Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO’s MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC.

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Background Human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (OPSCC) is a highly immunogenic tumor and differences in tumor microenvironment might contribute to the improved survival of HPV‐positive OPSCC patient. Methods A comprehensive multivariate analysis with clinical and immune variables (human leukocyte antigen [HLA] I/II, programmed death ligand 1 (PD‐L1), programmed death receptor 1 (PD1), T cells, and macrophages) was performed in 142 OPSCC patients. Results We found an inverse correlation between the expression of HLA class II molecules on tumor cells and CD68+ CD163+ tumor‐associated macrophages (TAMs). High HLA‐DP/DQ/DR expression and low number of TAMs were associated with longer disease‐specific survival and disease‐free survival (DFS). Furthermore, a new population of CD8+ FoxP3+ T cells was correlated with shorter DFS in multivariate analysis. Conclusions \We identified new prognostic markers for patients with oropharyngeal cancer, which can be used for selecting patients that can benefit from immunotherapy.

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Objective Most studies that report on salvage surgery after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) are small and heterogeneous. Subsequently, some relevant questions remain unanswered. We specifically focused on (1) difference in prognosis per tumor subsite, corrected for disease stage, and (2) differences in prognosis after salvage surgery for local, regional, and locoregional recurrences. Study Design Retrospective analysis. Setting Single-center study (2000-2016). Subjects and Methods Patients treated with salvage surgery for HNSCC recurrence after (chemo)radiotherapy. Results In total, 189 patients were included. Five-year overall survival (OS) was 33%, and median OS was 18 (95% confidence interval [CI], 11-26) months. Treatment-related mortality was 2%. Larynx carcinoma was associated with more favorable local (adjusted hazard ratio [HR] = 4.02; 95% CI, 1.46-11.10; P = .007) and locoregional control (adjusted HR = 5.34; 95% CI, 1.83-15.61; P = .002) than pharyngeal carcinoma. American Society of Anesthesiologists (ASA) score (≥3 vs 1-2: adjusted HR = 3.04; 95% CI, 1.17-7.91; P = .023), pT stage (3-4 vs 1-2: adjusted HR = 4.41; 95% CI, 1.65-11.82; P = .003), and salvage surgery for locoregional recurrences (locoregional vs local: adjusted HR = 3.81; 95% CI, 1.13-11.82; P = .021) were independent predictors for disease-free survival (DFS). Conclusion Salvage surgery for larynx carcinoma, regardless of disease stage and other prognostic factors, results in more favorable loco(regional) control but not favorable DFS than pharyngeal carcinoma. The observed difference in DFS between salvage surgery for local and regional recurrences was not significant after correction for confounders. However, survival following salvage surgery for locoregional disease is significantly worse. For this subgroup, we propose to consider T status and comorbidity for clinical decision making, as high pT stage and ASA score are independent predictors for worse DFS.

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BackgroundStaphylococcal species account for more than 50% of periprosthetic joint infections (PJI) and antimicrobial therapy with rifampin-based combination regimens has been shown effective. The present study evaluates the safety and efficacy of clindamycin in combination with rifampin for the management of staphylococcal PJI.MethodsIn this retrospective cohort study, patients were included who received clindamycin-rifampin combination therapy to treat a periprosthetic hip or knee infection by Staphylococcus aureus or coagulase-negative staphylococci. Patients were treated according to a standardized treatment algorithm and followed for a median of 54 months.Of the 36 patients with periprosthetic staphylococcal infections, 31 had an infection of the hip, and five had an infection of the knee. Eighteen patients underwent debridement and retention of the implant (DAIR) for an early infection, the other 18 patients underwent revision of loose components in presumed aseptic loosening with unexpected positive cultures.ResultsIn this study, we report a success rate of 86%, with five recurrent/persistent PJI in 36 treated patients. Cure rate was 78% (14/18) in the DAIR patients and 94% (17/18) in the revision group. Five patients (14%) discontinued clindamycin-rifampin due to side effects. Of the 31 patients completing the clindamycin-rifampin regimen 29 patients (94%) were cured.ConclusionCombined therapy with clindamycin and rifampin is a safe, well tolerated and effective regimen for the treatment of staphylococcal periprosthetic infection.