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Challenges in Interpreting MELATORCH Trial Outcomes—Reply

In Reply We thank Yuji and Li for their comments on the MELATORCH trial. We agree with the main point: the median progression-free survival (PFS) difference was small. However, a comparison of the treatment effect that considers only median survival time, a point estimate, is not sufficient to fully characterize the overall treatment effects. The MELATORCH study has evaluated the magnitude of efficacy by comparing the differences over the entire survival curves between the treatment arms, which is statistically measured by the hazard ratio (HR), its 95% CI from the Cox proportional hazards model, and the P value from the log-rank test. From the PFS Kaplan-Meier curves, the 2 treatment arms clearly separated after the median and the separation was sustained, demonstrating a statistically significant improvement in PFS of toripalimab over dacarbazine (HR, 0.71; 95% CI, 0.53-0.95; P =.02). In addition, we report the milestone PFS rates and restricted mean survival time (RMST): the difference in 6-month PFS rates was 1.0% (95% CI, −11.4 to 13.4), the difference in 12-month PFS rates was 9.7% (95% CI, −0.4 to 19.8), and the RMST difference was 1.2 months (95% CI, −0.23 to 2.6). Taken together, the overall treatment effects were not captured by the median PFS alone. Because immunotherapy often conveys delayed but long-lasting survival benefits, the antitumor activity can be further supported by the improvements in ORR and duration of response.

Stereotactic Radiotherapy vs Hippocampal-Avoidance Whole Brain Radiation

As patients live longer with advanced cancer, brain metastases are now becoming a frequent and even chronic condition managed with a variety of systemic agents and local treatments. Radiotherapy plays a key role in treatment of intracranial lesions. Whole brain radiation therapy (WBRT) has the benefit of treating both imaging-apparent and microscopic disease. This approach can offer general intracranial disease control, but can damage healthy brain tissue, resulting in neurocognitive impairment associated with irradiation of the hippocampus. The innovation of hippocampal-avoidance WBRT (HA-WBRT) maintains global intracranial disease control while reducing neurocognitive decline relative to traditional WBRT, even in the setting of the neuroprotectant memantine (0.74; 95% CI, 0.58-0.95; P =.02), making HA-WBRT a standard-of-care approach to appropriate patients. Nevertheless, HA-WBRT requires several weeks of daily treatments and often time off systemic therapy. Conversely, stereotactic radiation (SRT) is given over 1 to 3 treatments to the visible lesions, allowing for higher radiation dose, better focal disease control, and sparing of healthy brain tissue, which further reduces neurocognitive toxic effects. SRT is appropriate for patients with a finite number of visible lesions but may allow microscopic disease elsewhere in the brain to progress, necessitating subsequent treatments or even salvage WBRT. In addition, the higher dose of SRT can cause radiation necrosis and inflammation, requiring steroids or other medical and surgical interventions. The optimal balance of intracranial disease control with patient-reported outcomes (PROs) is of increasing importance as patients live longer with the subacute and chronic toxic effects of radiotherapy.

Illness, Providing Care, and Poetry

Poetry stereotypically elicits warm and comforting emotions, but sometimes it also provides a space for clinicians and patients alike to creatively grapple with more uncomfortable or unpleasant realities. The poem “Solo Climb” recounts several parallel stories, intertwining nature, illness, and extreme climbing within a wintry backdrop. Two individuals face adversity in different ways, one snowbound within her home deciding whether to stop chemotherapy and the other (the patient’s friend) who climbs steep steps to reach her third-floor sickroom to care for her. Together they watch a movie about an alpinist scaling a cliff steadfast against the winter elements. Poetry metaphorically likens their experiences, one as a patient and the other a caregiver. The reader feels both safely “perched” and dangerously “hanging” as they approach their respective precipices—yet their journeys, via the poem’s deft juxtapositions, ultimately become shared and equally fraught. Anticipatory language and tenuously enjambed line breaks build throughout the poem, eliciting the foreboding sense that a fall is imminent. These two faltering climbers are “huddled,” “cling[ing],” and yes, “then falling” as they face insurmountable odds and literal life or death choices. The line “I’m too terrified. I want to stop” is so piercing that it almost echoes across the icy chasm of the poem: whether facing difficult treatment or the personal challenges providing care brings, “Solo Climb” pushes readers to the brink. Although we may slip as we surmount our fears, in the “gentle squeeze” of another’s steady presence, we “slowly ascend,” alone and yet together.

JAMA Oncology —The Year in Review, 2025

This year, 2025, was an exciting year for JAMA Oncology. We published the short- and long-term results of several randomized clinical trials that impact clinical care of patients with cancer. The long-term outcomes of the NATALEE trial continue to underscore the benefit of CDK4/6 inhibitors with endocrine therapy in the treatment of hormone receptor–positive, ERBB2-negative early stage breast cancer, while critical studies of dose help control adverse events associated with these drugs. Randomized clinical trial data have helped optimized the care of patients at the end of life experiencing delirium by identifying a drug regimen that controls symptoms with the minimum of adverse effects. Numerous secondary analysis from randomized clinical trials have informed our understanding of cognitive changes after chemotherapy, the use of circulating tumor DNA to predict disease recurrence, and the potential effects of long-term low-dose aspirin use for cancer prevention in older adults. We hope that you enjoyed reading these and other important articles as much as we enjoyed choosing them for publication. The editorial board, our JAMA Oncology editors, and I are honored to have the opportunity to serve the oncology community by offering original, innovative, and timely scientific content that has a direct impact on researchers, clinicians, and patients.

A Scalable Model to Improve Cancer Care for Older Adults

Individuals aged 70 years and older account for more than 40% of patients with cancer in the US and 25% of those with incident cancers. Yet older adults have been largely neglected by cancer research and care improvement efforts. Less than 3% of older patients with cancer are enrolled in oncology clinical trials, and the landscape of treatments received by older adults is not well understood. Comorbid conditions, frailty, and resource limitations can necessitate modifications to cancer treatments and render older patients more vulnerable to complications. Moreover, many may be ineligible for or choose to forgo anticancer therapy and therefore see oncology practitioners infrequently—despite experiencing symptoms and conditions that require ongoing management. These complexities beg for scalable strategies to monitor and support older adults with cancer.

[Clinical Picture] High-output cardiac failure from a synovial sarcoma mimicking arteriovenous fistula

A 30-year-old woman presented to the Vascular Anomalies Centre at Shanghai Ninth People's Hospital in February, 2021, for a worsening and painful left inguinal arteriovenous fistula, which had been diagnosis 7 years previously following a strain 10 years ago. Initial endovascular embolisation in 2014 provided only transient relief, with subsequent symptom recurrence, progressive deep vein thrombosis, limb oedema, and claudication. By 2018, she had developed orthopnoea indicative of cardiac failure and required continuous diuretics, having received only symptomatic care until her presentation.

[Review] Development of a core outcome set for adolescents and young adults with cancer

Adolescents and young adults aged 15–39 years diagnosed with cancer are faced with unique challenges, which affect key developmental milestones and can create complex care needs. The aim of this study was to reach international consensus on the minimum set of outcomes to measure through the development of a core outcome set (COS). The COS development followed published methodological standards. A literature review and interviews with adolescents and young adults with cancer and health-care professionals generated a comprehensive list of 129 outcomes, spanning clinical and patient-reported outcomes relevant to adolescents and young adults with cancer.

[Policy Review] International consensus recommendations and alignment of terminology for the histopathological diagnosis of extranodal extension in head and neck squamous cell carcinoma: an HN-CLEAR initiative

Histopathologically detected extranodal extension leads to upstaging and treatment escalation in head and neck squamous cell carcinoma. There is considerable variation in the prevalence of histopathologically detected extranodal extension in comparable studies. The Head and Neck Cancer International Group, which includes 23 organisations managing patients with head and neck cancer, identified several challenges in evaluating histopathologically detected extranodal extension. Thus, the Head and Neck Consensus Language for Ease and Reproducibility (HN-CLEAR) and its global stakeholders prioritised developing diagnostic criteria and uniform terminology for histopathologically detected extranodal extension.

[Policy Review] A comprehensive framework for glioma surgery by the PIONEER Consortium and RANO resect group, part 2: perioperative recommendations for neurological, language, functional, and quality-of-life assessment

Historically, the assessment of surgical outcomes in patients with glioma has been focused on technical outcomes, such as volumetric analysis of the residual tumour, progression-free survival, and overall survival. Other outcomes, such as neurological deficits, can be challenging to assess in an objective, quantifiable, and comprehensive manner. As a result, no consensus is available on methods to systematically evaluate perioperative neurological, language, cognitive, and functional outcomes in patients with glioma.

[Policy Review] A comprehensive framework for glioma surgery by the PIONEER Consortium and RANO resect group, part 1: intraoperative recommendations for mapping, monitoring, and decision making

In adult patients with newly diagnosed or recurrent diffuse glioma, more extensive resection is associated with longer progression-free and overall survival. Intraoperative mapping techniques are used to safely increase the extent of resection by locating, monitoring, and preserving the function of potentially infiltrated brain during surgery. However, there is no consensus on the indications for intraoperative mapping, the optimal functional tests to be used intraoperatively, or intraoperative decision making.

[Articles] Tiragolumab plus atezolizumab and chemotherapy as first-line treatment for patients with unresectable oesophageal squamous cell carcinoma (SKYSCRAPER-08): a randomised, double-blind, placebo-controlled, phase 3 trial

Independent review facility-assessed progression-free survival and overall survival were significantly better in the tiragolumab plus atezolizumab and chemotherapy group compared with chemotherapy alone for unresectable locally advanced, unresectable recurrent, or metastatic oesophageal squamous cell carcinoma. These data support the rationale for exploring dual checkpoint inhibition added to chemotherapy for this group of patients with a high unmet need.

[Perspectives] Current landscape, successes, and key challenges in cancer vaccine clinical trials across the UK

Cancer vaccines represent a transformative frontier in oncology, offering the potential to elicit durable and specific immune responses against tumour-associated or tumour-specific antigens. This technology has the potential to treat established malignancy, reduce tumour relapse, and even prevent cancer formation—improving survival outcomes. Advances in neoantigen discovery, mRNA vaccine platforms, and personalised immunotherapy have substantially enhanced the feasibility and efficacy of cancer vaccines across various malignancies.

[News] UK Government launches first Men's Health Strategy

On Nov 19, 2025, the UK Government launched the first Men's Health Strategy for England. The policy paper noted that, over the past decade, healthy life expectancy for men has fallen by 1·5 years and that men in parts of the country with the most poverty die on average 10 years earlier than men in parts with the least poverty. Men are more likely than women to smoke, drink alcohol, or use drugs, and be overweight or have obesity. 19% of deaths in men over 35 years are attributable to smoking, seven percentage points higher than women in the same age group, and 68% of deaths from liver disease are in men.

[News] New South Wales expands cancer coverage for firefighters

On Nov 21, 2025, a ministerial media release announced a new legislation passed through Australian Parliament, expanding presumptive workers' compensation coverage for firefighters diagnosed with cancer. The new legislation extends the current list of 12 recognised malignancies in New South Wales, Australia, to include ten new cancers, including primary site lung, pancreatic, thyroid, and skin cancers. Reproductive cancers including cervical, ovarian, uterine, vaginal, vulval, and penile were also included.

[News] Gavi hits HPV vaccine milestone early but concerns surround future funding

Gavi, the Vaccine Alliance, a public–private global health partnership with the goal of increasing access to immunisation in developing countries, is celebrating after working with lower-income countries to reach a key target to vaccinate millions of girls with the human papillomavirus (HPV) vaccine for cervical cancer in mid-November, 2025—6 weeks ahead of its original 3-year target.