Search

IDH2 R172 mutations occur in sinonasal undifferentiated carcinoma (SNUC), large-cell neuroendocrine carcinoma (LCNEC), sinonasal adenocarcinomas, and olfactory neuroblastoma (ONB). We performed a clinical, pathologic, and genetic/epigenetic analysis of a large IDH2-mutated sinonasal tumor cohort to explore their distinct features. A total 165 sinonasal/skull base tumors included 40 IDH2 mutants studied by light microscopy, immunohistochemistry, and genome-wide DNA methylation, and 125 IDH2 wild-type tumors used for comparison. Methylation profiles were analyzed by unsupervised hierarchical clustering, t-distributed stochastic neighbor embedding dimensionality reduction and assessed for copy number alterations (CNA). Thirty-nine histologically assessable cases included 25 (64.1%) SNUC, 8 (20.5%) LCNEC, 2 (5.1%) poorly differentiated adenocarcinomas, 1 (2.7%) ONB, and 3 (7.7%) IDH2-mutated tumors with ONB features. All cases were high-grade showing necrosis (82.4%), prominent nucleoli (88.9%), and median 21 mitoses/10 HPFs. AE1/AE3 and/or CAM 5.2 were positive in all and insulinoma-associated protein 1 (INSM1) in 80% cases. All IDH2 mutants formed one distinct group by t-distributed stochastic neighbor embedding dimensionality reduction separating from all IDH2 wild-type tumors. There was no correlation between methylation clusters and histopathologic diagnoses. Recurrent CNA included 1q gain (79.3%), 17p loss (75.9%), and 17q gain (58.6%). No CNA differences were observed between SNUC and LCNEC. IDH2 mutants showed better disease-specific survival than SMARCB1-deficient (P=0.027) and IDH2 wild-type carcinomas overall (P=0.042). IDH2-mutated sinonasal tumors are remarkably homogeneous at the molecular level and distinct from IDH2 wild-type sinonasal malignancies. Biology of IDH2-mutated sinonasal tumors might be primarily defined by their unique molecular fingerprint rather than by their respective histopathologic diagnoses.

Background Patients with human papillomavirus–related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy. Methods In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided. Results Fifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation–related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03). Conclusions Deescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy.

PURPOSE The objective response rate (ORR) for single-agent anti–programmed death receptor 1 (anti–PD-1) therapy is modest in patients with metastatic or recurrent head and neck squamous cell carcinoma (HNSCC). We aimed to test whether radiotherapy may act synergistically with anti–PD-1 therapy to improve response through the abscopal effect. PATIENTS AND METHODS We conducted a single-center, randomized, phase II trial of nivolumab (anti–PD-1 therapy) versus nivolumab plus stereotactic body radiotherapy (SBRT) in patients with metastatic HNSCC. Patients had at least two metastatic lesions: one that could be safely irradiated and one measurable by RECIST version 1.1. Patients were randomly assigned (1:1), stratified by human papillomavirus status, to nivolumab (3 mg/kg intravenously every 2 weeks) or nivolumab (same dose) plus SBRT (9 Gy × 3) to 1 lesion. The primary end point was ORR in nonirradiated lesions, which was assessed by RECIST in patients with at least one available set of on-treatment images; safety was assessed in a per-protocol population. RESULTS Between March 11, 2016, and June 22, 2018, 62 patients were randomly assigned to nivolumab (n = 30) or nivolumab plus SBRT (n = 32). There was no statistically significant ORR difference between arms (34.5% [95% CI, 19.9% to 52.7%] v 29.0% [95% CI, 16.1% to 46.6%]; P = .86). There was no significant difference in overall survival ( P = .75), progression-free survival ( P = .79), or response duration ( P = .26). Grade 3-5 toxicities were similar (13.3% v 9.7%; P = .70). CONCLUSION We found no improvement in response and no evidence of an abscopal effect with the addition of SBRT to nivolumab in unselected patients with metastatic HNSCC.

Because of the national emergency triggered by the coronavirus disease 2019 (COVID‐19) pandemic, government‐mandated public health directives have drastically changed not only social norms but also the practice of oncologic medicine. Timely head and neck cancer (HNC) treatment must be prioritized, even during emergencies. Because severe acute respiratory syndrome coronavirus 2 predominantly resides in the sinonasal/oral/oropharyngeal tracts, nonessential mucosal procedures are restricted, and HNCs are being triaged toward nonsurgical treatments when cures are comparable. Consequently, radiation utilization will likely increase during this pandemic. Even in radiation oncology, standard in‐person and endoscopic evaluations are being restrained to limit exposure risks and preserve personal protective equipment for other frontline workers. The authors have implemented telemedicine and multidisciplinary conferences to continue to offer standard‐of‐care HNC treatments during this uniquely challenging time. Because of the lack of feasibility data on telemedicine for HNC, they report their early experience at a high‐volume cancer center at the domestic epicenter of the COVID‐19 crisis., Cancer care is undeniably affected by the coronavirus disease 2019 (COVID‐19) public health emergency, but quality cancer care must persist. A high‐volume cancer center from the domestic epicenter of the COVID‐19 crisis shares its multidisciplinary approach to integrating current public health restrictions and adopting telemedicine to optimize the care of patients with head and neck cancer; it is hoped that this center's experience will provide helpful insights to oncology colleagues.

Purpose Activation of the PI3K/mTOR signaling pathway is common in head and neck squamous cell carcinoma (HNSCC). BYL719 is an α-specific PI3K inhibitor that is synergistic and efficacious when combined with cetuximab, a Food and Drug Administration–approved radiosensitizing agent in the treatment of HNSCC. The agent independently has been shown to enhance radiosensitivity. This study evaluates the addition of BYL719 to cetuximab and radiation in the treatment of locally advanced HNSCC. Methods and Materials This is a single-institution, phase 1 study. Patients with American Joint Committee on Cancer seventh edition stage III to IVB HNSCC received standard cetuximab (400 mg/m2 intravenous loading dose) before intensity modulated radiation therapy (IMRT) followed by 250 mg/m2 weekly infusions during IMRT. BYL719 was given orally during IMRT in 3 dose levels: (1) 200 mg/d, (2) 250 mg/d, or (3) 300 mg/d in a standard 3 + 3 dose-escalation design. Results Eleven patients were evaluable. Dose level 2 was the maximum tolerated dose for BYL719. Two patients on dose level 3 had dose-limiting toxicities of oral mucositis that required a dose reduction of BYL719. One patient on dose level 2 had a dose-limiting toxicity of nausea that led to withdrawal of on-study treatment. Related grade 3 or higher adverse events consisted of decreased lymphocyte count, oral mucositis, dysphagia, hyperglycemia, maculopapular rash, and palmar-plantar erythrodysesthesia syndrome. All 11 patients had a complete response on posttreatment imaging, and 10 remain disease free. Of the 8 patients with mutational analysis, 1 had an activating PIK3CA mutation associated with a rapid response on serial intratreatment magnetic resonance imaging scans. Conclusions The recommended phase 2 dose of BYL719 is 250 mg/d in combination with cetuximab and IMRT in patients with locally advanced HNSCC. Further evaluation of the addition of BYL719 to the platinum-sparing regimen of cetuximab and IMRT in the treatment of locally advanced HNSCC is warranted.

Our understanding of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) and its molecular basis continues to evolve and produce important insights into customized therapeutic strategies. Novel therapeutics exploiting HPV-related targets are being evaluated in the incurable setting, while the favorable prognosis of locoregionally advanced disease has stimulated investigation into de-escalation strategies. There is much opportunity for better personalization of standard therapy according to HPV status. This review discusses both current and investigational therapeutic strategies for HPV-related OPC.

INTRODUCTION AND OBJECTIVE:Cytoreductive radical prostatectomy (cRP) might be an option in oligometastatic prostate cancer (PCa). However, no preoperative risk tool is available to select candidate...

ZusammenfassungDas Prostatakarzinom ist das häufigste solide Karzinom des Mannes. Die Inzidenz steigt mit zunehmendem Alter an. Durch die Etablierung neuer Therapiekonzepte insbesondere im progredienten Tumorstadium und in der metastasierten Erkrankung kann zum einen eine deutlich verbesserte Tumorkontrolle, damit verbunden aber auch eine erhöhte Belastung des Gesundheitssystems erreicht werden. Mittlerweile haben wir beim Prostatakarzinom, ähnlich wie beim Nierenzellkarzinom, die Möglichkeit aus einem Pool von verschiedenen Medikamenten zu wählen. Diese zeigen eine vergleichbare Effektivität bei einem unterschiedlichen Nebenwirkungsspektrum. Zur effektiven Diagnostik und Therapie des Prostatakarzinoms sind neben klinischen Parametern weitere Faktoren erforderlich, um ein individualisiertes Vorgehen zu erlauben. In der Diagnostik haben sich einige genetische Tests etabliert, während im metastasierten Tumorstadium eine intensivere genetische Aufarbeitung von liquid biopsies oder Gewebeproben zunehmend in der Routine Einklang findet. Möglichkeiten im kastrationsresistenten Prostatakarzinom mit der möglichen Patientenselektion zur individuellen Therapie sollen im folgenden Review aufgearbeitet werden.

PURPOSE Recurrent or metastatic adenoid cystic carcinoma (R/M ACC) is a malignant neoplasm of predominantly salivary gland origin for which effective therapies are lacking. We conducted a phase II trial evaluating the multitargeted tyrosine kinase inhibitor lenvatinib in patients with R/M ACC. PATIENTS AND METHODS This study was conducted with a two-stage minimax design. Patients with histologically confirmed R/M ACC of any primary site with radiographic and/or symptomatic progression were eligible. Any prior therapy was allowed except previous lenvatinib. Patients received lenvatinib 24 mg orally per day. The primary end point was overall response rate. Secondary end points were progression-free survival and safety. An exploratory analysis of how MYB expression and genomic alterations relate to outcomes was conducted. RESULTS Thirty-three patients were enrolled; 32 were evaluable for the primary end point. Five patients (15.6%) had a confirmed partial response, 24 patients (75%) had stable disease, two patients (6.3%) discontinued treatment as a result of toxicity before the first scan, and one patient (3.1%) had progression of disease as best response. Median progression-free survival time was 17.5 months (95% CI, 7.2 months to not reached), although only eight progression events were observed. Patients otherwise were removed for toxicity (n = 5), as a result of withdrawal of consent (n = 9), or at the treating physician’s discretion (n = 6). Twenty-three patients required at least one dose modification, and 18 of 32 patients discontinued lenvatinib for drug-related issues. The most common grade 3 or 4 adverse events were hypertension (n = 9; 28.1%) and oral pain (n = 3; 9.4%). Three grade 4 adverse events were observed (myocardial infarction, n = 1; posterior reversible encephalopathy syndrome, n = 1; and intracranial hemorrhage, n = 1). CONCLUSION This trial met the prespecified overall response rate primary end point, demonstrating antitumor activity with lenvatinib in R/M ACC patients. Toxicity was comparable to previous studies, requiring monitoring and management.

There is an ongoing change of paradigm in the treatment of metastatic prostate cancer (mPC). Taxan-based chemotherapy demonstrated a prolonged survival of patients in several randomized phase III trials. This is true in the situation of metastatic castration-resistent prostate cancer (mCRPC) as well as in the hormone-naive stage (metastatic castration-naive PC [mCNPC]). In patients with mCNPC, treatment with docetaxel in combination with androgen deprivation therapy (ADT) prolonged the median total survival time by 15 months in comparison to ADT alone. Comparable results were obtained by the endocrine combination treatment with ADT/abiraterone. With the current data in mind it seems to be useful to discuss the value of early combination therapy with ADT/docetaxel or ADT/abiraterone as well as the impact on further treatment options in the mCRPC setting and to define criteria for treatment decisions in clinical practice.

Background: Memorial Sloan Kettering Cancer Center (MSK) created the MSK Cancer Alliance in 2014, a dynamic and bidirectional collaboration with high-quality community providers to enhance access to state-of-the-art cancer care close to home. Hartford HealthCare Cancer Institute (HHC), joined the MSK Cancer Alliance as the first member in 2014. Research suggests that bone marrow transplant (BMT) is an underutilized definitive therapy (Yao et al, Biol Blood Bone Marrow Transplant 2013) for patients with hematologic malignancies and the timing of a referral for transplant has significant impact on patient outcomes (National Marrow Donor Program, available at: https://bethematchclinical.org/transplant-indications-and-outcomes/additional-outcomes/timing-impact-on-outcomes/). MSK and HHC developed the BMT Shared Care program to improve access to transplant, ensure BMT specialist consults for appropriate candidates occur during initial treatment planning, reduce burdensome travel for patients by facilitating care locally, and enhance seamless coordination between local oncologists and BMT providers from initial consult through post-transplant care. Methods: To achieve these goals, MSK and HHC physicians, nurses, and staff created a program that includes: HHC hiring a BMT nurse, who trained for 4 weeks at MSK, and works with MSK counterparts to create a streamlined referral process, pretransplant care at HHC, and travel logistics to MSK; MSK and HHC physicians hold virtual tumor boards to jointly evaluate patients and provide BMT consults at the optimal time; onsite lectures and observer-ships focused on advances in BMT, supportive care, and management of complications like graft versus host disease, leading to the integration of additional clinical services like infectious disease and dermatology; and research, including an MSK clinical trial open at HHC to identify and understand barriers to transplant in the community for patients with newly diagnosed or relapsed acute leukemia. Results: Since November 2015, HHC has referred 86 patients for BMT consult through this Shared Care program, with 35 patients transplanted or receiving immune effector cells (IEC) to date. Conclusions: The BMT Shared Care program effectively facilitates the referral and transplant of appropriate patients while allowing them to receive much of their pre- and post-transplant care in their local communities. Collaboration between BMT nurse coordinators and robust physician engagement are essential to this program. Future opportunities include expanding the use of telemedicine, enhancing electronic data sharing, quantifying and analyzing patient satisfaction, and expanding BMT research at HHC.

Purpose/Objective(s) Stage T4 larynx and hypopharynx cancers were poorly represented in the original organ preservation trials, so concerns over reduced outcomes with nonoperative management have led to a preference for surgery. For patients who refuse surgery or are not surgical candidates, there is little data to guide decision making and counseling. Therefore, we conducted a retrospective analysis of nonoperatively managed T4 larynx and hypopharynx cancer to report long-term therapeutic and functional outcomes. Materials/Methods Patients with primary larynx (n = 44) and hypopharynx (n = 53) cancer treated non-surgically with definitive radiation therapy (RT) or chemoradiation therapy (CRT) between 1/1/1997 and 12/31/2015 were included. Data collected included age, sex, KPS, smoking status, cancer site, T stage, N stage, CRT versus RT alone, IMRT versus non-IMRT, RT dose, resectability (as noted by surgeon), percutaneous endoscopic gastrostomy (PEG) and tracheostomy status, locoregional failure (LRF), distant metastases (DM), disease-free survival (DFS), and overall survival (OS). The Kaplan-Meier method was used to estimate time-to-event outcomes on univariate analysis (UVA). Results Median follow-up of surviving patients was 59 (range 15-154) and 45 (range 14-190) months for larynx and hypopharynx patients, respectively. The 2-/5-year OS rates were 73%/38% for larynx patients and 52%/29% for hypopharynx patients. LRF occurred in 25% (n = 11) and 19% (n = 10) of larynx and hypopharynx patients, respectively. Median disease-free interval to recurrence was 12 and 7 months in larynx and hypopharynx patients, respectively. On UVA of the larynx subset, N3 nodal status and non-IMRT treatment (n = 20, 45%) were significantly associated with detriment to OS (P = 0.046 and 0.037); treatment with RT alone impacted DFS (P = 0.028); age > 70 was significantly associated with LRF (P = 0.038, Gray's test). On UVA of the hypopharynx subset, only T4b status significantly impacted OS (P = 0.009) with no other predictive factors on outcomes analysis. In the larynx group, 75% required a tracheostomy and/or PEG, 55% of whom had neither device at most recent follow-up. Likewise, of the 86% of hypopharynx patients requiring tracheostomy and/or PEG, 27% had neither at last follow-up. Conclusion We report very encouraging disease control and survival for patients with stage T4 larynx and hypopharynx cancer who are not surgical candidates or refuse surgery. Overall, outcomes are better for larynx cancers than hypopharynx. With adequate supportive care and rehabilitation, patients are able to reach functional preservation, especially in the larynx subset. Given our analysis, we predict that both functional and therapeutic outcomes are further improved in the current IMRT era.

To identify potential risk factors for the development of venous thromboembolic events in testicular cancer patients receiving platinum-based chemotherapy. We performed a retrospective analysis including 255 patients with testicular germ cell tumors who received platinum-based chemotherapy from 2003 to 2018 as a multi-center observational cohort study. Patient and tumor characteristics of patients with and without a thromboembolic event were analyzed. 49 (19%) patients experienced a venous thromboembolic event, with the majority representing pulmonary embolism and deep venous thrombosis (47%). There were no significant differences regarding the development of a venous thromboembolic event between first- and second-line regimes. Multivariate analysis showed an increased risk for a venous thromboembolic event in patients with clinical stage ≥ IIC disease (OR 2.259 [95% CI 1.105–4.618], p = 0.026), elevated serum LDH (OR 2.162 [95% CI 1.018–4.593], p = 0.045), febrile neutropenia (OR 2.973 [95% CI 1.363–6.487], p = 0.006) and central venous access (OR 3.465 [95% CI 1.068–11.243], p = 0.039). Patients suffering from a venous thromboembolic event revealed a significantly reduced overall survival (p = 0.033) during a median follow-up of 8 months [IQR 2–18]. 19% of all patients treated by platinum-based chemotherapy due to testicular cancer suffered from a venous thromboembolic event, associated with reduced overall survival. As a result, monitoring of cancer patients at risk as well as the improvement of patients’ awareness of a thromboembolic event should thus be the main goal of their treating physicians.

Purpose of review Salvage surgeries are rarely offered and performed in prostate cancer except for isolated lymph node metastases. Meanwhile, data are sufficient that salvage radical prostatectomy is recommended by the guidelines. In the following review, we focus on different treatment strategies comparing open and DaVinci laparoscopic approach with regard to functional and oncologic outcome. Of further interest are palliative surgeries. Recent findings Salvage radical prostatectomy is mainly performed in high volume centres. Data are increasing on minimal invasive surgery, although data on functional outcome are conflicting. As patients with prostate cancer have longer life expectancy even in metastasized disease, the possibility of developing symptomatic progression increases as well. We need to be aware that the confrontation with symptomatic prostate cancer patients will be more frequent in the future and that there are surgical approaches to palliate these patients sufficiently. Summary Data on minimal invasive salvage radical prostatectomy are getting more valid and are an option in experienced centres. Salvage radical prostatectomy is a definitive curative option for the patients. To avoid local progression, palliative local surgeries need to be discussed with the patients.

Background Patient-reported outcomes (PROs) allow for the direct measurement of functional and psychosocial effects related to treatment. However, technological barriers, survey fatigue, and clinician adoption have hindered the meaningful integration of PROs into clinical care. The objective of the authors was to develop an electronic PROs (ePROs) program that meets a range of clinical needs across a head and neck multidisciplinary disease management team. Methods The authors developed the ePROs module using literature review and stakeholder input in collaboration with health informatics. They designed an ePROs platform that was integrated as the standard of care for personalized survey delivery by diagnosis across the disease management team. Tableau software was used to create dashboards for data visualization and monitoring at the clinical enterprise, disease subsite, and patient levels. All patients who were treated for head and neck cancer were eligible for ePROs assessment as part of the standard of care. A descriptive analysis of ePROs program implementation is presented herein. Results The Head and Neck Service at Memorial Sloan Kettering Cancer Center has integrated ePROs into clinical care. Surveys are delivered via the patient portal at the time of diagnosis and longitudinally through care. From August 1, 2018, to February 1, 2020, a total of 4154 patients completed ePROs surveys. The average patient participation rate was 69%, with a median time for completion of 5 minutes. Conclusions Integration of the head and neck ePROs program as part of clinical care is feasible and could be used to assess value and counsel patients in the future. Continued qualitative assessments of stakeholders and workflow will refine content and enhance the health informatics platform. Lay summary Patients with head and neck cancer experience significant changes in their quality of life after treatment. Measuring and integrating patient-reported outcomes as a part of clinical care have been challenging given the multimodal treatment options, vast subsites, and unique domains affected. The authors present a case study of the successful integration of electronic patient-reported outcomes into a high-volume head and neck cancer practice.

Introduction: The impact of teratomatous elements in orchiectomy specimens of metastasized testicular germ cell tumors (TGCT) regarding oncological outcome is still unclear. Methods: We performed a retrospective analysis including 146 patients with metastasized TGCT analysing patient characteristics. Results: Twenty-six (18%) of all patients showed teratomatous elements in the orchiectomy specimens. TGCT with teratomatous elements showed a significantly higher frequency of clinical-stage 2C-3 disease (73 vs. 49%, p = 0.031), visceral metastases (58 vs. 32%, p = 0.015), and poor prognosis (p = 0.011) than TGCT without teratomatous elements. Teratoma-containing TGCT revealed a significantly higher rate of post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND, 54 vs. 32%, p = 0.041), with teratomatous elements being more often present in the PC-RPLND specimens (43 vs. 11%, p = 0.020) than nonteratoma-containing primaries. In the Kaplan-Meier estimates, the presence of teratomatous elements in orchiectomy specimens was associated with a significantly reduced relapse-free survival (RFS) (p = 0.049) during a median follow-up of 36 months (10–115.5). Conclusions: The presence of teratomatous elements in orchiectomy specimens is associated with an advanced tumor stage, worse treatment response as well as a reduced RFS in metastasized TGCT. Consequently, the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients.

Background: To demonstrate the feasibility of resecting isolated locally relapsing seminal vesicle remnants after primary radical prostatectomy and radiotherapy. Early oncologic outcomes and prognostic risk factors for relapse are demonstrated. Objectives and Methods: A total of 32 patients underwent open resection of locoregional prostate cancer recurrence in seminal vesicles, as documented on either MRI, 11C-choline, or 68Ga-PSMA PET/CT scans. Age, PSA-DT, PSA, and time to recurrence after primary treatment resection status were used in a uni- and multivariate Cox regression analysis for biochemical relapse after surgery. Results: Median patient age at time of salvage surgery was 70 (57–77) years. Median PSA and PSA-DT was 2.79 (0.4–61.54) ng/mL and 5.4 (1.6–20.1) months, respectively. Median surgical time and hospital stay was 132 (75–313) min and 5.5 (4–13) days, respectively. After a mean follow-up of 29 (2–92) months, 3 patients died at 8, 14, and 40 months after salvage surgery, and 6 (18.75%) patients remain without biochemical relapse and further treatment. Median progression-free survival was 12 (1–81) months. In the univariable Cox regression analysis, age at time of surgery, preoperative PSA, and the time from primary treatment to salvage surgery were identified as significant parameters for biochemical relapse. Only the interval from primary to salvage surgery was significant in the multivariate analysis with a hazard ratio of 1.008 (95% CI: 1.001–1.015, p = 0.018). In the entire cohort, 4 adjunctive surgeries (3 ureteroneocystostomies and 1 nephrectomy) were needed due to local progressive disease. Conclusion: Seminal vesicle resection is feasible with no significant intra- or postoperative complications. Almost all patients progressed to biochemical or systemic relapse. Salvage surgery must be seen as a preventive for local symptoms, in our experience most often postrenal ipsilateral obstruction.

SMARCB1-deficient sinonasal carcinoma (SNC) is an aggressive malignancy characterized by INI1 loss mostly owing to homozygous SMARCB1 deletion. With the exception of a few reported cases, these tumors have not been thoroughly studied by massive parallel sequencing (MPS). A retrospective cohort of 22 SMARCB1-deficient SNCs were studied by light microscopy, immunohistochemistry, fluorescence in situ hybridization (n = 9), targeted exome MPS (n = 12), and Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) (n = 10), a bioinformatics pipeline for copy number/zygosity assessment. SMARCB1-deficient SNC was found in 13 (59%) men and 9 (41%) women. Most common growth patterns were the basaloid pattern (59%), occurring mostly in men (77%), and plasmacytoid/eosinophilic/rhabdoid pattern (23%), arising mostly in women (80%). The former group was significantly younger (median age = 46 years, range = 24-54, vs 79 years, range = 66-95, p 0.0001). Clear cell, pseudoglandular, glandular, spindle cell, and sarcomatoid features were variably present. SMARCB1-deficient SNC expressed cytokeratin (100%), p63 (72%), neuroendocrine markers (52%), CDX-2 (44%), S-100 (25%), CEA (4/4 cases), Hepatocyte (2/2 cases), and aberrant nuclear β-catenin (1/1 case). SMARCB1 showed homozygous deletion (68%), hemizygous deletion (16%), or truncating mutations associated with copy neutral loss of heterozygosity (11%). Coexisting genetic alterations were 22q loss including loss of NF2 and CHEK2 (50%), chromosome 7 gain (25%), and TP53 V157F, CDKN2A W110∗, and CTNNB1 S45F mutations. At 2 years and 5 years, the disease-specific survival and disease-free survival were 70% and 35% and 13% and 0%, respectively. SMARCB1-deficient SNCs are phenotypically and genetically diverse, and these distinctions warrant further investigation for their biological and clinical significance.

137 Background: Improved imaging modalities identify metastatic prostate cancer earlier. Atypical and oligometastatic disease is identified more often. Thus a more individual treatment approach in oligometastatic prostate cancer is getting more popular. We demonstrate our results in recurrent disease in seminal vesical remnants after radical prostatectomy and radiotherapy. Methods: A total of 33 patients underwent open resection of locoregional recurrence in seminal vesicals. In case of suspicious 68Ga-PSMA-PET findings in the small pelvis an additional ipsilateral lymph node dissection was performed in 10 patients. 11 patients already received hormone treatment fulfilling the definition of castration resistant prostate cancer. Age, PSA-DT, PSA, time to recurrence after primary treatment resection status were used in a uni and multivariate-cox regression analysis for biochemical relapse after surgery. Results: Median patient age at time of salvage surgery was 70(57-77) years. Median PSA and PSA-DT was 2.79(0.4-61.54)ng/ml and 5.4(1.6-20.1)months respectively. Median surgical time and hospital stay was 132 (75-313)min and 5.5(4-13)days. Median progression-free survival was 29 (8-47) months. After a mean follow-up of 22 months (3-68) months three patients died 8, 14, and 40 months after salvage surgery. In a univariable cox-regression analyses age at time of surgery, preoperative PSA and the time from primary treatment to salvage surgery have been identified as significant parameters for biochemichal relapse. Only the interval from primary to salvage surgery was significant with a Hazard ratio of 1.008 (95%-CI 1.001-1.015, p=0,018) in multivariate analysis. 4 adjunctive surgeries (Ureterovericoneostomy n=3 and one nephrectomy) were needed due to local progressive disease. Conclusions: Seminal vesicle resection is feasible with no significant intra and postoperative complications even in CRPC. Although there is a good median progression-free survival after 5 years almost all patients had biochemical or systemic relapse. Salvage surgery must be seen as prevention for local symptoms, to our experience most often postrenal ipsilateral obstruction.

INTRODUCTION AND OBJECTIVE:As has been shown recently guideline-compliance is suboptimal concerning the management of testis cancer. Guideline incompliance results in significantly impaired long-te...

INTRODUCTION AND OBJECTIVE:Certified Cancer Centers are instructed to present 100% of all cases at multidisciplinary tumor boards (MTD). Discussion of standard cases limits the time of more demandi...

INTRODUCTION AND OBJECTIVE:RPC is a biochemical diagnosis and it requires a positive prostate biopsy prior to RSP. A positive biopsy does not distinguish between locally recurrent or metastatic dis...

INTRODUCTION AND OBJECTIVE:Whereas radiation therapy of the local primary exerts longterm survival benefit in nmhPCA with low metastatic burden, the role of cRP is still unclear. It was the purpose...

INTRODUCTION AND OBJECTIVE:Androgen deprivation combined with apalutamide, abiraterone or docetexal represents the treatment of choice in mhnPCA. Cytoreductive radical prostatectomy (cRP) has been ...

INTRODUCTION AND OBJECTIVE:The STAMPEDE trial recently demonstrated a survival benefit for patients with oligometastatic prostate cancer (PCa) treated with androgen deprivation therapy (ADT) plus p...

INTRODUCTION AND OBJECTIVE:Cytoreductive radical prostatectomy (cRP) represents an option in oligo-metastatic prostate cancer (mPCa). However, the optimal multi-modal strategy of these men is unkno...

Testicular germ cell tumors (TGCT) are rare malignancies which affect young adults and adolescents between the ages of 15 and 40 years. In suspected malignant TGCT, the treatment of choice is radical orchiectomy. However, in specific cases this routine surgical approach has been challenged in favor of an organ-preserving approach with comparable oncological outcome. Thus, testis-preserving strategies should be considered in unilateral or bilateral synchronous or metachronous TGCT as well as incidentally found small testicular masses, which are mostly benign lesions including Sertoli cell tumors, Leydig cell tumors, adenomatoid tumors or epidermoid cysts. In case of a testis-preserving surgery, adjuvant postoperative radiation therapy (20 Gy) is recommended. The rational for this approach is that the remaining parenchyma harbors germ cell neoplasia in situ (GCNIS), which might lead to locally recurrent TGCT in 50% in the next following 5 years. However, testicular radiotherapy might result in infertility and 'Sertoli-cell only' syndrome because of radiation-induced destruction of germ cells as well as Leydig cell insufficiency in 20% of all patients leading to life-long androgen substitution. Therefore, radiation therapy should be delay or sperm banking be should performed in fertile patients wish to have children. This review provides an overview on literature regarding testis-preserving strategies in TGCT as well as GCNIS.

Objective: To investigate the diagnostic performance of gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) in patients with recurrent prostate cancer with regard to the presence of lymph node metastases (LNM) and local recurrences after primary radiotherapy. Patients and methods: We retrospectively reviewed 142 patients following salvage radical prostatectomy (sRP), 50 of which had a 68Ga-PSMA PET/CT performed as a preoperative staging module. Predictive clinical parameters were analysed in a multivariate Cox regression analysis. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and the accuracy of 68Ga-PSMA PET/CT were analysed with regard to LNM and local recurrence. Results: In all, 613 lymph nodes were resected in 40 patients and 23 lymph nodes had metastatic deposits in 14 patients. In all patients local recurrence could have been found with 68Ga-PSMA PET/CT. Sensitivity, specificity, PPV and NPV and accuracy on a per lymph node basis were 34.78% (16.38–57.2%), 100% (99.38–100%), 100%, 97.52% (96.69–98.15%) and 97.55% (96.00–98.62%). For detecting local recurrence, the sensitivity and PPV were both 100% with an accuracy of 100% (92.89–100%). Conclusion: 68Ga-PSMA PET/CT should be the standard imaging in biochemical recurrent prostate cancer. With this imaging module one detects first local recurrence and can detect locoregional and distant metastases more precisely than standard CT and bone scan.

Purpose of review Local treatment of the primary by either radical prostatectomy or radiation therapy is discussed controversially. The role of cytoreductive radical prostatectomy has been evaluated in few retrospective clinical studies but data of prospective randomized clinical phase-III trials are lacking. It is the purpose of this review to reflect the current knowledge on indication, functional and oncological outcomes of cytoreductive radical prostatectomy to objectively highlight what can be expected from this approach. Recent findings Cytoreductive radical prostatectomy (cRP) is associated with a long overall survival of more than 7 years and it is associated with a clinical progression-free survival of more than 6 years. When compared with nonsurgical approaches it becomes evident that about one-third of the patients will develop symptomatic local progression within 3 years whereas none of the surgically treated patients will experience such symptoms. cRP is associated with a low rate of significant complications and good functional outcome in well selected patients which do not differ from the results of a radical prostatectomy in treatment-naive patients. Summary Patients with low-volume/low-risk metastatic prostate cancer (mPCA), good response to neoadjuvant androgen deprivation therapy and a good Eastern Cooperative Onology Group performance status appear to be the best candidates for surgery. cRP might be an individualized treatment option in the multimodality management of mPCA. It is the purpose of the current to highlight the indication, surgical technique, treatment associated complications, functional and oncological outcome for cytoreductive radical prostatectomy.

Although perineural invasion (PNI) is recognized as an adverse prognostic factor in oral tongue squamous cell carcinoma (SCC), the patterns of failure are poorly defined.Patients with oral tongue SCC who received primary surgical treatment were identified. Specimens were reviewed by head and neck pathologists. Disease-specific survival (DSS) and locoregional recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant recurrence-free survival (DRFS) were calculated. The PNI and PNI characteristics were analyzed as predictors of outcome. The utility of grading the extent of PNI was assessed by quantifying the number of PNI foci per slide reviewed, nerve caliber, and percent circumference involved.Patients with PNI had a decreased DSS; however, PNI was not predictive of LRFS or RRFS. Patients with PNI were more likely to develop a distant recurrence and 19.40 (confidence interval [CI] 6.70-56.14; P .001) times more likely to develop a distant recurrence if PNI foci density was1.The presence of PNI in oral tongue SCC predicts worse DSS, with distant recurrence as the most common pattern of failure. High PNI foci density is associated with worse DRFS.

PURPOSE/OBJECTIVE(S): The COVID-19 pandemic triggered a national emergency which drastically affected the practice of medicine. Studies have already shown that delays in cancer screening/diagnosis/treatment have ensued, and some project this will translate into increased mortality. We aimed to evaluate if early oropharyngeal cancer (OPC) outcomes with radiation therapy (RT) were affected. MATERIALS/METHODS: On 3/17/2020, in response to the crisis in New York City, telemedicine consultations were implemented at our institution and patients followed prospectively. The Covid cohort (COV) includes new patients through July 2020. They were compared to a contemporary pre-Covid (PC) historical cohort of new patients from November 2019 to 3/16/2020. We reviewed medical records and collected clinicopathologic factors for OPC patients treated with curative intent RT. The Kaplan-Meier method was used to estimate time-to-event outcomes. RESULTS: Median follow-up was 8.6 [1.0-13.8] months for all (5.8 months COV, 10.1 months PC). Both cohorts encompassed ∼19 weeks, but half as many consults were seen during the pandemic (n = 38 COV, n = 78 PC). The COV cohort included: 74% telehealth, 92% definitive RT (no surgery), and 89% chemoRT. The PC cohort included: 0% telehealth, 88% definitive RT (no surgery), and 94% chemoRT. There was no difference in COV vs. PC median times from consultation to simulation (1.1 [0-6.4] weeks vs. 1.4 [0-10.6] weeks) or simulation to RT start (2.1 [1.3-4.9] weeks vs. 2.0 [1.1-9.9] weeks). There was no difference in 6 month outcomes between COV vs. PC cohorts: local control (100% vs. 100%, P = 0.70), regional control 100% vs. 100%, P = 0.70), distant control (95.2% vs. 97.2%, P = 0.91), cancer-specific survival (100% vs. 98.7%, P = 0.48). There was no difference in outcomes between telemedicine vs. in-person consults. There were numerically more patients with very advanced disease during the pandemic: T4 (13.2% COV vs. 7.7% PC) or N3/M1 (5.2% COV vs. 2.6% PC), but differences were not statistically significant due to limited numbers. More patients treated during the pandemic developed grade 3 dysphagia requiring feeding tubes (10.5% COV vs. 5.1% PC), not significant due to limited numbers. No patients diagnosed with COVID (1 before, 2 during, and 5 after RT) had recurrence at last follow-up. CONCLUSION: There was no difference in early 6 month outcomes between COV and PC cohorts, no difference in outcomes with telemedicine, and RT delivery was sustained at pre-pandemic timelines. Several important clinical trends were identified in the COV cohort: about half as many consultations were seen during the pandemic, patients appeared more likely to present with very advanced disease, and more patients required feeding tubes during treatment. These findings may have important post-pandemic healthcare delivery implications related to delays in diagnosis, threats to long-term outcomes, and increased supportive care needs.

6019 Background: Our previously published proof-of-concept trial using functional imaging to select patient with human papillomavirus (HPV) oropharyngeal carcinoma (OPC) for radiation de-escalation showed promising results. Here we report the outcome of a larger validation trial using the same paradigm where select HPV+ OPC patients received a definitive dose of 30Gy concurrently with chemotherapy and were subsequently observed. Methods: The trial enrolled patients who had p16+, T0-2, N1-N2c, M0 OPC by AJCC 7th TNM. Patients were required to have resection of the primary site (negative margin not required) or core biopsy of lymph node if unknown primary. In addition to standard positron emission tomography (PET), a pre-radiation dynamic 18F-FMISO (fluoromisonidazole) PET was performed to identify hypoxia in gross nodal disease. Patients with evidence of hypoxia ( > 1.2 tumor to muscle standard uptake value on 18F-FMISO) underwent repeat18F-FMISO PET around 2 weeks into radiation. Patients without pre-radiation hypoxia or with resolution of hypoxia on 18F-FMISO PET received 30Gy with 2 cycles of concurrent chemotherapy (cisplatin 100mg/m2 or carboplatin AUC 1.25 x 4 with 5-fluorouracil 2400 mg/m2). Results: From 11/2/17-1/4/21, 158 HPV+ OPC patients consented and were enrolled on trial. Patient characteristics were as follows: male (90%); ages 36-80 years; T-stage T0(26), T1(77), T2(55); N stage N1(19), N2a(15), N2b(95), N2c(29). Of the 114 patients with pre-treatment hypoxia, 24 had persistent hypoxia and received 70Gy. 128 patients were de-escalated to 30Gy and chemotherapy (86% cisplatin). 6 patients withdrew from trial [3 decided to receive standard of care; 3 refused 18F-FMISO PET]. Acute mucositis rates were 11% grade 0, 59% grade 1, and 30% grade 2, respectively. Acute xerostomia rates were 92% grade 1 and 8% grade 2, respectively. Weight loss was infrequent and only 19% complained of grade 1 and 5% complained of grade 2 weight loss. Six patients experienced grade 3 adverse events (diarrhea (2), syncope (2), vasovagal (1), dysphagia (1)). No patients required PEG tubes. With a median follow-up is 12 months (range: 2 months to 40 months), the 1-year locoregional control, distant metastasis-free overall survival rates were 94%, 100%, and 100%, respectively. Among the 30Gy de-escalated patients, none failed in the primary site. 8 patients had recurrent nodal disease underwent successful salvage surgery of which no additional therapy was given to 4 patients. Conclusions: Major de-escalation to 30Gy using patient specific treatment response based on hypoxia resolution resulted in excellent locoregional control with significant toxicity reduction. Updated results along with detailed correlative analysis will be presented. Clinical trial information: NCT03323463.

2502 Background: Human papillomavirus 16 (HPV16) is linked to several cancer types. Treatment options are limited for patients with HPV16 positive (HPV16+) recurrent or metastatic cancers. Generation and maintenance of HPV16+ malignant state require stable expression of HPV16-specific E7 and E6 oncoproteins, also a source of immunogenic neoantigens. HB-201 and HB-202 are replicating live-attenuated vectors based on lymphocytic choriomeningitis virus and Pichinde virus, respectively, which express the same non-oncogenic HPV16 E7E6 fusion protein to induce tumor-specific T-cell responses. This is a first-in-human phase 1/2 study of HB-201 monotherapy and HB-201 & HB-202 alternating 2-vector therapy. Dose escalation is ongoing with a 3+3 design. Methods: Phase 1 is assessing different regimens and dose levels of HB-201 monotherapy and HB-201 & HB-202 alternating 2-vector therapy given intravenously (IV) with or without an initial intratumoral administration. The patient population includes HPV16+ head and neck squamous cell carcinoma (HNSCC) and other HPV16+ cancers. Safety, tolerability, and preliminary antitumor activity by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or immune RECIST are assessed. Results: As of Jan 2021, 25 patients with a median of 3 prior anticancer treatments have been enrolled. All had HPV16+ confirmed genotype; the most common primary site was oropharynx (72%). No dose-limiting toxicities were reported. Treatment-emergent adverse events (TEAEs) occurred in 21 patients (84%), were generally mild or moderate, with events related to study drug reported in 14 patients (56%). TEAEs reported in >10% of patients regardless of causality included fatigue, pyrexia, nausea, decreased appetite, anemia, arthralgia, chills, constipation, diarrhea, hypertension, influenza-like illness, pneumonia, and vomiting. Serious TEAEs developed in 6 patients (24%), including 1 with grade 5 hemorrhagic shock deemed unrelated to study drug. Grade 3 fatigue was the only serious or grade ≥3 TEAE assessed as related to study drug. TEAEs caused no treatment discontinuation. There were 18 patients evaluable for efficacy. For the 16 patients on HB-201 monotherapy, assessment of target lesions showed 2 partial responses (including 1 patient with an unconfirmed immune CR) and 6 patients had stable disease (SD). For the 2 patients on HB-201 & HB-202 alternating therapy, both had SD. So far, the longest duration of response was 4.8 months (144 days) and the maximum decrease in tumor diameter was 60%, both seen in HNSCC patients receiving HB-201 IV. Conclusions: HB-201 monotherapy and HB-201 & HB-202 2-vector alternating therapy were generally well-tolerated and showed preliminary antitumor activity as monotherapy in heavily pre-treated patients with HPV16+ HNSCC and other solid tumors. Clinical trial information: NCT04180215.

Background Activating events along the PI3K/mTOR pathway are common in head and neck squamous cell carcinomas (HNSCC), and preclinical studies suggest additive or synergistic effects when combining mTORC1 inhibitors with carboplatin and paclitaxel chemotherapy. Patients and methods In this single-institution phase II study, the combination of temsirolimus 25 mg, carboplatin AUC 1.5, and paclitaxel 80 mg/m2 administered on days 1 and 8 of a 21-day cycle was evaluated in 36 patients with recurrent and/or metastatic (R/M) HNSCC. The primary end point was objective response rate after two cycles of treatment. Secondary end points include the safety and tolerability profile and overall survival. Correlative studies with exome mutational analysis were performed in pre-treatment biopsy samples from 21 patients. Results Fifteen (41.7%) patients had an objective response, which were all partial responses, and 19 (52.3%) patients had stable disease as best response. The two patients who were designated as ‘non-responders’ were removed from study prior to two cycles of treatment, but are included in the efficacy and safety analyses. The median duration on study was 5.3 months and the median progression-free survival and overall survival were 5.9 months (95% confidence interval, 4.8–7.1) and 12.8 months (95% confidence interval, 9.8–15.8), respectively. The most common grade 3 and 4 adverse events were hematologic toxicities. Three (3.8%) patients developed neutropenic fever on study. Three of four patients with PIK3CA mutations experienced tumor regressions, and responses were also seen in patients with other genetic alterations in the PI3K/mTOR pathway. Conclusion The combination of temsirolimus with low-dose weekly carboplatin and paclitaxel appears to have meaningful clinical efficacy in the treatment of R/M HNSCC. This regimen has a relatively high response rate compared to other treatments evaluated in R/M HNSCC, and potential associations with genetic alterations in the PI3K/mTOR pathway should be further explored.

BACKGROUND Patient safety is a critical concern in clinical oncology, but the ability to measure adverse events (AEs) across cancer care is limited by a narrow focus on treatment-related toxicities. The objective of this study was to assess the nature and extent of AEs among cancer patients across inpatient and outpatient settings. METHODS This was a retrospective cohort study of 400 adult patients selected by stratified random sampling who had breast (n = 128), colorectal (n = 136), or lung cancer (n = 136) treated at a comprehensive cancer center in 2012. Candidate AEs, or injuries due to medical care, were identified by trained nurse reviewers over the course of 1 year from medical records and safety-reporting databases. Physicians determined the AE harm severity and the likelihood of preventability and harm mitigation. RESULTS The 400-patient sample represented 133,358 days of follow-up. Three hundred four AEs were identified for an overall rate of 2.3 events per 1000 patient days (91.2 per 1000 inpatient days and 0.9 per 1000 outpatient days). Thirty-four percent of the patients had 1 or more AEs (95% confidence interval, 29%-39%), and 16% of the patients had 1 or more preventable or mitigable AEs (95% confidence interval, 13%-20%). The AE rate for patients with breast cancer was lower than the rate for patients with colorectal or lung cancer (P ≤ .001). The preventable or mitigable AE rate was 0.9 per 1000 patient days. Six percent of AEs and 4% of preventable AEs resulted in serious harm. Examples included lymphedema, abscess, and renal failure. CONCLUSIONS A heavy burden of AEs, including preventable or mitigable events, has been identified. Future research should examine risk factors and improvement strategies for reducing their burden. Cancer 2017;123:4728-4736. © 2017 American Cancer Society.

Background Patients with recurrent and/or metastatic, radioactive iodine-refractory thyroid carcinoma have limited treatment options. Sorafenib, an oral kinase inhibitor, is approved by the US Food and Drug Administration for the treatment of radioactive iodine-refractory thyroid carcinoma, although it demonstrated low response rates (12.2%) as a single agent in the first-line setting. The objective of the current study was to determine whether adding the mammalian target of rapamycin inhibitor temsirolimus to sorafenib could improve on these results. Methods In this single-institution, phase 2 study, 36 patients with metastatic, radioactive iodine-refractory thyroid carcinoma of follicular origin received treatment with the combination of oral sorafenib (200 mg twice daily) and intravenous temsirolimus (25 mg weekly). The receipt of prior systemic treatment with cytotoxic chemotherapy and targeted therapy, including sorafenib, was permitted. The primary endpoint was the radiographic response rate. Results The best response was a partial response in 8 patients (22%), stable disease in 21 (58%), and progressive disease in 1 (3%). Six patients were not evaluable for a response. Patients who had received any prior systemic treatment had a response rate of 10% compared with 38% of those who had not received prior systemic treatment. One of 2 patients with anaplastic thyroid cancer had an objective response. The progression-free survival rate at 1 year was 30.5%. The most common grade 3 and 4 toxicities associated with sorafenib and temsirolimus included hyperglycemia, fatigue, anemia, and oral mucositis. Conclusions Sorafenib and temsirolimus appear to be an active combination in patients with radioactive iodine-refractory thyroid carcinoma, especially in patients who received no prior treatment compared with historic data from single-agent sorafenib. Activity is also observed in patients who previously received sorafenib. This regimen warrants further investigation. Cancer 2017;123:4114-4121. © 2017 American Cancer Society.

Sinonasal undifferentiated carcinoma (SNUC) is a high-grade malignancy with limited treatment options and poor outcome. A morphological spectrum of 47 sinonasal tumours including 17 (36.2%) SNUCs was analysed at genomic level. Thirty carcinomas (cohort 1) were subjected to a hybridization exon-capture next-generation sequencing assay (MSK-IMPACT(TM) ) to interrogate somatic variants in 279 or 410 cancer-related genes. Seventeen sinonasal tumours (cohort 2) were examined only for the presence of IDH1/2 exon 4 mutations by Sanger sequencing. IDH2 R172 single nucleotide variants were overall detected in 14 (82.4%) SNUCs, in two (20%) poorly-differentiated carcinomas with glandular/acinar differentiation, and in one of two high-grade neuroendocrine carcinomas, large cell type (HGNECs). No IDH2 mutation was detected in any of five olfactory neuroblastomas or in any of five SMARCB1-deficient carcinomas. Among 12 IDH2-mutated cases in cohort 1, five (41.7%) harboured co-existing TP53 mutations, four (33.3%) CDKN2A/2B loss-of-function alterations, four (33.3%) MYC amplification, and three (25%) had concurrent SETD2 mutations. AKT1 E17K and KIT D816V hotspot variants were each detected in one IDH2-mutated SNUC. The vast majority of SNUCs and variable proportions of other poorly-differentiated sinonasal carcinomas may be amenable to IDH2-targeted therapy. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.

Background and Objectives Primary surgical treatment of patients with early T-classification (T1-T2) oropharyngeal squamous cell carcinoma (OPSCC) has increased. We sought to determine how often these patients receive postoperative chemoradiation (CRT). Methods Patients with T1-T2 OPSCC in the National Cancer Database who underwent primary surgery were evaluated for receipt of postoperative CRT. Postoperative CRT use was examined among patients with high risk factors (positive margins and/or extracapsular spread [ECS]), intermediate risk factors (negative margins, no ECS, and either pT3-4 and/or N2-N3), and no apparent risk factors. Results Of 4833 patients with T1-T2 OPSCC who underwent primary surgery, 43% had high risk pathologic factors, of whom only 63% received postoperative CRT. Another 31% had no apparent risk factors, of whom 16% nonetheless received postoperative CRT. On multivariable analysis, in addition to tumor and demographic factors, patients treated at community hospitals were more likely to receive postoperative CRT (O.R. 1.41 C.I. 1.18-1.87, P = 0.001). Conclusions Variation in postoperative CRT use indicates a lack of consensus and/or knowledge about its benefits and indications. Usage of postoperative CRT regardless of pathologic risk factors suggests an area where future efforts at implementation of best practices may be targeted.

Mucosal exposure to human papillomavirus (HPV) can lead to anogenital and head and neck (H&N) cancer. Vaccination at a young age can be almost 100% effective in preventing HPV infection with the viral subtypes in both men and women, at least for disease in the anogenital tract. Therapeutic strategies targeting HPV in cervical dysplasia and cancer are showing promise as well in regressing dysplasia and controlling disease. That HPV-positive H&N cancer is a different disease from HPV-negative disease, with different molecular and clinical features and prognosis, is becoming better appreciated. At this time, however, the NCCN Guidelines for H&N Cancers do not distinguish between the types. This is expected to change.

Snapping triceps corresponds to subluxation of the medial head of the triceps brachii over the medial epicondyle during active elbow flexion. It is a rare and misleading condition that is often associated with ulnar nerve instability. The latter can result in the snapping triceps being missed. Diagnosis requires a detailed clinical examination. Surgical treatment consists of anterior translocation of the nerve with an adipose flap to stabilize it and transfer of the distal attachment of the medial head of triceps brachii.

Testicular cancer affects mainly young men between 20 and 30 years of age. Due to the availability of effective chemotherapy, the majority of patients are cured. Despite an increased risk of metachronous testicular cancer, it should be carefully considered whether immediate orchiectomy is indicated. This mini review gives an account of the available literature on testis-sparing surgery in patients with unilateral or bilateral synchronous or metachronous testicular cancer.

For patients ineligible for cisplatin with definitive radiotherapy (CP-CRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), concurrent cetuximab (C225-RT) is a popular substitute. Carboplatin-based chemoradiation (CB-CRT) is another option; however, relative efficacies of CP-CRT, CB-CRT and C225-RT are unclear, particularly in the human papillomavirus (HPV)-unrelated population. We identified 316 patients with stage III-IVB cancers of the oropharynx (24.7%), larynx (58.2%) and hypopharynx (17.1%) undergoing definitive C225-RT (N = 61), CB-CRT (N = 74) or CP-CRT (N = 181). Kaplan-Meier and cumulative incidence functions were generated to estimate overall survival (OS), locoregional failure (LRF) and distant metastasis (DM). Cox proportional hazards were used to determine the association of survival endpoints with clinical characteristics. Respectively, 3-year cumulative incidences for CP-CRT, CB-CRT and C225-RT were: LRF (0.19, 0.18 and 0.48, p ≤ 0.001), DM (0.17, 0.12 and 0.25, p = 0.32). Kaplan-Meier estimates for 3 year OS were: CP-CRT: 71%; CB-CRT: 59% and C225-RT: 54%; p = 0.0094. CP-CRT (hazard ratio [HR] 0.336; 95% confidence interval [CI] 0.203-0.557, p < 0.01) and CB-CRT (HR 0.279; 95% CI 0.141-0.551, p < 0.01) were associated with reduced hazard for LRF on multivariable analysis. CP-CRT (HR 0.548; 95% CI 0.355-0.845, p < 0.01) and CB-CRT (HR 0.549; 95% CI 0.334-0.904, p = 0.02) were associated with a reduced hazard for death on multivariable analysis. Propensity matching confirmed reduced hazards with a combined CP/CB-CRT group compared to C225-RT for LRF: HR 0.384 (p = 0.018) and OS: HR 0.557 (p = 0.045) and CB-CRT group compared to C225-RT for LRF: HR 0.427 (p = 0.023). In conclusion, CB-CRT is an effective alternative to CP-CRT in HPV-unrelated LA-HNSCC with superior locoregional control and OS compared to C225-RT.

INTRODUCTION AND OBJECTIVES:Due to improved diagnostic tools salvage surgery is getting more popular after failure of primary local treatment as radical prostatectomy or radiotherapy. We analyzed P...

INTRODUCTION AND OBJECTIVES:Testicular cancer patients receiving platinum-based chemotherapy are at risk for the development of venous thromboembolic events. In this study, we aim to identify poten...