Cancer最新文献

Background

Risk-reducing surgeries are the most effective strategies for cancer prevention in patients with germline pathogenic variants in the BRCA1/BRCA2 genes; these surgeries are associated with early menopause, loss of childbearing potential, and cosmetic effects. The authors assessed women's preferences for tradeoffs related to risk-reducing surgical decision making.

Methods

Carriers of pathogenic mutations in BRCA1/BRCA2 aged 25–50 years without a personal history of breast, ovarian, peritoneal, or tubal cancer were recruited to complete one of four discrete choice surveys based on their age (younger than 40 years or 40 years and older) and BRCA mutation status (BRCA1 or BRCA2). Participants responded to a series of choices between a do-nothing strategy and two profiles representing various effects of surgical options on menopause, childbearing potential (those younger than 40 years only), breast appearance, and 10-year and lifetime risks of breast and ovarian cancer. A conditional logit model was used to quantify participants' choices as a function of surgical options and outcomes.

Results

In total, 298 participants completed the survey. Each cohort younger than <40 years more frequently chose profiles representing risk-reducing salpingo-oophorectomy (RRSO) at age 40 versus 30 years. The cohort aged 40 years and older with BRCA1 mutations favored RRSO at age 40 years but with a 56.6% choice probability of delayed RRSO after ages 35–40 years, as recommended by National Comprehensive Cancer Network guidelines. The cohort aged 40 and older with BRCA2 mutations favored RRSO at age 40, 45, or 50 years fairly equally, with a 33.0% choice probability of guideline-nonconcordant RRSO timing. All cohorts favored mastectomy at younger ages and with reconstruction versus no mastectomy.

Conclusions

These findings demonstrate the heterogeneity of preferences and support individualized discussion of treatment goals relating to risk-reducing surgical planning.

Introduction

Early detection of cancer improves survival following diagnosis. However, routine screening is limited to a few cancer types. Multicancer early detection (MCED) tests could revolutionize cancer screening by simultaneously detecting multiple cancer types. This study evaluates the potential impact of an MCED test on stage shift in the US general population.

Methods

A microsimulation model of 14 solid tumor cancer types that account for nearly 80% of cancer incidence and mortality was developed. The model was calibrated to reproduce annual incidence rates reported in the Surveillance, Epidemiology, and End Results database. Cancer diagnosis could arise from standard-of-care procedures or annual MCED testing. MCED sensitivities were derived from a large, multicenter, prospective, case control study. Ten-year disease progression was simulated for 5 million US adults aged 50 to 84 years. The primary outcome was stage shift resulting from MCED testing.

Results

Over 10 years, supplemental MCED testing led to a 10% increase in Stage I diagnoses, 20% increase in Stage II diagnoses, 34% increase in Stage III diagnoses, and 45% decrease in Stage IV diagnoses, relative to the standard of care alone. The largest absolute reductions in Stage IV diagnoses were in lung (400 vs. 765 per 100,000), colorectal (96 vs. 236), and pancreatic (89 vs. 211) cancer. The largest relative reductions were in cervical (83%), liver (74%), and colorectal (59%) cancer.

Conclusion

MCED testing has the potential to substantially reduce late-stage cancer diagnoses, improve outcomes across multiple cancer types, and address a critical gap in screening.

Background

The risk of subsequent ductal carcinoma in situ (DCIS) or invasive breast cancer (IBC) has been evaluated in either breast after a DCIS diagnosis; this study modeled competing risks of ipsilateral and contralateral DCIS or IBC subtypes by self-reported race.

Methods

A cohort of 198,827 women diagnosed with primary unilateral DCIS between 2000 and 2022 was identified from the US Surveillance, Epidemiology, and End Results tumor registries. Competing subdistributional hazard ratio (sHR) models were used to estimate DCIS or IBC laterality-associated risks overall and for the estrogen receptor (ER+) or progesterone receptor (PR+) overexpressing (ER+/PR+) and ER−PR− expressing tumor subtypes. Cox models were used for subanalysis to estimate the overall risk of a second event (DCIS or IBC).

Results

Within an average of 10 (±6.1) years of follow-up after the initial DCIS, 16,148 women had a subsequent event (25.7% DCIS; 74.3% IBC). Overall, compared with White women, Black women had an elevated risk of IBC for either tumor subtype, whereas Asian and Hispanic women had an elevated risk of ER−PR− IBC. For tumor aggressiveness by laterality, Black women had an elevated IBC risk in either breast for ER−PR− (sHR, 1.82; 95% CI, 1.53–2.17 in the ipsilateral breast; sHR, 1.512; 95% CI, 1.24–1.86 in the contralateral breast), as did Hispanic and Asian women in the ipsilateral breast only (with stronger association vs. ER+/PR+) (p_het = .0001).

Conclusions

These contemporary data reflect treatment patterns since 2000, which show an elevated risk of subsequent breast tumors in either breast among Black women after DCIS.

Background

There are no methods for the early detection of human papillomavirus–driven oropharyngeal squamous cell carcinoma (HPV+OPSCC); however, HPV16 E6 seropositivity has been identified as a promising screening marker. Although people living with HIV have a higher risk of developing HPV+OPSCC, few studies have evaluated the association between HPV16 antibodies and HPV+OPSCC.

Methods

The association between HPV16 seropositivity (L1, E1, E2, E4, E6, and E7) and OPSCC was assessed among 2331 men living with HIV (MLWH) aged ≥40 years who had blood specimens banked within the Tennessee Center for AIDS Research biorepository between 2001 and 2019; some samples were collected before OPSCC diagnosis, and others after. The association between HPV16 seropositivity and OPSCC was analyzed via univariable logistic regression.

Results

One hundred and thirty-five HPV16 E6 seropositive cases and 11 OPSCC cases were identified. HPV16 E6 seropositivity was associated with a 14-fold higher odds of OPSCC (odds ratio [OR], 14.04; 95% CI, 4.23–46.61; p < .001); five of the 11 OPSCC cases were HPV16 E6 seropositive (sensitivity, 45%; 95% CI, 17%–77%) compared to 6% of controls (specificity, 94%; 95% CI, 93%–95%). Seroreactivity against HPV16 E1 (OR, 7.14; 95% CI, 1.52–33.67; p = .013), HPV16 E2 (OR, 16.43; 95% CI, 4.94–54.65; p < .001), and HPV16 E7 (OR, 13.84; 95% CI, 3.99–48.11; p < .001) was also significantly associated with OPSCC. HPV16 E6 antibodies were detectable up to 9 years before and 19 years after OPSCC diagnosis.

Conclusions

Among MLWH, HPV16 E6 antibodies are strongly associated with OPSCC, yet point estimates of the sensitivity and specificity of HPV16 E6 antibodies for OPSCC were lower compared to studies in populations without HIV.

Background

Prognostication in pediatric and young adult osteosarcoma is typically limited to metastatic status at diagnosis and tumor necrosis after chemotherapy. Despite a complex genomic landscape, few molecular biomarkers are used clinically. This study evaluates the prognostic relevance of MYC amplification and MYC protein expression.

Methods

This study analyzed 105 patients with high-grade osteosarcoma. MYC copy number was assessed via targeted sequencing, and MYC protein expression was assessed via immunohistochemistry H score. Amplification (AMP) was defined as >7 copies; high expression (EXP) was defined as an H score of >150. Correlation between AMP and EXP was calculated, and overall survival (OS) was analyzed with Kaplan–Meier and Cox models.

Results

Among the 105 patients (42% female; median age, 14 years; interquartile range, 11–17 years), 16% had AMP, 22% had high EXP, and 8% had both AMP and high EXP. MYC copy number positively correlated with protein expression (r = 0.53; p < .0001). With accounting for metastatic status, AMP and high EXP had lower OS (AMP vs. non-AMP: 3-year OS, 27% vs. 74%; adjusted hazard ratio [HR], 3.4; high EXP vs. low EXP: 35% vs. 77%; adjusted HR, 4.9; both p < .0001). Patients with both AMP and high EXP had markedly lower survival compared to those with non-AMP and low EXP (3-year OS, 0% vs. 79%; adjusted HR, 17.7; p < .0001).

Conclusions

MYC amplification and high protein expression both independently and concurrently predict poor survival in pediatric and young adult osteosarcoma, beyond metastatic status. Incorporating MYC status into risk stratification may enhance prognostic accuracy and inform targeted therapeutic development.

Background

The relapse after chimeric antigen receptor (CAR) T-cell therapy remains a critical challenge, and the optimal timing and treatment strategies for CAR T urgently need to be explored. Autologous hematopoietic stem cell transplantation (auto-HSCT) demonstrates comparable leukemia-free survival (LFS) and overall survival (OS) in patients who rapidly achieve MRD-negative complete remission (CR) compared with allogeneic HSCT (allo-HSCT). Thus, combining CAR T cells with auto-HSCT may represent a promising treatment strategy.

The trial registration is ClinicalTrials.gov identifier NCT05470777.

Methods

This phase 2 trial evaluated the safety and efficacy of sequential CD22/CD19 CAR T cells combined with an auto-HSCT “sandwich” strategy in patients with Philadelphia chromosome–negative (Ph-negative) B-cell acute lymphoblastic leukemia (B-ALL), including adolescents and young adults (AYA) as well as adults who were unable or declined to allo-HSCT. The primary and secondary end points were OS and LFS, respectively.

The trial registration is ClinicalTrials.gov identifier NCT05470777.

Results

At a median follow-up of 28 months, the median OS and LFS were not reached. The 2-year OS and LFS rates were 97% (95% confidence interval [CI], 90%–100%) and 72% (95% CI, 58%–90%), respectively. All 35 patients who completed the sandwich strategy survived. Continuous MRD-negative CR rates after the second CAR T-cell infusion were 80% by multiparameter flow cytometry and 70% by next-generation sequencing of immunoglobulin H rearrangements. OS and LFS did not differ between poor and standard genetic risk groups. Compared with the allo-HSCT external control group, the sandwich strategy showed improved OS and comparable LFS. No cases of immune effector cell–associated neurotoxicity syndrome or severe cytokine release syndrome were observed.

The trial registration is ClinicalTrials.gov identifier NCT05470777.

Conclusion

The CD22/CD19 CAR T-cell and auto-HSCT sandwich strategy represents a promising approach for the treatment of Ph-negative B-ALL in AYA and adult patients, offering high efficacy and a favorable safety profile.

The trial registration is ClinicalTrials.gov identifier NCT05470777.