The role of whole‐brain radiation therapy in patients with cerebral metastases

Cancer, EarlyView.


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The role of whole‐brain radiation therapy in patients with cerebral metastases

Cancer, EarlyView.


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No association between circulating concentrations of vitamin D and risk of lung cancer: An analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3)

Abstract

Background

There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in pre-diagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3).

Patients and methods

The study included 5,313 lung cancer cases and 5,313 controls selected from. Blood samples for the cases were collected, on average, 5 years prior to lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in 5 categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D₂ (25(OH)D₂) and 25-hydroxyvitamin D₃ (25(OH)D₃) and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for 25(OH)D as both a continuous and categorical variable.

Results

Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% confidence interval: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology.

Conclusion

This study did not support an association between vitamin D concentrations and lung cancer risk.

https://ift.tt/2EctsuP

No association between circulating concentrations of vitamin D and risk of lung cancer: An analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3)

Abstract

Background

There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in pre-diagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3).

Patients and methods

The study included 5,313 lung cancer cases and 5,313 controls selected from. Blood samples for the cases were collected, on average, 5 years prior to lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in 5 categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D₂ (25(OH)D₂) and 25-hydroxyvitamin D₃ (25(OH)D₃) and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for 25(OH)D as both a continuous and categorical variable.

Results

Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% confidence interval: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology.

Conclusion

This study did not support an association between vitamin D concentrations and lung cancer risk.

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By the Numbers: Novel Drugs Approved by the FDA, 2011-2017 [News in Brief]

In 2017, the FDA approved 12 novel cancer drugs. The agency also approved two chimeric antigen receptor T-cell therapies for blood cancers.

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The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression [Research Briefs]

We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4⁺ T cells and CD8⁺ T-cell activation. Bacterial ablation also enabled efficacy for checkpoint-targeted immunotherapy by upregulating PD-1 expression. Mechanistically, the PDA microbiome generated a tolerogenic immune program by differentially activating select Toll-like receptors in monocytic cells. These data suggest that endogenous microbiota promote the crippling immune-suppression characteristic of PDA and that the microbiome has potential as a therapeutic target in the modulation of disease progression.

Significance: We found that a distinct and abundant microbiome drives suppressive monocytic cellular differentiation in pancreatic cancer via selective Toll-like receptor ligation leading to T-cell anergy. Targeting the microbiome protects against oncogenesis, reverses intratumoral immune tolerance, and enables efficacy for checkpoint-based immunotherapy. These data have implications for understanding immune suppression in pancreatic cancer and its reversal in the clinic. Cancer Discov; 8(4); 403–16. ©2018 AACR.

See related commentary by Riquelme et al., p. 386.

This article is highlighted in the In This Issue feature, p. 371

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Immunotherapy for Pancreatic Cancer: More Than Just a Gut Feeling [In the Spotlight]

Summary: Development of pancreatic cancer in spontaneous murine models is associated with enrichment of specific strains of gut and intratumoral bacteria that induce a tolerogenic immunosuppressive microenvironment favoring cancer progression and resistance to immunotherapies. Ablation of the microbiome with antibiotics reshapes the tumor microenvironment, inducing T-cell activation, improving immune surveillance, and increasing sensitivity to immunotherapy in established tumors. Cancer Discov; 8(4); 386–8. ©2018 AACR.

See related article by Pushalkar et al., p. 403.

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