Citations

Since the first approval for immune checkpoint inhibitors (ICIs) for the treatment of cutaneous melanoma more than a decade ago, immunotherapy has completely transformed the treatment landscape of this chemotherapy-resistant disease. Combination regimens including ICIs directed against programmed cell death protein 1 (PD-1) with anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) agents or, more recently, anti-lymphocyte-activation gene 3 (LAG-3) agents, have gained regulatory approvals for the treatment of metastatic cutaneous melanoma, with long-term follow-up data suggesting the possibility of cure for some patients with advanced disease. In the resectable setting, adjuvant ICIs prolong recurrence-free survival and several are FDA-approved. Although not yet approved, neoadjuvant ICIs have also shown to improve event-free survival and remains an ongoing area of investigation. Other immunotherapy strategies, such as oncolytic virotherapy for injectable cutaneous melanoma, bispecific T-cell engager therapy for HLA-A*02:01 genotype-positive uveal melanoma, and lifileucel, an autologous tumor-infiltrating lymphocyte therapy, for unresectable or metastatic melanoma are also available to patients. Despite the remarkable efficacy of these regimens for many patients with cutaneous melanoma, traditional immunotherapy biomarkers (ie, programmed death-ligand 1 expression, tumor mutational burden, T-cell infiltrate and/or microsatellite stability) have failed to reliably predict response. Furthermore, ICIs are associated with unique toxicity profiles, particularly for the highly active combination of anti-PD-1 plus anti-CTLA-4 agents. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop this clinical practice guideline on immunotherapy for the treatment of melanoma, including rare subtypes of the disease (eg, uveal, mucosal), with the goal of improving patient care by providing guidance to the oncology community. Drawing from published data and clinical experience, the Expert Panel developed evidence- and consensus-based recommendations for healthcare professionals using immunotherapy to treat melanoma, with topics including therapy selection in the advanced and perioperative settings, intratumoral immunotherapy, when to use immunotherapy for patients with BRAF V600-mutated disease, management of patients with brain metastases, evaluation of treatment response, special patient populations, patient education, quality of life, and survivorship, among others.

Abstract Isolated patellofemoral arthritis is a common debilitating condition in adults older than 40 years of age. Surgical options such as patellofemoral arthroplasty exist for those who failed to respond to nonoperative treatment. However, early patellofemoral arthroplasty techniques often resulted in poor outcomes due to mal‐tracking and malalignment of components. Robotic‐assisted surgery recently has been introduced as an alternative to classic patellofemoral arthroplasty, with the potential to improve the anatomical fit and reproducibility of implant positioning. We present the technique for minimally invasive robotic‐assisted patellofemoral arthroplasty system. Technique Video video See video under supplementary data.

Abstract Articular cartilage is critical for painless and low‐friction range of motion; however, disruption of articular cartilage, particularly in the knee joint, is common. Treatment options are based on the size and depth of the chondral defect, as well as involvement of subchondral bone. The gold standard for evaluation of articular cartilage is with arthroscopy, but it is limited by its ability to objectively judge the depth and severity of chondral damage. Optical reflection spectroscopy has been introduced to objectively assess the thickness of cartilage. We present a technique to systematically evaluate the articular cartilage of the knee using BioOptico optical reflection spectroscopy (Arthrex) to better evaluate those with visible chondral and subchondral defects. Technique Video video See video under supplementary data.

Study Design. Secondary analysis of a large administrative database. Objective. The objectives of this study are to: 1) identify the incidence and cause of 90-day readmissions following primary elective lumbar spine surgery, 2) offer insight into potential risk factors that contribute to these readmissions, and 3) quantify the cost associated with these readmissions. Summary of Background Data. As bundled-payment models for the reimbursement of surgical services become more popular in spine, the focus is shifting toward long-term patient outcomes in the context of 90-day episodes of care. With limited data available on national 90-day readmission statistics available, we hope to provide evidence that will aid in the development of more cost-effective perioperative care models. Methods. Using ICD-9 coding, we identified all patients 18 years of age and older in the 2014 Nationwide Readmissions Database (NRD) who underwent an elective, inpatient, primary lumbar spine surgery. Using multivariate logistic regression, we identified independent predictors of 90-day readmission while controlling for a multitude of confounding variables and completed a comparative cost analysis. Results. We identified 169,788 patients who underwent a primary lumbar spine procedure. In total 4268 (2.5%) were readmitted within 90 days. There was no difference in comorbidity burden between cohorts (readmitted vs. not readmitted) as quantified by the Elixhauser Comorbidity index. Independent predictors of increased odds of 90-day readmission were: anemia, uncomplicated diabetes and diabetes with chronic complications, surgical wound disruption and acute myocardial infarction at the time of the index admission, self-pay status, and an anterior surgical approach. Implant complications were identified as the primary related cause of readmission. These readmissions were associated with a significant cost increase. Conclusion. There are clearly identifiable risk factors that increase the odds of hospital readmission within 90 days of primary lumbar spine surgery. An overall 90-day readmission rate of 2.5%, while relatively low, carries significantly increased cost to both the patient and hospital. Level of Evidence: 3

Abstract Purpose: High-dose aldesleukin (HD IL2) received FDA approval for the treatment of metastatic renal cell carcinoma (MRCC) in 1992, producing a 14% objective response rate (ORR) and durable remissions. Retrospective studies suggested that clinical and pathologic features could predict for benefit. The Cytokine Working Group conducted this prospective trial to validate proposed predictive markers of response to HD IL2. Experimental Design: Standard HD IL2 was administered to prospectively evaluate whether the ORR of patients with mRCC with “good” predictive pathologic features based on an “integrated selection” model [ISM (e.g., clear-cell histology subclassification and carbonic anhydrase-9 (CA-9) IHC staining] was significantly higher than the ORR of a historical, unselected population. Archived tumor was collected for pathologic analysis including tumor programmed death-ligand 1 (PD-L1) expression. Results: One hundred and twenty eligible patients were enrolled between June 11 and September 7; 70% were Memorial Sloan Kettering Cancer Center (New York, NY) intermediate risk, 96% had clear cell RCC, and 99% had prior nephrectomy. The independently assessed ORR was 25% (30/120, 95% CI, 17.5%–33.7%, P = 0.0014; 3 complete responses, 27 partial responses) and was higher than a historical ORR. Thirteen patients (11%) remained progression free at 3 years and the median overall survival was 42.8 months. ORR was not statistically different by ISM classification (“good-risk” 23% vs. “poor-risk” 30%; P = 0.39). ORR was positively associated with tumor PD-L1 expression (P = 0.01) by IHC. Conclusions: In this prospective, biomarker validation study, HD IL2 produced durable remissions and prolonged survival in both “good” and “poor-risk” patients. The proposed ISM was unable to improve the selection criteria. Novel markers (e.g., tumor PD L1 expression) appeared useful, but require independent validation. Clin Cancer Res; 21(3); 561–8. ©2014 AACR.

Dysplastic Barrett's esophagus is a condition that offers multiple diagnostic and therapeutic challenges. The diagnosis of dysplasia within Barrett's esophagus currently relies on periodic endoscopic surveillance with multiple biopsies, a methodology limited by random sampling error, inconsistent histopathologic interpretation and delay in diagnosis. Optical spectroscopic and imaging techniques have the potential to identify dysplastic or early neoplastic lesions in real-time. These diagnostic modalities are needed to enhance the endoscopic surveillance of Barrett's esophagus in the future as well as help to define lesions for endoscopic therapy. Esophagectomy has been the standard of care for Barrett's esophagus with high-grade dysplasia although it is a procedure associated with significant morbidity and mortality. Minimally invasive endoscopic ablative therapies are attractive and less morbid alternatives to esophagectomy, with promising results obtained from the use of light-activated drugs (i.e., photodynamic therapy). The combination of novel optical diagnostic techniques and therapies will provide the endoscopist with much needed tools that can considerably enhance the management of patients with Barrett's esophagus. This article reviews the current status and future prospects of optical-based modalities for diagnosis and therapy of dysplastic Barrett's esophagus.