The effect of opioids on the efficacy of immunotherapy in recurrent/metastatic squamous cell carcinoma of the head and neck.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) causes severe pain and opioids, the mainstay of pain management, may have immunomodulatory effects. We evaluated the effect of opioids on immunotherapy efficacy in recurrent/metastatic (R/M) HNSCC patients. MATERIALS AND METHODS: In a retrospective study of 66 R/M HNSCC patients from 2015 to 2020, opioid dosage, calculated as mean morphine milligram equivalent per day, was assessed on the day of anti-PD-1 monoclonal antibody (mAb) treatment and most recent prior visit. Intratumoral T cells were evaluated by single cell RNAseq and immunohistochemistry prior to treatment. Univariable and multivariable Cox proportional hazards and logistic regression models were used to estimate the association between opioid usage, progression-free survival (PFS), overall survival (OS), disease control rate. RESULTS: Patients were 79% male, 35% oropharynx, 35% oral cavity, 40% locoregional recurrence, and 56% platinum failure. Higher opioid dosage by continuous variable was significantly associated with lower PFS (p = 0.016) and OS (p < 0.001). In multivariable analysis, including platinum failure status and PD-L1, higher opioids were associated with lower OS. Opioid usage by categorical variable was associated with significantly lower intratumoral CD8+ T cells. Opioid receptor, OPRM1, expression was identified in intratumoral and circulating T cells. CONCLUSIONS: In our study cohort of anti-PD-1 mAb treatment in R/M HNSCC patients, higher opioids were associated with significantly lower PFS and OS and lower CD8+ T cells in the tumor microenvironment. To our knowledge, this is the first analysis in R/M HNSCC patients and further research into the clinical and biologic effect of opioids is warranted.

Immunotherapy in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck.

Head and neck cancer is the 6th most common cancer worldwide with the most common histology being squamous cell carcinoma (HNSCC). While the majority of patients present at a stage where curative intent therapy is possible, when patients recur and/or develop metastatic disease, outcomes are generally poor, especially with systemic therapy alone, and they lag behind other solid tumors. Over the last decade immunotherapy has revolutionized the field of oncology, and anti-PD-1-based therapy has changed the standard of care in recurrent/metastatic (R/M) HNSCC as well. With these gains have come new questions to continue to move the field forward. In this review, we discuss the tumor immune microenvironment and predictive biomarkers and current status and future directions for immunotherapy in recurrent/metastatic head and neck cancer.

Etiologies of Extreme Thrombocytosis: A Contemporary Series.

OBJECTIVE: To describe the multifactorial etiologies of extreme thrombocytosis (EXT) in different care settings and the frequency of finding an occult malignancy. PATIENTS AND METHODS: We conducted a retrospective chart review at Mayo Clinic from January 1, 2011, through December 31, 2016. Adult patients who had at least 2 readings of platelet counts greater than 1000×109/L within 30 days of each other were included. We determined the causes of EXT on the basis of preset definitions of precipitating factors and identified the dominant causes on the basis of the trend of platelet counts. RESULTS: A total of 44,490 patients had thrombocytosis, and 305 patients (0.7%) had EXT. In 242 patients (79.3%), EXT was multifactorial. Surgical complications (54.1%) and hematologic malignancies (27.9%) were the 2 most dominant causes. Thirty-eight patients (12.5%) had new diagnoses of malignancies, mostly myeloproliferative neoplasms. In inpatients, surgical complications (71.9%), concurrent/previous splenectomy (50.5%), and infections (44.9%) were the most common causes, whereas hematologic malignancies (56.9%), iron deficiency (36.7%), and previous splenectomy (28.4%) were the most common causes in outpatients. Hematologic malignancy was 3.4 times more likely to be the cause of EXT in outpatients than in inpatients (56.9% vs 16.8%), and a new diagnosis of hematologic malignancy was 1.9 times more likely to be made in outpatients (15.6% vs 8.2%). Eighty-four percent of patients had resolution of EXT within 30 days. One patient died during the period of EXT. Nonsurgical patients with hematologic malignancies had the most prolonged period of EXT. CONCLUSION: Extreme thrombocytosis is a multifactorial hematologic condition, and its etiology differs substantially between inpatients and outpatients. Occult hematologic malignancies are uncommon in EXT when other major causes are present.

Characteristics of long-term survivors with multiple myeloma: A National Cancer Data Base analysis.

BACKGROUND: There exist insufficient data characterizing patients with multiple myeloma (MM) who experienced prolonged survival. A population-based analysis of long-term survivors was conducted to investigate the roles of sociodemographic factors and upfront stem cell transplantation (SCT). METHODS: The National Cancer Data Base is a US cancer database of approximately 34 million patients from >1500 cancer centers. Patients with MM were identified using the International Classification of Diseases for Oncology (ICD-O) code 9732 from January 2004 to December 2006 and were divided into 4 groups based on overall survival (OS). Sociodemographic characteristics, treatment facility, and use of SCT were recorded. The univariate and multivariate analyses were performed using multiple logistic regression and Pearson chi-square tests. RESULTS: A total of 26,986 patients with MM were identified. The median OS was 2.74 years. The majority of patients were male (54%), white (77%), insured (93%) and otherwise healthy (78%), lived in a metropolitan area (82%), were of high income (66%) and educational (58%) levels, and received treatment at nonacademic facilities (63%). Upfront SCT was used in 10% of patients. One in 6 patients (16%) were long-term survivors (group 4). When comparing group 4 (OS of ≥8.22 years) with the other groups (OS of <8.22 years), young age, female sex, high income and educational levels, residence in a rural area, insured status, no comorbidity, receipt of upfront SCT, and treatment at high-volume facilities were associated with long-term survival. CONCLUSIONS: Key differences in sociodemographic characteristics, patient volume at treatment facilities, and upfront SCT were associated with long-term survival. Improvements in health care access and health literacy, upfront SCT, and treatment at high-volume facilities might prolong patient survival.

Short-course versus long-course antibiotics in prosthetic joint infections: a systematic review and meta-analysis of one randomized controlled trial plus nine observational studies.

BACKGROUND: Prosthetic joint infections (PJIs) often require long-course antibiotic therapy. However, recent studies argue against the current practice and raise concerns such as the development of antibiotic resistance, side effects of medications and medical costs. OBJECTIVES: To review and compare the outcomes of short-course and long-course antibiotics in PJIs. METHODS: We conducted a systemic review and meta-analysis using a predefined search term in PubMed and EMBASE databases. Studies that met the inclusion criteria from inception to June 2018 were included. The quality of the included studies was assessed. RESULTS: A total of 10 articles and 856 patients were analysed, comprising 9 observational studies and 1 randomized controlled trial. Our meta-analysis showed no significant difference between short-course and long-course antibiotics (relative risk = 0.87, 95% CI = 0.62-1.22). Additionally, the older the studied group was, the more short-course antibiotics were favoured. CONCLUSIONS: When treating PJI patients following debridement, antibiotics and implant retention, an 8 week course of antibiotic therapy for total hip arthroplasty and a 75 day course for total knee arthroplasty may be a safe approach. For two-stage exchange, a shorter duration of antibiotic treatment during implant-free periods is also generally safe with the usage of antibiotic-loaded cement spacers.

Short- versus long-course antibiotics in osteomyelitis: A systematic review and meta-analysis.

Current practice of long-term antibiotic use in patients with osteomyelitis is controversial. Recent studies showed short-term antibiotic use to be non-inferior to long-term use, but the results of these studies have been inconsistent. In this review, the PubMed and Embase databases were searched from inception through to June 2018 for randomised controlled trials (RCTs), cohort studies or case-control studies comparing two different durations of antibiotic use. Short antibiotic courses were defined as antibiotics administered for a shorter period than the recommended 4-6 weeks. A random-effects model was used to calculate summary odds ratios (ORs) of treatment failure in patients treated with short-course antibiotics compared with long-course antibiotics. A total of 15 articles (5 RCTs and 10 observational studies) and 3598 patients were included. The overall OR of treatment failure in patients receiving short-course antibiotics was 1.50 [95% confidence interval (CI) 0.97-2.34]. Subgroup analysis revealed that a short course of antibiotic treatment was associated with an increased treatment failure rate in vertebral osteomyelitis (OR = 2.06, 95% CI 1.18-3.57) while having a similar rate to a long antibiotic course in acute osteomyelitis of childhood (OR = 1.86, 95% CI 0.75-4.64). Meta-regression found a higher proportion of Staphylococcus aureus infection was related to a higher risk of treatment failure in patients with vertebral osteomyelitis (Coef. = 4.996; P = 0.032). Short-course antibiotics are safe and effective in children with acute osteomyelitis. Long-course antibiotics may still be preferred in vertebral osteomyelitis, especially in patients with S. aureus infection.