JAMA Oncology

Our medical research library holds 6 studies published in JAMA Oncology (2017–2024). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 4 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 2 studies PubMed has no abstract for, we give the abstract printed in the article or, where there is none, a summary we wrote from it, each labeled as such.

About the journal

• Publisher: American Medical Association
• Published: 2015 to the present, United States
• Language: English
• ISSN: 2374-2437 (print), 2374-2445 (electronic)
• Its record in the NLM Catalog

2020s

• Pegargiminase Plus First-Line Chemotherapy in Patients With Nonepithelioid Pleural Mesothelioma: The ATOMIC-Meso Randomized Clinical Trial. P.W. Szlosarek, B.C. Creelan, T. Sarkodie, et al. 2024;10(4):475-483. Randomized trial PubMed · Publisher · Free full text

  Abstract

  Importance: Arginine deprivation using ADI-PEG20 (pegargiminase) combined with chemotherapy is untested in a randomized study among patients with cancer. ATOMIC-Meso (ADI-PEG20 Targeting of Malignancies Induces Cytotoxicity-Mesothelioma) is a pivotal trial comparing standard first-line chemotherapy plus pegargiminase or placebo in patients with nonepithelioid pleural mesothelioma.

  Objective: To determine the effect of pegargiminase-based chemotherapy on survival in nonepithelioid pleural mesothelioma, an arginine-auxotrophic tumor.

  Design, Setting, And Participants: This was a phase 2-3, double-blind randomized clinical trial conducted at 43 centers in 5 countries that included patients with chemotherapy-naive nonepithelioid pleural mesothelioma from August 1, 2017, to August 15, 2021, with at least 12 months' follow-up. Final follow-up was on August 15, 2022. Data analysis was performed from March 2018 to June 2023.

  Intervention: Patients were randomly assigned (1:1) to receive weekly intramuscular pegargiminase (36.8 mg/m2) or placebo. All patients received intravenous pemetrexed (500 mg/m2) and platinum (75-mg/m2 cisplatin or carboplatin area under the curve 5) chemotherapy every 3 weeks up to 6 cycles. Pegargiminase or placebo was continued until progression, toxicity, or 24 months.

  Main Outcomes And Measures: The primary end point was overall survival, and secondary end points were progression-free survival and safety. Response rate by blinded independent central review was assessed in the phase 2 portion only.

  Results: Among 249 randomized patients (mean [SD] age, 69.5 [7.9] years; 43 female individuals [17.3%] and 206 male individuals [82.7%]), all were included in the analysis. The median overall survival was 9.3 months (95% CI, 7.9-11.8 months) with pegargiminase-chemotherapy as compared with 7.7 months (95% CI, 6.1-9.5 months) with placebo-chemotherapy (hazard ratio [HR] for death, 0.71; 95% CI, 0.55-0.93; P = .02). The median progression-free survival was 6.2 months (95% CI, 5.8-7.4 months) with pegargiminase-chemotherapy as compared with 5.6 months (95% CI, 4.1-5.9 months) with placebo-chemotherapy (HR, 0.65; 95% CI, 0.46-0.90; P = .02). Grade 3 to 4 adverse events with pegargiminase occurred in 36 patients (28.8%) and with placebo in 21 patients (16.9%); drug hypersensitivity and skin reactions occurred in the experimental arm in 3 patients (2.4%) and 2 patients (1.6%), respectively, and none in the placebo arm. Rates of poststudy treatments were comparable in both arms (57 patients [45.6%] with pegargiminase vs 58 patients [46.8%] with placebo).

  Conclusions And Relevance: In this randomized clinical trial of arginine depletion with pegargiminase plus chemotherapy, survival was extended beyond standard chemotherapy with a favorable safety profile in patients with nonepithelioid pleural mesothelioma. Pegargiminase-based chemotherapy as a novel antimetabolite strategy for mesothelioma validates wider clinical testing in oncology.

  Trial Registration: ClinicalTrials.gov Identifier: NCT02709512.

• Structural Racism and Lung Cancer Risk: A Scoping Review. S.N. Bonner, R. Curley, K. Love, et al. 2024;10(1):122-128. PubMed · Publisher

  Abstract

  Importance: Structural racism is associated with persistent inequities in health and health outcomes in the US for racial and ethnic minority groups. This review summarizes how structural racism contributes to differential population-level exposure to lung cancer risk factors and thus disparate lung cancer risk across different racial and ethnic groups.

  Observations: A scoping review was conducted focusing on structural racism and lung cancer risk for racial and ethnic minority groups. The domains of structural racism evaluated included housing and built environment, occupation and employment, health care, economic and educational opportunity, private industry, perceived stress and discrimination, and criminal justice involvement. The PubMed, Embase, and MedNar databases were searched for English-language studies in the US from January 1, 2010, through June 30, 2022. The review demonstrated that racial and ethnic minority groups are more likely to have environmental exposures to air pollution and known carcinogens due to segregation of neighborhoods and poor housing quality. In addition, racial and ethnic minority groups were more likely to have exposures to pesticides, silica, and asbestos secondary to higher employment in manual labor occupations. Furthermore, targeted marketing and advertisement of tobacco products by private industry were more likely to occur in neighborhoods with more racial and ethnic minority groups. In addition, poor access to primary care services and inequities in insurance status were associated with elevated lung cancer risk among racial and ethnic minority groups. Lastly, inequities in tobacco use and cessation services among individuals with criminal justice involvement had important implications for tobacco use among Black and Hispanic populations.

  Conclusions And Relevance: The findings suggest that structural racism must be considered as a fundamental contributor to the unequal distribution of lung cancer risk factors and thus disparate lung cancer risk across different racial and ethnic groups. Additional research is needed to better identify mechanisms contributing to inequitable lung cancer risk and tailor preventive interventions.

• Nivolumab Plus Ipilimumab vs Nivolumab Alone in Advanced Cancers Other Than Melanoma: A Meta-Analysis. A.V. Serritella, N.K. Shenoy. 2023;9(10):1441-1446. PubMed · Publisher · Free full text

  Abstract

  Importance: Although the combination of nivolumab plus ipilimumab has unquestionable benefit over nivolumab monotherapy in advanced melanoma, currently no summative analyses have compared the combination with nivolumab monotherapy for advanced cancers other than melanoma.

  Objective: To examine whether the addition of ipilimumab to standard-dose nivolumab safely improves clinical outcomes in patients with advanced cancers other than melanoma.

  Data Sources: Electronic databases (PubMed, EBSCO Information Services, Embase, and Cochrane Library) were systematically searched for studies of standard-dose nivolumab plus ipilimumab vs nivolumab alone in the treatment of advanced cancers other than melanoma published from database inception to October 31, 2022.

  Study Selection: Eight studies (total patients, 1727; nivolumab plus ipilimumab group, 854; nivolumab monotherapy group, 873) met the selection criteria. Patients had squamous cell lung cancer, non-small cell lung cancer with programmed death ligand 1 level of 1% or higher, small cell lung cancer, pleural mesothelioma, urothelial carcinoma, esophagogastric carcinoma, sarcoma, or glioblastoma multiforme.

  Data Extraction And Synthesis: For comparison of overall survival (OS) and progression-free survival (PFS) outcomes, estimation of log(hazard ratios [HRs]) and SEs was initially performed for OS and PFS of each included study based on summary statistics extracted from individual Kaplan-Meier curves. Inverse-variance weighting was then used to compute pooled HRs (95% CIs). For comparison of dichotomous data (treatment-related grade 3 to 4 adverse events and discontinuations), odds ratios (ORs) were used, and the Mantel-Haenszel method was used to estimate pooled ORs (95% CIs).

  Results: Treatment with nivolumab plus ipilimumab was not associated with improvement in OS over treatment with nivolumab alone (pooled HR, 0.95; 95% CI, 0.85-1.06; P = .36), with 4 of the 8 studies having numerically lower median OS with the combination. Nivolumab plus ipilimumab combination therapy was associated with marginal, but not clinically meaningful, improvement in PFS over nivolumab alone (pooled HR, 0.88; 95% CI, 0.79-0.98; P = .02). The combination was associated with substantially higher treatment-related grade 3 to 4 adverse events (pooled OR, 1.84; 95% CI, 1.47-2.31; P < .001) and treatment-related discontinuations (pooled OR, 1.96; 95% CI, 1.44-2.65; P < .001). This finding was recapitulated in meta-analyses of individual grade 3 to 4 adverse events of hepatotoxicity, gastrointestinal toxicity, pneumonitis, endocrine dysfunction, dermatitis, fatigue.

  Conclusions And Relevance: In this meta-analysis of 8 advanced cancers other than melanoma, the differences detected in OS and PFS between nivolumab plus ipilimumab and nivolumab were not clinically meaningful (even though statistical significance was detected in PFS). Treatment-related higher-grade toxicity and discontinuations were substantially higher with the combination therapy. The data indicate that investigations of anti-programmed death 1 (PD1) plus anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapies in any nonmelanoma advanced cancer should be conducted along with anti-PD1 monotherapy to ensure that the net effect of the addition of anti-CTLA-4 to anti-PD1 can be clearly established for that cancer and setting and that unnecessary CTLA-4 inhibition with related toxic effects (both clinical and financial) can be avoided.

2010s

• High Time for Complete Ban on Asbestos Use in Developing Countries. T. Chen, X.M. Sun, L. Wu. 2019;5(6):779-780. PubMed · Publisher

  Summary

  In this viewpoint, three authors based in China, the United Kingdom and Canada argued for a complete ban on asbestos use in developing countries. They drew on discussions among Chinese delegates at the 14th meeting of the International Mesothelioma Interest Group, held May 2-5, 2018, in Ottawa, Canada. Citing the World Health Organization, they reported that about 125 million people worldwide were exposed to asbestos at work and more than 107 000 workers died from asbestos-related diseases each year. Using US Geological Survey figures, they stated that global asbestos consumption in 2016 was 1.37 million metric tons. India (308 000 tons), China (288 000), Russia (234 000), Brazil (120 000) and Indonesia (114 000) together accounted for about 80% of it. Global production was 1.28 million tons, with Russia producing 54% and Brazil and China about 16% each. The authors described China's position: it imported large quantities from Russia, and 2014 regulations required protective clothing for chrysotile workers but did not ban chrysotile. Exposure occurred at construction sites, building-material plants and shipyards, and near boilers and insulation pipes, and reached families through contaminated clothing. They noted that temporary contract work made epidemiological data hard to gather. They summarized international calls for bans since 2005 and presented a theoretical model linking consumption to expected mesothelioma incidence. They concluded that incidence would rise in Brazil, Russia, India and China over the coming decades.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

• Identification of ALK Rearrangements in Malignant Peritoneal Mesothelioma. Y.P. Hung, F. Dong, J.C. Watkins, et al. 2018;4(2):235-238. PubMed · Publisher · Free full text

  Abstract

  Importance: Malignant peritoneal mesothelioma is a rare, aggressive tumor arising from the peritoneal lining, induced by asbestos, therapeutic radiation, or germline mutations. Nevertheless, the molecular features remain largely unknown.

  Objective: To investigate anaplastic lymphoma kinase (ALK) rearrangements in a large series of peritoneal mesothelioma and characterize the mutational landscape of these tumors.

  Design, Setting, And Participants: We studied 88 consecutive patients (39 men, 49 women; median age 61, range 17-84 years) with peritoneal mesotheliomas diagnosed at a single institution between 2005 and 2015. We identified ALK-positive mesotheliomas by immunohistochemistry and confirmed ALK rearrangement by fluorescence in situ hybridization (FISH). In ALK-rearranged cases, we characterized the fusion partners using targeted next-generation sequencing of both tumor DNA and RNA. In select cases, we quantified asbestos fibers by combined scanning electron microscopy and x-ray spectroscopy. We also explored ALK rearrangement in a separate series of 205 patients with pleural mesothelioma.

  Main Outcomes And Measures: Identification and characterization of novel ALK rearrangements and correlations with clinicopathologic characteristics.

  Results: Anaplastic lymphoma kinase was positive by immunohistochemistry in 11 (13%) peritoneal mesotheliomas (focal weak in 8, diffuse strong in 3). In focal weak ALK-positive cases, no ALK rearrangement was detected by FISH or next-generation sequencing. In strong diffuse ALK-positive cases, FISH confirmed ALK rearrangements, and next-generation sequencing identified novel fusion partners ATG16L1, STRN, and TPM1. Patients with ALK-rearranged peritoneal mesotheliomas were women and younger than patients without ALK rearrangement (median age 36 vs 62; Mann-Whitney test, P = .02), but all other clinicopathologic characteristics (size of tumor nodules, histology, treatment, and survival) were not different. No asbestos fibers were detected in ALK-rearranged cases. Furthermore, loss of chromosomal region 9p or 22q or genetic alterations in BAP1, SETD2, or NF2 typically present in peritoneal mesothelioma were absent in the ALK-rearranged cases. All pleural mesotheliomas were ALK-negative by immunohistochemistry.

  Conclusions And Relevance: We identified unique ALK rearrangements in a subset of patients with peritoneal mesothelioma, each lacking asbestos fibers, therapeutic radiation, and cytogenetic and molecular alterations typically found in these tumors. Identification of clinically actionable ALK rearrangements may represent a novel pathogenetic mechanism of malignant peritoneal mesothelioma with promise for targeted therapy.

• Association of Asbestos Exposure With Malignant Mesothelioma Incidence in Eastern China. W. Mao, X. Zhang, Z. Guo, et al. 2017;3(4):562-564. PubMed · Publisher · Free full text

  Summary

  This research letter examined malignant mesothelioma (MM) and asbestos exposure in eastern China, where only 15% of MMs had been reported as linked to asbestos. The authors retrospectively reviewed tumors diagnosed as MM from January 2002 through December 2015 at two hospitals. One was Zhejiang Cancer Hospital (ZJCH) in Hangzhou, where there is no asbestos industry. The other was Yuyao People's Hospital, located 112 km away in a textile asbestos industrial area. Histologic review with an immunohistochemical panel confirmed MM in 52 of 92 cases: 28 from ZJCH and 24 from Yuyao. Trained oncologists assessed asbestos exposure by interviewing patients about occupational and family histories. The male to female ratio was approximately 1:4 and the pleural to peritoneal ratio approximately 1:3. Mean age at diagnosis was 50.6 years, compared with 72 years in the United States. Twenty of the 52 MMs (38%) occurred in asbestos-exposed individuals: 2 of 28 (7%) at ZJCH and 18 of 24 (75%) at Yuyao. Asbestos-related MMs occurred in 19 women and 1 man. Apart from asbestos exposure, no significant demographic differences were observed between the hospitals. The authors suggested that asbestos may not be the main cause of MM in these women, and that the findings offer an opportunity to investigate other causes of peritoneal MM. They noted that the sample was small and the results were not adjusted for confounding variables.

  PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

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