JNCI Cancer Spectrum 

About: JNCI Cancer Spectrum is an academic journal published by Oxford University Press. The journal publishes majorly in the area(s): Cancer & Medicine. It has an ISSN identifier of 2515-5091. It is also open access. Over the lifetime, 562 publications have been published receiving 5984 citations. The journal is also known as: Journal of the National Cancer Institute cancer spectrum & JNCI CS.

Physical Activity and Mortality in Cancer Survivors: A Systematic Review and Meta-Analysis

Abstract: Background: Recommendations for improved survival after cancer through physical activity (PA) exist, although the evidence is still emerging. Our primary objective was to conduct a systematic review and meta-analysis of the association between prediagnosis and postdiagnosis PA and survival (cancer-specific, all-cause, and cardiovascular disease mortality) for all cancers and by tumor site. Secondary objectives were to examine the associations within population subgroups, by PA domain, and to determine the optimal dose of PA related to survival. Methods: PubMed, EMBASE, and SportsDiscus databases were searched from inception to November 1, 2018. DerSimonian-Laird random-effects models were used to estimate the summary hazard ratios (HRs) and 95% confidence intervals (CI) for primary and secondary analyses and to conduct dose-response analyses. Results: Evidence from 136 studies showed improved survival outcomes with highest vs lowest levels of prediagnosis or postdiagnosis total or recreational PA for all-cancers combined (cancer specific mortality: HR = 0.82, 95% CI = 0.79 to 0.86, and HR = 0.63, 95% CI = 0.53 to 0.75, respectively) as well as for 11 specific cancer sites. For breast and colorectal cancers, greater reductions were observed for postdiagnosis PA (HR = 0.58-0.63) compared with prediagnosis PA (HR = 0.80-0.86) for cancer-specific and all-cause mortality. Survival benefits through PA were observed in most subgroups (within sex, body mass index, menopausal status, colorectal subtypes, and PA domain) examined. Inverse dose-response relationships between PA and breast cancer-specific and all-cause mortality were observed, with steep reductions in hazards to 10-15 metabolic equivalent hours per week. Conclusion: Higher prediagnosis and postdiagnosis levels of PA were associated with improved survival outcomes for at least 11 cancer types, providing support for global promotion of PA guidelines following cancer.

Change in Survival in Metastatic Breast Cancer with Treatment Advances: Meta-Analysis and Systematic Review

Abstract: Background Metastatic breast cancer (MBC) treatment has changed substantially over time, but we do not know whether survival post-metastasis has improved at the population level. Methods We searched for studies of MBC patients that reported survival after metastasis in at least two time periods between 1970 and the present. We used meta-regression models to test for survival improvement over time in four disease groups: recurrent, recurrent estrogen (ER)-positive, recurrent ER-negative, and de novo stage IV. We performed sensitivity analyses based on bias in some studies that could lead earlier cohorts to include more aggressive cancers. Results There were 15 studies of recurrent MBC (N = 18 678 patients; 3073 ER-positive and 1239 ER-negative); meta-regression showed no survival improvement among patients recurring between 1980 and 1990, but median survival increased from 21 (95% confidence interval [CI] = 18 to 25) months to 38 (95% CI = 31 to 47) months from 1990 to 2010. For ER-positive MBC patients, median survival increased during 1990-2010 from 32 (95% CI = 23 to 43) to 57 (95% CI = 37 to 87) months, and for ER-negative MBC patients from 14 (95% CI = 11 to 19) to 33 (95% CI = 21 to 51) months. Among eight studies (N = 35 831) of de novo stage IV MBC, median survival increased during 1990-2010 from 20 (95% CI = 16 to 24) to 31 (95% CI = 24 to 39) months. Results did not change in sensitivity analyses. Conclusion By bridging studies over time, we demonstrated improvements in survival for recurrent and de novo stage IV MBC overall and across ER-defined subtypes since 1990. These results can inform patient-doctor discussions about MBC prognosis and therapy.

Phase 1 Study of Molibresib (GSK525762), a Bromodomain and Extra-Terminal Domain Protein Inhibitor, in NUT Carcinoma and Other Solid Tumors.

Abstract: Background Bromodomain and extra-terminal domain proteins are promising epigenetic anticancer drug targets. This first-in-human study evaluated the safety, recommended phase II dose, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the bromodomain and extra-terminal domain inhibitor molibresib (GSK525762) in patients with nuclear protein in testis (NUT) carcinoma (NC) and other solid tumors. Methods This was a phase I and II, open-label, dose-escalation study. Molibresib was administered orally once daily. Single-patient dose escalation (from 2 mg/d) was conducted until the first instance of grade 2 or higher drug-related toxicity, followed by a 3 + 3 design. Pharmacokinetic parameters were obtained during weeks 1 and 3. Circulating monocyte chemoattractant protein-1 levels were measured as a pharmacodynamic biomarker. Results Sixty-five patients received molibresib. During dose escalation, 11% experienced dose-limiting toxicities, including six instances of grade 4 thrombocytopenia, all with molibresib 60-100 mg. The most frequent treatment-related adverse events of any grade were thrombocytopenia (51%) and gastrointestinal events, including nausea, vomiting, diarrhea, decreased appetite, and dysgeusia (22%-42%), anemia (22%), and fatigue (20%). Molibresib demonstrated an acceptable safety profile up to 100 mg; 80 mg once daily was selected as the recommended phase II dose. Following single and repeat dosing, molibresib showed rapid absorption and elimination (maximum plasma concentration: 2 hours; t1/2: 3-7 hours). Dose-dependent reductions in circulating monocyte chemoattractant protein-1 levels were observed. Among 19 patients with NC, four achieved either confirmed or unconfirmed partial response, eight had stable disease as best response, and four were progression-free for more than 6 months. Conclusions Once-daily molibresib was tolerated at doses demonstrating target engagement. Preliminary data indicate proof-of-concept in NC.

Sedentary Behaviors, TV Viewing Time, and Risk of Young-Onset Colorectal Cancer.

Abstract: Background Colorectal cancer (CRC) diagnosed before age 50 years, or young-onset CRC, is increasing globally with undefined etiology. A sedentary lifestyle is an emerging risk factor for CRC after age 50 years, but its role in young-onset CRC is unknown. Methods We prospectively evaluated sedentary behaviors, primarily time watching television (TV), and risk of young-onset CRC among 89 278 women in the Nurses' Health Study II ages 25-42 years at recruitment (1991-2011). We used Cox proportional hazards modelling to estimate relative risks (RR) and 95% confidence intervals (CIs). Statistical tests were two-sided. Results We documented 118 young-onset CRCs over 1 262 540 person-years. Sedentary TV viewing time was statistically significantly associated with increased risk of young-onset CRC, after adjusting for putative risk factors, including obesity and physical activity. Compared 7 hours, women with 7.1-14 hours per week of TV time had a multivariable relative risk (RR) of 1.12 (95% confidence interval [CI] = 0.72 to 1.75), further increased for greater than14 hours per week (RR = 1.69, 95% CI = 1.07 to 2.67, Ptrend = .03). This association was observed among participants without a CRC family history and was more pronounced for rectal cancer (RR for >14 vs <7 hours per week 2.44, 95% CI = 1.03 to 5.78, Ptrend = .04). Overweight or obese participants may be more susceptible. Conclusion Independent of exercise and obesity, prolonged sedentary TV viewing time, a surrogate for a more inactive lifestyle, was associated with increased risk of young-onset CRC, particularly of the rectum. These findings provide further evidence on the importance of maintaining an active lifestyle.

Burden of Human Papillomavirus (HPV)-Related Cancers Attributable to HPVs 6/11/16/18/31/33/45/52 and 58

Abstract: Background Many countries, mainly high- and upper-middle income, have implemented human papillomavirus (HPV) vaccination programs, with 47 million women receiving the full course of vaccine (three doses) in 2014. To evaluate the potential impact of HPV vaccines in the reduction of HPV-related disease, we aimed to estimate the HPV type distribution and burden of anogenital and head and neck cancers attributable to HPV types (HPVs 16/18/31/33/45/52/58/6/11) included in currently licensed HPV vaccines. Methods In all, 18 247 formalin-fixed paraffin-embedded specimens were retrieved from 50 countries. HPV DNA detection and typing were performed with the SPF-10 PCR/DEIA/LiPA25 system. With the exception of cervical cancer, HPV DNA-positive samples were additionally subjected to HPV E6*I mRNA detection and/or p16INK4a immunohistochemistry. For cervical cancer, estimates were based on HPV DNA, whereas for other sites, estimates were based on HPV DNA, E6*I mRNA, and p16INK4a biomarkers. Results The addition of HPVs 31/33/45/52/58 to HPVs 16/18/6/11 in the nonavalent HPV vaccine could prevent almost 90% of cervical cancer cases worldwide. For other sites, the nonavalent HPV vaccine could prevent 22.8% of vulvar, 24.5% of penile, 60.7% of vaginal, 79.0% of anal cancers, 21.3% of oropharyngeal, 4.0% of oral cavity, and 2.7% of laryngeal cancer cases. Conclusions Our estimations suggest a potential impact of the nonavalent HPV vaccine in reducing around 90% of cervical cancer cases and a global reduction of 50% of all the cases at HPV-related cancer sites.