Rogers J, Michael M, Tie J
… +6 more, Solomon BJ, Harris S, Underhill C, Wolfe R, Burbury K, Alexander M
J Natl Cancer Inst
· 2026 Mar · PMID 41795841
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Thromboembolism (TE) is a major cause of early mortality in cancer. TARGET-TP randomised high-risk patients with lung or gastrointestinal cancers, identified using a d-dimer/fibrinogen model, to enoxaparin or no thrombop...Thromboembolism (TE) is a major cause of early mortality in cancer. TARGET-TP randomised high-risk patients with lung or gastrointestinal cancers, identified using a d-dimer/fibrinogen model, to enoxaparin or no thromboprophylaxis; low-risk patients were observed. Thromboprophylaxis reduced TE and 6-month mortality. This study reports extended overall survival (OS) and progression-free survival (PFS) to 36 months. Among high-risk patients, thromboprophylaxis improved OS at 6 and 12 months, with convergence thereafter; no PFS differences were observed. Adjustment for on-study TE attenuated the OS effect, consistent with thrombosis-specific risk reduction. These findings describe the duration and extent of survival benefit achievable with biomarker-guided thromboprophylaxis and highlight that TARGET-TP is the first trial to demonstrate a survival advantage, likely driven by cohort enrichment for thrombotic risk. The improved risk-benefit profile supports real-world evaluation of d-dimer/fibrinogen-guided thromboprophylaxis in lung and gastrointestinal cancers, with validation of the model warranted in additional tumour groups.
Lu-Yao G, Nikita N, Keith SW
… +9 more, Gandhi K, Shaver AL, Sharma S, Steinbock-Malfer C, Yang H, Yang C, Zarrabi KK, Freedland SJ, Kelly WK
J Natl Cancer Inst
· 2026 Mar · PMID 41795824
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BACKGROUND: This population-based study aimed to quantify fracture risk after ARPIs in PCa patients by pre-existing health conditions. PATIENTS AND METHODS: Patients were identified from the SEER-Medicare files who recei...BACKGROUND: This population-based study aimed to quantify fracture risk after ARPIs in PCa patients by pre-existing health conditions. PATIENTS AND METHODS: Patients were identified from the SEER-Medicare files who received abiraterone with prednisone (AAP) or enzalutamide (ENZA) between 1/1/2013 and 12/31/2020. Health and fracture history were based on claims one year before ARPI with follow-up through 12/31/2020. The main outcome of the study was the cumulative fracture risk after first date of ARPI. Fine and Gray's sub-distribution hazard model was used to obtain adjusted relative risks with confounding factors. RESULTS: This study included 10,463 patients (6,037- AAP; 4,426-ENZA). The 3-year fracture risk after ARPI was high, exceeding 25% among those without a prior fracture. Among 1,445 men with a fracture the year before ARPI, 3-year fracture risk exceeded 50%, and remained high (above 44%) despite using bone health agents (BHA). A recent history of fracture was associated with a 2.84-fold fracture risk (aHR: 2.84, 95% CI 2.58-3.12). Pre-existing osteoporosis and a comorbidity score ≥ 2 were associated with 15% (aHR : 1.15, 95% CI 1.03-1.29) and 11% (aHR : 1.11, 95% CI 1.00 to 1.24) higher fracture risks. Bone health agent (BHA) use was associated with a 23% lower fracture risk (aHR: 0.77, 95% CI 0.70-0.83). CONCLUSION: Fracture risk after ARPI was high, exceeding 44% within 3 years in those with prior fractures despite BHA, suggesting limited benefit in patients with poor bone quality. Early identification and intervention for patients at high risk of fractures is critical.
Sampathkumar Y, Zakaria Z, O'Connell K
… +23 more, Bhimani J, Blinder VS, Burganowski R, Ergas IJ, Gallagher GB, Griggs JJ, Heon N, Kolevska T, Kotsurovskyy Y, Kroenke CH, Laurent CA, Liu R, Monroy-Iglesias MJ, Nakata KG, Persaud S, Roh JM, Tabatabai S, Valice E, Wang P, Bandera EV, Aiello Bowles EJ, Kushi LH, Kantor ED
J Natl Cancer Inst
· 2026 Mar · PMID 41782330
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BACKGROUND: Chemotherapy dose reductions are associated with poorer survival. To better understand the role of clinician- and facility-level factors in chemotherapy dosing, we conducted an analysis within a large, real-w...BACKGROUND: Chemotherapy dose reductions are associated with poorer survival. To better understand the role of clinician- and facility-level factors in chemotherapy dosing, we conducted an analysis within a large, real-world cohort of women with stages I-IIIA breast cancer. METHODS: Our cohort included 8,540 breast cancer patients receiving chemotherapy at Kaiser Permanente Northern California between 2006 and 2019. Patients were treated across 22 facilities by 198 clinicians. We evaluated associations between clinician- and facility-level factors related to dose reductions at the start of chemotherapy (first cycle dose proportion, FCDP, <90%) and throughout treatment (average relative dose intensity, ARDI, <90%). Prevalence ratios (PR) and corresponding 95% confidence intervals (CI) were estimated for the clinician and facility factors in relation to chemotherapy dose reductions. RESULTS: Factors associated with an increased likelihood of dose reduction were increased clinician years since medical school (FCDP < 90%: PR≥30 vs <10 years : 1.78, p-trend = 0.03; ARDI < 90%: PR≥30 vs <10 years : 1.29, p-trend = 0.03) and treatment at less urban facilities (ARDI < 90%: PR<100% vs 100% urban : 1.38, p-trend = 0.002). Factors associated with a decreased likelihood of dose reduction were higher annual clinician volume of stages I-IIIA breast cancer patients (FCDP < 90%: PR≥30 vs ≤15 patients : 0.64, p-trend = 0.03; ARDI < 90%: PR≥30 vs ≤15 patients : 0.76, p-trend = 0.01), higher treatment facility annual volume of stages I-IIIA breast cancer patients (ARDI < 90%: PR≥200 vs <75 patients : 0.85, p-trend = 0.03), and a larger practice size (FCDP < 90%: PR≥10 vs ≤5 oncologists : 0.53, p-trend = 0.02). CONCLUSIONS: Clinician- and facility-level factors were associated with chemotherapy dose reductions. Practice-level changes, such as increasing breast cancer patient volumes and practice size, may support optimal dosing practices.
Nugent SM, Ashare RL, Cullen J
… +12 more, Haque R, Hu J, Lee RT, Meghani SH, Potosky AL, Reboussin BA, Romero-Sandoval A, Wagoner KG, Wang Y, Worster B, Filipski KK, Freedman AN
J Natl Cancer Inst
· 2026 Feb · PMID 41746285
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Cannabis use for symptom management among patients with cancer has increased significantly in recent years, with many reporting benefits for pain, anxiety, sleep, nausea, appetite as well as other symptoms. However, rigo...Cannabis use for symptom management among patients with cancer has increased significantly in recent years, with many reporting benefits for pain, anxiety, sleep, nausea, appetite as well as other symptoms. However, rigorous prospective data on the potential benefits and harms of cannabis use in this population are lacking. This Commentary describes a United States National Cancer Institute (NCI)-led initiative addressing this research gap by supporting five prospective observational studies evaluating the benefits and harms of cannabis use among a large, heterogeneous samples of patients with cancer undergoing active systemic treatment. We provide an overview of each study, including cancer type, treatment modalities, inclusion/exclusion criteria, data collection methods, and both patient-reported and cancer-related outcomes.
Woolpert KM, Kjærsgaard A, Schapira L
… +2 more, Toft Sørensen H, Cronin-Fenton D
J Natl Cancer Inst
· 2026 Feb · PMID 41741377
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BACKGROUND: Pain is a common long-lasting effect of breast cancer treatment. However, adequate pain management can be a challenge in survivorship care. Opioids remain important for acute and chronic pain, yet prolonged u...BACKGROUND: Pain is a common long-lasting effect of breast cancer treatment. However, adequate pain management can be a challenge in survivorship care. Opioids remain important for acute and chronic pain, yet prolonged use carries risks of dependence and overdose. Denmark has historically had high opioid prescription rates, but the duration, strength, and intensity of use among breast cancer survivors is not well described. METHODS: We conducted a nationwide registry-based study of 84,610 Danish women diagnosed with stage I-III breast cancer (1997 - 2020). We described temporal trends in opioid-prescribing and examined associations between sociodemographic and clinical characteristics and five potentially harmful opioid-related outcomes after breast cancernew and prolonged use, long-term use, long-term strong use, concurrent use with sedative-hypnotics, and diagnosed substance-related disorder or overdose. RESULTS: Within one year of diagnosis, 18% of women filled at least one opioid prescription; this proportion declined steadily after 2015. Codeine, the most common initial opioid in the late 1990s, was gradually replaced by tramadol, morphine, and oxycodone. Across the cohort, 6.1% had long-term use, 2.0% long-term strong use, 3.6% concurrent opioid and sedative-hypnotic use, and 0.4% developed an substance-related disorder or overdose. Among 74,771 opioid-naïve patients, 1.7% became new and prolonged users. Odds of these opioid-related behaviors were higher among women with socioeconomic hardships, psychiatric morbidity, comorbidity, and advanced disease. DISCUSSION: Opioid use after breast cancer was uncommon and declined over time in Denmark. Nonetheless, social and clinical disparities persisted, highlighting the importance of survivorship care that balances safe prescribing with adequate pain management.
Jiang C, Rosenberg PS, Star J
… +4 more, Bandi P, Bednarczyk RA, Jemal A, Sung H
J Natl Cancer Inst
· 2026 Feb · PMID 41730310
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BACKGROUND: Despite well-documented national declines in cervical cancer incidence among young women following human papillomavirus (HPV) vaccine implementation, state-level data remain limited. METHODS: Using the US Can...BACKGROUND: Despite well-documented national declines in cervical cancer incidence among young women following human papillomavirus (HPV) vaccine implementation, state-level data remain limited. METHODS: Using the US Cancer Statistics Database, differences in cervical cancer incidence rates for women aged 20-31 between the pre-vaccination (2000-2005) and vaccination era (2016-2021) were estimated using rate ratios (RRs) across 47 states and the District of Columbia (DC). Associations between HPV vaccination rates from the National Immunization Survey-Teen and RRs were examined using Spearman's rank test and linear regression models, adjusted for screening rates from the Behavioral Risk Factor Surveillance System. RESULTS: Nationwide, cervical cancer incidence rates declined by 27% (RR = 0.73, 95%CI:0.70 to 0.75) during the vaccination era, from 5.1 to 3.7 per 100,000. Reductions exceeded 50% in DC (RR = 0.48, 95%CI : 0.15 to 0.81), Rhode Island (RR = 0.48, 95%CI : 0.21 to 0.76), Michigan (RR = 0.48, 95%CI : 0.38 to 0.57), and Hawaii (RR = 0.49, 95%CI : 0.21 to 0.78), with 28 additional states achieving statistically significant reductions of 15-50%. Ten states showed slower decreases (<15%). Notably, progress was lacking in Vermont (RR = 1.11; 95%CI : 0.21 to 2.00), West Virginia (RR = 1.09; 95%CI : 0.63 to 1.56), Idaho (RR = 0.97; 95%CI : 0.42-1.52), Arkansas (RR = 0.96; 95%CI : 0.64 to 1.29), and Alabama (RR = 0.96; 95%CI : 0.71 to 1.21). Across states, higher vaccination rates were correlated with lower RRs (i.e., faster decline) (rho=-0.42, P = .0027). Every 10% increase in vaccination rates was associated with an 11.5% (95%CI : -17.2% to -5.4%) reduction in RRs, adjusted for screening rates. CONCLUSIONS: Declines in cervical cancer incidence in young women during the HPV vaccination era varied substantially by state, aligning with HPV vaccination rates.
Danielsson O, Dar H, Nordenskjöld A
… +8 more, Perez-Tenorio G, Nordenskjöld B, Fornander T, Stål O, Tobin NP, Tutzauer J, Johansson A, Lindström LS
J Natl Cancer Inst
· 2026 Feb · PMID 41712503
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BACKGROUND: Patients with ER-positive breast cancer have a substantial late risk of distant recurrence, but the long-term subtype-specific tamoxifen benefit remains poorly understood. METHODS: Secondary analysis of the S...BACKGROUND: Patients with ER-positive breast cancer have a substantial late risk of distant recurrence, but the long-term subtype-specific tamoxifen benefit remains poorly understood. METHODS: Secondary analysis of the Stockholm Tamoxifen (STO) randomized trials (1976-1997, n = 3930) with 20-year follow-up. FFPE blocks were available for 2250 patients. 952 patients with ER-positive/HER2-negative tumors classified as luminal A (n = 688) and luminal B (n = 264) using Agilent microarrays were analyzed. Patients were randomized to at least 2 years of tamoxifen therapy or no endocrine therapy. Distant recurrence-free interval (DRFI) was assessed by Kaplan-Meier analysis and multivariable Cox proportional-hazards regression. RESULTS: Patients with luminal A tumors had low early risk and modest early benefit from tamoxifen therapy (5-year DRFI treated vs control: 93% vs 89%, absolute difference 4%) that increased over the 20-year follow-up (20-year DRFI: 76% vs 66%, absolute difference 10%), highlighting long-term benefit. In contrast, patients with luminal B tumors had larger early risk and treatment benefit (5-year DRFI: 72% vs 57%, absolute difference 15%), which remained stable over time (20-year DRFI: 55% vs 37%, 18% absolute difference).Multivariable analyses showed that luminal patients benefited from tamoxifen therapy (luminal A adjusted hazard ratio [aHR]=0.57, 95% CI 0.42-0.78 and luminal B aHR = 0.68, 95% CI 0.46-0.99). Patients with favorable tumor characteristics benefited regardless of luminal subtype. CONCLUSIONS: Tamoxifen reduces the long-term risk of distant recurrence in both luminal A and B tumors, although timing of benefit varies by subtype. Even after treatment, patients with luminal tumors have a substantial late risk, highlighting the need for long-term follow-up.
Tickle A, Offman J, North B
… +3 more, Jørgensen SF, Njor S, Sasieni P
J Natl Cancer Inst
· 2026 Jun · PMID 41707694
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BACKGROUND: This study examined whether breast cancer survival improvements with screening are explained solely by detection at early stages and whether mortality can be predicted using stage and diagnosis date alone. ME...BACKGROUND: This study examined whether breast cancer survival improvements with screening are explained solely by detection at early stages and whether mortality can be predicted using stage and diagnosis date alone. METHODS: We compared stage-specific net survival between never-screened, symptomatic ever-screened (past attenders and interval cancers), and screen-detected breast cancer cases in Denmark using individual-level electronic health records from January 1, 2010 to December 31, 2022. Lifetables were generated from women without breast cancer, separately for never-screened and ever-screened women. Age-specific all-cause mortality rates were used to calculate excess mortality in women with breast cancer, which was then transformed into net survival. RESULTS: Of 817 128 women, 32 827 had breast cancer, with 8% presenting as stage III or IV. Survival differences between symptomatic and screen-detected cases were minimal for stages I-III but reached 40% at stage IV, with 5-year net survival for stage IV screen-detected women (74.7%) resembling stage IIIc symptomatic survival in never-screened women (72.6%). Survival from stage IV breast cancer was strongly associated with treatment, with median survival (years) of 4.4-6.0 with surgery, 1.6-2.2 with nonsurgical treatment, and 0.03-0.13 with no treatment; 67% of screen-detected patients received surgery (compared with 23% of never-screened and 27% of symptomatic ever-screened). CONCLUSIONS: Greater survival in screen-detected stage IV cases suggests that breast cancer screening may not have come too late and deserves to be investigated further. Predicting breast cancer mortality using stage at diagnosis and stage-specific survival (without differentiating by route to diagnosis) will underestimate the impact of breast screening on mortality.
Corr BR, Romano KD, Toboni MD
… +11 more, Fuh KC, Han K, Harkenrider MM, Kocherginsky M, Lindwasser OW, Mackay H, Martin LP, Campos SM, Kohn EC, Viswanathan AN, Duska LR
J Natl Cancer Inst
· 2026 Feb · PMID 41706908
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Endometrial cancer (EC) is rising both in incidence and mortality, is involving younger women, and is leading in the US for gynecologic cancer incidence. The application of molecular characterization and targeting treatm...Endometrial cancer (EC) is rising both in incidence and mortality, is involving younger women, and is leading in the US for gynecologic cancer incidence. The application of molecular characterization and targeting treatment to selected molecular types of EC is exemplified by the marked benefit of mismatch repair deficient (dMMR) EC to immune checkpoint inhibitor (ICI) treatment. However, the response to immunotherapy has been less significant in other EC molecular types. We reported previously on the public health relevance of molecular analysis of endometrial cancer types to direct treatment considerations and discussed the limitation in biomarkers predictive of response to immunotherapy or available to examine for treatment selection, outside of mismatch repair deficiency. The current follow-on commentary addresses how new thinking can lead to optimization of immunotherapy applications for endometrial cancer molecular types, how to consider timing and sequencing of immunotherapy with other interventions, and directions for novel immunotherapy combinations. This report outlines key background studies and preclinical observations, directions to overcome inherent resistance, how to leverage ICI to augment clinical response to standard treatments, and considerations for how and when to re-expose patients to ICI treatment(s). The discussions led to potential clinical trial concepts now under development.
Majidi A, Rinaldi S, Truong T
… +2 more, Dossus L, Fournier A
J Natl Cancer Inst
· 2026 Feb · PMID 41706832
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BACKGROUND: Thyroid hormones influence reproductive and metabolic pathways that may affect ovarian cancer development and progression. However, epidemiological evidence is limited and inconsistent. We examined the associ...BACKGROUND: Thyroid hormones influence reproductive and metabolic pathways that may affect ovarian cancer development and progression. However, epidemiological evidence is limited and inconsistent. We examined the association between physician-diagnosed thyroid dysfunction and ovarian cancer risk and survival in a large prospective cohort. METHODS: We included 80,348 women from the E3N cohort who completed at least one biennial questionnaire enquiring about physician-diagnosed thyroid dysfunction (hyperthyroidism or hypothyroidism) between 1992 and 2014. We used Cox regression models with time-varying exposure to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ovarian cancer incidence through 2018 and, among women diagnosed with ovarian cancer, for overall survival through 2024. Models were adjusted for established ovarian cancer risk or prognostic factors. RESULTS: During follow-up (up to 2018), 589 ovarian cancer cases were identified. Overall, pre-diagnostic thyroid dysfunction was not associated with ovarian cancer risk. However, hypothyroidism diagnosed ≥5 years earlier was associated with reduced risk (HR = 0.65, 95% CI = 0.45-0.95) and hyperthyroidism diagnosed ≥5 years earlier and not using levothyroxine was associated with increased risk (HR = 1.70, 95%CI = 1.04-2.78). We found no meaningful association between pre-diagnostic thyroid dysfunction and survival following an ovarian cancer diagnosis. CONCLUSIONS: Hypothyroidism may be associated with decreased ovarian cancer risk, and hyperthyroidism with increased ovarian cancer risk. Neither hyperthyroidism nor hypothyroidism appeared to affect survival. Whether these associations are causal or whether levothyroxine use plays a role in the development of cancer should be investigated further.
Hoang T, Keski-Rahkonen P, Jenab M
… +3 more, Knaze V, Shin A, Park JY
J Natl Cancer Inst
· 2026 Feb · PMID 41706114
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BACKGROUND: Gastric cancer (GC) is often diagnosed at advanced stages, contributing to poor prognosis. Circulating metabolites have emerged as potential biomarkers for GC risk stratification or early detection. We conduc...BACKGROUND: Gastric cancer (GC) is often diagnosed at advanced stages, contributing to poor prognosis. Circulating metabolites have emerged as potential biomarkers for GC risk stratification or early detection. We conducted a systematic review of studies investigating the association between metabolites and GC, including both precancerous and cancerous gastric lesions. METHODS: We comprehensively searched PubMed, Embase, and Web of Science for articles published from 2004 to 2025. Eligible studies assessed endogenous metabolites using mass spectrometry- or nuclear magnetic resonance-based platforms in relation to precancerous gastric lesions, GC or GC subtypes. Data were extracted on study design, biospecimen type, analytical approaches, Helicobacter pylori infection, identified metabolites, and model performance. RESULTS: A total of 52 studies were included, comprising 12 case-only, 31 case-control, five nested case-control, and four cohort studies. Across studies, metabolites reported to differ between GC and non-GC groups and across stages of gastric lesion progression were primarily involved in metabolism of glucose, lipids, amino acids, nucleic acids, and vitamins. Several studies evaluated metabolite-based classification or prediction models, reporting a wide range of performance metrics for distinguishing GC from non-GC conditions and for classifying disease stages. Considerable heterogeneity was observed across studies, limiting direct comparability of findings. CONCLUSIONS: Previous studies have reported associations between metabolites and GC, as well as progression of precancerous lesions, providing insights into gastric carcinogenesis. However, substantial heterogeneity across studies highlights the need for standardized methodological approaches and adjustment for key confounders followed by independent validation and replication in large, well-designed, multi-population studies.