Peritoneal Metastases Of Colorectal Origin Research Articles

Should Cytoreductive Surgery Alone for Peritoneal Metastases of Colorectal Origin be Centralized? A National Study of 4159 Procedures.

Addition of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery (CRS) in the treatment of peritoneal metastases of colorectal origin (CRPM) did not show any survival benefit in the PRODIGE 7 trial (P7). This study aimed to investigate whether perioperative outcomes after CRS alone for CRPM patients is mediated by hospital volume and to determine the effect of P7 on French practice for CRPM patients treated respectively with CRS alone and CRS/HIPEC. Data from CRPM patients treated with CRS alone between 2013 and 2020 in France were collected through a national medical database. The study used a cutoff value of the annual CRS-alone caseload affecting the 90-day postoperative mortality (POM) determined from our previous study to define low-volume (LV) HIPEC and high-volume (HV) HIPEC centers. Perioperative outcomes were compared between no-HIPEC, LV-HIPEC, and HV-HIPEC centers. The trend between years and HIPEC rates was analyzed using the Cochrane-Armitage test. Data from 4159 procedures were analyzed. The patients treated in no-HIPEC and LV-HIPEC centers were older compared withHV-HIPEC centers (p < 0.0001) and had a higher Elixhauser comorbidity index (p < 0.0001) and less complex surgery (p < 0.0001). Whereas the major morbidity (MM) rate did not differ between groups (p = 0.79), the 90-day POM was lower in HV-HIPEC centers than in no-HIPEC and LV-HIPEC centers (5.4% vs 15% and 13.3%; p < 0.0001), with lower failure-to-rescue (FTR) (p < 0.0001). After P7, the CRS/HIPEC rate decreased drastically in Cancer centers (p < 0.001), whereas patients treated with CRS alone are still referred to expert centers. Centralization of CRS alone should improve patient selection as well as FTR and POM. After P7, CRS/HIPEC decreased mostly in Cancer centers, without any impact on the number of CRS-alone cases referred to expert centers.

Recurrence and Survival Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Synchronous and Metachronous Peritoneal Metastases of Colorectal Origin

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the 5-year survival for colorectal cancer (CRC) patients with peritoneal metastases (PM). Little is known about recurrence patterns and recurrence rates between synchronous (S) and metachronous (M) PM following CRS+HIPEC. We aimed to describe the recurrence patterns, overall survival (OS) and disease-free survival (DFS) in S-PM and M-PM patients after complete CRS+HIPEC. From June 2006 to December 2020, a prospective cohort study included 310 CRC patients, where 181 patients had S-PM (58.4%) and 129 patients had M-PM (41.6%). After a median 10.3-month follow-up, 247/310 (79.7%) patients experienced recurrence, and recurrence sites included isolated peritoneal (32.4%), multifocal (peritoneal and liver and/or lung(s)) (22.7%), isolated liver (17.8%), isolated lung (10.5%) and other (16.6%) sites. Recurrence patterns did not differ between S-PM and M-PM. M-PM patients had an impaired DFS compared to S-PM patients (9.4 months (95% CI: 7.3–12.1) vs. 12.5 months (95% CI: 11.2–13.9), p = 0.01). The median OS was similar for S-PM and M-PM (38.4 months (95% CI: 31.2–46.8) vs. 40.8 months (95% CI: 28.8–46.8), p = 0.86). Despite frequent recurrence at extraperitoneal locations, long-term survival was achievable after CRS+HIPEC in CRC patients with PM. The recurrence patterns and OS did not differ between groups, yet M-PM patients had a shorter DFS.

ASO Author Reflections: Peritoneal Metastases of Colorectal Origin Exhibit Distinct Histological Growth Patterns with a Potential Prognostic Value.

ASO Author Reflections: Peritoneal Metastases of Colorectal Origin Exhibit Distinct Histological Growth Patterns with a Potential Prognostic Value.

Cytoreductive surgery (CRS) and HIPEC for peritoneal metastasis of colorectal origin (CRPM): Use of mitomycin decrease postoperative morbidity by two

Cytoreductive surgery (CRS) and HIPEC for peritoneal metastasis of colorectal origin (CRPM): Use of mitomycin decrease postoperative morbidity by two

412P Phase I study of intraperitoneal irinotecan in combination with standard systemic chemotherapy in patients with extensive peritoneal metastases of colorectal origin: The INTERACT trial

The prognosis of patients diagnosed with peritoneal metastasized (PM) colorectal cancer who are ineligible for cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is poor. We hypothesize that adding intraperitoneal (IP) irinotecan to standard systemic palliative chemotherapy improves the prognosis of these patients. Therefore we conducted this phase I trial.

Long-term outcomes of elderly patients with peritoneal metastases of colorectal origin after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

IntroductionCytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) were reportedly safe for the elderly. However, long-term survival data in this subgroup of patients are scarce. Our aim was to evaluate the peri-operative and long-term outcomes of CRS + HIPEC in colorectal peritoneal metastases (CRC-PM) in patients ≥70 years of age. Material and methodsWe retrospectively analyzed our combined institutional databases for patients who underwent CRS + HIPEC for CRC-PM. Clinical and pathological characteristics, as well as overall survival (OS) and progression-free survival (PFS) were compared between the groups. Tumor extent was measured by the peritoneal carcinomatosis index (PCI) and completeness of cytoreduction by the CCR score. Major morbidity was defined according to Clavien-Dindo classification. ResultsThe dataset of 159 patients included 33 elderly and 126 non-elderly patients. Clinical characteristics between the groups differed only in medical comorbidities (Charlson comorbidity index 10 vs. 7, P < 0.001) and delivery of post-HIPEC adjuvant treatment (12.5% vs. 43.8%, P = 0.004). Overall PCI and CCR0 rates were similar between the groups, as were length of stay and major morbidity and mortality rates. Long-term outcomes in the elderly group were lower than those of the non-elderly (median OS: 21.8 vs. 40.5 months, P < 0.001; median PFS: 6 vs. 8 months, P = 0.02, respectively). ConclusionsCRS + HIPEC in selected elderly patients can be safe in terms of postoperative morbidity and mortality. However, despite the same surgical extents and radicality, their long-term outcomes are inferior, possibly due to under-usage of systemic chemotherapy.

Peritoneal Metastases of Colorectal Origin Treated with Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy: The Efficiency of Mitomycin C.

Survival of patients affected by colorectal cancerperitoneal metastases (CRC-PM) can be improved with combined complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Two chemotherapeutic agents are mainly used: mitomycin C (MMC) and oxaliplatin. A recent prospective randomized clinical trial showed that oxaliplatin-based HIPEC does notimprove survival compared with CCRS alone. The purpose of our study was to compare the survival effectiveness of MMC versus oxaliplatin-based HIPEC using a homogeneous surgical technique and drug protocol. This retrospective monocentric study included all patients prospectively registered for having undergone CCRS and HIPEC using MMC or oxaliplatin for CRC-PM in Strasbourg University Hospital, France, from December 2004 until December 2019. MMC-basedHIPEC and oxaliplatin-basedHIPEC groups were compared with an inverse probability of treatment weighting. A total of 137 patients were included. Groups were comparable for all baseline characteristics except for peritoneal carcinomatosis index. In the weighted multivariate analysis, disease-free survival (DFS) and peritoneal disease-free survival (PDFS) were significantly higher in the MMC-based HIPEC group compared with the oxaliplatin-based HIPEC group with a hazard ratio of 0.74 (CI 95% 0.56-0.98), p = 0.035 and 0.59 (CI 95% 0.40-0.98), p = 0.0084, respectively. There was no difference in overall survival or postoperative morbidity between groups. These results favor a superiority of MMC for DFS and PDFS in comparison with oxaliplatin in HIPEC after CCRS in treatment with curative intent for CRC-PM.

ASO Visual Abstract: Peritoneal Metastases of Colorectal Origin Treated with Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy-The Efficiency of Mitomycin C.

ASO Visual Abstract: Peritoneal Metastases of Colorectal Origin Treated with Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy-The Efficiency of Mitomycin C.

Multimodal CEA-targeted fluorescence and radioguided cytoreductive surgery for peritoneal metastases of colorectal origin

In patients with colorectal peritoneal metastases scheduled for cytoreductive surgery, accurate preoperative estimation of tumor burden and subsequent intraoperative detection of all tumor deposits remains challenging. In this study (ClinicalTrials.gov NCT03699332) we describe the results of a phase I clinical trial evaluating [111In]In-DOTA-labetuzumab-IRDye800CW, a dual-labeled anti-carcinoembryonic antigen (anti-CEA) antibody conjugate that enables both preoperative imaging and intraoperative radioguidance and fluorescence imaging. Primary study outcomes are safety and feasibility of this multimodal imaging approach. Secondary outcomes are determination of the optimal dose, correlation between tracer uptake and histopathology and effects on clinical strategy. Administration of [111In]In-DOTA-labetuzumab-IRDye800CW is well-tolerated and enables sensitive pre- and intraoperative imaging in patients who receive 10 or 50 mg of the tracer. Preoperative imaging revealed previously undetected lymph node metastases in one patient, and intraoperative fluorescence imaging revealed four previously undetected metastases in two patients. Alteration of clinical strategy based on multimodal imaging occurred in three patients. Thus, multimodal image-guided surgery after administration of this dual-labeled tracer is a promising approach that may aid in decision making before and during cytoreductive surgical procedures.

Postoperative mortality after cytoreductive surgery alone for peritoneal metastasis of colorectal origin need centralization in expert centers: a national study of 5,893 patients.

Background: Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreduction surgery (CRS) in peritoneal metastasis (PM) of colorectal origin did not show any survival benefit in PRODIGE-7 trial and additional value of other regimen-based HIPEC is under debate. However, centralization has been shown to improve post-operative mortality (POM) in CRS and HIPEC for PM of various origins. We aimed to evaluate the impact of centralization on POM after CRS alone.

FLUOZEROC trial (FLUOrescence as a tracker for a ZERO CC0 Cyto-reduction for Colo-rectal peritoneal metastases)

Background: The rate of recurrence after cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastasis of colorectal origin remains high despite important advances in multimodal treatment. Previous studies have demonstrated that there is remaining disease in the normal-looking peritoneum after a complete CRS and HIPEC in up to 30% of the patients. Fluorescence-guided (FG) surgery is revolutionizing oncologic surgery as it can signal in real time primary or metastatic lesions thanks to indocyanine green (ICG) or targeted dyes as EMI-137, a specific dye for colorectal cancer cells.

Treatment response after Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for peritoneal metastases of colorectal origin

Background: Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a safe and well-tolerated treatment for patients with peritoneal metastases (PM). Our aim was to report oncological outcomes after PIPAC for colorectal PM.

The impact of postoperative complications following cytoreductive surgery combined with oxaliplatin based heated intraperitoneal chemotherapy

IntroductionCytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) has become the mainstream treatment for peritoneal metastases of colorectal origin. This extensive treatment is known for its increased morbidity rate.In this study, the impact of postoperative complications on survival was evaluated in a high-volume centre. Patients and methodBetween November 2016 through October 2018, all 106 patients with peritoneal metastases of colorectal origin treated with CRS + HIPEC with oxaliplatin were evaluated. Data on patient characteristics, Peritoneal Carcinomatosis Index (PCI), operative procedure, post-operative complications (Clavien-Dindo classification grade III or higher) and survival were collected. In-hospital postoperative complications were analysed for their association with patient characteristics, tumour load (PCI), and operative procedure with logistic regression analyses. Survival was analysed with the Cox regression analysis. ResultsOf 106 patients, 78% had an un-eventful in-hospital recovery. Of those patients who experienced complications, 52% patients had one complication and 48% had more than one.The median follow-up time was 33.8 months. Median survival was 22.4 months (95% CI 12.2–NR) for patients who experienced complications and not reached for those who did not. Survival was significantly associated with complications (HR 2.2, 95% CI 1.2–4.0) as well as with PCI (HR 1.1, 95% CI 1.1–1.2) in univariate analyses. A stepwise Cox regression analysis showed both PCI and complications had an independent negative impact on survival. ConclusionPostoperative complications, independently of tumour load, led to reduced survival in patients with peritoneal metastases of colorectal origin when treated with CRS + HIPEC with oxaliplatin.

Systemic therapy in addition to cytoreduction and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: recent insights from clinical studies and translational research.

There is a lack of randomized or high-quality intention-to-treat cohort studies addressing the role of systemic therapy in addition to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) as part of the treatment of colorectal peritoneal metastases (PM). Therefore, the choice whether or not to treat patients with systemic therapy is currently mainly based on expert opinion. As a result, treatment with neoadjuvant and/or adjuvant systemic therapy is implemented in various ways around the world. The aim of this review was to provide an overview of recent insights with regard to the systemic treatment of PM of colorectal origin obtained from clinical studies and translational research.

Intraperitoneal collagenase as a novel therapeutic approach in an experimental model of colorectal peritoneal carcinomatosis

The usefulness of local collagenase in therapeutic approaches to solid tumors has been tested recently. In this study, we evaluate the safety and efficacy of intraperitoneal collagenase associated or not to mitomycin for treatment of colorectal peritoneal metastases in an experimental rat model. Using a fixed-dose procedure, we found that a dose of collagenase of 37 IU/mL administered for 15 min with a hyperthermia pump at 37.5 °C, both in isolation or associated to sequential treatment with intraperitoneal mitomycin, led to a macroscopic decrease in tumor volume as evaluated by the modified peritoneal cancer index (mPCI). Concerning the safety of the procedure, the animals showed no physiological or behavioral disorders during 8 weeks of follow-up. Local treatment for peritoneal metastases of colorectal origin with intraperitoneal collagenase has proved safe and effective in an experimental murine model. Therefore, the stroma-first approach by enzymatic breakdown of collagen from the tumor's extracellular matrix provides a new therapeutic target for colorectal peritoneal metastases.

The role of molecular biomarkers in outcomes and patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases of colorectal origin

BackgroundCytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is effective in select patients with peritoneal metastases of colorectal (CRC) origin. The impact of different biomarkers in predicting recurrence after CRS/HIPEC is unclear. MethodsRetrospective review of patients who underwent CRS/HIPEC for PC of CRC origin from 03/2007–08/2017. Molecular profile of the primary tumor was obtained from pathology reports, whenever available. ResultsOverall, 100 patients underwent CRS/HIPEC for peritoneal metastases of CRC origin. Most patients presented high grade tumor histology (G2/G3, n = 97, 97%), and a majority showed mucinous features (n = 61, 61%). At a median follow-up of 18 months, median DFS for the overall population was 13 months (95% CI 9.6, 16.4). Data reporting at least one mutational analysis was available in 64 patients. Microsatellite stability was detected in 42/50 (84%) patients, mKRAS in 25/51 (49%), and mBRAF in 5/35 (14.3%). On Kaplan–Meier analysis, BRAF was the only mutation associated with poor DFS (16 months, CI 95% 11.7–43.3 vs. 7 months, CI 95% 2.1–11.9, p = .008). On multivariate analysis, mBRAF independently predicted earlier recurrence (p = .032). ConclusionsIn this analysis, mBRAF was independently associated with earlier recurrence in patients undergoing CRS/HIPEC for CRC, leading to dismal median DFS (7 months). Strict patient selection is advisable in these patients.

Primary Tumor Location and Outcomes After Cytoreductive Surgery and Intraperitoneal Chemotherapy for Peritoneal Metastases of Colorectal Origin.

The aim of this study is to evaluate outcomes in patients with peritoneal metastasis of colorectal cancer (pmCRC) who underwent cytoreductive surgery and intraperitoneal chemotherapy (CRS/IPC) in relation to the location of the primary tumor. Regional therapy, including cytoreductive surgery and intraperitoneal chemotherapy, has been associated with improved survival in patients with pmCRC. Location of the primary tumor has been shown to be prognostic in patients with metastasis. A retrospective review was performed for all patients who underwent complete cytoreduction and intraperitoneal chemotherapy from 2010 to 2017, examining patient and tumor characteristics, overall and recurrence-free survival, recurrence patterns, and tumor mutational profiles. Ninety-three patients were included in the study: 49 (53%) with a right-sided and 44 (47%) with a left-sided primary tumor. Patients with a right-sided tumor had significantly shorter recurrence-free survival (median, 6.3months; 95% CI, 4.7-8.1months vs 12.3months; 95% CI, 3.6-21.7months; P = 0.02) and overall survival (median, 36.6months; 95% CI, 26.4-46.9months vs 83.3months; 95% CI 44.2-122.4months; P = 0.03). BRAF and KRAS mutations were more frequent in right-sided tumors, and APC and TP53 mutations were more frequent in left-sided tumors, which were more chromosomally instable. BRAF mutations were associated with early recurrence. Tumor sidedness is a predictor of oncological outcomes after CRS/IPC. Tumor sidedness and molecular characteristics should be considered when counseling patients regarding expected outcomes and when selecting or stratifying pmCRC patients for clinical trials of regional therapy.

Multimodal fluorescence-guided surgery of colorectal peritoneal metastases, a phase I/II clinical trial.

TPS4119 Background: Successful treatment of patients with colorectal peritoneal carcinomatosis highly depends on complete surgical tumor resection of all tumor. Oncological outcomes can potentially be improved by intraoperative imaging using a tumor-targeting antibody conjugated to a fluorophore and a radiotracer. This enables preoperative radionuclide imaging, real-time intraoperative fluorescence imaging and gamma detection. In this study we investigate the feasibility, accuracy and safety of CEA-targeted preoperative SPECT/CT and intraoperative fluorescence imaging in patients with colorectal PC. Methods: In this phase I/II single arm protein dose escalation study patients with peritoneal metastases of colorectal origin who are scheduled for cytoreductive surgery and HIPEC will receive an intravenous injection of the CEA-targeting tracer 111In-DOTA-labetuzumab-IRDye800CW. The first 15 patients will receive a single dose of 2,10 or 50 mg 6 to 7 days prior to surgery. Four to five days after injection SPECT/CT imaging of the thorax and abdomen is performed to determine intra-abdominal tumor load and detect extra-abdominal metatases. At day 6/7 after injection, standard cytoreductive surgical resection extended with real-time near-infrared fluorescence imaging and radio guidance is performed. After surgery, the peritoneal cavity will be re-examined for residual disease with fluorescence imaging. Resected specimens are analyzed microscopically, immunohistochemically (CEA and H&amp;E) and by gamma counting. Blood samples are drawn for farmacokinetics and safety analysis at 180 minutes, 4 days, 6 days and 3 weeks after tracer injection. In the phase II dose expansion cohort, 14 more patients will receive the optimal dose as determined in the phase I trial. The primary objectives of the trial are to assess the safety, feasibility and accuracy of preoperative SPECT/CT and intraoperative fluorescence imaging after administration of 111In- labetuzumab-IRDye800CW in patients with peritoneal carcinomatosis of colorectal origin who will undergo cytoreductive surgery and HIPEC. The secondary objectives are to assess whether additional malignant lesions can be visualized by fluorescence imaging after cytoreductive surgery, to assess the intensity of fluorescence in malignant and non-malignant tissue, to assess the correlation between localization of the dual-labeled antibody and CEA expression in tumor and healthy tissue and to determine blood concentrations of the dual labelled antibody at several time points in patients. Clinical trial information: NCT03699332 .

Prise en charge des tumeurs primitives et métastatiques du péritoine en période de pandémie CoViD-19. Pistes de réflexion et de priorisation du groupe RENAPE et BIG-RENAPE

RésuméLa pandémie de COVID-19 modifie profondément l’organisation et l’accès aux soins, en particulier pour les pathologies néoplasiques péritonéales, dont la prise en charge curative mobilise des moyens importants en personnel, bloc opératoire et réanimation. Les groupes BIG-RENAPE et RENAPE proposent des pistes de réflexion et de priorisation pour leur prise en charge. Un renforcement des critères habituels de sélection est nécessaire pour une prise en charge à visée curative : patients jeunes, avec peu de co-morbidités et une extension péritonéale limitée. Il est souhaitable de prioriser les pathologies pour lesquelles la chirurgie de cytoréduction associée ou non à une chimiohyperthermie intrapéritonéale (CHIP) est le traitement de référence et celles pour lesquelles la chimiothérapie systémique ne peut être une alternative temporaire ou prolongée : pseudomyxomes péritonéaux ; mésothéliomes péritonéaux malins résécables ; métastases péritonéales d’origine colorectale si résécables, non répondeuses à la chimiothérapie systémique et/ou après 12 cures, carcinoses ovariennes en 1re intention si résécables et limitées ou en situation intervallaire après un maximum de 6 cycles de chimiothérapie systémique. L’adjonction d’une CHIP devra être discutée au cas par cas, en centre expert. La priorisation des indications devra prendre en considération les conditions locales et la phase de la période épidémique pour permettre une prise en charge péri-opératoire optimale.

Treatment of primary and metastatic peritoneal tumors in the Covid-19 pandemic. Proposals for prioritization from the RENAPE and BIG-RENAPE groups.

SummaryThe Covid-19 pandemic is profoundly changing the organization of healthcare access. This is particularly so for peritoneal neoplastic diseases, for which curative treatment mobilizes substantial personnel, operating room and intensive care resources. The BIG-RENAPE and RENAPE groups have made tentative proposals for prioritizing care provision. A tightening of the usual selection criteria is needed for curative care: young patients with few or no comorbidities and limited peritoneal extension. It is desirable to prioritize disease conditions for which cytoreduction surgery with or without associated hyperthermic intraoperative peritoneal chemotherapy (HIPEC) is the gold-standard treatment, and for which systemic chemotherapy cannot be a temporary or long-term alternative: pseudomyxoma peritonei, resectable malignant peritoneal mesotheliomas, peritoneal metastases of colorectal origin if they are resectable and unresponsive to systemic chemotherapy after up to 12 courses, first-line ovarian carcinomatosis if resectable or in interval surgery after at most six courses of systemic chemotherapy. Addition of HIPEC must be discussed case by case in an expert center. The prioritization of indications must consider local conditions and the phase of the epidemic to allow optimal peri-operative care.