PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers.

Background: MET exon 14 alterations are actionable oncogenic drivers. Durable responses to MET inhibitors are observed in patients with advanced MET exon 14-altered lung cancers in prospective trials. In contrast, the activity of immunotherapy, PD-L1 expression and tumor mutational burden (TMB) of these tumors and are not well characterized. Patients and methods: Patients with MET exon 14-altered lung cancers of any stage treated at two academic institutions were identified. A review of clinicopathologic and molecular features, and an analysis of response to single-agent or combination immune checkpoint inhibition were conducted. PD-L1 immunohistochemistry was carried out and TMB was calculated by estimation from targeted next-generation sequencing panels. Results: We identified 147 patients with MET exon 14-altered lung cancers. PD-L1 expression of 0%, 1%-49%, and ≥50% were 37%, 22%, and 41%, respectively, in 111 evaluable tumor samples. The median TMB of MET exon 14-altered lung cancers was lower than that of unselected non-small-cell lung cancers (NSCLCs) in both independently evaluated cohorts: 3.8 versus 5.7 mutations/megabase (P < 0.001, n = 78 versus 1769, cohort A), and 7.3 versus 11.8 mutations/megabase (P < 0.001, n = 62 versus 1100, cohort B). There was no association between PD-L1 expression and TMB (Spearman's rho=0.18, P = 0.069). In response-evaluable patients (n = 24), the objective response rate was 17% (95% CI 6% to 36%) and the median progression-free survival was 1.9 months (95% CI 1.7-2.7). Responses were not enriched in tumors with PD-L1 expression ≥50% nor high TMB. Conclusion: A substantial proportion of MET exon 14-altered lung cancers express PD-L1, but the median TMB is lower compared with unselected NSCLCs. Occasional responses to PD-1 blockade can be achieved, but overall clinical efficacy is modest.

Ovarian masses in pediatric patients: a multicenter study of 98 surgical cases in Tunisia.

Ovarian masses requiring surgical intervention are uncommon in the pediatric population. Our aim is to report results of a multicentric Tunisian study concerning the clinical practice and the management of pediatric ovarian masses and to identify the factors that are associated with ovarian preservation. Between January 2000 and December 2015, 98 pediatric patients (<14 years) were surgically treated for ovarian masses at the five pediatric surgery departments in Tunisia. Ninety-eight patients were included in this study. The mean age of the patients at time of surgery was 8.46 ± 4.87 years. Sixty-three ovarian masses (64.3%) were non-neoplastic lesions, 24 (24.5%) were benign tumors, and 11 (11.2%) were malignant neoplasms. Conservative surgery (ovarian-preserving surgery) was successfully performed in 72.4% of the benign lesions, whereas only three patients (27.3%) with malignant tumors underwent ovary-sparing tumor resection (p < .001). The mean diameter of the tumors in the patients who underwent oophorectomy was significantly larger than that in the patients who underwent conservative surgery (7.8 ± 3.9 cm vs. 5.7 ± 2.9 cm, respectively, p = .001). In our study, the risk factors for oophorectomy were a malignant pathology and large tumor size. In accordance with the Gynecologic Cancer Intergroup consensus, we recommend that surgical management of ovarian masses in children should be based on ovarian-preserving surgery.