Pre-Existing Inflammatory Disease Predicts Cutaneous Immunotherapy Toxicity Development: A Multi-Institutional Cohort Study.

Background: Relationships between pre-existing inflammatory diseases (pIDs) and cutaneous immune-related adverse events (cirAEs) have not been well-studied. This study is to investigate associations between pIDs and cirAEs among immune-checkpoint inhibitor (ICI) recipients at the Mass General Brigham healthcare system. Methods: Electronic health records were reviewed to ascertain cirAE status. Patients' pID status was determined using International Classification of Diseases (ICD) codes. Cox proportional hazard, logistic regression, and linear regression models were performed. Results: Among 3607 ICI recipients, 1354 had pIDs, and 672 developed cirAEs. After covariate adjustments, patients with cutaneous pIDs (HR:1.56, p<0.001) or both cutaneous and non-cutaneous pIDs (HR:1.76, p<0.001) had increased cirAE risk in contrast to patients with non-cutaneous pIDs alone (HR:1.01, p=0.9). In adjusted ordinal logistic regression modeling, cutaneous pIDs (OR:1.55, p<0.0001) and the presence of both cutaneous pIDs and non-cutaneous pIDs (OR:1.71, p=0.002) were associated with increased cirAE severity. The time to cirAE onset was different between the cutaneous pID group and the non-cutaneous pID group (Mean: 98 vs. 146 days, p=0.021; Beta: -0.11, p=0.033). Conclusions: ICI recipients with cutaneous pIDs should have increased clinical monitoring due to their increased risk of cirAE development, severity, and earlier onset.

Objective response to immune checkpoint inhibitor therapy in NRAS-mutant melanoma: A systematic review and meta-analysis.

Introduction: NRAS mutations are common in melanoma and confer a worse prognosis. Although most patients with metastatic melanoma receive immune checkpoint inhibitors (ICIs), the impact of NRAS mutational status on their efficacy remains under debate. Methods: We performed a comprehensive literature search across several large databases. Inclusion criteria were trials, cohorts, and large case series that analyzed the primary outcome of objective response rate by NRAS mutational status in patients with melanoma treated with any line of ICI. At least two reviewers independently screened studies using Covidence software, extracted data, and assessed risk of bias. Standard meta-analysis was performed in R with sensitivity analysis and tests for bias. Results: Data on 1770 patients from ten articles were pooled for meta-analysis, and the objective response rate to ICIs was calculated to compare NRAS-mutant and NRAS-wildtype melanoma. The objective response rate was 1.28 (95% confidence interval: 1.01-1.64). Sensitivity analysis identified the study by Dupuis et al. with influential impact on the pooled effect size and heterogeneity, favoring NRAS-mutant melanoma. Discussion: In this meta-analysis evaluating the impact of NRAS mutational status on objective response to ICIs in metastatic melanoma, NRAS-mutant cutaneous melanoma demonstrated an increased likelihood of partial or complete tumor response, relative to NRAS-wildtype cutaneous melanoma. Genomic screening for NRAS mutations in patients with metastatic melanoma may improve predictive ability when initiating ICIs.

Association of Cutaneous Immune-Related Adverse Events With Increased Survival in Patients Treated With Anti-Programmed Cell Death 1 and Anti-Programmed Cell Death Ligand 1 Therapy.

IMPORTANCE: Despite the efficacy of immune checkpoint inhibitors (ICIs), cutaneous immune-related adverse events (cirAEs) occur in 20% to 40% of all treated patients. To our knowledge, little is known about the predictive value of these cutaneous eruptions and their subtypes regarding cancer survival. OBJECTIVE: To determine the association of developing cirAEs following treatment with anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) therapy with patient survival. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the TriNetX Diamond Network, a database of health records and claims data from more than 200 million US and European patients, to conduct a population-level cohort analysis. The study included 7008 eligible patients who developed cirAEs after treatment with anti-PD-1 or anti-PD-L1 therapy for malignant neoplasms of digestive organs, bronchus or lung, melanoma of skin, and urinary tract who were identified through the TriNetX Diamond Network along with 7008 matched controls. EXPOSURES: Development of cirAEs within 6 months following anti-PD-1 or anti-PD-L1 therapy. MAIN OUTCOMES AND MEASURES: A 6-month analysis using a Cox proportional hazards model was performed to determine the association of cirAEs with overall survival after adjusting for demographic characteristics, cancer type, and cancer stage. RESULTS: A total of 7008 patients (3036 women [43.3%]; mean [SD] age, 68.2 [11.2] years) were matched to 7008 (3044 women [43.4%]; mean [SD] age, 68.3 [11.1] years) controls. Pruritus (hazard ratio [HR], 0.695; 95% CI, 0.602-0.803; P < .001), drug eruption (HR, 0.755; 95% CI, 0.635-0.897; P = .001), xerosis (HR, 0.626; 95% CI, 0.469-0.834; P = .001), nonspecific rashes (HR, 0.704; 95% CI, 0.634-0.781; P < .001), and appearance of any cirAE (HR, 0.778; 95% CI, 0.726-0.834; P < .001) were significantly protective of mortality using a Benjamini-Hochberg correction with a significance level of .05. Additionally, psoriasis (HR, 0.703; 95% CI, 0.497-0.994; P = .045) and lichen planus/lichenoid dermatitis (HR, 0.511; 95% CI, 0.279-0.939; P = .03) were significant. Eczematous dermatitis (HR, 0.612; 95% CI, 0.314-1.195), vitiligo (HR, 0.534; 95% CI, 0.254-1.123), bullous pemphigoid (HR, 0.524; 95% CI, 0.140-1.956), and Grover disease (HR, 0.468; 95% CI, 0.115-1.898) were all associated with strong protective clinical effects. CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that the development of cirAEs is strongly associated with response to ICI therapy and patient survival.

Post-chemotherapy Laparoscopic Retroperitoneal Lymph Node Dissection for Mixed Malignant Germ Cell Testicular Tumors.

INTRODUCTION: Retroperitoneal lymph node dissection (RPLND) is performed to treat residual disease following chemotherapy for stage II and III testicular cancer. Significant morbidity can be associated with open RPLND. As such, laparoscopic techniques have been demonstrated to be safe and effective in select cases. Outcomes following post-chemotherapy laparoscopic RPLND for mixed malignant germ cell testicular tumors (MMGCT) are limited in the literature. PATIENTS AND METHODS: We performed a retrospective chart review for patients who underwent laparoscopic RPLND at our institution for MMGCT from May 2006 to October 2016. Patient clinical data and perioperative and oncologic outcomes were recorded. RESULTS: Twenty-three patients underwent post-chemotherapy laparoscopic RPLND. Thirty-five percent (8/23) underwent bilateral template dissection, whereas 65% (15/23) underwent a modified unilateral template dissection. Robotic assistance was utilized in 22% (5/23) of cases. Bilateral template was inferior to unilateral template RPLND in operative time, estimated blood loss, open conversion rate, length of hospital stay, and complication rate. The mean follow-up was 35.1 months and 43.3 months for the bilateral and unilateral template groups, respectively. The mean lymph node yield and recurrence rate were similar between the 2 cohorts. One recurrence of mature teratoma was noted 67 months after unilateral laparoscopic RPLND. CONCLUSIONS: In select patients, laparoscopic RPLND for stage II and III MMGCT is safe and effective in the post-chemotherapy setting. Bilateral template laparoscopic RPLND was associated with inferior perioperative outcomes, but similar oncologic outcomes compared with unilateral template. Patients requiring bilateral template RPLND should be considered for an open approach.

The Accuracy of Prostate Magnetic Resonance Imaging Interpretation: Impact of the Individual Radiologist and Clinical Factors.

OBJECTIVE: To compare test performance of multiparametric magnetic resonance imaging (mpMRI) for detection of prostate cancer between individual radiologists using the Prostate Imaging Reporting and Data System (PI-RADS) and to identify clinical factors that may predict test performance. MATERIALS AND METHODS: We examined our database of consecutive men who received prostate mpMRI prior to biopsy between September 2014 and December 2016 (n = 459). Test performance (eg, sensitivity, specificity, positive predictive value [PPV] and negative predictive value) were defined with PI-RADS classification 4 or 5 considered test positive and Gleason score ≥7 on biopsy from any targeted core considered outcome positive. Multivariate logistic regression was performed to identify clinical variables that affect test performance. RESULTS: No significant differences in test performance were found among individual radiologists. Prior biopsy (odds ratio [OR] 0.10, P = .01), radiologist experience >500 prostate mpMRI (OR 0.18, P = .04), transition zone location (OR 0.10, P = .04), and posterior location (OR 0.04, P = .03) were predictors of diminished sensitivity. Location of the mpMRI lesion in the TZ was a predictor of improved specificity (OR 2.53, P = .04). Increasing age (OR 1.07, P <.01) and prostate-specific antigen (OR 1.10, P <.01) predicted increased PPV, while prior biopsy predicted decreased PPV (OR 0.50, P <.01). CONCLUSION: Although variation exists in test performance among individual radiologists using PI-RADS, significant differences were not observed. Additional prostate mpMRI experience was not beneficial in improving accuracy of interpretation. Nonmodifiable patient variables-including prostate lesion location, prior biopsy history, prostate-specific antigen, and age-are predictive of prostate mpMRI test performance.