Tumor mutational burden (TMB), defined as the total number of somatic mutations per coding area of a tumor genome, is an emerging clinical biomarker associated with response to immune checkpoint inhibitor (ICI) therapy.^1,2 TMB has been shown to vary markedly among tumor types as well as among patients within tumor types.^3,4 Higher TMB is commonly observed in cancers associated with mutagens, such as ultraviolet light exposure in melanoma and smoking in non–small-cell lung cancer (NSCLC),⁴ with prevalence of high TMB (TMB-H; defined here as ≥10 mutations/megabase [mut/Mb]) in approximately 52% of patients with melanoma and 38% to 42% of patients with NSCLC.³ By comparison, less than 5% prevalence of TMB-H has been reported in other tumor types, including mesothelioma, sarcomas, and prostate cancers.³

Baek MH, et al. J Gynecol Oncol. 2024 May;35:e105. https://doi.org/10.3802/jgo.2024.35.e105

Objectives: The effectiveness and costs of new treatments should be assessed in relation to existing practice. We describe treatments, survival and costs for advanced or metastatic small cell lung cancer (SCLC) patients receiving systemic therapy in the period preceding the introduction of immunotherapies.Materials and Methods: This was a retrospective cohort study of patients aged ≥65 years, identified using linked Surveillance, Epidemiology, and End Results and Medicare databases. Individuals with a new primary diagnosis of SCLC between January 2007 and December 2013 were followed until December 2014. Chemotherapy treatments, health care visits and costs (in 2016 USD), and survival were determined by line of therapy.Results: A total of 11 812 patients were identified with SCLC. First‐line (1L) chemotherapy was received by 6509 (55.1%) patients, most (93.2%) with carboplatin‐ (71.0%) or cisplatin‐ (22.2%) based therapies, typically combined with etoposide (79.2%). Second‐ (2L) and third‐ (3L) line chemotherapies were received by 2238 (18.9%) and 679 (5.7%) patients, of which 48.4% and 30.9%, respectively, were platinum‐based. The median durations of 1L, 2L, and 3L carboplatin‐based therapies were 5.9, 4.8, and 5.4 months, respectively, and the corresponding durations of cisplatin‐based therapies were 5.3, 4.2, and 5.3 months. During 1L, 2L, and 3L chemotherapies, patients averaged 8.2, 7.4, and 7.3 health care visits per month, respectively, and incurred total mean health care costs of $60 223, $42 636, and $35 903 per patient, respectively. Median survival from the start of 1L, 2L, and 3L chemotherapy was 9.2, 6.0, and 5.7 months, respectively.Conclusion: First‐line chemotherapy was primarily platinum‐based, and a plethora of different regimens was used for 2L and 3L chemotherapies. Median survival from the start of 1L chemotherapy was 9 months, with an associated health care cost of $60 000. These data highlight an unmet medical need among SCLC patients receiving systemic therapy.

Patients with BRCA1/2 mutations (BRCAm), loss-of-function mutations in other homologous recombination repair (HRRm) genes, or tumors that are homologous recombination deficiency positivity (HRD+) demonstrate a robust response to PARPi therapy. We conducted a systematic literature review and meta-analysis to evaluate the prognostic value of BRCAm, HRRm, and HRD+ on overall survival (OS) among those treated by chemotherapy or targeted therapy other than PARPi across tumor types. A total of 135 eligible studies were included. Breast cancer (BC) patients with BRCA1/2m had a similar overall survival (OS) to those with wild-type BRCA1/2 (BRCA1/2 wt) across 18 studies. Ovarian cancer (OC) patients with BRCA1/2m had a significantly longer OS than those with BRCA1/2 wt across 24 studies reporting BRCA1m and BRCA2m, with an HR of 0.7 (0.60.8). Less OS data were reported for other tumors: 6 studies for BRCA2m compared with BRCA2 wt in prostate cancer with an HR of 1.9 (1.13.2) and 2 studies for BRCA1/2m compared with BRCA1/2 wt in pancreatic cancer with an HR of 1.5 (0.83.1). Only 4 studies reported HRD+ by either BRCA m or genomic instability score (GIS)42 and OS by HRD status. The HR was 0.67 (0.431.02) for OS with HRD+ vs. HRD. A total of 15 studies reported the association between HRRm and OS of cancers in which one or more HRR genes were examined. The HR was 1.0 (0.71.4) comparing patients with HRRm to those with HRR wild-type across tumors. Our findings are useful in improving the precision and efficacy of treatment selection in clinical oncology.

Objective. To describe chemotherapy treatments, associated health care use and costs, and survival for women diagnosed with cervical cancer in the United States. Methods. This was a retrospective cohort study of patients aged ≥65 years, identified in linked Surveillance, Epidemiology, and End Results (SEER) and Medicare databases. Women with a new primary diagnosis of cervical cancer between January 2007 and December 2013 were followed until December 2014. Systemic chemotherapy treatments, health care visits and costs (2016 USD), and survival were determined by line of therapy. Results. Of 1,651 women in the analysis, 810 (49.1%) were diagnosed at stages I or II, 411 (24.9%) at stage III, and 430 (26.0%) at stage IV. A total of 225 (13.6%) women received first-line (1L) systemic chemotherapy. Of those who received 1L chemotherapy, 73 (32.4%) received second-line (2L) chemotherapy, and 29 (12.9%) received third-line (3L) chemotherapy. During 1L and 2L chemotherapies, patients averaged 5.9 and 6.5 health care visits per month, respectively, and incurred total mean health care costs per patient per month of $7,098 and $8,770, respectively. Median survival from the start of 1L and 2L chemotherapy was 14.0 and 10.4 months, respectively. Conclusion. Elderly patients with advanced cervical cancer had a poor prognosis, with a median survival of 14 months or less, and had no standard of care for 2L therapy. Systemic chemotherapies pose a substantial economic burden in the range of $7,000 to $9,000 per patient per month. These results highlight the high unmet medical need among elderly patients with cervical cancer.

The classification of undifferentiated pleomorphic sarcoma (UPS) has been evolving with advances in immunohistochemistry and genomic profiling over the past 20 years. There is a lack of current information on UPS incidence. Due to the lack of designated histology codes for UPS in the Surveillance, Epidemiology, and End Results (SEERs) program, we estimated UPS incidence by three different definitions based on clinical opinions using the 2000–2020 data from 22 registries of the SEER program. The incidence varied widely across the three definitions with 0.06 per 100,000 persons for the least inclusive definition and 0.67 per 100,000 persons for the most inclusive definition in 2016–2020, making it challenging to estimate the exact incidence of UPS. Regardless, all the incidences decreased between 2000 and 2020. Guidelines in UPS diagnosis and classification need to be better implemented in the US.