Purpose: To characterize the role of B cells on human papilloma virus (HPV)-associated cancer patient outcomes and determine the effects of radiation and PD-1 blockade on Bcell populations.Experimental Design: Tumor RNA-sequencing data from over 800 patients with head and neck squamous cell carcinoma (HNSCC) and cervical cancer, including a prospective validation cohort, was analyzed to study the impact of B-cell gene expression on overall survival (OS). A novel murine model of HPV þ HNSCC was used to study the effects of PD-1 blockade and radiotherapy on B-cell activation, differentiation, and clonality including analysis by single-cell RNA-sequencing and B-cell receptor (BCR)sequencing. Human protein microarray was then used to quantify B-cell-mediated IgG and IgM antibodies to over 16,000 proteins in the serum of patients treated on a clinical trial with PD-1 blockade.Results: RNA-sequencing identified CD19 and IGJ as novel Bcell prognostic biomarkers for 3-year OS (HR, 0.545; P < 0.001). PD-1 blockade and radiotherapy enhance development of memory B cells, plasma cells, and antigen-specific B cells. BCRsequencing found that radiotherapy enhances B-cell clonality, decreases CDR3 length, and induces B-cell somatic hypermutation. Single-cell RNA-sequencing identified dramatic increases in B-cell germinal center formation after PD-1 blockade and radiotherapy. Human proteome array revealed enhanced IgG and IgM antibody responses in patients who derived clinical benefit but not those with progressive disease after treatment with PD-1 blockade.Conclusions: These findings establish a key role for B cells in patient outcomes and responses to PD-1 blockade in HPVassociated squamous cell carcinomas and demonstrate the need for additional diagnostics and therapeutics targeting B cells.
Background: The effect of concussions on professional athletes has been investigated in many sports. However, few studies have evaluated concussions in National Basketball Association (NBA) players. Hypothesis: We hypothesized that concussion incidence has increased, yet the return-to-play (RTP) rate will remain high following the institution of the NBA concussion policy (NBACP). We also hypothesized that the incidence of repeat concussions will be similar to first occurrences and that player performance and game availability will not be significantly affected by sustaining a concussion. Study Design: Descriptive epidemiology study. Methods: Publicly available records were searched to identify all concussions from NBA seasons 1999-2000 to 2017-2018. Player demographics and information regarding career history were tabulated. Incidence of concussion and RTP timing were evaluated before and after institution of the NBACP (2011). Minutes per game and game score per minute were evaluated pre- versus postconcussion. Player availability and performance were also compared with an age-, body mass index–, position-, and experience-matched control group of players who did not sustain a concussion. Results: A total of 189 concussions were reported in the NBA from 1999 to 2018, with a mean ± SD incidence of 9.7 ± 7.3 concussions per season. Following implementation of the NBACP, incidence significantly increased from 5.7 ± 2.8 to 16.7 ± 7.5 concussions per season ( P = .007). All players returned to play following first-time concussion after missing 7.7 ± 8.6 days and 3.5 ± 4.1 games. RTP time was not significantly different after implementation of the NBACP (games missed, P = .24; days missed, P = .27), and there was no difference in concussion-free time interval ( P = .29). Game score per minute and minutes per game were not significantly affected by sustaining a concussion (both P > .05). Conclusion: Concussion incidence in NBA players is approximately 17 instances per season since the 2011 institution of a league-wide concussion policy. The number of reported concussions significantly increased following the policy, in line with trends seen in other professional sports leagues. Players have retained a high rate of RTP after 3 to 4 missed games. Player performance and availability are not affected by sustaining a concussion following successful RTP.
BackgroundThe Cavernous Hemangioma Exclusively Endonasal Resection CHEER classification system was developed to standardize prospective outcome analysis following orbital cavernous hemangioma OCH resection The goal of this study was to retroactively apply the CHEER system to all prior existing reports of endoscopic resection of primary benign orbital tumors BOTs to compare patient presentations perioperative characteristics and outcomes between OCH and other BOTs and determine whether the CHEER categorization regime could be expanded to other BOTs Methods A systematic review of studies reporting exclusively endoscopic resections of OCH and other BOTs eg solitary fibrous tumor schwannoma and meningioma was performed Patient tumor characteristics and operative outcomes were recorded All tumors with adequate reporting were retrospectively assigned a CHEER stage Outcomes were compared using chi-square or Fisher's exact tests Results Ninety-three studies met inclusion criteria and sufficient data were available in studies comprising tumors n =OCHs n = other BOTs Baseline patient and tumor characteristics as well as intraoperative and short-term postoperative outcomes were not signifi-cantly different between OCHs and other BOTs Long-term outcomes eg visual deficits diplopia eye position and recurrence also did not differ when controlling for CHEER stage Conclusion This review represents the largest collection of outcomes data following exclusively endoscopic endonasal resection of BOTs Short-term and long-term outcomes appear similar between OCHs and other BOTs These results suggest that exclusively endoscopic resection of orbital tumors may be effective in a range of benign pathologies Furthermore these results support a broader application of the CHEER system to other benign primary orbital tumors
A need for extension of postoperative opioid pain control is not uncommon after ESS. Patient baseline clinical characteristics are predictive of a need for re-prescription of opioids. Surgical extent is not associated with need for prolonged postoperative opioid pain management.
BackgroundSinonasal squamous cell carcinoma (SNSCC) is the most common malignancy of the paranasal sinuses. Surgery is the mainstay of treatment, yet positive surgical margins (PSM) are common and the prognostic impact on overall survival (OS) is mixed. Given the heterogeneity of impact of PSM on OS within the literature, we hypothesized that extent of tumor extirpation (microscopic PSM vs macroscopic PSM) may play a role in OS.MethodsPatients with SNSCC were identified in the National Cancer Database (NCDB, n = 7808). Of these, 4543 patients underwent surgery, 3265 patients underwent nonsurgical therapy. Kaplan‐Meier curves were used to compare OS between negative surgical margin (NSM), micro‐PSM, and macro‐PSM cohorts vs patients undergoing primary nonsurgical therapy in a propensity‐score‒matched analysis. Multivariable analysis of factors associated with macro‐PSM was also performed.ResultsOne thousand thirty‐three (22.0%) of the surgery patients had PSM, and approximately half (n = 521, 50.6%) of these had macro‐PSM. When compared with nonsurgical treatment, propensity‐score‒matched results demonstrated improved OS in patients with NSM and micro‐PSM (p < 0.001), but macro‐PSM patients did not demonstrate improvement (p = 0.20). Tumor within the paranasal sinuses and advanced nodal classification (N2/N3) (odds ratio [OR], 1.18; p = 0.02; and OR, 15.09; p = 005, respectively) was associated with increased odds of macro‐PSM on multivariable analysis.ConclusionWe demonstrate that the degree of tumor extirpation correlates with OS. Macro‐PSM did not confer a benefit to OS when compared with nonsurgical therapy, and factors including tumor location and advanced nodal status affect whether surgery will result in macro‐PSM. Given these findings, informed, shared decisionmaking between patient and surgeon regarding nonsurgical alternatives should occur before electing to proceed with surgery in SNSCC.
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