Peritoneal Carcinomatosis Of Colorectal Origin Research Articles

Long-Term Outcomes following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis of Colorectal Origin.

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a major treatment of colorectal peritoneal carcinomatosis (CPC). The aim was to determine the disease-free survival (DFS) and overall survival (OS) of patients undergoing CRS-HIPEC for CPC and factors associated with long-term survival (LTS). consecutive CPC patients who underwent CRS-HIPEC at a HIPEC center between 2007 and 2021 were included. Actual survival was calculated, and Cox proportional hazards models were used to identify factors associated with OS, DFS and LTS. there were 125 patients with CPC who underwent primary CRS-HIPEC, with mean age of 54.5 years. Median follow-up was 31 months. Average intraoperative PCI was 11, and complete cytoreduction (CC-0) was achieved in 96.8%. Median OS was 41.6 months (6-196). The 2-year and 5-year OS were 68% and 24.8%, respectively, and the 2-year DFS was 28.8%. Factors associated with worse OS included pre-HIPEC systemic therapy, synchronous extraperitoneal metastasis, and PCI ≥ 20 (p < 0.05). Progression prior to CRS-HIPEC was associated with worse DFS (p < 0.05). Lower PCI, fewer complications, lower recurrence and longer DFS were associated with LTS (p < 0.05). CRS and HIPEC improve OS in CPC patients but they have high disease recurrence. Outcomes depend on preoperative therapy response, extraperitoneal metastasis, and peritoneal disease burden.

ASO Author Reflections: Achieving Long-Term Survival in Patients with Peritoneal Carcinomatosis of Colorectal Origin.

ASO Author Reflections: Achieving Long-Term Survival in Patients with Peritoneal Carcinomatosis of Colorectal Origin.

Actual 5-Year Survival After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Carcinomatosis of Colorectal Origin.

Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) improves survival compared with chemotherapy alone in patients with peritoneal carcinomatosis (PC) of colorectal (CRC) origin, however, long-term survival data are lacking. We report the actual survival of patients who underwent CRS/HIPEC for PC of CRC origin with a minimum potential 5-year follow-up period to identify factors that preclude long-term survival. We performed a retrospective analysis of a prospective database, analyzing patients undergoing CRS/HIPEC for PC of CRC origin from 2007 to 2017. Patients with aborted CRS/HIPEC, postoperative follow-up <90 days, or non-CRC histology were excluded. Overall survival (OS) and disease-free survival (DFS) were measured from date of surgery. Surviving patients with <60 months of follow-up were censored at date of last follow-up. A total of 103 patients met inclusion criteria and were analyzed. CC score 0-1 was achieved in 89.3% of patients, and median peritoneal cancer index (PCI) was 9 (interquartile range [IQR] 5-17). Ninety-day mortality was 2.9%. The median follow-up of survivors was 88 months. Five-year OS was 36%, and median OS was 42.5 months. Factors independently associated with poor survival included high PCI (PCI = 14-20, hazard ratio [HR] 3.1, p = 0.007, and PCI > 20, HR 5.3, p ≤ 0.001) and incomplete CRS (CC score-2, HR 2.96, p = 0.02). Patients with low PCI (0-6) had 5-year OS 60.7%. Actual 5-year OS was 36% and median OS was 42.5 months. Our study demonstrates that patients with PC from CRC origin with low PCI who undergo complete surgical resection can achieve favorable long-term survival.

From circulating and intraperitoneal tumour cells to cell free nucleic acids for a personalised treatment in peritoneal carcinomatosis of colorectal origin. A multicentric study proposition

From circulating and intraperitoneal tumour cells to cell free nucleic acids for a personalised treatment in peritoneal carcinomatosis of colorectal origin. A multicentric study proposition

Intraperitoneal irinotecan combined with systemic chemotherapy for extensive peritoneal carcinomatosis of colorectal origin: The phase I and phase II INTERACT trials

Intraperitoneal irinotecan combined with systemic chemotherapy for extensive peritoneal carcinomatosis of colorectal origin: The phase I and phase II INTERACT trials

Diagnosis of Peritoneal Carcinomatosis of Colorectal Origin Based on an Innovative Fuzzy Logic Approach.

Colorectal cancer represents one of the most important causes worldwide of cancer related morbidity and mortality. One of the complications which can occur during cancer progression, is peritoneal carcinomatosis. In the majority of cases, it is diagnosed in late stages due to the lack of diagnostic tools capable of revealing the early-stage peritoneal burden. Therefore, still associates with poor prognosis and quality of life, despite recent therapeutic advances. The aim of the study was to develop a fuzzy logic approach to assess the probability of peritoneal carcinomatosis presence using routine blood test parameters as input data. The patient data was acquired retrospective from patients diagnosed between 2010–2021. The developed model focuses on the specific quantitative alteration of these parameters in the presence of peritoneal carcinomatosis, which is an innovative approach as regards the literature in the field and validates the feasibility of using a fuzzy logic approach in the noninvasive diagnosis of peritoneal carcinomatosis.

Can peritoneal carcinomatosis of colorectal origin be treated with oral everolimus alone or in combination with capecitabine? Preliminary results

Can peritoneal carcinomatosis of colorectal origin be treated with oral everolimus alone or in combination with capecitabine? Preliminary results

Cytoreductive Surgery versus Systemic Chemotherapy alone in Isolated Peritoneal Carcinomatosis of Colorectal Origin.

To compare the overall survival and progression-free survival of front-line cytoreductive surgery (CRs) ± hyperthermic intraperitoneal chemotherapy versus intensive systemic chemotherapy alone, in patients with isolated peritoneal carcinomatosis of colorectal origin. Descriptive study. Departments of Medical Oncology and Surgical Oncology in University of Health Sciences, Umraniye Education and Research Hospital, from January 2017 to January 2020. Clinicopathological data of patients presented with isolated peritoneal carcinomatosis were categorised into two groups according to their treatment type as patients who received intensive systemic chemotherapy alone or underwent front-line CRS ± HIPEC. Overall and progression-free survival outcomes of the two approaches were quantified by survival analysis and compared with each other. The other collected variables were age, gender, performance status, tumor site and type of systemic chemotherapy. Overall, 109 patients were included. The median progression-free survival of patients treated with cytoreductive surgery ± hyperthermic intraperitoneal chemotherapy was 12 months; whereas, it was 9 months in those treated with intensive systemic chemotherapy alone (p=0.011). The median overall survival was estimated as 32 months in patients treated with cytoreductive surgery ± hyperthermic intraperitoneal chemotherapy, compared with 23 months for those treated with systemic chemotherapy alone (p=0.715). Although not translated into overall survival gain, extended progression-free survival, may give an advantage to cytoreductive surgery ± hyperthermic intraperitoneal chemotherapy when used with intensive systemic chemotherapy in the individualised treatment of isolated peritoneal carcinomatosis of colorectal carcinoma. Key Words: Colorectal carcinoma, Cytoreductive surgery, Hyperthermic intraperitoneal chemotherapy, Overall survival, Peritoneal carcinomatosis, Systemic chemotherapy.

Peritoneal carcinomatosis of colorectal origin treated by cytoreductive surgery and hyperthermic intraoperative peritoneal chemotherapy at the Bulovka University Hospital.

Peritoneal carcinomatosis (PK) of colorectal origin is a malignant tumour of the peritoneum caused by spreading of colorectal carcinoma (KRK) over the peritoneal surface of the abdominal cavity and its organs. PK occurs as a synchronous tumour in 1520% of patients, and as metachronous disease in 2550% of patients. A group of 66 patients operated on for PK was retrospectively evaluated; 18 patients were excluded due to insufficient data. We evaluated 48 patients in total (22 men and 26 women) with mean age of 58 and 53 years, respectively; 12 patients (25%) were aged over 65 years. The patients were operated on between 2000 and 2019 using the Sugarbaker´s method of maximal cytoreduction (CRS) + HIPEC (Hyperthermic Intraoperative Peritoneal Chemotherapy). We evaluated the length, median survival, the incidence of complications and lethality in relation to the Peritoneal Carcinoma Index (PCI) and the Completeness of Cytoreduction (CC) score. The patients were divided into two subgroups according to the PCI score (012 and &gt;12, respectively) and the CC score (CC 01 and CC 23, respectively). The mean survival was 26.3 months in the group with PCI up to 12 and 21.4 months in patients with PCI above 12 (p=0.02). In the group with CC 01 the mean survival was 27.1 months, while in the patients with the CC 23 it reached 12.6 months (p=0.06). The morbidity rate requiring an intervention was 18.7% and the lethality rate was 6.25% in the entire group. The median survival of the entire group was 22 months (1334 months). Literary references and our results are comparable, confirming the high efficiency of this method both in our country and worldwide. The use of CRS and HIPEC, associated with acceptable mortality and morbidity in selected patients with PK of colorectal origin, results in a significant extension of overall survival (OS).

Can peritoneal carcinomatosis of colorectal origin be treated with or everolimus or in combination with capecitabine? Preliminary results

Background: We wanted to evaluate the effectiveness of oral everolimus alone and in combination with capecitabine treatment on colorectal cancer-induced peritoneal carcinomatosis animal model. Methods: Caco-2 colon adenocarcinoma cells were injected intraperitoneally to BALB/cOlaHsd-Foxn1nu mice to establish peritoneal carcinomatosis. Mice were divided into four groups (everolimus, everolimus plus capecitabine, capecitabine, control group) with 2 mice in each group. Treatment was initiated 5 days after inoculation of Caco-2 cells. 7.5 mg/kg everolimus was administered orally every 2 days. 2.1 mmol/kg capecitabine was administered orally every 5 days a week. 22 days after inoculation of Caco-2 cells, mice were sacrificed. Results: The mean weight of the tumor was 25 ± 7.07 mg in the control group (n=2); 0.7 ± 0.7 mg in the everolimus group (n=2); 0.28 ± 0.36 mg in the capecitabine group; 0.48 ± 0.07 mg in the everolimus plus capecitabine group. Conclusion: Tumor samples excised from BALB/cOlaHsd-Foxn1nu mice revealed that everolimus alone, and in combination with capecitabine suppressed tumor growth. However, a comparison of tumor weights revealed no statistically significant difference within the four groups (p=0.227). To reach statistically significant data, the sample size should be increased.

Expanding Uses of HIPEC for Locally Advanced Colorectal Cancer: A European Perspective.

Locally advanced colorectal cancer is a challenge for surgeons and medical oncologist; 10 to 20% colorectal cancer debut as locally advanced disease, with tumors extending through the colon wall with perforation and/or invasion of adjacent organs or structures. Those locally advanced tumors have a worse prognostic at any stage due not only to systemic dissemination but also in a high percentage of patients, to locoregional recurrence, in fact, peritoneal carcinomatosis of colorectal origin is so predictable that we can assess the risk for each patient according to some histopathological and clinical features: small peritoneal nodules resected in the first surgery (70% probability), ovarian metastases (60%), perforated tumor onset or intraoperative tumor rupture (50%), positive cytology (40%), and pT4/mucinous pT3 up to 40%. Prophylactic or adjuvant hyperthermic intraperitoneal chemotherapy seems to be a promising strategy for patients with advanced colorectal cancer to prevent the development of peritoneal recurrence and improve prognosis of this group of patients.

Wide variation in tissue, systemic, and drain fluid exposure after oxaliplatin-based HIPEC: results of the GUTOX study

PurposeIn this exploratory study, the effect of postprocedural flushing with crystalloids after oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) on platinum concentrations in peritoneal tissue, blood, and drain fluid was studied. Interpatient variability in oxaliplatin pharmacokinetics and the relation between platinum concentration in peritoneal fluid and platinum exposure in tissue and blood was explored.MethodsTen patients with peritoneal carcinomatosis of colorectal origin were treated with HIPEC including postprocedural flushing, followed by ten patients without flushing afterwards. Tissue, peritoneal fluid, blood, and drain fluid samples were collected for measurement of total and ultrafiltered platinum concentrations.ResultsPeritoneal tissue concentration and systemic ultrafiltered platinum exposure showed large inter individual variability, ranging from 65 to 1640 µg/g dry weight and 10.5 to 28.0 µg*h/ml, respectively. No effect of flushing was found on geometric mean platinum concentration in peritoneal tissue (348 vs. 356 µg/g dry weight), blood (14.8 vs. 18.1 µg*h/ml), or drain fluid (day 1: 7.6 vs. 7.7 µg/ml; day 2: 1.7 vs. 1.9 µg/ml). The platinum concentration in peritoneal fluid at the start of HIPEC differed twofold between patients and was positively correlated with systemic exposure (p = .04) and peak plasma concentration (p = .04).ConclusionIn this exploratory study, no effect was found for postprocedural flushing on platinum concentrations in peritoneal tissue, blood, or drain fluid. BSA-based HIPEC procedure leads to large interpatient variability in platinum exposure in all compartments.The study was registered at ClinicalTrials.gov on 7 December 2017 under registration number NCT03364907.

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 .

Hyperthermic intraperitoneal chemotherapy with recombinant mutant human TNF-α and raltitrexed in mice with colorectal-peritoneal carcinomatosis.

Peritoneum is one of the most common metastatic sites of colorectal cancer (CRC). It has been reported that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) prolongs the lifespan of patients with peritoneal carcinomatosis of colorectal origin (CRC-PC), while the drugs used for HIPEC are limited. We investigated the application of recombinant mutant human tumor necrosis factor-α (rmhTNF) combined with raltitrexed in the HIPEC treatment in a mice model with CRC-PC. In vitro, we detected the cytotoxicity and apoptosis of human colorectal cancer cells by 3–(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, Western blot, and TdT-mediated dUTP Nick End Labeling (TUNEL) assay. In vivo, we established xenograft models of CRC-PC and assessed the antitumor effect by in vivo imaging, peritoneal cancer index scoring, and TUNEL assay. The results showed that the combination of rmhTNF and raltitrexed under hyperthermia with a temperature of 42°C inhibited the growth of colorectal cancer cells significantly in vitro, and after HIPEC treatments with rmhTNF and raltitrexed, peritoneal tumor growth was prohibited in vivo. Our findings about the efficacy of rmhTNF and raltitrexed used for HIPEC to treat CRC-PC will provide experimental data and basis for their potential clinical application. Impact statement Colorectal peritoneal carcinomatosis exhibits poor prognosis and presents a treatment challenge. At present, the main treatment is surgery, supplemented by hyperthermic intraperitoneal chemotherapy (HIPEC), but the drugs used for HIPEC are limited. Our study found that the combination of recombinant mutant human TNF-α (rmhTNF) and raltitrexed (RTX) under hyperthermia with a temperature of 42°C had antitumor effect both in vitro and vivo. The findings will provide experimental data and basis for the potential clinical application of rmhTNF and RTX, which might offer patients a new choice of therapeutic drugs.

Hyperthermic intraperitoneal chemotherapy post cytoreductive surgery in management of peritoneal carcinomatosis of colorectal primaries: Tertiary center experience.

28 Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) in addition to Cytoreductive surgery (CRS) has survival benefit observed in management of Peritoneal Carcinomatosis (PC) from Colo-rectal cancer (CRC)origin. We report the outcomes and prognostic factors of patients with CRC, who presented with PC and underwent CRS and HIPEC at King Faisal Specialist Hospital &amp; Research Center, Riyadh, Saudi Arabia. Methods: Patients presented with PC from CRC origin and underwent CRS and HIPEC; from February 2009 to September 2015 were recruited. Results: 52 patients identified. A total of 55 CRS procedures were performed, where 3 patients underwent repeated CRS and HIPEC for tumor recurrence. All except 3 used mitomycin-C for HIPEC, the remaining received either melphalan (2 patients) or cisplatin plus mitomycin-C regimen (1 patient). Melphalan used for patients who underwent repeated HIPEC as 2nd line chemotherapeutic agent. Intraoperative Radiation therapy performed in 5 patients with tumor invading the surrounding structures, where performing a safe or complete resection was either technically difficult or carried high risk. Complication assessment by Clavien-Dindo score, 62 % grade (I-II), while 31% had grade (3–4). Two patients (3.6%) died postoperatively; both from sepsis. Respiratory complications were the most commonly encountered morbidities. The 5-year overall survival(OS) was 50% with disease free survival (DFS) 29.5%. Univariate analysis showed poor OS and DFS encountered in; Signet-ring tumors (p &lt; 0.0001) for both, peritoneal cancer index (PCI) ≥ 6 (p &lt; 0.0009) for both, completeness of cytoreduction(CC) score &gt;1 (p &lt; 0.0001) for both, and high 3-month postoperative carcinoembryonic antigen value (p &lt;0.0001) for both. In multivariate analysis; DFS was significant for (PCI) ≥ 6 (p &lt; 0.0131) and (CC) score &gt;1 (p &lt; 0.0031) while PCI &gt; 6 was the only significant factor (p &lt; 0.0030) for OS. Conclusions: Addition of HIPEC to CRS was safe, and improved survival in patient with peritoneal Carcinomatosis of colo-rectal origin. PCI and CC score are prognostic factors of survival, signet-ring subtype may not benefit of this procedure.

Short-termoutcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy used as treatment of colo-rectal carcinomatosis: a multicentric study.

The aim of this study is to assess the morbidity and mortality related to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colo-rectal carcinomatosis. A retrospective multi-institutional study from seven Italian Centers was performed. One hundred and seventy-two patients, submitted to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) to treat carcinomatosis of colorectal origin, were recorded. Postoperative morbidity was evaluated in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Post-operative mortality was evaluated as patients' death within 60days from surgical procedures. Predictors of morbidity were evaluated with univariate and multivariate analyses. Post-operative morbidity occurred in 83 patients (48.3%): grades 1-2 in 29 cases (16.9%), and grades 3-4 in 54 (31.4%). Mortality occurred in four cases (2.3%). Number of anastomoses (OR 1.45; 95% CI 1.05-2.00; p = 0.024), number of blood transfusions (OR 1.31; 95% CI 1.11-1.54; p = 0.001) and chemotherapy regimen [Oxaliplatin (OX): OR 2.87; 95% CI 1.22-6.75; p = 0.015] remained, in multivariate analysis, in a statistically significant correlation with overall morbidity. The only variable that was proven to have statistically significant correlation with 3-4 morbidity was the number of blood transfusions (OR 1.25; 95% CI 1.07-1.46; p = 0.005). Morbidity and mortality do not preclude the use of CRS plus HIPEC in the treatment of peritoneal carcinomatosis of colorectal origin.

Concomitant intraperitoneal and systemic chemotherapy in patients with extensive peritoneal carcinomatosis of colorectal origin: Clinical trial protocol of the INTERACT trial

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has become standard of care for patients with peritoneal carcinomatosis (PC) of colorectal origin with a low/moderate abdominal disease load. In case of a Peritoneal Carcinomatosis Index (PCI) >20, CRS-HIPEC procedure is not considered to be beneficial. Patients who have undergone an open-close procedure are offered palliative/life prolonging systemic chemotherapy. Previous research shows that systemic chemotherapy is less effective against peritoneal carcinomatosis than it is against hematogeneous spread of colorectal cancer. Several studies suggested that in patients with PC, intraperitoneal chemotherapy may be superior to intravenous chemotherapy. The addition of intraperitoneal to systemic chemotherapy in patients with PC of ovarian and gastric origin showed promising results. As of yet, there are no studies investigating intraperitoneal chemotherapy for PC of colorectal origin in this specific patient population.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis of Colorectal Origin

目的:大腸癌腹膜播種に対する減量手術と腹腔内温熱化学療法（CRS+HIPEC）は有効な治療法であるが，高い合併症率や再発率など克服すべき問題がある．この研究の目的は，その安全性と有効性を検証することである．

Should Liver Metastases and Synchronous Peritoneal Carcinomatosis of Colorectal Origin Be Treated Simultaneously ?

Should Liver Metastases and Synchronous Peritoneal Carcinomatosis of Colorectal Origin Be Treated Simultaneously ?

Factors affecting the survival of patients with peritoneal carcinomatosis of colorectal origin

To determine the predictive factors of overall (OS) and disease-free survival (DFS) in CRC patients with PC after CS with HIPEC. From 2010 to 2018 years 102 patients with CRC and PC were included in the study. The cytoreduction was complete (CC0, according to Sugabaker scale) in 96 (94.2%) cases. The age median of patients was 65 years. There were 63 (62%) women. In 81 (79%) patients, the PC was synchronous. The median level of CEA was 8.5 ng/ml. The median peritoneal carcinomatous index (PCI) was 3 (1-23). The median of follow-up was 18 (11; 33) months. The median of DFS and OS were 13 (9;31) and 32 (17; n/d) months, respectively. Multifactorial Cox-regression analysis showed the localization of the primary tumor in the right colon (OR=1.66; 95% CI 1.1-2.5; p=0.013) and the level of the PCI (OR = 1.08; 95% CI 1.024-1.15; p=0.008) were independent negative factors of OS. The CS and HIPEC in patients with CRC with PC allowes to achieve five-year survival in a part of patients, especially with low PCI. Identifying adverse prognostic factors preoperatively can help in selecting patients for CS in the future.