Biomarker panel increases accuracy for identification of an MS relapse beyond sNfL.

BACKGROUND: For relapsing-remitting multiple sclerosis (RRMS), there is a need for biomarker development beyond clinical manifestations and MRI. Soluble neurofilament light chain (sNfL) has emerged as a biomarker for inflammatory activity in RRMS. However, there are limitations to the accuracy of sNfL in identifying relapses. Here, we sought to identify a panel of biomarkers that would increase the precision of distinguishing patients in relapse compared to sNfL alone. METHODS: We used a multiplex approach to measure levels of 724 blood proteins in two distinct RRMS cohorts. Multiple t-tests with covariate correction determined biomarkers that were differentially regulated in relapse and remission. Logistic regression models determined the accuracy of biomarkers to distinguish relapses from remission. RESULTS: The discovery cohort identified 37 proteins differentially abundant in active RRMS relapse compared to remission. The verification cohort confirmed four proteins, including sNfL, were altered in active RRMS relapse compared to remission. Logistic regression showed that the 4-protein panel identified active relapse with higher accuracy (AUC = 0.87) than sNfL alone (AUC = 0.69). CONCLUSION: Our studies confirmed that sNfL is elevated during relapses in RRMS patients. Furthermore, we identified three other blood proteins, uPA, hK8 and DSG3 that were altered during relapse. Together, these four biomarkers could be used to monitor disease activity in RRMS patients.

Computed tomography-planned interstitial brachytherapy for locally advanced gynecologic cancer: Outcomes and dosimetric predictors of urinary toxicity.

PURPOSE: To identify dosimetric predictors of outcome and toxicity in patients receiving CT-planned interstitial brachytherapy (ISBT) for gynecologic cancers. METHODS AND MATERIALS: Patients who received ISBT between 2009 and 2014 were reviewed. Demographic, disease specific, treatment, and toxicity data were collected. Logistic regression was used to model toxicity. A least absolute shrinkage and selection operator penalty was used to identify relevant predictors. Receiver operating characteristic curves were used to analyze the relation between dosimetric factors and urinary toxicity. RESULTS: Seventy-three patients received ISBT (21 at time of cancer recurrence and 52 at the first presentation). Thirty-six patients had cervical cancer, 16 had vaginal cancer, 13 had uterine cancer, and 8 had vulvar cancer. ISBT was performed using both high-dose-rate and low-dose-rate 192Ir sources (27 low dose rate and 46 high dose rate). With a median followup of 12 months, Grade 3 vaginal, urinary, and rectal toxicity occurred in 17.8%, 15.1%, and 6.8% of patients, respectively. No patients experienced Grade 4 or 5 toxicity. Dose to 0.1cc of urethra predicted for development of Grade 3 urinary toxicity (area under the curve of 0.81; 95% confidence interval: 0.66, 0.96). A 10% probability of a Grade 3 urinary toxicity associated with a dose of 23.1 equivalent dose in 2 Gy fractions (95% confidence interval: 9.51, 36.27 equivalent dose in 2 Gy fractions). CONCLUSIONS: ISBT is a safe treatment for gynecologic malignancies. The dose to 0.1cc significantly predicts for severe urinary toxicity. Our data suggests that dose to a small urethral volume may be the most significant predictor of urinary toxicity in patients receiving ISBT for gynecologic cancer.

Cyclical hypofractionated radiotherapy technique for palliative treatment of locally advanced head and neck cancer: institutional experience and review of palliative regimens.

BACKGROUND: Effective palliation in patients with locally advanced head and neck cancer is important. Cyclical hypofractionated radiotherapy (Quad Shot) is a short-course palliative regimen with good patient compliance, low rates of acute toxicity, and delayed late fibrosis. OBJECTIVE: To review use of the Quad Shot technique at our institution in order to quantify the palliative response in locally advanced head and neck cancer. METHODS: The medical records of 70 patients with head and neck squamous cell carcinoma who had been treated with the Quad Shot technique were analyzed retrospectively (36 had been treated with intensity-modulated radiation therapy and 34 with 3-D conformal radiotherapy). They had received cyclical hypofractionated radiotherapy administrated as 14.8 Gy in 4 fractions over 2 days, twice daily, repeated every 3 weeks for a total of 3 cycles. The total prescribed dose was 44.4 Gy. Primary endpoints were improvement in pain using a verbal numeric pain rating scale (range 1-10, 10 being severe pain) and dysphagia using the Food Intake Level Scale, and the secondary endpoints included overall survival (OS), local regional recurrence-free survival (LRRFS), progression-free survival (PFS) and time to progression. RESULTS: Pain response occurred in 61% of the patients. The mean pain scores decreased significantly from pre to post treatment (5.81 to 2.55, 𝑃 = .009). The mean initial dysphagia score improved from 2.20 to 4.77 55 (𝑃 = .045). 26% of patients developed mucositis (≤ grade 2), with 9% developing grade 3-level mucositis. 12 patients had tumor recurrence. The estimated 1-year PFS was 20.7%. The median survival was 3.85 months with an estimated 1-year OS of 22.6%. Pain response (hazard ratio [HR], 2.69; 95% confidence index [CI], I.552-1.77) and completion of all 3 cycles (HR, 1.71; 95% CI, 1.003-2.907) were predictive for improved OS. LIMITATIONS: This study is a retrospective analysis. CONCLUSION: Quad Shot is an appropriate palliative regimen for locally advanced head and neck cancer.

Computed tomography planned interstitial brachytherapy for recurrent gynecologic cancer.

PURPOSE: To report outcomes and identify predictors of toxicity in patients undergoing reirradiation with interstitial brachytherapy (ISBT) for recurrent cancers of the female reproductive tract. METHODS AND MATERIALS: Twenty-one patients received ISBT performed using (192)Ir sources (10 low dose rate and 11 high dose rate) at our institution between 2009 and 2013. Demographic, disease specific, treatment, toxicity, and outcome data were collected. Kaplan-Meier and proportional hazard models were used to estimate survival and logistic regression to model toxicity. A least absolute shrinkage and selection operator penalty was used to identify relevant predictors of outcome and toxicity. RESULTS: Eleven patients had uterine cancer, 7 patients had cervical cancer, and 3 patients had vulvar cancer. One-year actuarial freedom from local-regional failure, progression-free survival (PFS), and overall survival were 71.5%, 66.0%, and 82.2%, respectively. Tumor size was a significant predictor of worse PFS and overall survival (1 cm increase in tumor size = hazard ratio [HR], 1.61; 95% confidence interval [CI]: 1.16, 2.62 for PFS; HR, 2.02; 95% CI: 1.21, 3.38). Grade 3 or higher vaginal, urinary, and rectal toxicity occurred in 28.5%, 9.5%, and 19% of patients, respectively. Urethra D0.1cc predicted for grade 2 or higher urinary toxicity (one equivalent dose in 2 Gy fraction increase = HR, 1.156; 95% CI: 1.001, 1.335). CONCLUSIONS: Reirradiation with ISBT is both safe and effective. In patients with recurrent cancer, urethra D0.1cc predicts for increased urinary toxicity. Increased tumor size is a negative prognostic factor in patients receiving ISBT for cancer recurrence.

Risk for renal cell carcinoma in chronic hepatitis C infection.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) confers increased risk for chronic renal disease, and numerous reports suggest an association with renal cell carcinoma (RCC), a cancer with rapidly rising global incidence. We sought to determine whether HCV infection confers an increased risk for developing RCC. METHODS: With the use of administrative data from a large, integrated, and ethnically diverse healthcare system, we did a cohort study of 67,063 HCV-tested patients between 1997 and 2006 who were followed for the development of RCC until April 2008. RESULTS: A search of the health system cancer registry for patients with the diagnosis of kidney cancer showed that RCC was diagnosed in 0.6% (17 of 3,057) of HCV-positive patients versus 0.3% (177 of 64,006) of HCV-negative patients. The mean age at RCC diagnosis was much younger in HCV-positive individuals (54 versus 63; P < 0.001). The univariate hazard ratio for RCC among HCV patients was 2.20 (95% confidence interval, 1.32-3.67; P = 0.0025). In a multivariate model that included the risk factors age, African-American race, male gender, and chronic kidney disease, the overall hazard ratio for RCC among HCV patients was 1.77 (95% confidence interval, 1.05-2.98; P = 0.0313). CONCLUSION: Chronic HCV infection confers a risk for the development of RCC. IMPACT: Clinicians should consider newly identified renal lesions in patients with chronic HCV infection with a heightened suspicion for neoplasm, and newly diagnosed cases of RCC may require more careful surveillance for the presence of HCV infection. Additional studies are required to confirm these findings and to explore potential mechanisms of oncogenesis.