Justine V Cohen

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This study tracked 72 patients with advanced cutaneous squamous cell carcinoma whose disease progressed despite treatment with anti-PD-1 immunotherapy. Most developed widespread or regional disease after failing immunotherapy, and patients with inherently resistant tumors had lower tumor mutation burden—a marker of how many genetic errors a tumor has. Subsequent treatments including cetuximab helped some patients, but overall survival remained poor, highlighting the need for better strategies after immunotherapy failure.

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This review examined 49 studies covering 341 AI models built for acute care surgery, the high-stakes field of emergency operations. Most AI focused narrowly on predicting surgical risk before operations and was tested only on the data it was trained on, with almost none independently validated or approved for real use. The gap between what these tools promise and their actual readiness for clinical practice remains wide.

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This study measured anti-Mullerian hormone—a marker of egg reserve—in young women with melanoma who were treated with immunotherapy or targeted therapy. Both types of treatment were associated with a reduction in this fertility marker. The findings raise important questions about how these widely used cancer treatments affect fertility and support the need for fertility counseling before treatment.

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Researchers tested whether better instructor feedback leads to better skill acquisition, using an AI tool called Teach1 to rate the quality of feedback given to medical students learning a bedside procedure. Higher-quality feedback was directly tied to greater skill improvement, with every 10% increase in feedback quality corresponding to a measurable score gain. This shows that AI can objectively evaluate teaching quality and help standardize surgical education at scale.

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This case series characterized the skin cancer patterns in five women who carried inherited mutations in the SUFU gene, which is linked to a basal cell nevus syndrome. Unlike the more common PTCH1 mutation, SUFU carriers developed multiple slow-growing skin tumors in their 40s-60s, with some being indolent and others true basal cell carcinomas. Importantly, standard targeted drugs for basal cell carcinoma (smoothened inhibitors) are unlikely to work in SUFU patients because the mutation acts at a different point in the signaling pathway.

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This study analyzed which patient-reported symptoms were most strongly linked to melanoma recurrence during follow-up. The five most predictive symptoms—appetite change, tiredness, lymph node enlargement, abdominal pain, and shortness of breath—were compiled into the mnemonic ATLAS. Asking specifically about these symptoms during surveillance visits could help clinicians catch recurrences earlier.

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This phase II trial tested an ERK inhibitor drug (ulixertinib) in 13 patients with metastatic uveal melanoma, a rare eye cancer that does not respond well to most treatments. The drug produced no responses; the best result was stable disease in 4 patients with a median time to progression of only 2 months. ERK inhibition alone is not an effective strategy for uveal melanoma.

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Researchers used ultra-sensitive blood DNA sequencing to detect tumor-derived DNA in patients with metastatic uveal melanoma, aiming to find a non-invasive way to monitor disease. Tumor DNA was detectable in most patients, and the amount in the blood correlated with disease status—rising when the disease progressed. A specific chromosomal gain (8q) was consistently detectable and may serve as a useful blood-based biomarker for tracking this cancer.

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This study used specialized MRI techniques to measure the blood vessel architecture inside brain metastases treated with the immunotherapy drug pembrolizumab. Tumors that responded to treatment had more structurally balanced vasculature—a mix of small and large vessels—while non-responding tumors were dominated by abnormally large vessels. Changes in blood vessel patterns in the tissue surrounding the tumor also predicted growth before it was visible on standard scans.

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Using perfusion MRI in 44 patients with brain metastases treated with pembrolizumab, this study found that the blood vessel structure inside tumors predicted whether immunotherapy would work. Tumors that responded had balanced, efficient vascular networks and signs of immune activity, while resistant tumors had chaotic vasculature dominated by large vessels with poor immune infiltration. Measuring vascular architecture may help identify which patients are likely to benefit from brain metastasis immunotherapy.

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This phase 2 trial tested pembrolizumab in 57 patients with brain metastases from various cancer types, including untreated and previously treated tumors. 42% of patients achieved disease control (response or stability), and 7 patients were alive more than 2 years after treatment—a remarkable outcome given the typically dismal prognosis. The results support further study of pembrolizumab for brain metastases and the search for biomarkers to identify the best responders.

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Over five years, 68 surgical trainees completed a simulation-based training program for laparoscopic gastric bypass surgery using animal tissue models. Both objective skill scores and practical measures like anastomosis quality improved significantly after training. The program offers a structured, reproducible way to build proficiency in a technically demanding operation before performing it on patients.

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This phase 1 trial tested adding an HSP90 inhibitor (AT13387) to the standard BRAF+MEK inhibitor combination in 22 patients with BRAF-mutant cancers, mostly colorectal. The regimen was generally safe, but the overall response rate was just 9.5% and median survival was about 5 months. HSP90 inhibition adds limited benefit to BRAF/MEK therapy in this heavily pretreated population without a clear way to identify who might respond.

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This phase 1b study tested intravenous coxsackievirus A21 combined with ipilimumab in 11 patients with uveal melanoma that had spread to the liver. No patients responded to treatment; all progressed, and the combination had manageable but notable toxicity. The combination did not produce meaningful benefit in this difficult-to-treat cancer.

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This multicenter study documented neurological side effects in 58 patients treated with PD-1 inhibitors, either alone or combined with ipilimumab. Most neurological toxicities affected the peripheral nervous system and began within weeks of starting treatment. While the cancer itself continued to respond to immunotherapy in most patients, nearly a quarter did not fully recover from the neurological side effects—underscoring that these complications can be irreversible.

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This retrospective study examined whether developing immune-related colitis predicts better survival in patients with metastatic melanoma on anti-CTLA4 therapy. Patients who developed moderate colitis (managed with oral steroids only) had significantly better overall survival when on single-agent ipilimumab, but this pattern did not hold for combination immunotherapy. The finding suggests the immune activation that causes moderate colitis may reflect the same process killing cancer cells, at least with single-agent CTLA4 blockade.

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This prospective pilot study tested whether running blood-based DNA sequencing at the same time as the initial tumor biopsy in lung cancer patients would speed up the time to starting targeted therapy. Blood sequencing results were available before the first oncology visit in 85% of patients in the intervention group, versus only 9% with standard tissue testing, cutting the time to treatment start in half. This approach could meaningfully accelerate care for patients with treatable driver mutations.

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This international study compared how anti-PD-1 immunotherapy performs across different ethnic groups in patients with advanced melanoma. White patients with non-acral cutaneous or unknown primary melanoma had response rates of 54% versus 20% for East Asian, Hispanic, and African patients—a difference that held up after adjusting for other factors. No ethnic differences were seen in acral, mucosal, or uveal subtypes, pointing to biological differences linked to UV-driven mutations rather than access or other factors.

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This multicenter study of 463 patients with metastatic melanoma who received chemotherapy after failing immunotherapy found limited but real activity. The overall response rate was 12.4% and median progression-free survival was only 2.6 months, with single-agent taxanes performing best. Chemotherapy has a small but real role as a salvage option after immunotherapy failure, though it is far from curative.

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This randomized phase III trial compared one year of adjuvant pembrolizumab against older standard immunotherapy options (high-dose interferon or ipilimumab) after surgical removal of high-risk melanoma. Pembrolizumab significantly reduced the chance of recurrence (23% relative improvement) and caused far fewer severe side effects than the older treatments. It did not, however, improve overall survival during the follow-up period.

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This interim analysis of a basket trial reported intracranial activity of palbociclib—a CDK4/6 inhibitor—in patients with progressive brain metastases harboring specific CDK pathway alterations. The trial met its primary endpoint, providing early evidence that molecularly targeted therapy can work inside the brain. The results support testing tumor molecular profiles in patients with brain metastases to guide treatment selection.

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This phase 2 trial gave combined ipilimumab and nivolumab to 18 patients with leptomeningeal disease (cancer spreading into the fluid and membranes around the brain), which typically has a survival measured in weeks. Survival at 3 months was 44%—meeting the study's primary endpoint—and the combination was safe. While a fraction of patients showed meaningful benefit, the results justify larger trials to validate this approach.

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This multicenter real-world study looked at long-term outcomes in 84 melanoma patients with brain metastases who received PD-1-based immunotherapy. Survival outcomes varied dramatically based on a brain-specific prognostic score, and a low neutrophil-to-lymphocyte ratio emerged as a strong independent predictor of better survival. These practical markers, available from routine blood tests, can help clinicians identify which patients are most likely to benefit from immunotherapy for brain metastases.

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This study examined whether using high-dose steroids early in the course of immune-related adverse events affects cancer outcomes in patients on anti-PD-1 therapy. Patients who needed high-dose steroids within the first 8 weeks of treatment had significantly worse progression-free and overall survival compared to those who did not. The results suggest clinicians should be judicious about using high-dose steroids for early immune side effects and explore alternative management strategies.

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This retrospective study examined compliance with sentinel lymph node biopsy guidelines in invasive melanomas removed using Mohs surgery with special immune staining. Discussion of the procedure was documented in 92% of eligible patients, and it was performed in 62% of eligible cases. The lymph node was successfully identified in 90% of those biopsied, confirming that Mohs surgery and sentinel lymph node biopsy can be safely combined for specialty-site melanomas.

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A multidisciplinary expert panel developed standardized diagnostic definitions for neurological complications of immune checkpoint inhibitors, using a modified consensus process. Seven core disorders were defined—including encephalitis, neuropathy, and myopathy—each with descriptors for diagnostic certainty and severity. These consensus definitions aim to standardize how these rare but serious complications are classified and studied across centers.

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Researchers transplanted human moles (melanocytic nevi) into mice and found that most of them were spontaneously rejected by the immune system. The rejection was driven by CD4 T cells that had expanded specifically against melanocyte proteins within the mole itself. Mice that rejected moles were then protected against melanoma growth—suggesting that activating these T cells could be a strategy for both preventing and treating melanoma.

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This study found that cancer patients hospitalized with COVID-19 had very different immune responses depending on whether they had blood cancers or solid tumors. Blood cancer patients could not generate antibody responses against the virus, but those who maintained adequate CD8 T cell counts still survived at higher rates despite absent antibodies. The finding highlights the protective role of T cells in COVID-19 even when antibody immunity is impaired.

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This meta-analysis pooled data from 100 studies and nearly 14,000 head and neck melanomas to compare local recurrence rates after three different surgical approaches. Mohs surgery had the lowest local recurrence rate at 0.6%, followed by staged excision at 1.8% and standard wide excision at 7.8%. These results strongly support using Mohs or staged excision techniques for melanomas in complex anatomical locations on the head and neck.

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This study characterized nearly 500 immune-related adverse event hospitalizations at a major cancer center from 2011 to 2018. Gastrointestinal, pulmonary, and liver toxicities were most common, and patients on CTLA-4 or combination checkpoint therapy were admitted earlier and at higher rates than those on PD-1 monotherapy. Patients with multiple simultaneous toxicities had a fivefold increased risk of dying during their hospital stay.

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Researchers analyzed electrocardiogram data from 140 patients with checkpoint inhibitor-related myocarditis and found that the QRS duration—a measure of how long electrical conduction takes across the heart—was significantly prolonged at the time of myocarditis. Each 10-millisecond increase in QRS duration was associated with a 1.3-fold increased risk of a major cardiac event. This widely available ECG measurement could help identify and risk-stratify patients with this serious complication.

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This study re-analyzed immune and survival data from cancer patients hospitalized with COVID-19, focusing on whether CD8 T cells compensate when antibody responses are absent. Patients with hematologic cancers who lost antibody-producing B cells still survived at higher rates if they had adequate CD8 T cell counts, and those counts were the strongest survival predictor. The findings directly support prioritizing cellular immunity in vaccination and treatment strategies for this vulnerable population.

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This multicenter study tracked 85 melanoma patients who relapsed after receiving targeted therapy (BRAF and MEK inhibitors) as adjuvant treatment. Most responded well to subsequent anti-PD-1 immunotherapy—with response rates of 63%—and had 2-year survival rates of 84%. Patients who relapse after adjuvant targeted therapy can be effectively salvaged with immunotherapy.

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This retrospective study examined outcomes in 106 hospitalized cancer patients who received checkpoint inhibitor therapy while admitted, most of whom were too sick to enroll in standard trials. Half died during admission or within 30 days, and median overall survival from discharge was only one month. The findings argue for very careful patient selection before giving immunotherapy to hospitalized patients.

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This study examined liver biopsies from cancer patients on immune checkpoint inhibitors who developed liver enzyme abnormalities. Three main patterns of liver inflammation were identified—hepatitic, cholangitic, and mixed—each correlating with the type of liver enzyme elevation. Importantly, the pattern of inflammation did not predict whether patients would respond to steroids, underscoring the complexity of managing this complication.

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This is a publisher correction to the original single-arm phase 2 trial of pembrolizumab in leptomeningeal carcinomatosis. No new data were reported; the correction amends details in the original publication.

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This phase 2 trial gave pembrolizumab to 20 patients with leptomeningeal dissemination from solid tumors, most with breast cancer. Twelve of 20 patients were alive at 3 months, meeting the primary endpoint, and the treatment was generally well tolerated. Pembrolizumab shows promising activity in this typically fatal condition and justifies further investigation.

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This commentary from a multidisciplinary workshop discusses the challenges of diagnosing and managing immune-related adverse events in patients receiving combination PD-1/PD-L1 checkpoint therapy. A clinical case illustrates how these toxicities are complex and often require specialist input to disentangle. The article identifies gaps in current guidelines and opportunities to improve how these emerging regimens are studied and managed.

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This study analyzed cardiac MRI findings in 103 patients with checkpoint inhibitor-related myocarditis and found that late gadolinium enhancement—a standard MRI marker of heart damage—was present in less than half of patients even when heart disease was confirmed by other means. The presence or absence of this marker did not predict which patients had serious cardiac events. These data caution against relying solely on MRI findings to exclude or risk-stratify checkpoint inhibitor myocarditis.

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This retrospective analysis at a major cancer center catalogued severe neurological immune toxicities over 6 years of checkpoint inhibitor use, finding a spectrum of conditions including encephalitis, peripheral nerve damage, and neuromuscular junction disorders. Some patients were treated with combination therapy or rechallenged with immunotherapy, adding practical insights not addressed by current guidelines. The study supports the need for standardized reporting and management frameworks for these growing complications.

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This study measured global longitudinal strain—a sensitive echocardiographic metric of heart muscle function—in 101 patients with checkpoint inhibitor myocarditis and 92 controls. Strain was markedly reduced in patients with myocarditis even when the ejection fraction appeared normal, and lower strain values strongly predicted major cardiac events. This finding positions global longitudinal strain as a critical early detection and risk-stratification tool for immunotherapy heart complications.

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This multicenter study examined how often and how severely cancer patients with underlying inflammatory bowel disease (IBD) developed gastrointestinal side effects from checkpoint inhibitors. Forty-one percent developed GI complications—nearly four times the rate in patients without IBD—and four patients had serious bowel perforations. Pre-existing IBD substantially increases the risk of severe GI toxicity from checkpoint inhibitors, requiring extra vigilance.

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This review summarizes the progression of adjuvant therapy for resected high-risk melanoma over the past decade, from older interferon-based regimens to current approvals for nivolumab, pembrolizumab, and BRAF/MEK inhibitor combinations. These newer options dramatically improve recurrence-free survival with more manageable side effects. Ongoing questions focus on optimal patient selection, treatment sequencing, and long-term durability of benefit.