JNCI Journal of the National Cancer Institute最新文献

Background: The American Cancer Society recommends physicians inform average-risk women about endometrial cancer risk on reaching menopause, but new diagnoses are rising fastest in women aged younger than 50 years. Educating these younger women about endometrial cancer risks requires knowledge of risk factors. However, endometrial cancer in young women is rare and challenging to study in single study populations.

Methods: We included 13 846 incident endometrial cancer patients (1639 aged younger than 50 years) and 30 569 matched control individuals from the Epidemiology of Endometrial Cancer Consortium. We used generalized linear models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 6 risk factors and endometrial cancer risk. We created a risk score to evaluate the combined associations and population attributable fractions for these factors.

Results: In younger and older women, we observed positive associations with body mass index and diabetes and inverse associations with age at menarche, oral contraceptive use, and parity. Current smoking was associated with reduced risk only in women aged 50 years and older (Phet < .01). Body mass index was the strongest risk factor (OR≥35 vs<25 kg/m2 = 5.57, 95% CI = 4.33 to 7.16, for ages younger than 50 years; OR≥35 vs<25 kg/m2 = 4.68, 95% CI = 4.30 to 5.09, for ages 50 years and older; Phet = .14). Possessing at least 4 risk factors was associated with approximately ninefold increased risk in women aged younger than 50 years and approximately fourfold increased risk in women aged 50 years and older (Phet < .01). Together, 59.1% of endometrial cancer in women aged younger than 50 years and 55.6% in women aged 50 years and older were attributable to these factors.

Conclusions: Our data confirm younger and older women share common endometrial cancer risk factors. Early educational efforts centered on these factors may help mitigate the rising endometrial cancer burden in young women.

Background: Standard neoadjuvant chemotherapy for locally advanced esophageal or gastroesophageal junction squamous cancer, 5-fluorouracil plus platinum, is toxic and logistically challenging; alternative regimens are needed.

Methods: This was a phase III randomized open-label noninferiority trial at Tata Memorial Center, India, in resectable locally advanced esophageal or gastroesophageal junction squamous cancer. Patients were randomly assigned 1:1 to 3 cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin area under the curve 6) with paclitaxel 175 mg/m2 (day 1) or 5-fluorouracil 1000 mg/m2 continuous infusion (days 1-4), followed by surgery.

Results: Between August 2014 and June 2022, we enrolled 420 patients; 210 to each arm. Statistically significantly more patients on paclitaxel plus platinum (n =194, 92.3%) received all 3 chemotherapy cycles than on 5-fluorouracil with platinum (n = 170, 85.9%; P = .009). 5-fluorouracil plus platinum caused more grade 3 or higher toxicities (n = 124, 69.7%) than paclitaxel plus platinum (n = 97, 51.9%; P = .001). Surgery was performed in 131 (62.4%) patients on 5-fluorouracil plus platinum vs 139 (66.2%) on paclitaxel plus platinum (P = .415). Paclitaxel plus platinum resulted in higher pathologic primary tumor clearance (n = 33, 25.8%, vs n = 17, 15%; P = .04) and pathologic complete responses in 21.9% compared with 12.4% from 5-fluorouracil plus platinum (P = .053). Median overall survival was 27.5 months (95% confidence interval [CI] = 18.6 to 43.5 months) from paclitaxel plus platinum, which was noninferior to 27.1 months (95% CI = 18.8 to 40.7 months) from 5-fluorouracil plus platinum (hazard ratio [HR] = 0.89, 95% CI = 0.72 to 1.09; P = .346).

Conclusion: Neoadjuvant paclitaxel plus platinum chemotherapy is safer and results in similar R0 resections, higher pathologic tumor clearance and noninferior survival compared with 5-fluorouracil plus platinum. Paclitaxel plus platinum should replace 5-fluorouracil plus platinum as neoadjuvant chemotherapy for resectable locally advanced esophagealor gastroesophageal junction squamous cancer.

Clinical trials registry india number: CTRI/2014/04/004516.