Novel Application of a Dynamic, In-room Survey Platform to Measure Surgical Team Satisfaction.

OBJECTIVE: To elucidate the potential usage of continuous feedback regarding team satisfaction and correlations with operative performance and patient outcomes. BACKGROUND: Continuous, actionable assessment of teamwork quality in the operating room (OR) is challenging. This work introduces a novel, data-driven approach to prospectively and dynamically assess health care provider satisfaction with teamwork in the OR. METHODS: Satisfaction with teamwork quality for each case was assessed utilizing a validated prompt displayed on HappyOrNot Terminals placed in all ORs, with separate panels for circulators, scrub nurses, surgeons, and anesthesia providers. Responses were cross-referenced with OR log data, team familiarity indicators, efficiency parameters, and patient safety indicator events through continuous, semiautomated data marts. Deidentified responses were analyzed through logistic regression modeling. RESULTS: Over a 24-week period, 4123 responses from 2107 cases were recorded. The overall response rate per case was 32.5%. Greater scrub nurse specialty experience was strongly associated with satisfaction (odds ratio: 2.15, 95% CI: 1.53-3.03, P < 0.001). Worse satisfaction was associated with longer than expected procedure time (odds ratio: 0.91, 95% CI: 0.82-1.00, P = 0.047), nighttime (0.67, 95% CI: 0.55-0.82, P < 0.001), and add-on cases (0.72, 95% CI: 0.60-0.86, P < 0.001). Higher material costs (22%, 95% CI: 6-37, P = 0.006) were associated with greater team satisfaction. Cases with superior teamwork ratings were associated with a 15% shorter length of hospital stay (95% CI: 4-25, P = 0.006). CONCLUSIONS: This study demonstrates the feasibility of a dynamic survey platform to report actionable health care provider satisfaction metrics in real-time. Team satisfaction is associated with modifiable team variables and some key operational outcomes. Leveraging qualitative measurements of teamwork as operational indicators may augment staff engagement and measures of performance.

Fragmentation of Care in Patients with Peritoneal Metastases Undergoing Cytoreductive Surgery.

BACKGROUND: The delivery of multimodal treatment at a high-volume center is known to optimize the outcomes of gastrointestinal malignancies. However, patients undergoing cytoreductive surgery (CRS) for peritoneal metastases often must 'fragment' their surgical and systemic therapeutic care between different institutions. We hypothesized that this adversely affects outcomes. PATIENTS AND METHODS: Adults undergoing CRS for colorectal or appendiceal adenocarcinoma at our institution between 2016 and 2022 were identified retrospectively and grouped by care network: 'coordinated care' patients received exclusively in-network systemic therapy, while 'fragmented care' patients received some systemic therapy from outside-network providers. Factors associated with fragmented care were also ascertained. Overall survival (OS) from CRS and systemic therapy-related serious adverse events (SAEs) were compared across the groups. RESULTS: Among 85 (80%) patients, 47 (55%) had colorectal primaries and 51 (60%) received fragmented care. Greater travel distance [OR 1.01 (CI 1.00-1.02), p = 0.02] and educational status [OR 1.04 (CI 1.01-1.07), p = 0.01] were associated with receiving fragmented care. OS was comparable between patients who received fragmented and coordinated care in the colorectal [32.5 months versus 40.8 months, HR 0.95 (CI 0.43-2.10), p = 0.89] and appendiceal [31.0 months versus 27.4 months, HR 1.17 (CI 0.37-3.74), p = 0.55] subgroups. The frequency of SAEs (7.8% versus 17.6%, p = 0.19) was also similar. CONCLUSIONS: There were no significant differences in survival or SAEs based on the networks of systemic therapy delivery. This suggests that patients undergoing CRS at a high-volume center may safely receive systemic therapy at outside-network facilities with comparable outcomes.

Venous Thromboembolism in Peritoneal Mesothelioma: Uncovering the Hidden Risk.

INTRODUCTION: Venous thromboembolism (VTE) is a common complication in patients with abdominal malignancies. Despite known associations between pleural mesothelioma and increased VTE risk, the characteristics of VTE in patients with peritoneal mesothelioma (PeM) remain undescribed. METHODS: Patients treated for PeM were retrospectively identified from our institutional database. The frequency of VTE was assessed and logistic regression modeling was employed to assess VTE risk factors. The association between VTE and overall survival was also ascertained. Recommended thromboprophylaxis for patients who underwent surgery at our institution comprised a single preoperative dose of prophylactic anticoagulation, followed by daily dosing for four weeks postoperatively. RESULTS: Among 120 PeM patients, 26 (21.7%) experienced VTE, including 19/91 (20.9%) surgical patients, 4/23 (17.4%) patients who received systemic therapy, and 3/6 (50%) patients who underwent observation (p = 0.21). Most events were symptomatic (n = 16, 62%) and were attributable to pulmonary emboli (n = 16, 62%). The 90-day postoperative VTE rate was 4.4% (4/91), including 1 of 60 patients who underwent index surgical intervention at our institution and 3 patients with surgery elsewhere. A low serum albumin concentration was associated with VTE in non-surgical patients (odds ratio 0.12, confidence interval [CI] 0.02-0.72; p = 0.03). No significant difference in overall survival was observed between patients with and without VTE (median 46.0 months [CI 24.9-67.0] vs. 55.0 months [CI 27.5-82.5]; hazard ratio 0.98 [CI 0.54-1.81], p = 0.98). CONCLUSIONS: A high risk of VTE was observed in PeM patients, warranting suspicion throughout the disease trajectory. Postoperative VTE rates were within acceptable limits with 4-week thromboprophylaxis.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: Where do we stand?

PLAIN LANGUAGE SUMMARY: Patients with colorectal cancer that has spread to the lining of the abdomen (peritoneum) benefit from surgery to remove all the cancer. The addition of certain types of intra-abdominal chemotherapy during surgery improves survival for select patients.

Operative Team Familiarity and Specialization at an Academic Medical Center.

OBJECTIVE: To propose a framework for quantification of surgical team familiarity. BACKGROUND: Operating room (OR) teamwork quality is associated with familiarity among team members and their individual specialization. We describe novel measures of OR team familiarity and specialty experience. METHODS: Surgeon-scrub (SS) and surgeon-circulator (SC) teaming scores, defined as the pair's proportion of interactions relative to the surgeon's total cases in the preceding 6 months were calculated between 2017 and 2021 at an academic medical center. Nurse service-line (SL) experience scores were defined as the proportion of a nurse's cases performed within the given specialty. SS, SC, and nurse-SL scores were analyzed by specialty, case urgency, robotic approach, and surgeon academic rank. Two-sample Kolmogorov-Smirnov tests were used to determine heterogeneity between distributions. RESULTS: A total of 37,364 operations involving 150 attending surgeons and 222 nurses were analyzed. Median SS and SC scores were 0.08 (interquartile range: 0.03-0.19) and 0.06 (interquartile range: 0.03-0.13), respectively. Higher margin SLs, senior faculty rank, elective, and robotic cases were associated with greater SS, SC, and nurse-SL scores ( P <0.001). CONCLUSIONS: These novel measures of teaming and specialization illustrate the low levels of OR team familiarity and objectively highlight differences that necessitate a deliberate evaluation of current OR scheduling practices.

Role of Tumor-informed Personalized Circulating Tumor DNA Assay in Informing Recurrence in Patients With Peritoneal Metastases From Colorectal and High-grade Appendix Cancer Undergoing Curative-intent Surgery.

OBJECTIVE: To investigate the role of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay in informing recurrence in patients with peritoneal metastases (PM) from colorectal (CRC) and high-grade appendix (HGA) cancer after curative cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). BACKGROUND: Over 50% of patients with CRC/HGA-PM recur after optimal CRS-HIPEC. The limited sensitivity of axial imaging and diagnostic biomarkers is a significant cause of delay in the detection of recurrence and initiation of further therapies. Plasma ctDNA has a promising role in monitoring response to treatment and/or recurrence after primary cancer resection. METHODS: Patients with CRC/HGA-PM who underwent curative CRS-HIPEC and serial postresection ctDNA assessments were included. Patients with rising postoperative ctDNA levels were compared with those with stable, undetectable ctDNA levels. Primary outcomes were the percentage of patients with recurrence and disease-free survival (DFS). Secondary outcomes were overall survival, ctDNA sensitivity, lead time, and performance of ctDNA compared with carcinoembryonic antigen. RESULTS: One hundred thirty serial postresection ctDNA assessments [median 4, interquartile range (IQR), 3 to 5] were performed in 33 patients (n = 13 CRC, n = 20 HGA) who underwent completeness of cytoreduction-0/1 CRS with a median follow-up of 13 months. Of the 19 patients with rising ctDNA levels, 90% recurred versus 21% in the stable ctDNA group (n = 14, < 0.001). Median DFS in the rising ctDNA cohort was 11 months (IQR, 6 to 12) and not reached in the stable ( P = 0.01). A rising ctDNA level was the most significant factor associated with DFS (hazard ratio: 3.67, 95% CI: 1.06-12.66, P = 0.03). The sensitivity and specificity of rising ctDNA levels in predicting recurrence were 85% and 84.6%, respectively. The median ctDNA lead time was 3 months (IQR, 1 to 4). Carcinoembryonic antigen was less sensitive (50%) than ctDNA. CONCLUSIONS: This study supports the clinical validity of serial ctDNA assessment as a strong prognostic biomarker in informing recurrence in patients with CRC/HGA-PM undergoing curative resection. It also holds promises for informing future clinical trial designs and further research.

PI3K Pathway Alterations in Peritoneal Metastases are Associated with Earlier Recurrence in Patients with Colorectal Cancer Undergoing Optimal Cytoreductive Surgery.

BACKGROUND: Colorectal cancer with peritoneal metastasis (CRC-PM) represents a biologically heterogeneous disease; yet little is known regarding the impact of tumor biology on survival outcomes following optimal cytoreductive surgery (CRS). We analyzed the frequency of alterations in cancer signaling pathways in patients with CRC-PM and their impact on recurrence-free survival (RFS) following optimal CRS. METHODS: Thirty-five consecutive CRC-PM patients who underwent optimal CRS/HIPEC and next generation sequencing of peritoneal metastases were included in the study. Alterations in eight cancer-related signaling pathways were analyzed: Wnt/APC, p53, RTK-RAS, PI3K, TGF-B, Notch, Myc, and cell cycle. The association of pathway alterations with RFS and OS following optimal cytoreduction was estimated using Cox proportional hazard modeling. RESULTS: The most frequently altered pathways were Wnt/APC (63%), p53 (63%), RTK-RAS (60%), and PI3K (23%). Among optimally cytoreduced patients with CRC-PM, PI3K pathway alterations were an independent predictor of worse RFS (hazard ratio 3.2, 95% confidence interval CI 1.3-8.3, p = 0.01) with a clinically meaningful impact on median months to recurrence (5 vs. 13 months, p = 0.02). Alterations in p53, Wnt, and RTK-RAS pathways were not significantly associated with a difference in RFS following CRS. Alterations in the four pathways were not associated with differences in OS following CRS (median OS was 50 (interquartile range 23-80) months). CONCLUSIONS: In patients with CRC-PM, PI3K pathway alterations are associated with earlier recurrence following optimal CRS, which may represent a distinct molecular subtype. This novel finding can tailor clinical trials by using PIK3CA-directed interventions to reduce risk of recurrence after optimal CRS.

Design and Implementation of a Learner-Centered Self-Paced Peritoneal Oncology Education Program.

BACKGROUND: Current educational programs for peritoneal surface malignancies (PSM) are unstructured and often target advanced learners. The authors describe the design and implementation of a structured, self-paced course at a high-volume PSM center. METHODS: In 2020, a learner-centered course was designed using the Canvas educational platform in consultation with the Center for Teaching at the University of Chicago. The course consisted of disease-site-specific modules, perioperative care pathways, in-built voluntary quizzes, and multimedia supplements for advanced learners. Trainees were provided access during the PSM service rotation, and engagement was compared across training levels by measuring the time spent online. RESULTS: Course design and management required 71 h between 2020 and 2022, with the majority of time spent in the design phase. During 3 years, 62 personnel (21 [34%] medical students, 28 [45%] residents, 8 [13%] staff, and 5 [8%] fellows) were assigned the course. The overall engagement rate was 83.9% (86% of medical students, 75% of residents, 100% of staff and fellows), and the median time spent online was 12.4 min/week (interquartile range [IQR], 2.1-53.0 min/week). Fourth-year medical students and clinical fellows spent more time online than other learners (73 min/week [IQR, 24.5-100 min/week] vs 13.3 min/week [IQR, 7.3-26.5 min/week]) (p = 0.001). CONCLUSIONS: The design and implementation of a PSM-specific course was feasible and sustainable using an online learning platform. Higher engagement was noted among invested learners. Non-technical factors for reduced engagement need to be ascertained further to improve the next iteration of this course.

Insurance Authorization Barriers in Patients Undergoing Cytoreductive Surgery and HIPEC.

BACKGROUND: Indications for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) exist across multiple histologies, but little data exist on the impact of insurance authorization on access to these therapies. Given the evolving role of CRS/HIPEC, we sought to characterize insurance approval and delays in patients undergoing these therapies. PATIENTS AND METHODS: A retrospective review was performed at a high-volume tertiary center of patients who received CRS/HIPEC from 2017 to 2021. Collected data included patient demographics, tumor histologic characteristics, insurance type, approval/denial history, and time to prior authorization approval. Descriptive statistics were performed. RESULTS: In total, 367 patients received CRS/HIPEC during the study period. They had a median age of 59 (IQR 49-67) years, 35% were male, and 76% were white. Of the patients requiring prior authorization, 14 of 104 (13%) patients were denied prior authorization and required appeal. Median time between authorization request and approval was 33 (IQR 28-36) days. These cases generated 410 insurance authorization requests, 94 (23%) of which were not initially approved and required appeal. The rate of upfront denial was 21.1% in patients with public insurance compared with 23.4% in patients with private insurance. Gastric cancer was the most common histology among denied cases (55%), followed by colorectal, appendiceal, and gynecologic malignancies. CONCLUSIONS: Despite the broadening indications for and data supporting CRS/HIPEC, a significant proportion of patients still face hurdles in attaining insurance approval and coverage for these therapies. Addressing barriers to insurance approval is imperative to decrease therapeutic delay and improve access to data-driven care.

A Systematic Review of Operative Team Familiarity on Metrics of Efficiency, Patient Outcomes, Cost, and Team Satisfaction.

OBJECTIVE: This study seeks to systematically review the current literature on how surgical team familiarity relates to metrics of operative efficiency. BACKGROUND: The operating room (OR) is a complex environment involving numerous multidisciplinary interactions that must interface precisely to achieve a successful outcome. METHODS: A systematic search of the PubMed database was prospectively registered in the National Institute for Health Research PROSPERO database (CRD 42020181046) and performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Exposure variable was team familiarity and outcome measures included operative efficiency, patient outcomes, costs, and/or team satisfaction. RESULTS: Of 1123 articles screened, 15 studies involving 24,340 operations met inclusion criteria. All studies were limited to an individual specialty, procedure, or both. The effects of more familiar teams were most pronounced in decreasing operative times [standardized mean difference of -0.51 (95% confidence interval: -1.00, -0.02), P =0.04], whereas the reported impacts on patient clinical outcomes, material waste, and team satisfaction were much more heterogenous. CONCLUSIONS: Improving OR team familiarity is associated with superior operative efficiency and may be associated with other favorable measures. Further inferences are limited by literature heterogeneity, yet could be a novel focus for improving OR performance.

Phase II Prospective, Open-Label Randomized Controlled Trial Comparing Standard of Care Chemotherapy With and Without Sequential Cytoreductive Interventions for Patients with Oligometastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor Deoxyribose Nucleic Acid (ctDNA) Levels.

BACKGROUND: Metastatic adenocarcinomas of foregut origin are aggressive and have limited treatment options, poor quality of life, and a dismal prognosis. A subset of such patients with limited metastatic disease might have favorable outcomes with locoregional metastasis-directed therapies. This study investigates the role of sequential cytoreductive interventions in addition to the standard of care chemotherapy in patients with oligometastatic foregut adenocarcinoma. METHODS: This is a single-center, phase II, open-label randomized clinical trial. Eligible patients include adults with synchronous or metachronous oligometastatic (metastasis limited to two sites and amenable for curative/ablative treatment) adenocarcinoma of the foregut without progression after induction chemotherapy and having undetectable ctDNA. These patients will undergo induction chemotherapy and will then be randomized (1:1) to either sequential curative intervention followed by maintenance chemotherapy versus routine continued chemotherapy. The primary endpoint is progression-free survival (PFS), and a total of 48 patients will be enrolled to detect an improvement in the median PFS in the intervention arm with a hazard ratio (HR) of 0.5 with 80% power and a one-sided alpha of 0.1. Secondary endpoints include disease-free survival (DFS) in the intervention arm, overall survival (OS), ctDNA conversion rate pre/post-induction chemotherapy, ctDNA PFS, PFS2, adverse events, quality of life, and financial toxicity. DISCUSSION: This is the first randomized study that aims to prospectively evaluate the efficacy and safety of surgical/ablative interventions in patients with ctDNA-negative oligometastatic adenocarcinoma of foregut origin post-induction chemotherapy. The results from this study will likely develop pertinent, timely, and relevant knowledge in oncology.

Implementation of a high-resolution, high-contrast magnetic resonance imaging protocol with extended delayed phases for peritoneal mesothelioma.

Background: Imaging of peritoneal malignancies using conventional cross-sectional imaging is challenging, but accurate assessment of peritoneal disease burden could guide better selection for definitive surgery. Here we demonstrate feasibility of high-resolution, high-contrast magnetic resonance imaging (MRI) of peritoneal mesothelioma and explore optimal timing for delayed post-contrast imaging. Methods: Prospective data from inpatients with malignant peritoneal mesothelioma (MPM), imaged with a novel MRI protocol, were analyzed. The new sequences augmenting the clinical protocol were (I) pre-contrast coronal high-resolution T2-weighted single-shot fast spin echo (COR hr T2w SSH FSE) of abdomen and pelvis; and (II) post-contrast coronal high-resolution three-dimensional (3D) T1-weighted modified Dixon (COR hr T1w mDIXON) of abdomen, acquired at five delay times, up to 20 min after administration of a double dose of contrast agent. Quantitative analysis of contrast enhancement was performed using linear regression applied to normalized signal in lesion regions of interest (ROIs). Qualitative analysis was performed by three blinded radiologists. Results: MRI exams from 14 participants (age: mean ± standard deviation, 60±12 years; 71% male) were analyzed. The rate of lesion contrast enhancement was strongly correlated with tumor grade (cumulative nuclear score) (r=-0.65, P<0.02), with 'early' delayed phase (12 min post-contrast) and 'late' delayed phase (19 min post-contrast) performing better for higher grade and lower grade tumors, respectively, in agreement with qualitative scoring of image contrast. Conclusions: High-resolution, high-contrast MRI with extended post-contrast imaging is a viable modality for imaging peritoneal mesothelioma. Multiple, extended (up to 20 min post-contrast) delayed phases are necessary for optimal imaging of peritoneal mesothelioma, depending on the grade of disease.

A population-based evaluation of tunica vaginalis mesothelioma: An analysis of the National Cancer Database.

PURPOSE: Primary mesothelioma of the tunica vaginalis (TVM) is a rare and poorly understood malignancy with insufficient population-level data to guide management decisions. MATERIALS AND METHODS: A retrospective analysis of TVM cases recorded in the National Cancer Database from 2004 to 2015 was performed. Cases were identified using International Classification of Diseases for Oncology histology codes. Associations between demographic, clinical and therapeutic factors were analyzed using Kaplan-Meier survival estimates for overall survival (OS) and Cox proportional hazard modeling. Propensity score matching for receipt of systemic chemotherapy was performed to assess the impact on OS. RESULTS: One hundred fifty-one men with a median age of 65 years (interquartile range [IQR] 51-78) were included. Median OS from diagnosis was 72.5 months (IQR 20.2-Not Reached [NR]) after a median follow up of 34.9 months. Multivariate analysis demonstrated an increased risk of death for patients in the fourth quartile of age (hazard ratio [HR] 5.57, 95% confidence interval [CI] 1.70-18.17, P = 0.004), those with biphasic or fibrous histology (HR 2.59, 95% CI 1.15-6.42, P = 0.04) and positive surgical margins (HR 3.27, 95% CI 1.61-6.63, P = 0.001). There was no significant difference in OS associated with receiving chemotherapy (P = 0.5) even after propensity score matching (P = 0.07). CONCLUSIONS: Margin-negative surgical resection is paramount to improving OS. There are insufficient data to recommend for or against adjuvant systemic chemotherapy or RT, although the limited available data does not suggest apparent benefit in terms of OS.

Early Integrated Palliative Care Within a Surgical Oncology Clinic.

Importance: Advance directive (AD) designation is an important component of advance care planning (ACP) that helps align care with patient goals. However, it is underutilized in high-risk surgical patients with cancer, and multiple barriers contribute to the low AD designation rates in this population. Objective: To assess the association of early palliative care integration with changes in AD designation among patients with cancer who underwent surgery. Design, Setting, and Participants: This cohort study was a retrospective analysis of a prospectively maintained registry of adult patients who underwent elective surgery for advanced abdominal and soft tissue malignant tumors at a surgical oncology clinic in a comprehensive cancer center with expertise in regional therapeutics between June 2016 and May 2022, with a median (IQR) postoperative follow-up duration of 27 (15-43) months. Data analysis was conducted from December 2022 to April 2023. Exposure: Integration of ACP recommendations and early palliative care consultations into the surgical workflow in 2020 using electronic health records (EHR), preoperative checklists, and resident education. Main Outcomes and Measures: The primary outcomes were AD designation and documentation. Multivariable logistic regression was performed to assess factors associated with AD designation and documentation. Results: Among the 326 patients (median [IQR] age 59 [51-67] years; 189 female patients [58.0%]; 243 non-Hispanic White patients [77.9%]) who underwent surgery, 254 patients (77.9%) designated ADs. The designation rate increased from 72.0% (131 of 182 patients) before workflow integration to 85.4% (123 of 144 patients) after workflow integration in 2020 (P = .004). The AD documentation rate did not increase significantly after workflow integration in 2020 (48.9% [89 of 182] ADs documented vs 56.3% [81 of 144] ADs documented; P = .19). AD designation was associated with palliative care consultation (odds ratio [OR], 41.48; 95% CI, 9.59-179.43; P < .001), palliative-intent treatment (OR, 5.12; 95% CI, 1.32-19.89; P = .02), highest age quartile (OR, 3.79; 95% CI, 1.32-10.89; P = .01), and workflow integration (OR, 2.05; 95% CI, 1.01-4.18; P = .048). Patients who self-identified as a race or ethnicity other than non-Hispanic White were less likely to have designated ADs (OR, 0.36; 95% CI, 0.17-0.76; P = .008). AD documentation was associated with palliative care consulation (OR, 4.17; 95% CI, 2.57- 6.77; P < .001) and the highest age quartile (OR, 2.41; 95% CI, 1.21-4.79; P = .01). Conclusions and Relevance: An integrated ACP initiative was associated with increased AD designation rates among patients with advanced cancer who underwent surgery. These findings demonstrate the feasibility and importance of modifying clinical pathways, integrating EHR-based interventions, and cohabiting palliative care physicians in the surgical workflow for patients with advanced care.

Measuring Healthcare Worker Satisfaction in the Operating Room.

MINI-ABSTRACT: This report highlights the efficacy of using a 5-point Likert scale to measure healthcare worker satisfaction in the operating room. This assessment is significant because it is a critical step in assessing a novel scheduling apparatus that hopes to improve team satisfaction, operative efficiency, and operating room waste.

A Systematic Review of Conversion to Resectability in Unresectable Metastatic Colorectal Cancer Chemotherapy Trials.

OBJECTIVES: Metastasectomy in patients with metastatic colorectal cancer (mCRC) confers a significant survival benefit. We hypothesized that conversion to resectability (C2R) correlates with superior overall survival (OS) in patients with unresectable mCRC. METHODS: A prospectively registered systematic review (PROSPERO CRD42015024104) of randomized clinical trials published after 2003 was conducted. Exposure of interest was C2R with a primary outcome of OS. Clinical trials were classified based on difference in C2R between study arms (<2%, 2% to 2.9%, ≥3%). Generalized estimating equations were used to measure associations while adjusting for multiple observations from the same trial. RESULTS: Of 2902 studies reviewed, 30 satisfied selection criteria (n=13,618 patients). Median C2R was 7.3% (interquartile range [IQR]: 5% to 12.9%), with maximum C2R in the FOLFOX/FOLFIRI+cetuximab arm (28.6%). The median difference in C2R between 2 arms of the same study was 2.3% (IQR: 1.3% to 3.4%) with a maximum difference of 15.4% seen in FOLFOX/FOLFIRI+cetuximab versus FOLFOX/FOLFIRI. Median OS for the entire patient cohort was 20.7 months (IQR: 18.9 to 22.7 mo), with a between group difference of 1.3 months (IQR: -1.2 to 3.6 mo). The median survival difference between the 2 study arms with <2% C2R difference was 0.8 months versus 1.6 months with ≥3% C2R rates . Increasing C2R had an incremental dose-effect response on OS ( P =0.021), and higher response rates correlated with C2R rates ( P =0.003). CONCLUSIONS: C2R occurs infrequently and variably in clinical trials enrolling patients with unresectable mCRC. Prioritization of chemotherapeutic agents that enhance C2R might improve OS of patients.