Intraperitoneal Chemoperfusion Research Articles

ASO Visual Abstract: Normal CEA Levels After Neoadjuvant Chemotherapy and Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion Predict Improved Survival from Colorectal Peritoneal Metastases.

ASO Visual Abstract: Normal CEA Levels After Neoadjuvant Chemotherapy and Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion Predict Improved Survival from Colorectal Peritoneal Metastases.

Normal CEA Levels After Neoadjuvant Chemotherapy and Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion Predict Improved Survival from Colorectal Peritoneal Metastases.

Normal carcinoembryonic antigen (CEA) levels (≤ 2.5 ng/ml) after resection of localized colorectal cancer or liver metastases are associated with improved survival, however, these trends are understudied for colorectal peritoneal metastases (CRPM). We conducted a retrospective single-institution study of patients with CRPM undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) with and without neoadjuvant chemotherapy (NACT). CEA was measured before and after NACT and within 3 months after CRS/HIPEC. A total of 253 patients (mean age 55.3 years) with CRPM undergoing CRS/HIPEC had complete CEA data and 191 also underwent NACT with complete data. The median peritoneal carcinomatosis index score (PCI) of the overall cohort was 12 and 82.7% of patients had complete cytoreduction (CC0). In total, 64 (33.5%) patients had normal CEA levels after NACT with a median overall survival (OS) of 45.2 months compared with those with an elevated CEA (26.4 months, p = 0.004). Patients with normal CEA after NACT had a lower PCI found at the time of surgery than those with elevated CEA (10 versus 14, p < 0.001), 68 (26.9%) patients with an elevated preoperative CEA level experienced normalization after CRS/HIPEC, and 118 (46.6%) patients had elevated CEA after CRS/HIPEC. Patients who experienced normalization demonstrated similar OS to patients that had normal CEA levels pre- and post-surgery and improved OS compared with those with elevated postop CEA (median 41.9 versus 47 months versus 17.1 months, respectively, p < 0.001). Normal CEA levels after NACT and/or CRS/HIPEC are associated with improved survival for patients with CRPM. Patients that normalize CEA levels after surgery have similar survival to those with normal preoperative levels.

Safety of preventive HIPEC in combination with perioperative FLOT versus FLOT alone for resectable diffuse type gastric and gastroesophageal junction type II/III adenocarcinoma: An interim safety analysis from the phase III PREVENT trial of the AIO/CAOGI/ACO.

359 Background: Peritoneal relapse is seen in 60-70% of patients with diffuse type gastric cancer (gc), compared to 20-30% with intestinal type according to Laurens`s classification. Hyperthermic intraperitoneal chemoperfusion (HIPEC) is an increasingly used therapy method for patients (pts) with peritoneal metastases. The preventive use of HIPEC could represent an approach for diffuse type cell gc pts before macroscopic peritoneal seeding has evolved, since pts with operable disease are fit and may have potential risk of microscopic involvement, thus having a theoretical chance of cure with HIPEC even without the need for cytoreduction. Methods: This is a multicenter, randomized, controlled, open-label phase III study including a total of 200 pts with localized and locally advanced diffuse type cell adenocarcinoma of the stomach and type II/III gastroesophageal junction (i.e. ≥cT3 any N or any T N positive). A negative diagnostic laparoscopy before treatment and 3-6 pre-operative cycles of FLOT are a prerequisite for enrollment (Docetaxel 50 mg/m2; Oxaliplatin 85 mg/m2; Leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2wk). Pts were randomized 1:1 to receive surgery only and postoperative FLOT (Arm A-control arm) or surgery + intraoperative HIPEC (cisplatin 75mg/m2 solution at 42°C for 90 min) and postoperative FLOT (Arm B-experimental arm). Surgery is carried out as subtotal, total gastrectomy or transhiatal extended gastrectomy. The scope of the trial is to evaluate the efficacy as well as the safety and tolerability of the combination of perioperative chemotherapy combined with an intraoperative prophylactic HIPEC. Here, we show safety results from the pre-specified safety analysis after 20 pts had undergone surgical resection plus HIPEC and the corresponding 20 pts in the control arm. Results: Treatment arms were balanced regarding age, ECOG and tumor parameters like localization of the primary, of lymph nodes or cTN stage. Most pts in both arms received a subtotal or total gastrectomy. In 15 out of 20 arm B pts the HIPEC was 6 pts (30%) in Arm A and 7 pts (35%) in Arm B were seen with at least one SAE. Perioperative complications resulted in overall 7 SAEs in Arm A and in 4 SAEs in Arm B. One postoperative mortality (grade 5) was documented in Arm B due to septic complication. 11 pts showed no complications in both arms according to Clavien-Dindo-Classification. 6 pts in Arm A and 2 in Arm B showed grade 3. No patient was grade 4. Conclusions: The incidence of perioperative morbidity with surgical and/or medical complications were nearly equal in both treatment groups. The safety data showed no abnormalities or evidence increase in toxicity-rates including postoperative complications or increased severity of documented events within the experimental HIPEC arm. Clinical trial information: NCT04447352 .

CYTOKINE-MODULATING INFLUENCE OF HIPEC ON THE INTRAPERITONEAL HOMEOSTASIS FORMATION IN PATIENTS WITH OVARIAN CANCER

Background: Ovarian cancer (OC) has the greatest mortality rate among oncogynecological diseases. Most cases are diagnosed at the peritoneal dissemination stage, resulting in radical treatment. Most cases (75%) are diagnosed in III-IV stages at the stage of peritoneal dissemination, making the radical treatment impossible. Intraoperative hyperthermic intraperitoneal chemoperfusion (HIPEC), which has ceased to be an experimental technique over the past decade, is increasingly used among the methods of combating peritoneal carcinomatosis and demonstrates an increase in recurrence-free and overall survival in advanced stages of OC. Nevertheless, certain pathophysiological aspects of the effect of HIPEC on intra-abdominal homeostasis, and therefore on the further course of the disease, have not been elucidated. However, understanding this effect may be the key to the successful application of HIPEC and predicting its efficacy in each case of OC.&#x0D; Objectives: To access changes in intraperitoneal homeostasis in patients with advanced OC after HIPEC procedure (as a stage of cytoreductive surgery); in particular, to evaluate changes of TNF and TGF-β expression under the influence of HIPEC and systemic chemotherapy in the OC microenvironment.&#x0D; Materials and methods: The study included 33 OC patients treated at Lviv Regional Cancer Centre in 2016–2020. Twelve of them received HIPEC. The primary tumor cultures and primary cultures of peritoneal mesothelium and macrophages were obtained for all patients. The cytokines TNF and TGF-β activity were determined in their conditional media.&#x0D; Results: The decrease of TNF and TGF-β concentrations in the drainage exudate after HIPEC was revealed compared with the same parameters in the ascitic fluid before the operation. One-hour hyperthermia of the primary culture of peritoneal ascites-associated macrophages of recurrent OC patients decreased the TNF level in conditional media. A decline was found in 10 out of 12 cases.&#x0D; Conclusions: HIPEC has a cytokine-modulating effect on the intra-abdominal homeostasis of patients with OC, suppressing TNF expression by peritoneal macrophages. Reduced activity of TNF in supernatants of OC primary tumor cultures was associated with higher sensitivity to chemotherapy.

Effects of Hyperthermia and Hyperthermic Intraperitoneal Chemoperfusion on the Peritoneal and Tumor Immune Contexture.

Hyperthermia combined with intraperitoneal (IP) drug delivery is increasingly used in the treatment of peritoneal metastases (PM). Hyperthermia enhances tumor perfusion and increases drug penetration after IP delivery. The peritoneum is increasingly recognized as an immune-privileged organ with its own distinct immune microenvironment. Here, we review the immune landscape of the healthy peritoneal cavity and immune contexture of peritoneal metastases. Next, we review the potential benefits and unwanted tumor-promoting effects of hyperthermia and the associated heat shock response on the tumor immune microenvironment. We highlight the potential modulating effect of hyperthermia on the biomechanical properties of tumor tissue and the consequences for immune cell infiltration. Data from translational and clinical studies are reviewed. We conclude that (mild) hyperthermia and HIPEC have the potential to enhance antitumor immunity, but detailed further studies are required to distinguish beneficial from tumor-promoting effects.

ASO Visual Abstract: Impact of Primary Tumor Location and Genomic Alterations on Survival Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion for Colorectal Peritoneal Metastases.

ASO Visual Abstract: Impact of Primary Tumor Location and Genomic Alterations on Survival Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion for Colorectal Peritoneal Metastases.

Impact of Primary Tumor Location and Genomic Alterations on Survival Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion for Colorectal Peritoneal Metastases.

Colorectal cancer leads to peritoneal metastases (CRPM) in 10% of cases. Cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) improves survival. Primary tumor location and abnormalities in RAS, BRAF, and mismatch repair/microsatellite stability (MMR/MSI) may affect post-CRS-HIPEC survival, but studies have not been consistent. We estimated the effects of primary tumor site and genomic alterations on post-CRS-HIPEC survival. This retrospective cohort study included CRS-HIPEC cases for CRPM at a high-volume center from 2001 to 2020. Next-generation sequencing and microsatellite testing defined the RAS, BRAF, and MMR/MSI genotypes. Adjusted effects of tumor sidedness and genomics on survival were evaluated using a multivariable Cox proportional hazards model. We analyzed these variables' effects on progression-free survival and the effects of immune checkpoint-inhibitors. A total of 250 patients underwent CRS-HIPEC with testing for RAS, BRAF, and MMR/MSI; 50.8% of patients were RAS-mutated, 12.4% were BRAF-mutated, and 6.8% were deficient-MMR/MSI-high (dMMR/MSI-H). Genomic alterations predominated in right-sided cancers. After adjustment for comorbidities and oncological and perioperative variables, rectal origin [hazard ratio (HR) 1.9, p = 0.01], RAS mutation (HR 1.6, p = 0.01), and BRAF mutation (HR 1.7, p = 0.05) were associated with worse survival. RAS mutation was also associated with shorter progression-free survival (HR 1.6, p = 0.01 at 6 months post-operatively), and dMMR/MSI-H status was associated with superior survival (HR 0.3, p = 0.01 at 2 years). dMMR/MSI-H patients receiving immune checkpoint-inhibitors trended toward superior survival. Rectal origin, RAS mutations, and BRAF mutations are each associated with poorer survival after CRS-HIPEC for CRPM. Patients with CRPM and dMMR/MSI-H status have superior survival. Further research should evaluate benefits of immune checkpoint-inhibitors in this subgroup.

ASO Visual Abstract: Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion for Pancreatic Cancer with Low-Volume Peritoneal Metastasis-Results from a Prospective Pilot Study.

ASO Visual Abstract: Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion for Pancreatic Cancer with Low-Volume Peritoneal Metastasis-Results from a Prospective Pilot Study.

Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion for Pancreatic Cancer with Low-Volume Peritoneal Metastasis: Results from a Prospective Pilot Study.

Resection of oligometastatic pancreatic ductal adenocarcinoma (PDAC) has historically been ineffective, however modern systemic chemotherapy has improved survival. Thus, re-evaluating safety and outcomes of surgical resection in selected patients with limited peritoneal metastasis (PM) warrants consideration. From 2018 to 2021, patients with PDAC and positive cytology or limited PM without extraperitoneal metastasis and who had an objective response to ≥ 6 months of systemic chemotherapy were enrolled. Patients underwent laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin/mitomycin C. If amenable to a complete cytoreduction, patients went on to cytoreduction and HIPEC. Overall, 18 patients were enrolled and received a median of 14 (interquartile range [IQR] 12-17) cycles of chemotherapy; 16 (89%) patients received chemoradiation. Laparoscopic HIPEC was completed in 17 patients, with a median length of stay of 1day, and no grade III complications or hematological toxicities were observed. All 18 patients subsequently underwent a complete cytoreduction (CC-0) along with definitive treatment of the primary tumor, with formal resection (7/18), irreversible electroporation (IRE; 10/18), or intraoperative radiation therapy (IORT; 1/18). Median PCI was 2 (IQR 0-4), median LOS was 7 days (IQR 6-8), and 7 (39%) patients were readmitted. Eight (44%) patients experienced grade 3 or higher complications, including one 30-day mortality. At a median follow-up of 16 months, the median progression-free survival was 20 months and the median overall survival was 26 months. Cytoreduction and HIPEC for selected patients with low-volume PMfrom PDAC is safe and feasible with favorable short-term outcomes. A phase II trial (NCT04858009) is now enrolling to further assess this multimodality approach in select patients.

Socioeconomic Barriers to CRS HIPEC for Appendiceal Cancer within a Regional Academic Hospital System.

Appendiceal cancer with peritoneal metastases (ACPM) is a complex disease requiring multidisciplinary care. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS HIPEC) can significantly improve survival but requires evaluation by a surgical oncologist and significant treatment endurance. The impacts of socioeconomic status (SES) and other social determinants of health on rates of surgical evaluation and treatment have not been examined. We conducted a retrospective cohort study examining all patients with ACPM from 2010 to 2018 in a regional healthcare system. Patient characteristics, oncologic details, treatment strategies, and survival were examined. The primary outcomes of interest were referral to Surgical Oncology, receipt of CRS HIPEC, and survival. Of 194 patients identified, 94% had synchronous ACPM. The majority of patients (95%) were referred to surgical oncology. Advanced age was the only predictor of nonreferral (p < 0.001). A total of 147 patients (76%) ultimately underwent CRS HIPEC. After adjusting for medical and tumor characteristics, CRS HIPEC was less likely for patients who were unmarried [odds ratio (OR) 0.253, p = 0.004] or of low SES (OR 0.372, p = 0.03). On subanalysis of patients undergoing CRS HIPEC, median overall survival was worse for patients of low SES [51 months versus not reached (NR), p = 0.05], and this disparity persisted on multivariate analysis [hazard ratio (HR) = 2.278, p = 0.001]. This analysis is the first to evaluate barriers to CRS HIPEC for ACPM. While most patients were evaluated by a multidisciplinary team, nonmedical factors may play a role in the treatment received and ultimate outcomes. Addressing these disparities is crucial for ensuring equitable outcomes and improving patient care.

Role of hyperthermic intraperitoneal chemotherapy in combination with an intraperitoneal port system in the treatment of patients with advanced ovarian cancer

Background. The survival rate of patients with ovarian malignancies depends on the prevalence of the tumor process, the volume of surgical treatment, and the size of the residual tumor. At the first stage, an «aggressive» surgical tactic of removing all macroscopically determined tumor foci with subsequent antitumor drug therapy is recommended. However, the results of treatment remain unsatisfactory, which dictates the need to search for new methods of treatment.Objective: to evaluate the effectiveness of implantable port systems for intraperitoneal chemotherapy administration in the treatment of patients with advanced stages of ovarian cancer.Materials and methods. 37 cases of stage IIIC ovarian cancer were studied for the period 2018–2019. At the first stage of treatment, a cytoreductive operation was performed. At the second stage, the patients were randomly randomized into three groups: group 1 (n = 9) – installation of a port system + hyperthermic intraperitoneal chemoperfusion followed by intraperitoneal chemotherapy; group 2 (n = 11) – hyperthermic intraperitoneal chemoperfusion followed by systemic intravenous chemotherapy; group 3 (n = 17) – control group, intravenous administration of antitumor drugs. The observation period is 27 months. In the study groups, the indicators of age distribution, the degree of malignancy of the neoplasm, the volume of the residual tumor, and the relapse-free survival were analyzed.Results. Trends towards differences in progression-free survival were found in all study groups. In group 1, there was no relapse in all patients. In group 2, relapses amounted to 18.2 %, in group 3–23.5 %. G3 ovarian cancer (6 (66.7 %) and 6 (54.5 %) cases, respectively) prevailed in groups 1 and 2; G1 ovarian cancer (9 (52.9 %) cases) prevailed in group 3. Discussion. Features of the chemical composition and method of administration of the drug increase the effectiveness of local exposure to tumor cells. The introduction  of cytostatic agents into the abdominal cavity leads to minimal systemic toxicity, which exceeds the results of standard intravenous therapy.Conclusion. An advantage in the relapse-free survival of patients after hyperthermic intraperitoneal chemoperfusion in combination with an implantable port system was found in comparison with standard methods of treatment.

Preventive HIPEC in combination with perioperative FLOT versus FLOT alone for resectable diffuse type gastric and gastroesophageal junction type II/III adenocarcinoma \u2013 the phase III \u201cPREVENT\u201d- (FLOT9) trial of the AIO /CAOGI /ACO

BackgroundThe main reason for treatment failure after curative surgical resection of gastric cancer is intra-abdominal spread, with 40–50% peritoneal seeding as primary localization of recurrence. Peritoneal relapse is seen in 60–70% of tumors of diffuse type, compared to only 20–30% of intestinal type.Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) is an increasingly used therapy method for patients with peritoneal metastases. The preventive use of HIPEC could represent an elegant approach for patients (pts) before macroscopic peritoneal seeding, since pts. with operable disease are fit and may have potential risk of microscopic involvement, thus having a theoretical chance of cure with HIPEC even without the need for cytoreduction.No results from a PCRT from the Western hemisphere have yet been published.MethodsThis is a multicenter, randomized, controlled, open-label study including a total of 200 pts. with localized and locally advanced diffuse or mixed type (Laurens’s classification) adenocarcinoma of the stomach and Type II/III GEJ.All enrolled pts. will have received 3–6 pre-operative cycles of biweekly FLOT (Docetaxel 50 mg/m2; Oxaliplatin 85 mg/m2; Leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2wk).Pts will be randomized 1:1 to receive surgery only and postoperative FLOT (control arm) or surgery + intraoperative HIPEC (cisplatin 75 mg/m2 solution administered at a temperature of 42 °C for 90 min) and postoperative FLOT (experimental arm). Surgery is carried out as gastrectomy or transhiatal extended gastrectomy. Primary endpoint is PFS/DFS, major secondary endpoints are OS, rate of pts. with peritoneal relapse at 2 and 3 years, perioperative morbidity/mortality and quality of life.The trial starts with a safety run-in phase. After 20 pts. had curatively intended resection in Arm B, an interim safety analysis is performed.Recruitment has already started and first patient in was on January 18th, 2021.DiscussionIf the PREVENT concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, pts. with gastric cancer and no peritoneal involvement will not be treated with HIPEC during surgery.Trial registrationThe study is registered on June 25th, 2020 under ClinicalTrials.gov Identifier: NCT04447352; EudraCT: 2017-003832-35.

1440TiP Preventive HIPEC in combination with perioperative FLOT versus FLOT alone for resectable diffuse type gastric and gastroesophageal junction type II/III adenocarcinoma: The phase III “PREVENT” trial of the AIO/CAOGI/ACO

Peritoneal relapse is seen in 60-70% of tumors of diffuse type gastric cancer (gc), compared to only 20-30% of intestinal type according to Laurens`s classification. Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) is an increasingly used therapy method for patients with peritoneal metastases. The preventive use of HIPEC could represent an elegant approach for signet ring cell gc patients (pts) before macroscopic peritoneal seeding has happened, since patients with operable disease are fit and may have potential risk of microscopic involvement, thus having a theoretical chance of cure with HIPEC even without the need for cytoreduction.

Cytoreductive Surgery with Hyperthermic Intrathoracic Chemotherapy for Patients with Intrapleural Dissemination of Peritoneal Surface Malignancies.

Peritoneal surface malignancies (PSM) can disseminate into the pleural cavity, increasing morbidity and mortality. While cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) improves outcomes for PSM with intra-abdominal spread, the optimal approach for patients with pleural dissemination from PSM remains unclear. It seems reasonable to apply peritoneal carcinomatosis management principles to patients with pleural lesions using CRS and hyperthermic intrathoracic chemotherapy (HITHOC). We conducted a descriptive study to evaluate outcomes of PSM patients who underwent CRS/HITHOC for pleural dissemination using a high-volume PSM center's prospective database from October 1994-June 2020. CRS/HITHOC was performed via either diaphragmatic window during CRS/HIPEC (CRS/HIPEC+HITHOC) or thoracotomy as a separate procedure (CRS/HITHOC). Of 852 completed CRS/HIPECs, 18 HITHOCs in 15 patients were identified: 10 CRS/HIPEC+HITHOCs, and 8 CRS/HITHOCs. CRS/HIPEC+HITHOC primary tumors included: 4 appendix, 4 ovary, 1 colon, and 1 unknown. All (n = 8) CRS/HITHOC patients had recurrent appendiceal neoplasms. Complete cytoreduction was achieved in 90% of CRS/HIPEC+HITHOCs and 75% of CRS/HITHOCs. Major complications occurred in 20% of CRS/HIPEC+HITHOCs and 13% of CRS/HITHOCs with no 30-day mortality in either group. After median follow-up of 22 months, overall survival at 1, 3, and 5 years was 93.3%, 67.9%, and 67.9%, while 1-, 3-, and 5-year progression-free survival was 70.9%, 20.3%, and 20.3%. Intrapleural recurrence occurred in 1 CRS/HIPEC+HITHOC and 2 CRS/HITHOC patients. CRS/HITHOC performed via diaphragm or thoracotomy at high-volume centers is a safe option for PSM with pleural dissemination. Further comparative studies with longer follow-up are needed to evaluate survival by tumor type.

Preventive HIPEC in combination with perioperative FLOT versus FLOT alone for resectable diffuse type gastric and gastroesophageal junction type II/III adenocarcinoma: The phase III “PREVENT” trial of the AIO /CAOGI /ACO.

TPS4149 Background: The main reason for treatment failure after curative surgical resection of gastric cancer is intra-abdominal spread, with 40- 50% peritoneal seeding as primary localization of recurrence. Peritoneal relapse is seen in 60-70% of tumors of diffuse type, compared to only 20-30% of intestinal type. Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) is an increasingly used therapy method for patients with peritoneal metastases. The preventive use of HIPEC could represent an elegant approach for patients (pts) before macroscopic peritoneal seeding, since patients with operable disease are fit and may have potential risk of microscopic involvement, thus having a theoretical chance of cure with HIPEC even without the need for cytoreduction. No results from a PCRT from the Western hemisphere have yet been published. Methods: This is a multicenter, randomized, controlled, open-label study including a total of 200 pts with localized and locally advanced diffuse and mixed type (Laurens`s classification) adenocarcinoma of the stomach and Type II/III GEJ (i.e. ≥cT3 any N or any T N positive). All enrolled pts will have received 3-6 pre-operative cycles of biweekly FLOT (Docetaxel 50 mg/m²; Oxaliplatin 85 mg/m²; Leucovorin 200 mg/m²; 5-FU 2600 mg/m², q2wk). Pts will be randomized 1:1 to receive surgery only and postoperative FLOT (Arm A- Control arm) or surgery + intraoperative HIPEC (cisplatin 75mg/m2 solution administered at a temperature of 42°C for 90 minutes) and postoperative FLOT (Arm B- experimental arm). Surgery is carried out as gastrectomy or transhiatal extended gastrectomy. Primary endpoint is PFS/DFS, major secondary endpoints are OS, R0 resection rate, perioperative morbidity/mortality including VAS pain score and quality of life as assessed by EORTC QLQ C30 questionnaire. The trial starts with a safety run-in phase. After 20 patients had curatively intended resection in Arm B, an interim safety analysis is performed assessing feasibility, safety, and tolerability in Arm B. First patient was randomized on 18JAN2021. Currently one patient is recruited. EudraCT: 2017-003832-35; ClinicalTrials.gov ID: NCT04447352. Clinical trial information: NCT04447352.

Efficacy and Safety of Systemic and Locoregional Cisplatin Chronotherapy in Rats with Ovarian Carcinoma.

AimAlterations in circadian rhythms caused by tumor growth are thought to be clinically relevant as they affect the prognosis and treatment response. We aimed to evaluate the chronotherapeutic approach in rats with ovarian cancer receiving cisplatin intravenously (IV) or with hyperthermic intraperitoneal chemoperfusion (HIPEC) and to assess daily variations in tumor and intestinal epithelium proliferation.MethodsIn the pilot study, we used 12 intact rats and 12 rats with transplantable ovarian cancer, which were euthanized at ZT0 (08:00, lights on), ZT6, ZT12 and ZT18. In the main study, we used 45 rats with transplantable ovarian cancer. Animals were randomized into five groups: control, HIPEC with cisplatin at ZT0 (08:00), HIPEC with cisplatin at ZT12 (20:00), IV cisplatin at ZT0 and IV cisplatin at ZT12. We assessed the proliferation rate of tumor and small intestinal epithelium, apoptosis in small intestinal epithelium, and levels of γ-H2AX (DNA damage/repair marker) in kidneys and liver. Survival was calculated in each group.ResultsAscitic ovarian cancer disrupted daily variations in intestinal epithelium proliferation and DNA damage/repair in rats. Ovarian carcinoma exhibited no daily variation in mitotic activity. In animals receiving IV cisplatin, massive cell damage in the renal medulla and cystic changes within renal tubules were observed, unlike in rats receiving HIPEC. Tumor mitotic activity was lower in morning-treated groups. The median survival of rats in the control group was 8.5 days (95% CI 6.0–22.0), in HIPEC at ZT0 40.5 days (95% CI 28.0–47.0, p<0.001) and in HIPEC at ZT12 32.0 days (95% CI 28.0–37.0, p<0.001).ConclusionIn a rat model, ovarian tumor growth disrupted daily variations in intestinal epithelium proliferation and caused genotoxic stress in tumor-free tissues. HIPEC with cisplatin at ZT0 had a better efficacy/toxicity profile than HIPEC with cisplatin at ZT12 and IV administration at both time points.

Impact of Socioeconomic Status on Presentation and Outcomes in Colorectal Peritoneal Metastases Following Cytoreduction and Chemoperfusion: Persistent Inequalities in Outcomes at a High-Volume Center

BackgroundCytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS HIPEC) can offer significant survival advantage for select patients with colorectal peritoneal metastases (CRPM). Low socioeconomic status (SES) is implicated in disparities in access to care. We analyze the impact of SES on postoperative outcomes and survival at a high-volume tertiary CRS HIPEC center.Patients and MethodsWe conducted a retrospective cohort study examining patients who underwent CRS HIPEC for CRPM from 2000 to 2018. Patients were grouped according to SES. Baseline characteristics, perioperative outcomes, and survival were examined between groups.ResultsA total of 226 patients were analyzed, 107 (47%) low-SES and 119 (53%) high-SES patients. High-SES patients were younger (52 vs. 58 years, p = 0.01) and more likely to be White (95.0% vs. 91.6%, p = 0.06) and privately insured (83% vs. 57%, p < 0.001). They traveled significantly further for treatment and had lower burden of comorbidities and frailty (p = 0.01). Low-SES patients more often presented with synchronous peritoneal metastases (48% vs. 35%, p = 0.05). Following CRS HIPEC, low-SES patients had longer length of stay and higher burden of postoperative complications, 90-day readmission, and 30-day mortality. Median overall survival following CRS HIPEC was worse for low-SES patients (17.8 vs. 32.4 months, p = 0.02). This disparity persisted on multivariate survival analysis (low SES: HR = 1.46, p = 0.03).ConclusionsDespite improving therapies for CRPM, low-SES patients remain at a significant disadvantage. Even patients who overcome barriers to care experience worse short- and long-term outcomes. Improving access and addressing these disparities is crucial to ensure equitable outcomes and improve patient care.

Comparative analysis of regional chemotherapy methods on an experimental rat model with peritoneal carcinomatosis

Peritoneal carcinomatosis is a variant of implantation metastasis of tumors sprouting the serous membrane of an organ. At the moment, the most effective treatment for this disease is regional chemotherapy. Systemic chemotherapy is not effective enough. The standard for the treatment of peritoneal carcinomatosis was cytoreductive interventions followed by open or closed hypertermic intraperitoneal chemoperfusion (HIPEC) or pressurized intraperitoneal aerosol chemotherapy (PIPAC).&#x0D; Purpose of the study: in an animal experiment to compare the efficacy and safety of regional chemotherapy methods HIPEC and PIPAC&#x0D; Materials and methods: the study was conducted on 44 rats of Wistar females. To simulate carcinomatosis, a strain of ascites ovarian tumor (OA) from the Russian Oncology Cancer Research Center N.N. Petrova. was used. The safety of the technique was evaluated clinically and based on laboratory blood tests. Efficiency - based on mass spectrometry, pathomorphological data and in assessing the life expectancy of animals.&#x0D; Results: the conducted methods HIPEC (open, closed) and PIPAC have shown their safety in experiments on laboratory animals. The closed HIPEC technique is most effective. The analysis of the incidence of postoperative complications demonstrated a greater aggressiveness of open and closed techniques compared to the more “sparing” PIPAC method.&#x0D; Conclusions: the experiment showed comparable safety of all animals tested. Due to the peculiarities of the technique, the PIPAC method can be used as an option for multi-stage treatment in cases where CPC and HIPEC are not possible due to a high index of peritoneal carcinomatosis, and as a neoadjuvant treatment to prevent peritoneal carcinomatosis. In any case, the prospects for using this method require further research.

Debulking and HIPEC for ovarian cancer: effects of perfusion temperature on morbidity and cisplatin pharmacokinetics

Background: In patients with stage III epithelial ovarian cancer (EOC), the addition of hyperthermic intraperitoneal chemoperfusion (HIPEC) to interval debulking was recently shown to improve survival compared to surgery alone. However, the added benefit of hyperthermia remains unknown. Here, we report secondary outcomes of the OvIP study (NCT02567253), a multicenter randomized trial investigating tumor tissue platinum penetration after normothermic (37°C) versus hyperthermic (41°C) chemoperfusion with cisplatin at 75 or 120 mg/m2.

THE EFFECT OF CYTOREDUCTIVE SURGERY AND INTRAPERITONEAL HYPERTHERMIC CHEMOPERFUSION (HIPEC) ON THE CLINICAL OUTCOME OF TREATMENT OF PATIENTS WITH ADVANCED GASTRIC CANCER

Introduction. For gastric cancer (GC), metastatic peritoneal carcinomatosis (PC) is a typical process. PC and its consequences usually lead to the death of 20-40 % of patients with GC. For carefully selected patients, intraperitoneal hyperthermic chemoperfusion may be considered. The aim of the study was to investigate the effect of cytoreductive surgery in combination with HIPEC on the clinical course of the postoperative period, the frequency of postoperative complications and side effects of chemotherapeutic drugs in the treatment of advanced GC. Materials and methods. The results of treatment of 34 patients with advanced GC were considered. The patients were divided into two groups: IA group — 24 patients with advanced GC, who first underwent complete primary cytoreductive surgery (CRS) with adjuvant chemotherapy (ACT) according to the FLOT scheme and IB group — 10 patients with advanced GC treated by CRS + ACT + HIPEC. Results. Comparing the number of patients with postoperative complications in groups IA (CRS + ACT) and IB (CRS + HIPEC + ACT) using the exact bilateral Fisher’s test p&gt; 0. 05. Comparing the frequency of side effects of chemotherapeutic treatment in the FLOT mode in groups IA (CRS + ACT) and IB (CRS + HIPEC + ACT), the values ??of χ2 = 20. 750, χ2Cr = 28. 568 (p = 0. 0622) were obtained. Conclusions. The usage of HIPEC in combination with complete CRS and ACT is a promising method of treatment of this group of patients. As a result of this study, it was proved that there is no statistically significant effect on the clinical course of the postoperative period due to the increase in the frequency of postoperative complications or side effects of chemotherapeutic drugs.