Mustafa Raoof

Liver Resection With Extrahepatic Disease: A Population‐Based Analysis of Thoughtful Selection

ABSTRACT Background The oncologic benefit of liver resection for colorectal liver metastases (CRLM) in the setting of concurrent extrahepatic disease (EHD) is controversial. We performed a population‐based, cross‐sectional study to determine the practice patterns and overall survival (OS) of patients with CRLM + EHD who underwent liver resection. Methods Patients with CRLM + EHD were identified using the California Cancer Registry from 2000 to 2019. Records were linked to the Office of Statewide Health Planning Inpatient Database. Patient demographics, clinical characteristics, and survival were compared between CRLM + EHD patients with and without liver resection. Results Of 170 978 patients with CRLM, 62 003 (36%) had concurrent EHD (CRLM + EHD). In all, 3736 (6%) of CRLM + EHD underwent liver resection compared to 22% of patients with liver limited CRLM. Compared to CRLM + EHD without liver resection, CRLM + EHD with resection were younger, had fewer comorbidities, received higher frequencies of perioperative chemotherapy, and were more likely to have only a single site of EHD rather than multiple sites. Median OS was significantly higher for CRLM + EHD with resection compared to without (52 vs. 27 months, HR 0.46 [95% CI 0.44–0.47], p  < 0.001). Regarding the location of EHD, this survival benefit was observed with liver resection for lung, peritoneal, intraabdominal lymph nodes, ovarian, and bone metastases. Conclusions In a large population‐based setting, subsets of CRLM + EHD patients that undergo liver resection are associated with prolonged survival. These results support surgery with thoughtful patient selection to optimize survival outcomes in this population.

Hyperthermic Intraperitoneal Chemotherapy–Induced Molecular Changes in Humans Validate Preclinical Data in Ovarian Cancer

PURPOSE Hyperthermic intraperitoneal chemotherapy (HIPEC) confers a survival benefit in epithelial ovarian cancer (EOC) and in preclinical models. However, the molecular changes induced by HIPEC have not been corroborated in humans. PATIENTS AND METHODS A feasibility trial evaluated clinical and safety outcomes of HIPEC with cisplatin during optimal cytoreductive surgery (CRS) in patients with EOC diagnosed with stage III, IV, or recurrent EOC. Pre- and post-HIPEC biopsies were comprehensively profiled with genomic and transcriptomic sequencing to identify mutational and RNAseq signatures correlating with response; the tumor microenvironment was profiled to identify potential immune biomarkers; and transcriptional signatures of tumors and normal samples before and after HIPEC were compared to investigate HIPEC-induced acute transcriptional changes. RESULTS Thirty-five patients had HIPEC at the time of optimal CRS; all patients had optimal CRS. The median progression-free survival (PFS) was 24.7 months for primary patients and 22.4 for recurrent patients. There were no grade 4 or 5 adverse events. Anemia was the most common grade 3 adverse event (43%). Hierarchical cluster analyses identified distinct transcriptomic signatures of good versus poor responders to HIPEC correlating with a PFS of 29.9 versus 7.3 months, respectively. Among good responders, significant HIPEC-induced molecular changes included immune pathway upregulation and DNA repair pathway downregulation. Within cancer islands, % programmed cell death protein 1 expression in CD8+ T cells significantly increased after HIPEC. An exceptional responder (PFS 58 months) demonstrated the highest programmed cell death protein 1 increase. Heat shock proteins comprised the top differentially upregulated genes in HIPEC-treated tumors. CONCLUSION Distinct transcriptomic signatures identify responders to HIPEC, and preclinical model findings are confirmed for the first time in a human cohort.

Surgery and Chemotherapy With or Without Chemotherapy After Surgery in Treating Patients With Ovarian, Fallopian Tube, Uterine, or Peritoneal Cancer

This phase I trial studies the side effects and how well surgery and heated chemotherapy with or without non-heated chemotherapy after surgery works in treating patients with ovarian, fallopian tube, uterine, or peritoneal cancer. Giving a dose of heated chemotherapy into the abdomen during surgery that is done to remove ovarian, fallopian tube, uterine, or peritoneal cancer may help lower the risk of the cancer coming back. Giving unheated chemotherapy drugs directly into the abdomen after surgery may kill more tumor cells.