BACKGROUND: In 2020, 24,000 new cancer cases were diagnosed among adolescents and young adults (AYAs) in Mexico. Cancer-related infertility affects 30%-75% of AYAs and is associated with poor quality of life, relationshi...BACKGROUND: In 2020, 24,000 new cancer cases were diagnosed among adolescents and young adults (AYAs) in Mexico. Cancer-related infertility affects 30%-75% of AYAs and is associated with poor quality of life, relationship satisfaction, and self-worth. This study examines the association between infertility, anxiety, and depression among AYA cancer survivors in Mexico. METHODS: Data for AYAs (ages 15-39) in the Registro de Supervivientes de Cancer (Cancer Survivor Registry) developed by the Instituto Nacional de Cancerología in Mexico was utilized. A self-report survey was conducted during 2014-2018. Logistic regression models were used to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs). RESULTS: AYA cancer survivors (N = 1168) had a median age of 31 (interquartile range: 25-36), were predominantly women (75%), and 42% had a college education or higher. The most common cancers were breast (33%), lymphoma (12%), cervical (10%), and testicular (9%) with the majority being Stage III (19%) tumors. Approximately 1 in 8 AYAs (12%) reported infertility. Across men and women, after adjusting for age at diagnosis, time since the end of treatment, education level, geographical region, stage, treatment type, and cancer type, AYAs who reported infertility were more likely to experience depression (OR 1.52, 95% CI: 1.02-2.26) symptoms than those who did not report infertility. There was no association between infertility and anxiety among all AYA cancer survivors combined. CONCLUSIONS: Infertility is associated with depression symptoms among AYA Mexican cancer survivors. Mexican AYA cancer survivors experiencing infertility may need additional support to address unmet care needs.
BACKGROUND: Cancer accounts for about 20% of late maternal deaths in the United States. This study described nationwide patterns of pregnancy-associated cancer mortality among women aged 15-54 years from 2018 to 2023. ME...BACKGROUND: Cancer accounts for about 20% of late maternal deaths in the United States. This study described nationwide patterns of pregnancy-associated cancer mortality among women aged 15-54 years from 2018 to 2023. METHODS: We conducted a serial cross-sectional study using CDC WONDER data, including all live births and pregnancy-associated cancer deaths from 2018 to 2023. Mortality rates were estimated by census region, state, and race and ethnicity, and the proportional contribution of specific cancers was assessed. RESULTS: During 2018-2023, 731 pregnancy-associated cancer deaths occurred, a rate of 3.3 per 100 000 live births. Non-Hispanic Black women had the highest rate (4.8 per 100 000). Rates varied geographically, with the South highest and the West, particularly California, lowest. Breast cancer, hematologic malignancies, and colorectal cancer together accounted for nearly half of deaths. CONCLUSIONS: Pregnancy-associated cancer mortality varied by region, state, and race and ethnicity, with breast, hematologic, and colorectal cancers as leading causes.
Likasitwatanakul P, Blinka SM, Zarka JG
… +14 more, Gebrael G, Weg E, Longoria O, Moore JA, Sharp A, de Bono J, Sternberg CN, Agarwal N, Swami U, Orme JJ, Schweizer MT, Sloan L, Hwang JH, Antonarakis ES
BACKGROUND: Clival metastases are a rare and clinically aggressive manifestation of advanced prostate cancer, associated with cranial nerve palsy and poor survival. The molecular features of prostate cancers giving rise...BACKGROUND: Clival metastases are a rare and clinically aggressive manifestation of advanced prostate cancer, associated with cranial nerve palsy and poor survival. The molecular features of prostate cancers giving rise to clivus metastases remain unknown. PATIENTS AND METHODS: We performed a multi-center retrospective study across six institutions, identifying prostate cancer patients with radiographically confirmed clival metastases and available next-generation sequencing (NGS) data. Baseline characteristics and clinical outcomes were collected. Genomic alterations from tissue- and/or blood-based assays were aggregated at the patient level and compared with a publicly available metastatic castration-resistant prostate cancer (mCRPC) cohort (SU2C/PCF). RESULTS: Fifty-nine patients with clival metastases contributed 87 molecular assays. More than half of patients had Gleason grade group 5 cancer and presented with de novo metastatic (M1) disease. The median interval from initial prostate cancer diagnosis to clival metastasis was 71.4 months (95% CI, 42.0-101.7), while median overall survival following clival involvement was only 15.3 months (95% CI, 6.9-22.8). Compared with the SU2C/PCF mCRPC cohort, clival metastases showed significant enrichment of BRAF and CHEK2 alterations as well as homologous recombination repair (HRR) with relative depletion of AR-related, PI3K pathway, and G2-M pathway alterations. CONCLUSION: Prostate cancers giving rise to clival metastases exhibit a distinct molecular profile enriched for DNA damage-repair and RAF kinase alterations, suggesting unique metastatic biology and potential therapeutic vulnerabilities.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for patients with diabetes, obesity, and cardiometabolic disease. This trend has led to a growing number of patients taking these medicati...Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for patients with diabetes, obesity, and cardiometabolic disease. This trend has led to a growing number of patients taking these medications while receiving cancer treatment, including radiation therapy (RT). The delivery of RT relies on weight stability and anatomic reproducibility, which may be influenced by GLP-1 RA-related weight loss, delayed gastric emptying, and associated side effects. While current research has largely focused on perioperative outcomes and metabolic effects, we discuss the impact that GLP-1 RA use may have on radiation treatment planning, the need for adaptive radiation techniques, and RT related toxicity. We propose strategies to support safe RT and highlight the need for consensus recommendations regarding the use of GLP-1 RAs in patients requiring cancer treatment.
Ota K, Uemura M, Tanida T
… +35 more, Nakata K, Kudo T, Kagawa Y, Haraguchi N, Minami S, Matsuura Y, Ota H, Hiraki M, Yasui M, Takahashi H, Iwamoto K, Nishida N, Hata T, Nishizawa Y, Fukunaga M, Komori T, Takahashi Y, Tokuyama S, Tamagawa H, Naito A, Yoshihara T, Suzuki R, Sugimoto S, Miyake M, Takiguchi N, Tei M, Tamai K, Fukada A, Ogino T, Miyoshi N, Satoh T, Yamamoto H, Murata K, Doki Y, Eguchi H
BACKGROUND: First-line chemotherapy with maintenance therapy is expected to be well-tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). This study evaluated the efficacy and safety of tri...BACKGROUND: First-line chemotherapy with maintenance therapy is expected to be well-tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). This study evaluated the efficacy and safety of trifluridine/tipiracil (TAS-102) plus bevacizumab (Bev) as maintenance therapy for mCRC, omitting both oxaliplatin and fluoropyrimidines. MATERIALS AND METHODS: Patients with untreated mCRC initially received induction chemotherapy with fluoropyrimidine, oxaliplatin plus bevacizumab for 3-4 months. After achieving stable disease or better on imaging, 52 patients transitioned to maintenance therapy with TAS+Bev: TAS-102 (35 mg/m2, twice daily on days 1-5 and 8-12) plus Bev (5.0 mg/kg on Days 1 and 15, intravenously). Progression-free survival 1 (PFS1), defined as the time from the start of maintenance therapy to disease progression or death, was evaluated as the primary endpoint. RESULTS: The median cumulative dose of oxaliplatin during induction was 529 mg/m2. Median PFS1 during TAS+Bev maintenance was 8.7 months (95% CI: 5.5-12.3). The response rate and disease control rate during maintenance were 59.6% and 94.2%, respectively. Oxaliplatin reintroduction was feasible in 53.8% (28/52) of patient with a median total first-line chemotherapy duration was 16.2 months (95% CI: 14.5-20.6). Safety outcomes, including dose intensity and adverse events, were acceptable. CONCLUSION: This strategy of switching to first-line maintenance therapy with TAS+Bev demonstrated promising efficacy and safety. This strategy effectively avoided cumulative neurotoxicity, preserved quality of life and enabled reintroduction of oxaliplatin, suggesting it may represent a promising alternative strategy for patients ineligible for prolonged oxaliplatin-based treatment. Overall survival analysis is currently ongoing. [UMIN Trial ID: UMIN000031317].
BACKGROUND: The prognostic role of multifocality in medullary thyroid carcinoma (MTC) is controversial. This study evaluated multifocality's association with aggressiveness, lymph node metastasis (LNM), and survival, foc...BACKGROUND: The prognostic role of multifocality in medullary thyroid carcinoma (MTC) is controversial. This study evaluated multifocality's association with aggressiveness, lymph node metastasis (LNM), and survival, focusing on multifocality-related parameters (such as number of tumor foci, tumor diameter). METHODS: We retrospectively analyzed 186 MTC cases (136 unifocal, 50 multifocal) with a median 59-month follow-up (95% CI: 52-66). Multivariate logistic analysis and Cox regression models assessed multifocality's impact on LNM and recurrence, with detailed subgroup analyses. Diagnostic performance of tumor size parameters was evaluated using receiver operating characteristic (ROC) analysis, while survival outcomes were assessed via Kaplan-Meier method. RESULTS: Multifocal tumors exhibited significantly more aggressive features, including: (1) higher preoperative calcitonin (1226.7 ± 751.9 vs 706.6 ± 704.2 ng/L, P < .001); (2) increased capsular invasion (68% vs 32%, odds ratio [OR] = 5.8, 95% CI: 2.32-14.53); and (3) more frequent intraglandular spread (54% vs 18%, OR = 6.05, 95% CI: 1.47-24.92). Multifocality independently predicted both LNM (OR = 3.35, 95% CI: 1.22-9.25, P = .019) and recurrence (hazard ratio [HR] = 6.59, 95% CI: 2.48-17.53, P < .001). ROC analysis identified optimal LNM cut-offs at 13.5 mm (largest focus) and 16.5 mm (total tumor diameter). Subgroup analyses revealed: (1) bifocal conferred highest LNM risk (OR = 8.51 vs unifocal, 95% CI: 1.74-41.69, P = .008); (2) recurrence risk showed dose-response relationship with lesion number (bifocal: HR = 4.89, 95% CI: 1.88-12.70, P = .001; ≥3 foci: HR = 5.86, 95% CI: 1.54-22.33, P = .01). Survival analysis demonstrated significantly worse progression-free survival in multifocal cases (P < .001), persisting beyond 2 years (P = .001), though overall survival difference was nonsignificant (P = .168). CONCLUSION: Multifocal MTC exhibits aggressive behavior with high LNM and recurrence risks, driven by the number of tumor foci, demonstrating a dose-response relationship. These findings support incorporating multifocality into risk stratification for optimized management.
Kotani D, Inoue E, Denda T
… +15 more, Inagaki C, Kashiwada T, Mihara Y, Sugaya A, Suwa Y, Ohta T, Kuramochi H, Oshima K, Yuki S, Shiozawa M, Tsuji A, Muro K, Ichikawa W, Fujii M, Sunakawa Y
BACKGROUND: Triplet therapy (encorafenib, cetuximab, and binimetinib) is recommended in Japan for BRAF V600E mutated metastatic colorectal cancer (mCRC) patients with poor prognostic factors (PFs) based on subgroup analy...BACKGROUND: Triplet therapy (encorafenib, cetuximab, and binimetinib) is recommended in Japan for BRAF V600E mutated metastatic colorectal cancer (mCRC) patients with poor prognostic factors (PFs) based on subgroup analyses of the BEACON CRC trial. We, therefore, conducted a nationwide prospective observational study to evaluate the real-world effectiveness of triplet versus doublet therapy (encorafenib plus cetuximab). PATIENTS AND METHODS: The BEETS trial (UMIN000045530) enrolled BRAF-mutated mCRC patients who received triplet or doublet as second- or third-line treatment. The primary endpoint was overall survival (OS). Exploratory analyses using inverse probability weighting (IPW) based on propensity scores were performed to adjust for poor PFs (ECOG performance status ≥1, ≥3 metastatic sites, elevated C-reactive protein, or unresected primary tumor). RESULTS: In 203 enrolled patients, 195 patients were evaluable. Median age was 67 years; 52% were male. Dose intensity for encorafenib and cetuximab was comparable between the triplet and doublet cohorts. In the overall cohort, median OS and progression-free survival (PFS) were 12.9 and 4.9 months, respectively. After IPW adjustment, median OS was 14.0 months in the triplet cohort and 12.9 months in the doublet cohort (HR 0.87, 95%CI 0.57-1.33). Median PFS was 5.3 versus 4.2 months (HR 0.75, 95%CI 0.48-1.19). Among patients with at least one poor PF, both OS and PFS numerically favored the triplet regimen. CONCLUSIONS: In real-world clinical practice, triplet and doublet therapies showed comparable survival outcomes, consistent with the BEACON trial. Triplet therapy may provide potential clinical benefit in patients with poor PFs.
BACKGROUND: Dual mitogen-activated protein kinase (MAPK) pathway and autophagy inhibition show synergistic antitumor activity in preclinical models of RAS-mutant cancers. We hypothesized that autophagy blockade with hydr...BACKGROUND: Dual mitogen-activated protein kinase (MAPK) pathway and autophagy inhibition show synergistic antitumor activity in preclinical models of RAS-mutant cancers. We hypothesized that autophagy blockade with hydroxychloroquine (HCQ) could overcome resistance to MEK inhibition with binimetinib (BINI) and provide clinical benefit in previously treated, KRAS-mutated, metastatic pancreatic ductal adenocarcinoma (PDAC). METHODS: This investigator-led, single-arm, open-label, phase I dose escalation/expansion trial evaluated the safety and tolerability of BINI + HCQ in patients with previously treated, metastatic PDAC (NCT04132505). Key eligibility criteria: ECOG 0-1, adequate organ function, ≥1 prior line of therapy for metastatic disease, and presence of KRAS mutation. Dose escalation followed a Bayesian optimal interval design. The primary endpoint was the maximum-tolerated dose (MTD). Secondary endpoints included safety, objective response rate (ORR), disease control rate (DCR), progression-free survival, and overall survival (OS). RESULTS: From December 2019 to August 2024, 34 patients were enrolled in dose escalation (n = 17) and dose expansion (n = 17). Two dose-limiting toxicities occurred among the first 3 patients treated at dose level 1 (BINI 45 mg + HCQ 600 mg): grade 3 creatine phosphokinase elevation with renal impairment (BINI) and grade 3 QT prolongation (HCQ). Following dose de-escalation due to poor tolerance, the MTD was determined to be BINI 30 mg + HCQ 600 mg twice daily and used in the expansion. Out of 31 response-evaluable patients, 2 patients achieved a partial response and 9 patients achieved stable disease, yielding ORR 6.5% and DCR 35.5%, respectively. Median progression-free survival was 1.9 months, and median OS was 5.3 months. CONCLUSION: The combination of BINI + HCQ demonstrated a challenging toxicity profile and limited clinical activity in patients with chemorefractory metastatic PDAC.
BACKGROUND: Lung cancer is the leading cause of cancer-related deaths globally, with dietary factors such as low fruit intake potentially contributing to regional disparities. However, establishing causality remains chal...BACKGROUND: Lung cancer is the leading cause of cancer-related deaths globally, with dietary factors such as low fruit intake potentially contributing to regional disparities. However, establishing causality remains challenging. This study utilized a triangulated approach combining Global Burden of Disease (GBD) data, Mendelian randomization (MR), and a hospital-based cohort to investigate the association between fruit intake and lung cancer risk. METHODS: GBD 2021 data (1990-2021) were analyzed by sex, age, and socio-demographic index (SDI) using age-period-cohort models, decomposition, and ARIMA forecasting. Two-sample MR using UK Biobank instruments for fresh and dried fruit was applied to European GWAS of lung cancer and subtypes, with IVW as the primary estimator with multiple sensitivity analyses. Findings were validated in a Chinese hospital cohort (n = 641) using a food frequency questionnaire, multivariable logistic regression, and a composite Non-Diet Risk Index (NDRI). FINDINGS: In 2021, approximately 66 000 deaths and 1.44 million DALYs were attributable to low-fruit diets. Although absolute numbers rose since 1990, age-standardized rates declined. The burden was highest in medium-SDI regions, with notable geographic and sex disparities. ARIMA projections indicate a continued decline in global rates by 2050, particularly among males. MR supported a protective effect of genetically predicted fruit intake, though sensitivity analyses showed some inconsistency. In the Chinese cohort, higher fruit intake remained significantly protective after adjusting for key confounders, including NDRI. CONCLUSION: This multi-method study strengthens evidence that insufficient fruit intake may increase lung cancer risk, with consistent findings across population-level, genetic, and clinical data.
Manji GA, Chung V, Oh DY
… +13 more, Lacy J, Lopez CD, Ponz-Sarvisé M, Macarulla T, Thomas R, George B, Alistar A, Siveke JT, Xu Y, Lau J, Cha E, Kim KP, O'Reilly EM
BACKGROUND: The MORPHEUS platform comprised multiple open-label, randomized, phase Ib/II trials to identify early signals with different treatment combinations across multiple cancers. MORPHEUS-PDAC (NCT03193190) evaluat...BACKGROUND: The MORPHEUS platform comprised multiple open-label, randomized, phase Ib/II trials to identify early signals with different treatment combinations across multiple cancers. MORPHEUS-PDAC (NCT03193190) evaluated atezolizumab combinations in pancreatic ductal adenocarcinoma (PDAC). We describe outcomes with atezolizumab plus either motixafortide, cobimetinib, or two simlukafusp alfa regimens. METHODS: Eligible patients with advanced, pretreated PDAC were randomized to receive second-line (2 L) atezolizumab plus either motixafortide (BL8040; n = 15), cobimetinib (n = 14), simlukafusp alfa every 2 weeks (q2w; n = 15), or simlukafusp alfa every 3 weeks (q3w; n = 16); or control (mFOLFOX6 [n = 25] or gemcitabine plus nab-paclitaxel [n = 25]). Patients experiencing disease progression or toxicity who met eligibility criteria were enrolled to receive third-line (3 L) atezolizumab plus cobimetinib (n = 14), or atezolizumab plus simlukafusp alfa q2w (n = 1) or q3w (n = 6). Primary endpoints were objective response rates (ORRs) per RECIST 1.1 and safety. RESULTS: ORRs were 7.1% with atezolizumab-simlukafusp alfa q2w, 8.7% with mFOLFOX6 (both 2 L; 0% in other arms), 14.3% with atezolizumab-cobimetinib, and 16.7% with atezolizumab-simlukafusp alfa q3w (both 3 L). Grade 3-5 adverse event rates were 53.3% (2 L atezolizumab-motixafortide), 64.3% (2 L atezolizumab-cobimetinib), 57.1% (2 L atezolizumab-simlukafusp alfa q2w), 53.3% (2 L atezolizumab-simlukafusp alfa q3w), 63.0% (2 L mFOLFOX6 or gemcitabine-nab-paclitaxel), 50.0% (3 L atezolizumab-cobimetinib), and 100% (3 L atezolizumab-simlukafusp alfa q3w). CONCLUSIONS: The overall safety of atezolizumab combinations was manageable and consistent with each agent's known safety profile. This novel trial design enabled rapid evaluations of 3 atezolizumab combinations; all had limited efficacy as 2 L or 3 L treatment for metastatic PDAC. New treatments are needed to improve outcomes in previously treated PDAC.
BACKGROUND: Cognitive impairment related to chemotherapy-commonly referred to as "chemo brain"-is a well-documented phenomenon among breast cancer patients. These impairments affect memory, attention, executive function,...BACKGROUND: Cognitive impairment related to chemotherapy-commonly referred to as "chemo brain"-is a well-documented phenomenon among breast cancer patients. These impairments affect memory, attention, executive function, and social cognition, yet remain understudied in low- and middle-income countries. In Peru, where populations present a high proportion of Amerindian ancestry and distinct sociocultural factors, evidence is scarce. METHODS: We conducted a longitudinal study of 143 Peruvian women aged 28-64 years, newly diagnosed with early-stage breast cancer and naïve to chemotherapy, treated at the National Institute of Neoplastic Diseases (INEN) in Lima. Cognitive function was assessed using the Addenbrooke's Cognitive Examination (ACE), the INECO Frontal Screening Test (IFS), and a Facial Emotion Recognition (FER) task to evaluate social cognition. Baseline tests were performed before the start of treatment for each patient, and post-treatment tests were performed every 3 months. Global genetic ancestry was estimated using the ADMIXTURE algorithm based on the Affymetrix Precision Medicine Research Array. RESULTS: Native American ancestry accounted for 77.8% of the study population. Post-chemotherapy assessments revealed cognitive impairment in 21% of patients based on FER, 15% on ACE, and 12% on IFS. Higher educational attainment was associated with better cognitive performance across all domains. CONCLUSION: Chemotherapy was associated with measurable cognitive decline in a subset of Peruvian breast cancer patients. Brief and culturally adaptable tools such as the FER test offer a promising approach for routine cognitive screening in oncology settings, particularly in resource-limited contexts. Incorporating these assessments into standard care may facilitate early detection and more personalized supportive interventions.
BACKGROUND: Patient navigators are increasingly utilized in cancer care but ensuring patients are properly identified and referred to navigators is a significant challenge. The primary objective was to compare time from...BACKGROUND: Patient navigators are increasingly utilized in cancer care but ensuring patients are properly identified and referred to navigators is a significant challenge. The primary objective was to compare time from radiographic report to biopsy, oncology visit, and treatment before versus after implementation of a computationally assisted navigation referral stream. Secondary objectives included evaluating care delivery across demographic groups and assessing survival outcomes. MATERIALS AND METHODS: A quality initiative at Northwell Health compared care delivery metrics between 2 cohorts of patients with suspected pancreatic cancer: those identified retrospectively using computational methods in January 2023 and those identified and navigated prospectively in June 2023. Radiology reports from a centralized health information exchange were analyzed by an ML-based natural language processing (NLP) model to detect findings suspicious of pancreatic cancer. Participants deemed eligible for navigation were contacted by a navigator to improve the likelihood and expediency of follow-up care. RESULTS: Seventy-one patients were included, with 38 patients in the retrospective cohort and 33 patients in the prospective cohort. The prospective cohort showed numeric reduction in time to biopsy (12-6 days, P = 0.173), oncology appointment (27-17 days, P = 0.192), and treatment (56-35 days, P = 0.136), though these results were not statistically significant. These metrics showed a significant reduction in standard deviation (P < 0.001), including among racial and ethnic minorities. The survival of patients in both cohorts was comparable (hazard ratio [HR] = 0.82, P = 0.66). CONCLUSION: This study provides promising evidence that an NLP-assisted identification workflow can improve care delivery and investigation in a larger study is warranted to validate these findings.
BACKGROUND: Health care costs are rising due to increasing cancer incidence and the expanding use of high-cost anticancer medicines. Early treatment discontinuation (ETD) may signal inefficiencies in medicine use or refl...BACKGROUND: Health care costs are rising due to increasing cancer incidence and the expanding use of high-cost anticancer medicines. Early treatment discontinuation (ETD) may signal inefficiencies in medicine use or reflect appropriate or inevitable clinical decisions. Despite its clinical and economic relevance, national-level data on ETD remain limited. This study aims to quantify ETD rates and associated costs for the highest budget anticancer medicines in the Netherlands and assess trends from 2018 to 2022. METHODS: We performed a retrospective analysis using real-world data from the Dutch national claims database. ETD was defined as treatment discontinued within 90 days. The study focused on the 30 highest-budget impact anticancer medicines in 2022, assessing ETD rates, related medicine costs, and trends over 5 years (2018-2022). RESULTS: In 2022, these medicines accounted for €783 million in expenditures, with ETD representing 9.9% (€77 million). Among 30 343 treatments, 29.7% (9025) were discontinued within 90 days. From 2018 to 2022, total medication costs increased by 27.1%, while ETD costs rose by 9.6%. ETDs increased from 7287 to 9025 (+23.9%), with substantial variation among medicines. For most medicines, survivors accounted for most ETD spending, while ETD followed by death remained 9%. CONCLUSIONS: Approximately 30% of anticancer treatments are discontinued early, accounting for nearly 10% of medicine costs. While ETD highlights opportunities to improve efficiency, it also includes clinically justified and unavoidable discontinuations. Efforts to reduce avoidable ETD through improved patient selection, toxicity prediction, and treatment optimization are essential for more rational and equitable use of high-cost anticancer therapies.
BACKGROUND: Treatment-related thyroid dysfunction (trTD) frequently occurs in advanced nasopharyngeal carcinoma (NPC) patients treated with PD-1 inhibitors. Its clinical features, incidence, and prognostic value remain u...BACKGROUND: Treatment-related thyroid dysfunction (trTD) frequently occurs in advanced nasopharyngeal carcinoma (NPC) patients treated with PD-1 inhibitors. Its clinical features, incidence, and prognostic value remain unclear. This study aimed to characterize trTD and assess its impact on survival. METHODS: We retrospectively analyzed 168 advanced NPC patients who received PD-1 inhibitor therapy between 2019 and 2022. Cox proportional hazards models and Kaplan-Meier analysis were used to assess the prognostic significance of trTD. Clinical factors associated with trTD were identified through logistic regression. A predictive nomogram was constructed and evaluated using receiver operating characteristic (ROC) and calibration curves. Spearman correlation analysis was performed to assess the dynamic relationship between thyroid function indicators and treatment duration. RESULTS: TrTD developed in 49.4% of patients, mostly mild, including hyperthyroidism, hypothyroidism, and biphasic dysfunction. TrTD was independently associated with improved progression free survival (PFS). Female, elevated ALB, ALT, and TBIL were independent risk factors for trTD. The nomogram constructed by combining these factors and thyroid indicators had good prediction accuracy (AUC = 0.781). Dynamic analysis revealed that TSH levels significantly increased after the fourth treatment cycle, preceding changes in FT3 and FT4, suggesting TSH as a potential early biomarker for trTD onset. CONCLUSION: This study identifies trTD as a common event associated with improved survival in advanced NPC patients treated with PD-1 inhibitors. A predictive nomogram and early TSH elevation provide valuable tools for risk stratification and personalized immunotherapy monitoring.
BACKGROUND: LGBTQ+ (lesbian, gay, bisexual, transgender, queer, other sexual or gender minority) people experience unique challenges in cancer care. This study describes LGBTQ+ survivors' and caregivers' experiences inte...BACKGROUND: LGBTQ+ (lesbian, gay, bisexual, transgender, queer, other sexual or gender minority) people experience unique challenges in cancer care. This study describes LGBTQ+ survivors' and caregivers' experiences interacting with cancer care providers and their recommendations for delivering care with cultural humility. METHODS: We conducted a secondary analysis of qualitative focus group data to extract community members' suggestions for providers. We conducted 10 focus groups with 52 LGBTQ+ cancer survivors and caregivers. Participants were recruited as survivor/caregiver dyads in which at least one member (the survivor and/or the caregiver) identified as LGBTQ+. Focus groups were analyzed using qualitative thematic analysis. A community advisory board participated in one focus group and was consulted on study design, findings, and dissemination. RESULTS: Participants identified several recommendations for healthcare providers to improve cancer care delivery for LGBTQ+ survivors and their caregivers. This included, understanding that many LGBTQ+ patients experience minority stress during their cancer care; creating a welcoming space for LGBTQ+ people in care settings with visual indications of inclusivity; using affirming or unassuming language; not shying away from sexual health discussions; offering additional resources, ideally LGBTQ+-specific resources, to LGBTQ+ survivors and caregivers; and incorporating patient-centered approaches. CONCLUSION: Acting on LGBTQ+ cancer survivors' and caregivers' perspectives and recommendations for providers can help improve cancer care delivery for the LGBTQ+ community. This feedback can be utilized to inform medical trainings and innovative support programs to improve provider-patient communication and care.
BACKGROUND: The relationship between thyroid hormone sensitivity and the risk of recurrence in patients with papillary thyroid carcinoma (PTC) has not been thoroughly investigated, and it remains unclear whether factors...BACKGROUND: The relationship between thyroid hormone sensitivity and the risk of recurrence in patients with papillary thyroid carcinoma (PTC) has not been thoroughly investigated, and it remains unclear whether factors such as thyroid-stimulating hormone suppression efficacy or underlying autoimmune mechanisms mediate this association. The primary objective of the present study was to examine the complex interrelationships among thyroid hormone sensitivity indices and their collective utility as biomarkers for predicting recurrence. METHODS: This study retrospectively analyzed a cohort of 196 patients who underwent initial surgical resection and received a pathological confirmation of PTC between January 2015 and July 2016. Logistic regression analysis was employed to evaluate the potential association of thyroid hormone sensitivity indices-specifically, the thyrotropin index (TSHI) and thyrotroph T4 resistance index (TT4RI)-with PTC recurrence, as well as to assess their predictive utility. RESULTS: In patients with PTC, multivariate logistic regression identified both TSHI ≥ 3.6 and TT4RI ≥ 54.2 as independent prognostic factors associated with reduced recurrence risk (TSHI: OR = 0.107, 95% CI: 0.012-0.948, P = .045; TT4RI: OR = 0.158, 95% CI: 0.026-0.529, P = .005). Furthermore, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses revealed that the inclusion of thyroid hormone sensitivity indices significantly enhanced the predictive accuracy for recurrence events (TSHI: NRI = 0.292, 95% CI: -0.001-0.602, P = .064; IDI = 0.032, 95% CI: 0.013-0.051, P = .001; TT4RI: NRI = 0.663, 95% CI: 0.376-0.951, P < .001; IDI = 0.053, 95% CI: 0.025-0.082, P < .001). Finally, receiver operating characteristic curve analysis demonstrated that the combination of TSHI and TT4RI yielded superior predictive performance, with an area under the curve of 0.790 (P < .001), significantly outperforming either index alone. CONCLUSION: In conclusion, thyroid hormone resistance, indicated by elevated TSHI and TT4RI, represents an independent protective factor against recurrence in PTC. The integration of these indices significantly improves recurrence prediction, with their combination offering superior discriminative ability, highlighting their collective utility as clinically relevant biomarkers for optimizing postoperative surveillance and management strategies in PTC.
Adoptive cell therapies (ACTs) include chimeric antigen receptors (CARs), bispecific T-cell engagers (BiTES), tumor-infiltrating lymphocytes, and T-cell receptor (TCR) gene-modified T-cells. ACTs have significantly impro...Adoptive cell therapies (ACTs) include chimeric antigen receptors (CARs), bispecific T-cell engagers (BiTES), tumor-infiltrating lymphocytes, and T-cell receptor (TCR) gene-modified T-cells. ACTs have significantly improved patient outcomes associated with hematologic malignancies. Recent advances have demonstrated their potential in solid tumors with promising clinical trial results signaling that they represent paradigm shift in oncologic care. As these therapies become standard care in solid tumors, medical oncologists must become adept at recognizing and managing their unique toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). This review synthesizes the latest clinical data on ACTs in solid tumors, highlighting key findings, and toxicity profiles. In addition, the review provides an overview of early recognition and evidence-based management of CRS and ICANS. Equipping clinicians with the necessary knowledge to navigate toxicity management will be essential in optimizing patient outcomes as ACTs are increasingly adopted in solid tumor oncology.