Experience on the diagnosis and treatment of multiple active primary cancers in our Institution.
Authors: Jiang Shiyu , Liu Xin , Zhang Xiaowei , Luo Zhiguo , Hu Silong , Li Wentao , Zhou Xiaoyan , WANG Qifeng , Wang Yan-Li , Wang Yaohui , Hu Xichun 
Published: June 2021

e15097 Background: Multiple active primary cancers (MAPC) deal with synchronous multiple primary cancers and heterochronous multiple primary cancers needing concurrent treatment for each primary. There are no standards in the diagnosis and treatment of MAPC. Here, we report our experiences with MAPC cases. Methods: Overall, 31 patients with MAPC between Apr 2017 and Dec 2020 were included. All of them had received treatment for their MAPC, either local intervention or systemic treatment. Results: Of the 31 MAPC, 5 cases having triple and 26 having double primary neoplasms. The most common primary sites were breast (n = 20) and lung (n = 13). The contribution of each diagnostic approach in the establishment of MAPC diagnosis were as follows: atypical metastatic spread, lymphatic or vascular; lesions in other organ sites indicating suspected primary tumor by imaging (11/26) and PET-CT (5/17); atypical increase of tumor marker panel (3/24) or clinical manifestations (7/31) not parallel or specific to the prior documented primary tumor; and patients with genetic predisposition (one germline BRCA2 mutation and one TP53 mutation). If biopsy was not available, utilization of other optimal imaging techniques, such as FES- and PSMA-PET-CT could be helpful in selected patients. Treatment decisions of patients with MAPC should be made with joint effort of the multidisciplinary team. Radical surgery or radiotherapy (17/31) was done in the setting when any primary cancer was considered localized. The severity of each primary malignance (aggressiveness, symptom, staging and etc.) was also evaluated, and the predominant primary tumor was handled with priority. Systemic therapy was administered in consideration of each active cancer, and any new drug combinations should be evaluated for drug interactions. Unexpectedly, use of palbociclib in a patient with breast cancer and chronic lymphoblastic leukemia might aggravate the leukemia, because one week of palbociclib plus letrozole led to a sharp WBC increase with a lymphocyte predominance and quickly reduced to the baseline after drug discontinuation. Notably, NGS in circulating tumor DNA was also useful since it might indicate a common treatment strategy for MAPC and a hint to the predominant cancer. Six MAPC patients including 1 ROS-1 rearranged lung cancer, 4 EGFR mutant lung cancer, and 2 HER2 positive breast cancer were treated with corresponding targeted agents (crizotinib, gefitinib and lapatinib). Four responses (1 CR and 3 PR) and 2 stable disease (PFS 33+ and 132 months) were observed. Three of the four responders had a PFS of 1+, 29+ and 27 months, whereas Case 13 who had multiple combinations of EGFR-TKI, chemotherapy and anti-HER2 treatment for her simultaneously advanced breast and lung cancers, was alive at 66 months. Conclusions: The diagnosis and treatment of MAPC has no standards and should integrate all available resources by a specific multidisciplinary team.