Neoadjuvant Chemotherapy plus Interval Cytoreductive Surgery with or without Hyperthermic Intraperitoneal Chemotherapy (NIHIPEC) in the Treatment of Advanced Ovarian Cancer: A Multicentric Propensity Score Study

Simple Summary Advanced ovarian cancer (Stages III-IV) continues to be one of the gynecological tumors with the highest mortality. Standard treatment consists of debulking surgery and subsequent adjuvant chemotherapy. Recently, some authors have postulated that the administration of hyperthermic chemotherapy during surgery could increase the survival of patients, especially in cases in which chemotherapy had already been administered before surgery to reduce tumor volume. Our study is important because it collects data from 11 tertiary hospitals in Spain, and the data are subjected to a statistical technique that reproduces the data that we would find in a prospective study but using retrospective data (propensity score matching). It also offers a current view of the status of ovarian cancer treatment in our country.Abstract Introduction: Epithelial ovarian cancer (EOC) is primarily confined to the peritoneal cavity. When primary complete surgery is not possible, neoadjuvant chemotherapy (NACT) is provided; however, the peritoneum-plasma barrier hinders the drug effect. The intraperitoneal administration of chemotherapy could eliminate residual microscopic peritoneal tumor cells and increase this effect by hyperthermia. Intraperitoneal hyperthermic chemotherapy (HIPEC) after interval cytoreductive surgery could improve outcomes in terms of disease-free survival (DFS) and overall survival (OS). Materials and Methods: A multicenter, retrospective observational study of advanced EOC patients who underwent interval cytoreductive surgery alone (CRSnoH) or interval cytoreductive surgery plus HIPEC (CRSH) was carried out in Spain between 07/2012 and 12/2021. A total of 515 patients were selected. Progression-free survival (PFS) and OS analyses were performed. The series of patients who underwent CRSH or CRSnoH was balanced regarding the risk factors using a statistical analysis technique called propensity score matching. Results: A total of 170 patients were included in each subgroup. The complete surgery rate was similar in both groups (79.4% vs. 84.7%). The median PFS times were 16 and 13 months in the CRSH and CRSnoH groups, respectively (Hazard ratio (HR) 0.74; 95% CI, 0.58-0.94; p = 0.031). The median OS times were 56 and 50 months in the CRSH and CRSnoH groups, respectively (HR, 0.88; 95% CI, 0.64-1.20; p = 0.44). There was no increase in complications in the CRSH group. Conclusion: The addition of HIPEC after interval cytoreductive surgery is safe and increases DFS in advanced EOC patients

Progress in the management of primary and recurrent ovarian carcinomatosis with peritonectomy procedure and HIPEC in a high volume centre.

The treatment of advanced primary or recurrent ephitelial ovarian cancer still remains an open and a critical question. The addition of HIPEC to cytoreductive surgery has shown improving overall survival rates. The aim of our study is to describe the progress in its management in our Unit and what we have learned after more than 350 HIPEC procedures. From 1997 to 2016 we conducted a retrospective analysis from a prospective database. We described and analyzed 4 cut-points, 1997-2004, 2009, 2012 and 2016. From 1997 to September 2016, 358 patients have been operated in our Unit by CRS with peritonectomy procedures plus HIPEC for stage IIIc and IV ovarian cancer. The HIPEC procedures rate was 4,7 HIPEC per years in the first years up to 35 HIPEC/year in last era. Mean age was 56,7 years (28-78). Median PCI was 15,8. (range 3-36). R0-cytoreduction was 95%. Severe morbidity and mortality were observed in 15 % and 2%, respectively. The 3 y OS was 77% in primary and 79% in recurrent ovarian cancer. The stage IV was not a risk factor for survival. R1 cytoreduction and positive lymph nodes were risk factors in multivariate analysis. The addition of HIPEC to CRS improves overall survival rates for primary and recurrent ovarian cancer. This therapeutic strategy was incorporated twenty years ago for a few teams in the world and today there is an emerging and strong evidence that could consider it as an standard treatment for the ovarian carcinomatosis

Gastrointestinal stromal tumors: A multidisciplinary challenge.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors located in the alimentary tract. Its usual manifestation is gastrointestinal bleeding. However, small asymptomatic lesions are frequently detected as incidental finding. Characteristically, most GISTs (> 95%) are positive for the KIT protein (CD117) by IHC staining and approximately 80%-90% of GISTs carry a mutation in the c-KIT or PDGFRA genes. Mutational analysis should be performed when planning adjuvant and neoadjuvant therapy, due to its possible resistance to conventional treatment. The arise of tyrosine kinase inhibitor has supposed a revolution in GISTs treatment being useful as adjuvant, neoadjuvant or recurrence disease treatment. That is why a multidisciplinary approach to this disease is required. The correct characterization of the tumor at diagnosis (the diagnosis of recurrences and the evaluation of the response to treatment with tyrosine kinase inhibitors) is fundamental for facing these tumors and requires specialized Endoscopist, Radiologists and Nuclear Medicine Physician. Surgery is the only potentially curative treatment for suspected resectable GIST. In the case of high risk GISTs, surgery plus adjuvant Imatinib-Mesylate for 3 years is the standard treatment. Neoadjuvant imatinib-mesylate should be considered to shrink the tumor in case of locally advanced primary or recurrence disease, unresectable or potentially resectable metastasic tumors, and potentially resectable disease in complex anatomic locations to decrease the related morbidity. In the case of Metastatic GIST under Neoadjuvant treatment, when there are complete response, stable disease or limited disease progression, complete cytoreductive surgery could be a therapeutic option if feasible

Residual tumour less than 0.25 centimetres and positive lymph nodes are risk factors for early relapse in recurrent ovarian peritoneal carcinomatosis treated with cytoreductive surgery, HIPEC and systemic chemotherapy.

The cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has showed promising results for the survival in patients with recurrent ovarian carcinomatosis, however, some of them will recur within the first year. The aim of this study is focussed on identifying the risk factors to develop the recurrence within the first year after an optimal CRS-HIPEC in patients with recurrent ovarian carcinomatosis. A total of 100 patients with peritoneal carcinomatosis from recurrent ovarian cancer treated by CRS + HIPEC were selected for analysis. Multivariate logistic regression analysis was performed to evaluate the relationship between the variables and the early recurrence. The mean follow-up was 42.5 months. The mean age was 56.2 years. Early recurrence was observed in the 36%. The group early recurrence presented a higher rate of optimal cytoreductions CC1 (16.2% vs. 3.5%), lymph nodes (32.5% vs. 15%) and the use of hemoderivates (40.5% vs. 33%). Others parameters as Peritoneal Cancer Index, major morbidity? 3, re-operations rate and time to adjuvant chemotherapy were similar in both groups. The five years OS was 58%, for the non-early recurrence was higher than the early recurrence group (64% vs. 41%). In the multivariate analysis, CC-1 (OR 5.73; 1.16-32.04) and positive lymph nodes (OR 2.26; 1.01-4.32) proved to be independent factors for the early recurrence. The combination of both (CC1 and positive lymph nodes) makes that the indication of CRS and HIPEC should be individualised. However, the major morbidity, stage IV and the time to the adjuvant treatment were not associated with an early recurrence, so that, a major aggressiveness is recommended to achieve a CC0

Peritoneal metastasis of advanced epithelial ovarian carcinoma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A retrospective international multicentric data analysis

Introduction: The purpose of our study was to evaluate outcome data after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis originating from advanced epithelial ovarian carcinoma (PMOC). Patients and methods: A retrospective international multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group. Results: One thousand four hundred and ninety-one patients from 11 specialized units underwent CRS and HIPEC that of those 326 (21.9%) upfront surgeries, 504 (33.8%) interval surgery, and 661(44.3%) recurrent cases. Complete Cytoreduction(CC0/1) was achieved in 1213 patients (81.3%). Treatment -related mortality was 0.8%, major operative complications (Grades 3-5) was 25.1%. Factors associated with major operative complications include prior surgical score (PSS for recurrent cases; RC) PSS>2,p = 0.000), PCI(≤15, >15 cut-off level; p ≤ 0.000), completeness of cytoreduction (CC, p=0.000), high CA125 levels (>25 mg/dl), presence of ascites, high CRP (>5 mg/dl) levels and low albumin levels (below to 2.5 mg/dl) (p ≤ 0.05). The median survival was 58 months in upfront surgery(UFS), 60 months in interval surgery(IS), and 42 months in RC. The overall survival for five years was 45% for UFS, 37% for IS, 28% for RC cases. CCscore (p = 0.000), CA125, CRP and albumin levels (p ≤ 0.05) were predictors for progression free survival. PCI(p ≤ 0.000), major postoperative complications (p = 0.004), incomplete CRS(CC2/3)(p < 0.001), prior chemotherapy (hazard ratio [HR], 3-8; p < 0.001) and PSS>2 for RC were independent predictors of poor overall survival. Conclusion: The combined treatment strategy for PMOC may be performed safely with acceptable morbidity and mortality in the specialized units