Predicting Disease Progression and/or Recurrence in Cancer

Study Overview
=================
Brief Summary
-----------------
This is a prospective study addressing the challenge of predicting disease progression and/or recurrence in patients diagnosed with metastatic colorectal, pancreatobiliary, or esophagogastric cancer that are receiving anti-cancer therapy.

Detailed Description
-----------------
This research study is evaluating how patient-reported outcomes (e.g. symptoms, quality of life) and biomarkers compare to standard of care clinical assessments such as imaging and tumor markers in predicting the clinical outcomes (e.g. disease progression and survival) in patient populations with colorectal, pancreatobiliary, or esophagogastric cancer that are receiving anti-cancer therapy Massachusetts General Hospital Cancer Center Patient reported outcomes will be collected through a series of self-administered questionnaires and blood draws will be used to obtain bio and tumor marker information. Information will also be collected from the participants electronic medical record. Tissue may be obtained for next-generation sequencing. The study will conclude after participants are no longer receiving anti-cancer therapies. It is expected that about 200 people will take part in this research study

Official Title
-----------------
Tumor Markers, Liquid Biopsies, and Patient Reported Outcomes in Metastatic Colorectal, Pancreas, Biliary, and Esophagogastric Cancers

Conditions
-----------------
Patient Reported Outcome Measures, Colorectal Cancer, Pancreatic Cancer, Biliary Tract Cancer, Esophageal Cancer, Metastatic Cancer, Disease Progression, Survival Analysis

Intervention / Treatment
-----------------
* Behavioral: Observational Cohort


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must have histologically confirmed colorectal, pancreatobiliary, or esophagogastric cancer. Diagnosed with metastatic disease Age > 18 years. Patients must be starting new line of anti-cancer therapy. Patient must be English-speaking. Exclusion Criteria Unwilling or unable to participate in the study Non-metastatic disease Not starting new anti-cancer treatment Cognitive issues interfering with ability to participate. Active, unstable, untreated serious mental illness interfering with ability to participate. Patient does not speak English.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Main Cohort<br>Patient-reported outcomes (e.g. symptoms, quality of life) and biomarkers compare to standard of care clinical assessments such as imaging and tumor markers in predicting the clinical outcomes (e.g. disease progression and survival) Prior to starting anti-cancer therapy and at subsequent designated visits (every one month) Collections include: Blood sample Questionnaires quality of life, mood, and symptoms Tissue may be obtained for next-generation sequencing. | Behavioral: Observational Cohort<br>* Patients will be followed by collecting clinical data, biospecimens, and quality of life assessment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Response at 1st Scan | The primary outcome is treatment response (RECIST 1.1) at first scan (>1 month post-treatment start). Both response status (PR vs SD or PD [including death]) and clinical benefit status (PR or SD vs PD [including death]) will be examined. Primary analyses will compare one month change from baseline in tumor markers, MAF of the selected clonal mutation in ctDNA, and PROs (symptoms, mood, and QOL) individually and a composite score in predicting response and clinical benefit (CB) at first scan. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Response at 1st Scan - Continuous Outcome | Change from baseline to one month for each variable (tumor markers [CEA, CA19-9], ctDNA, and PROs [symptoms, mood, QOL]) will be evaluated individually as a predictor of percent change in tumor measurements at first scan (RECIST 1.1). | 6 months | 
| Progression Free Survival - KMC | Estimate distributions of progression free survival using the Kaplan-Meier method. | 1 year | 
| Progression Free Survival - HR | Use Cox proportional hazards models to obtain hazard ratios for Progression Free Survival for change in tumor markers, ctDNA and PROs. | 1 year | 
| Overall Survival - KMC | Estimate distributions of overall survival using the Kaplan-Meier method. | 1 year | 
| Overall Survival - HR | Use Cox proportional hazards models to obtain hazard ratios for Overall Survival for change in tumor markers, ctDNA and PROs. | 1 year | 
| ROC Curves | The investigators will compare the predictive ability of change in tumor markers, ctDNA, and PROs in these models using time-dependent ROC curves evaluated at specific timepoints including 6 and 12 months. | 1 year | 
| PROs and Biomarkers as predictor of survival using cox proportional hazards model | The investigators will run multivariable Cox proportional hazards regression with purposeful selection of covariates to explore combinations of variables (change in tumor markers [CEA, CA19-9], ctDNA, and PROs [symptoms, mood, QOL]) as predictors of survival (PFS and OS). | 6 months | 
| Association between baseline PROs, biomarkers and tumor response | The investigators will look at correlations between baseline ctDNA levels, baseline tumor markers and baseline PRO assessments and tumor response. | 6 months | 
| Associations between baseline PROs, biomarkers, and 6-month survival outcomes | The investigators will look at correlations between baseline ctDNA levels, baseline tumor markers and baseline PRO assessments and 6-month survival outcomes (PFS, OS) | 6 months | 
| Sarcopenia Analysis | As an exploratory outcome the investigators will compare differences in demographic and clinical characteristics, PROs, and clinical outcomes, between patients with and without sarcopenia. | 1 year | 
| Skeletal Muscle Analyses | As an exploratory outcome the investigators will compare differences in demographic and clinical characteristics, PROs, and clinical outcomes, between patients by skeletal muscle index and density. | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Patient Reported Outcome Measures, Colorectal Cancer, Pancreatic Cancer, Biliary Tract Cancer, Esophageal Cancer, Metastatic Cancer, Disease Progression, Survival Analysis