Exploring Potential Therapeutic Benefits of Spatially Fractionated Radiation Therapy

The work presented in this dissertation focuses on investigating new and safe ways to use radiation for enhancing cancer treatment via preclinical studies of Spatially Fractionated Radiation Therapy (SFRT). SFRT is a very promising, yet poorly understood, cancer radiotherapy approach that has recently gained traction due to its remarkable tissue selectivity, eradicating tumors effectively with little treatment toxicity, as well as its easy implementation on a wide range of clinical radiotherapy machines. Decades of clinical and preclinical research have demonstrated that SFRT may be used as a safe and effective way to shrink very large, bulky tumors in patients for whom other modern treatment approaches have been ineffective. Despite its very high therapeutic ratio and potential to satisfy several unmet needs in cancer treatment, SFRT remains largely an experimental approach, and a lack of preclinical SFRT research leaves many important questions unanswered. This body of work investigates the development of a novel SFRT-delivery system and its implementation in a variety of preclinical SFRT research scenarios in the hopes of shedding light on some of the unanswered questions that hinder clinical translation of this promising treatment technology. In this work, systemic studies investigate key unique SFRT dosimetric parameters and their correlations with treatment response, as well as SFRT’s specific advantages over conventional radiotherapy, particularly those enhancing multi-modality cancer therapy approaches such as anti-cancer immunotherapy and nanoparticle chemotherapy drug-delivery to tumors. SFRT is a low-toxicity and low-cost radiation therapy treatment that offers hope for many cancer patients, especially those failed by current cancer treatment technologies. The work presented here aims to improve the understanding of this treatment approach and contribute to the effective and accessible treatment of cancer.Doctor of Philosoph

Radiobiology of Combining Radiotherapy with Other Cancer Treatment Modalities

editorial reviewedIn this chapter, we address the role of radiation as treatment modality in the context of oncological treatments given to patients. Physical aspects of the use of ionizing radiation (IR)—by either photons, neutrons, or charged (high linear energy transfer) particles—and their clinical application are summarized. Information is also provided regarding the radiobiological rationale of the use of conventional fractionation as well as alternative fractionation schedules using deviating total dose, fraction size, number of fractions, and the overall treatment time. Pro- and contra arguments of hypofractionation are discussed. In particular, the biological rationale and clinical application of Stereotactic Body Radiation Therapy (SBRT) are described. Furthermore, background information is given about FLASH radiotherapy (RT), which is an emerging new radiation method using ultra-high dose rate allowing the healthy, normal tissues and organs to be spared while maintaining the antitumor effect. Spatial fractionation of radiation in tumor therapy, another method that reduces damage to normal tissue is presented. Normal tissue doses could also be minimized by interstitial or intraluminal irradiation, i.e., brachytherapy, and herein an overview is given on the principles of brachytherapy and its clinical application. Furthermore, details are provided regarding the principles, clinical application, and limitations of boron neutron capture therapy (BNCT). Another important key issue in cancer therapy is the combination of RT with other treatment modalities, e.g., chemotherapy, targeted therapy, immunotherapy, hyperthermia, and hormonal therapy. Combination treatments are aimed to selectively enhance the effect of radiation in cancer cells or to trigger the immune system but also to minimize adverse effects on normal cells. The biological rationale of all these combination treatments as well as their application in clinical settings are outlined. To selectively reach high concentrations of radionuclides in tumor tissue, radioembolization is a highly interesting approach. Also, radioligand therapy which enables specific targeting of cancer cells, while causing minimal harm surrounding healthy tissues is presented. A brief overview is provided on how nanotechnology could contribute to the diagnosis and treatment of cancer. Last but not least, risk factors involved in acquiring secondary tumors after RT are discussed.3. Good health and well-bein

The Radiochemical Basis of FLASH and Minibeam Radiotherapy: Investigating H2O2 Production and Diffusion

Background: FLASH and minibeam radiotherapy (MBRT) have emerged as promising approaches to enhance the therapeutic ratio in radiation therapy by selectively sparing normal tissues while maintaining effective tumor control. Despite their potential, the underlying radiochemical mechanisms remain incompletely understood, particularly regarding hydrogen peroxide (H2O2) production and diffusion under ultra-high dose rate (UHDR) conditions. Purpose: This dissertation investigates the radiochemical basis of FLASH and MBRT, focusing on the dose-rate dependency of H2O2 production and its diffusion dynamics in both pure water and biological-relevant tissues. By elucidating these processes, this work aims to provide insights into radiochemical mechanism and advancing the clinical implementation of these novel radiation therapy modalities. Methods: H2O2 production was quantified under different radiation sources—including electron, X-ray, and carbon-ion beams—across UHDR and conventional dose rates (CONV). And the impact of scavengers, carbon dioxide (CO₂), and multiple UHDR pulses on H2O2 kinetics was also examined. Additionally, a novel diffusion-absorption model was developed to simulate the H2O2 distribution under MBRT, and compared with previous aniaml experiments. Results: The findings revealed a significant dose-rate dependency in H2O2 production, with UHDR irradiation leading to lower H2O2 yields than CONV. This effect was attributed to the enhanced removal of hydroxyl radicals (•OH) under UHDR, mediated by solvated electrons. Experimental results also demonstrated that CO2 presence increased H2O2 production, further influencing radiochemical kinetics. In MBRT, H2O2 diffusion played a crucial role in dose homogenization over time, with the refined diffusion model accurately predicting its various MBRT treatment outcome. Conclusion: This dissertation provides novel insights into the radiochemical foundations of FLASH and MBRT, particularly concerning H2O2 production and diffusion mechanisms. The results contribute to refining theoretical models and optimizing treatment strategies for these emerging radiotherapy techniques. Future research should focus on validating these findings in preclinical and clinical settings to facilitate the translation of FLASH and MBRT into routine clinical practice

Recurrence of Primary Mucosal Head and Neck Squamous Cell Carcinoma in Solid Organ Transplant Recipients

Background: Patients that undergo a solid organ transplant have been shown to have a higher risk of developing cancer and even subsequent recurrences due to the immunosuppressants required to prevent rejection. Most established literature has been in the setting of cutaneous malignancies. In this study, we examine patients diagnosed with primary mucosal head and neck squamous cell carcinomas (HNSCC) diagnosed post-transplant to analyze their disease characteristics and clinical outcomes. Objectives: To retrospectively characterize patients with primary mucosal HNSCC with history of prior solid organ transplant to define patient and tumor factors as well as analyze their long-term outcomes. Methods: IRB approval was obtained for a retrospective evaluation utilizing our institutional head and neck cancer database. The analysis included patients who had previously undergone a solid organ transplant and subsequently were diagnosed with a primary mucosal HNSCC. These included patients diagnosed from March 2006 to March 2021. The onset of recurrence was analyzed to identify long-term health implications for this patient cohort. Kaplan-Meier analyses were performed to calculate overall and disease-free survival. Results: Out of 1,221 patients in our database, 24 patients met the inclusion criteria. Three patients were excluded due to lack of treatment or follow-up information, creating a sample of 21 patients. Of these, 13 (61.9%) received a liver, 4 (19%) received a kidney, 1 (4.8%) received a lung, and 3 (14.3%) received two transplants. After receiving the transplant, the median time to a HNSCC diagnosis was 6.4 years (range of 0.5 y to 18.5 y). The primary tumors included 8 (36.3%) oropharyngeal, 8 (36.3%) oral cavity, 5 (22.7%) laryngeal, and 1 (4.5%) hypopharyngeal lesion for a total of 22 lesions, with one patient having concurrent primaries of the oral cavity and oropharynx. The cohort included 1 (4.7%) stage 0, 7 (33.3%) stage I, 3 (14.3%) stage II, 3 (14.3%) stage III, and 7 (33.3%) stage IV; no patients had distant metastasis at time of diagnosis. Of the patients, 7 (33.3%) were treated with surgery alone, 6 (28.6%) received post-operative radiation/chemoradiation, 6 (28.6%) were treated with definitive chemoradiation, and 2 (9.5%) received definitive radiation. Median overall survival was 31 months. After treatment, 6 (28.6%) patients experienced a recurrence. Disease-free survival was 72.1% at 12 months. All patients who had a recurrence also died within the follow-up period. The median time of death after recurrence for all six patients was 11.5 months (range of 1 month to 22 mo). Conclusions: Solid organ transplant patients are at a higher risk of developing many different cancers. Treatment of primary mucosal HNSCC is frequently done with curative intent and can be associated with significant morbidity. A better understanding of how solid organ transplant history modifies the disease course can help properly guide treatment decisions. In particular, this series highlights a high rate of mortality among patients who experience a disease recurrence. Further research is needed to better understand the risks associated with recurrence in solid organ transplant patients

Surgery After Neoadjuvant Stereotactic MRI Guided Adaptive Radiation in Pancreatic Cancer: Multi-institutional Toxicity and Survival Outcomes

Background: Favorable toxicity and survival outcomes after dose escalated stereotactic MR guided adaptive radiation therapy (SMART) have been recently published for locally advanced (LA) and borderline resectable (BR) pancreatic cancer. Perioperative morbidity and mortality are not well understood after ablative radiation therapy, which may temper enthusiasm for offering surgery. Objectives: The purpose of this study was to investigate survival and toxicity in resected pancreas cancer patients after neoadjuvant ablative SMART. Methods: In this IRB approved analysis, we retrospectively reviewed 33 consecutive patients with resectable, BR, and LA pancreatic cancer based on NCCN 2.2021 staging criteria who were treated at 2 institutions from 2017-2020 with neoadjuvant SMART 50 Gy in 5 fractions on a 0.35T MR Linac and later underwent definitive surgical resection. Overall survival (OS) and locoregional control (LRC) were evaluated by Kaplan-Meier method. Results: Median follow up was 22.4 months from diagnosis and 17.8 months from last day of RT. Most had BR (55%), otherwise initially resectable (33%) or LA (12%) pancreatic cancer. Median duration of induction chemotherapy was 3.5 (SD 1.6) months with most common regimens being FOLFIRINOX (74%), gemcitabine/abraxane (24%) and FOLFOX (3%). Performance status was ECOG 0, 1, 2 in 16 (48.5%), 12 (36.4%), and 5 (15.2%), respectively. Whipple was performed in 27 (82%) of patients, distal pancreatectomy in 4 (12%), and total pancreatectomy in 2 (6%). The median duration from SMART completion to surgery was 6.9 weeks (4.7-44.1). R0 resections were achieved in 28 (84.8%) of patients with the rest being R1, all in BR patients. Vascular resection/reconstruction was performed of the portal vein (PV) in 8 (24.2%) patients, SMV in 4 (12%), SMA in 1 (3%), and common hepatic artery in 2 (6%). Vascular resection/reconstruction was performed in all LA patients. Median OS, 1-year OS, and 2-year OS from diagnosis were 29.6 months, 93.8%, 81.5%, respectively. Median OS from RT was not yet reached; 1-year OS was 90.9%. LRC at 1 and 2 years was 97% and 93%, respectively. Radiation related acute and late grade 3+ gastrointestinal toxicity was seen in 2 (6%) and 2 (6%) patients. Post-op mortality at 30 and 90 days was seen 2 (6%) and 3 (9%) of patients with 1 death from GI bleed attributed to surgery and 1 death from hepatic ischemia related to PV resection. Conclusions: To the best of our knowledge, this is the first report suggesting that surgery for pancreas cancer after dose escalated 5-fraction SMART is feasible. Further clarification is needed with respect to ideal patient selection and timing for surgery, the safety of arterial versus venous resection/reconstruction, and histopathologic response after delivery of ablative versus non-ablative radiation dose

Expanding Our Understanding of Adherence: The Role of Health Literacy and Cognitive Function in Adherence and Outcomes in Head and Neck Cancer

Background: Health literacy is the degree to which a person has the capacity to obtain, process, and understand basic information and services needed to make decisions about their health care. Poor health literacy has been associated with difficulties managing medications, assessing and evaluating health information, completing medical and financial forms, and comparing nutritional information of foods. As such, health literacy is closely related to adherence to medical treatment. Cognitive function contributes to one\u27s health literacy, though also independently contributes to adherence. Patients with head and neck cancers require complex, often multimodal care, and both health literacy and cognitive function have been found to be lower than the general population. However no study has examined the interaction between cognitive function and health literacy within treatment for head and neck cancer and outcomes. Objectives: To examine the role of cognitive function and health literacy in adherence to definitive and adjuvant radiotherapy and chemoradiotherapy and disease-free and overall survival in patients with head and neck cancer. Methods: 149 patients who received either definitive or adjuvant radiotherapy or chemoradiotherapy for squamous cell carcinoma of the head and neck and were assessed by psycho-oncology provider before initiating treatment were included. Patients between August 2017 through March 2020 were included. Patients were administered the Montreal Cognitive Assessment (MoCA) and the Rapid Estimate of Adult Literacy in Medicine (REALM-SF) by the psych-oncologist before starting treatment. Cancer and treatment related variables, including adherence, were obtained via chart review. Adherence was defined as having completed the treatment recommended by the Multi-disciplinary Tumor Board. Results: Patients were predominantly male (78%), white (73%), with an average age of 62 years (SD=9.1). The average years of education was 13.6 years (SD=2.6). The mean health literacy score was 6.3 out of 7 (SD=1.3, range 0-7), indicating reading at 7-8th grade level. The mean cognitive function score was 23.8 out of 30 (SD=3.6, range 10-30, scores less than 26 are indicative of cognitive impairment). Sixteen percent of patients were non-adherent to treatment recommendations and this was not associated with either health literacy or cognitive function (P=0.5 & 0.36, respectively). Lower health literacy was associated with later stage at presentation (P\u3c0.05). Health literacy was not associated with disease-free or overall survival (P=0.66 & 0.11, respectively). However, cognitive function was associated with overall survival (P\u3c0.0001) but not disease-free survival (P=0.22). Conclusions: Psychosocial variables such as health literacy and cognitive function are infrequently considered or studied in head and neck cancer. However, there exists significant evidence that patients with head and neck cancer tend to have higher rates of cognitive impairment and lower health literacy than the general population. Further, literacy and cognitive function are known to contribute to health outcomes in other populations. The current study found that cognitive impairment, but not health literacy, is associated with overall survival, while not being associated with treatment adherence. Further research is needed into the pathways that cognitive function interacts with cancer care and survival. This study highlights the need for assessment of cognitive function in patients with head and neck cancer, as identification and intervention with these patients can aid in survival outcomes and quality of life

Stereotactic MRI-guided Adaptive Radiation Therapy for Non-metastatic Pancreatic Cancer; Outcomes and Toxicity Analysis for Patients Treated in an Underserved Urban Center

Background: Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) is an emerging technology for treatment of pancreatic cancer patients. Initial results show favorable survival and toxicity. However, data is still sparse overall, and especially in underserved patient populations. The purpose of this study is to review SMART outcomes at our underserved urban academic cancer. Objectives: Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) is an emerging technology for treatment of pancreatic cancer patients. Initial results show favorable survival and toxicity. However, data is still sparse overall, and especially in underserved patient populations. The purpose of this study is to review SMART outcomes at our underserved urban academic cancer. Methods: In this IRB approved retrospective chart review we reviewed 98 patients with non-metastatic pancreatic cancer, who completed SMART between November 2018-January 2021. All 98 patients were treated with 50 Gy in 5 daily fractions with adaptive technique as deemed appropriate by treating radiation oncologist. The primary endpoints were overall survival (OS), progression free survival (PFS), and both acute and late grade 3+ GI toxicity. OS, PFS, locoregional control and distant control were estimated by Kaplan-Meier method and compared using log-rank test. The effect of clinical features on OS was assessed using univariate and multivariate Cox proportional hazard models. OS and PFS were calculated from completion of radiation. Grade 3+ GI toxicity probably or definitively related to radiation was recorded. All incidences of GI bleeding, regardless of attribution, were also recorded. Results: Median follow up was 20.9 months from time of diagnosis and 14 months from radiation. 21 (21%) patients were borderline resectable, 42 (43%) locally advanced, 22 (22%) medically inoperable and 13 (13%) resectable. Neoadjuvant chemotherapy was given to 86 (88%) patients with a median of 3.5 months of chemotherapy (range 1-12), leaving 11 (12%) patients who did not have systemic chemotherapy. Median overall survival from radiation for the whole group was 15.7 months, and 1-year OS was 58%. There was a statistically significant worsening of overall survival from diagnosis between ECOG 2+ and ECOG 0/1 patients (HR 1.94, 1.05-3.57). 27 (27%) patients went on to have surgical resection with 23 (82%) having R0 resection, and 3 (11%) have an R1 resection. Improved OS was seen in patients with surgical resection (HR 0.06, 0.02-0.23). Acute grade 3+ GI toxicity from radiation was seen in 4 (4%) patients and late toxicity from radiation was seen in 6 (6%) patients. GI bleeding was seen in 16(16%) patients, 10 (62%) of which were on anticoagulation at the time of GI bleed and 5 (19%) of which had surgery. Portal vein complications occurred with 7 (7%) having portal vein thrombosis and 6 (6%) portal vein stenosis. Conclusions: SMART showed durable responses in pancreatic cancer patients with an acceptable toxicity profile. Attention needs to be paid to the moderate incident of GI bleeding, however further work is necessary to determine if bleeding was due to radiation, surgery, or disease progression. Surgical resection as well as performance status of ECOG 0-1 were associated with improved overall survival. Further follow up will be necessary to determine further durability of treatment response and long-term survival in these patients

Survival Outcomes and Patterns of Recurrence After Adjuvant Vaginal Cuff Brachytherapy and Chemotherapy in Early-Stage Uterine Serous Carcinoma

Background: Uterine serous carcinoma (USC) is a relatively rare histology that portends a poor prognosis. The optimal adjuvant therapy for early-stage USC remains controversial; however, adjuvant vaginal cuff brachytherapy (VB) and chemotherapy is a commonly utilized strategy. Objectives: We sought to characterize predictors of survival endpoints and determine recurrence patterns in women with early-stage USC who received adjuvant VB and chemotherapy. Methods: We queried our prospectively maintained database for patients with 2009 FIGO stages I-II USC who underwent adequate surgical staging at our institution and received adjuvant chemotherapy with carboplatin and paclitaxel along with VB. We excluded women with synchronous malignancies. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed by Kaplan-Meier and log-rank tests. Univariate (UVA) and multivariate analyses (MVA) were performed to identify statistically significant predictors of survival endpoints. Variables with P\u3c0.1 on UVA were included in a MVA and any variable with P\u3c0.05 was considered statistically significant. Results: We identified 77 women who met our inclusion criteria who underwent surgical staging between 1991 and 2018. The median follow-up time was 36 months (range 6-125). The median age was 66 years. Of the cohort, 70% were FIGO stage IA, 17% were stage IB, and 13% were stage II. The median number of dissected lymph nodes (LN) was 22. There were 10 women (13%) diagnosed with a recurrence with a median time to recurrence of 12.0 months. The main site of initial recurrence was distant in seven patients (70%) with the remaining recurrences being pelvic/para-aortic. The 5-year RFS for patients who experienced a distant recurrence was 87% (95% Confidence Interval [CI] 0.75-0.94). For the entire cohort, 5-year OS, DSS, and RFS were 83% (95% CI 0.68-0.91), 92% (95% CI 0.78-0.97), and 83% (95% CI 0.71-0.91), respectively. The sole predictor of 5-year OS on UVA was receipt of omentectomy (P=0.09). The predictors of 5-year DSS on UVA were presence of positive peritoneal cytology (P=0.03), number of LN examined (Hazard Ratio [HR] 1.10, 95% CI 1.00-1.21, P=0.05), and number of para-aortic LN examined (HR 1.16 [95% CI 1.01-1.32], P=0.03). The sole independent predictor of DSS was the presence of positive peritoneal cytology (HR 0.03 [95% CI 0.00-0.72], P=0.03). Predictors of five-year RFS on UVA were robotic vs open surgery technique (P=0.06), presence of positive peritoneal cytology (P=0.01), percent myometrial invasion (HR 5.59 [95% CI 0.84-37.46], P=0.08), and presence of lymphovascular space invasion (LVSI) (P=0.05). Conclusions: Five-year survival outcomes were promising in this cohort of women with early-stage USC treated with adjuvant chemotherapy and VB; however, this study shows that the predominant pattern of relapse in this population is distant, suggesting the need to optimize systemic therapy. Possible predictors of worse outcomes include positive peritoneal cytology, deep myometrial invasion, and presence of LVSI. Multi-institutional pooled analyses are warranted to confirm our study results

Sex Differences in Health Related Quality of Life in Head & Neck Cancer One Year After Treatment

Background: Head and neck cancer (HNC) makes up about 3% of all cancers and is treated with systemic therapy, radiation, surgery, or a combination of these. HNC treatment can be associated with decreased patient reported health related quality of life (HR-QoL), which can lead to depression. The majority of studies found that females reported worse patient reported HR-QoL than males, however, there were a few that did not have a significant difference in overall patient reported QoL. With the discovery of patient oriented outcomes (PROs) in clinical practice affecting patient satisfaction, provider-patient relationship, and overall patient mortality, it is vital to include PROs in the creation of treatment plans. Objectives: The objectives of this project are to highlight the differences in HR-QoL between men and women. Ultimately, using these PROs clinically will help to improve patient care, augment patient-provider trust, and optimize treatment plans. Using PROs and recognizing where unconscious biases of providers come into play is pinnacle, and this project aims to highlight how men and women\u27s experiences are different in the treatment of HNC. Methods: Participants were given the FACT-H&N instrument one year after treatment for head and neck cancer at a single tertiary academic center to assess different aspects of Hr-QoL. Sex differences were analyzed between the groups. A Wilcoxon Rank Sum test was performed to assess associations with sex and survey responses, as well as to assess associations with total laryngectomy and survey responses. Results: There were 100 participants from a single academic center of which 73% were men and 27% women. Several of the questions had significant differences between men and women: I feel ill (P=0.0299), I am satisfied with my family communication about my illness P=0.0075), I am satisfied with my sex life (P=0.0496), My voice has its usual quality and strength (P=0.0057), I can swallow naturally and easily (P=0.0437), and I can eat solid foods (P=0.0248). There were no significant differences between men and women with laryngectomies. Conclusions: Overall, men felt more ill, were less satisfied with their sex lives, were less likely to feel a normal strength and quality of voice, felt decreased ability to swallow normally, and felt they could not eat solid foods; women were less satisfied with communication about their disease to their families. For those who had undergone laryngectomy, there were no significant differences between men and women. Different aspects of quality of life for men and women are affected by head and neck cancer. Monitoring PROs are becoming increasingly standard of care for patients, and providers need to be equipped understand how to interpret data accordingly and understand the inherent biases

Assessing Oral Intake Outcomes in Head and Neck Cancer Patients Treated with Definitive Radiation with or Without Chemotherapy

Background: Head and neck cancer treatment modalities can significantly impact functional outcomes of patients, especially oral intake (Brizel, et al N Engl J Med 1998; Kamal, et al Support Care Cancer 2019). Radiation therapy in particular has been associated with posttreatment xerostomia and dysphagia (Adelstein, et al J Clin Oncol 2003; Hutcheson, et al Cancer 2013) which can affect quality of life and impair weight gain, contributing to worse long-term outcomes (Payakachat, et al Head Neck, 2013). Early speech-language pathology intervention has shown to be effective in improving these functional outcomes in this population (Greco, et al Int J Radiat Oncol Biol Phys 2018). Objectives: The purpose of this study is to evaluate oral intake outcomes of patients undergoing definitive radiation therapy with or without chemotherapy for head and neck squamous cell carcinoma. Methods: A cohort of patients with stage III or IV squamous cell carcinoma of the oropharynx, larynx, and hypopharynx treated with definitive radiation therapy with or without chemotherapy were extracted from system database. Patients with evidence of distant metastases were excluded. Swallow function was assessed both pre- and post-treatment (within four months of treatment initiation or conclusion) with the Functional Oral Intake Scale (FOIS) (Crary et al, Arch Phys Med Rehabil, 2005) as measured by a Speech-Language Pathologist (SLP) involved in the patient\u27s care. Body mass index (BMI) was evaluated within four months of treatment initiation and one year after treatment completion. The use of enteral feeding at one-year post-treatment was also assessed. Data was analyzed with descriptive statistical methods, Wilcoxon sign rank tests, and [chi]2d tests. Results: The sample included 152 patients. Table 1 highlights patient baseline characteristics, tumor location, and treatment. FOIS scores decreased from pre-treatment to post-treatment, with 75% of patients having a FOIS of 7 at pre-treatment compared with only 13.8% at the post-treatment time point (Table 1). Median BMI also decreased from pre-treatment to one-year post-treatment (Table 2). At one-year post-treatment, 23.7% patients (n=33) required enteral feeding. Conclusions: Definitive radiation therapy with or without chemotherapy in the treatment of head and neck cancer is associated with impaired oral intake. Treatment is also associated with decreases in BMI and longer use of enteral feeding, which may reflect sequelae of impaired oral intake. These factors have a negative impact on quality of life and can lead to long-term morbidity. Integrative treatment plans would therefore benefit from speech-language pathology interventions throughout the treatment process