Genomic characterization and detection of potential therapeutic targets for peritoneal mesothelioma in current practice.

Peritoneal mesothelioma (PeM) is an aggressive tumor with limited treatment options. The current study aimed to evaluate the value of next generation sequencing (NGS) of PeM samples in current practice. Foundation Medicine F1CDx NGS was performed on 20 tumor samples. This platform assesses 360 commonly somatically mutated genes in solid tumors and provides a genomic signature. Based on the detected mutations, potentially effective targeted therapies were identified. NGS was successful in 19 cases. Tumor mutational burden (TMB) was low in 10 cases, and 11 cases were microsatellite stable. In the other cases, TMB and microsatellite status could not be determined. BRCA1 associated protein 1 (BAP1) mutations were found in 32% of cases, cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) and neurofibromin 2 (NF2) mutations in 16%, and ataxia-telangiectasia mutated serine/threonine kinase (ATM) in 11%. Based on mutations in the latter two genes, potential targeted therapies are available for approximately a quarter of cases (i.e., protein kinase inhibitors for three NF2 mutated tumors, and polyADP-ribose polymerase inhibitors for two ATM mutated tumors). Extensive NGS analysis of PeM samples resulted in the identification of potentially effective targeted therapies for about one in four patients. Although these therapies are currently not available for patients with PeM, ongoing developments might result in new treatment options in the future.

Peritoneal carcinomatosis in mouse models.

Peritoneal carcinomatosis (PCa) represents a metastatic stage of a disease with unmet therapeutic options. Malignant cells from primary tumors (gastrointestinal or gynecologic malignancies) invade the peritoneal cavity and eventually seed onto peritoneal surfaces, with the omentum being the most common nest area. With a median survival of less than 6 months, PCa has a dismal prognosis that can be improved with treatments only available to a select few individuals with low tumor burden. Thus, the discovery of novel and effective therapies for this disease depends on reliable animal models. Here, we describe a method to generate syngeneic PCa mouse models based on intraperitoneal (i.p.) administration of tumor cells. This model allows to follow-up cancer progression in PCa models from ovarian and colorectal origins monitoring mice bodyweight changes, ascites development and overall survival. Moreover, luciferase-expressing tumor cells can also be used to assess tumor growth after i.p. injection through in vivo bioluminescence quantification. The establishment of reliable, easy-to-monitor and reproducible intraperitoneal syngeneic tumors models, as described here, is the first step to develop cutting-edge therapies against PCa.

Phase 1b study of intraperitoneal ipilimumab and nivolumab in patients with recurrent gynecologic malignancies with peritoneal carcinomatosis.

BACKGROUND: Intravenous immune checkpoint blockade (ICB) has shown poor response rates in recurrent gynecologic malignancies. Intraperitoneal (i.p.) ICB may result in enhanced T cell activation and anti-tumor immunity. METHODS: In this phase 1b study, registered at Clinical. TRIALS: gov (NCT03508570), initial cohorts received i.p. nivolumab monotherapy, and subsequent cohorts received combination i.p. nivolumab every 2 weeks and i.p. ipilimumab every 6 weeks, guided by a Bayesian design. The primary objective was determination of the recommended phase 2 dose (RP2D) of the combination. Secondary outcomes included toxicity, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). FINDINGS: The trial enrolled 23 patients: 18 with ovarian cancer, 2 with uterine cancer, and 3 with cervical cancer. Study evaluable patients (n = 16) received a median of 2 prior lines of therapy (range: 1-8). Partial response was observed in 2 patients (12.5%; 1 ovarian, 1 uterine), and complete response was observed in 1 patient (6.3%) with cervical cancer, for an ORR of 18.8% (95% confidence interval: 4.0%-45.6%). The median duration of response was 14.8 months (range: 4.1-20.8), with one complete response ongoing. Median PFS and OS were 2.7 months and not reached, respectively. Grade 3 or higher immune-related adverse events occurred in 2 (8.7%) patients. CONCLUSIONS: i.p. administration of dual ICB is safe and demonstrated durable responses in a subset of patients with advanced gynecologic malignancy. The RP2D is 3 mg/kg i.p. nivolumab every 2 weeks plus 1 mg/kg ipilimumab every 6 weeks. FUNDING: This work was funded by Bristol Myers Squibb (CA209-9C7), an MD Anderson Cancer Center Support Grant (CA016672), the Ovarian Cancer Moon Shots Program, the Emerson Collective Fund, and a T32 training grant (CA101642).

Efficacy of hyperthermic intraperitoneal chemotherapy in colorectal cancer: A phase I and III open label randomized controlled registry-based clinical trial protocol.

Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15-30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.

[Long-Term Suppression with First-Line Chemotherapy(FOLFIRI plus BV)for Peritoneal Metastasis].

A 72-year-old man underwent right hemicolectomy for transverse colon cancer(pT4aN1aM0, Stage ⅢB), after which he received adjuvant chemotherapy(capecitabine plus oxaliplatin[CAPOX])for 6 months. Three years after the first surgery, FDG-PET/CT revealed a tumor in the abdomen. He underwent a tumorectomy and adjuvant chemotherapy(CAPOX plus bevacizumab[BV])performed for 6 months. Two years after a tumorectomy, the CEA level rose again. He was diagnosed peritoneal metastasis again. A central venous(CV)port was implanted for access to the right internal jugular vein, and he received systemic chemotherapy(fluorouracil, Leucovorin, and irinotecan[FOLFIRI]plus BV)as an outpatient. One year after this recurrence, no peritoneal dissemination was detected by CT. Thereafter, total 49 courses of FOLFIRI plus BV were introduced, but chemotherapy was discontinued due to CV port-related infection. Three months later, low back pain appeared and became a diagnosis of spondylodiscitis. He had surgery, but follow-up CT performed 8 years after the first surgery detected multiple liver metastasis. It was considered necessary to take infection control measures during long-term chemotherapy.

[A Case Report of Metastatic Breast Cancer with Peritoneal Metastasis and Massive Ascites Responding to CDK4/6 Inhibitor(Palbociclib)].

A 52-year-old woman was presented with abdominal distension. Chest-abdominal CT showed some tumors in the left breast, enlarged axillary lymph nodes, ovary metastasis peritoneal thickening, a large amount of ascites. The diagnosis of needle biopsy in the breast mass was invasive ductal carcinoma, Luminal A type. The large amount of ascites decreased after the start of administration of fulvestrant and CDK4/6 inhibitor(PAL). Also chest and abdominal CT showed reduction of all lesions. We found the high expression of cyclin D1 protein and the negative of p16 protein in tissues of the needle biopsy. Fifty months later, she continues to do good ADL and PR status. We experienced a case of metastatic breast cancer with massive ascites and peritoneal metastasis that was successfully treated with a CDK4/6 inhibitor(PAL)and achieved long- term survival.

Imaging-guided prognostic score-based approach to assess the benefits of combotherapy versus monotherapy with immune checkpoint inhibitors in metastatic MSI-H colorectal cancer patients.

BACKGROUND: This retrospective study determined survival responses to immune checkpoint inhibitors (ICIs), comparing mono- (mono) and combo-immunotherapy (combo) in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) by analyzing quantitative imaging data and clinical factors. METHODS: One hundred fifty patients were included from two centers and divided into training (n = 105) and validation (n = 45) cohorts. Radiologists manually annotated chest-abdomen-pelvis computed tomography and calculated tumor burden. Progression-free survival (PFS) was assessed, and variables were selected through Recursive Feature Elimination. Cutoff values were determined using maximally selected rank statistics to binarize features, forming a risk score with hazard ratio-derived weights. RESULTS: In total, 2258 lesions were annotated with excellent reproducibility. Key variables in the training cohort included: total tumor volume (cutoff: 73 cm3), lesion count (cutoff: 20), age (cutoff: 60) and the presence of peritoneal carcinomatosis. Their respective weights were 1.13, 0.96, 0.91, and 0.38, resulting in a risk score cutoff of 1.36. Low-score patients showed similar overall survival and PFS regardless of treatment, while those with a high-score had significantly worse survivals with mono vs combo (P = 0.004 and P = 0.0001). In the validation set, low-score patients exhibited no significant difference in overall survival and PFS with mono or combo. However, patients with a high-score had worse PFS with mono (P = 0.046). CONCLUSIONS: A score based on total tumor volume, lesion count, the presence of peritoneal carcinomatosis, and age can guide MSI-H mCRC treatment decisions, allowing oncologists to identify suitable candidates for mono and combo ICI therapies.

Hyperthermic pressurized intraperitoneal aerosol drug delivery system in a large animal model: a feasibility and safety study.

BACKGROUND: We developed a novel drug delivery system called hyperthermic pressurized intraperitoneal aerosol chemotherapy (HPIPAC) that hybridized Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). The present study aims to assess the feasibility and safety of HPIPAC system in a large animal survival model. METHODS: Eleven pigs (eight non-survival models and three survival models) were used in the experiment. The heat module in the HPIPAC controller circulates hyperthermic CO2 in a closed-loop circuit and creates gas-based dry intraperitoneal hyperthermia. Three 12 mm trocars were placed on the abdomen. The afferent CO2 tube wound with heat generating coil was inserted into a trocar, and the efferent tube was inserted into another trocar. Heated CO2 was insufflated and circulated in a closed circuit until the intra-abdominal and peritoneal surface temperature reached 42 °C. 100 ml of 5% dextrose in water was nebulized for 5 min and the closed-loop circulation was resumed for 60 min at 42 °C. Tissue biopsies were taken from several sites from the pigs in the survival model. RESULTS: The average change in core temperature of the pigs was 2.5 ± 0.08 °C. All three pigs displayed no signs of distress, and their vital signs remained stable, with no changes in their diet. In autopsy, inflammatory and fibrotic responses at the biopsy sites were observed without serious pathologic findings. CONCLUSIONS: We successfully proved the feasibility and safety of our novel HPIPAC system in an in-vivo swine survival model.

[Contribution of intraperitoneal chemotherapy in the treatment of colorectal peritoneal carcinoma. HIPEC, PIPAC, state of the art and future directions]. / La chimiothérapie intra-péritonéale dans le traitement de la carcinose péritonéale d'origine colorectale. CHIP, PIPAC, état des lieux et perspectives.

After more than a decade of good results using the combination of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinosis of colorectal origin, the PRODIGE7 study, which specifically evaluated the role of HIPEC, failed to show any superiority in terms of overall and disease-free survival for the CRS+HIPEC combination compared with CRS alone. This study constituted a radical change in the knowledge and therapeutic attitudes observed to date. After reviewing the literature and the consensus of national and international experts, a synthesis is provided, together with an outlook on the questions raised and the therapeutic trials and innovations of the near future. An analysis of recent advances due to the advent of a new technique, PIPAC, is also proposed, as well as a review of current therapeutic trials in this field.

Paclitaxel as HIPEC-Drug after Surgical Cytoreduction for Ovarian Peritoneal Metastases: A Randomized Phase III Clinical Trial (HIPECOVA).

Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I-II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien-Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.

Real-world outcomes of third-line immune checkpoint inhibitors versus irinotecan-based chemotherapy in patients with advanced gastric cancer: a Korean, multicenter study (KCSG ST22-06).

BACKGROUND: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. METHODS: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). RESULTS: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy. CONCLUSIONS: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).

Efficacy and safety of bevacizumab in patients with low-grade serous ovarian cancer.

Aim: To investigate the efficacy and safety of bevacizumab in patients with recurrent low-grade serous ovarian carcinoma. Materials & methods: The data of patients who received at least two cycles of bevacizumab in combination with chemotherapy were retrospectively recorded. Results: The median age of 51 patients was 56 (range: 33-75) years. The complete response rate was 10.4% and the partial response rate was 43.7%. The objective response rate was 54.1%. Median progression-free survival was 15.9 months (95% CI: 9.1-22.6) and median overall survival was 42.5 months (95% CI: 37.2-47.8). Conclusion: Bevacizumab with chemotherapy is an effective option for treating recurrent ovarian low-grade serous carcinoma.

High-grade B-cell lymphoma, not otherwise specified, presenting as primary peritoneal lymphomatosis and successfully treated with dose-adjusted EPOCH-R.

Peritoneal lymphomatosis (PL) is a rare lymphoma-associated condition defined as the dissemination of lymphoma cells in the peritoneum. An 82-year-old man presented with abdominal pain, heartburn, and high fever. Radiological findings, including positron emission tomography-computed tomography (PET-CT), and gastrointestinal fiberscopy, showed diffuse thickening of the peritoneum, omentum, and mesentery; however, no lymphadenopathy, hepatosplenomegaly, or gastrointestinal lesions were observed. Under suspicion of peritonitis carcinomatosa of unknown origin, exploratory laparoscopy was performed that revealed multiple white nodules and masses on the surfaces of the peritoneum, mesentery, and intestinal serosa. The histopathological and cytogenetic findings of the peritoneum revealed high-grade B-cell lymphoma, not otherwise specified, and a gain of MYC by fluorescence in-situ hybridization. The patient was treated with two cycles of R-CHOP therapy, followed by six cycles of dose-adjusted EPOCH-R therapy, and a complete metabolic response was confirmed by PET-CT. Since there are no specific radiological findings to confirm the diagnosis of PL, a histopathological diagnosis is usually required. Most PL exhibit an aggressive lymphoma phenotype and can be cured by appropriate chemotherapy. Therefore, early diagnosis and treatment are desirable.

A case of metachronous oligo-hepatic and peritoneal metastases of pancreatic cancer with a favorable outcome after conversion surgery combined with perioperative sequential chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, and the prognosis for its recurrence after surgery is very poor. Here, we report a case of metachronous oligo-hepatic and peritoneal metastases in a patient who survived without recurrence for 3 years after conversion surgery combined with perioperative sequential chemotherapy using gemcitabine plus nab-paclitaxel (GnP) and modified FOLFIRINOX (mFOLFIRINOX). The patient was a 70-year-old man with pancreatic ductal carcinoma, classified as cT3N0M0, cStage IIA, who underwent a distal pancreatosplenectomy. At 1 year and 4 months later, two liver metastases and one peritoneal metastasis were detected. A systemic 9-month course of chemotherapy was administered with GnP and mFOLFIRINOX as the first- and second-line chemotherapeutic agents, respectively. The two liver metastases were judged as showing a partial response, but one dissemination was considered stable disease. After receiving informed consent from the patient, we performed resection of the disseminated tumor and lateral segmentectomy of the liver. Adjuvant chemotherapy using mFOLFIRINOX and GnP was administered for 10 months. The patient has now been alive for 5 years and 6 months after the initial pancreatosplenectomy, and 3 years and 3 months after the conversion surgery, without subsequent tumor recurrence. Thus, a multidisciplinary treatment approach including surgery and perioperative sequential chemotherapy using GnP and mFOLFIRINOX may be beneficial for treating metachronous oligo-hepatic and peritoneal metastases, depending on the patient's condition.

Organoids derived from patients provide a new opportunity for research and individualized treatment of malignant peritoneal mesothelioma.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an extremely rare and highly invasive tumor. Due to the lack of accurate models that reflect the biological characteristics of primary tumors, studying MPM remains challenging and is associated with an exceedingly unfavorable prognosis. This study was aimed to establish a new potential preclinical model for MPM using patient-derived MPM organoids (MPMOs) and to comprehensively evaluate the practicality of this model in medical research and its feasibility in guiding individualized patient treatment. METHODS: MPMOs were constructed using tumor tissue from MPM patients. Histopathological analysis and whole genome sequencing (WGS) were employed to determine the ability of MPMOs to replicate the original tumor's genetic and histological characteristics. The subcutaneous and orthotopic xenograft models were employed to assess the feasibility of establishing an in vivo model of MPM. MPMOs were also used to conduct drug screening and compare the results with retrospective analysis of patients after treatment, in order to evaluate the potential of MPMOs in predicting the effectiveness of drugs in MPM patients. RESULTS: We successfully established a culture method for human MPM organoids using tumor tissue from MPM patients and provided a comprehensive description of the necessary medium components for MPMOs. Pathological examination and WGS revealed that MPMOs accurately represented the histological characteristics and genomic heterogeneity of the original tumors. In terms of application, the success rate of creating subcutaneous and orthotopic xenograft models using MPMOs was 88% and 100% respectively. Drug sensitivity assays demonstrated that MPMOs have different medication responses, and these differences were compatible with the real situation of the patients. CONCLUSION: This study presents a method for generating human MPM organoids, which can serve as a valuable research tool and contribute to the advancement of MPM research. Additionally, these organoids can be utilized as a means to evaluate the effectiveness of drug treatments for MPM patients, offering a model for personalized treatment approaches.

Eliminating the need for preoperative intravenous hyperhydration: Sodium thiosulfate as nephrotoxicity prevention in HIPEC-treated patients - A retrospective analysis.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for peritoneal metastases. However, HIPEC with cisplatin is associated with renal toxicity. Sodium thiosulfate (ST) has been shown to prevent cisplatin-induced toxicity. METHODS: A retrospective, single-center analysis of patients treated curatively for peritoneal surface malignancy, who underwent cytoreductive surgery with cisplatin-based HIPEC between 2015 and 2020. Patients were categorized into three groups based on the management of cisplatin-induced renal toxicity: preoperative hyperhydration alone (PHH), preoperative hyperhydration with ST (PHH + ST), and ST alone. Renal function and complications, in terms of Acute (AKI) and chronic kidney injury (CKI), were monitored and analyzed during 3 postoperative months. RESULTS: This study included 220 consecutive patients. Mean serum creatinine levels were 95, 57 and 61 mmol/L, for PHH, PHH + ST and ST groups, respectively (p < 0.001). Glomerular Filtration Rate (GFR) were 96, 94 and 78 ml/min/1.73 m2, respectively (p < 0.001). AKI and CKI are respectively for PHH, PHH + ST and ST groups were 21 % (n = 46), 1 % (n = 2) and 0 % vs 19 % (n = 42), 0 % and 0 % (p < 0.001), for pairwise analysis did not show any difference between PHH + ST and ST alone combination, regarding nephrological outcomes. All patients were followed 3 months postoperatively. CONCLUSION: There is no need for preoperative hyperhydration when sodium-thiosulfate is used to prevent cisplatin-induced nephrotoxicity in patients undergoing cytoreductive surgery with HIPEC. These findings have implications for improving and simplifying the management of patients with peritoneal metastases undergoing HIPEC with cisplatin.

Hyperthermic intraperitoneal chemotherapy in patients with incomplete cytoreduction for appendiceal pseudomyxoma peritonei: a 10-year treatment experience in China.

BACKGROUND: To explore the application value of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with incomplete cytoreduction for appendiceal pseudomyxoma peritonei (PMP). METHODS: We retrospectively analyzed the clinical data of 526 patients with incomplete cytoreduction for appendiceal PMP to discover its prognostic factors, and the therapeutic value of HIPEC. RESULTS: The 5-year and 10-year overall survival rates of patients after cytoreductive surgery (CRS) treated with HIPEC were significantly higher than those without HIPEC (5y-OS: 58% vs. 48%, 10y-OS: 37% vs. 16%, P = 0.032). The median progression-free survival (PFS) following CRS was 20 months, with a 20% 3-year PFS. The median PFS following CRS + HIPEC was 33 months, with a 60% 3-year PFS (P = 0.000). Univariate analysis indicated that HIPEC, gender, completeness of cytoreduction (CCR) and pathological grade had statistical difference. Multivariate analysis showed that CRS without HIPEC and high pathological grade were independent risk factors for poor prognosis and rapid tumor progression. CONCLUSIONS: HIPEC may prolong the survival in patients with incomplete cytoreduction for low-grade appendiceal PMP. High pathological grade indicates poor survival and rapid tumor progression.

Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients With Locally Advanced Colon Cancer (COLOPEC): 5-Year Results of a Randomized Multicenter Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Whether adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) might prevent peritoneal metastases after curative surgery for high-risk colon cancer is an ongoing debate. This study aimed to determine 5-year oncologic outcomes of the randomized multicenter COLOPEC trial, which included patients with clinical or pathologic T4N0-2M0 or perforated colon cancer and randomly assigned (1:1) to either adjuvant systemic chemotherapy and HIPEC (n = 100) or adjuvant systemic chemotherapy alone (n = 102). HIPEC was performed using a one-time administration of oxaliplatin (460 mg/m2, 30 minutes, 42°C, concurrent fluorouracil/leucovorin intravenously), either simultaneously (9%) or within 5-8 weeks (91%) after primary tumor resection. Outcomes were analyzed according to the intention-to-treat principle. Long-term data were available of all 202 patients included in the COLOPEC trial, with a median follow-up of 59 months (IQR, 54.5-64.5). No significant difference was found in 5-year overall survival rate between patients assigned to adjuvant HIPEC followed by systemic chemotherapy or only adjuvant systemic chemotherapy (69.6% v 70.9%, log-rank; P = .692). Five-year peritoneal metastases rates were 63.9% and 63.2% (P = .907) and 5-year disease-free survival was 55.7% and 52.3% (log-rank; P = .875), respectively. No differences in quality-of-life outcomes were found. Our findings implicate that adjuvant HIPEC should still be performed in trial setting only.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus R0 resection for resectable colorectal cancer with peritoneal metastases and low peritoneal cancer index scores: a collaborative observational study from Korea and Japan.

BACKGROUND: The benefits of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) for colorectal cancer with peritoneal metastasis (CPM) remain controversial. R0 resection without peritoneal stripping might be as effective as CRS plus HIPEC. The authors aimed to compare the long-term oncological outcomes of patients with CPM and peritoneal cancer index (PCI) scores less than or equal to 6 who underwent R0 resection in Japan with those who underwent CRS plus HIPEC in Korea. MATERIALS AND METHODS: This international, retrospective cohort study was conducted in Korea and Japan using a prospectively collected clinical database. Patients who underwent surgery from July 2014 to December 2021 for CPM with a PCI score of less than or equal to 6 and completeness of the cytoreduction score-0 were included. The primary outcome was relapse-free survival (RFS), and the secondary outcomes were overall survival, peritoneal RFS (PRFS), and postoperative outcomes. RESULTS: The 3-year RFS was significantly longer in the CRS+HIPEC group than in the R0 resection group: 35.9% versus 6.9% ( P <0.001); 31.0% versus 6.7% ( P =0.040) after propensity score matching. The median PRFS was significantly longer in the CRS+HIPEC group than in the R0 resection group: 24.5 months versus 17.2 months ( P =0.017). The 3-year overall survival and postoperative complications did not significantly differ between the two groups. CONCLUSIONS: RFS and PRFS rates were significantly prolonged after CRS plus HIPEC, whereas postoperative complications and length of hospital stay were not increased. Therefore, curative CRS plus HIPEC may be considered a treatment strategy for selected patients with resectable CPM and low PCI scores.