JNCI Cancer Spectrum最新文献

Background: Incidence of early-onset colorectal cancer (EOCRC) has increased globally in recent decades. We examined EOCRC incidence trends worldwide for potential cohort effects, defined as changes associated with time of birth (e.g., early-life exposure to carcinogens), and period effects, defined as changes associated with calendar periods (e.g., screening programs).

Methods: We obtained long-term incidence data for EOCRC diagnosed at age 20-49 through Year 2012 for 35 countries in the Cancer Incidence in Five Continents database. We used a smoothing method to help compare cohort and period trends of EOCRC, and used an age-period-cohort model to estimate cohort and period effects.

Results: Cohort effects had a more dominant role than period effects in the EOCRC incidence in Shanghai (China), the United Kingdom, Australia, New Zealand, Canada, the United States, and Osaka (Japan). The smoothed trends show the specific birth cohorts when EOCRC began to increase: the 1940s-1950s birth cohorts in the United States; the 1950s-1960s birth cohorts in other western countries; the 1960s birth cohorts in Osaka (Japan); and the 1970s-1980s birth cohorts in Shanghai (China). Such increases occurred earlier for early-onset cancers of the rectum than the colon. For the other countries, the results were less clear.

Conclusions: Recent birth cohorts may have been exposed to risk factors different than earlier cohorts, contributing to increased EOCRC incidence in several developed countries or regions in the West and Asia. Such increases began in earlier birth cohorts in western countries than in developed regions of Asia.

Background: Surrogate endpoints for overall survival in patients with resectable non-small cell lung cancer receiving neoadjuvant therapy are needed to provide earlier treatment outcome indicators and accelerate drug approval. This study's main objectives were to investigate the association among pathological complete response, major pathological response, event-free survival and overall survival and to determine whether treatment effects on pathological complete response and event-free survival correlate with treatment effects on overall survival.

Methods: A comprehensive systematic literature review was conducted to identify neoadjuvant studies in resectable non-small cell lung cancer. Analysis at the patient level using frequentist and Bayesian random effects (hazard ratio [HR] for overall survival or event-free survival by pathological complete response or major pathological response status, yes vs no) and at the trial level using weighted least squares regressions (hazard ratio for overall survival or event-free survival vs pathological complete response, by treatment arm) were performed.

Results: In both meta-analyses, pathological complete response yielded favorable overall survival compared with no pathological complete response (frequentist, 20 studies and 6530 patients: HR = 0.49, 95% confidence interval = 0.42 to 0.57; Bayesian, 19 studies and 5988 patients: HR = 0.48, 95% probability interval = 0.43 to 0.55) and similarly for major pathological response (frequentist, 12 studies and 1193 patients: HR = 0.36, 95% confidence interval = 0.29 to 0.44; Bayesian, 11 studies and 1018 patients: HR = 0.33, 95% probability interval = 0.26 to 0.42). Across subgroups, estimates consistently showed better overall survival or event-free survival in pathological complete response or major pathological response compared with no pathological complete response or no major pathological response. Trial-level analyses showed a moderate to strong correlation between event-free survival and overall survival hazard ratios (R2 = 0.7159) but did not show a correlation between treatment effects on pathological complete response and overall survival or event-free survival.

Conclusion: There was a strong and consistent association between pathological response and survival and a moderate to strong correlation between event-free survival and overall survival following neoadjuvant therapy for patients with resectable non-small cell lung cancer.

Background: Long-term survivors of childhood cancer face elevated risk for financial hardship. We evaluate whether childhood cancer survivors live in areas of greater deprivation and the association with self-reported financial hardships.

Methods: We performed a cross-sectional analysis of data from the Childhood Cancer Survivor Study between 1970 and 1999 and self-reported financial information from 2017 to 2019. We measured neighborhood deprivation with the Area Deprivation Index (ADI) based on current zip code. Financial hardship was measured with validated surveys that captured behavioral, material and financial sacrifice, and psychological hardship. Bivariate analyses described neighborhood differences between survivors and siblings. Generalized linear models estimated effect sizes between ADI and financial hardship adjusting for clinical factors and personal socioeconomic status.

Results: Analysis was restricted to 3475 long-term childhood cancer survivors and 923 sibling controls. Median ages at time of evaluation was 39 years (interquartile range [IQR] = 33-46 years and 47 years (IQR = 39-59 years), respectively. Survivors resided in areas with greater deprivation (ADI ≥ 50: 38.7% survivors vs 31.8% siblings; P < .001). One quintile increases in deprivation were associated with small increases in behavioral (second quintile, P = .017) and psychological financial hardship (second quintile, P = .009; third quintile, P = .014). Lower psychological financial hardship was associated with individual factors including greater household income (≥$60 000 income, P < .001) and being single (P = .048).

Conclusions: Childhood cancer survivors were more likely to live in areas with socioeconomic deprivation. Neighborhood-level disadvantage and personal socioeconomic circumstances should be evaluated when trying to assist childhood cancer survivors with financial hardships.

Background: Traditional constraints specify that 700 cc of liver should be spared a hepatotoxic dose when delivering liver-directed radiotherapy to reduce the risk of inducing liver failure. We investigated the role of single-photon emission computed tomography (SPECT) to identify and preferentially avoid functional liver during liver-directed radiation treatment planning in patients with preserved liver function but limited functional liver volume after receiving prior hepatotoxic chemotherapy or surgical resection.

Methods: This phase I trial with a 3 + 3 design evaluated the safety of liver-directed radiotherapy using escalating functional liver radiation dose constraints in patients with liver metastases. Dose-limiting toxicities were assessed 6-8 weeks and 6 months after completing radiotherapy.

Results: All 12 patients had colorectal liver metastases and received prior hepatotoxic chemotherapy; 8 patients underwent prior liver resection. Median computed tomography anatomical nontumor liver volume was 1584 cc (range = 764-2699 cc). Median SPECT functional liver volume was 1117 cc (range = 570-1928 cc). Median nontarget computed tomography and SPECT liver volumes below the volumetric dose constraint were 997 cc (range = 544-1576 cc) and 684 cc (range = 429-1244 cc), respectively. The prescription dose was 67.5-75 Gy in 15 fractions or 75-100 Gy in 25 fractions. No dose-limiting toxicities were observed during follow-up. One-year in-field control was 57%. One-year overall survival was 73%.

Conclusion: Liver-directed radiotherapy can be safely delivered to high doses when incorporating functional SPECT into the radiation treatment planning process, which may enable sparing of lower volumes of liver than traditionally accepted in patients with preserved liver function.

Trial registration: NCT02626312.

Background: Internationally, 20% to 50% of cancer is diagnosed through emergency presentation, which is associated with lower survival, poor patient experience, and socioeconomic disparities, but population-based evidence about emergency diagnosis in the United States is limited. We estimated emergency department (ED) involvement in the diagnosis of cancer in a nationally representative population of older US adults, and its association with sociodemographic, clinical, and tumor characteristics.

Methods: We analyzed Surveillance, Epidemiology, and End Results Program-Medicare data for Medicare beneficiaries (≥66 years old) with a diagnosis of female breast, colorectal, lung, and prostate cancers (2008-2017), defining their earliest cancer-related claim as their index date, and patients who visited the ED 0 to 30 days before their index date to have "ED involvement" in their diagnosis, with stratification as 0 to 7 or 8 to 30 days. We estimated covariate-adjusted associations of patient age, sex, race and ethnicity, marital status, comorbidity score, tumor stage, year of diagnosis, rurality, and census-tract poverty with ED involvement using modified Poisson regression.

Results: Among 614 748 patients, 23% had ED involvement, with 18% visiting the ED in the 0 to 7 days before their index date. This rate varied greatly by tumor site, with breast cancer at 8%, colorectal cancer at 39%, lung cancer at 40%, and prostate cancer at 7%. In adjusted models, older age, female sex, non-Hispanic Black and Native Hawaiian or Other Pacific Islander race, being unmarried, recent year of diagnosis, later-stage disease, comorbidities, and poverty were associated with ED involvement.

Conclusions: The ED may be involved in the initial identification of cancer for 1 in 5 patients. Earlier, system-level identification of cancer in non-ED settings should be prioritized, especially among underserved populations.

Background: Industry payments to US cancer centers are poorly understood.

Methods: US National Cancer Institute (NCI)-designated comprehensive cancer centers were identified (n = 51). Industry payments to NCI-designated comprehensive cancer centers from 2014 to 2021 were obtained from Open Payments and National Institutes of Health (NIH) grant funding from NIH Research Portfolio Online Reporting Tools (RePORT). Given our focus on cancer centers, we measured the subset of industry payments related to cancer drugs specifically and the subset of NIH funding from the NCI.

Results: Despite a pandemic-related decline in 2020-2021, cancer-related industry payments to NCI-designated comprehensive cancer centers increased from $482 million in 2014 to $972 million in 2021. Over the same period, NCI research grant funding increased from $2 481  million to $2 724  million. The large majority of nonresearch payments were royalties and licensing payments.

Conclusion: Industry payments to NCI-designated comprehensive cancer centers increased substantially more than NCI funding in recent years but were also more variable. These trends raise concerns regarding the influence and instability of industry payments.

Background: Nintedanib is a tyrosine kinase inhibitor with efficacy in bevacizumab-resistant colorectal cancer models. This phase I/II study evaluated the recommended phase II dose and efficacy of nintedanib and capecitabine in refractory metastatic colorectal cancer.

Methods: Key eligibility criteria included refractory metastatic colorectal cancer and ECOG performance status of 1 or lower. The primary endpoint was 18-week progression-free survival (PFS). A 1-sided binomial test (at α = .1) compared the observed 18-week PFS with a historic control of .25.

Results: Forty-two patients were enrolled, including 39 at the recommended phase II dose. The recommended phase II dose was established to be nintedanib 200 mg by mouth twice daily and capecitabine 1000 mg/m2 by mouth twice daily. The protocol was evaluated for efficacy in 36 patients. The 18-week PFS was 42% (15/36 patients; P = .0209). Median PFS was 3.4 mo. Median overall survival was 8.9 mo. Sixteen (44%) patients experienced a grade 3/4 adverse event, most commonly fatigue (8%), palmoplantar erythrodysesthesia (8%), aspartate aminotransferase elevation (6%), asthenia (6%), pulmonary embolus (6%), and dehydration (6%). Osteopontin levels at cycle 1, day 1 and cycle 3, day 1 as well as ΔCCL2 levels correlated to disease control at 18 weeks.

Conclusions: The combination of nintedanib and capecitabine is well tolerated. Clinical efficacy appears to be superior to regorafenib or tipiracil hydrochloride monotherapy. Further investigation of similar combinations is warranted.

Clinicaltrials.gov identifier: NCT02393755.

The COVID-19 pandemic caused widespread disruptions in cancer care. We hypothesized that the greatest disruptions in diagnosis occurred in screen-detected cancers. We identified patients (≥18 years of age) with newly diagnosed cancer from 2019 to 2020 in the US National Cancer Database and calculated the change in proportion of early-stage to late-stage cancers using a weighted linear regression. Disruptions in early-stage diagnosis were greater than in late-stage diagnosis (17% vs 12.5%). Melanoma demonstrated the greatest relative decrease in early-stage vs late-stage diagnosis (22.9% vs 9.2%), whereas the decrease was similar for pancreatic cancer. Compared with breast cancer, cervical, melanoma, prostate, colorectal, and lung cancers showed the greatest disruptions in early-stage diagnosis. Uninsured patients experienced greater disruptions than privately insured patients. Disruptions in cancer diagnosis in 2020 had a larger impact on early-stage disease, particularly screen-detected cancers. Our study supports emerging evidence that primary care visits may play a critical role in early melanoma detection.

Background: Considering the persistent nature and higher prevalence of insomnia in cancer patients and survivors compared with the general population, there is a need for effective management strategies. This systematic review and meta-analysis aimed to comprehensively evaluate the available evidence for the efficacy of pharmacological and nonpharmacological interventions for insomnia in adult cancer patients and survivors.

Methods: Following the PRISMA guidelines, we analyzed data from 61 randomized controlled trials involving 6528 participants. Interventions included pharmacological, physical, and psychological treatments, with a focus on insomnia severity and secondary sleep and non-sleep outcomes. Frequentist and Bayesian analytical strategies were employed for data synthesis and interpretation.

Results: Cognitive-Behavioral Therapy for Insomnia (CBT-I) emerged as the most efficacious intervention for reducing insomnia severity in cancer survivors and further demonstrated significant improvements in fatigue, depressive symptoms, and anxiety. CBT-I showed a large postintervention effect (g = 0.86; 95% confidence interval [CI] = 0.57 to 1.15) and a medium effect at follow-up (g = 0.55; 95% CI = 0.18 to 0.92). Other interventions such as bright white light therapy, sleep medication, melatonin, exercise, mind-body therapies, and mindfulness-based therapies showed benefits, but the evidence for their efficacy was less convincing compared with CBT-I. Brief Behavioral Therapy for Insomnia showed promise as a less burdensome alternative for patients in active cancer treatment.

Conclusions: CBT-I is supported as a first-line treatment for insomnia in cancer survivors, with significant benefits observed across sleep and non-sleep outcomes. The findings also highlight the potential of less intensive alternatives. The research contributes valuable insights for clinical practice and underscores the need for further exploration into the complexities of sleep disturbances in cancer patients and survivors.

Type II diabetes is associated with cancer risk in the general population but has not been well studied as a risk factor for subsequent malignancies among cancer survivors. We investigated the association between diabetes and subsequent cancer risk among older (66-84 years), 1-year breast cancer survivors within the linked Surveillance Epidemiology and End Results (SEER)-Medicare database using Cox regression analyses to quantify hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Among 133 324 women, 29.3% were diagnosed with diabetes before or concurrent with their breast cancer diagnosis, and 10 452 women developed subsequent malignancies over a median follow-up of 4.3 years. Diabetes was statistically significantly associated with liver (HR = 2.35, 95% CI = 1.48 to 3.74), brain (HR = 1.94, 95% CI = 1.26 to 2.96), and thyroid cancer risks (HR = 1.38, 95% CI = 1.01 to 1.89). Future studies are needed to better understand the spectrum of subsequent cancers associated with diabetes and the role of diabetes medications in modifying subsequent cancer risk, alone or in combination with cancer treatments.