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Background Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting. Methods This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non–African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score. Results The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non–African American men). A higher proportion of African American men with National Comprehensive Cancer Network–classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non–African American men. Self-identified African American men were twice more likely than non–African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes. Conclusions Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.

Objective The study aimed to evaluate the impact of late swallowing dysfunction leading to percutaneous endoscopic gastrostomy (PEG) tube dependence on the overall survival (OS) in a cohort of locally advanced head and neck cancer patients treated and cured with definitive radiotherapy (RT) and concurrent systemic therapy (CST). Materials and methods A total of 62 patients with locally advanced head and neck cancer were included in the analysis based on the following selection criteria: stage III, IVA, or IVB disease, treated with definitive RT and CST, no major head and neck surgery, no evidence of local or distant recurrent disease, and at least one post-RT modified barium swallow study. Patients were classified as PEG dependent or PEG independent at the time of the last follow-up. Estimates of OS were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to evaluate the impact of various clinical factors on OS. Results The median follow-up was 48 months (range: 7.6-235 months). The five-year OS was 64.3% in the PEG-dependent group and 86.1% in the PEG-independent group (p=0.022). Age over 70 at diagnosis was also associated with poorer OS (p=0.044). On univariate analysis, PEG dependency maintained a significantly worse OS (hazard ratio [HR]: 2.59; 95% confidence interval [CI]: 1.11-5.99, p=0.028). On multivariate analysis, PEG dependency (HR: 4.25; 95% CI: 1.33-13.62; p=0.015), advanced N stage (HR: 4.74; 95% CI: 1.17-19.26, p=0.035), and older age at diagnosis (HR: 4.37; 95% CI: 1.21-15.84; p=0.025) were significantly associated with worse OS. Conclusions Late PEG dependency is associated with poor OS in head and neck cancer patients cured with definitive RT and CST. Interventions designed to help head and neck cancer patients maintain swallowing function may result in improved outcomes.

5005 Background: Risk stratification of prostate cancer (PC) using routine clinical variables remains suboptimal as they do not account for underlying tumor biology. The genomic classifier provides information on underlying biology and independently predicts an individual patient’s risk of metastasis. Although the performance of the genomic classifier has been tested across different cohorts primarily comprised of White men, its validation as an optimal genomic risk classifier for African American men (AAM) is thus far lacking in a prospective trial. We report the initial results on the prospective validation of the genomic classifier in a matched cohort of AAM and non-AAM (NAAM). Methods: This was a multisite, prospective validation trial of the genomic classifier i.e. Decipher score in AAM. Participants were recruited on a 1:1 enrollment ratio of AAM to NAAM diagnosed with low-intermediate risk PC. Patient on active surveillance were ineligible. NAAM were matched to AAM on PSA, age, biopsy Gleason score, clinical stage, and percent positive biopsy cores. Diagnostic biopsy specimens were processed at a CLIA certified laboratory and Decipher score was assessed using whole transcriptome profiling platform. Total target accrual was 250 men treated for low-intermediate PC over three years. Statistical analyses include categorical comparison of race dependent risk group migration between NCCN risk group and genomic classifier. Relative risk of metastasis was estimated using negative binomial model. Results: Final analytical cohort included 207 evaluable cases (AAM = 102 and NAAM = 107) with comprehensive genomic information. Risk of metastasis was determined based on pretreatment biopsy Decipher score, and patients were classified as low, favorable-, and unfavorable intermediate risk. Despite achieving a robustly matched clinical cohort, we observed significant genomic heterogeneity between AAM and NAAM across NCCN risk groups. In a comparative analysis, 49% of low-favorable intermediate risk AAM harbored high genomic risk tumors as compared to only 10% NAAM, p = 0.02. Similarly, using the modified clinico-genomic risk classifier (cGC), comprised of both Decipher score and clinical variables, AAM experienced an extreme deviation of risk status (difference [δ] between cGC and NCCN ≥ 2) as compared to NAAM (26.8% vs 8.1%, p = 0.03). In a binomial model, low-favorable NCCN risk AAM were 3.9 times more likely to be reclassified as high genomic risk for distant metastasis compared to NAAM (RR = 3.99, 95% CI, 1.15 – 13.86, p = 0.02). Conclusions: Clinical NCCN risk classification is an inadequate surrogate of tumor biology and offers suboptimal risk stratification for AAM with PC. Integration of patient specific genomic classifier into standard of care will improve accuracy in disease risk classification and treatment recommendations for AAM. Clinical trial information: NCT02723734.

BACKGROUND: The objective of this phase 2 study was to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated-boost (SIB), intensity-modulated radiation therapy (IMRT) into a well described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. METHOD: Patients with stage IVA and IVB or high-risk stage III squamous cell carcinomas of the head and neck were enrolled on a phase 2 trial. Prior organ-conserving surgery or induction chemotherapy was allowed off protocol. SIB-IMRT was prescribed to low-risk volumes (43.2 gray [Gy] to 48 Gy) and intermediate-risk volumes (54-63 Gy). A separate IMRT cone-down plan was targeted to macroscopic disease (72 Gy). The median radiation dose was 72 Gy (range, 60-72 Gy) administered in 1.5 Gy fractions twice daily during Weeks 1, 3, 5, 7 and 9. Concurrent systemic therapy consisted of 5-FU (600 mg/m2), HU (500 mg twice daily), and cetuximab (250 mg/m2). RESULTS: From January 2007 through April 2008, 33 patients were enrolled. At a median follow-up of 24 months, the 2-year rates of locoregional control, distant control, disease-free survival, and overall survival were 83%, 79%, 69%, and 86%, respectively. Grade 3 toxicity consisted of mucositis in 33% of patients, radiation dermatitis in 15%of patients, anemia in 18% of patients, leukopenia in 18% of patients, neutropenia in 12% of patients, and thrombocytopenia in 3% of patients. Most patients (64%) were able to tolerate treatment without a feeding tube, and there were no acute or late grade ≥4 adverse events. CONCLUSIONS: The current results indicated that concurrent 5-FU, HU, and cetuximab plus SIB-IMRT is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy into curative therapy for patients with locally advanced head and neck cancer. Cancer 2011. © 2010 American Cancer Society.

To describe long-term outcomes and toxicity after salvage brachytherapy (BT) for local failure after initial radiotherapy for prostate cancer.Between 1994 and 2008, 37 men with local failure after initial prostate radiotherapy (32 external-beam radiation therapy [EBRT] and 5 BT) underwent salvage BT with (103)Pd or (125)I. Estimates of freedom from biochemical failure (FFbF, Phoenix definition) and cause-specific survival (CSS) were calculated using the Kaplan-Meier method. Toxicities were graded using CTCv3.0.Median follow-up was 86 months (range, 2-156). The median dose to 90% of the prostate volume was 122 Gy (range, 67-166). The 10-year FFbF and CSS were 54% and 96%, respectively. On univariate analysis, prostate-specific antigen (PSA)10 ng/mL at initial diagnosis was significantly associated with FFbF (p = 0.01), and there were trends for both age70 years (p = 0.08) and PSA6 ng/mL (p = 0.08) at the time of salvage BT. On multivariate analysis, only presalvage PSA6 ng/mL (p = 0.046) was significantly associated with improved FFbF. There were three Grade 3 toxicities and one Grade 4 toxicity. Pelvic lymph node dissection before salvage BT was the only variable significantly associated with Gradeor = 2 toxicity (p = 0.03).With a median follow-up of 86 months, salvage prostate BT was associated with a 10-year FFbF of 54% and CSS of 96%. Improved FFbF was associated with a presalvage PSA6 ng/mL. Toxicity was worse in patients who had undergone pelvic lymph node dissection before salvage BT. Careful patient selection for salvage BT may result in improved outcomes and reduced toxicity.

To evaluate the influence of patient- and treatment-related factors on freedom from biochemical failure (FFbF) in patients with intermediate-risk prostate cancer.From a prospectively collected database of 2250 men treated at Mount Sinai Hospital from 1990 to 2004 with low-dose-rate brachytherapy for prostate cancer, 558 men with either one or more intermediate-risk features (prostate-specific antigen [PSA] level 10-20 ng/mL, Gleason score 7, or Stage T2b) were identified who had a minimum follow-up of 24 months and postimplant CT-based dosimetric analysis. Biologically effective dose (BED) values were calculated to compare doses from different isotopes and treatment regimens. Patients were treated with brachytherapy with or without hormone therapy and/or external-beam radiotherapy. Patient- and treatment-related factors were analyzed with respect to FFbF. The median follow-up was 60 months (range, 24-167 months). Biochemical failure was defined according to the Phoenix definition. Univariate analyses were used to determine whether any variable was predictive of FFbF. A two-sided p value of0.05 was considered significant.Overall, the actuarial FFbF at 10 years was 86%. Dose (BED150 Gy(2) vs.or=150 Gy(2)) was the only significant predictor of FFbF (p0.001). None of the other variables (PSA, external-beam radiotherapy, Gleason score, treatment type, hormones, stage, and number of risk factors) was found to be a statistically significant predictor of 10-year FFbF.Radiation dose is an important predictor of FFbF in intermediate-risk prostate cancer. Treatment should continue to be individualized according to presenting disease characteristics until results from Radiation Therapy Oncology Group trial 0232 become available.

The objective of this study was to determine whether an association exists between certain single nucleotide polymorphisms (SNPs), which have previously been linked with adverse normal tissue effects resulting from radiotherapy, and the development of radiation injury resulting from radiotherapy for prostate cancer. A total of 135 consecutive patients with clinically localized prostate cancer and a minimum of 1 year of follow-up who had been treated with radiation therapy, either brachytherapy alone or in combination with external-beam radiotherapy, with or without hormone therapy, were genotyped for SNPs in SOD2, XRCC1 and XRCC3. Three common late tissue toxicities were investigated: late rectal bleeding, urinary morbidity, and erectile dysfunction. Patients with the XRCC1 rs25489 G/A (Arg280His) genotype were more likely to develop erectile dysfunction after irradiation than patients who had the G/G genotype (67% compared to 24%; P=0.048). In addition, patients who had the SOD2 rs4880 T/C (Val16Ala) genotype exhibited a significant increase in grade 2 late rectal bleeding compared to patients who had either the C/C or T/T genotype for this SNP (8% compared to 0%; P=0.02). Finally, patients with the combination of the SOD2 rs4880 C/T genotype and XRCC3 rs861539 T/C (Thr241Met) genotype experienced a significant increase in grade 2 late rectal bleeding compared to patients without this particular genotypic arrangement (14% compared to 1%; P=0.002). These results suggest that SNPs in the SOD2, XRCC1 and XRCC3 genes are associated with the development of late radiation injury in patients treated with radiation therapy for prostate adenocarcinoma.

Purpose Combined brachytherapy and external beam radiation therapy (EBRT) of the prostate and seminal vesicles (SVs) is evolving as a successful treatment option for high-risk prostate cancer. Dose–volume histogram (DVH) analysis of the SV was performed in patients with biopsy-positive SV who received implantation of the SV and prostate. Methods and materials Fifteen consecutive patients with high-risk features (prostate-specific antigen [PSA] ≥ 10 ng/mL, Gleason score ≥7, or clinical stage ≥T2b) and a positive SV biopsy were treated with a 103Pd implant of the prostate and SV followed by 45 Gy of EBRT. DVHs were generated for the prostate and total SV volume (SVT). In addition, the SV was divided into 3-mm-thick volumes identified as SV1, SV2, SV3, SV4, SV5, and SV6 starting from the junction of the prostate and SV and extending distally. Delivered dose was defined as the D90 (dose delivered to 90% of the organ on DVH). Results The median number of seeds implanted into the prostate and the SVT was 59 (41–94) and 9 (4–21), respectively. The median D90 values for the prostate, SVT, SV1, SV2, SV3, SV4, SV5, and SV6 were 103.2 (87.4–137.1), 46.2 (4.0–69.4), 76.0 (31.2–147), 63.4 (25.1–145.9), 49.7 (15.3–118), 27.4 (9.3–135.1), 14.2 (2.3–100.3), and 3.9 (0–61.5) Gy, respectively. Conclusions Implantation of the SV using a real-time intraoperative approach is technically feasible and results in higher doses to the SV than has been reported with implantation of the prostate alone. Although dose distribution in the SV can be variable and unpredictable, these doses, in combination with 45 Gy of EBRT, may be adequate to control disease spread in these organs.

Purpose The risk of secondary lung malignancy (SLM) is a significant concern for women treated with whole-breast radiation therapy after breast-conserving surgery for early-stage breast cancer. In this study, a biologically based secondary malignancy model was used to quantify the risk of secondary lung malignancies (SLMs) associated with several common methods of delivering whole-breast radiation therapy (RT). Methods and Materials Both supine and prone computed tomography simulations of 15 women with early breast cancer were used to generate standard fractionated and hypofractionated whole-breast RT treatment plans for each patient. Dose–volume histograms (DVHs) of the ipsilateral breast and lung were calculated for each patient on each plan. A model of spontaneous and radiation-induced carcinogenesis was used to determine the relative risks of SLMs for the different treatment techniques. Results A higher risk of SLMs was predicted for supine breast irradiation when compared with prone breast irradiation for both the standard fractionation and hypofractionation schedules (relative risk [RR] = 2.59, 95% confidence interval (CI) = 2.30–2.88, and RR = 2.68, 95% CI = 2.39–2.98, respectively). No difference in risk of SLMs was noted between standard fractionation and hypofractionation schedules in either the supine position (RR = 1.05, 95% CI = 0.97–1.14) or the prone position (RR = 1.01, 95% CI = 0.88–1.15). Conclusions Compared with supine whole-breast irradiation, prone breast irradiation is associated with a significantly lower predicted risk of secondary lung malignancy. In this modeling study, fractionation schedule did not have an impact on the risk of SLMs in women treated with whole-breast RT for early breast cancer.

To evaluate retrospectively the biochemical outcomes of young men treated with low-dose-rate brachytherapy for prostate cancer.From 1990 to 2005, 1,665 men with clinically localized prostate cancer were treated with low-dose-rate brachytherapy +/- hormone therapy (HT) +/- external beam radiotherapy and underwentor = 2 years of follow-up. Patients were stratified on the basis of age:or = 60 (n = 378) and60 years (n = 1,287). Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/mL. Univariate and multivariate analyses were used to determine the association of variables with freedom from biochemical failure (FFbF).Median follow-up was 68 months (range, 24-180) for menor = 60 years and 66 months (range, 24-200) for men60. For the entire group, the actuarial 5- and 8-year FFbF rates were 94% and 88%, respectively. Menor = 60 demonstrated similar 5- and 8-year FFbF (95% and 92%) compared with men60 (93% and 87%; p = 0.071). A larger percent of young patients presented with low-risk disease; lower clinical stage, Gleason score (GS), and pretreatment PSA values; were treated after 1997; did not receive any HT; and had a high biologic effective dose (BED) of radiation (all ps0.001). On multivariate analysis, PSA (p = 0.001), GS (p = 0.005), and BED (p0.001) were significantly associated with FFbF, but age was not (p = 0.665).Young men achieve excellent 5- and 8-year biochemical control rates that are comparable to those of older men after prostate brachytherapy. Young age should not be a deterrent when considering brachytherapy as a primary treatment option for clinically localized prostate cancer.

Head and neck cancer is best managed in a multidisciplinary setting. Surgery, radiation therapy, chemotherapy and, more recently, biologic therapy are often employed in various combinations in an attempt to eradicate both clinically apparent and occult disease. The goals of treatment include maximizing tumor control while maintaining function and quality of life. Most patients present with locally advanced disease, and multimodality organ-conserving therapy is often employed for these patients based on the results of multiple Phase III clinical trials. This article focuses on the rationale and evidence supporting the use of concurrent chemotherapy and radiation therapy in the management of locally advanced head and neck cancers.

Purpose To investigate whether the presence of single nucleotide polymorphisms (SNPs) located within TGFB1 might be predictive for the development of adverse quality-of-life outcomes in prostate cancer patients treated with radiotherapy. Methods and Materials A total of 141 prostate cancer patients treated with radiotherapy were screened for SNPs in TGFB1 using DNA sequencing. Three quality-of-life outcomes were investigated: ( 1 ) prospective decline in erectile function, ( 2 ) urinary quality of life, and ( 3 ) rectal bleeding. Median follow-up was 51.3 months (range, 12–138 months; SD, 24.4 months). Results Those patients who possessed either the T/T genotype at position −509, the C/C genotype at position 869 (pro/pro, codon 10) or the G/C genotype at position 915 (arg/pro, codon 25) were significantly associated with the development of a decline in erectile function compared with those who did not have these genotypes: 56% (9 of 16) vs. 24% (11 of 45) ( p = 0.02). In addition, patients with the −509 T/T genotype had a significantly increased risk of developing late rectal bleeding compared with those who had either the C/T or C/C genotype at this position: 55% (6 of 11) vs. 26% (34 of 130) ( p = 0.05). Conclusions Possession of certain TGFB1 genotypes is associated with the development of both erectile dysfunction and late rectal bleeding in patients treated with radiotherapy for prostate cancer. Therefore, identification of patients harboring these genotypes may represent a means to predict which men are most likely to suffer from poor quality-of-life outcomes after radiotherapy for prostate cancer.

Purpose: To examine whether possession of genetic alterations in the ATM (ataxia telangiectasia) gene is associated with rectal bleeding in a dose-dependent and volume-dependent manner. Methods and Materials: One hundred eight prostate cancer patients who underwent brachytherapy using either an 125 I implant, a 103 Pd implant, or the combination of external beam radiotherapy with a 103 Pd implant and had a minimum of 1 year follow-up were screened for DNA sequence variations in the 62 coding exons of the ATM gene using denaturing high-performance liquid chromatography. Rectal dose was reported as the volume (in cubic centimeters) of rectum receiving the brachytherapy prescription dose. The two-sided Fisher exact test was used to compare differences in proportions. Results: A significant correlation between the presence of any ATM sequence alteration and Grade 1 to 2 proctitis was obtained when the radiation dose to rectal tissue was quantified. Rectal bleeding occurred in 4 of 13 patients (31%) with a variant versus 1 of 23 (4%) without a genetic alteration for patients who had 3 of rectal tissue receiving the implant prescription dose ( p = 0.05). Of patients in whom 0.7–1.4 cm 3 of the rectum received the implant prescription, 4 of 11 (36%) with an ATM alteration exhibited Grade 1 to 2 proctitis, whereas 1 of 21 (5%) without a variant ( p = 0.04) developed this radiation-induced late effect. Conclusions: The possession of genetic variants in the ATM gene is associated with the development of radiation-induced proctitis after prostate cancer radiotherapy for patients who receive the full prescription dose to either a low or a moderate volume of rectal tissue.

Purpose/Objective(s): Locally advanced non-small cell lung carcinoma remains a therapeutic challenge for clinicians. Currently the standard of care is multimodality therapy, but sequencing of multimodality therapy is unclear. Population based studies suggest that neoadjuvant radiation (N-RT) offers an overall and cause-specific survival benefit over adjuvant radiation (A-RT) in the treatment of Stage III NSCLC. The goal of this study was to identify the factors which affect the survival benefit of neoadjuvant radiation in Stage III NSCLC.

e15162 Background: The risk of secondary rectal malignancies (SRMs) is a significant concern following radiation therapy for prostate cancer patients. Modern prostate radiotherapy techniques include the use of intensity modulated radiation therapy (IMRT) and rectal balloons to decrease treatment related toxicity. These technologies may also lower the likelihood of radiation-induced SRMs. In this study, a novel biologically-based carcinogenesis model was used to quantify and to compare the predicted risks of SRMs in men treated with or without a rectal balloon in place using either standard 3-D conformal radiotherapy (3D-CRT) or IMRT radiotherapy. Methods: Treatment plans were developed for ten clinically localized prostate cancer patients using CT scans obtained both with and without a rectal balloon in place. Target and normal structures were contoured, and dose-volume histograms (DVHs) for these organs were determined with a planned 3D-CRT dose of 75.6 Gy or with a planned IMRT dose of 81 Gy. A biologically-based mathematical model of spontaneous and radiation-induced carcinogenesis was used to determine the excess absolute risk of SRMs for each plan. These risks were then compared to one another and to the baseline population. Results: Treatment with IMRT and a rectal balloon in place resulted in a significantly lower mean rectal wall dose in all patients compared with treatment with 3D-CRT without a rectal balloon. The average mean rectal wall dose with IMRT and a rectal balloon in place was 31.0 Gy versus 40.1 Gy with 3D-CRT without the rectal balloon (p < 0.001). A significantly higher risk of SRMs was predicted for patients treated with 3-D CRT without rectal balloons when compared with patients treated with IMRT with balloons in place (p < 0.001, relative risk 1.30; 95% confidence interval 1.16-1.44). Conclusions: For prostate cancer patients treated with definitive radiotherapy, the use of IMRT and rectal balloons during radiation, when compared to treatment with 3-D conformal radiotherapy, is associated with a significant reduction in the predicted risk of secondary rectal malignancies.

1085 Background: The risk of secondary lung malignancy (SLM) is a concern for women treated with breast radiation therapy after breast conserving surgery for early stage breast cancer. The purpose of this study was to estimate the absolute and relative risks of developing secondary lung malignancies in patients treated either with supine or prone whole breast radiotherapy or with Mammosite brachytherapy. Methods: Twenty-two women treated with breast radiotherapy were enrolled in the study. Fifteen patients underwent CT simulation and standard fractionated and hypofractionated whole breast radiation treatment planning in both the prone and the supine positions. Seven patients underwent CT simulation and treatment planning for Mammosite brachytherapy. Dose-volume histograms of the ipsilateral breast and the lungs were calculated and incorporated into a biologically-based mathematical model of spontaneous and radiation-induced carcinogenesis to quantitatively predict the lifetime absolute and relative risks ...

6014 Background: This phase II study was conducted to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated boost intensity modulated radiation (SIB-IMRT) into a well-described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. Endpoints included overall survival (OS), locoregional (LRC) and (DC), quality of life and toxicity. Methods: Patients with stage IVa-IVb or high-risk stage III squamous cell carcinomas were enrolled on a phase II trial. Prior organ-conserving surgical therapy or induction chemotherapy was allowed off protocol. SIB-IMRT was prescribed to low (43.2 to 48 Gy) and intermediate (54 to 63 Gy) risk volumes. A separate IMRT conedown plan was targeted to gross disease (72 Gy). The median radiation dose was 72 Gy (range 60 to 72 Gy) administered in 1.5 Gy fractions BID on weeks 1, 3, 5, 7 ± 9. Concurrent systemic therapy consisted of 5-FU (600 mg/m2), HU (500 mg BID) and cetuximab (250 mg/m2). Results: From January 2007 to April 2008, 33 subjects enrolled. Characteristics included 24 males; median age 59; ECOG performance status was 0 in 12. Disease was stage IVa-b disease in 31 (94%), T3–4 in 16 (48%), N2–3 in 23 (70%), and oropharynx primary in 15 (45%). Median follow-up in surviving patients is 15 months (range 6 to 22 months). The 1 year LRC, DC and OS is 91%, 82%, and 92%, respectively. Grade 3 toxicity consisted of mucositis (33%), radiation dermatitis (15%), anemia (15%), and leukopenia (15%), and neutropenia (9%). There were no grade 4–5 events. The majority of patients (64%) were able to tolerate treatment without a feeding tube. Median patient reported University of Washington QOL-R scores before, immediately after, 3 months and 8 months after chemoradiation were 85.5 (±14), 65 (±13), 76.5 (±15), and 84.5 (±9), respectively. Conclusions: Concurrent 5-FU, HU, cetuximab, and SIB-IMRT is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy in the curative therapy of locally advanced head and neck cancer. [Table: see text]