Does rest interval between unilateral exercise protocols influences on contralateral neuromuscular responses in untrained individuals?

INTRODUCTION: Effects on strength performance and muscle activation in the contralateral limb have been observed after training with the ipsilateral limb (IL). Cross fatigue effects in the contralateral limb (CL) can occur at intervals of up to 48 h after a training session performed with the ipsilateral limb. The objective of this study was to verify the effect of a training session in the ipsilateral limb, on the strength and activation of the muscles in the contralateral limb also submitted to the training protocol. METHODS: 10 untrained men (mean ± SD: age = 23.7 ± 4.9 years) performed unilateral knee extension with both limbs in equated protocols, in two conditions with different intervals between limbs - 20 min and 24 h. RESULTS: There were no differences in the comparison of the force produced between the pre x post interventions with the CL limb, as well as in the activation of the quadriceps during its performance. These results were similar for the two different intervals between the protocols. CONCLUSION: It was concluded that when the CL member performs the protocol after the IL, the responses in the CL depend mainly on the requirement imposed on the protocol performed by this member, without influence of the training protocol performed previously with the IL member.

Rates of Occult Invasive Disease in Patients With Biopsy-Proven Oral Cavity Squamous Cell Carcinoma in Situ.

Importance: The likelihood that an oral cavity lesion harbors occult invasive disease after biopsy demonstrating carcinoma in situ (CIS) is unknown. While de-escalated treatment strategies may be appealing in the setting of CIS, knowing whether occult invasive disease may be present and its association with survival outcomes would lead to more informed management decisions. Objective: To evaluate rate of occult invasive disease and clinical outcomes in patients with oral cavity CIS. Design, Setting, and Participants: This was a retrospective population-based cohort study using the National Cancer Database and included adults with biopsy-proven oral cavity CIS as the first diagnosis of cancer between 2004 and 2020. Data were analyzed from October 10, 2022, to June 25, 2023. Exposures: Surgical resection vs no surgery. Main Outcomes and Measures: Analyses calculated the rate of occult invasive disease identified on resection of a biopsy-proven CIS lesion. Univariate and multivariate logistic regression with odds ratios and 95% CIs were used to identify significant demographic and clinical characteristics associated with risk of occult invasion (age, year of diagnosis, sex, race and ethnicity, oral cavity subsite, and comorbidity status). Kaplan-Meier curves for overall survival (OS) were calculated for both unresected and resected cohorts (stratified by presence of occult invasive disease). Results: A total of 1856 patients with oral cavity CIS were identified, with 122 who did not undergo surgery (median [range] age, 65 [26-90] years; 48 female individuals [39.3%] and 74 male individuals [60.7%]) and 1458 who underwent surgical resection and had documented pathology (median [range] age, 62 [21-90] years; 490 female individuals [33.6%] and 968 male individuals [66.4%]). Of the 1580 patients overall, 52 (3.3%) were Black; 39 (2.5%), Hispanic; 1365 (86.4%), White; and 124 (7.8%), other, not specified. Among those who proceeded with surgery with documented pathology, 408 patients (28.0%) were found to have occult invasive disease. Higher-risk features were present in 45 patients (11.0%) for final margin positivity, 16 patients (3.9%) for lymphovascular invasion, 13 patients (3.2%) for high-grade invasive disease, and 14 patients (3.4%) for nodal involvement. For those patients with occult disease, staging according to the American Joint Committee on Cancer's AJCC Cancer Staging Manual, eighth edition, was pT1 in 341 patients (83.6%), pT2 in 41 (10.0%), and pT3 or pT4 disease in 26 (6.4%). Factors associated with greater odds of occult invasive disease at resection were female sex, Black race, and alveolar ridge, vestibule, and retromolar subsite. With median 66-month follow-up, 5-year OS was 85.9% in patients who proceeded with surgical resection vs 59.7% in patients who did not undergo surgery (difference, 26.2%; 95% CI, 19.0%-33.4%). Conclusions and Relevance: This cohort study assessed the risk of concurrent occult invasion with biopsy-proven CIS of the oral cavity, demonstrating that 28.0% had invasive disease at resection. Reassuringly, even in the setting of occult invasion, high-risk disease features were rare, and 5-year OS was nearly 80% with resection. The findings support the practice of definitive resection if feasible following biopsy demonstrating oral cavity CIS.

Clinical predictors of premature radiotherapy terminations in senior adults with oral cavity and laryngeal carcinoma.

INTRODUCTION: The underlying factors that contribute to early radiotherapy (RT) termination are understudied, especially in the era of hypofractionated treatment regimens. In this retrospective investigation, we examined the characteristics and causes of premature RT terminations in senior adults (>70 years old) with oral cavity (OC) and laryngeal carcinomas. METHODS: Hundred and eighty-eight patients treated with RT ± systemic therapy for OC and laryngeal cancer from 2017 to 2022 were identified. Premature termination was defined as completion of less than 95% of the prescribed RT. Logistic regression analysis was performed to examine factors predictive of premature termination, and survival was determined using the Kaplan-Meier method. RESULTS: Twenty patients (10.6%) experienced premature RT terminations. On regression analysis, ECOG score at initiation of RT was the only covariate studied to be independently associated with premature termination (OR 2.00, 95%CI: [1.21, 3.30], p = 0.007). Three-year overall survival (49.1% vs. 77.3%) was significantly reduced in the termination cohort (p < 0.0001). CONCLUSIONS: This analysis demonstrated over 1 in 10 patients had premature RT termination, which prognosticated inferior survival outcomes. Poor performance status may highlight patients at risk for premature termination and thus identify good candidates for hypofractionated protocols.

Efficacy of ketamine mouthwash in the management of oral and pharyngeal toxicity associated with head and neck chemoradiotherapy: protocol for a phase II, Simon's two-stage trial.

INTRODUCTION: Curative intent treatment of head and neck cancer (HNC) is frequently radiation therapy over 7 weeks with concurrent chemotherapy. This regimen is effective but carries a burden of toxicity leading to severe pain and treatment breaks portending inferior outcomes. Conventional palliation methods include opioids, anticonvulsants and local anaesthetics. Breakthrough toxicities are nevertheless ubiquitous and present an urgent unmet need. Ketamine is an inexpensive drug with mechanisms of analgesia outside the opioid pathway including N-methyl-D-aspartate (NMDA) receptor antagonism and a pharmacologically unique property of opioid desensitisation. Systemic ketamine is validated in randomised controlled trials for efficacy in reducing pain and/or opioid burden in the oncologic setting. Literature supports peripherally administered ketamine for pain control without systemic toxicity. These data support our rationale of using ketamine mouthwash to decrease acute toxicity of curative treatment of HNC, the efficacy of which is our aim to elucidate. METHODS AND ANALYSIS: This is a phase II, Simon's two-stage trial. Patients have pathologically confirmed HNC and an intended regimen of 70 Gy of radiation with concurrent cisplatin. The protocol is initiated on diagnosis of grade 3 mucositis and consists of 2 weeks of 4 times daily (QID) ketamine mouthwash use. The primary endpoint is pain response defined as a combination of pain score and opioid use. 23 subjects will be enrolled in stage 1. If statistical criteria are met, 33 subjects will be enrolled in stage 2. Secondary endpoints include daily pain, daily opioid use, dysphagia at baseline and completion, nightly sleep quality, feeding tube placement and any unscheduled treatment breaks. ETHICS AND DISSEMINATION: All trial data will be stored in an Institutional Review Board (IRB) approved database. The protocol is registered under Northwell IRB registration number #22-0292 and U.S. Food and Drug Administration (FDA) Investigational New Drug (IND) approval has been granted under IND number 161609. Results are intended to be published in an open-source journal and further data, statistics and source documents are available on request. TRIAL REGISTRATION NUMBER: NCT05331131.

Feast or famine: How is global change affecting forage supply for Yellowstone's ungulate herds?

The ecological integrity of US national parks and other protected areas are under threat in the Anthropocene. For Yellowstone National Park (YNP), the impacts that global change has already had on the park's capacity to sustain its large migratory herds of wild ungulates is incompletely understood. Here we examine how two understudied components of global change, the historical increase in atmospheric CO2 and the spread of nonnative, invasive plant species, may have altered the capacity of YNP to provide forage for ungulates over the last 200-plus years. We performed two experiments: (1) a growth chamber study that determined the growth rates of important invasive and native YNP grasses that are forages for ungulates under preindustrial (280 ppm) versus modern (410 ppm) CO2 levels and (2) a field study that compared the effect of defoliation (clipping) on the shoot growth of invasive and native mesic grassland plants under ambient CO2 conditions in 2019. The growth chamber experiment revealed that modern CO2 increased the growth rates of both invasive and native grasses, and invasive grasses grew faster regardless of CO2 conditions. The field results showed a continuum of positive to negative responses of shoot growth to defoliation, with a subgroup of invasive species responding most positively. Altogether the results indicated that the historical increase in CO2 and the spread of invasive species, some of which were planted to provide forage for ungulates in the early and mid-1900s, have likely increased the capacity of forage production in YNP. However, rising CO2 has also resulted in regional warming and increased aridity in YNP, which will likely reduce grassland productivity. The challenge for global change biologists and park managers is to determine how competing components of global change have already affected and will increasingly affect forage dynamics and the sustainability of Yellowstone's iconic ungulate herds in the Anthropocene.

Osteoradionecrosis versus Cancer Recurrence: An Unresolved Clinical Dilemma.

INTRODUCTION: Osteoradionecrosis is a rare and debilitating risk of definitive chemoradiotherapy for head and neck squamous cell carcinoma. It is difficult to distinguish between osteoradionecrosis and recurrent or progressive disease, as clinical and radiologic features may be similar. Our aim was to compare the clinical presentation and radiologic features of osteonecrosis with those of recurrent or progressive cancer. METHODS: We conducted a single-center case series of 19 patients with head and neck squamous cell carcinoma diagnosed between 2011 and 2019 who subsequently developed clinical and/or radiological suspicion of osteoradionecrosis. The population was a referred sample from head and neck cancer physicians at Northwell Health Cancer Institute. Clinician notes and imaging reports were reviewed to assign a final diagnosis of either cancer, osteonecrosis, or indeterminate. RESULTS: No differences were found in the clinical presentation or radiologic features between groups. Median time between treatment and development of symptoms was longer in patients with a final diagnosis of osteoradionecrosis than recurrent or progressive disease (5 vs. 3 months), but this difference was not statistically significant. Radiation dose and type were not associated with diagnosis. Mean standard uptake value maximums on positron emission tomography/computed tomography were significantly higher in the cancer group (median 14.8 vs. 9.1, p < 0.0152). At 1 year after first suspicion of osteoradionecrosis, 100% of osteoradionecrosis patients were alive, versus 28.6% of cancer patients. DISCUSSION/CONCLUSION: There is significant overlap in clinical and radiologic features of osteoradionecrosis and cancer. Standard uptake maximums may be helpful in predicting diagnosis. Occurrence of symptoms within 6 months of completing chemoradiotherapy should raise the concern for malignancy.

Oropharyngeal tumor cells induce COX-2 expression in peripheral blood monocytes by secretion of IL-1α.

Oropharyngeal squamous cell cancer (OPC) accounts for 3% of all cancers and greater than 1.5% of all cancer deaths in the United States, with marked treatment-associated morbidity in survivors. More than 80% of OPC is caused by HPV16. Tumors induced by HPV have been linked to impaired immune functions, with most studies focused on the local tumor microenvironment. Fewer studies have characterized the effects of these tumors on systemic responses in OPC, especially innate responses that drive subsequent adaptive responses, potentially creating feed-back loops favorable to the tumor. Here we report that elevated plasma levels of PGE2 are expressed in half of patients with OPC secondary to overexpression of COX-2 by peripheral blood monocytes, and this expression is driven by IL-1α secreted by the tumors. Monocytes from patients are much more sensitive to the stimulation than monocytes from controls, suggesting the possibility of enhanced immune-modulating feed-back loops. Furthermore, control monocytes pre-exposed to PGE2 overexpress COX-2 in response to IL-1α, simulating responses made by monocytes from some OPC patients. Disrupting the PGE2/IL-1α feed-back loop can have potential impact on targeted medical therapies.

Similar Inflammatory Adaptation in Women following 10 Weeks of Two Equalized Resistance Training with Different Muscle Action Duration.

This study is aimed at evaluating the profile of inflammatory markers and components of redox regulation in untrained women after 10 weeks of resistance training using equalized protocols but different muscle action duration (MAD). Twenty-two women underwent progressive resistance training exercising the knee extensor muscles for 10 weeks-3x/week, with 3-5 sets of 6 repetitions at 50% of the 1 repetition maximum strength test (1RM), with a rest of 180 s between the series, following the training protocol (i) 5 s of concentric muscle action for 1 s of eccentric muscle action (5C-1E) and (ii) 1 s of concentric muscle action for 5 s of eccentric muscle action (1C-5E). Quadriceps muscle hypertrophy maximum strength (1RM) and redox regulation/muscle damage/inflammatory markers (CAT, SOD, TBARS, FRAP, CH, LDH, CXCL8, and CCL2) were evaluated. Plasma markers were evaluated before and 30 minutes after the first and last training sessions. A similar gain in hypertrophy and maximum strength was observed in both groups. However, in the 5C-1E, a significant major effect was observed for SOD (F 1.19 = 10.480, p = 0.004) and a significant major time effect, with a reduction in the last training session, was observed for CXCL8 (F 1.37 = 27.440, p < 0.001). In conclusion, similar protocols of resistance training, with different MAD, produced similar inflammatory and adaptive responses to strength training. As the training load is progressive, the maintenance of this inflammatory and redox regulation profile suggests an adaptive response to the proposed strength training.

Fast but steady: An integrated leaf-stem-root trait syndrome for woody forest invaders.

Successful control and prevention of biological invasions depend on identifying traits of non-native species that promote fitness advantages in competition with native species. Here, we show that, among 76 native and non-native woody plants of deciduous forests of North America, invaders express a unique functional syndrome that combines high metabolic rate with robust leaves of longer lifespan and a greater duration of annual carbon gain, behaviours enabled by seasonally plastic xylem structure and rapid production of thin roots. This trait combination was absent in all native species examined and suggests the success of forest invaders is driven by a novel resource-use strategy. Furthermore, two traits alone-annual leaf duration and nuclear DNA content-separated native and invasive species with 93% accuracy, supporting the use of functional traits in invader risk assessments. A trait syndrome reflecting both fast growth capacity and understorey persistence may be a key driver of forest invasions.

Does the Muscle Action Duration Induce Different Regional Muscle Hypertrophy in Matched Resistance Training Protocols?

ABSTRACT: Diniz, RCR, Tourino, FD, Lacerda, LT, Martins-Costa, HC, Lanza, MB, Lima, FV, and Chagas, MH. Does the muscle action duration induce different regional muscle hypertrophy in matched resistance training protocols? J Strength Cond Res 36(9): 2371-2380, 2022-The manipulation of the muscle action duration (MAD) can influence the instantaneous torque along the range of motion, which can lead to adaptations of regional muscle hypertrophy. The aim of this study was to compare the effects of matched resistance training (RT) on the knee extension machine with different MAD in the cross-sectional area (CSA) responses within the quadriceps femoris (QF) and its muscles. Forty-four subjects were allocated into a control and 3 experimental groups. For a period of 10 weeks, subjects in the experimental groups performed the training protocols that were different only by the MAD: group 5c1e (5s concentric action [CON] and 1s eccentric action [ECC]; group 3c3e (3s CON and 3s ECC) and group 1c5e (1s CON and 5s ECC). Magnetic resonance imaging was performed (before and after the intervention) to determine the relative change (%) in CSA of the QF muscles along proximal (30%), middle (50%), and distal regions (70% distal of the femur). The change in CSA of the rectus femoris at the middle region are greater in 5c1e (6.8 ± 6.5%) and 1c5e (7.4 ± 6.0%) groups than 3c3e (3.4 ± 6.6%) and control groups (0.2 ± 1.8%). In addition, vastus lateralis at the distal region (5c1e = 15.9 ± 11.8%; 1c5e = 14.4 ± 10.0%) presenting greater increases in change of CSA than the others vastus only 5c1e (vastus lateralis [VI] = 5.0 ± 4.7%; vastus medialis [VM] = 4.2 ± 3.2%) and 1c5e groups (VI = 4.7 ± 3.6%; VM = 3.4 ± 3.1%). In conclusion, this study showed that matched RT protocols with different MAD resulted in different region-specific muscle hypertrophic across the individual muscles of QF.

Impact of Treatment Parameters on Racial Survival Differences in Oropharyngeal Cancer: National Cancer Database Study.

OBJECTIVE: To investigate how differences in treatment parameters account for survival differences between races of patients with oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database. METHODS: Data of patients with OPSCC undergoing radiation therapy (RT) or concurrent chemoradiation therapy as primary treatment were obtained from the National Cancer Database from 2004 to 2016. We analyzed 4 treatment-related time intervals to determine their impact on survival between races when controlling for human papilloma virus (HPV) status. Cox proportional hazards models, stepwise logistic regressions, covariate adjustments, and propensity score matching were performed. RESULTS: A total of 3152 patients were identified (2877 White, 275 Black). In HPV- cases, Black patients with prolonged radiation duration had a significantly worse overall survival as compared with White patients (hazard ratio, 1.77; 95% CI, 1.03-3.05; P = .039). In a logistic regression model, the only covariate that was significantly associated with prolonged RT was facility type. When further adjusted for facility type, the survival difference between Black and White patients with HPV- status and prolonged RT times was no longer significant (hazard ratio, 1.55; 95% CI, 0.90-2.69; P = .116). CONCLUSIONS: There is a significant disparity in overall survival between Black and White patients with HPV- OPSCC when RT duration is prolonged. Clinicians should be aware of the negative impact of prolonged RT, especially in Black patients, so that they can attempt to decrease treatment-related time intervals. Facility type was also found to affect the outcomes of patients with OPSCC, and efforts should be made to improve patient access to well-equipped, high-volume facilities.

Resistance training intervention performed with different muscle action durations influences the maximal dynamic strength without promoting joint-angle specific strength gains.

The present study investigated the effect of 10-week matched (range of motion, volume, intensity, rest, and repetition duration) training protocols with varying muscle action duration (MAD) on maximal voluntary isometric contraction (MVIC) test at eight different knee angles and one-repetition maximum (1RM) test after in seated knee extensor machine. Forty women were allocated into one control and three training groups with varying MAD: 5C1E (5s concentric action [CON] and 1s eccentric action [ECC]), 3C3E (3s CON and 3s ECC), and 1C5E (1s CON and 5s ECC). All training groups (5C1E, 3C3E, and 1C5E) showed a greater relative response in 1RM performance than the control group (0.1 ± 3.5%, p ≤ 0.05). The 1C5E group presented greater relative increases in the 1RM performance (22.1 ± 11.6%) compared to 5C1E (13.6 ± 9.2%; p ≤ 0.05) and 3C3E (14.1 ± 5.5%, p ≤ 0.05) groups. The training groups increased the MVIC performance more than the control group (p ≤ 0.05), although there were no significant differences between the training groups. This study demonstrated that isoinertial resistance training protocols with shorter CON MAD showed greater maximum dynamic strength performance response than matched training protocols with other MAD configurations. However, the configuration of MAD did not induce angle-specificity to increase the maximum isometric strength.

Density-dependent plant growth drives grazer stimulation of aboveground net primary production in Yellowstone grasslands.

The mechanisms by which grazing animals influence aboveground net primary production (ANPP) in grasslands have long been an area of active research. The prevailing wisdom is that grazing can increase ANPP by increasing the availability of growth-limiting resources such as nitrogen and water, but recent theory suggests that the density-dependent growth of grassland vegetation can lead to grazer-stimulation of ANPP simply by removing shoot biomass and increasing relative growth rate (RGR). We compared the relative roles of resource availability and density-dependent growth in driving positive responses of ANPP to grazing in Yellowstone National Park. We measured the effects of clipping (50% simulated grazing intensity) and natural grazing on soil nitrogen availability, soil moisture, and shoot growth over 2 months in two grassland plant communities (mesic and dry) grazed primarily by bison. Clipping increased RGR by over 100% in both grassland types but had no effect on N availability or soil moisture during the same growth periods. Clipping stimulated ANPP only at mesic grassland, and the magnitude of this effect was strongly related to the initial plant biomass at the time of clipping relative to estimated peak biomass, supporting the density-dependent framework. Bison grazing had qualitatively similar effects on ANPP and RGR to clipping with no accompanying effects on N availability or soil moisture. Our results show how grazing can stimulate ANPP independent of a direct influence on resource availability simply by exploiting the dynamics of density-dependent plant growth.

A Mobile Patient-Facing App for Tracking Patient-Reported Outcomes in Head and Neck Cancer Survivors: Single-Arm Feasibility Study.

BACKGROUND: Patients with head and neck cancer (HNC) frequently experience disease-related symptoms and treatment adverse effects that impact their overall quality of life. Cancer-specific mobile health apps for patient-related outcomes allow patients to communicate with their clinicians and proactively track their symptoms, which have been shown to improve clinical management and disease outcomes. OBJECTIVE: The purpose of this study was to evaluate the feasibility of LogPAL, a novel iPhone-based mobile health app designed to help HNC survivors track and manage their posttreatment symptoms. METHODS: Patients who completed curative treatment for HNC in the preceding 24 months were recruited from 2 clinical sites within a single institution. Upon enrollment, participants completed a brief sociodemographic survey, downloaded the app onto their iPhone devices, and were asked to complete a series of biweekly questionnaires (based on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events) via the app for an 8-week study period. The primary feasibility endpoints included retention (retaining >80% of the enrolled participants for the duration of the study period), adherence (>50% of the participants completing 100% of the questionnaires over the study period), and usability (a mean system usability scale [SUS] score >68). Additional postintervention questions were collected to assess perceived usefulness, acceptance, and overall satisfaction. RESULTS: Between January and October 2019, 38 participants were enrolled in the study. Three participants dropped out, and 3 were classified as nonusers. The remaining 32 (87%) were eligible for analysis. Their mean age was 57.8 (SD 12.3) years (range 24-77 years, 81% [26/32] male). Overall, 375 of 512 (73.2%) questionnaires were completed, with 17 (53%) of the 32 participants adherent. Participant-reported usability was acceptable; the mean SUS score was 71.9 (95% CI 64.3-79.5) with high satisfaction of LogPAL usefulness and likelihood to recommend to other cancer survivors. CONCLUSIONS: This single-arm prospective pilot study showed that LogPAL is a feasible, regularly used, accepted app for HNC survivors, justifying a full-scale pilot. Based on the findings from this study, future iterations will aim to improve usability and test intervention efficacy.

Dental radiation dosimetric maps from intensity-modulated radiation therapy planning for head and neck cancers.

BACKGROUND: The purpose of this study was to create dental radiation maps to calculate the mean dose to individual teeth, maxilla and mandible using intensity-modulated radiation therapy (IMRT). METHODS: Eighteen common clinical settings were chosen. Radiation plans were extracted, and each tooth was contoured at its junction with the gingiva and labeled based on the Universal/American numbering system. RESULTS: All patients were treated with prescribed doses of 50-70 Gy in 1.66-2 Gy/fraction. Patients receiving mean doses >50 Gy to the teeth, mandible, and maxilla included those with advanced tumors of the oral cavity and gross lymphadenopathy of level 1b. CONCLUSION: We believe this to be the first study generating dosimetric maps of estimated doses to each tooth and each third of the mandible and the maxilla for common examples of head and neck cancer faced by radiation oncologists. Adoption of these dental maps may help improve clinical workflow efficiency.

Impact of stereotactic body radiation therapy on geriatric assessment and management for older patients with head and neck cancer using G8.

PURPOSE: Management of head and neck cancers (HNC) in older adults is a common but challenging clinical scenario. We assess the impact of Stereotactic Body Radiation Therapy (SBRT) on survival utilizing the Geriatric-8 (G8) questionnaire. MATERIALS AND METHODS: 171 HNC patients, deemed medically unfit for definitive treatment, were treated with SBRT ± systemic therapy. G8 questionnaires were collected at baseline, at 4-6 weeks, and at 2-3 months post-treatment. Patients were stratified according to their baseline G8 score: <11 as 'vulnerable', 11-14 as 'intermediate', and >14 as 'fit'. Overall survival (OS) was assessed through univariate Kaplan Meier analysis. Repeated measures ANOVA was used to determine if baseline characteristics affected G8 score changes. RESULTS: Median follow-up was seventeen months. 60% of patients presented with recurrent HNC, 30% with untreated HNC primaries, and 10% with metastatic non-HNC primaries. Median age was 75 years. Median Charlson Comorbidity Index score was 2. 51% of patients were 'vulnerable', 37% were 'intermediate', and 12% were 'fit' at baseline, with median survival of 13.2, 24.3, and 41.0 months, respectively (p = .004). Patients who saw a decrease in their follow-up G8 score (n = 69) had significantly lower survival than patients who had stable or increased follow-up G8 scores (n = 102), with median survival of 8.6 vs 36.0 months (p < .001). CONCLUSION: The G8 questionnaire may be a useful tool in upfront treatment decision-making to predict prognosis and prevent older patients from receiving inappropriate anti-cancer treatment. Decline in follow-up G8 scores may also predict worse survival and aid in goals of care following treatment.

Phase I trial of dose-escalated stereotactic radiosurgery (SRS) boost for unfavorable locally advanced oropharyngeal cancer.

BACKGROUND AND PURPOSE: Patients with locally advanced oropharynx squamous cell carcinoma have suboptimal outcomes with standard chemoradiation. Here, we evaluated toxicity and oncologic outcomes of dose escalation using radiosurgical boost for patients with unfavorable oropharynx squamous cell carcinoma. MATERIALS AND METHODS: Between 2010-2017, Thirty four patients with intermediate- or high-risk oropharynx squamous cell carcinoma were enrolled onto this prospective phase I trial. Each patient received concurrent cisplatin and fractionated radiotherapy totaling 60 Gy or 66 Gy followed by radiosurgery boost to areas of residual gross tumor: single fraction of 8 Gy or 10 Gy, or two fractions of 5 Gy each. Primary endpoint was treatment toxicity. Secondary endpoints were local, regional, and distant disease control. RESULTS: Eleven, sixteen and seven patients received radiosurgery boost with 8 Gy in 1 fraction, 10 Gy in 1 fraction, and 10 Gy in 2 fractions respectively. Acute toxicities include 4 patients with tumor necrosis causing grade 3 dysphagia, of which 3 developed grade 4 pharyngeal hemorrhage requiring surgical intervention. At 24 months after treatment, 7%, 9%, and 15% had grade 2 dysgeusia, xerostomia, and dysphagia, respectively, and two patients remained feeding tube dependent. No grade 5 toxicities occurred secondary to treatment. Local, regional, and distant control at a median follow up of 4.2 years were 85.3%, 85.3% and 88.2%, respectively. Five patients died resulting in overall survival of 85.3%. CONCLUSIONS: This study is the first to report the use of radiosurgery boost dose escalation in patients with unfavorable oropharynx squamous cell carcinoma. Longer follow-up, larger cohorts, and further refinement of boost methodology are needed prior to implementation in routine clinical practice. TRIAL REGISTRATION: Northwell Health Protocol #09-309A (NCT02703493) ( https://clinicaltrials.gov/ct2/show/NCT02703493 ).

Evaluating of HPV-DNA ISH as an adjunct to p16 testing in oropharyngeal cancer.

AIM: Current guidelines recommend p16 immunohistochemistry (IHC) for testing human papillomavirus (HPV) in oropharyngeal carcinoma (OPSCC). We evaluated the value of adding DNA in situ hybridization (ISH) to p16 IHC. METHODS: Fifty patients with OPSCC were analyzed. Concordance between HPV-DNA ISH and p16 IHC was measured by Gwet's agreement coefficient. RESULTS: p16 IHC was positive in 35/48 (72.9%), negative in 8/48 (16.7%) patients. Wide spectrum DNA-ISH was positive in 9/23 (39%) and negative in 14/23 (60.9%) patients. High-risk 16/18 (HR) HPV DNA-ISH was positive in 11/23 (47.8%) and negative in 12 (52.2%) patients. The agreement between HPV DNA-ISH and p16 IHC is fair (Gwet's AC1 = 0.318). CONCLUSION: The agreement between p16 IHC and HPV-DNA ISH was fair. However, ISH sensitivity was low. Our findings add to the current data that p16 IHC testing is reliable and may be enough as a stand-alone test for HPV detection in OPSCC.

Improving post-CRT neck assessment in patients with HPV-associated OPSCC (Review).

The positive predictive value (PPV) of 12-week post-therapy FDG-PET/CT is low in patients with Human Papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) after treatment with definitive chemoradiation (CRT). Moreover, the diagnostic performance of post-CRT fine needle aspiration (FNA) in detecting persistent disease is unknown in this population. Given these important shortcomings in post-CRT treatment assessment, head and neck oncologists are limited in appropriately selecting patients for consolidative neck dissection, which results in over-treatment of a favorable risk population. Using the PubMed database, we performed a literature review of published series in HPV-associated OPSCC to investigate potential strategies for improvement of post-CRT neck assessment. Several different approaches were found, including continued surveillance with PET/CT, delayed timing of restaging PET/CT, initial response evaluation with multimodality or alternative imaging, and detection of circulating HPV DNA. At present, the optimal approach to post-CRT treatment assessment is unclear; further investigation and incorporation of new technologies and surveillance protocols will be highly beneficial for patients with HPV-associated OPSCC.

Stereotactic body radiotherapy as primary treatment for elderly and medically inoperable patients with head and neck cancer.

BACKGROUND: Patients with head and neck cancer (HNC) who are not candidates for definitive treatment represent an increasing challenge, with limited data to guide management. Conventional local therapies such as surgery and chemoradiation can significantly impact quality of life (QoL). There has been limited data published using stereotactic body radiotherapy (SBRT) as primary treatment in previously unirradiated patients. We hypothesize that SBRT provides high rates of control while limiting toxicity. METHODS: A total of 66 medically unfit previously unirradiated patients with HNC were treated with SBRT, consisting of 35-40 Gy to gross tumor volume and 30 Gy to clinical target volume in five fractions. RESULTS: Median age was 80 years. Local control (LC) and overall survival (OS) at 1 year were 73% and 64%. Two patients experienced grade 3 toxicity. CONCLUSION: SBRT shows acceptable outcomes with relatively low toxicity in previously unirradiated patients with HNC who are medically unfit for conventional treatment. SBRT may provide an aggressive local therapy with high rates of LC and OS while maintaining QoL.