Peritoneal metastases from rare ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

Objectives: There are limited treatment options and no consensus on the management of advanced rare ovarian malignancies. Rare ovarian malignancies can present with peritoneal metastases (PM), featuring a similar presentation to more common ovarian subtypes. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an effective treatment for PM of non-gynecologic origin and, recently, epithelial ovarian cancer. We evaluated the feasibility of CRS/HIPEC in the management of PM from rare ovarian malignancies and report postoperative outcomes on these patients. Methods: A retrospective review of a single center, prospective database (1994-2021) was performed to identify patients with rare ovarian malignancies treated with CRS/HIPEC. Clavien-Dindo 90-day morbidity/mortality and Kaplan-Meier overall (OS) and progression-free survival (PFS) were analyzed. Results: Of 44 patients identified, 28 underwent CRS/HIPEC. Six were aborted due to extensive disease. Histologic subtypes included: clear cell (5/28, 17.9 %), endometrioid (5/28, 17.9 %), granulosa cell (3/28, 10.7 %), low-grade serous (6/28, 21.4 %), mesonephric (1/28, 3.6 %), mucinous (6/28, 21.4 %), and small cell (2/28, 7.1 %) carcinomas. Eight (28.6 %) patients had primary and 20 (71.4 %) had recurrent disease. Median peritoneal cancer index (PCI) was 21 (IQR: 6-29). Complete cytoreduction (<2.5 mm residual disease) was achieved in 27/28 (96.4 %). Grade III/IV complications occurred in 9/28 (32.1 %) with one (3.6 %) mortality. After a median follow-up of 65.8 months, 20 patients were alive. Five-year OS and PFS were 68.5 and 52.6 %, respectively. Conclusions: In patients with PM from rare ovarian malignancies, CRS/HIPEC is feasible and has an acceptable safety profile. Longer follow-up and multicenter trials are needed.

Collaborative expertise of gynecological and surgical oncologists in managing advanced epithelial ovarian cancer.

BACKGROUND: Most patients with epithelial ovarian cancer (EOC) present with significant peritoneal spread. We assessed collaborative efforts of surgical and gynecological oncologists with expertise in cytoreductive surgery (CRS) in the management of advanced EOC. METHODS: Using a prospective single-center database (2014-2022), we described the operative and oncologic outcomes of stage IIIC-IVA primary and recurrent EOC perioperatively managed jointly by gynecological and surgical oncologists both specializing in CRS and presented components of this collaboration. RESULTS: Of 199 identified patients, 132 (66 %) had primary and 53 (27 %) had recurrent EOC. Due to inoperable disease, 14 (7 %) cases were aborted and excluded from analysis. Median peritoneal cancer index (PCI) in primary and recurrent patients was 21 (IQR: 11-28) and 21 (IQR: 6-31). Upper abdominal surgery was required in 95 % (n = 125) of primary and 89 % (n = 47) of recurrent patients. Bowel resections were performed in 83 % (n = 110) and 72 % (n = 38), respectively. Complete cytoreduction (CC-0/1) with no disease or residual lesions <2.5 mm was achieved in 95 % (n = 125) of primary and 91 % (n = 48) of recurrent patients. Ninety-day Clavien-Dindo grade III-IV morbidity was 12 % (n = 16) and 21 % (n = 11), respectively. Median follow-up was 44 (95%CI: 33-55) months. Median overall survival in primary and recurrent EOC was 68 (95%CI: 45-91) and 50 (95%CI: 16-84) months. Median progression-free survival was 26 (95%CI: 22-30) and 14 (95%CI: 7-21) months, respectively. CONCLUSIONS: Perioperative collaboration between surgical and gynecological oncologists specializing in CRS allows safe performance of complete cytoreduction in the majority of patients with primary and recurrent EOC, despite high tumor burden.

Sufficient Regional Lymph Node Examination for Staging Adenocarcinoma of the Appendix.

BACKGROUND: The presence of lymph node (LN) metastasis is a known negative prognostic factor in appendix cancer (AC) patients. However, currently the minimum number of LNs required to adequately determine LN negativity is extrapolated from colorectal studies and data specific to AC is lacking. We aimed to define the lowest number of LNs required to adequately stage AC and assess its impact on oncologic outcomes. METHODS: Patients with stage II-III AC from the National Cancer Database (NCDB 2004-2019) undergoing surgical resection with complete information about LN examination were included. Multivariable logistic regression assessed the odds of LN positive (LNP) disease for different numbers of LNs examined. Multivariable Cox regressions were performed by LN status subgroups, adjusted by prognostic factors, including grade, histologic subtype, surgical approach, and documented adjuvant systemic chemotherapy. RESULTS: Overall, 3,602 patients were included, from which 1,026 (28.5%) were LNP. Harvesting ten LNs was the minimum number required without decreased odds of LNP compared with the reference category (≥ 20 LNs). Total LNs examined were < 10 in 466 (12.9%) patients. Median follow-up from diagnosis was 75.4 months. Failing to evaluate at least ten LNs was an independent negative prognostic factor for overall survival (adjusted hazard ratio 1.39, p < 0.01). CONCLUSIONS: In appendix adenocarcinoma, examining a minimum of ten LNs was necessary to minimize the risk of missing LNP disease and was associated with improved overall survival rates. To mitigate the risk of misclassification, an adequate number of regional LNs must be assessed to determine LN status.

Patterns of Recurrence in Appendix Cancer After Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: It is thought that low-grade (LG) appendiceal cancer (AC) demonstrates predominantly intraperitoneal recurrence (IPR) after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), whereas high-grade (HG) tumors progress both intra- and extraperitoneally (EPR). However, evidence supporting this conception is lacking; therefore, we assessed recurrence in various AC histologies. METHODS: A retrospective, cohort study was conducted by using a single-center database (1998-2022). Recurrence patterns (IPR, EPR, combined) were identified for LG, HG, high-grade with signet ring cells (SRC), and goblet cell carcinoma (GCC). RESULTS: We included 432 complete (CC-0/1) CRS/HIPECs: 200 LG, 114 HG, 72 SRC, and 46 GCC. Median follow-up was 78 (95% confidence interval [CI] 70-86) months. Overall, 34% (n = 148) of patients recurred. IPR was the most common (LG 16%, HG 27%, SRC 36%, GCC 26%) with median time to recurrence (MTR) of 21 (IQR: 12-40) months. EPR (liver, lung, pleura, lymph nodes, or bones) occurred in LG 3%, HG 9%, SRC 22%, and GCC 7%. MTR was 11 (IQR: 4-16) months. Combined pattern occurred in LG 0%, HG 8%, SRC 7%, and GCC 0%. MTR was 13 (IQR: 7-18) months. Iterative surgery was performed in 53% IPR, 18% EPR, and 51% combined. Median post-recurrence survival was longer after IPR compared with EPR and combined recurrence: 36 (95% CI 25-47) versus 13 (95% CI 7-19) and 18 (95% CI 6-30) months (p < 0.01). CONCLUSIONS: After complete CRS/HIPEC, IPR was the predominant pattern in all AC histologies and occurred later. Post-recurrence survival after IPR was longer. Knowing AC recurrence patterns can help to understand its biology and plan follow-up and post-relapse management.

Achieving Intraperitoneal Disease Control Using Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Two Cases of Metastatic Breast Cancer.

Peritoneal metastases from breast cancer (PMBC) tend to occur late in the disease course and are challenging to manage. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) provide peritoneal disease control in other malignancies and may achieve similar results in PMBC. We assessed intraperitoneal disease control and outcomes in two PMBC patients after CRS/HIPEC. Patient 1, diagnosed at age 64, had hormone-positive/human epidermal growth factor receptor 2 (HER2)-negative lobular carcinoma treated with mastectomy. Prior to salvage CRS/HIPEC at age 72, five cycles of intraperitoneal chemotherapy via an indwelling catheter failed to control recurrent peritoneal disease. Patient 2, diagnosed at age 52, had hormone-positive/HER2-negative ductal-lobular carcinoma and received lumpectomy, hormonal therapy, and target therapy. Prior to salvage CRS/HIPEC at age 59, she had recurring ascites that was resistant to hormonal therapy and required multiple paracenteses. Both underwent complete CRS/HIPEC with melphalan. The only major complication was anemia, which required a transfusion in both patients. They were discharged on postoperative days 8 and 13, respectively. Patient 1 had peritoneal recurrence 26 months post-CRS/HIPEC and died of disease at 49 months. Patient 2 never had peritoneal recurrence and died of extraperitoneal progression at 38 months. In conclusion, CRS/HIPEC is safe and can provide intraperitoneal disease and symptom control in select patients with PMBC. Thus, CRS/HIPEC can be offered to these rare patients who have failed standard treatments.