Uterine mesenchymal tumors harboring ALK fusions and response to ALK-targeted therapy.

Inflammatory myofibroblastic tumor (IMT) of the uterus is a rare but aggressive malignancy that is often misdiagnosed. Approximately 50% of uterine IMTs (UMT) harbor rearrangements involving the ALK gene on chromosome 2p23 with subsequent overexpression of the ALK protein. Molecular characterization and wider availability of immunohistochemistry (IHC) and next generation sequencing (NGS) have improved clinical recognition and accurate diagnosis of UMT. The discovery of ALK fusions as a genomic driver led to the FDA approval of ALK inhibitors in ALK-altered lung cancers, but there are limited data to date on the spectrum of ALK fusions or patterns of response and resistance to ALK inhibitors in ALK-altered UMT. In this report we describe the genomic and histopathological characteristics and the response to ALK-targeted therapy in four patients with UMT. In all four patients, clinical activity of ALK inhibition was observed, with durable responses lasting 12 months or more. Moreover, three patients derived benefit from a second-generation ALK inhibitor after progression of disease or intolerance to the first-generation inhibitor crizotinib. Our report advocates for consideration of expanding the current National Comprehensive Cancer Network (NCCN) guidelines to include later-generation ALK inhibitors for the treatment of ALK-rearranged UMTs.

Intraperitoneal chemotherapy after interval debulking surgery for advanced-stage ovarian cancer: Feasibility and outcomes at a comprehensive cancer center.

OBJECTIVES: Intraperitoneal (IP)-based chemotherapy following primary debulking surgery (PDS), although associated with substantial toxicity, is supported by a strong evidence base. We sought to determine feasibility and outcomes of IP chemotherapy after interval debulking surgery (IDS) among patients deemed ineligible for PDS. METHODS: We identified all patients with high-grade, stage III/IV ovarian cancer treated at our institution with neoadjuvant chemotherapy (NACT) followed by IDS and postoperative chemotherapy from 1/2008-5/2013. IP and intravenous (IV) regimens were defined; demographic and clinical data were analyzed using appropriate statistics. RESULTS: Of 128 evaluable patients, 118 (92%) achieved ≤1cm residual disease at IDS and 74 (58%) achieved a complete gross resection (CGR). An IP port was placed in 54/128 patients (42%), with 89% port utilization. Forty-eight (38%) of 128 patients received IP chemotherapy, 17 (13%) weekly IV paclitaxel/q3week carboplatin, and 63 (49%) q3week IV carboplatin/paclitaxel. Patients completed a median of 3 IP cycles (range, 2-6), with 3 (5.5%) of 54 ports removed due to complications. Overall survival (OS) for patients with a CGR treated with IP and weekly IV chemotherapy was 53.2months (range, 24.7-NE), and 44.2months (range, 30.2-NE) with any visible residual disease (p<0.001). Median OS was 53.2months (range, 44.5-NE) for IP-, not reached for weekly IV-, and 34.2months (range, 27.5-49.8) for q3week IV-treated patients (p=0.1). CONCLUSIONS: Patients administered IP after IDS had a high rate of successful port utilization, with few regimen switches. Oncologic outcomes were optimal in patients with a CGR at IDS, regardless of chemotherapy used.

Neoadjuvant chemotherapy and primary debulking surgery utilization for advanced-stage ovarian cancer at a comprehensive cancer center.

OBJECTIVE: The aim of this study was to evaluate the use of neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) before and after results from a randomized trial were published and showed non-inferiority between NACT and PDS in the management of advanced-stage ovarian carcinoma. METHODS: We evaluated consecutive patients with advanced-stage ovarian cancer treated at our institution from 1/1/08-5/1/13, which encompassed 32 months before and 32 months after the randomized trial results were published. We included all newly diagnosed patients with high-grade histology and stage III/IV disease. Associations between the use of NACT and clinical variables over time were evaluated. RESULTS: Our study included 586 patients. Median age was 62 years (range, 30-90); 406 patients (69%) had stage III disease, and 570 (97%) had disease of serous histology. Twenty-six percent (154/586) were treated with NACT and 74% (432/586) with PDS. NACT use increased significantly from 22% (56/256) before 2010 (at which point the results of the randomized trial were published) to 30% (98/330) after 2010 (p=0.037). Although patients who underwent PDS were more likely to experience grade 3/4 surgical complications than those who underwent NACT, those selected for PDS had a median OS of 71.7 months (CI, 59.8-not reached) compared with 42.9 months (CI 37.1-56.3) for those selected for NACT. CONCLUSIONS: In this single-institution analysis, the best survival outcomes were observed in patients who were deemed eligible for PDS followed by platinum-based chemotherapy. Selection criteria for NACT require further definition and should take institutional surgical strategy into account.