Biological responses of human solid tumor cells to X-ray irradiation within a 1.5-Tesla magnetic field generated by a magnetic resonance imaging-linear accelerator.

Devices that combine magnetic resonance imaging with linear accelerators (MRL) represent a novel tool for MR-guided radiotherapy. However, whether magnetic fields (MFs) generated by these devices affect the radiosensitivity of tumors is unknown. We investigated the influence of a 1.5-T MF on cell viability and radioresponse of human solid tumors. Human head/neck cancer and lung cancer cells were exposed to single or fractionated 6-MV X-ray radiation; effects of the MF on cell viability were determined by cell plating efficiency and on radioresponsiveness by clonogenic cell survival. Doses needed to reduce the fraction of surviving cells to 37% of the initial value (D0s) were calculated for multiple exposures to MF and radiation. Results were analyzed using Student's t-tests. Cell viability was no different after single or multiple exposures to MRL than after exposure to a conventional linear accelerator (Linac, without MR-generated MF) in 12 of 15 experiments (all P > 0.05). Single or multiple exposures to MF had no influence on cell radioresponse (all P > 0.05). Cells treated up to four times with an MRL or a Linac further showed no changes in D0s with MF versus without MF (all P > 0.05). In conclusion, MF within the MRL does not seem to affect in vitro tumor radioresponsiveness as compared with a conventional Linac. Bioelectromagnetics. 37:471-480, 2016. © 2016 Wiley Periodicals, Inc.

Head and neck cancers, version 2.2013. Featured updates to the NCCN guidelines.

These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).

Laryngeal cancer in the United States: changes in demographics, patterns of care, and survival.

BACKGROUND: Survival has decreased among patients with laryngeal cancer during the past 2 decades in the United States. During this same period, there has been an increase in the nonsurgical treatment of laryngeal cancer. OBJECTIVE: The objectives of this study were to identify trends in the demographics, management, and outcome of laryngeal cancer in the United States and to analyze factors contributing to the decreased survival. STUDY DESIGN: The authors conducted a retrospective, longitudinal study of laryngeal cancer cases. METHODS: Review of the National Cancer Data Base (NCDB) revealed 158,426 cases of laryngeal squamous cell carcinoma (excluding verrucous carcinoma) diagnosed between the years 1985 and 2001. Analysis of these case records addressed demographics, management, and survival for cases grouped according to stage, site, and specific TNM classifications. RESULTS: This review of data from the NCDB analysis confirms the previously identified trend toward decreasing survival among patients with laryngeal cancer from the mid-1980s to mid-1990s. Patterns of initial management across this same period indicated an increase in the use of chemoradiation with a decrease in the use of surgery despite an increase in the use of endoscopic resection. The most notable decline in the 5-year relative survival between the 1985 to 1990 period and the 1994 to 1996 period occurred among advanced-stage glottic cancer, early-stage supraglottic cancers, and supraglottic cancers classified as T3N0M0. Initial treatment of T3N0M0 laryngeal cancer (all sites) in the 1994 to 1996 period resulted in poor 5-year relative survival for those receiving either chemoradiation (59.2%) or irradiation alone (42.7%) when compared with that of patients after surgery with irradiation (65.2%) and surgery alone (63.3%). In contrast, identical 5-year relative survival (65.6%) rates were observed during this same period for the subset of T3N0M0 glottic cancers initially treated with either chemoradiation or surgery with irradiation. CONCLUSIONS: The decreased survival recorded for patients with laryngeal cancer in the mid-1990s may be related to changes in patterns of management. Future studies are warranted to further evaluate these associations.

Inhibition of EGFR or IGF-1R signaling enhances radiation response in head and neck cancer models but concurrent inhibition has no added benefit.

Interaction between the epidermal growth factor receptor (EGFR) and the insulin-like growth factor receptor (IGF-1R) has been well established in many cancer types. We investigated the effects of cetuximab (EGFR antibody) and IMC-A12 (IGF-1R antibody) on the response of head and neck squamous cell carcinoma (HNSCC) to radiation therapy (RT). The effects of cetuximab and IMC-A12 on cell viability and radiosensitivity were determined by clonogenic cell survival assay. Formation of nuclear γ-H2AX and 53BP1 foci was monitored by immunofluorescence. Alterations in target signaling were analyzed by Western blots. In vivo tumor growth delay assay was performed to determine the efficacy of triple therapy with IMC-A12, cetuximab, and RT. In vitro data showed that cetuximab differentially affected the survival and the radiosensitivity of HNSCC cells. Cetuximab suppressed DNA repair that was evident by the prolonged presence of nuclear γ-H2AX and 53BP1 foci. IMC-A12 did not have any effect on the cell survival. However, it increased the radiosensitivity of one of the cell lines. EGFR inhibition increased IGF-1R expression levels and also the association between EGFR and IGF-1R. Addition of IMC-A12 to cetuximab did not increase the radiosensitivity of these cells. Tumor xenografts exhibited enhanced response to RT in the presence of either cetuximab or IMC-A12. Concurrent treatment regimen failed to further enhance the tumor response to cetuximab and/or RT. Taken together our data suggest that concomitant inhibition of both EGFR and IGF-1R pathways did not yield additional therapeutic benefit in overcoming resistance to RT.

Uncertainties in physical and biological targeting with radiation therapy.

Advances in radiation therapy over the past decade have resulted from increased accuracy of imaging and highly conformal three dimensional treatment planning and delivery of radiation therapy. Three-dimensional conformal radiation therapy (3D CRT) with higher doses than previously considered tolerable is now standard for many types of cancer. Intensity modulated radiation therapy (IMRT) with x-rays, proton beam treatments and intensity modulated proton therapy (IMPT) are major areas of research. Tumor motion between and even during radiation treatments represents a major uncertainty. Tumor heterogeneity results in additional uncertainties affecting tumor control with radiation therapy. Imaging the heterogeneous targets within tumors offers new opportunities for tumor delineation. Molecular therapeutic agents enhance the effects of ionizing radiations in murine systems. Clinical trials combining molecular targeting agents with conformal radiation therapy are being initiated.

EGFR expression and survival in patients given cetuximab and chemoradiation for stage III non-small cell lung cancer: a secondary analysis of RTOG 0324.

PURPOSE: We investigated whether expression of epidermal growth factor receptor (EGFR) was associated with survival and disease control in this secondary analysis of a phase II trial of cetuximab+chemoradiation for stage III non-small cell lung cancer. METHODS: Patients received cetuximab weekly before and during radiation (63 Gy/35 fractions/7 weeks) with weekly carboplatin + paclitaxel. We analyzed EGFR expression by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in pretreatment biopsy specimens and compared findings with overall and progression-free survival (OS, PFS) and time to progression (TTP). RESULTS: Specimens for IHC and FISH were collected from 51 and 45 of 87 evaluable patients. Pretreatment characteristics did not differ for patients with (n = 51) or without (n= 36) EGFR IHC data, or with (n = 45) or without (n = 42) FISH data. However, patients without IHC data had worse OS (HR = 1.63, P = 0.05), worse PFS (HR = 1.88, P = 0.008), and worse TTP [HR = 1.99, P = 0.01] than those with IHC data. EGFR protein expression was not related to pretreatment characteristics or OS; FISH-positive disease was associated with better performance status but not with OS, PFS, or TTP. CONCLUSIONS: Surprisingly, outcomes differed not by EGFR expression but by the availability of samples for analysis, underscoring the importance of obtaining biopsy samples in such trials.

Targeted therapies for squamous cell carcinoma of the head and neck: current knowledge and future directions.

Despite progress in the therapeutic management of patients with squamous cell carcinoma of the head and neck (SCCHN), the mortality rate of patients presenting with advanced disease remains high. One approach to improve treatment efficacy is to add novel molecular targeted agents to the classical treatment regimens. Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have shown clinical benefits in palliative and curative settings. However, only a minority of patients presenting with recurrent or metastatic (R/M) SCCHN have meaningful tumor regression with these agents and virtually all who do develop acquired tumor resistance after a few months of treatment. For these reasons, other inhibitors of EGFR or molecules that interfere with known molecular pathways activated in SCCHN are of considerable interest, either as single agents or in combination with other treatment modalities. In this review, we discuss the different molecular therapeutic approaches explored in SCCHN. We also briefly outline new trial designs that could be used to accelerate the investigation of emerging therapeutic agents in this disease.

Clinical characteristics of patients with multiple potentially human papillomavirus-related malignancies.

BACKGROUND: Human papillomavirus (HPV) is a causative factor in squamous cell carcinomas of the anus, penis, vagina, vulva, and head and neck, and adenocarcinoma of the cervix. We examined the demographics, clinical characteristics, and timing of multiple potentially HPV-related cancers in individual patients. METHODS: One hundred forty-three patients were identified with 300 potentially HPV-related cancers. The median follow-up from index and second cancer was 18.5 years and 3.2 years, respectively. RESULTS: Median age at index and second cancer was 45 and 60.5 years of age, respectively, with a median interval of 11 years. Cervical cancer was the most common initial diagnosis (61.7%), whereas head and neck squamous cell carcinoma (HNSCC) was the most common second cancer (57.6%). CONCLUSION: These data suggest differential patterns for development of multiple HPV-related cancers based upon clinical characteristics. Prospective longitudinal and population-based studies are warranted to understand the impact of these findings and opportunities for intervention and screening.

Spot-scanning beam proton therapy vs intensity-modulated radiation therapy for ipsilateral head and neck malignancies: a treatment planning comparison.

Radiation therapy for head and neck malignancies can have side effects that impede quality of life. Theoretically, proton therapy can reduce treatment-related morbidity by minimizing the dose to critical normal tissues. We evaluated the feasibility of spot-scanning proton therapy for head and neck malignancies and compared dosimetry between those plans and intensity-modulated radiation therapy (IMRT) plans. Plans from 5 patients who had undergone IMRT for primary tumors of the head and neck were used for planning proton therapy. Both sets of plans were prepared using computed tomography (CT) scans with the goals of achieving 100% of the prescribed dose to the clinical target volume (CTV) and 95% to the planning TV (PTV) while maximizing conformity to the PTV. Dose-volume histograms were generated and compared, as were conformity indexes (CIs) to the PTVs and mean doses to the organs at risk (OARs). Both modalities in all cases achieved 100% of the dose to the CTV and 95% to the PTV. Mean PTV CIs were comparable (0.371 IMRT, 0.374 protons, p = 0.953). Mean doses were significantly lower in the proton plans to the contralateral submandibular (638.7 cGy IMRT, 4.3 cGy protons, p = 0.002) and parotid (533.3 cGy IMRT, 48.5 cGy protons, p = 0.003) glands; oral cavity (1760.4 cGy IMRT, 458.9 cGy protons, p = 0.003); spinal cord (2112.4 cGy IMRT, 249.2 cGy protons, p = 0.002); and brainstem (1553.52 cGy IMRT, 166.2 cGy protons, p = 0.005). Proton plans also produced lower maximum doses to the spinal cord (3692.1 cGy IMRT, 2014.8 cGy protons, p = 0.034) and brainstem (3412.1 cGy IMRT, 1387.6 cGy protons, p = 0.005). Normal tissue V10, V30, and V50 values were also significantly lower in the proton plans. We conclude that spot-scanning proton therapy can significantly reduce the integral dose to head and neck critical structures. Prospective studies are underway to determine if this reduced dose translates to improved quality of life.

Aortic dose constraints when reirradiating thoracic tumors.

BACKGROUND AND PURPOSE: Improved radiation delivery and planning has allowed, in some instances, for the retreatment of thoracic tumors. We investigated the dose limits of the aorta wherein grade 5 aortic toxicity was observed after reirradiation of lung tumors. MATERIAL AND METHODS: In a retrospective analysis, 35 patients were identified, between 1993 and 2008, who received two rounds of external beam irradiation that included the aorta in the radiation fields of both the initial and retreatment plans. We determined the maximum cumulative dose to 1 cm(3) of the aorta (the composite dose) for each patient, normalized these doses to 1.8 Gy/fraction, and corrected them for long-term tissue recovery between treatments (NIDR). RESULTS: The median time interval between treatments was 30 months (range, 1-185 months). The median follow-up of patients alive at analysis was 42 months (range, 14-70 months). Two of the 35 patients (6%) were identified as having grade 5 aortic toxicities. There was a 25% rate of grade 5 aortic toxicity for patients receiving composite doses ≥120.0 Gy (vs. 0% for patients receiving <120.0 Gy) (P=0.047). CONCLUSIONS: Grade 5 aortic toxicities were observed with composite doses ≥120.0 Gy (NIDR ≥90.0 Gy) to 1cm(3) of the aorta.

Human papillomavirus as a marker of the natural history and response to therapy of head and neck squamous cell carcinoma.

There has been a gradual change in the demographics of head and neck carcinoma. Although relatively uncommon, the incidence of oropharyngeal carcinoma has been increasing despite declining tobacco consumption and contrary to a diminishing incidence of cancers at other head and neck sites. It is now clear that the incidence of human papillomavirus (HPV)-associated oropharyngeal cancers is rising, likely as a consequence of changing life styles and sexual behaviors. Many studies have contributed to understanding the characteristics of HPV-related oropharyngeal carcinoma, which usually presents as nonkeratinizing squamous cell carcinoma of low to intermediate T-category and affects middle-aged white men, having higher socioeconomic status and no or brief history of tobacco consumption. The diagnosis of this distinct neoplastic entity can be firmly established by a combination of p16 immunohistochemical and in situ hybridization assays. Compared with the traditional smoking-associated head and neck squamous cell carcinoma, HPV-related oropharyngeal carcinoma has a favorable natural history and responds better to treatment. Consequently, patients with this cancer have better long-term survival than those with HPV-unrelated head and neck squamous cell carcinoma (eg, 5-year overall survival rate of >80% versus ∼40% for patients with stage III-IV tumors), and hence they are more likely to experience chronic therapy-induced morbidity. Therefore, changes in evaluation, staging, and treatment are needed for this patient group. However, attempts to change the treatment for HPV-associated oropharyngeal carcinoma should take place in a closely monitored clinical trial setting. In this article, we summarize the epidemiology, diagnosis, and clinical behavior of HPV-associated oropharyngeal carcinoma, with emphasis on prognostic and biomarker discovery aspects, and discuss briefly the current thoughts on changing the treatment paradigms aimed at reducing morbidity while preserving the high tumor control probability through well-coordinated prospective trials.

C-Met inhibitor MK-8003 radiosensitizes c-Met-expressing non-small-cell lung cancer cells with radiation-induced c-Met-expression.

INTRODUCTION: The radiation doses used to treat unresectable lung cancer are often limited by the proximity of normal tissues. Overexpression of c-Met, a receptor tyrosine kinase, occurs in about half of non-small-cell lung cancers (NSCLCs) and has been associated with resistance to radiation therapy and poor patient survival. We hypothesized that inhibiting c-Met would increase the sensitivity of NSCLC cells to radiation, enhancing the therapeutic ratio, which may potentially translate into improved local control. METHODS: We tested the radiosensitivity of two high-c-Met-expressing NSCLC lines, EBC-1 and H1993, and two low-c-Met-expressing lines, A549 and H460, with and without the small-molecule c-Met inhibitor MK-8033. Proliferation and protein expression were measured with clonogenic survival assays and Western blotting, respectively. γ-H2AX levels were evaluated by immunofluorescence staining. RESULTS: MK-8033 radiosensitized the high-c-Met-expressing EBC-1 and H1993 cells but not the low-c-Met-expressing cell lines A549 and H460. However, irradiation of A549 and H460 cells increased the expression of c-Met protein at 30 minutes after the irradiation. Subsequent targeting of this up-regulated c-Met by using MK-8033 followed by a second radiation dose reduced the clonogenic survival of both A549 and H460 cells. MK-8033 reduced the levels of radiation-induced phosphorylated (activated) c-Met in A549 cells. CONCLUSIONS: These results suggest that inhibition of c-Met could be an effective strategy to radiosensitize NSCLC tumors with high basal c-Met expression or tumors that acquired resistance to radiation because of up-regulation of c-Met.

Anaplastic thyroid cancer: Clinical outcomes with conformal radiotherapy.

BACKGROUND: The aim of this study was to review institutional outcomes for anaplastic thyroid cancer treated with conformal 3-dimensional radiotherapy (3DRT) or intensity-modulated radiotherapy (IMRT). METHODS: In all, 53 consecutive patients were analyzed. Thirty-one (58%) patients were irradiated with curative intent. Median radiation dose was 55 Gray (Gy; range, 4-70 Gy). Thirteen (25%) patients received IMRT to a median 60 Gy (range, 39.9-69.0 Gy). Thirty-nine (74%) patients received chemotherapy with radiation. RESULTS: The Kaplan-Meier estimate of overall survival (OS) at 1 year for definitively irradiated patients was 29%. Patients without distant metastases receiving >or=50 Gy had superior survival outcomes; 5 such patients had no evidence of disease at last follow-up. Use of IMRT versus 3DRT did not influence toxicity. CONCLUSIONS: Outcomes for anaplastic thyroid cancer treated with 3DRT or IMRT remain equivalent to historical results. Healthy patients with localized disease who tolerate full dose irradiation can potentially enjoy prolonged survival. Biologically targeted radiosensitization merits prioritized investigation.

Quality-adjusted survival analysis of Radiation Therapy Oncology Group (RTOG) 90-03: phase III randomized study comparing altered fractionation to standard fractionation radiotherapy for locally advanced head and neck squamous cell carcinoma.

BACKGROUND: To evaluate quality-adjusted survival (QAS) of patients with locally advanced squamous cell carcinoma of the head and neck treated with 4 different radiation fractionation schedules. METHODS: QAS was calculated using the quality-adjusted time without toxicity or relapse (Q-TWiST) methodology. Utilities (patient preferences for certain health states) were obtained by threshold analysis. Q-TWiST therefore equaled TWiST + ([weight for toxicity] x [time spent in toxicity]) + ([weight for relapse] x [time spent in relapse]). RESULTS: A statistically significant increase in QAS existed for patients treated with hyperfractionated radiotherapy compared with standard fractionated radiotherapy (SFX) with a toxicity utility > or = 0.57 and relapse utility < or = 0.72. No statistically significant difference was observed for patients treated with the other 2 fractionation schedules compared with SFX. CONCLUSION: Q-TWiST analysis identified patient groups that would benefit from more aggressive therapy. Further investigation with patient-generated utilities is needed.

Final report of RTOG 9610, a multi-institutional trial of reirradiation and chemotherapy for unresectable recurrent squamous cell carcinoma of the head and neck.

BACKGROUND: Our objectives were to determine the incidence of acute and late toxicities and to estimate the 2-year overall survival for patients treated with reirradiation and chemotherapy for unresectable squamous cell carcinoma of the head and neck (SCCHN). METHODS: Patients with recurrent squamous cell carcinoma or a second primary arising in a previously irradiated field were eligible. Four weekly cycles of 5-fluorouracil 300 mg/m2 IV bolus and hydroxyurea 1.5 g by mouth were used with 60 Gy at 1.5 Gy twice-daily fractions. Toxicity was scored according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. RESULTS: Seventy-nine of the 86 patients enrolled were analyzable. The worst acute toxicity was grade 4 in 17.7% and grade 5 in 7.6%. Grade 3 and 4 late toxicities were found in 19.4% and 3.0%, respectively. The estimated cumulative incidence of grade 3 to 4 late effects occurring at >1 year was 9.4% (95% confidence interval [CI]: 0, 19.7) at 2 and 5 years. The 2- and 5-year cumulative incidence for grade 4 toxicity was 3.1% (95% CI: 0, 9.3). The estimated 2- and 5-year survival rates were 15.2% (95% CI: 7.3, 23.1) and 3.8% (95% CI: 0.8, 8.0), respectively. Patients who entered the study at >1 year from initial radiotherapy (RT) had better survival than did those who were <1 year from prior RT (median survival, 9.8 months vs 5.8 months; p = .036). No correlation was detected between dose received and overall survival. Three patients were alive at 5 years. CONCLUSION: This is the first prospective multi-institutional trial testing reirradiation plus chemotherapy for recurrent or second SCCHN. The approach is feasible with acceptable acute and late effects. The results serve as a benchmark for ongoing RTOG trials.

Postoperative radiotherapy for advanced medullary thyroid cancer--local disease control in the modern era.

BACKGROUND: The purpose of this study is to catalog modern-era postoperative radiotherapy (external beam radiotherapy [EBRT]) outcomes for advanced medullary thyroid cancer. METHODS: Thirty-four consecutive patients with stage IVa-c disease were evaluated. Ten patients had recurrent disease, 16 had mediastinal involvement, and 10 had distant metastasis. Positive surgical margins were present in 12 cases. Median pre-EBRT serum calcitonin was 556. All patients received conformal EBRT or intensity-modulated radiotherapy. Median EBRT dose was 60 Gy and median follow-up was 46.5 months. RESULTS: Kaplan-Meier estimates of locoregional relapse-free survival, disease-specific survival, and overall survival at 5 years were 87%, 62%, and 56%, respectively. Disease in 3 patients with gross residual disease was controlled locoregionally. Distant disease at the time of EBRT did not predict survival. Two (9%) patients reported symptomatic chronic morbidity. CONCLUSION: Surgery followed by EBRT provided durable locoregional disease control with limited morbidity. Postoperative EBRT merits consideration in cases of advanced disease at high risk for locoregional recurrence.

NCCN Task Force Report. prevention and management of mucositis in cancer care.

Oral mucositis (OM) has emerged as a common cause of dose delays and interruptions of cancer therapies such as multicycle chemotherapy, myeloablative chemotherapy, and radiotherapy with or without concurrent chemotherapy of head and neck cancer. Research into both preventive and management strategies has lagged behind research into the common cancer treatment-related morbidities of nausea, vomiting, and cytopenias. This disparity is related to the complex risk assessment of multifactorial patient and treatment factors and different techniques of rating mucositis. In addition, relatively few clinical trials have focused on mucositis as a specific outcome. Currently, the only effective preventive strategies include the use of palifermin to prevent OM in the setting of hematopoietic stem cell transplantation and oral cryotherapy used in conjunction with bolus 5-FU, melphalan, or edatrexate. For the most part, managing OM relies on supportive care and symptom palliation. However, OM is a common problem associated with significant patient morbidity and increased resource use. The magnitude of the problem demands innovative approaches based on expert judgment as evidence accumulates to support specific recommendations. To improve this situation, the NCCN convened a multidisciplinary task force to address key issues. This report integrates expert judgment with a review of key literature on risk assessment, prevention, and treatment strategies, and provides recommendations for the overall management of OM.

Impact of nutrition support on treatment outcome in patients with locally advanced head and neck squamous cell cancer treated with definitive radiotherapy: a secondary analysis of RTOG trial 90-03.

BACKGROUND: The aim was to evaluate the relationship between nutrition support (NS) on host toxicity and cancer outcome in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) undergoing definitive radiotherapy (XRT). METHODS: We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 90-03, a prospective randomized trial evaluating four definitive XRT fractionation schedules in patients with locally advanced HNSCC, which prospectively collected data on NS delivered before treatment (BNS), during treatment (TNS), and after definitive XRT. NS data and pretreatment characteristics of the 1073 evaluable patients were analyzed against therapy toxicity and outcome. RESULTS: Patients receiving BNS experienced significantly less weight loss by the end of treatment and less grade 3 to 4 mucositis than patients not receiving BNS. However, patients receiving BNS had a poorer 5-year actuarial locoregional control rate than patients receiving TNS or no NS (29%, 55%, and 57%, respectively, p < .0001) and a poorer 5-year overall survival rate (16%, 36%, and 49%, respectively, p < .0001). Patients receiving BNS were significantly more likely to have a higher T classification, N status, and overall American Joint Committee on Cancer (AJCC) stage and initial presentation with greater pretreatment weight loss, and a poorer Karnofsky Performance Status (KPS) than patients not receiving BNS. After adjusting for the impact of these prognostic factors through a recursive partition analysis, a multivariate analysis with a stratified Cox model found that BNS was still a highly significant independent prognostic factor for increased locoregional failure (hazards ratio [HR], 1.47; 95% confidence interval [CI], 1.21-1.79; p < .0001) and death (HR, 1.41; 95% CI, 1.19-1.67; p < .0001). CONCLUSION: In this study, the largest prospective evaluation of nutrition data in treated patients with cancer, BNS was associated with inferior treatment outcome in the patients with HNSCC undergoing XRT. These results should be considered hypothesis generating and encourage prospective clinical research and identification of the mechanisms underlying this finding.