There have been dramatic changes in the staging and treatment of Hodgkin's lymphoma (HL) over the past 30 years. We undertook this study to determine if a stage migration had occurred and also examined if treatment associated with later years has improved survival. Patients with stage I‐IV HL between 1983 and 2011 were selected from the Surveillance, Epidemiology, and End Results database. Multivariable analysis (MVA) was performed using Cox proportional hazards modeling. The study cohort included 35,680 patients. The stage breakdown in 1983 according to A and B symptoms was follows: 18%, 21%, 12%, and 5% for stage IA, IIA, IIIA, and IVA disease, respectively, and 6%, 11%, 12%, and 15% for stage IB, IIB, IIIB, and IVB disease. The stage breakdown in 2011 according to A and B symptoms was follows: 9%, 29%, 10%, and 6% for stage IA, IIA, IIIA, and IVA disease, respectively, and 4%, 16%, 12%, and 13% for stage IB, IIB, IIIB, and IVB disease. The median follow‐up for the entire cohort is 6.1 years. On MVA, the HR for mortality of patients diagnosed in 2006 was 0.60 (95% Confidence Interval (CI): 0.52–0.70) compared to 1983. For stage I and II patients diagnosed in 2006 the HR was 0.62 (95% CI: 0.44–0.87) and 0.40 (95% CI: 0.30–0.55), respectively, compared to patients diagnosed in 1983. For stage III and IV patients diagnosed in 2006 the HR was 0.72 (95% CI: 0.53–0.98) and 0.74 (95% CI: 0.56–0.99), respectively, compared to patients diagnosed in 1983. This is the first study to demonstrate a significant stage migration in early stage Hodgkin's lymphoma. Furthermore, these results demonstrate an improvement in survival over time for patients with Hodgkin's lymphoma which was particularly notable for those with early stage disease.

Vitamin D deficiency increases the risk of lethal prostate adenocarcinomas (PCa) and the majority of older men are deficient. Although PCa arises from the epithelium, the surrounding stroma has hormonal regulatory control over the epithelium and contributes to carcinogenesis. Herein, we describe regulation of microRNAs (miRs) by the active hormone dihydroxyvitamin D (1,25(OH)2D) in human prostate stroma. 1,25(OH)2D binds the vitamin D receptor (VDR) transcription factor to regulate gene expression, including miRs, which have emerged as potent regulators of protein expression. 1,25(OH)2D -regulated miRs were identified by profiling in primary human prostatic stromal cells (PrS) and three miRs, miR-126-3p, miR 154-5p and miR-21-5p were subsequently validated in laser-capture micro-dissected prostate stromal tissue from a vitamin D3 clinical trial (N=45). Regulation of these miRs by 1,25(OH)2D was VDR-dependent. Network analysis of known and putative mRNA targets of these miRs was enriched with cancer and inflammation pathways, consistent with known roles of stroma and of vitamin D in carcinogenesis. Expression of the miR processing ribonuclease, DICER1, positively correlated with vitamin D metabolite levels in the clinical trial specimens. High epithelial/stromal ratios of DICER1 were significantly associated biochemical recurrence (OR 3.1, p=0.03) in a tissue microarray of 170 matched PCa patients. In summary, these results underscore the role of the prostate stroma in regulating responses to the hormone 1,25(OH)2D and identified miRs and DICER1 as being regulated in human prostate stroma. Regulation of stromal DICER1 by 1,25(OH)2D may also have clinical relevance in protection against aggressive PCa.

The NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 is the standard for oncology toxicity encoding and grading despite limited validation. We assessed inter-rater reliability (IRR) in multi-reviewer toxicity identification. Methods and Materials: Two reviewers independently reviewed 100 randomly selected notes for weekly on-treatment visits during radiotherapy from the electronic health record (EHR). Discrepancies were adjudicated by a third reviewer for consensus. Term harmonization was performed to account for overlapping symptoms in CTCAE. IRR was assessed based on unweighted and weighted Cohen's kappa coefficients. Results: Between reviewers, unweighted kappa was 0.68 (95% CI 0.65-0.71) and weighted kappa 0.59 (0.22-1.00). IRR was consistent between noted present or absent symptoms with kappa of 0.6 (0.66-0.71) and 0.6 (0.65-0.69), respectively. Conclusions: Significant discordance suggests toxicity identification, particularly retrospectively, is a complex and error prone task. Strategies to minimize IRR, including training and simplification of the CTCAE criteria, should be considered in trial design and future terminologies.

Objectives Expert abstraction of acute toxicities is critical in oncology research but is labor-intensive and variable. We assessed the accuracy of a natural language processing (NLP) pipeline to extract symptoms from clinical notes compared to physicians. Materials and Methods Two independent reviewers identified present and negated National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 symptoms from 100 randomly selected notes for on-treatment visits during radiation therapy with adjudication by a third reviewer. A NLP pipeline based on Apache clinical Text Analysis Knowledge Extraction System was developed and used to extract CTCAE terms. Accuracy was assessed by precision, recall, and F1. Results The NLP pipeline demonstrated high accuracy for common physician-abstracted symptoms, such as radiation dermatitis (F1 0.88), fatigue (0.85), and nausea (0.88). NLP had poor sensitivity for negated symptoms. Conclusion NLP accurately detects a subset of documented present CTCAE symptoms, though is limited for negated symptoms. It may facilitate strategies to more consistently identify toxicities during cancer therapy.

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hazards modeling were used for statistical analyses. Propensity score (PS) adjustments were used to reduce the effects confounding variables. Results: One hundred and seventy-two lesions treated with FB-SRS (n Z 79) or LA-SRS (n Z 93) were included. Median overall follow up was 12 months (FB-SRS) and 6.7 months (LA-SRS) (p<0.001). Median SRS dose was 24Gy in both cohorts (range 12-24). Tumors were 2cm in 92% (n Z 73) and 87% (n Z 81) (p Z 0.26) and adenocarcinoma histology in 73% (n Z 58) and 69% (n Z 64) (p Z 0.22) of lesions treated with FB-SRS and LA-SRS, respectively. Concurrent systemic therapy was given for 41% (n Z 32) and 12% (n Z 11) of lesions treated with FB-SRS and LA-SRS, respectively (p <0.001). The rate of symptomatic RN was 1.4% (95% CI 0.1-6.6) (FB-SRS) and 9.9% (95% CI: 3.8-19.6) (LA-SRS) (p Z 0.03). One-year LC was 95% (95% CI 87.1-98.7) (FB-SRS) and 81.9% (95% CI 57.6-96.6) (LA-SRS) (p Z 0.07). Overall survival and distant brain failure rate at one year were 28.6% (95% CI 18.5-38.7) and 32.1% (95% CI 21.7-42.4) for the entire cohort. On MVA after PS adjustments, FB-SRS was the only covariate significant for LC (HR 0.07, 95% CI 0.01-.56: p Z 0.01). Conclusion: In our retrospective cohort, we found a significantly lower incidence of symptomatic RN and a trend towards improved LC in patients treated with FB-SRS compared to LA-SRS. FB-SRS was the only covariate associated with improved local control on Cox regression analysis after PS adjustment. Further study with prospective cohorts is required to validate these observations.

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