Women With Synchronous or Metachronous Lung and Ovarian Cancer: A Multi-Institutional Report

Abstract

Background/aim: Double diagnosis of lung cancer (LC) and ovarian cancer (OC) is rare. Here, we describe patients with synchronous/metachronous LC and OC to identify common clinical and pathological patterns.

Patients and methods: Clinical, pathological and molecular data of patients diagnosed and treated at 30 European Institutions from 2008 to 2018 were retrieved and analysed. Whenever tissue was available, centralized pathology revision was performed.

Results: A total of 19 cases were found; one was excluded at pathology revision. Most LCs were adenocarcinomas (15/18) and most OCs were high-grade serous (15/18) carcinomas. Of the 9 patients analysed, 7 carried oncogene-addicted LC (4 EGFR, 1 B-RAF and 2 ALK) and five out of 7 carried BRCA mutations. One patient with a germline-BRCA1 mutation received olaparib, resulting in a durable response of both malignancies. Median overall survival was 33 months.

Conclusion: In our series, most synchronous/metachronous LCs and OCs showed genetic alterations. Further analyses with wide NGS panel could shed light on the biological mechanisms driving their occurrence.

Keywords: Lung cancer; homologous recombination deficiency; immunohistochemistry; ovarian cancer; women.

Figure 1. Overall survival in our case-series: median overall survival was 33 months (95%CI=1.98-55.5).

Figure 2. Immunohistochemistry images from specimens obtained from Patient 1 representing (A) lung primary TTF-1 and (B) lung metastasis PAX- 8. MF, Never smoker, 78 years old at the time of diagnosis of lung adenocarcinoma, EGFR mutated on exon 21, IV stage. She received afatinib as 1st line treatment. Twenty-nine months later, disease progression with new brain and lung lesions, for which she underwent a re-biopsy on a lung metastasis, showing an undifferentiated malignancy with loss of EGFR mutation, TTF-1 (-). One month later, onset of a pelvic mass, at the agobiopsy poor differentiated ovarian carcinoma, PAX-8 (+), ER 10%. Patient died two months later. At the pathology revision, the lung metastasis was revealed to be a secondary lesion from the ovarian carcinoma (see Figure 1B).

Figure 3. Immunohistochemistry images from specimens obtained from Patient 2 representing (A) lung primary H/E and (B) ovarian primary H/E. GU, Never smoker, 51 years old at the time of diagnosis of lung adenocarcinoma, EGFR and KRAS wild type. Lung disease at stage I, thus an upper left lobectomy was performed. Three months later, onset of a pelvic mass, involving both uterus and left ovary. At the pathological examination, synchronous endometrioid carcinoma of the uterus and the ovary was diagnosed. Following hystero-annessiectomy, patient underwent adjuvant chemotherapy. Three years later, the patient developed breast cancer and BRCA examination was performed, revealing a BRCA2 mutation of unknown significance. Patient died one year later.