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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.

Echoing Medicine in Poetry

The otherworldliness of health care, for those who tirelessly diagnose and treat illness in its hospitals’ labyrinthine wards, units, and imaging suites, can come to seem normal. Even the strangest or most alienating clinical occurrences can become unremarkable realities. Another blood draw, lumbar puncture, or even surgery can seem quotidian to clinicians, yet profoundly foreign or even frightening to patients. Although movies, TV shows, or individual experience offer glimpses into medicine’s mysteries, so too does art—particularly poetry. The poem “Echo” reverberates with the eeriness of health care, to which many seasoned clinicians may become inured. The speaker, a patient undergoing an echocardiogram, reflects on the instant intimacy of her relationship with an echocardiography technician she has just met. She describes their dimly lit journey together during the procedure, conjuring an image reminiscent of both a cave and a heart, replete with shadows, chambers, and whorls, similar perhaps to the echocardiogram’s ethereal black and white. The final echo of the poem poses an ironic question—perhaps asked internally by the patient or spoken tentatively into the depths of this metaphorical deep place—“What’s that sound?” What the void returns, surprisingly, is a kind of redemption of medicine’s foreignness. Just as medical technology can offer insights to patients, it gives clinicians something as well. Through poetry, we are invited to reexperience not only the uncanniness that can come with healing but also the privilege we hold in our understanding, and interpretation of, its mysteriousness: “It’s your heart.”

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.

Communicating Dyspnea Through Poetry

“Asthmanaut” evokes the experience of an asthma exacerbation through the metaphor of an astronaut navigating the thin air between Earth and outer space. The speaker, struggling to “[t]ake strangled sips,” describes feeling as though he were “[i]n [a] vacuum,” “pull[ed]” by the gravity of stars as he attempts to return to Earth. Through vivid images and descriptive phrases, the poem conveys the substantial morbidity of this disease. Nevertheless, the speaker does not merely describe the almost surreal experience of an asthma exacerbation but also reproduces the sensation of dyspnea through the poem itself. Form and content reflect one another in numerous ways: the lines are short, invoking shallow breaths, and the poem’s visual outline resembles an alveolus or branching airway. Additionally, the frequent use of alliteration, onomatopoeia, harsh consonants, and multisyllabic words (eg, “lungs filched, folded/excoriated”) induces labored breaths while reading the poem aloud, which are accentuated by the lack of punctuation, aside from commas. Fortunately, the sounds and images at the end of the poem become more euphonic as the speaker describes “[coming] down/…to stoop and kiss the earth//And savor one sweet gulp/of atmosphere.” The poem subsequently invites us to complete the journey of the asthmanaut by simulating the breath of relief that the speaker imagines. Returning to Earth along with the speaker, who invokes weightlessness by omitting a concluding period, we float (if only temporarily) “unhounded.”

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.

Medical vs Surgical Management of Acute Appendicitis

In managing acute uncomplicated appendicitis, patient outcomes are clearly the highest priority. Acute appendicitis ranks among the most common surgical emergencies globally, with an estimated lifetime incidence of 7% to 8% and a peak occurrence between 20 and 40 years of age. The 2015 Appendicitis Acuta (APPAC) trial, in which adult participants with acute uncomplicated appendicitis without appendicolith were randomized to either open appendectomy or antibiotics (intravenous ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole), demonstrated that 72.7% of patients treated with antibiotics did not require an appendectomy within the first year. The antibiotic treatment success rate was 63% at 2 years, 62% at 3 years, and 61% at 5 years. Similarly, the 2020 Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which included patients with appendicolith, demonstrated that antibiotics were noninferior to appendectomy; 60% of patients in the antibiotic group did not require an appendectomy by 1 year, 54% by 2 years, and 51% at 3 and 4 years. These 2 major European and American randomized clinical trials (RCTs) found antibiotics to be a feasible and safe alternative to appendectomy in adults with uncomplicated acute appendicitis confirmed by computed tomography, although a milieu of uncertainty regarding recurrent appendicitis has remained.

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.

The Year in Review, 2025

What a difference a year makes. When I wrote my 2024 Year in Review editorial in January 2025, I could scarcely have imagined the roller coaster ride our field would be on throughout 2025. Medical research, publishing, and practice are under intense scrutiny as society’s relationship with science and medicine continues to evolve. The field of psychiatry was specifically in focus in the Make America Healthy Again Commission report released by the US Department of Health and Human Services, as concerns about the quality of our evidence and magnitude of our impact on patient outcomes were aired out. I wrote about my views on this complex topic in June. In that article, I argued that our field can be justifiably critiqued for many reasons and there is room for meaningful reform. But I also stated that the path forward in this endeavor must pass through rigorous research and practice in the service of patients and families, and not through simplistic critiques and poorly conceived alternative treatments. In this context, we strive to position our journal as a beacon that demonstrates how new knowledge should be generated and incorporated into practice. We do not resort to credentials or authority, rather, we engage in the difficult work of asking questions and searching for answers in the Original Investigations that we publish. We then strive to provide examples of how scientific research is best perceived and interpreted, critiquing studies as appropriate and incorporating findings into a broader context in our Viewpoints and Editorials. A concrete example of our efforts from the past year is an editorial on understanding placebo mechanisms to reduce attrition in clinical trials.

Poetry and Intimacy in the Patient-Physician Relationship

Love and intimacy informing poetry is as old as poetry itself. Perhaps poetry’s abiding association with the erotic contributes to medicine’s unease with it, where professional boundaries are essential to safeguarding patients who make themselves vulnerable both by disclosing personal information and the exposure of the physical examination. Yet poetry can be invaluable to medicine as a means for articulating and exploring this charged and omnipresent aspect of clinical care, as few if any other idioms can speak in the face of such strong taboos. In “By the Skin,” the speaker immediately acknowledges the physical closeness felt between himself as patient—“shirtless, pantless, in boxers”—and his dermatologist, who attentively eyes his unclothed skin. The healing naturalness of giving oneself to another’s care is poetically reinforced by the untroubled diction and the implied likening, however distant, of patient and physician to any other “couple.” Their connection is at once warm, as they almost longingly share details of “Our recent holidays in the sun,” and yet circumscribed by how it is “soundtracked,” a deliberately distancing term. Thus poetry achieves here what the dry language of ethics committees only abstractly conveys: a lovely expression of the care and tenderness that exist between patient and physician, acutely constrained by mutual admiration and respect and the trust they engender. As the speaker ironically concludes himself, after musing about walks on the beach and collecting seashells, “Back to my skin, of course I applied sunscreen/Much as I enjoy this undivided, clinical attention.”

Shiga Toxin–Producing Escherichia coli Daycare Outbreak

This cohort study describes health care resource utilization, clinical outcomes, and outcomes associated with daily laboratory monitoring for thrombotic microangiopathy in a large, single-source Shiga toxin–producing Escherichia coli outbreak in Canadian daycare centers.

Consciousness and Controlled Donation After Circulatory Determination of Death

This Perspective discusses the limitations of reliable assessment of consciousness in critically ill, behaviorally unresponsive patients in light of recent situations in which such patients exhibited signs of consciousness moments before initiation of organ recovery surgery.

Patient Safety Begins With Access

This Viewpoint discusses the need to frame delays and failures in access to health care as patient safety events and to apply high-reliability organization principles to these access-related events to incorporate systematic analysis, leadership attention, and organizational accountability.

Mixed-Methods Evaluation of Surgeon Workplace Support and Obstetric Complications

This survey study examines responses from surgeon-parents to analyze the prevalence of obstetric complications among childbearing surgeons and childbearing partners of surgeons, identify occupational risk factors, and explore the respondents’ lived experiences.

The Challenge of Becoming a Surgeon-Parent

Despite a majority of surgeons having children and many institutions having policies in place intended to support pregnant surgeons, obstetric complications remain high for both childbearing surgeons and childbearing partners of surgeons. Halix et al provide a first-of-its-kind survey of both childbearing surgeons as well as surgeons whose partners gave birth to assess obstetric complication rates, identify risk factors among the groups, and assess the cultural context of these complications related to the field of surgery. Despite a majority of surgeons having children and many institutions having policies in place intended to support pregnant surgeons, obstetric complications remain high for both childbearing surgeons and childbearing partners of surgeons. Halix et al provide a first-of-its-kind survey of both childbearing surgeons as well as surgeons whose partners gave birth to assess obstetric complication rates, identify risk factors among the groups, and assess the cultural context of these complications related to the field of surgery.

Treat-to-Target Urate-Lowering Treatment and Cardiovascular Outcomes in Patients With Gout

This cohort study evaluates the association between achieving a serum urate treatment target lower than 6 mg/dL and cardiovascular events among patients with gout who were newly prescribed urate-lowering treatment.