoot[C]{\footnotesize Evidence-Based Clinical Guideline - For Professional Use Only}
|
||||
|
||||
\begin{document}
|
||||
|
||||
% Title block
|
||||
\begin{center}
|
||||
{\fontsize{14}{16}\selectfont\bfseries\color{headerblue} EVIDENCE-BASED TREATMENT RECOMMENDATIONS}\\[2pt]
|
||||
{\fontsize{12}{14}\selectfont\bfseries [Disease/Condition - e.g., HER2+ Metastatic Breast Cancer]}\\[2pt]
|
||||
{\fontsize{10}{12}\selectfont [Institution/Organization]}\\[1pt]
|
||||
{\fontsize{9}{11}\selectfont Version X.X | Effective Date: [Date] | Next Review: [Date]}
|
||||
\end{center}
|
||||
|
||||
\vspace{4pt}
|
||||
|
||||
% Recommendation Strength Legend
|
||||
\begin{tcolorbox}[colback=highlightgray,colframe=black,title=\textbf{Recommendation Strength Key},fonttitle=\bfseries\small,coltitle=black]
|
||||
{\small
|
||||
\begin{itemize}
|
||||
\item \colorbox{stronggreen!30}{\textbf{STRONG (Grade 1)}} - Benefits clearly outweigh risks; most patients should receive intervention
|
||||
\item \colorbox{conditionalyellow!30}{\textbf{CONDITIONAL (Grade 2)}} - Trade-offs exist; shared decision-making essential
|
||||
\item \colorbox{researchblue!30}{\textbf{RESEARCH (Grade R)}} - Insufficient evidence; clinical trial enrollment preferred
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Evidence Quality}: \textbf{A} = High (RCTs), \textbf{B} = Moderate (RCTs with limitations), \textbf{C} = Low (observational), \textbf{D} = Very low (expert opinion)
|
||||
}
|
||||
\end{tcolorbox}
|
||||
|
||||
\vspace{2pt}
|
||||
|
||||
\section{Clinical Context}
|
||||
|
||||
\subsection{Disease Overview}
|
||||
|
||||
[Brief description of disease state, epidemiology, natural history]
|
||||
|
||||
\subsection{Patient Population}
|
||||
|
||||
\textbf{Target Population}:
|
||||
\begin{itemize}
|
||||
\item [Demographic characteristics - e.g., Adults $\geq$18 years]
|
||||
\item [Disease stage/severity - e.g., Metastatic disease, Stage IV]
|
||||
\item [Biomarker status - e.g., HER2-positive (IHC 3+ or FISH+)]
|
||||
\item [Performance status - e.g., ECOG 0-2]
|
||||
\item [Line of therapy - e.g., First-line, previously untreated]
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Exclusions}:
|
||||
\begin{itemize}
|
||||
\item [Contraindications to recommended therapies]
|
||||
\item [Comorbidities affecting eligibility]
|
||||
\end{itemize}
|
||||
|
||||
\section{Evidence Review}
|
||||
|
||||
\subsection{Key Clinical Trials}
|
||||
|
||||
\textbf{[Trial Name 1]} (Author, Journal Year):
|
||||
\begin{itemize}
|
||||
\item \textbf{Design}: Phase 3 RCT, n=XXX, [Treatment A] vs [Treatment B]
|
||||
\item \textbf{Population}: [Key eligibility criteria]
|
||||
\item \textbf{Primary Endpoint}: [Outcome] - XX vs XX months (HR X.XX, 95\% CI X.XX-X.XX, p<X.XXX)
|
||||
\item \textbf{Secondary Endpoints}: [Additional outcomes]
|
||||
\item \textbf{Safety}: Grade 3-4 AEs XX\% vs XX\%
|
||||
\item \textbf{Quality}: \textbf{High} (low risk of bias, adequate power, intention-to-treat analysis)
|
||||
\end{itemize}
|
||||
|
||||
\textbf{[Trial Name 2]} (Author, Journal Year):
|
||||
\begin{itemize}
|
||||
\item \textbf{Design}: Phase 3 RCT, n=XXX, [Treatment C] vs [Standard of care]
|
||||
\item \textbf{Primary Endpoint}: [Outcome and results]
|
||||
\item \textbf{Quality}: \textbf{Moderate} (some limitations)
|
||||
\end{itemize}
|
||||
|
||||
\subsection{Guideline Concordance}
|
||||
|
||||
\begin{table}[H]
|
||||
\centering
|
||||
\small
|
||||
\begin{tabular}{lll}
|
||||
\toprule
|
||||
\textbf{Guideline} & \textbf{Recommendation} & \textbf{Evidence Level} \\
|
||||
\midrule
|
||||
NCCN vX.XXXX & [Specific recommendation] & Category 1 (preferred) \\
|
||||
ASCO Year & [Recommendation] & Strong, Evidence A \\
|
||||
ESMO Year & [Recommendation] & Grade I, A \\
|
||||
\bottomrule
|
||||
\end{tabular}
|
||||
\caption{Major guideline recommendations}
|
||||
\end{table}
|
||||
|
||||
\section{Treatment Options}
|
||||
|
||||
\subsection{First-Line Therapy}
|
||||
|
||||
\begin{tcolorbox}[enhanced,colback=stronggreen!10,colframe=stronggreen,
|
||||
title={\textbf{Option 1: [Regimen Name]} \hfill \colorbox{white}{\textbf{STRONG (1A)}}},
|
||||
fonttitle=\bfseries\small,coltitle=black]
|
||||
{\small
|
||||
\textbf{Regimen}:
|
||||
\begin{itemize}
|
||||
\item [Drug A]: XX mg [IV/PO] [schedule]
|
||||
\item [Drug B]: XX mg [IV/PO] [schedule]
|
||||
\item Cycle length: XX days
|
||||
\item Duration: Until progression or unacceptable toxicity
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Evidence Basis}:
|
||||
\begin{itemize}
|
||||
\item Primary study: [Trial name], n=XXX
|
||||
\item Primary outcome: [Endpoint] XX vs XX months (HR X.XX, p<X.XXX)
|
||||
\item ORR: XX\% vs XX\% (control)
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Indications}:
|
||||
\begin{itemize}
|
||||
\item [Biomarker-defined population or all patients]
|
||||
\item [Performance status requirement]
|
||||
\item [Organ function requirements]
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Key Toxicities}:
|
||||
\begin{itemize}
|
||||
\item Grade 3-4 AEs: XX\%
|
||||
\item Common: [List 3-5 most common AEs with incidence]
|
||||
\item Serious: [SAEs, discontinuation rate]
|
||||
\item Management: [Key mitigation strategies]
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Monitoring}:
|
||||
\begin{itemize}
|
||||
\item Labs: [Specific tests, frequency]
|
||||
\item Imaging: Every [X weeks] (RECIST v1.1)
|
||||
\item Clinical assessment: Every cycle
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Recommendation Strength}: \textbf{STRONG} - Benefits clearly outweigh risks\\
|
||||
\textbf{Evidence Quality}: \textbf{HIGH} - Well-designed RCT with consistent results
|
||||
}
|
||||
\end{tcolorbox}
|
||||
|
||||
\vspace{3pt}
|
||||
|
||||
\begin{tcolorbox}[enhanced,colback=conditionalyellow!10,colframe=conditionalyellow,
|
||||
title={\textbf{Option 2: [Alternative Regimen]} \hfill \colorbox{white}{\textbf{CONDITIONAL (2B)}}},
|
||||
fonttitle=\bfseries\small,coltitle=black]
|
||||
{\small
|
||||
\textbf{Regimen}: [Dosing details]
|
||||
|
||||
\textbf{Evidence Basis}: [Moderate-quality evidence or specific population subset]
|
||||
|
||||
\textbf{Indications}: [When to consider this option - e.g., patient preference for oral therapy, specific contraindication to Option 1]
|
||||
|
||||
\textbf{Trade-offs}:
|
||||
\begin{itemize}
|
||||
\item Advantages: [e.g., Oral administration, better tolerability]
|
||||
\item Disadvantages: [e.g., Lower response rate, less survival benefit]
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Recommendation Strength}: \textbf{CONDITIONAL} - Patient values important in decision\\
|
||||
\textbf{Evidence Quality}: \textbf{MODERATE} - Some limitations in evidence base
|
||||
}
|
||||
\end{tcolorbox}
|
||||
|
||||
\vspace{3pt}
|
||||
|
||||
\begin{tcolorbox}[enhanced,colback=researchblue!10,colframe=researchblue,
|
||||
title={\textbf{Option 3: Clinical Trial} \hfill \colorbox{white}{\textbf{RESEARCH (R)}}},
|
||||
fonttitle=\bfseries\small,coltitle=black]
|
||||
{\small
|
||||
\textbf{Recommendation}: Consider clinical trial enrollment for [specific scenario - e.g., biomarker-selected patients, refractory disease]
|
||||
|
||||
\textbf{Available Trials}: [List relevant trials if known, or state "ClinicalTrials.gov search"]
|
||||
|
||||
\textbf{Rationale}: [Why clinical trial appropriate - e.g., novel mechanism, unmet medical need, investigational biomarker]
|
||||
}
|
||||
\end{tcolorbox}
|
||||
|
||||
\subsection{Second-Line and Beyond}
|
||||
|
||||
\textbf{At Progression on First-Line Therapy}:
|
||||
|
||||
\begin{itemize}
|
||||
\item \textbf{Biomarker Re-Testing}: [If applicable - e.g., liquid biopsy for resistance mutations]
|
||||
\item \textbf{Second-Line Options}:
|
||||
\begin{itemize}
|
||||
\item Preferred: [Regimen] (Evidence level)
|
||||
\item Alternative: [Regimen] (Evidence level)
|
||||
\end{itemize}
|
||||
\item \textbf{Third-Line Options}: [Subsequent therapy options]
|
||||
\end{itemize}
|
||||
|
||||
\section{Special Populations}
|
||||
|
||||
\subsection{Elderly Patients ($\geq$70 years)}
|
||||
|
||||
\textbf{Considerations}:
|
||||
\begin{itemize}
|
||||
\item Geriatric assessment recommended (G8 screening tool)
|
||||
\item Dose reductions: [Specific adjustments for frail patients]
|
||||
\item Monitoring: More frequent assessments for toxicity
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Regimen Modifications}:
|
||||
\begin{itemize}
|
||||
\item [Reduced-intensity regimens if appropriate]
|
||||
\item [Single-agent vs combination considerations]
|
||||
\end{itemize}
|
||||
|
||||
\subsection{Renal Impairment}
|
||||
|
||||
\begin{table}[H]
|
||||
\centering
|
||||
\footnotesize
|
||||
\begin{tabular}{lll}
|
||||
\toprule
|
||||
\textbf{eGFR (mL/min/1.73m²)} & \textbf{Category} & \textbf{Dose Adjustment} \\
|
||||
\midrule
|
||||
$\geq$60 & Normal/Mild & Standard dosing \\
|
||||
30-59 & Moderate & [Specific adjustment - e.g., Reduce 25\%] \\
|
||||
15-29 & Severe & [Specific adjustment - e.g., Reduce 50\% or avoid] \\
|
||||
<15 or dialysis & ESRD & [Use with caution or contraindicated] \\
|
||||
\bottomrule
|
||||
\end{tabular}
|
||||
\caption{Dose adjustments for renal impairment}
|
||||
\end{table}
|
||||
|
||||
\subsection{Hepatic Impairment}
|
||||
|
||||
[Similar table for hepatic dose adjustments using Child-Pugh class or bilirubin/transaminases]
|
||||
|
||||
\section{Clinical Decision Algorithm}
|
||||
|
||||
% Simple flowchart example - can be expanded with more complex TikZ
|
||||
\begin{center}
|
||||
\begin{tikzpicture}[node distance=1.8cm, auto,
|
||||
decision/.style={diamond, draw, fill=conditionalyellow!30, text width=4.5em, text centered, inner sep=1pt, font=\tiny},
|
||||
process/.style={rectangle, draw, fill=stronggreen!20, text width=5.5em, text centered, rounded corners, minimum height=2em, font=\tiny},
|
||||
terminal/.style={rectangle, draw, fill=highlightgray, text width=5.5em, text centered, rounded corners=6pt, minimum height=2em, font=\tiny},
|
||||
alert/.style={rectangle, draw=warningred, line width=1pt, fill=warningred!10, text width=5.5em, text centered, rounded corners, minimum height=2em, font=\tiny\bfseries},
|
||||
arrow/.style={thick,->,>=stealth}]
|
||||
|
||||
\node [terminal] (start) {[Disease] Diagnosis Confirmed};
|
||||
\node [decision, below of=start, node distance=1.8cm] (biomarker) {Biomarker\\ Positive?};
|
||||
\node [process, left of=biomarker, node distance=3.5cm] (optionA) {Targeted\\ Therapy};
|
||||
\node [process, right of=biomarker, node distance=3.5cm] (optionB) {Standard\\ Therapy};
|
||||
\node [terminal, below of=biomarker, node distance=2.5cm] (monitor) {Monitor Response\\ Every X weeks};
|
||||
|
||||
\draw [arrow] (start) -- (biomarker);
|
||||
\draw [arrow] (biomarker) -- node[above] {Yes} (optionA);
|
||||
\draw [arrow] (biomarker) -- node[above] {No} (optionB);
|
||||
\draw [arrow] (optionA) |- (monitor);
|
||||
\draw [arrow] (optionB) |- (monitor);
|
||||
\end{tikzpicture}
|
||||
\end{center}
|
||||
|
||||
{\footnotesize \textit{Figure 1: Simplified treatment selection algorithm. See detailed algorithm in references for complete decision pathway.}}
|
||||
|
||||
\section{Monitoring Protocol}
|
||||
|
||||
\subsection{On-Treatment Monitoring}
|
||||
|
||||
\begin{table}[H]
|
||||
\centering
|
||||
\footnotesize
|
||||
\begin{tabular}{lccl}
|
||||
\toprule
|
||||
\textbf{Assessment} & \textbf{Baseline} & \textbf{Frequency} & \textbf{Rationale} \\
|
||||
\midrule
|
||||
CBC with differential & $\checkmark$ & Before each cycle & Myelosuppression \\
|
||||
Comprehensive metabolic panel & $\checkmark$ & Before each cycle & Organ function \\
|
||||
[Specific biomarker] & $\checkmark$ & Every X cycles & [Reason] \\
|
||||
Imaging (CT chest/abd/pelvis) & $\checkmark$ & Every X weeks & Response assessment \\
|
||||
ECOG performance status & $\checkmark$ & Every visit & Functional status \\
|
||||
Toxicity assessment (CTCAE) & - & Every visit & Safety monitoring \\
|
||||
\bottomrule
|
||||
\end{tabular}
|
||||
\caption{Recommended monitoring schedule}
|
||||
\end{table}
|
||||
|
||||
\subsection{Dose Modification Guidelines}
|
||||
|
||||
\textbf{Hematologic Toxicity}:
|
||||
\begin{itemize}
|
||||
\item \textbf{ANC <1.0 or Platelets <75k}: Delay treatment, recheck weekly, dose reduce 20\% when recovered
|
||||
\item \textbf{ANC <0.5 or Platelets <50k}: Hold treatment, G-CSF support, dose reduce 25-40\%
|
||||
\item \textbf{Febrile neutropenia}: Hold, hospitalize, antibiotics, dose reduce 25\% when recovered
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Non-Hematologic Toxicity}:
|
||||
\begin{itemize}
|
||||
\item \textbf{Grade 2}: Continue with supportive care, consider dose modification if persistent
|
||||
\item \textbf{Grade 3}: Hold until $\leq$Grade 1, resume at reduced dose (20-25\% reduction)
|
||||
\item \textbf{Grade 4}: Discontinue treatment or hold pending recovery (case-by-case)
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Specific Toxicity Management}:
|
||||
\begin{itemize}
|
||||
\item \textbf{[Specific AE]}: [Management approach - e.g., Diarrhea Grade 3: Hold treatment, loperamide, hydration, resume at reduced dose when $\leq$Grade 1]
|
||||
\item \textbf{[Immune-related AE]}: [Management - e.g., Pneumonitis Grade 2+: Hold immunotherapy, corticosteroids, pulmonology consultation]
|
||||
\end{itemize}
|
||||
|
||||
\section{Treatment Recommendations by Clinical Scenario}
|
||||
|
||||
\subsection{Scenario 1: [Specific Clinical Situation]}
|
||||
|
||||
\begin{tcolorbox}[enhanced,colback=stronggreen!10,colframe=stronggreen,
|
||||
title={\textbf{RECOMMENDATION} \hfill \textbf{GRADE: 1A}},
|
||||
fonttitle=\bfseries\small,coltitle=black]
|
||||
{\small
|
||||
\textbf{We recommend} [specific intervention] for [patient population].
|
||||
|
||||
\textbf{Evidence}:
|
||||
\begin{itemize}
|
||||
\item [Primary supporting evidence with results]
|
||||
\item [Guideline concordance - NCCN, ASCO, ESMO]
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Benefits}: [Quantified improvements - e.g., 8.7-month PFS benefit, HR 0.46]
|
||||
|
||||
\textbf{Harms}: [Quantified risks - e.g., 15\% grade 3-4 immune-related AEs]
|
||||
|
||||
\textbf{Balance}: Benefits clearly outweigh harms for most patients
|
||||
}
|
||||
\end{tcolorbox}
|
||||
|
||||
\subsection{Scenario 2: [Alternative Clinical Situation]}
|
||||
|
||||
\begin{tcolorbox}[enhanced,colback=conditionalyellow!10,colframe=conditionalyellow,
|
||||
title={\textbf{RECOMMENDATION} \hfill \textbf{GRADE: 2B}},
|
||||
fonttitle=\bfseries\small,coltitle=black]
|
||||
{\small
|
||||
\textbf{We suggest} [intervention] for [patient population] who value [specific outcome].
|
||||
|
||||
\textbf{Evidence}: [Moderate-quality evidence summary]
|
||||
|
||||
\textbf{Trade-offs}:
|
||||
\begin{itemize}
|
||||
\item \textbf{Advantages}: [e.g., Oral administration, less frequent monitoring]
|
||||
\item \textbf{Disadvantages}: [e.g., Lower response rate, more out-of-pocket cost]
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Patient Values}: Substantial variability in how patients value outcomes; shared decision-making essential
|
||||
}
|
||||
\end{tcolorbox}
|
||||
|
||||
\section{Alternative Approaches}
|
||||
|
||||
\subsection{Non-Recommended Options}
|
||||
|
||||
\begin{tcolorbox}[enhanced,colback=warningred!10,colframe=warningred,
|
||||
title={\textbf{NOT RECOMMENDED}},
|
||||
fonttitle=\bfseries\small,coltitle=white,colbacktitle=warningred]
|
||||
{\small
|
||||
\textbf{[Intervention X]} is \textbf{not recommended} for [population].
|
||||
|
||||
\textbf{Reason}: [Evidence of harm, lack of benefit, or superior alternatives available]
|
||||
|
||||
\textbf{Evidence}: [Supporting data showing no benefit or harm]
|
||||
}
|
||||
\end{tcolorbox}
|
||||
|
||||
\section{Supportive Care}
|
||||
|
||||
\subsection{Symptom Management}
|
||||
|
||||
\begin{itemize}
|
||||
\item \textbf{Pain Control}: [Analgesic recommendations, WHO ladder]
|
||||
\item \textbf{Nausea Prevention}: [Antiemetics - e.g., 5-HT3 antagonists, NK1 antagonists for highly emetogenic]
|
||||
\item \textbf{Bone Health}: [e.g., Bisphosphonates or denosumab if bone metastases]
|
||||
\item \textbf{Nutritional Support}: [Consult if weight loss >5\%, cachexia management]
|
||||
\item \textbf{Psychosocial Support}: [Depression screening, support groups, palliative care early integration]
|
||||
\end{itemize}
|
||||
|
||||
\subsection{Growth Factor Support}
|
||||
|
||||
\textbf{G-CSF Prophylaxis}:
|
||||
\begin{itemize}
|
||||
\item \textbf{Primary prophylaxis}: If febrile neutropenia risk $\geq$20\%
|
||||
\item \textbf{Secondary prophylaxis}: After prior febrile neutropenia episode
|
||||
\item Agent: [Pegfilgrastim 6 mg SC day 2 or filgrastim 5 mcg/kg SC daily days 3-10]
|
||||
\end{itemize}
|
||||
|
||||
\section{Follow-Up and Surveillance}
|
||||
|
||||
\subsection{During Active Treatment}
|
||||
|
||||
[Schedule outlined in Monitoring Protocol section above]
|
||||
|
||||
\subsection{Post-Treatment Surveillance}
|
||||
|
||||
\begin{table}[H]
|
||||
\centering
|
||||
\footnotesize
|
||||
\begin{tabular}{lccc}
|
||||
\toprule
|
||||
\textbf{Time Period} & \textbf{Imaging} & \textbf{Labs} & \textbf{Clinical Visits} \\
|
||||
\midrule
|
||||
Year 1 & Every 3 months & Every 3 months & Every 3 months \\
|
||||
Year 2 & Every 3-4 months & Every 3-4 months & Every 3-4 months \\
|
||||
Years 3-5 & Every 6 months & Every 6 months & Every 6 months \\
|
||||
Year 5+ & Annually & Annually & Annually \\
|
||||
\bottomrule
|
||||
\end{tabular}
|
||||
\caption{Post-treatment surveillance schedule (adjust based on risk of recurrence)}
|
||||
\end{table}
|
||||
|
||||
\section{Clinical Trial Opportunities}
|
||||
|
||||
\textbf{When to Consider Clinical Trials}:
|
||||
\begin{itemize}
|
||||
\item After progression on standard therapies
|
||||
\item High-risk disease with poor prognosis on standard therapy
|
||||
\item Novel biomarker potentially predictive of response
|
||||
\item Patient preference for investigational approach
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Resources}:
|
||||
\begin{itemize}
|
||||
\item ClinicalTrials.gov search: [Specific keywords]
|
||||
\item [Institution] clinical trials office: [Contact information]
|
||||
\end{itemize}
|
||||
|
||||
\section{Shared Decision-Making}
|
||||
|
||||
\subsection{Key Discussion Points}
|
||||
|
||||
\textbf{Goals of Care}:
|
||||
\begin{itemize}
|
||||
\item Curative intent vs prolonged disease control vs palliation
|
||||
\item Quality of life vs quantity of life trade-offs
|
||||
\item Functional independence goals
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Treatment Options Counseling}:
|
||||
\begin{itemize}
|
||||
\item Expected benefits (median survival, response rates)
|
||||
\item Potential harms (toxicity profile, quality of life impact)
|
||||
\item Treatment schedule and logistics (frequency of visits, IV vs oral)
|
||||
\item Financial considerations (out-of-pocket costs, time off work)
|
||||
\end{itemize}
|
||||
|
||||
\textbf{Decision Aids}:
|
||||
\begin{itemize}
|
||||
\item Number Needed to Treat: [e.g., Treat X patients to prevent 1 progression event]
|
||||
\item Survival benefit visualization: [X-month improvement in median survival]
|
||||
\end{itemize}
|
||||
|
||||
\section{References}
|
||||
|
||||
\begin{enumerate}
|
||||
\item [Primary clinical trial reference]
|
||||
\item [Secondary supporting trial]
|
||||
\item [NCCN Guidelines, version]
|
||||
\item [ASCO/ESMO Guideline reference]
|
||||
\item [Meta-analysis or systematic review if applicable]
|
||||
\item [Biomarker validation reference]
|
||||
\end{enumerate}
|
||||
|
||||
\vspace{10pt}
|
||||
|
||||
\hrule
|
||||
\vspace{4pt}
|
||||
{\footnotesize
|
||||
\textbf{Guideline Development Committee}:\\
|
||||
[Names and titles of committee members, affiliations]
|
||||
|
||||
\textbf{Evidence Review Date}: [Date]\\
|
||||
\textbf{Guideline Effective Date}: [Date]\\
|
||||
\textbf{Next Scheduled Review}: [Date] (or earlier if practice-changing evidence published)
|
||||
|
||||
\textbf{Conflicts of Interest}: [None / See disclosure statements]
|
||||
|
||||
\textbf{Methodology}: GRADE framework for evidence evaluation and recommendation development. Systematic literature review conducted [date range]. Guidelines concordance checked with NCCN, ASCO, ESMO current versions.
|
||||
|
||||
\textbf{For Questions}: Contact [Name], [Title] at [Email/Phone]
|
||||
}
|
||||
|
||||
\end{document}
|
||||
|
||||
Reference in New Issue
Block a user