Search

PURPOSE: Accelerated by the COVID-19 pandemic, the virtual platform has become a prominent medium to deliver mind-body therapies, but the extent to which patients engage in virtual mind-body programming remains unclear. This study aims to assess oncology patient engagement in a virtual mind-body program. METHODS: We surveyed oncology patients enrolled in a live-streamed (synchronous) virtual mind-body program in May 2021. Patients self-reported engagement by weekly attendance. We applied multivariate regression to identify associations of engagement with sociodemographic and clinical factors. As an exploratory analysis, we used machine learning to partition engagement subgroups to determine preferential interest in prerecorded (asynchronous) mind-body therapy videos. RESULTS: Among 148 patients surveyed (response rate: 21.4%), majority were female (94.5%), White (83.1%), age 65 years or older (64.9%), retired (64.2%), and in survivorship (61.8%). Patient engagement ranged from 1 to 13 classes/week (mean [standard deviation]: 4.23 [2.56]) and was higher for female (β, .82; 95% CI, 0.01 to 1.62), non-White (β, .63; 95% CI, 0.13 to 1.13), and retired patients (β, .50; 95% CI, 0.12 to 0.88). The partition model identified three engagement subgroups: employed (low engagers), retired White (intermediate engagers), and retired non-White (high engagers). Particularly, low engagers had preferential interest in meditation videos (odds ratio, 2.85; 95% CI, 1.24 to 6.54), and both low and high engagers had preferential interest in Tai Chi videos (odds ratio, 2.26; 95% CI, 1.06 to 4.82). CONCLUSION: In this cross-sectional study among oncology patients, engagement in virtual mind-body programming was higher for female, non-White, and retired patients. Our findings suggest the need for both synchronous and asynchronous mind-body programming to meet the diverse needs of oncology patients.

BACKGROUND: Metastatic anaplastic thyroid cancer (ATC) has a poor prognosis. This pilot study aims to evaluate tremelimumab plus durvalumab with stereotactic body radiotherapy (SBRT) to improve overall survival (OS). METHODS: Eligible patients received up to 4 doses tremelimumab (75 mg) given q4 weeks and up to 1 year of durvalumab (1500 mg) given q4 weeks. SBRT at 9 Gy × 3 fractions was given within the first 2 weeks of the start of treatment. Paired biopsies (pretreatment and between 3 and 10 weeks after the first dose of the drug treatment) were done in the medically qualified patients. Major inclusion criteria are metastatic ATC, Eastern Cooperative Oncology Group (ECOG) performance status 0–2, no prior immunotherapy, and last anticancer treatment >7 days before starting the study. The primary endpoint was 1 year OS with the combination of durvalumab, tremelimumab, and SBRT in metastatic ATC patients with a target of 1 year OS in ≥2 out of 12 patients. RESULTS: A total of 13 patients signed consent but only 12 patients ultimately participated in this trial. One patient who consented to the protocol became ineligible for this study due to continued decline in performance status. Patient characteristics were as follows: male (n = 6) with a median age of 71 years (range: 49–82), and ECOG = 1. Nine patients had prior neck radiation and nine patients had prior chemotherapy. Next-generation sequencing and PD-L1 staining were done in the nine patients where tissue was available. High microsatellite instability (MSI) corresponding to mismatch repair defect was noted in two patients. There were zero confirmed responses and only one patient had stable disease and was treated with ≥4 cycles of study drugs. The median time that the patients were under treatment was 11 weeks (1–28 weeks). MSI status did not affect treatment response. High MSI patients were on treatment for 8–14 weeks before disease progression. The median OS was 14.5 weeks with only 1 patient alive beyond 1 year. The presence of a BRAF or p53 mutation did not appear to affect treatment outcome. CONCLUSIONS: Tremelimumab and durvalumab with SBRT did not improve OS for ATC. Future research is needed to examine other novel immunotherapy combinations with or without radiotherapy in the treatment of ATC. Clinical Trial Registration: NCT03122496.

Local treatment for bone metastases is becoming increasingly complex. National guidelines traditionally focus only on radiation therapy (RT), leaving a gap in clinical decision support resources available to clinicians. The objective of this study was to reach expert consensus regarding multidisciplinary management of non-spine bone metastases, which would facilitate standardizing treatment within an academic-community partnership.A multidisciplinary panel of physicians treating metastatic disease across the Memorial Sloan Kettering (MSK) Cancer Alliance, including community-based partner sites, was convened. Clinical questions rated of high importance in the management of non-spine bone metastases were identified via survey. A literature review was conducted, and panel physicians drafted initial recommendation statements. Consensus was gathered on recommendation statements through a modified Delphi process from a full panel of 17 physicians from radiation oncology, orthopaedic surgery, medical oncology, interventional radiology, and anesthesia pain. Consensus was defined a priori as 75% of respondents indicating "agree" or "strongly agree" with the consensus statement. Strength of Recommendation Taxonomy was employed to assign evidence strength for each statement.Seventeen clinical questions were identified, of which 11 (65%) were selected for the consensus process. Consensus was reached for 16 of 17 answer statements (94%), of which 12 were approved after Round 1 and additional 4 approved after Round 2 of the modified Delphi voting process. Topics included indications for referral to surgery or interventional radiology, radiation fractionation and appropriate use of stereotactic approaches, and the handling of systemic therapies during radiation. Evidence strength was most commonly C (n = 7), followed by B (n = 5) and A (n = 3).Consensus among a multidisciplinary panel of community and academic physicians treating non-spine bone metastases was feasible. Recommendations will assist clinicians and potentially provide measures to reduce variation across diverse practice settings. Findings highlight areas for further research such as pathologic fracture risk estimation, pre-operative radiation, and percutaneous ablation.

BACKGROUND: Oncogenic activation of mitogen-activated protein kinase (MAPK) signaling is associated with radioiodine refractory (RAIR) thyroid cancer. Preclinical models suggest that activation of the receptor tyrosine kinase erbB-3 (HER3) mitigates the MAPK pathway inhibition achieved by BRAF inhibitors in BRAF(V600E) mutant thyroid cancers. We hypothesized that combined inhibition of BRAF and HER3 using vemurafenib and the human monoclonal antibody CDX-3379, respectively, would potently inhibit MAPK activation and restore radioactive iodine (RAI) avidity in patients with BRAF-mutant RAIR thyroid cancer. METHODS: Patients with BRAF(V600E) RAIR thyroid cancer were evaluated by thyrogen-stimulated iodine-124 ((124)I) positron emission tomography–computed tomography (PET/CT) at baseline and after 5 weeks of treatment with oral vemurafenib 960 mg twice daily alone for 1 week, followed by vemurafenib in combination with 1000 mg of intravenous CDX-3379 every 2 weeks. Patients with adequate (124)I uptake on the second PET/CT then received therapeutic radioactive iodine ((131)I) with vemurafenb+CDX-3379. All therapy was discontinued two days later. Treatment response was monitored by serum thyroglobulin measurements and imaging. The primary endpoints were safety and tolerability of vemurafenib+CDX-3379, as well as the proportion of patients after vemurafenb+CDX-3379 therapy with enhanced RAI incorporation warranting therapeutic (131)I. RESULTS: Seven patients were enrolled; six were evaluable for the primary endpoints. No grade 3 or 4 toxicities related to CDX-3379 were observed. Five patients had increased RAI uptake after treatment; in 4 patients this increased uptake warranted therapeutic (131)I. At 6 months, 2 patients achieved partial response after (131)I and 2 progression of disease. Next-generation sequencing of 5 patients showed that all had co-occurring telomerase reverse transcriptase promoter alterations. A deleterious mutation in the SWItch/Sucrose Non-Fermentable (SWI/SNF) gene ARID2 was discovered in the patient without enhanced RAI avidity after therapy and an RAI-resistant tumor from another patient that was sampled off-study. CONCLUSIONS: The endpoints for success were met, providing preliminary evidence of vemurafenib+CDX-3379 safety and efficacy for enhancing RAI uptake. Preclinical data and genomic profiling in this small cohort suggest SWI/SNF gene mutations should be investigated as potential markers of resistance to redifferentiation strategies. Further evaluation of vemurafenib+CDX-3379 as a redifferentiation therapy in a larger trial is warranted (ClinicalTrials.gov: NCT02456701).

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

We performed an integrated biomarker evaluation in pembrolizumab-treated patients with R/M HNSCC enrolled in KEYNOTE-012 or KEYNOTE-055. The relationship between biomarkers and HPV status was explored.We evaluated PD-L1 (combined positive score [CPS]), TMB, T-cell-inflamed gene expression profile (TcellTwo hundred and fifty-seven patients (KEYNOTE-012, n = 106; KEYNOTE-055, n = 151) had TMB data available; of these, 254 had PD-L1 and 236 had TcellTMB and the inflammatory biomarkers PD-L1 and Tcell

Background WHO states that 9 out of 10 persons in the world do not breath clean air and 8 million people die prematurely from air pollution each year. The problem is well understood, but actions to mitigate it are lacking. The purpose of the EU-funded AQ-WATCH Project is precisely to develop effective tools based on the most advanced science technologies to help decision-makers in government and the private sector to address air pollution issues in regions of the world where they operate. Objectives AQ-WATCH aims to develops a supply chain to generate innovative downstream products for improving air quality forecasts and attribution based on existing space/in-situ observations to improve public health and to optimize renewable energy in regions of the world. The project consortium includes research and business-oriented partners, who brings together the required expertise to define the optimal functionalities of these products to bring them to the market. Results The AQ-WATCH products are organized into 5 modules: (1) Air quality atlas, (2) Air quality attribution & mitigation, (3) Dust and fire forecast, (4) Fracking analysis, and (5) Air quality forecast. They are developed for 3 target regions (Beijing, Colorado and Santiago de Chile) and are integrated into a unified user-interface, the AQ-WATCH Toolkit. Product developers and prime users in the target regions are constantly interacting, and the user feedback is collected, analyzed and included during the product development. Conclusions Collaborative work done in AQ-WATCH shows strategic interaction between our research and business-oriented partners. Contributions from local parties are proven to be valuable for regional adaption of the products. A throughout dissemination including regional workshops is essential to ensure proper knowledge uptake by the target audience. Constant exchange with the private sector is required for a smooth transfer from scientific results to commercialized marketable products. Key messages • The AQ-WATCH Project follows EU’s initiative to utilize its space observations with added values to develop easily-accessible tools to fight air pollution applicable to regions of the world. • The AQ-WATCH Toolkit is developed with iterative feedback exchanges between product developers and local users to address air pollution issues, and will be eventually exploited to the market.

The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long-term morbidities with chemoradiation and the favorable prognosis of HPV-positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head-and-neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de-escalation. National database studies estimate that up to one third of patients receive nonstandard de-escalated treatments, which have subspecialty-specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV-positive OPC de-escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de-escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy-based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de-escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real-time surveillance.

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.

Patients with head and neck cancer experience a broad array of negative quality-of-life issues, but particularly common are dental complications following radiation therapy, and compromised nutrition with significant weight loss. At the NCCN 2021 Virtual Annual Conference, a panel of experts used a case-based approach to discuss some of these common adverse effects of head and neck cancer and its treatment, as well as optimal supportive care strategies to manage them.

Treatment patterns for head and neck squamous cell carcinoma (HNSCC) vary among older adults because of concerns about their health status. Geriatric assessment may guide treatment for older adults with HNSCC by assessing their health status.We conducted a retrospective review of adjuvant treatment received by older patients with HNSCC who completed a novel geriatric assessment, the electronic Rapid Fitness Assessment, before treatment. The electronic Rapid Fitness Assessment yields an accumulated geriatric deficits (AGD) score. Higher AGD score indicates greater frailty. Comparators were age and performance status. The Wilcoxon rank sum test compared differences between those who did and did not receive adjuvant radiation therapy and chemotherapy.The cohort included 73 patients, of whom 56 (77%) had oral cavity cancer. The most common geriatric deficits were major distress, social activity limitation, depression, and impaired activities of daily living. AGD score, age, and performance status were not associated with receipt of adjuvant radiation. Patients who received adjuvant chemotherapy had a significantly lower median AGD score than those who did not (3 vs 6;Receipt of adjuvant chemotherapy was associated with frailty. Rates of chemotherapy utilization were very low, indicating the need for novel strategies to mitigate the toxicity burden in this patient population. Receipt of adjuvant radiation therapy was not associated with frailty; however, there was a trend toward lower frailty among those who did receive radiation therapy.

PURPOSE: Community-academic partnerships have the potential to improve access to clinical trials for under-represented minority patients who more often receive cancer treatment in community settings. In 2017, the Memorial Sloan Kettering (MSK) Cancer Center began opening investigator-initiated clinical trials in radiation oncology in targeted community-based partner sites with a high potential to improve diverse population accrual. This study evaluates the effectiveness of a set of implementation strategies for increasing overall community-based enrollment and the resulting proportional enrollment of Hispanic patients on trials on the basis of availability in community-based partner sites. METHODS: An interrupted time series analysis evaluating implementation strategies was conducted from April 2018 to September 2021. Descriptive analysis ofHispanic enrollment on investigator-initiated randomized therapeutic radiation trials open at community-based sites was compared with those open only at themain academic center. RESULTS: Overall, 84 patients were enrolled in clinical trials in the MSK Alliance, of which 48 (56%) identified as Hispanic. The quarterly patient enrollment pre- vs postimplementation increased from 1.39 (95% CI, –3.67 to 6.46) to 9.42 (95% CI, 2.05 to 16.78; P5 .017). In the investigator-initiated randomized therapeutic radiation trials open in the MSK Alliance, Hispanic representation was 11.5% and 35.9% in twometastatic trials and 14.2% in a proton versus photon trial. Inmatched trials open only at the main academic center, Hispanic representation was 5.6%, 6.0%, and 4.0%, respectively. CONCLUSION: A combination of practice-level and physician-level strategies implemented at community-based partner sites was associated with increased clinical trial enrollment, which translated to improved Hispanic representation. This supports the role Q:2 of strategic community-academic partnerships in addressing disparities in clinical trial enrollment.

High-dose (HD) cisplatin remains the standard of care with chemoradiation for locally advanced oropharyngeal cancer (OPC). Cooperative group trials mandate bolus-HD (100 mg/m2 × 1 day, every 3 weeks) cisplatin administration at the beginning of the week to optimize radiosensitization-a requirement which may be unnecessary. This analysis evaluates the impact of chemotherapy administration day of week (DOW) on outcomes. We also report our institutional experience with an alternate dosing schedule, split-HD (50 mg/m2 × 2 days, every 3 weeks). We retrospectively reviewed 435 definitive chemoradiation OPC patients from 10 December 2001 to 23 December 2014. Those receiving non-HD cisplatin regimens or induction chemotherapy were excluded. Data collected included DOW, dosing schedule (bolus-HD vs split-HD), smoking, total cumulative dose (TCD), stage, Karnofsky Performance Status, human papillomavirus status and creatinine (baseline, peak and posttreatment baseline). Local failure (LF), regional failure (RF), locoregional failure (LRF), distant metastasis (DM), any failure (AF, either LRF or DM) and overall survival (OS) were calculated from radiation therapy start. Median follow-up was 8.0 years (1.8 months-17.0 years). DOW, dosing schedule and TCD were not associated with any outcomes in univariable or multivariable regression models. There was no statistically significant difference in creatinine or association with TCD in split-HD vs bolus-HD. There was no statistically significant association between DOW and outcomes, suggesting that cisplatin could be administered any day. Split-HD had no observed differences in outcomes, renal toxicity or TCD compared to bolus-HD cisplatin. Our data suggest that there is some flexibility of when and how to give HD cisplatin compared to clinical trial mandates.

Fine particulate air pollution (PM2.5) is decreasing in most areas of the United States, except for areas most affected by wildfires, where increasing trends in PM2.5 can be attributed to wildfire smoke. The frequency and duration of large wildfires and the length of the wildfire season have all increased in recent decades, partially due to climate change, and wildfire risk is projected to increase further in many regions including the western United States. Increasingly, empirical evidence suggests differential health effects from air pollution by class and race; however, few studies have investigated such differential health impacts from air pollution during a wildfire event. We investigated differential risk of respiratory health impacts during the 2008 northern California wildfires by a comprehensive list of socio-economic status (SES), race/ethnicity, and smoking prevalence variables. Regardless of SES level across nine measures of SES, we found significant associations between PM2.5 and asthma hospitalizations and emergency department (ED) visits during these wildfires. Differential respiratory health risk was found by SES for ED visits for chronic obstructive pulmonary disease where the highest risks were in ZIP codes with the lowest SES levels. Findings for differential effects by race/ethnicity were less consistent across health outcomes. We found that ZIP codes with higher prevalence of smokers had greater risk of ED visits for asthma and pneumonia. Our study suggests that public health efforts to decrease exposures to high levels of air pollution during wildfires should focus on lower SES communities.

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.

Zusammenfassung Hintergrund Das Klassifikationssystem zur Prognoseeinschätzung der International Germ Cell Cancer Cooperative Group (IGCCCG) für testikuläre Keimzelltumoren basiert auf dem histologischen Subtyp, der Lokalisation des Primärtumors und der Metastasen sowie der Serumkonzentrationen der Tumormarker vor Chemotherapie. Fragestellung Ziel der Arbeit war die Evaluation des Einflusses der Verwendung der Tumormarkerserumkonzentrationen vor Ablatio testis im Vergleich zu denen vor Chemotherapie im Hinblick auf die Eingruppierung entsprechend der IGCCCG-Klassifikation. Material und Methoden Wir führen eine retrospektive Datenanalyse an 135 Patienten mit metastasiertem testikulärem Keimzelltumor durch, die eine Primärtherapie mit einer Chemotherapie erhalten haben. Es erfolgte die Analyse von klinischen Parametern mit Fokus auf der Tumormarkerserumkonzentration vor Ablatio testis und vor Chemotherapie, die zur Eingruppierung in eine Prognosegruppe entsprechend der IGCCCG-Klassifikation führten. Ergebnisse Die Verwendung der Tumormarkerserumkonzentrationen zur Berechnung der IGCCCG-Klassifikation vor der Ablatio testis im Vergleich zu denen vor Chemotherapie führte bei 8 % (11/135) aller Patienten zu einer veränderten Prognosegruppe sowie daraus folgend nicht-leitliniengerechten Therapieschemata. Es zeigt sich ein „up-staging“ bei 8 der 11 Patienten und somit 6 % (8/135) der gesamten Patientenkohorte, d. h. die Serumkonzentrationen der Tumormarker sind nach Ablatio bis zum Beginn der Chemotherapie abgefallen. Bei 3 der 11 Patienten bzw. 2 % (3/135) der gesamten Patientenkohorte, kam es zu einem „down-staging“, d. h. die Tumormarker sind bis zum Beginn der Chemotherapie angestiegen. Diskussion Die Verwendung der Tumormarkerserumkonzentrationen vor Ablatio testis im Vergleich zu denen vor Chemotherapie kann zu einer signifikanten IGCCCG-Fehlklassifikation und somit inkorrekter Therapie führen. Für ein leitlinienkonformes „staging“ der Patienten sollten folglich die Tumormarker vor der Chemotherapie verwendet werden.

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.

Testikulare Keimzelltumoren (TGCT) stellen die haufigste Neoplasie des jungen Mannes dar. Die hohen Ansprechraten auf eine cisplatinbasierte Chemotherapie fuhrt bei diesen Tumoren selbst in metastasierten Stadien zu exzellenten Heilungsraten. Die in diesem Zusammenhang haufig auftretenden thromboembolischen Komplikationen konnen diesen Therapieerfolg kompromittieren und sollten vermieden werden. Dieser Artikel gibt einen Uberblick uber die aktuell verfugbare Literatur im Hinblick auf Inzidenz, Lokalisation, Folgen und Risikofaktoren in der Entstehung von venosen thromboembolischen Komplikationen sowie die Moglichkeiten der Thromboseprophylaxe. Es erfolgte eine Literaturrecherche via PubMed. Thromboembolische Komplikationen treten bei bis zu 19 % aller TGCT-Patienten auf, die eine cisplatinbasierte Chemotherapie erhalten. Sie prasentieren sich v. a. in Form einer Lungenembolie oder tiefen Beinvenenthrombose und konnen letztlich zu einer erhohten Morbiditat und Mortalitat fuhren. Als Risikofaktoren fur die Entstehung von venosen thromboembolischen Komplikationen wurden eine ausgedehnte Lymphknotenmetastasierung, erhohte LDH-Serumwerte, Gefasschaden sowie ein zentraler venoser Zugang identifiziert. Internationale Leitlinien empfehlen prophylaktische Masnahmen bei Hochrisikopatienten, dezidierte Empfehlungen fur Keimzelltumorpatienten liegen jedoch aktuell nicht vor. TGCT-Patienten, die eine cisplatinbasierte Chemotherapie erhalten, haben ein deutlich erhohtes Risiko fur die Entstehung von venosen thromboembolischen Komplikationen, was mit einer hohen Morbiditat vergesellschaftet sein kann. Weitere Studien sind notig, um eine geeignete Risikostratifizierung fur diese Patienten festzulegen.

OBJECTIVES: Ribavirin inhibits eukaryotic translation initiation factor 4E (eIF4E), thereby decreasing cap-dependent translation. In this two-part study, we assessed the pharmacodynamic effects and therapeutic potential of ribavirin in human papillomavirus (HPV)–related malignancies. METHODS: In the pharmacodynamic study, ribavirin (400 mg BID for 14 days) was evaluated in 8 patients with HPV-positive localized oropharyngeal carcinoma with phosphorylated-eIF4E (p-eIF4E) ≥30%. In the therapeutic study, ribavirin (1400 mg BID in 28-day cycles, continuously dosed) was evaluated in 12 patients with recurrent and/or metastatic HPV-related cancer. Dose interruptions or reductions were allowed according to prespecified criteria. Toxicities were assessed in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events version 4; response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Patients remained on study until disease progression or unacceptable toxicity. RESULTS: Six patients were evaluable in the pharmacodynamic study: 4 had decreased p-eIF4E after 14 days of ribavirin. In the therapeutic study, 12 patients were evaluable for toxicity, and 9 were evaluable for response. Among these, median follow-up was 3.5 months, and best overall response was stable disease in 5 patients and progression of disease in 4 patients. Median progression-free survival was 1.8 months. The most common treatment-related adverse events (grade >2) were anemia, dyspnea, and hyperbilirubinemia. All patients had anemia (grades 1–3), with 33% having at least 1 dose reduction. CONCLUSION: Oral ribavirin decreases p-eIF4E levels and is well-tolerated. However, a clear signal of efficacy in patients with recurrent and/or metastatic HPV-related cancers was not observed. (NCT02308241, NCT01268579)

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.