Validating a tool to measure spiritual beliefs, needs and resources in serious illness: The I-SPIRIT.

BACKGROUND: Seriously ill patients rely on spiritual and existential beliefs to support coping and approach crucial treatment and healthcare decisions. Yet, we lack gold standard, validated approaches to gathering information on those spiritual beliefs. Therefore, we developed I-SPIRIT, a spiritual needs and beliefs inventory for those with serious illness (IIR-10-050). METHODS: In prior work to develop measure content, we interviewed a total of 74 participants: 20 patients (veterans with Stage IV cancer, CHF, COPD, ESRD), 19 caregivers, 14 chaplains, 10 social workers, 12 nurses, and 5 physicians. Using directed content analyses, we identified over 50 attributes of spiritual experience comprising five domains: overall importance of spirituality; affiliations and practices; impact on decisions; spiritual needs; and spiritual resources. We then translated these attributes into individual items with Likert response scales. In the quantitative validation of I-SPIRIT, we administered the instrument and a battery of comparison measures to 249 seriously ill veterans. The comparison measures captured general spiritual well-being, religious coping, and emotional functioning. Convergent and discriminant validity was examined with the FACIT-sp (faith, meaning, and purpose), BMMRS (religious/spirituality), POMS and PHQ-8 (emotional function), and FACT-G (quality of life). We administered the I-SPIRIT a week later, for test-retest reliability. RESULTS: Psychometric analyses yielded a final I-SPIRIT Tool including 30 items. Results demonstrated reliability and validity and yielded a tool with three main components: Spiritual Beliefs (seven items); Spiritual Needs (nine items); and Spiritual Resources (14 items). The Spiritual Beliefs items include key practices and affiliations, and impact of beliefs on healthcare. Higher levels of Spiritual Needs were associated with higher anxiety and depression. CONCLUSION: The I-Spirit measures relevance of spirituality, spiritual needs and spiritual resources and demonstrates validity, reliability, and acceptability for patients with serious illness.

Distance Traveled and Disparities in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: The impact of distance traveled on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) outcomes needs further investigation. METHODS: This retrospective study reviewed a prospectively managed single-center CRS/HIPEC 1992-2022 database. Zip codes were used to calculate distance traveled and to obtain data on income and education via census data. Patients were separated into three groups based on distance traveled in miles (local: ≤50 miles, regional: 51-99 miles, distant: ≥100 miles). Descriptive statistics, Kaplan-Meier method, and Cox regression were performed. RESULTS: The 1614 patients in the study traveled a median distance of 109.5 miles (interquartile range [IQR], 53.36-202.29 miles), with 23% traveling locally, 23.9% traveling regionally, and 53% traveling distantly. Those traveling distantly or regionally tended to be more white (distant: 87.8%, regional: 87.2%, local: 83.2%), affluent (distant: $61,944, regional: $65,014, local: $54,390), educated (% without high school diploma: distant: 10.6%, regional: 11.5%, local: 13.0%), less often uninsured (distant: 2.3%, regional: 4.6%, local: 5.2%) or with Medicaid (distant: 3.3%, regional: 1.3%, local: 9.7%). They more often had higher Peritoneal Carcinomatosis Index (PCI) scores (distant: 15.4, regional: 15.8, local: 12.7) and R2 resections (distant: 50.3%, regional: 52.2%, local: 40.5%). Median survival did not differ between the groups, and distance traveled was not a predictor of survival. CONCLUSION: More than 50% of the patients traveled farther than 100 miles for treatment. Although regionalization of CRS/HIPEC may be appropriate given the lack of survival difference based on distance traveled, those who traveled further had fewer health care disparities but higher PCI scores and more R2 resections, which raises concerns about access to care for the underserved, time to treatment, and surgical quality.

Quality-of-Life Outcomes for Patients Taking Opioids and Psychotropic Medications Before Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: The impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) on quality of life (QoL) for patients taking opioids and psychotropic medications preoperatively is unclear. METHODS: This study retrospectively reviewed a CRS-HIPEC single-center prospectively maintained database for 2012-2016. Demographics and clinical data on opioids/psychotropic medication use were collected via chart review. The study collected QoL outcomes at baseline, then 3, 6, and 12 months postoperatively via the Center for Epidemiologic Studies Depression Scale (CES-D), Brief Pain Inventory, Functional Assessment of Cancer Therapy, and 36-Item Short-Form Health Survey. Differences in QoL between the groups were calculated using repeated measures analysis of variance regression. Descriptive statistics and Kaplan-Meier analyses were performed. RESULTS: Of 388 patients, 44.8% were taking opioids/psychotropic medications preoperatively. At baseline, those taking opioids/psychotropic medications preoperatively versus those not taking these medications had significantly worse QoL. By 1 year postoperatively, the QoL measures did not differ significantly except for emotional functioning (e.g., no medications vs. opioids/psychotropic medications: CES-D, 5.6 vs. 10.1). Median survival did not differ significantly (opioids/psychotropic medications vs. no medications: 52.3 vs. 60.6 months; p = 0.66). At 1 year after surgery, a greater percentage of patients were taking opioids, psychotropic medications, or both than at baseline (63.2% vs. 44.8%; p < 0.001). CONCLUSION: Despite worse baseline QoL, patients who took opioids/psychotropic medications had QoL scores 1 year postoperatively similar to the scores of those who did not except in the emotional domains. These data point to the potential utility of a timed psychosocial intervention to enhance emotional adaptation and further support the role of CRS-HIPEC in improving QoL.

Team-Based Qualitative Rapid Analysis: Approach and Considerations for Conducting Developmental Formative Evaluation for Intervention Design.

Qualitative rapid analysis is one of many rapid research approaches that offer a solution to the problem of time constrained health services evaluations and avoids sacrificing the richness of qualitative data that is needed for intervention design. We describe modifications to an established team-based, rapid analysis approach that we used to rapidly collect and analyze semi-structured interview data for a developmental formative evaluation of a cardiovascular disease prevention intervention. Over 18 weeks, we conducted and analyzed 35 semi-structured interviews that were conducted with patients and health care providers in the Veterans Health Administration to identify targets for adapting the intervention in preparation for a clinical trial. We identified 12 key themes describing actionable targets for intervention modification. We highlight important methodological decisions that allowed us to maintain rigor when using qualitative rapid analysis for intervention adaptation and we provide practical guidance on the resources needed to execute similar qualitative studies. We additionally reflect on the benefits and challenges of the described approach when working within a remote research team environment.ClinicalTrials.gov: NCT04545489.

Pivotal Role of Genetic Counselors in the Uptake of Germline Genetic Testing in Non-Metastatic Breast Cancer and the Impact of Testing on Surgical Decision Making.

BACKGROUND: Genetic testing is increasingly utilized in breast cancer patients; however, testing rates remain low. We aimed to evaluate the rate of genetic testing at a tertiary academic medical center utilizing a multidisciplinary clinic model including genetic counselor. METHODS: A single-center retrospective chart review was performed on a cohort of newly diagnosed breast cancer patients from January 2018 through February 2019. Patients were reviewed for genetic screening eligibility, consultation with a genetic counselor, and test results. RESULTS: Final analysis included 426 patients. 261 (61.3%) were found to meet National Comprehensive Cancer Network guidelines for genetic testing, of which 178 patient (68.2%) underwent testing and 32 patients (12.3%) declined testing. Of the 165 not eligible for testing, 5 patients were tested. A total of 183 patients underwent testing and 116 (63.4%) had a negative result, 17 (9.3%) were positive for at least one gene mutation and 50 (27.3%) were identified to have a variant of unknown significance (VUS). There was a positive association between those patients who met with a genetic counselor and eligibility for testing (OR 31.1, 95% CI 16.0-60.5). CONCLUSIONS: Genetic testing result has become an increasingly important factor when defining optimal surgical treatment for breast cancer patients. Increasing the availability of genetic consultation for breast cancer patients can improve testing rates and patient selection.

Conditional Survival After Hepatectomy for Colorectal Liver Metastasis: Results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC).

INTRODUCTION: Complete resection of colorectal liver metastasis (CLM) improves long-term survival in colorectal cancer. However, there is limited recent data on conditional survival (CS) as postoperative survival milestones are achieved post-hepatectomy. METHODS: A retrospective analysis was performed on the penta-institutional Colorectal Liver Operative Metastasis International Collaborative (COLOMIC), with 906 consecutive CLM hepatectomy cases. CS was calculated using Bayes' theorem and Kaplan-Meier analysis. Additional CS analyses were performed on additional clinicopathologic risk factors, including colon cancer laterality, KRAS mutation status, and extrahepatic disease. RESULTS: The 5-year CS was 40.6%, 45.3%, 52.8%, and 65.3% at 0, 1, 2, and 3 years postoperatively, with significant improvements each year (p < 0.005). CS was not significantly different between right-sided and left-sided colorectal cancers by 3 years postoperatively. Patients with KRAS mutations had worse CS at all timepoints (p < 0.001). Extrahepatic disease was a poor prognostic factor for OS and CS (p < 0.001). However, CS for patients with KRAS mutations or extrahepatic disease improved significantly as 2-year, postoperative survival was achieved (p < 0.05). CONCLUSIONS: Five-year CS after hepatectomy for CLM improved with each passing year of survival postoperatively. Although extrahepatic disease and KRAS mutations are poor prognostic factors for OS, these populations still had improved CS after 2 years postoperatively.

Long-Term Survival in Patients Treated with Cytoreduction and Heated Intraperitoneal Chemotherapy for Peritoneal Mesothelioma at a Single High-Volume Center.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare diagnosis with a dismal prognosis if untreated. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is shown to significantly improve survival. Our institution is uniquely positioned to report long-term outcomes in MPM with CRS-HIPEC, due to our robust peritoneal surface disease program existing over the past three decades. METHODS: Our prospectively maintained, single-institution database of CRS-HIPEC cases was reviewed, identifying 111 consecutive patients with MPM over 28 years (1993-2021). Prognostic, operative, and pathologic factors were reviewed. Overall survival (OS) and conditional survival (CS) analyses were performed. RESULTS: The average age was 55.1 years; 58.6% of patients were male; 17 of 111 patients (15.3%) had a second CRS-HIPEC. At first CRS-HIPEC, the average PCI score was 18.7, and the perfusate drugs were platinum-based (72.1%) and mitomycin C (27.9%). The resection status at first CRS-HIPEC was R2a (46.4%), followed by R0-1 (29.1%), and R2b-c (24.5%). Median OS was 3.3 years for the entire cohort, with 75th and 25th percentiles at 10.7 months and 10.6 years. Median CS was improved if patients survived to the 1-year postoperative mark (4.9 years, p < 0.01) and trended toward further improvement with each passing year. If 3-year postoperative survival was achieved, the median CS improved to 6.1 years. CONCLUSIONS: This represents one of the largest and lengthiest, single-center, longitudinal, case series of peritoneal mesothelioma treated with CRS-HIPEC. The OS suggests efficacy for CRS-HIPEC for MPM. Long-term survival improves significantly after patients achieve the 1-year, postoperative mark.

Determinants of inter-organizational implementation success: A mixed-methods evaluation of Veteran Directed Care.

BACKGROUND: Veteran Directed Care (VDC) aims to keep Veterans at risk for nursing home placement in their communities. VA medical centers (VAMCs) purchase VDC from third-party organizational providers who then partner with them during implementation. Experiences with VDC implementation have varied. OBJECTIVES: We sought to identify conditions differentiating partnerships with higher enrollment (implementation success). METHODS: We conducted a case-based study with: qualitative data on implementation determinants two and eight months after program start, directed content analysis to assign numerical scores (-2 strong barrier to +2 strong facilitator), and mathematical modeling using Coincidence Analysis (CNA) to identify key determinants of implementation success. Cases consisted of VAMCs and partnering non-VAMC organizations who started VDC during 2017 or 2018. The Consolidated Framework for Implementation Research (CFIR) guided analysis. RESULTS: Eleven individual organizations within five partnerships constituted our sample. Two CFIR determinants- Networks & Communication and External Change Agent-uniquely and consistently identified implementation success. At an inter-organizational partnership level, Networks & Communications and External Change Agent +2 (i.e., present as strong facilitators) were both necessary and sufficient. At a within-organization level, Networks & Communication +2 was necessary but not sufficient for the non-VAMC providers, whereas External Change Agent +2 was necessary and sufficient for VAMCs. CONCLUSION: Networks & Communication and External Change Agent played difference-making roles in inter-organizational implementation success, which differ by type of organization and level of analysis. IMPLICATIONS: This multi-level approach identified crucial difference-making conditions for inter-organizational implementation success when putting a program into practice requires partnerships across multiple organizations.

Outcomes after repeat hepatectomy for colorectal liver metastases from the colorectal liver operative metastasis international collaborative (COLOMIC).

BACKGROUND: Resection of colorectal liver metastasis (CLM) is beneficial when feasible. However, the benefit of second hepatectomy for hepatic recurrence in CLM remains unclear. METHODS: The Colorectal Liver Operative Metastasis International Collaborative retrospectively examined 1004 CLM cases from 2000 to 2018 from a total of 953 patients. Hepatic recurrence after initial hepatectomy was identified in 218 patients. Kaplan-Meier analysis was performed for overall survival (OS) and recurrence-free survival (RFS). Propensity score matching (PSM) was performed to offset selection bias. Cox proportional-hazards regression was performed to identify risk factors associated with OS. RESULTS: A total of 51 patients underwent second hepatectomy. Unadjusted median OS was 60.1 months in repeat-hepatectomy versus 38.3 months in the single-hepatectomy group (p = 0.015). In the PSM population, median OS remained significantly better in the repeat-hepatectomy group (60.1 vs. 33.1 months; p = 0.0023); median RFS was 12.4 months for the repeat-hepatectomy group, versus 9.8 months in the single-hepatectomy group (p = 0.0050). Repeat hepatectomy was associated with lower risk of death (hazard ratio: 0.283; p = 0.000012). Obesity, tobacco use, and high intraoperative blood loss were associated with significant risk of death (p < 0.05). CONCLUSION: In CLM with hepatic recurrence, second hepatectomy was beneficial for OS. With PSM, the OS benefit of performing a second hepatectomy remained significant.

Association of primary tumor laterality with surgical outcomes for colorectal liver metastases: results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC).

BACKGROUND: Primary laterality of colorectal cancer is thought to be associated with differences in outcomes. Liver metastasis is the most common site of solitary colorectal cancer spread. However, how primary colorectal cancer laterality affects outcomes in colorectal liver metastasis remains unclear. METHODS: The Colorectal Liver Operative Metastasis International Collaborative (COLOMIC) of operative hepatectomy cases for colorectal liver metastasis was compiled from five participating institutions. This included consecutive cases from 2000 to 2018 at all sites. A total of 884 patients were included in this study. Univariate, multivariate, and Kaplan-Meier analyses were performed. RESULTS: Patients with left-sided versus right-sided cancers had significantly better overall survival: 49.4 vs. 41.8 months (p < 0.05). Patients with KRAS mutations had significantly worse median overall survival compared to KRAS wild-type (43.6 vs 56.1 months; p < 0.001). In left-sided cancers, KRAS mutations were associated with significantly worse median overall survival compared to KRAS wild-type cancers (43.6 vs 56.6 months; p < 0.01). This association was absent in patients with right-sided primary tumors. Multivariate Cox regression analysis revealed different variable sets (non-overlapping) were associated with overall survival, when comparing left-sided and right-sided cancers. CONCLUSION: Understanding how primary tumor laterality and related biological aspects affect long-term outcomes can potentially inform treatment decisions for patients with colorectal liver metastases.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Management of Colorectal Cancer with Peritoneal Dissemination: 30 Years of Experience at a Single Institution.

BACKGROUND: Cytoreductive surgery (CRS) is at the forefront of treatment for colorectal cancer with peritoneal metastasis or "carcinomatosis" (CRC-PC). We report outcomes of the operative management of CRC-PC at a single center. STUDY DESIGN: We retrospectively reviewed our database from 1992 through 2021. The Kaplan-Meier method was used to estimate survival. Proportional hazards regression and multivariable models were used for assessments. RESULTS: This study included 345 patients with mean age 53.5 years. Multivariate analysis revealed performance and resection status were associated with overall survival (OS; p < 0.001). Within the R0/R1 group, adverse impact on OS was found with increasing Peritoneal Cancer Index (PCI) score starting at 9 (hazard ratio [HR] = 1.98, CI 1.39-2.82, p = 0.0001) with the most significant hazard noted at PCI >14 (HR = 2.35, CI 1.52-3.63, p = 0.0001). Incomplete resection (R2) had significantly worse OS compared with complete CRS 33.4 (n = 206) vs R2: 12.7 months (n = 139; p < 0.0001. When stratified by PCI for the R0/R1 group, median OS for PCI less than 10, 10 to 15, and greater than 15 was 38.2, 19.7, and 22.2 m, respectively (p = 0.0007 comparing PCI less than 10 and greater than 15). Ten-year increments-1991 through 2000, 2001 through 2010, 2011 through 2020-revealed improvement in median OS (13.4 [n = 66], 19.3 [n = 139], and 29.1 months [n = 140]). However, by resection status, median OS remained stable for R0/R1 (32.3 [n = 23], 31.1 [n = 76], and 34.1 months [n = 107]) and improved for R2 (5.2 [n = 43], 14.4 [n = 63], and 14.6 months [n = 33]). Clavien-Dindo complication rate (greater than or equal to grade III) was 29.4%. CONCLUSION: CRS improves outcomes for CRC-PC compared with historic outcomes with nonoperative management. This benefit is greatest with complete resection and lower disease burden. Results of CRS (with or without heated intraperitoneal chemotherapy) are improving, and surgery for CRC-PC should be routinely considered.

Timing of Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Recurrent Low-Grade Appendiceal Mucinous Neoplasms.

BACKGROUND: Low-grade appendiceal mucinous neoplasm (LAMN) with peritoneal involvement is a common indication for cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC). With peritoneal recurrence, patients are increasingly being offered repeat CRS/HIPECs, however optimal timing for a second CRS/HIPEC remains unknown. METHODS: A prospectively maintained 30-year database at our high-volume HIPEC center was analyzed retrospectively for patients with LAMNs and peritoneal recurrence receiving one or two CRS/HIPECs. Kaplan-Meier survival analysis, linear regression modeling, and Cox proportional hazards regression analyses were performed. RESULTS: Overall, 143 patients with LAMNs who underwent CRS/HIPECs had confirmed postoperative peritoneal recurrence. Of these patients, 85 underwent one CRS/HIPEC and 58 underwent two CRS/HIPECs. The groups had significant differences in age, with younger patients more likely to undergo a second CRS/HIPEC (48.5 vs. 58.0 years; p < 0.001). The median overall survival (OS) for the group undergoing two CRS/HIPECs was approximately four times longer compared with the group undergoing one CRS/HIPEC (227.1 vs. 54.5 months; p < 0.0001). The time from recurrence to the second CRS/HIPEC was not significantly associated with OS from the time of the first operation. Instead, a shorter time between the first CRS/HIPEC and recurrence was significantly associated with shorter OS from the time of the first operation (p = 0.037). CONCLUSION: In peritoneal LAMNs with recurrence, receiving two CRS/HIPECs was associated with better OS compared with receiving one CRS/HIPEC. Longer time to recurrence was a good prognostic factor. Delay between recurrence and second CRS/HIPEC had no apparent impact on OS from the first CRS/HIPEC; thus, immediate or delayed reoperative intervention are both reasonable approaches.

Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Cancers with Peritoneal Metastasis: A 30-year Institutional Experience.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) improves survival in abdominal cancer patients with metastatic disease limited to the peritoneal cavity. Patients are increasingly being offered repeat CRS-HIPECs for peritoneal recurrence. However, in this rare clinical scenario, the survival benefit of performing repeat CRS-HIPEC operations remains unclear. METHODS: A retrospective review of the CRS-HIPEC database at Wake Forest Baptist Medical Center was performed over a 30-year timespan. From 1547 patients with appendix cancers, colorectal cancers, mesotheliomas, and other miscellaneous cancers, 156 received more than one CRS-HIPEC. Kaplan-Meier survival analysis was performed using overall survival (OS) from the time of surgery as the primary endpoint. Multi-variable Cox proportional hazards regression modelling was performed on pertinent clinical variables. RESULTS: Patients who received multiple CRS-HIPECs had significantly better median OS (10.7 years) versus those who received one CRS-HIPEC (2.5 years), with appendix cancers faring best (12.9 years). Resection status R2a or better was achieved in 76.4% of repeat CRS-HIPECs. There were no significant changes in complication rates after repeat CRS-HIPEC. On multivariate analysis of repeat CRS-HIPEC, patients with appendix and colorectal cancers, heart disease, and poor functional status were independently associated with poor OS. Factors not independently associated with OS were age, sex, body mass index, race, diabetes, lung disease, smoking history, and systemic chemotherapy between CRS-HIPECs. CONCLUSIONS: Performing multiple CRS-HIPEC operations on appropriate surgical candidates may significantly prolong survival. Appendix cancers derived the greatest benefit. Satisfactory resection margins and complication rates are comparable to first cases and achievable in repeat CRS-HIPEC procedures.

How can equitable video visit access be delivered in primary care? A qualitative study among rural primary care teams and patients.

OBJECTIVE: The COVID-19 pandemic sparked exponential growth in video visit use in primary care. The rapid shift to virtual from in-person care exacerbated digital access disparities across racial groups and rural populations. Moving forward, it is critical to understand when and how to incorporate video visits equitably into primary care. We sought to develop a novel clinical algorithm to guide primary care clinics on how and when to employ video visits as part of care delivery. DESIGN: Qualitative data collection: one team member conducted all patient semistructured interviews and led all focus groups with four other team members taking notes during groups. SETTING: 3 rural primary care clinics in the USA. PARTICIPANTS: 24 black veterans living in rural areas and three primary care teams caring for black veterans living in rural areas. PRIMARY AND SECONDARY OUTCOME MEASURES: Findings from semistructured interviews with patients and focus groups with primary care teams. RESULTS: Key issues around appropriate use of video visits for clinical teams included having adequate technical support, encouraging engagement during video visits and using video visits for appropriate clinical situations. Patients reported challenges with broadband access, inadequate equipment, concerns about the quality of video care, the importance of visit modality choice, and preferences for in-person care experience over virtual care. We developed an algorithm that requires input from both patients and their care team to assess fit for each clinical encounter. CONCLUSIONS: Informed matching of patients and clinical situations to the right visit modality, along with individual patient technology support could reduce virtual access disparities.

Coordinating assessment of spiritual needs: a cross-walk of narrative and psychometric assessment tools used in palliative care.

Addressing spiritual needs of patients in healthcare settings improves patient experiences and clinical outcomes; however, non-chaplain providers typically assess spiritual needs differently (quantitative psychometric) than healthcare chaplains (long form narrative) and thus there is little shared language or cross-disciplinary evaluation frameworks across disciplines. This discrepancy impedes the provision of both team-based and patient-centered care. This paper used scoping review methodology to illustrate the overlap between narrative and psychometric assessment tools, comparing four narrative tools against eight psychometric tools. The SpNQ-120 and Brief RCOPE demonstrated consistent domain coverage across the four chaplain narrative tools. This work provides preliminary resources to aid clinicians and researchers in choosing an appropriate tool. Additionally, for those who do not work closely with chaplains, it provides a sense of what domains chaplains prioritize, from their professional and lived experience, in assessing the spiritual life of the patient. This improves interdisciplinary communication, and therefore, patient care.

Patterns of peritoneal dissemination and response to systemic chemotherapy in common and rare peritoneal tumours treated by cytoreductive surgery: study protocol of a prospective, multicentre, observational study.

INTRODUCTION: Despite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery (CRS) for peritoneal metastases (PM). Apart from the Peritoneal Cancer Index (PCI), completeness of cytoreduction and tumour grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy (SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilisation of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilisation of these factors in clinical decision making and the extent of peritoneal resection performed for different tumours. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors. METHODS AND ANALYSIS: There is no therapeutic intervention in the study. All patients with biopsy-proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a prespecified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumour nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centres will be studied. ETHICS AND DISSEMINATION: The study protocol has been approved by the Zydus Hospital ethics committee (27 July, 2020) and Lyon-Sud ethics committee (A15-128). TRIAL REGISTRATION NUMBER: CTRI/2020/09/027709; Pre-results.

Prognostic Impact and Utility of Immunoprofiling in the Selection of Patients with Colorectal Peritoneal Carcinomatosis for Cytoreductive Surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND: Recent studies have shown an association in non-metastatic colorectal cancer between patient survival and immunoprofiling (expression of CD3, CD4, CD8, CD45, and FOXP3 T cells at the invasive margin (IM) and the tumor center (TC)) regardless of stage. Patients with peritoneal carcinomatosis have a dismal prognosis, but survival can be significantly improved in selected patients who undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, current patient selection for CRS/HIPEC is suboptimal. The purpose of this study is to evaluate immune profiles of patients with peritoneal carcinomatosis and their correlation with overall survival (OS). METHODS: The study cohort included patients from a prospectively maintained database of adults with colorectal peritoneal carcinomatosis who underwent CRS/HIPEC. Immunohistochemistry (IHC) using antibodies to CD3, CD4, CD8, CD45RO, and FOXP3 T cells was performed. IHC image density was calculated using ImageJ software, and an immunoscore was determined. RESULTS: Eighty tumors were evaluated from 66 patients. These included 14 primary sites and 66 metastatic sites. R0/R1 resection was achieved in 44 (66.7%) patients. Known prognostic factors including resection status (HR 1.99, p = 0.004) and lymph node status (HR 3.49, p = 0.002) were associated with overall survival. On multivariate analysis, increased CD3/CD4 IM (HR 0.54, p = 0.03) ratio positively was associated with improved OS. DISCUSSION: This is the first study to assess the utility of subtypes of T cells as prognostic markers in patients with colorectal peritoneal carcinomatosis, which may play a role in patients with low-volume disease. Further studies into immune mechanisms may improve patient selection for cytoreductive surgery and HIPEC as well as provide novel pathways for effective immunotherapy.