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Updates in the Management of Neuroblastoma

Presented by: Rochelle Bagatell

Treatment of children with neuroblastoma depends on accurate assessment of the risk of relapse. Factors used in risk stratification for patients with neuroblastoma include disease stage, MYCN amplification status, age, tumor histology, presence or absence of segmental chromosome aberrations, and tumor cell ploidy. The goal of treatment for patients with low-risk neuroblastoma is cure with minimal toxicity. However, for those with high-risk neuroblastoma, the treatment approach involves multiple therapeutic modalities, including multi-agent chemotherapy at conventional doses, surgery, high-dose chemotherapy with autologous stem cell rescue, external-beam radiotherapy, a differentiating agent, and immunotherapy. Multidisciplinary collaboration is essential for optimal care.

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Updates in the Management of Small Cell Lung Cancer

Presented by: Apar Kishor Ganti

The standard treatment for limited-stage small cell lung cancer (SCLC) is concurrent chemoradiation, with a small subset of patients that could potentially benefit from surgery. For extensive-stage SCLC, the current standard of care is chemoimmunotherapy with a PD-1/PD-L1 inhibitor. The role of prophylactic cranial irradiation in SCLC is currently under debate, and is being investigated in the ongoing MAVERICK trial. Despite high initial response rates to chemoradiotherapy, relapse is common, and outcomes for these patients remain poor. However, recent advances in understanding the molecular biology of SCLC have led to the identification of potential new targets for treatment, including the combination of temozolomide with PARP inhibitors and DLL3-targeted bispecific T-cell engager therapy, both of which have shown activity in early studies.

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Updates in the Treatment of Metastatic Urothelial Cancer

Presented by: Thomas W. Flaig

The past decade has seen a host of advancements in the management of metastatic urothelial carcinoma. Although efforts to identify novel systemic therapies are still ongoing, immune checkpoint inhibitors have become the preferred treatment option in this patient population. Recommendations for optimal treatment strategies—based on a patient’s eligibility for cisplatin—have been outlined in the NCCN Guidelines for Bladder Cancer in both the first-line and subsequent-line settings.

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Updates to the Management of Cutaneous Melanoma

Presented by: Douglas B. Johnson

The systemic therapeutic landscape for cutaneous melanoma continues to evolve, with numerous diverse options currently available. Several clinical trials have resulted in approvals from the FDA and subsequent revisions to the NCCN Guidelines, which reflect the most up-to-date, evidence-based data relating to the evaluation and management of these malignant neoplasms. Combination checkpoint blockades, anti–PD-1 and anti–CTLA-4 monotherapies, and mutation-directed therapies are among the NCCN-recommended approaches across the neoadjuvant, first-line, and later-line settings. Tumor-infiltrating lymphocyte therapy, a recent addition in the later-line setting, may mark a new era in the management of metastatic disease.

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Updates to the Management of Endometrial Cancer

Presented by: Nadeem R. Abu-Rustum

Endometrial cancer has moved from being a histologic diagnosis alone to one that also considers the molecular classification of the tumor. Molecular classification is not only feasible but highly recommended because it improves the diagnostic classification and provides prognostic information that may guide treatment. The NCCN Cervical/Uterine Cancers Guidelines recognize the novel approach proposed by FIGO, but has concerns about the 2023 FIGO staging system and therefore does not recommend its use by clinicians. Advances in systemic treatment, particularly the introduction of immunotherapy, has greatly improved outcomes in endometrial cancer, especially for patients with mismatch repair–deficient tumors.

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Updates to the Management of HR-Positive, HER2-Negative Breast Cancer

Presented by: William J. Gradishar

Metastatic hormone receptor–positive, HER2-negative breast cancer treatment is increasingly individualized as more of the tumor landscape is described and targeted therapies are developed. CDK4/6 inhibitors have demonstrated consistency in prolonging progression-free survival across several clinical trials in advanced disease. Research in endocrine therapy highlighted the noninferiority of fulvestrant compared with aromatase inhibitors after disease progression. Studies such as the PEARL and Young-PEARL trials challenged the superiority of chemotherapy over endocrine therapy in certain populations, including premenopausal women. Sequential CDK4/6 inhibitor therapy after disease progression showed potential benefits, though definitive data are lacking. Targeting the PI3 kinase pathway, particularly with capivasertib in patients with pathway alterations, showed significant improvements in progression-free survival. ESR mutations have been identified as a key factor in resistance to endocrine therapy, with elacestrant showing promise in overcoming this challenge. Finally, in early-stage cancer, the question of whether ovarian suppression along with endocrine therapy can show the same results as chemotherapy is being explored, but the answer remains to be seen.

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Updates to the Management of Multiple Myeloma

Presented by: Natalie S. Callander and Shaji K. Kumar

Patients with smoldering myeloma should undergo periodic risk assessment—if they are deemed at high risk for disease progression, clinical trials or lenalidomide with or without dexamethasone should be considered. The initial treatment of newly diagnosed myeloma should be based on the patient’s risk, fitness, and preferences. Induction with a quadruplet regimen, followed by autologous transplantation and maintenance therapy, remains the standard of care, especially for those with high-risk disease. For patients with standard-risk disease not undergoing immediate transplantation, triplet or quadruplet induction followed by maintenance is the standard. Appropriate treatment of relapsed disease depends on response to previous treatment, residual side effects, and comorbidities. T-cell–redirecting therapies and other novel agents have shown activity, even in heavily pretreated patients. Most patients will require multiple lines of therapy over the course of the disease.

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Updates to Treatment of Recurrent Metastatic Head and Neck Cancers

Presented by: Cristina P. Rodriguez

The introduction of immune checkpoint inhibitors (ICIs), such as pembrolizumab and nivolumab, has significantly improved overall survival in both the first- and second-line settings for patients with head and neck squamous cell carcinomas. In nasopharyngeal carcinomas, the combination of gemcitabine + cisplatin with PD-1 inhibitors has demonstrated impressive response rates and overall survival benefits. However, the unique immune-related adverse events associated with ICIs require patient counseling. Ongoing clinical trials are exploring novel combinations of ICIs with EGFR monoclonal antibodies, tyrosine kinase inhibitors, and therapeutic vaccines to further improve treatment outcomes. Biomarkers, such as circulating HPV-DNA and actionable molecular alterations (eg, HRAS mutations), may help guide treatment decisions and predict patient responses in the future.

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Decline in Smartphone-Assessed Physical Activity Level is Associated With Clinical Outcomes in Phase I/II Clinical Cancer Trials

Calvin G. Brouwer, Joeri A.J. Douma, Evelien J.M. Kuip, Sonja Zweegman, Niels W.C.J van de Donk, Maria T.E. Hopman, Myra E. van Linde, Henk M.W. Verheul, and Laurien M. Buffart

Background: A decline in physical function may be an early predictor for complications of cancer treatment. This study examined whether repeated objective smartphone measurements of physical activity and exercise capacity in patients with cancer are feasible during early-phase clinical trials (EPCTs) and whether a decline in physical function is associated with clinical outcomes. Methods: Physical activity (steps/day) and exercise capacity (6-minute walk test [6MWT]) were measured with a smartphone before EPCT start (T0) and after 4 weeks (T1) and 8 weeks (T2). Univariable logistic regression analyzed associations between a decline in step count (≥20%), 6MWT distance (≥10%), or deterioration of ECOG performance status (PS) and trial discontinuation at 8 weeks and 90 days. Cox proportional hazards models were used to examine associations with progression-free survival (PFS) and overall survival (OS), adjusting for trial phase (I vs II), cancer type (hematologic malignancy vs solid tumor), and PS (0 vs ≥1). Results: Among 117 included patients, valid step count and 6MWT measurements were available for 96.6% and 76.7% of patients at T0, 74.4% and 53.3% at T1, and 89.7% and 54.4% at T2, respectively. Patients experiencing step count decline between T0 and T1 had higher odds of trial discontinuation at 8 weeks (odds ratio, 8.67; 95% CI, 1.94–61.43), and decline between T1 and T2 was associated with discontinuation at 90 days (odds ratio, 5.20; 95% CI, 1.43–21.14). Step count decline was significantly associated with shorter PFS (hazard ratio, 3.54; 95% CI, 2.06–6.08) and OS (hazard ratio, 2.31; 95% CI, 1.26–4.23). Declines in 6MWT distance or deterioration in ECOG PS were not associated with trial discontinuation or survival. Conclusions: Repeated smartphone measurements of physical activity are feasible in patients participating in EPCTs. Additionally, physical activity decline is significantly associated with trial discontinuation, PFS, and OS. Hence, we envision that objective smartphone measurements of physical activity will contribute to optimal treatment development for patients with cancer.

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Enhancing Readability of Online Patient-Facing Content: The Role of AI Chatbots in Improving Cancer Information Accessibility

Andres A. Abreu, Gilbert Z. Murimwa, Emile Farah, James W. Stewart II, Lucia Zhang, Jonathan Rodriguez, John Sweetenham, Herbert J. Zeh III, Sam C. Wang, and Patricio M. Polanco

Background: Internet-based health education is increasingly vital in patient care. However, the readability of online information often exceeds the average reading level of the US population, limiting accessibility and comprehension. This study investigates the use of chatbot artificial intelligence to improve the readability of cancer-related patient-facing content. Methods: We used ChatGPT 4.0 to rewrite content about breast, colon, lung, prostate, and pancreas cancer across 34 websites associated with NCCN Member Institutions. Readability was analyzed using Fry Readability Score, Flesch-Kincaid Grade Level, Gunning Fog Index, and Simple Measure of Gobbledygook. The primary outcome was the mean readability score for the original and artificial intelligence (AI)–generated content. As secondary outcomes, we assessed the accuracy, similarity, and quality using F1 scores, cosine similarity scores, and section 2 of the DISCERN instrument, respectively. Results: The mean readability level across the 34 websites was equivalent to a university freshman level (grade 13±1.5). However, after ChatGPT’s intervention, the AI-generated outputs had a mean readability score equivalent to a high school freshman education level (grade 9±0.8). The overall F1 score for the rewritten content was 0.87, the precision score was 0.934, and the recall score was 0.814. Compared with their original counterparts, the AI-rewritten content had a cosine similarity score of 0.915 (95% CI, 0.908–0.922). The improved readability was attributed to simpler words and shorter sentences. The mean DISCERN score of the random sample of AI-generated content was equivalent to “good” (28.5±5), with no significant differences compared with their original counterparts. Conclusions: Our study demonstrates the potential of AI chatbots to improve the readability of patient-facing content while maintaining content quality. The decrease in requisite literacy after AI revision emphasizes the potential of this technology to reduce health care disparities caused by a mismatch between educational resources available to a patient and their health literacy.