JNCI Journal of the National Cancer Institute最新文献

The prognosis of a patient with a primary cutaneous melanoma is known to be related to the Breslow thickness of their tumor. This study sought to determine long-term (30-year) survival rates for the four AJCC 8th Edition T-categories by analyzing Australian registry data for 210,042 melanoma patients diagnosed from 1982-2014. The 30-year incidence rates of death due to melanoma and non-melanoma causes (with 95% confidence intervals) were 7.1% (CI 6.9-7.3%) and 32.8% (CI 32.3-33.3%), respectively. For T2 melanomas, the corresponding rates were 21.6% (CI 21.0-22.3%) and 35.6% (CI 34.7-36.6%), for T3 melanomas 34.2% (CI 33.4-35.1%) and 39.6% (CI 38.5-40.8%), and for T4 melanomas 44.3% (CI 43.2-45.3%) and 39.6% (CI 38.3-41.0%). A plateau in melanoma-related deaths occurred in T4 patients after 20 years but there were ongoing melanoma-related deaths for the other T-categories beyond 30 years. A progressive rise in the risk of death from other causes occurred across all T-categories.

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

Methods: We included 13,846 incident EC patients (1,639 < 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 EC risk. We created a risk score to evaluate the combined associations and population attributable fractions of these factors.

Results: In younger and older women, we observed positive associations with BMI and diabetes, and inverse associations with age at menarche, oral contraceptive use, and parity. Current smoking was associated with reduced risk only in women ≥50 years (PHet<0.01). BMI was the strongest risk factor [OR≥35 vs <25 kg/m2=5.57 (95% CI:4.33-7.16) for <50 years; OR≥35 vs <25 kg/m2=4.68 (95% CI : 4.30-5.09) for ≥50 years; PHet=0.14]. Possessing ≥4 risk factors was associated with ∼9-fold increased risk in women <50 years and ∼4-fold increased risk in women ≥50 years (PHet<0.01). Together, 59.1% of ECs in women <50 and 55.6% in women ≥50 were attributable to these factors.

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

Improvements in cancer prevention and control are poised to be main contributors in reducing the burden of cancer in the US. We quantify top opportunities to accelerate progress using projected life years gained (LYG) and deaths averted as measures. We project that over the next 25 years, realistic gains from tobacco control can contribute 0.4 to 17 million additional LYG per intervention and 8.4 million additional LYG from improving uptake of screening programs over the lifetime of 25 annual cohorts. Additional opportunities include addressing modifiable risk factors (excess weight, alcohol consumption), improving methods to prevent or treat oncogenic infections, and reducing cancer health disparities. Investment is needed in the pipeline of new preventive agents and technologies for early detection to continue progress. There is also a need for additional research to improve the access to and uptake of existing and emerging interventions for cancer prevention and control and to address health disparities. These gains are undeniably within our power to realize for the US population.

Introduction: The NCCN considers "baseline staging" (whole body CT or PET scan +/- brain MRI) for all asymptomatic melanoma patients with a positive sentinel lymph node biopsy. The true yield of these workups is unknown.

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

Results: 10,371 patients were SLNB[+], 55,172 were SLNB[-], and 4,012 were cN[+] and pN[+]. The proportion of patients with any metastatic disease (brain metastases) were as follows: SLNB[+]: 1.4% (0.3%); SLNB[-] 0.3% (<0.1%); cN[+] and pN[+] 11.6% (1.6%). On multivariable regression, Breslow depth > 4, ulceration, and lymphovascular invasion were associated with greater risk of metastatic disease. A supervised decision tree for SLNB[+] and SLNB[-] patients found the only groups with >2% risk of metastases were T4 tumors or T2/T3 tumors with ulceration and LVI. Most groups had a negligible risk (<0.1%) of brain metastases.

Conclusion: This is the first large analysis to guide the use of imaging for cutaneous melanoma. Among clinically node negative patients, 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.

Purpose: Standard neoadjuvant chemotherapy (NACT) for locally advanced esophageal/gastroesophageal junction squamous cancer (LAEGSC), 5-fluorouracil (5FU)+platinum, is toxic and logistically challenging; alternative regimens are needed.

Patients and methods: Phase III randomized open-label non-inferiority trial at Tata Memorial Center, India, in resectable LAEGSC. Patients were randomized 1:1 to three cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin AUC 6) with paclitaxel 175 mg/m2 (day 1) or 5FU 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. Significantly more patients on paclitaxel + platinum (194 (92.3%)] received all 3 chemotherapy cycles than on 5FU+platinum (170 [85.9%]), P = .009. 5FU + platinum caused more grade ≥ 3 toxicities (124 [69.7%]) than paclitaxel + platinum (97 [51.9%]), P = .001. Surgery was performed in 131 (62.4%) patients on 5FU + platinum vs 139 (66.2%) on paclitaxel + platinum, P = .415. Paclitaxel + platinum resulted in higher pathologic primary tumor clearance (33 [25.8%]) vs 17 [15%]; P = .04), and pathologic complete responses in 21.9% compared to 12.4% from 5FU + platinum, P = .053. Median OS was 27.5 months (95% CI, 18.6-43.5) from paclitaxel + platinum, which was non-inferior to 27.1 months (95% CI, 18.8-40.7) from 5FU + platinum; HR, 0.89 (95% CI, 0.72-1.09); P = .346.

Conclusion: Neoadjuvant paclitaxel + platinum chemotherapy is safer, and results in similar R0 resections, higher pathologic tumor clearance and non-inferior survival, compared to 5FU + platinum. Paclitaxel + platinum should replace 5FU + platinum as NACT for resectable LAEGSC.

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

Background: The Affordable Care Act (ACA) increased private nonemployer health insurance options, expanded Medicaid eligibility, and provided preexisting health condition protections. We evaluated insurance coverage among long-term adult survivors of childhood cancer pre- and post-ACA implementation.

Methods: Using the multicenter Childhood Cancer Survivor Study, we included participants from 2 cross-sectional surveys: pre-ACA (2007-2009; survivors: n = 7505; siblings: n = 2175) and post-ACA (2017-2019; survivors: n = 4030; siblings: n = 987). A subset completed both surveys (1840 survivors; 646 siblings). Multivariable regression models compared post-ACA insurance coverage and type (private, public, uninsured) between survivors and siblings and identified associated demographic and clinical factors. Multinomial models compared gaining and losing insurance vs staying the same among survivors and siblings who participated in both surveys.

Results: The proportion with insurance was higher post-ACA (survivors pre-ACA 89.1% to post-ACA 92.0% [+2.9%]; siblings pre-ACA 90.9% to post-ACA 95.3% [+4.4%]). Post-ACA insurance increase in coverage was higher among those aged 18-25 years (survivors: +15.8% vs +2.3% or less ages 26 years and older; siblings +17.8% vs +4.2% or less ages 26 years and older). Survivors were more likely to have public insurance than siblings post-ACA (18.4% vs 6.9%; odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.1 to 2.6). Survivors with severe chronic conditions (OR = 4.7, 95% CI = 3.0 to 7.3) and those living in Medicaid expansion states (OR = 2.4, 95% CI = 1.7 to 3.4) had increased odds of public insurance coverage post-ACA. Among the subset completing both surveys, low- and mid-income survivors (<$40 000 and <$60 000, respectively) experienced insurance losses and gains in reference to highest household income survivors (≥$100 000), relative to odds of keeping the same insurance status.

Conclusions: Post-ACA, more childhood cancer survivors and siblings had health insurance, although disparities remain in coverage.

Background: Targeted cancer drugs (TCDs) have revolutionized oncology but vary in clinical benefit and patient out-of-pocket (OOP) costs. The American Society of Clinical Oncology (ASCO) Value Framework uses survival, toxicity, and symptom palliation data to quantify the net health benefit (NHB) of cancer drugs. We evaluated associations between NHB, uptake, and spending on oral TCDs.

Methods: We conducted a retrospective cohort study of patients aged 18-64 years with an incident oral TCD pharmacy claim in 2012-2020 in a nationwide deidentified commercial claims dataset. TCDs were categorized as having high (>60), medium (40-60), and low (<40) NHB scores. We plotted the uptake of TCDs by NHB category and used standard descriptive statistics to evaluate patient OOP and total spending. Generalized linear models evaluated the relationship between spending and TCD NHB, adjusted for cancer indication.

Results: We included 8524 patients with incident claims for 8 oral TCDs with 9 first-line indications in advanced melanoma, breast, lung, and pancreatic cancer. Medium- and high-NHB TCDs accounted for most TCD prescriptions. Median OOP spending was $18.78 for the first 28-day TCD supply (interquartile range [IQR] = $0.00-$87.57); 45% of patients paid $0 OOP. Median total spending was $10 118.79 (IQR = $6365.95-$10 600.37) for an incident 28-day TCD supply. Total spending increased $1083.56 for each 10-point increase in NHB score (95% confidence interval = $1050.27 to $1116.84, P < .01 for null hypothesis H0 = $0).

Conclusion: Low-NHB TCDs were prescribed less frequently than medium- and high-NHB TCDs. Total spending on oral TCDs was high and positively associated with NHB. Commercially insured patients were largely shielded from high OOP spending on oral TCDs.

Background: Anal cancer risk is elevated among people with HIV. Recent anal cancer incidence patterns among people with HIV in the United States and Canada remain unclear. It is unknown how the incidence patterns may evolve.

Methods: Using data from the North American AIDS Cohort Collaboration on Research and Design, we investigated absolute anal cancer incidence and incidence trends nationally in the United States and Canada and in different US regions. We further estimated relative risk compared with people without HIV, relative risk among various subgroups, and projected future anal cancer burden among American people with HIV.

Results: Between 2001 and 2016 in the United States, age-standardized anal cancer incidence declined 2.2% per year (95% confidence interval = ‒4.4% to ‒0.1%), particularly in the Western region (‒3.8% per year, 95% confidence interval = ‒6.5% to ‒0.9%). In Canada, incidence remained stable. Considerable geographic variation in risk was observed by US regions (eg, more than 4-fold risk in the Midwest and Southeast compared with the Northeast among men who have sex with men who have HIV). Anal cancer risk increased with a decrease in nadir CD4 cell count and was elevated among those individuals with opportunistic illnesses. Anal cancer burden among American people with HIV is expected to decrease through 2035, but more than 70% of cases will continue to occur in men who have sex with men who have HIV and in people with AIDS.

Conclusion: Geographic variation in anal cancer risk and trends may reflect underlying differences in screening practices and HIV epidemic. Men who have sex with men who have HIV and people with prior AIDS diagnoses will continue to bear the highest anal cancer burden, highlighting the importance of precision prevention.

Implementation of primary human papillomavirus (HPV) testing has been slow in the United States perhaps because of concerns of decreased sensitivity compared with concurrent HPV and cytology testing ("cotesting"). We used the National Breast and Cervical Cancer Early Detection Program and the Kaiser Permanente of Northern California cohort to quantify potential trade-offs with primary HPV compared with cotesting in 4 US populations with differing precancer or cancer prevalence. In all settings, cotesting required more lab tests and more colposcopies compared with primary HPV testing. Additional cervical intraepithelial neoplasia grade 3 or cancer immediately detected from cotesting vs primary HPV decreased with decreasing population-average cervical intraepithelial neoplasia grade 3 or cancer prevalence from 71 per 100 000 screened among never or rarely screened individuals in the National Breast and Cervical Cancer Early Detection Program (prevalence = 1212 per 100 000) to 4 per 100 000 screened among individuals with prior HPV-negative results in Kaiser Permanente of Northern California (prevalence = 86 per 100 000). These data suggest that cotesting confer an unfavorable benefit-to-harm ratio over primary HPV testing.