Neutrophil-lymphocyte ratio as a predictive biomarker for response to high dose interleukin-2 in patients with renal cell carcinoma.

BACKGROUND: Immunotherapy with high-dose interleukin-2 (HD-IL2) results in long-term survival in some metastatic renal cell carcinoma (mRCC) patients but has significant acute toxicities. Biomarkers predicting response to therapy are needed to better select patients most likely to benefit. NLR (absolute neutrophil count (ANC)/absolute lymphocyte count (ALC)) is a prognostic and predicative biomarker in various malignancies. The goal was to determine whether NLR can predict response to HD-IL2 in this setting. METHODS: Patients with clear cell mRCC treated with HD-IL2 were identified from an institutional database from 2003-2012. Baseline variables for the assessment of IMDC risk criteria, and neutrophil and lymphocyte count, were collected. Best response criteria were based on RECIST 1.0. Wilcoxon rank-sum test was used to evaluate the association of continuous baseline variables with disease control. NLR was stratified by ≤4 or >4. Progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and Cox proportional hazard models assessed associations of NLR with survival. RESULTS: In 71 eligible patients, median NLR in those with an objective response (n = 14, 20%) was 2.3 vs 3.4 in those without (n = 57, 80%, p = 0.02). NLR ≤4 was associated with improved progression free and overall survival. After adjustment for IMDC risk criteria, NLR remained a significant predictor of OS (ANC/ALC ≤4 vs >4, HR 0.41, 95% CI 1.09-5.46, p = 0.03; ANC/ALC continuous variable per unit change in NLR, HR 1.08, 95% CI 1.01-1.14, p = 0.03). CONCLUSIONS: In this discovery set, NLR predicts overall survival in patients treated with HD-IL2 in mRCC, and may allow better patient selection in this setting. Data needs validation in an independent cohort.

The Clinical Cell-Cycle Risk (CCR) Score Is Associated With Metastasis After Radiation Therapy and Provides Guidance on When to Forgo Combined Androgen Deprivation Therapy With Dose-Escalated Radiation.

PURPOSE: The clinical cell-cycle risk (CCR) score, which combines the University of California, San Francisco's Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT). METHODS AND MATERIALS: This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N = 741). Patients were treated with dose-escalated RT with or without ADT. The primary outcome was time to metastasis. RESULTS: The CCR score prognosticated metastasis with a hazard ratio (HR) per unit score of 2.22 (95% confidence interval [CI], 1.71-2.89; P < .001). The CCR score better prognosticated metastasis than NCCN risk group (CCR, P < .001; NCCN, P = .46), CAPRA score (CCR, P = .002; CAPRA, P = .59), or CCP score (CCR, P < .001; CCP, P = .59) alone. In bivariable analyses, CCR score remained highly prognostic when accounting for ADT versus no ADT (HR, 2.18; 95% CI, 1.61-2.96; P < .001), ADT duration as a continuous variable (HR, 2.11; 95% CI, 1.59-2.79; P < .001), or ADT given at or below the recommended duration for each NCCN risk group (HR, 2.19; 95% CI, 1.69-2.86; P < .001). Men with CCR scores below or above the multimodality threshold (CCR score, 2.112) had a 10-year risk of metastasis of 3.7% and 21.24%, respectively. Men with below-threshold scores receiving RT alone had a 10-year risk of metastasis of 3.7%, and for men receiving RT plus ADT, the 10-year risk of metastasis was also 3.7%. CONCLUSIONS: The CCR score accurately and precisely prognosticates metastasis and adds clinically actionable information relative to guideline-recommended therapies based on NCCN risk in men undergoing dose-escalated RT with or without ADT. For men with scores below the multimodality threshold, adding ADT may not significantly reduce their 10-year risk of metastasis.

Pink pigtail in a skin biopsy: What is your diagnosis?

Sarcoptes scabiei is an obligate ectoparasite, which burrows into the stratum granulosum of the epidermis and lays its eggs. The resultant host inflammatory response leads to intensely pruritic papules. CASE SYNOPSIS: A 63-year-old man undergoing treatment for immunoproliferative disease was suspected of having a pruritic drug eruption. Subsequent skin biopsy revealed an intracorneal burrow containing three pink, refractile pigtail-like structures, believed to be empty eggshells of S. scabiei. CONCLUSION: Traditionally, the presence of adult mites or eggs in skin scrapings or a skin biopsy is required for a definitive diagnosis of scabies. However, our case and similar cases suggest that the diagnosis of scabies can also be made on the basis of pink pigtail-like structures, remnants of eggshells, within the intracorneal burrow.

Durable Response to Treatment With Combination Radiotherapy and High-dose Interleukin-2 in Metastatic Chromophobe Variant Renal Cell Carcinoma.

This is a report of chromophobe renal cell carcinoma (ChRCC), a rare entity that accounts for 6% to 11% of cases of renal cell carcinoma (RCC). ChRCC is considered to yield a good prognosis as it typically presents as an early stage tumor with longer overall survival when compared with clear cell RCC; however, metastatic disease negates this survival difference and is characterized by poor prognosis. The available clinical investigations supporting the guidelines for treatment of metastatic RCC are predominantly based on clear cell RCC studies. There are no data supporting the applicability of guidelines used to treat clear cell to the management of patients with the ChRCC. This case report describes a male patient who initially presented with locally advanced chromophobe variant RCC, pathologically staged T3aN1M0, initially treated with radical nephrectomy. After developing pathologically confirmed metastatic disease, the patient was treated with repeated cycles of combined hypofractionated radiotherapy to symptomatic metastatic disease sites followed by high-dose intravenous interleukin-2 (HD IL-2) subsequently achieving a near complete and durable response. Three months after initiation of HD IL-2 and radiotherapy, the patient achieved a partial response, and after 6 months he achieved a near complete response. At the time of most recent follow-up, over 36 months after the diagnosis of metastatic disease, the patient remained in remission. On the basis of this experience, we hypothesize that immunomodulation from the radiation potentiated an immune response to HD IL-2 leading to near complete and a durable response in this patient with metastatic ChRCC.