Apostol AI, Gronwald J, Cybulski C
… +22 more, Kim RH, Møller P, Karlan BY, Bordeleau L, Schrader I, Ramón Y Cajal T, Pal T, Eisen A, Singer CF, Couch FJ, Zakalik D, Metcalfe K, Olopade O, Tung N, Fruscio R, Foulkes WD, Aeilts A, Sun P, Lubinski J, Narod SA, Kotsopoulos J, Hereditary Breast Cancer Clinical Study Group
PURPOSE: carriers face high risks of developing both breast and ovarian/fallopian tube cancers (hereafter referred to as ). Among carriers with ovarian cancer, it is not clear whether the risk of breast cancer is suffi...PURPOSE: carriers face high risks of developing both breast and ovarian/fallopian tube cancers (hereafter referred to as ). Among carriers with ovarian cancer, it is not clear whether the risk of breast cancer is sufficiently high that risk-reducing mastectomy should be offered. This study aimed to assess the risk of breast cancer carriers after a diagnosis of ovarian cancer. METHODS: We included women with a pathogenic/likely pathogenic variant in or , a diagnosis of ovarian cancer, and no other cancer history and no risk-reducing bilateral mastectomy. Women were followed for incident breast cancer from the date of ovarian cancer diagnosis or the date of baseline questionnaire, whichever came last. The 5-, 10-, and 15-year cumulative risks of breast cancer were compared for women with ovarian cancer and an age-matched set of control women without ovarian cancer. RESULTS: A total of 960 participants with ovarian cancer were identified (814 and 146 carriers). After a mean follow-up of 4.9 years, 41 women (4.3%) developed breast cancer, at a mean age at diagnosis of 57.5 years (range, 39-74). Actuarial cumulative breast cancer risks after ovarian cancer were 4.4%, 8.9%, and 11.5% at 5, 10, and 15 years, respectively. Only three breast cancer-related deaths occurred. Among 741 age-matched carriers ovarian cancer, actuarial cumulative risks of breast cancer were 20.9%, 38.6%, and 47.2% at 5, 10, and 15 years, respectively. The hazard ratio for breast cancer, after an ovarian cancer diagnosis, compared with no ovarian cancer, was 0.18 ([95% CI, 0.12 to 0.27]; < .0001). CONCLUSION: After ovarian cancer, carriers have a relatively low risk of breast cancer. Risk-reducing mastectomy should not be recommended routinely, but might be considered for long-term survivors. Magnetic resonance imaging surveillance and/or mammography is a realistic alternative.
Yan W, Du C, Lv R
… +16 more, Zou H, Zhang S, Yu T, Yan Y, Zhang Y, Peng S, Wang T, Deng S, Huang W, Yi S, Zou D, Cheng T, Wang J, Chang AH, Qiu L, An G
PURPOSE: Patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for or not proceeding to autologous stem-cell transplantation (ASCT)-often because of age or frailty-have limited opportunities to receive...PURPOSE: Patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for or not proceeding to autologous stem-cell transplantation (ASCT)-often because of age or frailty-have limited opportunities to receive multiple effective lines of therapy, underscoring the need for novel frontline strategies. METHODS: In this phase II, open-label, single-arm trial (ClinicalTrials.gov identifier: NCT05860036), patients received 3-4 cycles of protocol-allowed induction, followed by B-cell maturation antigen (BCMA) CAR-T infusion, and subsequent consolidation and lenalidomide maintenance. The primary end point was the rate of minimal residual disease (MRD) negativity (10) at Month three postinfusion. RESULTS: Between April 4, 2023, and December 26, 2024, 43 patients were screened, 40 were enrolled, and 36 received infusion (median age, 68 years [46-75]). In the infused cohort, the MRD negativity rate at Month three postinfusion was 100% (36 of 36; 95% CI, 90.3 to 100.0). With a median follow-up of 15.8 months postinfusion (range, 4.3-26.0), no MRD recurrence was observed. The complete response rate (CRR) increased from 33.3% (12 of 36; 95% CI, 18.6 to 51.0) preinfusion to 69.4% (25 of 36; 95% CI, 51.9 to 83.7) at Month 3% and 94.4% (34 of 36; 95% CI, 81.3 to 99.3) at last follow-up. The most common grade 3 to 4 adverse events were transient cytopenia, including lymphopenia (100%), neutropenia (88.9%), leukopenia (80.6%), thrombocytopenia (19.4%), and anemia (8.3%). Cytokine release syndrome occurred in 52.8% of patients (all grade 1 to 2), immune effector cell-associated neurotoxicity in 5.6% (all grade 1), and infections in 30.6% (grade ≥3 in 19.4%). No deaths or disease progressions occurred by cutoff. CONCLUSION: Frontline BCMA CAR-T therapy induces deep, rapid, and durable remissions with a manageable safety profile in the NDMM population ineligible for or not proceeding to ASCT. These findings support its investigation as a potentially practice-changing strategy for this population.
UNLABELLED: .. PURPOSE: To provide updated recommendations for immunotherapy and targeted therapy for patients with advanced gastroesophageal cancer. METHODS: ASCO convened an Expert Panel to conduct a systematic revie...UNLABELLED: .. PURPOSE: To provide updated recommendations for immunotherapy and targeted therapy for patients with advanced gastroesophageal cancer. METHODS: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS: Twelve newly published or updated phase III randomized controlled trials met the inclusion criteria for the systematic review. RECOMMENDATIONS: The target population for these recommendations is patients with unresectable locally advanced, advanced, or metastatic gastroesophageal cancer. Results from testing for actionable biomarkers should be available as soon as possible to inform treatment decision making. Immunotherapy with doublet chemotherapy is recommended for patients with proficient mismatch repair (pMMR)/microsatellite stable (MSS) human epidermal growth factor receptor 2 (HER2)-negative gastroesophageal adenocarcinoma or squamous cell carcinoma and PD-L1 expression ≥1; patients with higher PD-L1 expression are more likely to benefit from immunotherapy. Zolbetuximab is recommended for patients with gastroesophageal adenocarcinoma, PD-L1 <1, and positive CLDN18.2 expression. Patients with dual PD-L1 and CLDN18.2 positivity should engage in shared decision making, considering the factors outlined in the guideline. Doublet chemotherapy alone is recommended for patients who are not positive for actionable biomarkers or are not considered candidates for targeted therapy or immunotherapy. For patients with pMMR/MSS HER2-positive gastric/gastroesophageal junction (GEJ) adenocarcinoma, trastuzumab and doublet chemotherapy is recommended; for patients with PD-L1 expression ≥1, the addition of pembrolizumab is recommended. Immunotherapy alone or with doublet chemotherapy is recommended for patients with mismatch repair deficient/microsatellite instability-high gastroesophageal cancer. Second-line therapy options include ramucirumab with paclitaxel, trastuzumab deruxtecan for HER2-positive gastric/GEJ adenocarcinoma, and immunotherapy for PD-L1 ≥1 esophageal squamous cell carcinoma after first-line combination chemotherapy without immunotherapy.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.
Armstrong AJ, Morris MJ, Abida W
… +48 more, Aggarwal RR, Antonarakis ES, Attard G, Beltran H, Bryce A, Carducci MA, Cheng HH, Chen DL, Chi KN, Childs DS, Dahut W, Emmett L, Fizazi K, Gafita A, George DJ, Hermann K, Hofman MS, Hope T, Hussain M, Kelly WK, Kessler E, Kuo PH, Lang J, Liu G, Marshall CH, Morgans AK, McKay RR, Nanus D, Nelson P, Paller C, Reichert ZR, Ryan CJ, Sartor AO, Schöder H, Schwartz LH, Sharifi N, Stadler WM, Stein M, Sternberg CN, Szmulewitz RZ, Tagawa ST, Sokolova AO, Wyatt AW, Yamoah K, Yu EY, Halabi S, Scher HI, PCWG4 Writing Group
J Clin Oncol
· 2026 May · PMID 41744290
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PURPOSE: The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine termi...PURPOSE: The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer. METHODS: We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer. RESULTS: PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)-defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. CONCLUSION: PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator-naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.
PURPOSE: Smoking cessation after a cancer diagnosis improves survival, but widespread adoption of evidence-based cessation assistance has not been demonstrated. American College of Surgeons' accredited cancer programs pa...PURPOSE: Smoking cessation after a cancer diagnosis improves survival, but widespread adoption of evidence-based cessation assistance has not been demonstrated. American College of Surgeons' accredited cancer programs participated in the nationwide Beyond ASK quality improvement (QI) initiative to increase the proportion of currently smoking patients with cancer offered cessation assistance as part of cancer care delivery. METHODS: A national QI project was employed between January 2023 and January 2024 following the Plan-Do-Study-Act methodology, and five longitudinal surveys were administered. Participating programs received educational webinars, an online practice change package that contained information about evidence-based smoking assessment and cessation assistance tools, training opportunities, and electronic health record guidance. Primary outcomes included identification of current smoking among patients with newly diagnosed cancer and rate of providing cessation assistance among currently smoking patients. RESULTS: A total of 324 programs (164 [50.8%] community programs) enrolled in Beyond ASK. Participation rates were high with 300 (92.6%) programs completing all five surveys. Among 446,015 reported patients newly diagnosed with cancer, 52,794 (11.8%) were identified as currently smoking of which 33,638 (63.7%) received cessation assistance. The mean assist rate increased from 48.0% (95% CI, 43.7 to 52.2) at baseline to 67.5% (95% CI, 63.6 to 71.3) at final. Full adoption was reported by 65.4% of programs. Delivery of cessation assistance increased over time for in-office brief counseling (33.9%-65.8%, = .0002), in-office behavioral counseling (7.1%-18.5%, = .02), referral to in-house program (14.5%-27.3%, = .02), referral to community program (12.1%-29.5%, = .002), and referral to web-based programs (12.2%-33.9%, = .0002). CONCLUSION: Scaled improvement in smoking cessation assistance across accredited cancer programs is feasible and achievable relatively quickly. Findings provide a framework to guide national adoption for smoking cessation assistance as standard care for all patients with newly diagnosed cancer.
Liberio N, Allbee-Johnson M, Ahn KW
… +18 more, Moskop A, Phelan R, Shaw BE, Page KM, Schultz KR, Phillips CL, Mehta PA, Qayed M, Sharma A, Lipsitt AE, Symons H, Bolaños-Meade J, Kharbanda S, Dvorak CC, Kapoor N, Doherty EE, Chavan RS, Broglie L
J Clin Oncol
· 2026 Apr · PMID 41740085
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PURPOSE: Critical guidance on selecting haploidentical donors for pediatric patients is lacking. It is unclear whether parents, siblings, and extended family affect acute and chronic graft-versus-host disease (aGVHD and...PURPOSE: Critical guidance on selecting haploidentical donors for pediatric patients is lacking. It is unclear whether parents, siblings, and extended family affect acute and chronic graft-versus-host disease (aGVHD and cGVHD) differently. METHODS: We analyzed 1,069 pediatric (<19 years) recipients of hematopoietic cell transplant during 2013-2019. Primary end points were aGVHD frequency at 100 days and cumulative incidence of cGVHD at 2 years, assessed by donor age (<18 years, 18-35, >35 years) and donor relationship, with multivariable analysis. RESULTS: Donor age: Increased grade II-IV aGVHD occurred with older donors: >35 years (31%, odds ratio [OR], 1.7 [95% CI, 1.0 to 2.8]; = .05) and 18-35 years (23%, OR, 2.5 [95% CI, 1.5 to 4.2]; = .0003), versus < 18 years (15%, reference OR, 1). Increased cGVHD occurred in older donors: >35 years (incidence 30% [95% CI, 28 to 32]; hazard ratio [HR], 2.2 [95% CI, 1.3 to 3.9]; = .004) and 18-35 years (incidence 26% [95% CI, 23 to 29]; HR, 2.1 [95% CI, 1.3 to 3.5]; = .0028) compared with <18 years (incidence 16% [95% CI, 12 to 20]; reference HR, 1). Donor relationship: Patients with parental donors had higher aGVHD risk than siblings (mother: OR, 1.9 [95% CI, 1.3 to 2.8]; = .001; father: OR, 1.7 [95% CI, 1.1 to 2.5]; = .009). Patients with maternal donors had a significantly higher risk of cGVHD than paternal (HR, 2.3 [95% CI, 1.6 to 3.3]; < .0001) and sibling donors (HR, 2.3 [95% CI, 1.7 to 3.4]; < .0001). Age-relationship interaction: Maternal donors were associated with more GVHD than siblings, regardless of age (aGVHD II-IV, mothers >35 years, HR, 2.53 [95% CI, 1.46 to 4.41]; mothers 18-35 years, HR, 2.05 [95% CI, 1.14 to 3.69]) (cGVHD: mothers >35 years, HR, 3.10 [95% CI, 1.72 to 5.60]; mothers 18-35 years, HR, 3.35 [95% CI, 1.8 to 6.25]). CONCLUSION: Donors <18 years are associated with reduced aGVHD and cGVHD, whereas maternal donors are associated with increased cGVHD risk. For pediatric patients, sibling donors should be considered to reduce GVHD.
PURPOSE: To update the ASCO guideline on use of hematopoietic colony-stimulating factors (CSFs) in patients with cancer. METHODS: A systematic review identified randomized controlled trials (RCTs), meta-analyses, and sys...PURPOSE: To update the ASCO guideline on use of hematopoietic colony-stimulating factors (CSFs) in patients with cancer. METHODS: A systematic review identified randomized controlled trials (RCTs), meta-analyses, and systematic reviews that addressed use of CSFs for the prevention or treatment of neutropenic events, or for mobilization of stem cells, in adults with cancer. PubMed and the Cochrane Library were searched for articles published from September 1, 2014, to August 22, 2025. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: The updated systematic review included 33 RCTs and 16 systematic reviews. Additions to the body of evidence include approval of new CSFs and additional biosimilars, and approval of an additional CXCR4 inhibitor that may be used with CSFs for the mobilization of hematopoietic stem cells. RECOMMENDATIONS: Prophylactic use of CSFs to reduce the risk of febrile neutropenia is warranted when the risk of febrile neutropenia from chemotherapy is approximately 20% or higher and no other equally effective and safe regimen that does not require CSFs is available. For patients receiving chemotherapy with a <20% risk of febrile neutropenia, primary prophylaxis with a CSF may be warranted if patients are at a high risk of febrile neutropenia based on age, medical history, or disease characteristics. For stem-cell mobilization, CSFs may be used either alone, after chemotherapy, or in combination with plerixafor or motixafortide. The guideline also provides information about the dosing and selection of CSFs.Additional information is available at www.asco.org/supportive-care-guidelines.
Zhu HD, Fan WJ, Zhao C
… +28 more, Wang S, Li YL, Jin ZC, Zhang ZW, Guo JH, Cheng HT, Zhang Q, Lu J, Zeng YY, Lv WF, Xu H, Shao HB, Xu WG, Zhao XY, Gu SZ, Lin HL, Zheng WH, Piao LZ, Song YS, Zhao JB, Wang YC, Hou ZG, Sun Y, Guan N, Huang M, Yang WZ, Ji JS, Teng GJ
J Clin Oncol
· 2026 Apr · PMID 41734362
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PURPOSE: Transarterial chemoembolization (TACE) alone has shown limited efficacy in improving survival among patients with unresectable hepatocellular carcinoma (HCC). This phase II trial compared TACE combined with camr...PURPOSE: Transarterial chemoembolization (TACE) alone has shown limited efficacy in improving survival among patients with unresectable hepatocellular carcinoma (HCC). This phase II trial compared TACE combined with camrelizumab (anti-PD-1 antibody) and rivoceranib (vascular endothelial growth factor receptor 2 inhibitor) versus TACE in unresectable HCC. METHODS: Patients with unresectable HCC (Barcelona Clinic Liver Cancer stage A to C without extrahepatic metastases) and Child-Pugh class A liver function were randomly assigned (1:1), stratified by macrovascular invasion, previous tyrosine kinase inhibitor treatment, and number of previous TACE procedures, to receive TACE combined with camrelizumab (200 mg once every 3 weeks) and rivoceranib (250 mg once daily; TACE-C-R) or TACE alone. The primary end point was progression-free survival (PFS) per composite criteria (progression per Response Evaluation Criteria in Cancer of the Liver version 5, transient deterioration to Child-Pugh class C, or TACE failure or refractoriness) in the intention-to-treat population. RESULTS: Between December 28, 2020, and October 29, 2023, 200 patients were randomly assigned (100 in each group). Median PFS per composite criteria was significantly longer with TACE-C-R than with TACE (10.8 months [95% CI, 8.8 to 13.7] 3.2 months [95% CI, 2.4 to 4.2]; hazard ratio, 0.34 [95% CI, 0.24 to 0.50], < .001). Grade ≥3 treatment-related adverse events occurred in 74.5% (70 of 94) of patients with TACE-C-R and 22.3% (23 of 103) of patients with TACE, with the most common being increased AST (29 [30.9%] and 13 [12.6%]) and increased ALT (23 [24.5%] and 14 [13.6%]). CONCLUSION: The addition of camrelizumab and rivoceranib to TACE showed statistically significant improvement in PFS for patients with unresectable HCC, with a manageable safety profile. Follow-up for further overall survival analysis is ongoing.
Scherpereel A, Baas P, Nowak AK
… +17 more, Tsao AS, Fujimoto N, Peters S, Mansfield AS, Popat S, Bautista Aragon Y, Talbot T, Grossi F, Kowalski D, Kaplan MA, Cardona AF, Soomro R, Hu N, Lee A, Ip V, Hung YH, Zalcman G
J Clin Oncol
· 2026 Mar · PMID 41734361
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In this 5-year follow-up from the CheckMate 743 study in patients with unresectable pleural mesothelioma (PM), we evaluated updated efficacy and safety outcomes and biomarkers and performed treatment-switching analyses w...In this 5-year follow-up from the CheckMate 743 study in patients with unresectable pleural mesothelioma (PM), we evaluated updated efficacy and safety outcomes and biomarkers and performed treatment-switching analyses with first-line nivolumab plus ipilimumab versus chemotherapy. With a median follow-up of 66.8 months, nivolumab plus ipilimumab demonstrated continued overall survival (OS) benefit versus chemotherapy in all randomly assigned patients (5-year OS rates, 14% 6%; hazard ratio [HR], 0.74 [95% CI, 0.62 to 0.88]); similar benefit was observed regardless of tumor histology. Of biomarker-evaluable patients treated with nivolumab plus ipilimumab (n = 242), high baseline monocytic myeloid-derived suppressor cell (M-MDSC) levels correlated with worse OS versus low M-MDSC levels (HR, 1.25 [95% CI, 1.09 to 1.43]). After adjusting for 24% of patients in the chemotherapy arm who received subsequent immunotherapy, nivolumab plus ipilimumab demonstrated continued OS benefit versus chemotherapy (HR, 0.64 [95% CI, 0.53 to 0.78]). No new safety signals were observed. These results demonstrate long-term, durable clinical benefit with nivolumab plus ipilimumab versus chemotherapy, which continued to be preserved even after treatment-switching adjustment in the chemotherapy arm. Exploratory analyses suggested greater benefit with nivolumab plus ipilimumab in the low M-MDSC subgroup. These results further support first-line nivolumab plus ipilimumab as standard of care for unresectable PM.
Garcia-Carbonero R, Benavent M, Jimenez-Fonseca P
… +22 more, Alonso-Gordoa T, Teulé A, Custodio A, Tafuto S, La Casta A, Spada F, López C, Ibrahim T, Iranzo V, García-Alfonso P, González-Flores E, Villanueva Silva MJ, Grande E, Panzuto F, Crespo G, Navarro M, Castellano D, Hernando J, Morales-Herrero R, Iglesias Álvarez G, Soldevilla B, Capdevila J
J Clin Oncol
· 2026 Mar · PMID 41719493
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PURPOSE: Angiogenesis plays an essential role in neuroendocrine tumors (NETs). This study evaluates efficacy and safety of axitinib in extrapancreatic (ep)-NETs. PATIENTS AND METHODS: AXINET was an international, randomi...PURPOSE: Angiogenesis plays an essential role in neuroendocrine tumors (NETs). This study evaluates efficacy and safety of axitinib in extrapancreatic (ep)-NETs. PATIENTS AND METHODS: AXINET was an international, randomized, double-blind, placebo-controlled, phase II/III trial including patients age 18 years and older, with unresectable/metastatic G1-2 epNETs and up to two previous treatment lines. Patients were randomly assigned (1:1) to axitinib 5 mg or placebo, both orally twice a day, in combination with intramuscular octreotide long-acting release 30 mg once every 28 days until disease progression or unacceptable toxicity. Randomization was stratified by primary tumor site, Ki-67 index (≤5% or >5%), and time from diagnosis (> or ≤12 months). The primary end point was investigator-assessed progression-free survival (PFS). Efficacy was also assessed by a blinded independent central review (BICR). RESULTS: From October 2011 to May 2019, 256 patients were assigned to axitinib (n = 126) or placebo (n = 130). Investigator-assessed median PFS was 17.2 months (95% CI, 13.6 to 24.7) versus 13.1 months (95% CI, 10.9 to 18.6) in the axitinib and placebo groups, respectively (hazard ratio [HR], 0.86 [95% CI, 0.65 to 1.15]). The median BICR PFS was 16.6 months (95% CI, 13.5 to 24.2) versus 9.9 months (95% CI, 8.2 to 13.9) in the axitinib and placebo groups, respectively (HR, 0.71 [95% CI, 0.54 to 0.94], = .017). Objective response rate (ORR) was significantly greater for axitinib per investigator assessment (17.5% 4.6%; = .001) and BICR (12.8% 3.2%; .005). Most common grade ≥3 toxicities were hypertension (24.0% 9.2%) and diarrhea (13.6% 1.5%). CONCLUSION: Axitinib significantly increased PFS per BICR assessment and ORR both per investigator and BICR assessment compared with placebo, although the primary study end point was not met. Toxicity profile was manageable with no new safety concerns.
Urbini M, Eleveld TF, Polano M
… +15 more, Scarpi E, Menna C, Gianni C, Janssen FW, Schepisi G, Gurioli G, Kucerova L, Gillis AJM, Virga A, Bleve S, Rosti G, Ulivi P, Mego M, Looijenga LHJ, De Giorgi U
J Clin Oncol
· 2026 Mar · PMID 41712877
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PURPOSE: High-dose chemotherapy (HDCT) is one of the salvage therapy options for patients with relapsed/refractory germ cell tumors (rGCT) after failure of first-line chemotherapy. We aimed to identify circulating biomar...PURPOSE: High-dose chemotherapy (HDCT) is one of the salvage therapy options for patients with relapsed/refractory germ cell tumors (rGCT) after failure of first-line chemotherapy. We aimed to identify circulating biomarkers predicting clinical response and outcome of HDCT. METHODS: Baseline and on-treatment plasma samples from 69 HDCT-treated and 26 conventional-dose chemotherapy (CDCT)-treated GCT patients were analyzed by shallow whole-genome sequencing. Tumor fraction (TF) and copy-number alterations (CNAs) were determined using ichorCNA, compared with miR-371a-3p levels, and correlated with progression-free survival (PFS) and overall survival (OS). CNA profiles from external tissue GCT cohorts were used for validation. RESULTS: TF was detectable in 75.4% of baseline plasma of HDCT patients. High TF was strongly associated with worse OS in HDCT-treated nonseminomas ( = .021). This was confirmed in the CDCT cohort ( = .039), where shorter median OS was observed in high-TF patients compared with the HDCT cohort. Conversely, miR-371a-3p levels were not prognostic. Plasma CNA profiling confirmed the high frequency of chromosome 3p gain in rGCT cases and revealed other alterations linked to poor HDCT outcomes, including 9q and 11q gains and 6q loss. These CNAs were enriched in a cluster predominantly composed of GCT with extra-embryonic histology (yolk sac and choriocarcinoma). Unsupervised clustering of CNA profile of plasma identified 13 patients in this high-risk cluster, who had significantly worse PFS and OS compared with other rGCT cases. CONCLUSION: Analysis of cell free DNA provides valuable prognostic information in rGCTs. High baseline TF and specific CNA patterns linked to extra-embryonic histology identify patients at higher risk of poor outcomes. HDCT seems to be more effective than CDCT in high-TF patients. These minimally invasive biomarkers could refine risk stratification and guide selection of salvage therapies in rGCTs.
Mei WJ, Wang XZ, Zhang X
… +37 more, Sun YM, Yang CK, Lin JZ, Wu ZG, Zhang R, Wang W, Li Y, Zhuang YZ, Lei J, Wan XB, Ren YK, Cheng Y, Li WL, Wang ZQ, Xu DB, Mo XW, Ju HX, Ye SW, Zhao JL, Zhang H, Gao YH, Zeng ZF, Xiao WW, Zhang XP, Li YF, Xie E, Feng YF, Tang JH, Wu XJ, Chen G, Li LR, Lu ZH, Wan DS, Bei JX, Pan ZZ, Yu JH, Ding PR
PURPOSE: The neoadjuvant chemoradiotherapy (nCRT) might accentuate surgical complications and toxicity in the treatment of locally advanced rectal cancer (LARC) while neoadjuvant chemotherapy (nCT) alone shows promise as...PURPOSE: The neoadjuvant chemoradiotherapy (nCRT) might accentuate surgical complications and toxicity in the treatment of locally advanced rectal cancer (LARC) while neoadjuvant chemotherapy (nCT) alone shows promise as an alternative treatment. However, which patients deserve most from the nCT need further clarify. This trial aimed to assess the non-inferiority of nCT with capecitabine plus oxaliplatin (CAPOX) versus nCRT with capecitabine in LARC with uninvolved mesorectal fascia (MRF). METHODS: Patients with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to receive 4 cycles of CAPOX chemotherapy alone (nCT group) or CRT with concurrent Capecitabine (nCRT group). The primary end point is 3-year locoregional recurrence-free survival (LRRFS). Secondary end points, such as 3-year disease-free survival (DFS), 3-year overall survival (OS), and adverse events (AEs), were also reported. RESULTS: A total of 663 patients were enrolled and 589 patients received the allocated treatment (nCT, n = 300; nCRT, n = 289). LRRFS was analyzed with a median follow-up of 48 months. 3-year LRRFS was 97.4% (95% CI, 95.5 to 99.3) in the nCRT group and 96.3% (95% CI, 94.0 to 98.6) in the nCT group, resulting in a hazard ratio (HR) of 1.40 (95% CI, 0.53 to 3.68). The nCT and nCRT achieved similar 3-year DFS (89.2% 87.9%; HR, 0.88 [95% CI, 0.54 to 1.44]) and 3-year OS (95.0% 94.1%; HR, 0.86 [95% CI, 0.42 to 1.76]). The nCT group showed a lower incidence of grade 2 to 4 long-term AEs (16.0% 26.3%, = 0.002) and proctitis (33.6% 41.7%, = 0.049) compared with nCRT group. CONCLUSIONS: The non-inferiority of nCT was not confirmed with a very low incidence of local recurrence in both group. But nCT offers comparable DFS and OS while mitigating the burden of toxicity as compared to nCRT. These insights shed light on a potential paradigm shift in the treatment for LARC with uninvolved MRF.
Qualitative analysis of narrative essays authored by cancer care professionals offer insights into what it means to be a "good oncologist."Qualitative analysis of narrative essays authored by cancer care professionals offer insights into what it means to be a "good oncologist."
Wentzensen N, Egemen D, Clarke MA
… +13 more, Poitras N, Grewal K, Goldhoff P, Hosfield E, Schiffman M, Hyer M, Castle PE, Fuller L, Rydzak G, Cheung LC, Kinney W, Suh-Burgmann B, Lorey T
PURPOSE: Primary human papillomavirus (HPV) testing has the best tradeoff of benefits and harms for cervical screening but requires triage to determine management among HPV positives. We conducted a prospective observati...PURPOSE: Primary human papillomavirus (HPV) testing has the best tradeoff of benefits and harms for cervical screening but requires triage to determine management among HPV positives. We conducted a prospective observational study to evaluate triage of women who are HPV-positive using dual stain (DS) and HPV genotyping. MATERIALS AND METHODS: We included 9,645 consecutive women who are HPV-positive undergoing cervical screening in two periods between 2015 and 2017 in the organized cervical screening program at Kaiser Permanente Northern California. Absolute risk and clinical performance of DS and cytology for detection of cervical intraepithelial neoplasia grade 3 and greater (CIN3+) were estimated overall and by HPV genotype and by age. Cumulative absolute risk of CIN3+ was modeled over 5 years using a prevalence-incidence mixture model, which allows estimating risk accounting for differences in disease ascertainment, surveillance intervals, and compliance. RESULTS: The baseline risk of CIN3+ was 9.4% and 0.8% for women testing positive and negative for DS, respectively, and 6.9% and 2.0% for women testing positive and negative for cytology, respectively. Sensitivity, specificity, and predictive values for CIN3+ detection were better for DS compared with cytology over 5 years ( < .001 for all comparisons). Risk in women with HPV16-positive/negative for intraepithelial lesion or malignancy was substantially higher than the risk in women with HPV16-positive/DS-negative (7.5% 2.9%, < .001). DS had better triage performance compared with cytology in all age groups and in women positive for HPV types other than HPV16 or HPV18. CONCLUSION: Long-term reassurance of low risk among DS negatives suggests that DS detects molecular changes earlier in the carcinogenic pathway than cytology. DS has better risk stratification than cytology overall, within HPV risk strata, and across all screening age groups and is a better option for triage of vaccinated populations.
PURPOSE: To examine the associations between Medicaid expansion and stage at diagnosis, timely initiation and receipt of guideline-concordant treatment, and 5-year overall survival (OS) among people with non-small cell l...PURPOSE: To examine the associations between Medicaid expansion and stage at diagnosis, timely initiation and receipt of guideline-concordant treatment, and 5-year overall survival (OS) among people with non-small cell lung cancer (NSCLC). METHODS: Individuals newly diagnosed with stage I to IV NSCLC at age 18-64 years between January 1, 2004, and December 31, 2023, in 50 states and Washington, DC, were identified from the National Cancer Database. We examined the association of Medicaid expansion and (1) early-stage diagnosis (I and II); (2) timely initiation of guideline-concordant treatment within 30 days after diagnosis; (3) receipt of all first-course guideline-concordant treatment; and (4) 5-year OS. We applied conventional and updated (Sun and Abraham) difference-in-differences (DID) approaches to examine the changes in study outcomes associated with Medicaid expansion using multivariable linear probability models to estimate stage and treatment and multivariable flexible parametric survival models to investigate survival overall and by key factors. RESULTS: Compared with people in nonexpansion states (n = 164,228), people in expansion states (n = 350,290) were more likely to be female, non-Hispanic White, or living in areas with higher family income or in nonmetropolitan areas. Medicaid expansion was associated with increases in early-stage NSCLC diagnosis (DID: 1.02 percentage points [ppt; 95% CI, 0.52 to 1.52]), timely treatment initiation (2.10 ppt [95% CI, 0.05 to 4.15]), and higher 5-year OS (1.79 ppt [95% CI, 1.32 to 2.26]). In stratified analyses, people living in areas with lower household income were more likely to benefit from Medicaid expansion. CONCLUSION: Medicaid expansion was associated with improvements in early detection, timeliness of guideline-concordant treatment, and survival for people with NSCLC. Anticipated Medicaid coverage losses may jeopardize these gains.