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Background Selected patients with peritoneal metastases of colorectal cancer (PM-CRC) can benefit from potentially curative cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC), with a median overall survival (OS) of more than 40 months. Objective The aims of this evidence-based consensus were to define the indications for HIPEC, to select the preferred HIPEC regimens, and to define research priorities regarding the use of HIPEC for PM-CRC. Methods The consensus steering committee elaborated and formulated pertinent clinical questions according to the PICO (patient, intervention, comparator, outcome) method and assessed the evidence according to the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) framework. Standardized evidence tables were presented to an international expert panel to reach a consensus (4-point, weak and strong positive/negative) on HIPEC regimens and research priorities through a two-round Delphi process. The consensus was defined as ≥ 50% agreement for the 4-point consensus grading or ≥ 70% for either of the two combinations. Results Evidence was weak or very weak for 9/10 clinical questions. In total, 70/90 eligible panelists replied to both Delphi rounds (78%), with a consensus for 10/10 questions on HIPEC regimens. There was strong negative consensus concerning the short duration, high-dose oxaliplatin (OX) protocol (55.7%), and a weak positive vote (53.8–64.3%) in favor of mitomycin-C (MMC)-based HIPEC (preferred choice: Dutch protocol: 35 mg/m 2 , 90 min, three fractions), both for primary cytoreduction and recurrence. Determining the role of HIPEC after CRS was considered the most important research question, regarded as essential by 85.7% of the panelists. Furthermore, over 90% of experts suggest performing HIPEC after primary and secondary CRS for recurrence > 1 year after the index surgery. Conclusions Based on the available evidence, despite the negative results of PRODIGE 7, HIPEC could be conditionally recommended to patients with PM-CRC after CRS. While more preclinical and clinical data are eagerly awaited to harmonize the procedure further, the MMC-based Dutch protocol remains the preferred regimen after primary and secondary CRS.

Background CRS/HIPEC patients face unique quality of life (QoL) challenges due to advanced disease (peritoneal carcinomatosis), the extent of procedure, and risk for long-term complications. Standard QoL questionnaires are generic, focusing on tumor type and standard treatments, and likely do not capture this select population’s full experience, suggesting the need for tailored instruments. We aimed to characterize the QoL challenges faced by CRS/HIPEC cancer survivors and determine whether these were captured by a standard QoL questionnaire. Patients and Methods An anonymous, semi-structured individual interview was conducted with CRS/HIPEC patients addressing their experience at diagnosis, challenges related to CRS/HIPEC, and access to CRS/HIPEC information. Verbatim transcripts were interpreted using thematic analysis. Code and theme identification was inductive. Questions addressing common themes that were not encompassed by a standard QoL questionnaire were developed. Results We interviewed eight patients. Median age was 55 (range 30–71) years and 75% ( n = 6) were women. Primary tumor sites included appendix ( n = 4), ovarian ( n = 3), and peritoneal mesothelioma ( n = 1). Median time from CRS/HIPEC was 40.1 (range 3.1–216.3) months. Overall, 133 codes were identified and categorized into 9 themes. The most recurring were physical symptoms after CRS/HIPEC (specifically gastrointestinal symptoms), adjusting to survivorship, mental health, expectations from CRS/HIPEC, and access to care. A total of 22 questions that did not overlap with a standardized QoL questionnaire were developed. Conclusions There is an unmet need to understand the unique QoL challenges CRS/HIPEC patients encounter. Patient-centered QoL questionnaires based on CRS/HIPEC patient experiences can capture these unique challenges and help guide future studies and care.

Background Select patients with peritoneal metastases are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). We assayed for intra- and interpatient drug response heterogeneity through testing of patient-derived tumor organoids (PDTOs). Methods PDTOs were generated from CRS/HIPEC patients from December 2021 to September 2022 and subjected to an in vitro HIPEC drug screen. Drug response was assessed with a cell viability assay and cleaved caspase-3 staining. Results A total of 31 patients were consented for tissue collection. Viable tissue was harvested from 23, and PDTO generation was successful in 13 (56%). PDTOs were analyzed from six appendiceal, three colorectal, two small bowel, one gastric, and one adrenal tumor. Drug screen results were generated in as few as 7 days (62%), with an average time of 12 days. Most patients received mitomycin-C (MMC) intraoperatively ( n  = 9); however, in only three cases was this agent considered the optimal choice in vitro . Three sets of PDTOs were resistant (defined as > 50% PDTO viability) to all agents tested and two were pan-sensitive (defined as 3 or more agents with < 50% PDTO viability). In three patients, organoids were generated from multiple metastatic sites and intrapatient drug response heterogeneity was observed. Conclusions Both intra- and interpatient drug response heterogeneity exist in patients undergoing CRS/HIPEC for nongynecologic abdominal cancers. Caution must be used when interpreting patient response to chemotherapeutic agents based on a single site of testing in those with metastatic disease.

BackgroundCytoreductive surgery (CRS) and administration of hyperthermic intraperitoneal chemotherapy (HIPEC) have shown their efficacy in multiple malignancies and also could offer a prognostic benefit for patients with advanced ovarian cancer. MethodsA prospective, single-center, parallel-group, randomized phase 3 clinical trial analyzed patients with a diagnosis of carcinomatosis from ovarian cancer treated with neoadjuvant systemic chemotherapy (NACT). In this trial, 71 patients were randomized to receive CRS alone (36 patients) or CRS with HIPEC (35 patients) using cisplatin (75 mg/m2 for 60 min at 42 °C). The primary end point was disease-free survival (DFS). Overall survival (OS), morbidity, and quality of life (QoL) were the secondary end points.ResultsDuring a median follow-up period of 32 months, the median DFS was 12 months in the control group (CRS) and 18 months in the experimental group (CRS and HIPEC). The findings showed HIPEC to be an independent protective factor against the development of recurrence (hazard ratio [HR], 0.12, 95 % confidence interval [CI], 0.02–0.89; p = 0.038). The median OS was 45 months in the control group and 52 months in the experimental group. The respective morbidity rates for any grade (1 to 5) were respectively 58.3 % and 45.7 % (p > 0.05), with a mortality rates of 2.8 % and 2.9 % (p > 0.05). In the dimensions evaluated, CRS with or without HIPEC had no impact on QoL.ConclusionsFor patients who had advanced ovarian cancer treated with NACT, CRS and HIPEC was associated with better DFS and OS, but without a difference in postoperative morbidity, mortality, or in the QoL evaluation.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of appendiceal neoplasms specifically related to the management of peritoneal surface malignancies. These guidelines are developed with input from leading experts including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

BackgroundExtent of tumor load is an important factor in the selection of ovarian cancer patients for cytoreductive surgery (CRS). The Peritoneal Cancer Index (PCI) gives exact information on tumor load but still is not standard in ovarian cancer surgery. The aim of this study was to find a PCI cutoff for incomplete CRS. The secondary aims were to identify reasons for open-close surgery and to compare surgical complications in relation to tumor burden.MethodsThe study included 167 women with stage III or IV ovarian cancer scheduled for CRS. Possible predictors of incomplete surgery were evaluated with receiver operator curves, and a PCI cutoff was identified. Surgical complications were analyzed by one-way analysis of variance and Chi square tests.ResultsThe median PCI score for all the patients was 22 (range 3–37) but 33 (range 25–37) for the patients with incomplete surgery (n = 19). The PCI predicted incomplete CRS, with an area under the curve of 0.94 (95% confidence interval [CI], 0.91–0.98). Complete CRS was obtained for 67.2% of the patients with a PCI higher than 24, who experienced an increased rate of complications (p = 0.008). Overall major complications were found in 16.9% of the cases. Only 28.6% of the patients with a PCI higher than 33 achieved complete CRS. The reason for open-close surgery (n = 14) was massive carcinomatosis on the small bowel in all cases.ConclusionThe study found PCI to be an excellent predictor of incomplete CRS. Due to a lower surgical success rate, the authors suggest that neoadjuvant chemotherapy could be considered if the PCI is higher than 24. Preoperative radiologic assessment should focus on total tumor burden and not necessarily on specific regions.

BackgroundThe development of multimodality treatment, including cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC), has led to promising results in selected patients with peritoneal disease of gastric origin. The aim of this study was to investigate the short- and long-term outcomes of CRS/HIPEC in the treatment of synchronous peritoneal metastasis in gastric cancer.MethodsThe Italian Peritoneal Surface Malignancies Oncoteam—S.I.C.O. retrospective registry included patients with synchronous peritoneal malignancy from gastric cancer submitted to gastrectomy with CRS and HIPEC between 2005 and 2018 from 11 high-volume, specialized centers.ResultsA total of 91 patients with a median age of 58 years (range 26–75) were enrolled. The median overall survival (OS) time for the whole group of patients was 20.2 months (95% confidence interval [CI] 11.8–28.5] and the median recurrence-free survival (RFS) was 7.3 months (95% CI 4–10.6). The completeness of cytoreduction score (CCS) of 0 and Peritoneal Cancer Index (PCI) score of ≤ 6 groups showed a significantly better long-term survival (median OS 40.7 and 44.3 months, respectively) compared with the incomplete resected groups (median OS 10.7 months, p = 0.003) and PCI score of > 6 group (median OS 13.4 months, p = 0.005). A significant difference was observed in the survival rate according to neoadjuvant treatment (untreated patients: 10.7 months, 95% CI 5.1–16.2; treated patients: 35.3 months, 95% CI 2.8–67.8; p = 0.022).ConclusionsIn referral centers, CRS and HIPEC after neoadjuvant treatment significantly improved survival in selected patients. Patients with a PCI score ≤ 6, complete cytoreduction, negative nodal involvements, and negative cytology had encouraging results, showing a clinically meaningful survival.

Background The PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumors) is a prospective, multicenter, observational study. This report from phase I of PRECINCT outlines variations in recording the surgical peritoneal cancer index (sPCI) at experienced peritoneal malignancy centers and the incidence of pathologically confirmed disease in morphologically different peritoneal lesions (PL). Methods The sPCI was recorded in a prespecified format that included the morphological appearance of PL. Six prespecified morphological terms were provided. The surgical and pathological findings were compared. Results From September 2020 to December 2021, 707 patients were enrolled at 10 centers. The morphological details are routinely recorded at two centers, structure bearing the largest nodule, and exact size of the largest tumor deposit in each region at four centers each. The most common morphological terms used were normal peritoneum in 3091 (45.3%), tumor nodules in 2607 (38.2%) and confluent disease in 786 (11.5%) regions. The incidence of pathologically confirmed disease was significantly higher in ‘tumor nodules’ with a lesion score of 2/3 compared with a lesion score of 1 (63.1% vs. 31.5%; p  < 0.001). In patients receiving neoadjuvant chemotherapy, the incidence of pathologically confirmed disease did not differ significantly from those undergoing upfront surgery [751 (47.7%) and 532 (51.4%) respectively; p  = 0.069] . Conclusions The sPCI was recorded with heterogeneity at different centers. The incidence of pathologically confirmed disease was 49.2% in ‘tumor nodules’. Frozen section could be used more liberally for these lesions to aid clinical decisions. A large-scale study involving pictorial depiction of different morphological appearances and correlation with pathological findings is indicated.

BackgroundThe surgical peritoneal cancer index (sPCI) is calculated based on a subjective evaluation of the extent of peritoneal disease during surgery. The pathologic PCI (pPCI) may be a more accurate and objective method for determining the PCI. This study aimed to compare the sPCI and pPCI and to study the potential pitfalls and clinical implications of using the pPCI.MethodsThis prospective study (July to December 2018) included all patients undergoing cytoreductive surgery (CRS). The pPCI was calculated for each patient and compared with the sPCI. The impact of potential confounding factors on the difference between pPCI and sPCI was evaluated.ResultsAmong 191 patients undergoing CRS at four centers, the pPCI and sPCI were concordant for 37 patients (19.3%). The pPCI was lower than the sPCI for 125 patients (65.4%) and higher for 29 patients (15.1%). The concordance between the two groups was maximum for gastric cancer (38.8%) and colorectal cancer (27.6%) and least for mesothelioma (6.7%) and rare primary tumors (5.6%) (p = 0.04). The difference was 0 to 3 points for 119 patients (62.3%), 4 to 5 points for 27 patients (14.1%), and more than 5 points for 45 patients (23.5%). The rate of concordance was not influenced by the use of neoadjuvant chemotherapy (NACT) (p = 0.4), but the difference was greater when NACT was used (p = 0.03).ConclusionsThe pPCI strongly differs from the sPCI for patients undergoing CRS for peritoneal disease and may provide a more accurate evaluation of the peritoneal disease extent. Further studies are needed to determine its prognostic value compared with sPCI, and consensus guidelines are needed for calculating it.