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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Staphylococcal 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.Methods: In 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.Results: In 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.Conclusion: Combined therapy with clindamycin and rifampin is a safe, well tolerated and effective regimen for the treatment of staphylococcal periprosthetic infection. [ABSTRACT FROM AUTHOR]

Impaction bone grafts (IBG) in two-stage revision for prosthetic hip infection (PHI) might be more susceptible for infection, therefore antibiotic mixing through these grafts has been suggested. However, outcomes have not been compared with IBG without antibiotics and no long-term results are available. Therefore, we evaluated long-term infection-free outcome after the use of IBG without antibiotic supplement in two-stage revision for PHI. Patients were divided into positive (group 1, n = 8) and negative (group 2, n = 28) cultures at re-implantation and followed up to 18 years after re-implantation. Five of 36 patients died from non-orthopaedic causes (median 37, range 24-149 months). Five patients had a re-operation not related to infection (median 39, range 7-140 months). These were censored in the Kaplan-Meier estimator at the last outpatient evaluation. We found an overall re-infection rate of 2.8% within two years, which matches comparative studies in which antibiotic impregnated bone grafts had been used. In group 1, there was one re-infection after 44 months. In group 2, all three infections occurred within 56 months with an estimated infection-free percentage at 10 years of 87% (95% CI 66-96). Follow-up should be extended beyond two years and randomised clinical trials are needed for further comparison with IBG impregnated with antibiotics. [ABSTRACT FROM AUTHOR]

To dissect the effect of neoadjuvant PD-1 and CTLA4 blockade on intratumoral T cells in treatment-naive head and neck squamous cell carcinoma, we analyzed primary tumor immune infiltrates from responding and nonresponding patients. At baseline, a higher ratio between active (4-1BB/OX40+) and inactive regulatory CD4+ T cells was associated with immunotherapy response. Furthermore, upon therapy, this active regulatory T-cell (Treg) population showed a profound decrease in responding patients. In an analogous process, intratumoral dysfunctional CD8+ T cells displayed decreased expression of activity and dysfunction-related genes in responding patients, whereas in clinical nonresponders, natural killer cells showed an increased cytotoxic profile early upon treatment. These data reveal immunologic changes in response to dual PD-1/CTLA4 blockade, including a parallel remodeling of presumed tumor-reactive Treg and CD8+ T-cell compartments in responding patients, and indicate that the presence of activated Tregs at baseline may be associated with response., Significance: In head and neck squamous cell carcinoma, neoadjuvant PD-1/CTLA4 blockade has shown substantial response rates (20%-35%). As recognition of tumor antigens by T cells appears to be a critical driver of therapy response, a better understanding of alterations in T-cell state that are associated with response and resistance is of importance. This article is featured in Selected Articles from This Issue, p. 2109., (©2023 The Authors; Published by the American Association for Cancer Research.)

Objective: In this review, the concept of (synchronous) oligometastatic disease in patients with non-oncogene-driven non-small cell lung cancer (NSCLC) will be placed in the context of tumor biology and metastatic growth patterns. We will also provide considerations for clinical practice and future perspectives, which will ultimately lead to better patient selection and oligometastatic disease outcome., Background: The treatment landscape of metastasized NSCLC has moved from "one-size fits all" to a personalized approach. Prognosis has traditionally been poor but new treatment options, such as immunotherapy and targeted therapy, brighten future perspectives. Another emerging development is the recognition of patients with so-called "oligometastatic" state of disease. Oligometastatic disease has been recognized as a distinct clinical presentation in which the tumor is stated to be early in its evolution of metastatic potential. It is suggested that this stage of disease has an indolent course, comes with a better prognosis and therefore could be considered for radical multimodality treatment., Methods: Narrative overview of the literature synthesizing the findings of literature retrieved from searches of computerized databases, hand searches, and authoritative texts., Conclusions: Oligometastatic NSCLC is a broad spectrum disease, with a variable prognosis. Although the biology and behavior of "intermediate state" of metastatic disease are not fully understood, there is evidence that a subgroup of patients can benefit from local radical treatment when integrated into a multimodality regime. The consensus definition of oligometastatic NSCLC, including accurate staging, may help to uniform future trials. The preferable treatment strategy seems to sequential systemic treatment with subsequent local radical treatment in patients with a partial response or stable disease. Prognostic factors such as N-stage, number and site of distant metastases, tumor volume, performance status, age, and tumor type should be considered. The local radical treatment strategy has to be discussed in a multidisciplinary team meeting, taking into account patient characteristics and invasiveness of the procedure. However, many aspects remain to be explored and learned about the cancer biology and characteristics of intermediate state tumors., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-21-265). The series “Oligometastatic NSCLC: definition and treatment opportunities” was commissioned by the editorial office without any funding or sponsorship. DWD reports consulting fees from Roche, MSD, Novartis, Pfizer, Astra Zeneca, BMS, outside the submitted work. RC reports speaker fee from Roche, Pfizer and BMS, personal fees from Advisory board of MSD, Roche and Spectrum, outside the submitted work. AMCD reports personal fees from Roche, eli Lilly, Boehringer Ingelheim, Astra Zeneca, Pfizer, BMS, Amgen, Novartis, Takeda, Pharmamar and MSD, grants from BMS and Amgen, non-financial support from Abbvie, outside the submitted work. The authors have no other conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Background and Purpose: Radiotherapy (RT) with cetuximab is an alternative for advanced-stage head and neck squamous cell carcinoma (HNSCC) patients who are unfit for cisplatin treatment. As 5-year overall survival is below 50%, it is of interest to test PD-L1 immune checkpoint blockade (avelumab) with cetuximab-RT in the curative setting., Materials and Methods: Phase-I feasibility trial (planned n = 10, NCT02938273) of conventional cetuximab-RT with avelumab (concurrent 10 mg/kg Q2W + 4 months maintenance) for advanced-stage HNSCC patients unfit for cisplatin treatment., Results: One of ten included patients experienced grade 2 cetuximab-related infusion reaction and withdrew from the study before avelumab was administered. One patient discontinued treatment after 2 courses of avelumab and 12×2Gy RT for personal reasons. In 2/8 remaining patients, avelumab was stopped after 4 and 8 courses because of toxicity and tumor progression, respectively. There was no grade 4-5 toxicity. Grade 3 immune-related toxicity was manageable and occurred in 4 patients. One patient was treated with topical steroids for grade 3 maculopapular rash and 3 patients received high-dose prednisone for grade 3 elevated liver enzymes (n = 1) and pneumonitis (n = 2). Seven patients experienced grade 3 RT-related toxicity with no severe specific cetuximab-related toxicity. Tumor recurrence occurred in 4/8 patients (50%) after a median of 12 (8-26) months follow-up., Conclusion: Cetuximab-RT plus avelumab is feasible in patients with advanced-stage HNSCC who are unfit for cisplatin treatment. Immune-related toxicity was transient and manageable and radiotherapy-related toxicity was in accordance with standard of care. This pilot study provides grounds for larger efficacy trials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To compare outcome after definitive (chemo)radiotherapy (CRT group) with standard of care (surgery group) for advanced stage oral cavity carcinoma (OCC). Although definitive (chemo)radiotherapy is assumed to be inferior to surgery with regard to disease control, data on outcome of this approach are scarce., Methods: Retrospective analysis by chart review (2000-2013). Endpoints were locoregional control (LRC), disease-free survival (DFS), disease specific survival (DSS) and overall survival (OS)., Results: Between the CRT-group (n = 100) and Surgery-group (n = 109), baseline characteristics were equally distributed except stage and local tumor diameter (all p ≤ .001). In the CRT group, at 5 years the LRC rate was 49%, DFS 22%, DSS 39% and OS 22%. In the surgery group, at 5 years the LRC rate was 77%, DFS 45%, DSS 64% and OS 45%. The survival curves of the two groups significantly differed for LRC (p < .001), DFS and DSS (p = .001) and OS (p = .002). After adjusting for confounders and prognostic factors, we found a significant difference between the treatment groups in LRC (adjusted HR = 2.88, 95%CI 1.35-6.16, p = .006). Within 100 days, 5 patients (5%) died from treatment-related toxicity in CRT group and 1 patient after surgery (p = .21)., Conclusions: Although surgery with adjuvant radiotherapy for advanced stage OCC results in favorable locoregional control, definitive (chemo)radiotherapy is a curative alternative in patients often considered beyond cure and should be considered when surgery is not feasible., (Copyright © 2017 Elsevier Ltd. All rights reserved.)