Background: The role and optimal sequencing of systemic therapy in patients with high-volume peritoneal mesothelioma (PeM) undergoing curative-intent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains unclear. We compared perioperative outcomes in patients undergoing upfront CRS/HIPEC (U-CRS) versus those receiving neoadjuvant therapy (NAT). Methods: This single-institution retrospective study included patients with PeM (2009-2023) who underwent CRS/HIPEC with a peritoneal carcinomatosis index (PCI) > 20. Primary outcomes were prolonged operative time (OT), defined as > 75th percentile for the study cohort, and 90-day postoperative complications. Secondary outcomes included complete cytoreduction with CC-0 score, recurrence-free survival (RFS), and overall survival (OS). Results: Of 45 patients, 14 (31 %) underwent U-CRS and 31 (69 %) received NAT. Most NAT patients (94 %) were treated with a platinum agent and pemetrexed, with or without bevacizumab, for a median of 6 cycles. Median PCI was similar between groups (U-CRS: 28; NAT: 27; p = 0.73). Median OT was 572 min (U-CRS) vs. 645 min (NAT; p = 0.17). Grade III-V complications occurred in 50 % of U-CRS vs. 32 % of NAT patients (p = 0.42). NAT was not independently associated with prolonged OT or severe complications on multivariable analyses. Rates of CC-0 resection, RFS, and OS were similar between groups. Conclusions: NAT is feasible and safe in patients with high-volume PeM undergoing CRS/HIPEC, without negatively affecting perioperative outcomes. The neoadjuvant setting offers a valuable platform for investigating novel therapies aimed at improving long-term outcomes in PeM. Synopsis: Neoadjuvant systemic therapy before CRS/HIPEC for high-volume peritoneal mesothelioma is feasible and safe with similar operative times and complication rates as upfront surgery, supporting its use as a platform to evaluate novel therapies to improve long-term outcomes in peritoneal mesothelioma.

BACKGROUND:Although 2016 consensus guidelines defined high-grade appendiceal mucinous neoplasms (HAMNs) as a distinct histologic entity, their clinical course and optimal management remain poorly characterized. Comparative data with low-grade appendiceal mucinous neoplasms (LAMNs) are limited. This study aims to detail the clinical management and outcomes of patients with HAMN and those with LAMN. METHODS:This retrospective cohort study was conducted at a large academic cancer center. An internal database was queried to identify patients with LAMN or HAMN who underwent appendectomy between 2016 and 2024. Kaplan-Meier survival analyses were used to assess the impact of primary tumor type and peritoneal disease (PD) on recurrence-free survival (RFS) and overall survival (OS). RESULTS:Of the 375 patients, 276 (73.6%) had LAMN and 99 (26.4%) had HAMN. Localized disease was most common (187 patients [49.9%]). Acellular mucin, low-grade mucinous carcinoma peritonei (LGMCP), and high-grade mucinous carcinoma peritonei (HGMCP) were observed in 14.9, 25.3, and 9.9% of patients, respectively. HAMNs were associated with increased PD (69.7% vs 43.1%, P < 0.001) and HGMCP (19.2% vs 6.5%, P < 0.001). Patients with localized disease or acellular mucin experienced almost no recurrences (99.2%). Patients with HAMN trended towards worse 5 year RFS (80.7% vs 90.4%, P = 0.083). OS was similar (91.1% vs LAMN 93.4%, P = 0.23). CONCLUSIONS:This is the largest cohort of patients with HAMN characterized to date. HAMNs are associated with more frequent and higher-grade PD than are LAMNs. The presence and type of PD influence both RFS and OS for patients with AMN. Overall, there is a trend towards decreased RFS in patients with HAMN than with LAMN, but OS was similar.

INTRODUCTION:Many patients with mucinous appendiceal adenocarcinoma experience peritoneal recurrence despite complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prior work has demonstrated that repeat CRS/HIPEC can prolong survival in select patients. We sought to validate these findings using outcomes from a high-volume center.PATIENTS AND METHODS:Patients with mucinous appendiceal adenocarcinoma who underwent CRS/HIPEC at MD Anderson Cancer Center between 2004 and 2021 were stratified by whether they underwent CRS/HIPEC for recurrent disease or as part of initial treatment. Only patients who underwent complete CRS/HIPEC were included. Initial and recurrent groups were compared.RESULTS:Of 437 CRS/HIPECs performed for mucinous appendiceal adenocarcinoma, 50 (11.4%) were for recurrent disease. Patients who underwent CRS/HIPEC for recurrent disease were more often treated with an oxaliplatin or cisplatin perfusion (35%/44% recurrent vs. 4%/1% initial, p < 0.001), had a longer operative time (median 629 min recurrent vs. 511 min initial, p = 0.002), and had a lower median length of stay (10 days repeat vs. 13 days initial, p < 0.001). Thirty-day complication and 90-day mortality rates did not differ between groups. Both cohorts enjoyed comparable recurrence free survival (p = 0.82). Compared with patients with recurrence treated with systemic chemotherapy alone, this select cohort of patients undergoing repeat CRS/HIPEC enjoyed better overall survival (p < 0.001).CONCLUSIONS:In appropriately selected patients with recurrent appendiceal mucinous adenocarcinoma, CRS/HIPEC can provide survival benefit equivalent to primary CRS/HIPEC and that may be superior to that conferred by systemic therapy alone in select patients. These patients should receive care at a high-volume center in the context of a multidisciplinary team.

Appendiceal neoplasms have a propensity for peritoneal dissemination. The standard of care for select individuals is CRS/HIPEC. In the current 8th AJCC Staging system, a finding of only intraperitoneal acellular mucin (M1a) is classified as Stage IVa. There is concern that the current AJCC system may over-stage patients. This was a single-institution retrospective review of 164 cases of mucinous appendiceal neoplasm. Patients undergoing CRS/HIPEC with M1a disease were compared to patients with peritoneal deposits containing tumor cells (well-differentiated adenocarcinoma; low-grade mucinous carcinoma peritonei—M1b,G1). Overall and recurrence-free survival were assessed. Median age was 51 years, 70

Supplementary Methods, Figures and Tables

PDF file - 58K, Demographics and clinical characteristics of enrolled patients

Sensitivity and Specificity CTC Detection Table and ROC Curve

Abstract Malignant peritoneal mesothelioma (MPeM) is a rare but aggressive malignancy with limited treatment options. VEGF inhibition enhances efficacy of immune-checkpoint inhibitors by reworking the immunosuppressive tumor milieu. Efficacy and safety of combined PD-L1 (atezolizumab) and VEGF (bevacizumab) blockade (AtezoBev) was assessed in 20 patients with advanced and unresectable MPeM with progression or intolerance to prior platinum–pemetrexed chemotherapy. The primary endpoint of confirmed objective response rate per RECISTv1.1 by independent radiology review was 40% [8/20; 95% confidence interval (CI), 19.1–64.0] with median response duration of 12.8 months. Six (75%) responses lasted for >10 months. Progression-free and overall survival at one year were 61% (95% CI, 35–80) and 85% (95% CI, 60–95), respectively. Responses occurred notwithstanding low tumor mutation burden and PD-L1 expression status. Baseline epithelial–mesenchymal transition gene expression correlated with therapeutic resistance/response (r = 0.80; P = 0.0010). AtezoBev showed promising and durable efficacy in patients with advanced MPeM with an acceptable safety profile, and these results address a grave unmet need for this orphan disease. Significance: Efficacy of atezolizumab and bevacizumab vis-à-vis response rates and survival in advanced peritoneal mesothelioma previously treated with chemotherapy surpassed outcomes expected with conventional therapies. Biomarker analyses uncovered epithelial–mesenchymal transition phenotype as an important resistance mechanism and showcase the value and feasibility of performing translationally driven clinical trials in rare tumors. See related commentary by Aldea et al., p. 2674. This article is highlighted in the In This Issue feature, p. 2659

Malignant mesothelioma of the peritoneum in women is an uncommon tumor. In this study, we present the clinicopathologic features of 164 such cases seen in our institution over a period of 42 years (1974-2016). Clinical information, pathologic findings, immunohistochemical results, and follow-up were recorded. Hematoxylin and eosin–stained slides were reviewed in all cases. Patients ranged in age from 3 to 85 years, median: 49 years. Most patients presented with abdominal/pelvic pain, although some were asymptomatic, presented with paraneoplastic syndromes or cervical lymphadenopathy. Overall, 9% of patients had a history of direct or indirect exposure to asbestos. In total, 31% and 69% of patients had either a personal or family history of other tumors; most of these tumors are currently recognized as part of a syndrome. Genetic testing information was available in 5 patients: BAP-1 germline mutation (1), type 2 neurofibromatosis (1), Lynch syndrome (1), McCune-Albright syndrome (1), no BAP-1 or TP53 mutation (1). Most cases had gross and microscopic features typical of malignant mesothelioma of the peritoneum in women; however, some had confounding features such as gelatinous appearance, signet ring or clear cells, and well-differentiated papillary mesothelioma-like areas. Calretinin and WT-1 were the markers more frequently expressed, and up to 23% of the cases showed PAX-8 expression. Patients’ treatments predominantly included: chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy. On multivariate analysis, the predominance of deciduoid cells, nuclear grade 3, and the absence of surgical treatment were associated with worse overall survival (OS). For all patients, the 3- and 5-year OS were 74.3% and 57.4%, respectively. The 3- and 5-year OS for patients treated with cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy were 88.9% and 77.8%, respectively.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of colorectal cancer specifically as it relates to the management of peritoneal surface malignancy. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of peritoneal mesothelioma. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness of the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

Abstract Purpose: There is a need for sensitive, reproducible biomarkers for patients with stage III melanoma to guide clinical decision making. Circulating tumor cells (CTCs) can be detected in patients with melanoma; however, there are limited data regarding their significance in stage III disease. The aim of this study was to determine whether CTCs are associated with early relapse in stage III melanoma. Experimental Design: We prospectively assessed CTCs at first presentation in clinic (baseline) for 243 patients with stage III melanoma. CTCs were measured using the CellSearch System. Relapse-free survival (RFS) was compared between patients with one or more baseline CTC versus those with no CTCs. Log-rank test and Cox regression analysis were applied to establish associations of CTCs with RFS. Results: At least one baseline CTC was identified in 90 of 243 (37%) patients. Forty-five (19%), 67 (28%), 118 (49%), and 13 (5%) patients were stage IIIA, IIIB, IIIC, or IIID, respectively. CTC detection was not associated with substage, or primary tumor characteristics. Multivariable analysis demonstrated that the detection of ≥1 baseline CTC was significantly associated with decreased 6-month RFS [log-rank, P < 0.0001; HR, 3.62, 95% confidence interval (CI), 1.78–7.36; P < 0.0001] and 54-month RFS (log-rank, P = 0.01; HR, 1.69; 95% CI, 1.13–2.54; P = 0.01). Conclusions: ≥1 CTC was independently associated with melanoma relapse, suggesting that CTC assessment may be useful to identify patients at risk for relapse who could derive benefit from adjuvant therapy.

Of the estimated 140,250 patients diagnosed with colon and rectal cancer (CRC) in 2018, approximately 13% will present with or ultimately develop peritoneal-dominant disease. 1 Jayne D.G. Fook S. Loi C. Seow-Choen F. Peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2002; 89: 1545-1550 Crossref PubMed Scopus (569) Google Scholar With conventional systemic chemotherapy, patients with peritoneal disease have historically had a worse prognosis, with a median survival of 16.3 months compared with patients with isolated liver (19.1 months) or lung metastases (24.6 months). 2 Franko J. Shi Q. Meyers J.P. et al. Analysis and Research in Cancers of the Digestive System (ARCAD) GroupPrognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database. Lancet Oncol. 2016; 17: 1709-1719 Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar This poorer prognosis has fueled enthusiasm for cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC). However, recent studies do not support the premise that CRS and HIPEC improve survival in colorectal carcinomatosis.