Faculty Bibliography

Lymphangiomatosis, a rare disorder of the lymphatic system characterized by the abnormal proliferation of lymphatic vessels, is a typically benign disorder that at times can exhibit invasive or malignant behavior. While generally considered a diagnosis of childhood, in adults the majority of cases are asymptomatic and found incidentally. Rarely, lymphatic overgrowth can occur, causing growth of lesions on imaging mimicking a metastatic process and occasionally, resulting in substantial morbidity and mortality. Here, we present such a case of lymphangiomatosis with multi-organ system involvement in liver, bone, and spleen. In addition to details of the clinical presentation and the pathologic review which led to the diagnosis, we describe our use of the tyrosine kinase inhibitor pazopanib, which may cause stabilization of lymphangiomatosis through blockade of vascular endothelial growth factor (VEGF) signaling, for systemic treatment in this unusual case.

Cancers of the digestive tract account for 338,090 new cases and 169,280 deaths annually in the United States. Although the overall mortality from these cancers is decreasing, this has been countered ...

TPS4651Background: E/GEJ adenocarcinoma has a high mortality rate despite curative intent treatment. A pathologic complete response (pCR) is associated with better overall survival (OS) but occurs in less than 30% of pts. Immunotherapy is effective in the metastatic setting. Here we aim to evaluate the contribution of immunotherapy in the neoadjuvant and adjuvant settings in pts with locoregional E/GEJ cancer. Methods: This is a multi-center, randomized phase II/III trial. Surgical candidates with locoregional E/GEJ adenocarcinoma receive carboplatin AUC 2 IV and paclitaxel 50 mg/m2 IV, both weekly x 5 during concurrent radiation (50.4 Gy) either with or without nivolumab 240 mg IV during weeks 1 and 3, followed by surgery. Pts with no post-operative disease receive nivolumab 240 mg IV every 2 weeks for 12 cycles either with or without ipilimumab 1 mg/kg IV every 6 weeks for 4 cycles. Eligibility criteria include pts with T1-N1-3M0 or T2-3N0-2M0 disease whom are candidates for surgery, no prior chemotherapy or radiation for this disease, no prior immunotherapy, no significant autoimmune disease. Pts must be disease free for adjuvant treatment. Primary neoadjuvant endpoint is pCR rate; primary adjuvant endpoint is disease free survival (DFS). Secondary endpoints include toxicity, DFS and OS. Pre- and mid-treatment diffusion weighted imaging MRI will be conducted during the neoadjuvant portion of the study. A neoadjuvant safety run in of 30 pts is underway. Overall, 278 pts will be needed to detect an absolute improvement of 15% in pCR rate in pts receiving and not receiving neoadjuvant nivolumab and 236 pts will be needed to detect a HR of 0.65 in favor of adjuvant ipilimumab/nivolumab over nivolumab (90% power, one sided alpha of 0.10). Accrual is expected over 34 months at a rate of 8 patients per month. If favorable at interim analysis. Clinical trial information: NCT03604991.

TPS9092 Background: The incidence of SCCS has increased over the past two decades, including a high risk subset with aggressive behavior. Due to a lack of high-quality clinical trials in this population, there is no standard systemic therapy for advanced SCCS. The epidermal growth factor receptor (EGFR), often highly expressed in SCCS, is implicated in UV-induced skin carcinogenesis and SCCS development. Cetuximab, a monoclonal antibody that competitively inhibits EGFR, improved disease control as first line therapy in unresectable SCCS in a single arm phase II trial. Despite impressive responses with cetuximab in some, most treated SCCS patients do not respond, and there is a need for predictive biomarkers. We hypothesize that the use of cetuximab will improve clinical outcomes in patients with advanced SCCS in the neoadjuvant setting, and that measures of antibody dependent cytotoxicity (ADCC) in tumor and/or specific genomic features of the tumor may predict response to therapy. Methods: In this pilot trial (NCT 02324608), we will enroll 20 patients with relapsed locally advanced SCCS or SCCS unamenable to definitive local therapy. The primary endpoint will measure response rate to cetuximab by RECIST criteria with secondary endpoints of progression free and overall survival, and conversion to resectability. Molecular tumor correlates include analyzing DNA mutations and measuring downstream activation of EGFR signaling and ADCC, correlating these with clinical benefit. Patients will receive cetuximab at 400mg/m2 ? 1 followed by weekly doses of 250mg/m2 for 8 weeks prior to surgery. Patients will be evaluated for subsequent definitive surgical resection, or definitive radiotherapy if surgical resection is not possible. Postoperative adjuvant radiotherapy will be permitted. Patients will undergo pretreatment biopsies, and post-treatment tissue will be harvested at surgery or through a biopsy at the conclusion of cetuximab. Paired skin and tumor samples will be evaluated through partial DNA (FoundationOne??) and RNA sequencing, IHC analysis of EGFR signaling components, and measurement of ADCC. The trial is currently screening eligible subjects. Clinical trial information: 02324608.