Correlation of Morphological Appearance of Peritoneal Lesions at Laparotomy and Disease at Pathological Assessment in Patients Undergoing Cytoreductive Surgery for Peritoneal Malignancy: Results of Phase I of the PRECINCT Study in 707 Patients.

BACKGROUND: The PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumors) is a prospective, multicenter, observational study. This report from phase I of PRECINCT outlines variations in recording the surgical peritoneal cancer index (sPCI) at experienced peritoneal malignancy centers and the incidence of pathologically confirmed disease in morphologically different peritoneal lesions (PL). METHODS: The sPCI was recorded in a prespecified format that included the morphological appearance of PL. Six prespecified morphological terms were provided. The surgical and pathological findings were compared. RESULTS: From September 2020 to December 2021, 707 patients were enrolled at 10 centers. The morphological details are routinely recorded at two centers, structure bearing the largest nodule, and exact size of the largest tumor deposit in each region at four centers each. The most common morphological terms used were normal peritoneum in 3091 (45.3%), tumor nodules in 2607 (38.2%) and confluent disease in 786 (11.5%) regions. The incidence of pathologically confirmed disease was significantly higher in 'tumor nodules' with a lesion score of 2/3 compared with a lesion score of 1 (63.1% vs. 31.5%; p < 0.001). In patients receiving neoadjuvant chemotherapy, the incidence of pathologically confirmed disease did not differ significantly from those undergoing upfront surgery [751 (47.7%) and 532 (51.4%) respectively; p = 0.069]. CONCLUSIONS: The sPCI was recorded with heterogeneity at different centers. The incidence of pathologically confirmed disease was 49.2% in 'tumor nodules'. Frozen section could be used more liberally for these lesions to aid clinical decisions. A large-scale study involving pictorial depiction of different morphological appearances and correlation with pathological findings is indicated.

Assessment of Intraoperative Scoring Systems for Predicting Cytoreduction Outcome in Peritoneal Metastatic Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Cytoreductive surgery (CRS) is a widely acknowledged treatment approach for peritoneal metastasis, showing favorable prognosis and long-term survival. Intraoperative scoring systems quantify tumoral burden before CRS and may predict complete cytoreduction (CC). This study reviews the intraoperative scoring systems for predicting CC and optimal cytoreduction (OC) and evaluates the predictive performance of the Peritoneal Cancer Index (PCI) and Predictive Index Value (PIV). METHODS: Systematic searches were conducted in Embase, MEDLINE, and Web of Science. Meta-analyses of extracted data were performed to compare the absolute predictive performances of PCI and PIV. RESULTS: Thirty-eight studies (5834 patients) focusing on gynecological (n = 34; 89.5%), gastrointestinal (n = 2; 5.3%) malignancies, and on tumors of various origins (n = 2; 5.3%) were identified. Seventy-seven models assessing the predictive performance of scoring systems (54 for CC and 23 for OC) were identified with PCI (n = 39/77) and PIV (n = 16/77) being the most common. Twenty models (26.0%) reinterpreted previous scoring systems of which ten (13%) used a modified version of PIV (reclassification). Meta-analyses of models predicting CC based on PCI (n = 21) and PIV (n = 8) provided an AUC estimate of 0.83 (95% confidence interval [CI] 0.79-0.86; Q = 119.6, p = 0.0001; I2 = 74.1%) and 0.74 (95% CI 0.68-0.81; Q = 7.2, p = 0.41; I2 = 11.0%), respectively. CONCLUSIONS: Peritoneal Cancer Index models demonstrate an excellent estimate of CC, while PIV shows an acceptable performance. There is a need for high-quality studies to address management differences, establish standardized cutoff values, and focus on non-gynecological malignancies.

Does the choice of platinum doublet matter? A study to evaluate the impact of platinum doublet choice for treatment of platinum-sensitive ovarian cancer recurrence on the development of future PARP inhibitor and platinum resistance.

OBJECTIVES: The use of a platinum doublet for the treatment of platinum-sensitive epithelial ovarian cancer (EOC) recurrence is well established. The impact of the non­platinum chemotherapy used as part of a platinum doublet on PARP inhibitor (PARPi) and platinum sensitivity it not known. We aimed to describe oncologic outcomes in cases of recurrent EOC receiving PARPi as maintenance therapy based on preceding platinum doublet. METHODS: Retrospective study of patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancer treated with platinum doublet followed by maintenance PARPi from 1/1/2015 and 1/1/2022. Comparisons were made between patients receiving carboplatin + pegylated liposomal doxorubicin (CD) versus other platinum doublets (OPDs). Descriptive statistics, Kaplan-Meier and univariate survival analyses were performed. RESULTS: 100 patients received PARPi maintenance following a platinum doublet chemotherapy regimen for platinum-sensitive recurrence. 25/100 (25%) received CD and 75/100 (75%) received OPDs. Comparing CD and OPDs, median progression-free survival was 8 versus 7 months (p = 0.26), median time to platinum resistance was 15 versus 13 months (p = 0.54), median OS was 64 versus 90 months (p = 0.28), and median OS from starting PARPi was 25 versus 26 months (p = 0.90), respectively. CONCLUSIONS: Using pegylated liposomal doxorubicin as part of a platinum doublet preceding maintenance PARPi for platinum-sensitive recurrence does not seem to hasten PARPi resistance or platinum resistance compared to OPDs. Although there was a non-significant trend towards increased OS among patients who received a platinum doublet other than CD prior to PARPi, the OS from PARPi start was similar between groups. Given the retrospective nature of this study and small study population, further research is needed to evaluate if the choice of platinum doublet preceding PARPi maintenance impacts PARPi resistance, platinum resistance and survival.

Impact of Previous Abdominal Surgery and Timing of Peritoneal Metastases on Accuracy of Imaging in Predicting the Surgical PCI: A Report From the PRECINCT Study.

BACKGROUND AND AIM: In this report from Phase 1 of the prospective, observational, PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumours) study, a correlation was performed between the radiological PCI (peritoneal cancer index; rPCI) and surgical PCI (sPCI). The impact of timing of peritoneal malignancy (PM) and previous abdominal surgery was also studied. METHODS: The rPCI and sPCI were considered the 'same' if they differed by ≤ 3 points. The agreement was assessed using Bland-Altman analysis and the strength of the agreement was assessed using the concordance correlation coefficient (CCC). The extent of prior surgery was classified according to prior surgical score (PSS). RESULTS: In 707 (79.4%) patients, rPCI and sPCI concurred in 280 (39.6%). In the Bland-Altman analysis, < 40% patients were in the ±3 PCI points limit of acceptable difference. The average difference between the two scores was 4.5 points (95% CI- -5.16 to -3.92). The CCC- was 0.59 for the whole cohort ('moderate' concordance) and was not influenced by imaging modality, timing of PM or PSS. CONCLUSIONS: The rPCI underestimated sPCI by an average of 4.5 points. The role of peritoneal MRI in patients undergoing iterative procedures and the performance of imaging according to sites of recurrence need further evaluation.

Critical reappraisal of prognostic indicators for 949 mucinous appendiceal neoplasm patients.

BACKGROUND AND OBJECTIVES: The standard of care for treatment of an appendiceal mucinous neoplasm with peritoneal dissemination is cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). These two treatments are combined in the operating room. A crucial requirement for benefit long-term is proper patient selection. Clinical and histopathologic prognostic indicators are used, along with the patient's fitness for surgery, to select patients to receive CRS and HIPEC. METHODS: This study seeks to identify the reliable prognostic indicators for four different groups of patients. They are (1) the low-grade appendiceal mucinous neoplasms (LAMN) with a complete CRS, (2) the mucinous appendiceal adenocarcinomas (MACA) with complete CRS, (3) MACA with lymph node metastases (MACA-LN) with complete CRS, and (4) all histologic subtypes with incomplete cytoreduction. The prognostic indicators were evaluated for their impact on overall survival in these four groups of patients. RESULTS: The completeness of cytoreduction (CC) score statistically significantly showed survival differences in all three histologic subtypes. The peritoneal cancer index (PCI) showed significance with LAMN and MACA-LN but not with MACA and not with incomplete CRS. The prior surgical score (PSS) was a prognostic indicator that predicted the outcome with LAMN, MACA-LN, and incomplete CRS patients but not with the MACA group. Patients who were symptomatic or who had extensive systemic chemotherapy before CRS had a significantly reduced survival. CONCLUSION: The utility of prognostic indicators varied greatly within our four different groups of appendiceal mucinous neoplasms. CC score was always a reliable prognosticator. Surprisingly, PCI was not.

Extremely high peritoneal cancer index in colorectal peritoneal metastases demonstrates safety and overall survival benefit in selected patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy.

BACKGROUND: Colorectal peritoneal metastases are a devastating consequence of colorectal cancer (CRC) with extremely poor prognosis. Patients that can undergo complete cytoreduction by cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) have a markedly improved overall survival. Traditionally, patients with extremely high peritoneal cancer index (PCI), PCI >20, are not offered CRS/HIPEC. METHODS: We performed a retrospective analysis of our prospectively maintained CRS/HIPEC database and evaluated all patients with CRC peritoneal metastases between 2012 and 2022. We divided the cohorts between those with low operative PCI (PCI<20) and high operative PCI (PCI =>20). We examined demographic, clinicopathologic data, perioperative, and oncological outcomes between the cohorts. RESULTS: Of the 691 patients who underwent CRS/HIPEC, 289 were evaluable with CRC metastases, 234 with PCI <20 and 43 with PCI => 20. Median radiologic preoperative and operative PCI was 4 and 10 versus 7 and 24.5 in the low and high PCI cohorts, respectively. Operative time was longer (6 vs. 4 h) and blood loss higher (500 vs. 400 mL) in the high PCI cohort. All other demographic, clinicopathological, and operative characteristics were similar. Median disease free survival (DFS) was longer in the low PCI cohort (11.5 vs. 7 months) but overall survival (OS) showed benefit (41.3 vs. 31.8 months), (p = 0.001 and p = 0.189, respectively), comparatively with an only chemotherapy strategy. CONCLUSIONS: Appropriately selected patients with CRC metastases and extremely high PCI demonstrate similar perioperative safety outcomes in experienced tertiary referral centers. Despite a shorter median DFS, these carefully selected patients demonstrated similar median OS.

The role of cytoreductive surgery and HIPEC for the treatment of primary and secondary peritoneal malignancies-experience from a tertiary care center in Germany.

PURPOSE: Peritoneal surface malignancies (PSM) are commonly known to have a dismal prognosis. Over the past decades, novel techniques such as cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been introduced for the treatment of PSM which could improve the overall survival and quality of life of patients with PSM. The decision to proceed with CRS and HIPEC is often challenging due the complexity of the disease, the extent of the procedure, associated side effects, and potential risks. Here, we present our experience with CRS and HIPEC to add to the ongoing discussion about eligibility criteria, technical approach, and expected outcomes and contribute to the evolution of this powerful and promising tool in the multidisciplinary treatment of patients with primary and secondary PSM. METHODS: A single-center retrospective chart review was conducted and included a total of 40 patients treated with CRS and HIPEC from April 2020 to September 2022 at the University Hospital Münster Department of Surgery. All patients had histologically confirmed primary or secondary peritoneal malignancies of various primary origins. RESULTS: Our study included 22 patients with peritoneal metastases from gastric cancer (55%), 8 with pseudomyxoma peritonei (20%), 4 with mesothelioma of the peritoneum (10%), and 6 patients with PSM originating from other primary tumor locations. Median PCI at time of cytoreduction was 4 (0-25). Completeness of cytoreduction score was 0 in 37 patients (92.5%), 1 in two patients (5%), and 2 in one patient (2.5%). Median overall survival across all patients was 3.69 years. CONCLUSION: Complete cytoreduction during CRS and HIPEC can be achieved for patients with low PCI, for patients with high PCI in low-grade malignancies, and even for patients with initially high PCI in high-grade malignancies following a significant reduction of cancer burden due to extensive preoperative treatment with PIPAC and systemic chemotherapy.

The importance of integrating diagnostic modalities in patient selection for CRS-HIPEC in colorectal peritoneal metastases.

BACKGROUND: Despite thorough preoperative work-up for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), so called open-close (OC) procedures as a result of irresectable disease remain common. Currently, diagnostic laparoscopy (DLS) is considered the gold standard, and consequently overrules the results of computed tomography (CT) scans; however, certain regions of the abdomen are difficult to assess and postoperative adhesion formation may further compromise staging during DLS. PURPOSE: To determine whether better clinical assessment could be achieved by combining the results of DLS and preoperative CT scans during a multidisciplinary team (MDT) meeting. MATERIAL AND METHODS: All patients who were eligible for CRS-HIPEC after DLS, but eventually underwent an OC procedure between 2010 and 2018 were selected. Radiological reassessment of CT scans was performed and combined with assessment of the DLS during a MDT meeting. The MDT was blinded for the outcome of the procedure (OC vs. CRS-HIPEC). RESULTS: The majority of the OC procedures (69%) was correctly predicted by the MDT. In most patients (88%), this conclusion was based on the combination of the radiological and surgical peritoneal cancer index (PCI). CT was particularly accurate for detection of larger tumor deposits in the abdominal regions, as 84%-86% was detected. Assessment of lesions in the small bowel regions is troublesome; 72% of lesions are missed on the preoperative CT scan. CONCLUSIONS: A combination of radiological and surgical assessment of the PCI may lead to improved preoperative patient selection for CRS-HIPEC.

Optimal peritoneal cancer index cutoff point for predicting surgical resectability of pseudomyxoma peritonei in treatment-naive patients.

BACKGROUND: The peritoneal cancer index (PCI) has been used to predict surgical outcomes for pseudomyxoma peritonei (PMP). The present study aimed to establish the optimal cutoff point for PCI to predict surgical resectability of PMP. METHODS: A total of 366 PMP patients were included. The patients were divided into low-grade and high-grade groups. Based on the completeness of the cytoreduction (CC) score, both low-grade and high-grade PMP patients were further divided into complete cytoreductive surgery (CRS) and maximal tumor debulking (MTD) subgroups. The ability to predict surgical resectability of total and selected PCI (regions 2 + 9 to 12) was analyzed through receiver operating characteristic (ROC) curves. RESULTS: Both total and selected PCI demonstrated excellent discriminative ability in predicting surgical resectability for low-grade PMP patients (n = 266), with the ROC-AUC of 0.940 (95% CI: 0.904-0.965) and 0.927 (95% CI: 0.889-0.955). The corresponding optimal cutoff point was 21 and 5, respectively. For high-grade PMP patients (n = 100), both total and selected PCI exhibited good performance in predicting surgical resectability, with the ROC-AUC of 0.894 (95% CI: 0.816-0.946) and 0.888 (95% CI: 0.810-0.943); correspondingly, the optimal cutoff point was 25 and 8, respectively. The discriminative ability between total and selected PCI in predicting surgical resectability did not show a statistical difference. CONCLUSIONS: Both total and selected PCI exhibited good performance and similarity in predicting complete surgical resection for both low-grade and high-grade PMP patients. However, the selected PCI was simpler and time-saving in clinical practice. In the future, new imaging techniques or predictive models may be developed to better predict PCI preoperatively, which might assist in confirming whether complete surgical resection can be achieved.

Is extereme cytoreductive surgery beneficial to survival in malignant peritoneal mesothelioma?

INTRODUCTION: Malign peritoneal mesothelioma (MPM) is an uncommon disease that is difficult to treat. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) are the gold standards for treating MPM. Sometimes extreme cytoreductive surgery (eCRS) is required to achieve complete cytoreduction, which is one of the most important prognostic factors. There is limited information in the literature about the contribution of eCRS in patients with MPM. In this study, we aimed to investigate the impact of eCRS on survival and perioperative outcomes. METHODS: The Department of Surgical Oncology at Cumhuriyet University database was retrospectively reviewed for MPM patients who underwent CRS-HIPEC between January 2004 and December 2018. Patients who underwent CRS-HIPEC were divided into eCRS and less extensive CRS (leCRS) groups. A resection of ≥5 organs or ≥3 small bowel anastomoses were defined as eCRS. Both groups were compared regarding survival, demographic information, and perioperative outcomes. RESULTS: A total of 31 patients were included. eCRS-HIPEC was used in 15 patients. Complete cytoreduction (CC score 0/1) was achieved in all 31 patients. Compared to leCRS, the eCRS group had a longer median length of stay, longer intensive care unit stay, a higher median peritoneal cancer index (PCI), higher intraoperative blood loss, more frequent occurrence of any complication, and a longer operative time (all p values < 0.001). Clavien Dindo 3-4 complications, ASA, and gender were similar in both groups of patients (p > 0.05). It was found that there was no significant difference between the OS of the eCRS and leCRS groups (37.5 vs. 42.8 months, p = 0.895). CONCLUSIONS: Rates of serious complications and morbidity are similar in patients undergoing eCRS compared to leCRS. In patients with high PCI and multiorgan involvement, complete cytoreduction can be achieved by performing eCRS, and survival results equivalent to those with low PCI can be achieved.

Same day service: A genetic testing station model to improve germline genetic testing in patients with ovarian cancer.

OBJECTIVE: Genetic testing for ovarian cancer (OC) patients is essential to consideration of PARP inhibitor therapy. To improve access, we piloted a Genetic Testing Station (GTS) allowing patients to have a same-day genetic testing visit facilitated by Genetic Counselor Assistants (GCAs) under the supervision of Genetic Counselors (GCs). METHODS: The GTS was implemented December 2018 and operated through February 2020. Gynecologic Oncologists offered ovarian cancer patients a same-day GTS visit with a GCA. The patient received education via videos designed by GCs and then provided consent, a brief family history, and a sample for a standardized 133-gene panel. Results were provided by a GC. Patients were retrospectively identified by querying the medical record for OC patients seen 12 months prior to and 18 months after GTS implementation. RESULTS: A total of 482 patients pre-GTS were compared to 625 patients post-GTS. Genetic testing increased from 68.5% to 75.4% (p = 0.012) after implementation, primarily in patients with epithelial histologies (80% vs 89% in pre-GTS vs post-GTS, p = 0.005). Time from referral for genetic testing to obtaining results was evaluated in the post-GTS cohort, comparing patients who had traditional counseling to those who utilized the GTS. Time to obtaining results was 21 days in the GTS group (95% CI [10, 34]) compared to 56 days (95% CI [41,76]) in the traditional genetic counseling group. CONCLUSIONS: The GTS reduces barriers to care and facilitates discussion of precision treatment within a timely fashion while optimizing GC clinic time. Access improvement remains integral to improving uptake of genetic testing.

Combined ultrasonography and CT for prognosis and predicting clinical outcomes of patients with pseudomyxoma peritonei.

OBJECTIVES: This study aimed to identify the diagnostic accuracy of combined ultrasonography (US) and computed tomography (CT) in evaluating the tumor burden of pseudomyxoma peritonei (PMP). Besides, we assessed the ability of this combination to predict the likelihood of complete resection. METHODS: This retrospective study involved 504 patients diagnosed with PMP and scheduled for cytoreduction surgery. We compared tumor burden-quantified as peritoneal cancer index (PCI) by preoperative US and CT (US-CT-PCI)-with surgical findings. Next, we assessed the prognostic value of US-CT PCI and imaging features in determining the completeness of cytoreduction (CCR) score using multivariate analysis. RESULTS: US-CT PCI demonstrated a high PCI evaluation accuracy under moderate tumor burden. Higher US-CT PCI could predict incomplete resection. In addition, we identified imaging features such as mesenteric involvement as an independent predictor of incomplete resection (hazard ratio (HR) = 2.006; p = 0.007). CONCLUSIONS: US-CT PCI allowed us to predict the completeness of cytoreductive surgery in patients with PMP. Moreover, the combined US and CT imaging detected several features indicating incomplete cytoreduction. KEY POINTS: • Ultrasonography (US) can act as a complementary diagnostic modality in peritoneal cancer index (PCI) evaluation by combining CT in the small bowel area and US in the abdominal area. • A modified peritoneal cancer index (US-CT PCI) helps preoperatively evaluate tumor burden with high accuracy and allows to predict incomplete resection. • US-CT PCI of 20 or above and the involvement of particular structures such as mesentery, independently indicate incomplete resection.

Prognostic indicators for colorectal peritoneal metastases are different for patients with complete versus incomplete cytoreductive surgery.

BACKGROUND: In the management of peritoneal metastases in patients with colorectal cancer, the completeness of cytoreduction has consistently been the most prominent prognostic indicator. Other clinical and histologic features have been described that may also have an impact on survival. METHODS: The colorectal peritoneal metastases patients treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy were divided into two groups. One group had complete CRS and the second group had an incomplete CRS. The prognostic variables in these two groups of patients were statistically analyzed for their impact on survival. RESULTS: In the complete CRS group of 124 patients lymph node positivity, poorly differentiated histopathology, asymptomatic status following treatment with systemic chemotherapy, incomplete response to systemic chemotherapy, and moderate to high peritoneal cancer index showed a significantly reduced survival. All five of these prognostic variables ceased to show statistical significance in the group of 82 patients with incomplete cytoreduction. CONCLUSION: The cause for significance of five prognostic indicators identified in patients with complete cytoreduction versus loss of significance of these indicators in patients with incomplete cytoreduction has not been determined. An absence of residual disease in complete CRS patients and a widely variable extent of residual disease in incomplete CRS patients may be important. Prognostic indicators in patients with colorectal peritoneal metastases find their greatest usefulness in patients who have had a complete cytoreduction.

ARTISTRY-7: phase III trial of nemvaleukin alfa plus pembrolizumab vs chemotherapy for platinum-resistant ovarian cancer.

Standard single-agent nonplatinum chemotherapy provides only modest benefit in a small proportion of patients with platinum-resistant/-refractory ovarian cancer, with objective response rates of 6-20% and progression-free survival of ≈3-4 months. Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel cytokine designed to capture and expand the therapeutic potential of high-dose interleukin-2 (IL-2) while mitigating its associated toxicity issues. Nemvaleukin preferentially activates cytotoxic CD8+ T cells and natural killer cells with minimal, non-dose-dependent effects on CD4+ regulatory T cells. The global, randomized, open-label, phase III ARTISTRY-7 trial will compare efficacy and safety of nemvaleukin plus pembrolizumab with chemotherapy in patients with platinum-resistant ovarian cancer. The primary end point is investigator-assessed progression-free survival. Clinical Trial Registration: GOG-3063; ENGOT-OV68; NCT05092360 (ClinicalTrials.gov).

In many patients with ovarian cancer who are treated with platinum-based chemotherapy, the tumor comes back after a few months and fails to respond to repeated treatment. This type of disease is called platinum-resistant ovarian cancer (PROC). Researchers are searching for new medicines to help more patients with PROC. One treatment approach that has shown promise in different cancers is called immunotherapy. These medicines work by helping the body's immune system attack cancer cells. One of the immunotherapies being studied is called nemvaleukin. It is designed to trigger specific immune responses that may result in the immune system attacking cancer cells while potentially avoiding other immune responses that can block the attack or cause certain unwanted side effects. Nemvaleukin is being studied in a variety of cancer types. In a worldwide clinical trial called ARTISTRY-7, researchers are investigating how nemvaleukin works in patients with PROC when given with another immunotherapy called pembrolizumab. Patients who participate in this trial will be randomly assigned to one of four treatment groups: the combination of nemvaleukin and pembrolizumab, nemvaleukin by itself, pembrolizumab by itself, or a type of chemotherapy selected by the treating physician. The main purpose of ARTISTRY-7 is to understand whether the combination of nemvaleukin and pembrolizumab helps patients with PROC live longer without their cancer getting worse. At the time of this writing, ARTISTRY-7 is open for new patients to join.

Prognostic significance of the immuno-peritoneal cancer index in peritoneal metastatic patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

PURPOSE: A valid comparison of immune function among different patients with different primary pathologies or even with different tumour burdens requires the common use of a reliable assessment of the patient's condition. The combined immuno-PCI system can translate a complex clinical situation into a simple point value to improve postoperative outcomes to assess the prognostic significance of combined immuno-PCI in peritoneal metastatic patients treated with cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC). PATIENTS AND METHODS: Four hundred twenty-four patients from the prospectively maintained database of Dokuz Eylul University Peritoneal Surface Malignancy Center were retrospectively analysed. In addition to the demographic findings and the well-known clinicopathologic factors, several systemic inflammation-based prognostic scores, including the modified Glasgow prognostic score (mGPS), CRP-albumin ratio (CAR), neutrophil-lymphocyte ratio (NLR), neutrophil-thrombocyte ratio (NTR), and thrombocyte count, were all searched and stratified into scoring categories as prognostic determinants of surgical complications, final oncologic outcomes, recurrent disease, disease-free survival (DFS), and overall survival (OS). ROC analyses were performed, and cut-off values were obtained for all immune parameters by using the Youden index method. RESULTS: There were 314 (74%) women and 110 (26%) men. The median age was 56 (ranging from 18 to 86) years. The most frequent sites of peritoneal metastasis were colorectal (n = 204; 48%) and gynaecologic carcinomas (n = 187; 44%). Thirty-three patients (8%) had primary malignant peritoneal mesothelioma. The median follow-up was 37.8 (ranging from 1 to 124) months. The overall survival was 51.7%. The 1-year, 3-year, and 5-year survival rates were estimated as 80%, 48.4%, and 32.6%, respectively. PCI-CAR-NTR (1 to 3) (p < .001) scoring was an independent prognostic factor for DFS. In a Cox backwards regression analysis, anastomotic leak (p = .002), completeness of cytoreduction (p = .0014), number of organ resections (p = .002), lymph node involvement (p = .003), and PCI-CAR-NTR (1 to 3) scoring (p = .001) were found to be independently significant prognostic factors for overall survival. CONCLUSION: The PCI is a reliable and consistently valid prognostic factor to evaluate the tumour burden and tumour extent in patients treated with CRS/HIPEC. Staging the host by combining the PCI with an immunoscore may help to improve the outcomes of complications and overall survival in these complex cancer patients. The aggregate maximum immuno-PCI tool may be a better prognostic measure for outcome evaluation.

Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual Patient Report for 2020 and Annual Treatment Report for 2015.

AIM: To provide information including the trend of gynecological malignancies in Japan, we hereby present the annual patient report for 2020 and the Annual Treatment Report for 2015, on the outcomes of patients who started treatment in 2015. METHODS: The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2020 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2015 was analyzed by using the Kaplan-Meier, log-rank, and Wilcoxson tests. RESULTS: Treatment was initiated in 2020 for 7689 patients with cervical cancer, 13 113 with endometrial cancer, 8004 with ovarian, tubal, and peritoneal cancer, 2152 with ovarian borderline tumors, and with the others (260 vulvar cancer, 157 vaginal cancer, 464 uterine sarcoma, 50 uterine adenosarcoma, 136 trophoblastic diseases). This clinicopathological information was summarized as the patient annual report. The 5-year survival rates of the patients with cervical cancer were 92.3%, 76.2%, 56.5%, and 32.2% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 93.9%, 87.6%, 71.4%, and 29.3% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 91.7%, 80.6%, 50.8%, and 39.7% for Stages I, II, III, and IV, respectively. CONCLUSION: The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

Mainstream genetic testing for high-grade ovarian, tubal and peritoneal cancers: A tertiary referral centre experience.

BACKGROUND: Fifteen percent of ovarian, tubal, and peritoneal (OTP) invasive epithelial cancers are linked to an underlying heritable pathogenic variant (PV) in the BRCA1/2 cancer susceptibility genes. Identifying a PV has management implications for an affected individual and relatives. Cancer team-facilitated genetic testing (mainstreaming) aims to provide equitable systematic access to genetic testing for appropriate patients. AIM: To evaluate a multi-disciplinary team (MDT)-led mainstream germline genetic testing program for OTP cancer at a tertiary referral centre. MATERIALS AND METHODS: We conducted a retrospective review of our MDT-led mainstream genetic testing program initiated in June 2017. We included all patients diagnosed with OTP cancer registered with the hospital gynaecological oncology MDT from program initiation to December 2020. Patients were considered eligible for testing if they were diagnosed with a high-grade epithelial OTP AND ≤70 years, OR if >70 with a first/second degree relative with breast and/or ovarian cancer OR Jewish ancestry. RESULTS: Of 205 women diagnosed with high-grade epithelial OTP cancer, 140 were eligible for mainstreaming. Eight-five percent were mainstreamed, with the gynae-oncologists facilitating 64.5% of tests. The overall PV detection rate in BRCA1/2 was 10.1% (BRCA1 n = 9, BRCA2 n = 3). The median turnaround time (TAT) was 44.5 days (range 16-118). All women with PV were referred to the Familial Cancer Service for further assessment and five (of six eligible; 83%) were subsequently treated with polyadenosine diphosphate ribose polymerase inhibitors. Cascade testing was undertaken in 75% of families with a mean of three relatives tested per proband. CONCLUSION: Mainstreamed genetic testing is feasible, with an acceptable TAT, ensuring adequate opportunity to inform treatment decisions. Tumour testing and inclusion of moderate-risk cancer predisposition genes in mainstreaming represent potential pathways that will require further exploration.

Efficacy and safety of standard of care with/without bevacizumab for platinum-resistant ovarian/fallopian tube/peritoneal cancer previously treated with bevacizumab: The Japanese Gynecologic Oncology Group study JGOG3023.

We investigated the efficacy and safety of further bevacizumab therapy in patients with platinum-resistant ovarian cancer whose disease had progressed after bevacizumab plus chemotherapy. In this multicenter, open-label, phase II trial (JGOG3023), patients were randomized 1:1 to a single-agent chemotherapy alone (either pegylated liposomal doxorubicin [40 or 50 mg/m2 administered intravenously], topotecan [1.25 mg/m2 intravenously], paclitaxel [80 mg/m2 intravenously], or gemcitabine [1000 mg/m2 intravenously]) or single-agent chemotherapy + bevacizumab (15 mg/m2 intravenously). The primary endpoint was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary endpoints were overall survival (OS), objective response rate (ORR), and response rate according to Gynecological Cancer Intergroup cancer antigen 125 criteria. In total, 103 patients were allocated to chemotherapy (n = 51) or chemotherapy + bevacizumab (n = 52). Median investigator-assessed PFS was 3.1 and 4.0 mo in each group, respectively (hazard ratio [HR] = 0.54, 95% confidence interval [CI]: 0.32-0.90, P = .0082). Median OS was 11.3 and 15.3 mo in each group, respectively (HR = 0.67, 95% CI: 0.38-1.17, P = .1556). Respective ORRs were 13.7% and 25.0% (P = .0599) and response rates were 16.7% and 21.4% (P = .8273). The incidence of grade ≥3 treatment-related AEs was 42.0% in the chemotherapy group and 54.9% in the chemotherapy + bevacizumab group; AEs were well tolerated, with only 2 and 12 events leading to discontinuation of therapy, respectively. Bevacizumab was effective beyond progressive disease and AEs were manageable. The observed improvement in PFS requires further verification.

Incomplete cytoreduction with peritoneal metastases from appendiceal mucinous neoplasms.

BACKGROUND: Complete cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy is the standard of care for mucinous appendiceal neoplasms with peritoneal metastases. Despite many publications regarding selection factors favoring a complete CRS, incomplete CRS does occur. Patients with an incomplete CRS are the focus of this manuscript. METHODS: A retrospective analysis of prospective, histologic, and perioperative data was performed. Overall survival was the endpoint for the numerous assessments. Judgments regarding when to and when not to proceed with an incomplete CRS were sought. RESULTS: From a database of 949 patients who underwent an index CRS for appendiceal mucinous neoplasm, 264 patients (27.8%) had an incomplete CRS. The median overall survival was 1.8 years. Low-grade histopathology and absence of tense ascites or bowel obstruction were significantly associated with increased overall survival. More extensive surgery suggested a more favorable outcome. CONCLUSIONS: When a surgeon is confronted by a procedure that will inevitably end with an incomplete CRS, a current trend is to close quickly and always avoid complications. Patients with low-grade neoplasms who present in the absence of tense ascites or bowel obstruction may gain years of survival by surgical reduction of tumor burden.

Revised prognostic indicators for treatment of lymph node positive colorectal peritoneal metastases.

BACKGROUND: Peritoneal metastases from colon and rectal cancer presents a new target for a regional approach to treatment. Proper patient selection requires an understanding of the natural history of the disease progression. METHODS: Data from colorectal cancer patients treated for peritoneal metastases by cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy and the records from the primary colon or rectal cancer surgery were analyzed to assess their impact on survival. Data regarding the anatomic sites of colorectal peritoneal metastases was gathered at the time of a complete CRS. RESULTS: A cohort of 73 patients with peritoneal metastases and lymph node metastases but no liver metastases provided the information. All patients had a complete cytoreduction. Left-sided primary cancer and a complete or near complete response to neoadjuvant chemotherapy (NAC) indicated improved survival. Tumor progression within the abdominal incision, carcinoembryonic antigen (CEA) >10, peritoneal cancer index >9 and peritoneal metastases present in the abdominopelvic regions 6 and 11 carried an especially guarded prognosis. CONCLUSIONS: Reduced survival occurred with a right-sided or rectal primary cancer, a CEA >10, tumor cell entrapment, and involvement of abdominopelvic regions 6 and 11. Effective NAC showed a favorable outcome.