Journal: Cancer medicine
Varicella zoster virus (VZV) is a neurotropic α-herpesvirus that causes chickenpox and establishes life-long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case-Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two-stage random-effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65-0.96). Furthermore, the protective effect of chickenpox was stronger for high-grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta-analyses of the literature and investigations of the potential biological mechanism, are warranted.
Limited information is available on risk of peritoneal mesothelioma after asbestos exposure, and in general on the risk of cancer after cessation of asbestos exposure. We updated to 2013 the follow-up of a cohort of 1083 female and 894 male textile workers with heavy asbestos exposure (up to 100 fb/mL), often for short periods. A total of 1019 deaths were observed, corresponding to a standardized mortality ratio (SMR) of 1.68 (95% confidence interval [CI]: 1.57-1.78). SMRs were 29.1 (95% CI: 21.5-38.6) for peritoneal cancer, 2.96 (95% CI: 2.50-3.49) for lung cancer, 33.7 (95% CI: 25.7-43.4) for pleural cancer, and 3.03 (95% CI: 1.69-4.99) for ovarian cancer. For pleural and peritoneal cancer, there was no consistent pattern of risk in relation to time since last exposure, whereas for lung cancer there was an indication of a decline in risk after 25 years since last exposure. The findings of this unique cohort provide novel data for peritoneal cancer, indicating that - as for pleural cancer - the excess risk does not decline up to several decades after cessation of exposure.
Earlier detection of colorectal cancer greatly improves prognosis, largely through surgical excision of neoplastic polyps. These include benign adenomas which can transform over time to malignant adenocarcinomas. This progression may be associated with changes in full blood count indices. An existing risk algorithm derived in Israel stratifies individuals according to colorectal cancer risk using full blood count data, but has not been validated in the UK. We undertook a retrospective analysis using the Clinical Practice Research Datalink. Patients aged over 40 with full blood count data were risk-stratified and followed up for a diagnosis of colorectal cancer over a range of time intervals. The primary outcome was the area under the receiver operating characteristic curve for the 18-24-month interval. We also undertook a case-control analysis (matching for age, sex, and year of risk score), and a cohort study of patients undergoing full blood count testing during 2012, to estimate predictive values. We included 2,550,119 patients. The area under the curve for the 18-24-month interval was 0.776 [95% confidence interval (CI): 0.771, 0.781]. Performance improves as the time interval reduces. The area under the curve for the age-matched case-control analysis was 0.583 [0.574, 0.591]. For the population risk-scored in 2012, the positive predictive value at 99.5% specificity was 8.8% with negative predictive value 99.6%. The algorithm offers an additional means of identifying risk of colorectal cancer, and could support other approaches to early detection, including screening and active case finding.
Recurrence will develop in 30-50% of colorectal cancer (CRC) cases despite apparent clearance following treatment. Carcinoembryonic antigen (CEA) is the only guideline-recommended blood test for monitoring cases for recurrence, but its sensitivity and specificity are suboptimal. This observational study compared a novel 2-gene (methylated BCAT1 and IKZF1 DNA) blood test with CEA for detection of recurrent CRC. We conducted a paired comparison of the BCAT1/IKZF1 test with CEA (cut-off 5 ng/mL) in blood from patients in remission after treatment for primary CRC and undergoing surveillance. Blood collected in the 12 months prior to or 3 months after complete investigational assessment of recurrence status were assayed and the results compared by McNemar’s test. Of 397 patients enrolled, 220 underwent satisfactory assessment for recurrence and 122 had blood testing performed within the prescribed period. In 28 cases with recurrent CRC, CEA was positive in 9 (32%; 95% CI 16-52%) compared to 19 (68%; 95% CI 48-84%) positive for methylated BCAT1/IKZF1 (P = 0.002). All samples that were CEA positive were also BCAT1/IKZF1 positive. In 94 patients without clinically detectable recurrence, CEA was positive in 6 (6%, 95% CI 2-13%) and BCAT1/IKZF1 in 12 (13%, 95% CI 7-21%), P = 0.210. The odds ratio of a positive CEA test for recurrence was 6.9 (95% CI 2-22) compared to 14.4 (5-39) for BCAT1/IKZF1. The BCAT1/IKZF1 test was more sensitive for recurrence than CEA and the odds of recurrence given a positive test was twice that of CEA. The BCAT1/IKZF1 test should be further considered for monitoring cases for recurrence.
Adaptive magnetic resonance imaging-guided radiation therapy (MRgRT) can escalate dose to tumors while minimizing dose to normal tissue. We evaluated outcomes of inoperable pancreatic cancer patients treated using MRgRT with and without dose escalation.
Advances in early diagnosis and curative treatment have reduced high mortality rates associated with non-small cell lung cancer. However, racial disparity in survival persists partly because Black patients receive less curative treatment than White patients.
Young adult cancer survivors (YAs) are confronted with immense financial challenges in the wake of their treatment. Medical bills and loss of savings may cause YAs to forgo recommended medications or follow-up appointments. Young survivors with financial concerns also report depression, stress and anxiety. The Samfund is a national nonprofit organization that provides financial support to YAs post-treatment. To quantify the financial burden of cancer in YAs, a retrospective analysis was performed of data collected from Samfund grant applications of 334 YA cancer survivors. Grants were awarded between 2007 and 2013 and grant recipients were consented electronically in 2014 for retrospective data analysis. Recipients ranged from 19 to 39 years of age at the time of their grant applications. Descriptive statistics were calculated and compared to the Medical Expenditure Panel Survey (MEPS) and U.S. census data on age-matched peers. Financial indicators of YA cancer survivors are worse in many domains than those of age-matched controls. Furthermore, YA survivors in their 30s report more perilous prefunding financial situations than younger grant recipients. Cancer has a devastating and age-specific impact on the finances of YAs. Philanthropic grants from the cancer support community, in conjunction with healthcare policy reforms, have the potential to break the cycle of financial need and help YAs move forward with their lives after cancer treatment.
Pre-clinical studies suggest that metformin and statins may delay prostate cancer (PCa) metastases; however, data in humans are limited. To the best of our knowledge, this is the first human study aimed to quantify the individual and joint effects of statin and metformin use among patients with high-risk PCa.
Colorectal cancer (CRC) remains one of the most common types of cancer and a leading cause of death worldwide. Previous studies indicated that statins may have a potential protective effect on CRC.
Malignant ascites caused by peritoneal dissemination of gastric cancer is chemotherapy-resistant and associated with poor prognosis. We conducted a pilot study to evaluate the safety of weekly intraperitoneal injections of in vitro expanded Vγ9Vδ2 T cells together with zoledronate for the treatment of such malignant ascites. Patient peripheral blood mononuclear cells were stimulated with zoledronate (5 μmol/L) and interleukin-2 (1000 IU/mL). After 14 days culture, Vγ9Vδ2 T-cells were harvested and administered intraperitoneally in four weekly infusions. The day before T-cell injection, patients received zoledronate (1 mg) to sensitize their tumor cells to Vγ9Vδ2 T-cell recognition. Seven patients were enrolled in this study. The number of Vγ9Vδ2 T-cells in each injection ranged from 0.6 to 69.8 × 10(8) (median 59.0 × 10(8) ). There were no severe adverse events related to the therapy. Intraperitoneal injection of Vγ9Vδ2 T cells allows them access to the tumor cells in the peritoneal cavity. The number of tumor cells in the ascites was significantly reduced even after the first round of therapy and remained substantially lower over the course of treatment. IFN-γ was detected in the ascites on treatment. Computed tomography revealed a significant reduction in volume of ascites in two of seven patients. Thus, injection of these antitumor Vγ9Vδ2 T-cells can result in local control of malignant ascites in patients for whom no standard therapy apart from paracentesis is available. Adoptively transferred Vγ9Vδ2 T-cells do indeed recognize tumor cells and exert antitumor effector activity in vivo, when they access to the tumor cells.