title: Objective response to mTOR inhibition in a metastatic collision tumor of the liver composed of melanoma and adenocarcinoma with TSC1 loss: a case report.
abstract: Collision tumors are uncommon but well described clinical entities composed of distinct tumor histologies occurring within the same anatomic site. Optimal management of patients with collision tumors remains highly variable and depends on clinical characteristics such as the involved tumor types, predominant histology, as well as the extent of disease. Comprehensive genomic profiling is a means of identifying genomic alterations to suggest benefit from targeted therapy.
  
  
  
  A 78-year-old woman presented to medical oncology with liver metastases occurring within the background of a 1-year history of uveal melanoma. Biopsy of the liver metastases revealed presence of adenocarcinoma along with nests of malignant melanoma consistent with a collision tumor. The disease was refractory to several lines of conventional cytotoxic chemotherapy, and the patient later developed pulmonary metastases while on chemotherapy. The patient's tumor tissue was assayed by comprehensive genomic profiling which revealed presence of a TSC1 partial loss. The patient was subsequently initiated on temsirolimus 15 mg intravenously weekly for 4 months. Restaging imaging demonstrated a partial response to therapy by RECIST 1.1 criteria and clinical benefit for 6 months until the patient passed away secondary to unrelated causes.
  
  
  
  We report the first case of a collision tumor composed of adenocarcinoma and melanoma with a TSC1 mutation that objectively and durably responded to mTOR inhibition.
authors.affiliation: Division of Hematology Oncology, Scripps Clinic, 10666 N. Torrey Pines Ave, La Jolla, CA, 92037, USA. bhangoo.munveer@scrippshealth.org.
authors.forename: Munveer S
authors.initials: MS
authors.lastname: Bhangoo
authors.affiliation: Department of Internal Medicine, Scripps Mercy Hospital, San Diego, CA, USA.
authors.forename: Jenny Y
authors.initials: JY
authors.lastname: Zhou
authors.affiliation: Foundation Medicine, Cambridge, MA, USA.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Foundation Medicine, Cambridge, MA, USA.
authors.forename: Russell
authors.initials: R
authors.lastname: Madison
authors.affiliation: Foundation Medicine, Cambridge, MA, USA.
authors.forename: Alexa B
authors.initials: AB
authors.lastname: Schrock
authors.affiliation: Division of Hematology Oncology, Scripps Clinic, 10666 N. Torrey Pines Ave, La Jolla, CA, 92037, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Costantini
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000368:Aged; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C000624650:TSC1 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Carcinoma Undetermined Primary; Case Report; Collision tumor; Melanoma; Next Generation Sequencing; TSC1 mutation; Temsirolimus; Uveal melanoma; mTOR inhibition