JNCI Journal of the National Cancer Institute最新文献

Background: The National Comprehensive Cancer Network considers "baseline staging" (whole body computed tomography or positron emission tomography scans with or without brain magnetic resonance imaging scans) for all patients with asymptomatic melanoma who had a positive sentinel lymph node biopsy result. The true yield of these workups is unknown.

Methods: We created cohorts of adult patients with malignant melanoma using the National Cancer Database (2012-2020) to mimic 3 common scenarios: 1) clinically node-negative disease, with positive sentinel lymph node biopsy results; 2) clinically node-negative disease, with negative sentinel lymph node biopsy results; and 3) clinically node-positive disease, with confirmed lymph node metastases. Multivariable regression, supervised decision trees, and nomograms were constructed to assess the risk of metastases based on key features.

Results: In total, 10 371 patients were in scenario 1, 55 172 were in scenario 2, and 4012 were in scenario 3. The proportion of patients with any metastatic disease (brain metastases) were as follows: 1.4% (0.3%) in scenario 1, 0.3% (<0.1%) in scenario 2, and 11.6% (1.6%) in scenario 3. On multivariable regression, Breslow depth greater than 4, ulceration, and lymphovascular invasion were associated with greater risk of metastatic disease. A supervised decision tree for patients in scenarios 1 and 2 found that the only groups with more than 2% risk of metastases were groups with T4 tumors or T2/T3 tumors with ulceration and lymphovascular invasion. Most groups had a negligible risk (<0.1%) of brain metastases.

Conclusion: This study is the first large analysis to guide the use of imaging for cutaneous melanoma. Among patients with clinically node negative disease, metastatic disease is uncommon, and brain metastases are exceedingly rare. Further investigation could promote a tailored approach to metastatic workups guided by individual risk factors.

Background: Early-onset cancer (diagnosed under age 50) generally manifests as an aggressive disease phenotype. The association between healthy lifestyle and early-onset cancer and whether it varies by common genetic variants remains unclear.

Methods: We analyzed a prospective cohort of 66 308 participants who were under age 50 and free of cancer at baseline in the UK Biobank. Using Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for early-onset total and breast cancer based on sex-specific composite total cancer polygenic risk scores (PRSs), a breast cancer-specific PRS, and sex-specific health-associated lifestyle scores (HLSs).

Results: In multivariable-adjusted analyses with 2-year latency, higher genetic risk (highest vs lowest tertile of PRS) was associated with significantly increased risks of early-onset total cancer in females (HR, 95% CI = 1.83, 1.49 to 2.26) and males (2.03, 1.51 to 2.73) as well as early-onset breast cancer in females (3.06, 2.20 to 4.26). An unfavorable lifestyle (highest vs lowest category of HLS) was associated with higher risk of total cancer and breast cancer in females across genetic risk categories; the association with total cancer and breast cancer was stronger in the highest genetic risk category than the lowest: HRs (95% CIs) were 1.55 (1.12 to 2.14) and 1.69 (1.11 to 2.57) in the highest genetic risk category and 1.03 (0.64 to 1.67) and 0.81 (0.36 to 1.85) in the lowest.

Conclusions: Genetic and lifestyle factors were independently associated with early-onset total and breast cancer risk. Individuals with a high genetic risk may benefit more from adopting a healthy lifestyle in preventing early-onset cancer.

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.