Oncology & Hematology

A 65-year-old woman presented with a 6-month history of postmenopausal vaginal bleeding, and endometrial biopsy showed grade 2 endometrioid adenocarcinoma. What would you do next?

This cross-sectional study uses a large natural language processing model to examine unmet medical and social needs based on cancer-related fundraising stories in the US.

To the Editor A recently published article sparked our interest. The meta-analysis included 24 randomized clinical trials and conducted a random-effects meta-analysis to estimate risk ratios for the incidence of primary outcomes. The conclusion was that addition of androgen receptor–signaling inhibitors to traditional androgen deprivation therapy was associated with an increased risk of cardiovascular events across the prostate cancer disease spectrum. However, we found some problems in the progress of the meta-analysis that need to be addressed.

In Reply We appreciate the interest in our recently published article. We thank Tang et al for their careful review of our meta-analysis of 24 randomized clinical trials that assessed the incidence of cardiovascular events with the addition of androgen receptor–signaling inhibitors to standard of care in locally advanced and metastatic prostate cancer.

This nonrandomized clinical trial examines whether matched-targeted therapy based on tumor mutation status with a PD-L1 inhibitor is associated with improved overall survival among patients with anaplastic thyroid carcinoma.

This cohort study examines whether there is an association of diet quality and dietary inflammatory potential with prostate cancer grade reclassification in men with grade group 1 disease undergoing active surveillance.

In the Original Investigation titled “Risk-Directed Ambulatory Thromboprophylaxis in Lung and Gastrointestinal Cancers: the TARGET Randomized Clinical Trial,” published online September 21, 2023, and in the November 2023 print issue, in Figure 3A and B, a formatting error was corrected to delineate data for arterial thromboembolism and those for bleeding. Also, data in the progression and death categories were revised; an explanation for these changes to the data is given in an online Comment accompanying the article. This article has been corrected online.

As the number of individuals experiencing gender incongruence seeking health care increases worldwide, it is imperative to continue to improve cancer screening and diagnosis and treatment approaches to achieve more equitable outcomes for transgender and gender-diverse people. For transgender women, we must ensure equitable access to knowledgeable and competent high-quality health care, and prostate cancer screening and treatment is no exception.

This cohort study assesses the long-term adverse effects and complications of prostate cancer treatment in treated patients compared with a general population of older males.

This phase 1b/2 nonrandomized clinical trial evaluates whether equecabtagene autoleucel can benefit patients with relapsed or refractory multiple myeloma and determines the overall response rate after infusion.

In Reply We appreciate the thoughtful comments to this Viewpoint by Karahan et al that emphasize the importance of considering additional predictive parameters when determining immunotherapy treatment strategies for patients with advanced melanoma. In patients with treatment-naive unresectable or metastatic melanoma and no central nervous system metastases, various clinical and molecular biomarkers, including programmed cell death ligand 1 (PD-L1) status (1% cut-off), liver metastases, BRAF mutational status, and the number of involved metastatic organs may help guide the shared decision-making process for dual checkpoint inhibition with ipilimumab plus nivolumab vs anti–programmed cell death 1 (PD-1) monotherapy. In addition, acknowledging the challenges in precisely defining this population in clinical trials and clinical studies, patients with rapidly progressing and/or symptomatic disease, very high tumor burden, or disease localization in organs at high risk (eg, close to critical anatomic structures like the spinal cord or upper airways) might obtain superior benefit from combination therapy with ipilimumab plus nivolumab due to the fast kinetics of response. To our knowledge, no defined biomarkers, other than PD-L1 at the 1% cut-off, exist for guiding the choice between the combination of relatlimab plus nivolumab and anti-PD-1 monotherapy.

To the Editor We read with great interest the comments by Donia and Prasad suggesting that for patients with tumors exhibiting positive staining (≥1%) for programmed cell death ligand 1 (PD-L1), nivolumab monotherapy offers maximal benefit while cautioning against the necessity of the combination therapy due to toxic effects and cost. However, we wish to address certain points and express our reservations regarding this stance.

JAMA Oncology is committed to publishing influential original research, opinions, and reviews that advance the science of oncology and improve the clinical care of patients with cancer.

In Reply We thank Thorat for their comments and the opportunity to respond to their concerns. In a meta-analysis of 13 studies, the false-negative rate (FNR) of sentinel lymph node biopsy (SLNB) with removal of 3 or more SLNs was 4%. In the same analysis, when a dual tracer was used, it was 11%, compared with 19% with a single tracer. Selective removal of the sampled and marked lymph node results in an FNR of 4% to 12%, and when this is combined with SLNB (targeted axillary dissection [TAD]), the FNR ranges between 2% and 4%. Only patients treated with SLNB with dual mapping or TAD were included in the study. Although retrieval of at least 3 or more SLNs was not mandatory at all participating sites, only 47 of 666 patients (7%) in the SLNB group had fewer than 3 SLNs removed.

To the Editor We read with great interest the retrospective study by Swenson et al in which the authors highlight substantial disparities regarding the accessibility of clinical trials for advanced-stage cancer in the US with the ClinicalTrials.gov database, particularly for rural populations and racial and ethnic minority groups. Although this research has made a substantial contribution, we have several suggestions for future advancement.

This Viewpoint discusses the importance of formulating more stable local treatment guidelines because international guidelines and even resource-stratified guidelines may not be as applicable in low- to middle-income countries.

In Reply On behalf of my coauthors, I appreciate the thoughtful response to our article on the disparities in clinical trial access for patients with advanced-stage cancer. The Letter raises important points that we would like to address. Our study identified the presence of a registered clinical trial open for enrollment at specific zip codes to determine access. As noted, the database may not have captured all clinical trials, particularly those unregistered, even though sponsors and investigators in the US are mandated to submit information to ClinicalTrials.gov. It is possible that some US trials were not listed, which could have affected the comprehensiveness of our findings. Additionally, we acknowledge that age disparities between trial participants and the diagnosed disease population exist, especially in breast, prostate, colon, and lung cancer trials, as described by Zhao et al, with such disparities increasing over time. This is a critical area for further investigation.

In the Original Investigation titled “Efficacy of Adding Veliparib to Temozolomide for Patients With MGMT-Methylated Glioblastoma: A Randomized Clinical Trial,” published online October 31, 2024, and in the December 2024 issue, there were errors in the legend of Figure 2. The curve labeled “TMZ + placebo” should have been labeled “TMZ + veliparib,” and the curve labeled “TMZ + veliparib” should have been labeled “TMZ + placebo.” In Figure 3, the label on the left side of the forest plot should read “Favors veliparib,” not “Favors no increase in overall survival,” and the label on the right side of the forest plot should read “Favors placebo,” not “Favors increase in overall survival.” This article was corrected online.

This randomized clinical trial evaluates the combination of veliparib and temozolomide in treating glioblastoma.

This Viewpoint explores whether the Inflation Reduction Act’s provisions and price negotiations could affect investment in trials of new oncology therapies or indications.

This cohort study evaluates the survival outcomes of currently smoking patients with cancer who entered into a smoking cessation treatment program based on the time between diagnosis and program entry.

To the Editor Whether interventions by lay health workers (LHWs) can improve end-of-life care for patients with advanced cancer is a worthy but still uncertain research question. We appreciate the efforts of Patel and colleagues in conducting the EPAC randomized clinical trial and updating the results regarding the long-term effects. We would like to raise a few concerns.

a word that means this disease, so vicious and vengeful, has spread.

In Reply We thank Kang and Wu for the questions they raised. Our study reported on long-term follow-up, nearly 10 years after the first patient was randomized to a 6-month lay health worker–led advance care planning education and engagement intervention layered onto usual cancer care (intervention group) vs usual cancer care alone (control group). All patients randomized to the intervention group received the intervention for a duration of 6 months or until death, whichever was first, by 1 lay health worker with a Bachelors of Arts degree. The results report on the sustained associated benefit of the intervention on several key outcomes nearly 10 years after the intervention was completed for the participants. We agree that more evidence is needed regarding the scalability of such an intervention. Hence, our team has several ongoing multisite trials to evaluate whether the intervention is effective on these key outcomes at scale.

This Viewpoint outlines the missions of academic cancer centers and how they are being affected by the oncology industrial complex along with challenges and suggestions for an aligned way forward.

This randomized clinical trial evaluates whether the combination of lenvatinib plus ifosfamide and etoposide improves outcomes in children and young adults with relapsed osteosarcoma.

A 72-year-old man with a history of polycythemia vera (positive for JAK2 V617F) presented with several months of functional decline and weight loss. An 18F-fluorodeoxyglucose positron emission tomography/computed tomography showed soft tissue infiltrates and sclerosis of the perirenal spaces with fluorodeoxyglucose uptake. What is your diagnosis?

Over the last several years, the prognosis for patients with nasopharyngeal cancer has improved due to therapeutic advances. As a result, the staging system has lagged behind, creating a discrepancy between expected and actual treatment outcomes. Given this incongruence, an updated staging system is warranted to accurately capture the successful change in patient survival. In JAMA Oncology, Pan et al present the American Joint Committee on Cancer (AJCC) version 9 TNM Staging System for nasopharyngeal carcinoma (NPC). They retrospectively analyzed tumor biological features and overall survival of 4914 patients from an international cohort diagnosed with NPC. Based on their results, they propose reclassification of stage I to III for localized disease, stage IV distant metastatic disease, while also adding radiological extranodal extension (ENE) as a criterion for N3.

Immunotherapy has represented a novel and cutting-edge approach to treating patients with many types of metastatic cancers in recent years, transforming outcomes for patients who previously had limited options. Immunotherapy enhances the body’s natural defenses to target and eliminate cancer cells. The agents used are immune checkpoint inhibitors that target specific sites within the immune system, particularly focusing on T cells and their interactions with cancer cells or antigen-presenting cells. The primary sites at T cells of action include the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis and cytotoxic T-lymphocyte–associated protein 4 (CTLA-4). The US Food and Drug Administration (FDA) has approved several immunotherapy agents, and each could have different modes of action targeting these sites in various cancers. In 2020, pembrolizumab, a PD-1 inhibitor, was approved for the treatment of patients with anaplastic thyroid carcinoma. In 2 nonrandomized phase 2 clinical trials in this issue of JAMA Oncology, Sehgal et al and Cabanillas et al explored the applications of immunotherapy in treating patients with aggressive thyroid cancer.

To the Editor Montagna and colleagues should be congratulated for their effort in assembling a global multi-institutional academic collaboration to address an important clinical question in axillary management. This study demonstrates the oncological safety of axillary surgical de-escalation in node-positive breast cancer that downstages to ypN0 with neoadjuvant chemotherapy (NACT). However, the authors’ statement that “surgeons should be reassured that [sentinel node biopsy (SLNB)] with dual-tracer mapping and [targeted axillary dissection (TAD)] have similar outcomes” needs to be interpreted cautiously.