Radiation Therapy For Oropharyngeal Carcinoma Research Articles

P-64 Incidence and risk factors of osteoradionecrosis of the mandible after modern radiotherapy for oropharyngeal carcinoma

P-64 Incidence and risk factors of osteoradionecrosis of the mandible after modern radiotherapy for oropharyngeal carcinoma

Radiotherapy for Oropharyngeal Carcinoma With an Uninvolved Contralateral Neck: The Safety of Omission of Contralateral High Level II and Retropharyngeal Lymph Nodes From Elective Target Volumes

AimsTo analyse outcomes and patterns of failure in patients with oropharyngeal carcinoma (OPC) treated with definitive volumetric modulated arc therapy with omission of contralateral high level II lymph nodes (HLII) and retropharyngeal lymph nodes (RPLN) in the contralateral uninvolved neck. Materials and methodsPatients with OPC treated between January 2016 and July 2019 were retrospectively identified. In the absence of contralateral neck disease, institutional protocols allowed omission of contralateral HLII and contralateral RPLN in the additional absence of ipsilateral RPLN, soft palate/posterior pharyngeal wall primary. ResultsIn total, 238 patients with OPC and an uninvolved contralateral neck received definitive (chemo)radiotherapy with bilateral neck treatment. The median follow-up was 30.6 months. Two-year local control, regional control and overall survival were 91.0, 91.6 and 86.5%, respectively. Contralateral HLII were omitted in 159/238 (66.8%) patients; this included 106 patients in whom the primary tumour was at/crossed the midline. The contralateral RPLN region was omitted from elective target volumes for 175/238 (73.5%); this included 114 patients with a primary tumour at/crossed the midline. The mean contralateral parotid dose when contralateral HLII and RPLN were both omitted was 24.4 Gy, compared with 28.3 Gy without HLII/RPLN omission (P < 0.001). Regional progression occurred in 18/238 (7.6%) patients, all involving the ipsilateral neck with one bilateral. There were no recurrences in the contralateral HLII or RPLN regions. ConclusionIn patients with OPC and an uninvolved contralateral neck receiving bilateral (chemo)radiotherapy, the omission of contralateral RPLN and HLII from elective target volumes was safe and could lead to reduced contralateral parotid doses.

Healthcare resource utilization following unilateral versus bilateral radiation therapy for oropharyngeal carcinoma

PurposeTo describe differences in healthcare resource utilization between patients treated with bilateral vs. unilateral neck radiation therapy (RT) for lateralized oropharyngeal cancer. MethodsA propensity score matching strategy was used to identify two otherwise clinically similar cohorts of tonsillar cancer patients treated with either bilateral or unilateral neck RT. Cohorts were matched based on similar propensity scores for age, sex, ECOG performance status, pack-year smoking history, cT-category, cN-category, HPV-status, and use of concurrent chemotherapy. Short term (from start of RT to 3 months following end of RT) resource utilization included: 1) outpatient supportive care visits, 2) hospital admission, and 3) interventions (feeding tube insertion and outpatient intravenous hydration). Long-term resource utilization included feeding tube dependency at 1-year. ResultsAmong 559 patients with tonsillar cancer treated between 2004–2017, propensity score matching identified a unilateral neck RT cohort (n = 81) and bilateral neck RT cohort (n = 81) with similar clinical and treatment characteristics. Bilateral neck RT was associated with a higher likelihood of hospitalization (33% vs 12%, p < 0.01), outpatient IV hydration (33% vs 17%, p = 0.03), and feeding tube insertion (33% vs 10%, p < 0.001); a greater number of total days of hospitalization (110 vs 47 days, p < 0.01) and outpatient IV hydration (135 vs 72 days, p = 0.02); and higher total number of supportive clinic visits (1226 vs 1053 days, p = 0.04). In the long-term, bilateral RT was associated with higher rate of feeding tube dependency at 1-year (7% vs 0%, p < 0.001). ConclusionBilateral RT for tonsillar cancer resulted in significant increase in health resource utilization.

XRCC1 (rs25487) polymorphism is associated with severe oral mucositis and poor treatment response after radiotherapy for oropharyngeal carcinoma

To investigate the association of Single Nucleotide Polymorphisms of DNA repair genes and patient-specific clinical characteristics with the risk of developing severe acute radiotoxicities and treatment response in Oropharyngeal Carcinoma. 179 cases of Oropharyngeal Carcinoma treated with 2-D radical radiotherapy were evaluated for acute radiotoxicity end-points viz; oral mucositis, dermatitis, dysphagia, and xerostomia; and the resultant requirement of nasogastric feeding tube, significant (> 10%) weight loss during treatment and treatment break(s). Eleven Single Nucleotide Polymorphisms of DNA repair genes were analyzed using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism and correlated with the severity of these radiotoxicities (Common Toxicity Criteria for Adverse Events v4.0 grading) and the treatment response. Clinical parameters like age, Karnofsky Performance Status, smoking and tobacco chewing, etc. were also analysed in relation to the above. Homozygous AA genotype of XRCC1 (rs25487) (p = 0.024*, OR 2.629, 95% CI 1.136–6.087), Karnofsky Performance Status < 80 (p = 0.050*, OR 2.723, CI 1.000–7.418) and history of tobacco chewing (p = 0.030*, OR 2.615, 95% CI 1.099–6.222) were independent predictive factors for increased risk of severe (≥ grade 3) mucositis. Also, the presence of Homozygous AA genotype of XRCC1(rs25487) was significantly associated with poor response to radiotherapy in these patients (p = 0.014, OR 2.235, 95% CI 1.074–5.744). Our findings illustrate that patients with Homozygous AA genotype of XRCC1 (rs25487) and certain clinical characteristics are likely to develop severe acute mucositis after radiotherapy for Oropharyngeal Carcinoma and the presence of this polymorphism is also associated with poor response to treatment.

Radiation-Induced Hypothyroidism After Radical Intensity Modulated Radiation Therapy for Oropharyngeal Carcinoma

PurposeTo evaluate 2 published normal tissue complication probability models for radiation-induced hypothyroidism (RHT) on a large cohort of oropharyngeal carcinoma (OPC) patients who were treated with intensity-modulated radiation therapy (IMRT). Methods and MaterialsOPC patients treated with retrievable IMRT Digital Imaging and Communications in Medicine (DICOMs) data and available baseline and follow-up thyroid function tests were included. Mean dose (Dmean) to the thyroid gland (TG) and its volume were calculated. The study outcome was clinical HT at least 6 months after radiation therapy, which was defined as grade ≥2 HT per Common Terminology Criteria for Adverse Events grading system (symptomatic hypothyroidism that required thyroid replacement therapy). Regression analyses and Wilcoxon rank-sum test were used. Receiver operating characteristic curves and area under the curve for the fitted model were calculated. ResultsIn the study, 360 OPC patients were included. The median age was 58 years. Most tumors (51%) originated from the base of tongue. IMRT-split field was used in 95%, and median radiation therapy dose was 69.96 Gy. In the study, 233 patients (65%) developed clinical RHT that required thyroid replacement therapy. On multivariate analysis higher Dmean and smaller TG volume maintained the statistically significant association with the risk of clinical RHT (P < .0001). Dmean was significantly higher in patients with clinical RHT versus those without (50 vs 42 Gy, P < .0001). Patients with RHT had smaller TG volume compared with those without (11.8 compared with 12.8 mL, P < .0001). AUC of 0.72 and 0.66 were identified for fitted model versus for the applied Boomsma et al and Cella et al models, respectively. ConclusionsVolume and Dmean of the TG are important predictors of clinical RHT and shall be integrated into normal tissue complication probability models for RHT. Dmean and thyroid volume should be considered during the IMRT plan optimization in OPC patients.

Changes in Physical and Emotional Quality of Life following Radiation Therapy for Oropharyngeal Carcinoma

Changes in Physical and Emotional Quality of Life following Radiation Therapy for Oropharyngeal Carcinoma

Emotional Quality of Life After Radiation Therapy for Oropharyngeal Carcinoma

PurposeSubstantial research exists on the physical toxicities from radiation therapy (RT) for oropharyngeal cancers, but emotional quality of life is understudied. The purpose of this study is to map the effects and time course of radiation-related changes in mood and anxiety and to investigate the physical factors that drive these changes. Methods and materialsWe prospectively collected University of Washington Quality of Life questionnaires and identified patients with oropharyngeal cancer who were treated with curative-intent RT between 2013 and 2016 and had completed questionnaires within 12 months after RT (n = 69). We analyzed swallow, saliva, taste, chewing, speech, pain, mood, and anxiety scores, using a scale from 0 to 100. We conducted a multivariate regression analysis to identify physical functioning predictors of worse emotional scores. ResultsPhysical functioning scores declined from before RT to 3 months after RT and then began improving but did not rebound to baseline levels within 12 months. Patient mood slightly declined, but anxiety improved immediately after RT, with both generally improving such that scores were higher at the 12-month follow-up than at initial consult. Analysis showed that longer duration of treatment is associated with a higher likelihood of worse mood scores at 12 months (odds ratio [OR], 1.446; P < .01). Worse swallow score is associated with a greater likelihood of worse mood score at 3 months (OR, 0.971; P < .01) and 12 months (OR, 0.975; P < .01). A worse taste score is associated with a greater likelihood of worse anxiety score at 3 months (OR, 0.979; P < .05) and 12 months (OR, 0.982; P < .05). ConclusionsEmotional changes are associated with certain treatment-associated toxicities. A patient's emotional health is complex and likely multifactorial in nature. Our study identified key associations and time points to potentially intervene upon.

Radiation-Induced Hypothyroidism after Radical Intensity-Modulated Radiation Therapy for Oropharyngeal Carcinoma

This work aims to apply an existing normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism (RHT) on a large cohort of oropharyngeal carcinoma (OPC) patients, to identify the clinical and dosimetric parameters for a more robust multivariate NTCP model. The relationship between dose, volume, and thyroid function is explored. Head and neck cancer (HNC) patients treated with radical RT from 2005 to 2013 were reviewed. We identified 1180 HNC patients treated with RT without thyroidectomy. OPC patients treated with retrievable IMRT plan/dose DICOMs and available baseline and follow-up thyroid function tests were included. Mean dose (Dmean) to the thyroid gland (TG) and its volume were calculated. Biochemical HT was defined as a serum TSH level > the normal value for at least two subsequent labs. Clinical HT was defined as grade ≥ 2 HT per CTC-AE, v4 grading system. Univariable and multivariable analyses were carried out for predictors of clinical HT. Dmean and volume of TG for those with HT were compared to others, using Wilcoxon rank-sum test. Other dosimetric parameters including; the percentage of thyroid volume exceeding 10, 20, 30, 40 and 50 Gy (V10, V20, V30, V40 and V50) were considered. Receiver Operating Characteristic (ROC) curves and area under the curve (AUC) for the fitted model vs the Boomsa et al model were calculated. Four hundred seventy-one OPC patients were included. The median age was 57 years and 396 were males. Most tumors (52%) originated from base of tongue, and (93%) were node positive. 61% had received concurrent and 36% induction chemotherapy, respectively. IMRT-split field was utilized in 94%, and median RT dose was 69.96 (range 60-72) Gy. 295 patients (63%) developed clinical HT after RT. Univariate analysis revealed that positive nodal disease, higher Dmean to TG and smaller TG volume were associated with clinical HT (p=0.002, <0.0001 and 0.004, respectively). On multivariate analysis Dmean (Odds Ratio 1.06 (1.04-1.09)) and TG volume (OR 0.879(0.827-0.932)) remained statistically significant, (p<0.0001). Dmean was significantly higher in patients with clinical HT vs. those without (50 vs.45 Gy, p<0.0001). Patients with HT had smaller TG volume compared to those without (11.7 compared to 12.96 cc, p<0.0001). AUC of 0.67 (0.61-0.71) for fitted model vs. 0.67 (0.62-0.72) for the applied Boomsa et al model to current cohort was identified. Volume and Dmean of the TG are important predictors of clinical HT and shall be integrated in NTCP models for RHT. Dmean should be considered during the IMRT plan optimization without compromising target coverage in OPC patients. More effort is needed to develop more robust NTCP model for RHT that accounts for more potential clinical and dosimetric predictors of RHT.

EP-1107: Sparing the superficial lobe of the parotid during radical radiotherapy for oropharyngeal carcinoma

EP-1107: Sparing the superficial lobe of the parotid during radical radiotherapy for oropharyngeal carcinoma

Health-Related Quality of Life Following Radiation Therapy for Oropharyngeal Carcinoma

Health-Related Quality of Life Following Radiation Therapy for Oropharyngeal Carcinoma

A predictive model for residual disease after (chemo) radiotherapy in oropharyngeal carcinoma: Combined radiological and clinical evaluation of tumor response

Background and purposeEarly detection of Residual disease (RD) is vital for salvage possibilities after (chemo) radiatiotherapy for oropharyngeal carcinoma (OPC). We standardized clinical investigation to test its added value to MRI response evaluation and investigated the benefit of FDG-PET/CT. Materials and methodsRadiological response evaluation using Ojiri-score was done for 234 patients with OPC, using MRI 12weeks after (chemo) radiotherapy between 2010 and 2014. The presence of mucosal lesions and/or major complaints (still completely tube feeding-dependent and/or opiate-dependent because of swallowing problems) was scored as clinical suspicion (CS). Retrospectively, the performance of Ojiri to predict RD was compared to CS and both combined using Pearson Chi-squared. Of the whole group, FDG-PET/CT metabolic response (MR) was available in 50 patients. ResultsTwelve out of 234 patients (5.1%) had RD. Ojiri and CS had excellent negative predictive value (NPV) (98% and 100% respectively). The combination of CS and Ojiri reduced false positives by 32% (38–26 patients) without lowering NPV (98%). No patients with complete MR (n=39) at the FDG-PET/CT had RD compared to 5 (45%) with partial MR. ConclusionFor response evaluation in OPC, the combination of CS and Ojiri-score improved the predictive accuracy by reducing false positives compared to them individually. FDG-PET/CT is promising to further reduce false positives.

Impact of selective neck dissection on chronic dysphagia after chemo-intensity-modulated radiotherapy for oropharyngeal carcinoma.

Conflicting results are reported regarding the impact of neck dissection on radiation-associated dysphagia. The purpose of this study was to reexamine this question specific to oropharyngeal intensity-modulated radiotherapy (IMRT). Three hundred forty-nine patients with oropharyngeal cancer treated with bilateral IMRT with systemic therapy (induction and/or concurrent) were reviewed. Chronic dysphagia was defined by aspiration, stricture, pneumonia, and/or gastrostomy dependence ≥12 months post-IMRT. Selective neck dissection was performed after IMRT in 75 patients (21%). Overall, 41 patients (12%) developed chronic dysphagia. Neck dissection did not increase the rate of chronic dysphagia (9% neck dissection; 12% no neck dissection; p = .464) or gastrostomy duration (p = .482). On multivariate analysis, age (odds ratio [OR] per 5-year = 1.25; 95% confidence interval [CI] = 1.04-1.51), baseline abnormal diet (OR = 2.78; 95% CI = 1.31-5.88), and IMRT dose (OR per 5-Gy = 5.11; 95% CI = 1.77-14.81) significantly predicted dysphagia. In the setting of selective neck dissection for residual adenopathy after IMRT, neck dissection did not impact dysphagia. © 2015 Wiley Periodicals, Inc. Head Neck 38: 886-893, 2016.

Development of a chemoradiation therapy toxicity staging system for oropharyngeal carcinoma.

Develop an innovative tool to standardize representation of treatment toxicity and enable shared decision making by mapping provider-based outcome descriptions to four overall stages of toxicity from chemoradiation therapy for oropharyngeal carcinoma. Cross-sectional, provider-based questionnaire. Five short-term and five long-term treatment outcomes of cisplatin and intensity-modulated radiation therapy for oropharyngeal carcinoma were chosen by a focus group of head and neck oncologists. A pilot survey was developed in an online platform, and feedback from extramural head and neck oncologists was used to refine it for institutional review board submission and formal deployment. Respondents were surgical, radiation, and medical oncologists with experience in treating oropharyngeal carcinoma. One hundred five responses were analyzed, of which 67% were from providers with >10 years in practice and 79% were from providers who treat >15 new oropharyngeal carcinoma patients per year. A particular overall chemoradiation toxicity class is accounted for by two adjoining distress levels (>90% occurrence) for both short-term and long-term outcomes. Providers deemed mucositis and nausea, and pain and xerostomia the most distressing short-term and long-term toxicities, respectively. Providers were split as to their impression of the relative importance that patients place on short-term versus long-term outcomes when considering treatment options. A clinical tool to represent overall chemoradiation toxicity considering short-term and long-term outcomes has been developed by analyzing provider-centric responses to a realistic clinical scenario. Results from this pilot study enhance patient counseling and shared decision making, and serve as foundational information for a prospective, longitudinal patient-centric observational study.

Intensity‐modulated versus conventional radiation therapy for oropharyngeal carcinoma: Long‐term dysphagia and tumor control outcomes

The purpose of this study was to determine the relative clinical benefits of intensity-modulated radiation therapy (IMRT) versus conventional radiotherapy (CRT) in the treatment of patients with oropharyngeal carcinoma. We compared tumor control and toxicity outcomes in 132 patients with stage III to IVA/B oropharyngeal carcinoma treated with definitive chemoradiation in the human papillomavirus (HPV) era. Patients treated with IMRT had lower rates of xerostomia (p = .01) and shorter duration of gastrostomy-tube dependence (p < .0001), but increased risk of cervical esophageal stricture (p = .03). The overall rates of late dysphagia were not different between the 2 groups (p = .40). In multivariate analysis, IMRT was a significant predictor of decreased disease-specific mortality (hazard ratio [HR] = 0.24; p = .03) after adjustment for T-category and active smoking. After adjustment for T classification, IMRT use was associated with a trend toward a significant decrease in locoregional failure (HR = 0.17; p = .08). The incidence of late dysphagia is similar in IMRT and CRT, but the mechanism of dysphagia is different.

Intensity Modulated Radiation Therapy for Oropharyngeal Carcinoma: Clinical Outcomes and Longitudinal Analysis of Late Effects

Intensity Modulated Radiation Therapy for Oropharyngeal Carcinoma: Clinical Outcomes and Longitudinal Analysis of Late Effects

Effect of oral nutritional supplementation on weight loss and percutaneous endoscopic gastrostomy tube rates in patients treated with radiotherapy for oropharyngeal carcinoma

Malnutrition in the head and neck cancer population is a widely recognized factor contributing to negative outcomes. The goal of this study was to determine if providing complimentary oral nutritional supplementation for patients undergoing definitive radiation therapy for oropharyngeal carcinoma reduced weight loss and the need for percutaneous endoscopic gastrostomy (PEG) tube placement. The data from 79 patients undergoing radiotherapy for oropharyngeal cancer were extracted and analyzed retrospectively from an institutional Human Investigation Committee approved database for the study of advanced radiation therapy techniques for head and neck cancer. Forty patients were treated before the initiation of a nutritional supplementation program, and 39 patients received supplementation. Patients were stratified by type of treatment (radiation alone or chemoradiation) and whether or not they had a PEG tube. All patient groups receiving supplementation manifested a significant decrease in weight loss compared to those who did not receive it. Nutritional supplementation was associated with a 40% relative reduction in weight loss in patients treated with radiotherapy alone (6.1 vs 10.1%, p = 0.008) and a 37% reduction in weight loss in patients treated with chemoradiotherapy (6.7 vs 10.7%, p = 0.007). When patients were stratified by the presence or absence of a PEG tube, both groups experienced a 39% relative reduction in weight loss (with PEG, 5.7 vs 9.3%, p = 0.028; without PEG, 6.9 vs 11.2%, p = 0.002). Supplementation was associated with a decreased need for PEG tube placement (31% decreased to 6%) in patients treated with radiotherapy alone. Providing complimentary oral nutritional supplementation significantly decreases weight loss and the need for PEG tube placement in patients undergoing radiation therapy for oropharyngeal cancer.

Intensity-modulated radiation therapy for oropharyngeal carcinoma: impact of tumor volume

Purpose To assess the therapeutic outcomes in oropharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT) and analyze the impact of primary gross tumor volume (GTV) and nodal GTV (nGTV) on survival and locoregional control rates. Methods and materials Between February 1997 and September 2001, 74 patients with squamous cell carcinoma of the oropharynx were treated with IMRT. Thirty-one patients received definitive IMRT; 17 also received platinum-based chemotherapy. Forty-three patients received combined surgery and postoperative IMRT. The median follow-up for all patients was 33 months (range, 9–60 months). Fifty-two patients (70.3%) had Stage IV disease, 17 patients (23%) had Stage III, 3 patients (4.1%) had Stage II, and 2 patients (2.7%) had Stage I tumors. The mean prescription dose was 70 and 66 Gy, respectively, for the definitive and postoperative cohorts. The daily fraction dose was either 1.9 or 2 Gy, five times weekly. The GTV and/or nGTV were determined and derived using the Computational Environment for Radiotherapy Research, a free software package developed at Washington University. The mean GTV was 30.5 ± 22.3 cm 3, and the mean nGTV was 23.2 ± 20.6 cm 3. Results Ten locoregional failures were observed. Six patients died of disease and three died of concurrent disease. Distant metastasis developed in 6 patients. The 4-year estimate of overall survival was 87%, and the 4-year estimate of disease-free survival was 81% (66% in the definitive vs. 92% in the postoperative RT group). The 4-year estimate of locoregional control was 87% (78% in the definitive vs. 95% in the postoperative RT group); the 4-year estimate of distant metastasis-free survival was 90% (84% in the definitive vs. 94% in the postoperative group). Multivariate analysis showed that GTV and nGTV were independent risk factors determining locoregional control and disease-free survival for definitive oropharyngeal IMRT patients. The worst late toxicities documented were as follows: 32 patients with Grade 1 and 9 with Grade 2 xerostomia; 2 with Grade 1 and 1 with Grade 2 skin toxicity; 3 with Grade 1 late mucositis; and 3 with Grade 1 trismus. Seventeen patients required gastrostomy tube placement. Conclusion IMRT is an effective treatment modality for locally advanced oropharyngeal carcinoma. The GTV and nGTV are the most important factors predictive of therapeutic outcome.

Hyperfractionated compared with conventional radiotherapy in oropharyngeal carcinoma: an EORTC randomized trial

Hyperfractionated compared with conventional radiotherapy in oropharyngeal carcinoma: an EORTC randomized trial