Purpose:To estimate the radiobiological parameters of four popular NTCP models that describe the dose‐response relations of salivary glands to the severity of patient reported dry mouth 6 months post chemo‐radiotherapy. To identify the glands, which best correlate with the manifestation of those clinical endpoints. Finally, to evaluate the goodness‐of‐fit of the NTCP models.Methods:Forty‐three patients were treated on a prospective multiinstitutional phase II study for oropharyngeal squamous cell carcinoma. All the patients received 60 Gy IMRT and they reported symptoms using the novel patient reported outcome version of the CTCAE. We derived the individual patient dosimetric data of the parotid and submandibular glands (SMG) as separate structures as well as combinations. The Lyman‐Kutcher‐Burman (LKB), Relative Seriality (RS), Logit and Relative Logit (RL) NTCP models were used to fit the patients data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC) and the Odds Ratio methods.Results:The AUC values were highest for the contralateral parotid for Grade ≥ 2 (0.762 for the LKB, RS, Logit and 0.753 for the RL). For the salivary glands the AUC values were: 0.725 for the LKB, RS, Logit and 0.721 for the RL. For the contralateral SMG the AUC values were: 0.721 for LKB, 0.714 for Logit and 0.712 for RS and RL. The Odds Ratio for the contralateral parotid was 5.8 (1.3–25.5) for all the four NTCP models for the radiobiological dose threshold of 21Gy.Conclusion:It was shown that all the examined NTCP models could fit the clinical data well with very similar accuracy. The contralateral parotid gland appears to correlated best with the clinical endpoints of severe/very severe dry mouth. An EQD2Gy dose of 21Gy appears to be a safe threshold to be used as a constraint in treatment planning.

Purpose: To estimate the radiobiological parameters of four NTCP models that describe the dose‐response relations of pharyngeal constrictors and proximal esophagus regarding the severity of patient reported swallowing problems 6 months post chemo‐radiotherapy. To identify the section/structure that best correlates with the manifestation of the clinical endpoints. Finally, to compare the goodness‐of‐fit of those models. Methods: Forty‐three patients were treated on a prospective multi‐institutional phase II study for oropharyngeal squamous cell carcinoma. All the patients received 60 Gy IMRT and they reported symptoms using the novel patient reported outcome version of the CTCAE. We derived the individual patient dosimetric data of superior, medium and inferior sections of pharyngeal constrictors (SPC, MPC and IPC), superior and inferior sections of esophagus (SES and IES) as separate structures as well as combinations. The Lyman‐Kutcher‐Burman (LKB), Relative Seriality (RS), Logit and Relative Logit (RL) NTCP models were used to fit the patient data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC) and the Odds Ratio methods. Results: The AUC values were highest for the SPC for Grade ≥ 2 (0.719 for the RS and RL models, and 0.716 for LKB and Logit). For Grade ≥ 1, the respective values were 0.699 for RS, LKB and Logit and 0.676 for RL. For MPC the AUC values varied between 0.463–0.477, for IPC between 0.396–0.458, for SES between 0.556–0.613 and for IES between 0.410–0.519. The Odds Ratio for the SPC was 15.6 (1.7–146.4) for RS, LKB and Logit for NTCP of 55%. Conclusion: All the examined NTCP models could fit the clinical data with similar accuracy. The SPC appear to correlate best with the clinical endpoints of swallowing problems. A prospective study could establish the use of NTCP values of SPC as a constraint in treatment planning.

Purpose: To investigate the correlation between different dosimetric indices of salivary glands (as separate or combined structures) to patient‐reported dry mouth 6 months post radiotherapy using the novel patient reported outcome version of the CTCAE (PRO‐CTCAE). Methods: Forty‐three patients with oropharyngeal squamous cell carcinoma were treated on a prospective multi‐institutional study. All patients received de‐intensified 60 Gy intensity modulated radiotherapy. Dosimetric constraints were used for the salivary glands (e.g. mean dose to the contralateral‐parotid < 26 Gy). We investigated correlations of individual patient dosimetric data of the parotid and submandibular glands (as separate or combined structures) to their self‐reported 6 month post‐treatment dry mouth responses. Moderate dry mouth responses were most prevalent and were used as the clinical endpoint indicating response. The correlation of Dmean, Dmax and a range of dosevolume (VD) points were assessed through the area under the Receiver Operating Characteristic curve (ROC) and Odds Ratios (OR). Results: Patients reporting non/mild dry mouth response (N=22) had average Dmean = 19.6 ± 6.2Gy to the contralateral‐parotid compared to an average Dmean = 28.0 ± 8.3Gy and an AUC = 0.758 for the patients reporting moderate/severe/very severe dry mouth (N=21). Analysis of the range of VD's for patients who had reported dry mouth showed that for the contralateral‐parotid the indices V18 through V22 had the highest area under the curves (AUC) (0.762 – 0.772) compared to a more traditional dosimetric index V30, which had an AUC = 0.732. The highest AUC was observed for the combination of contralateral parotid and contralateral submandibular glands, for which V16 through V28 had AUC = 0.801 – 0.834. Conclusion: Patients who report moderate/severe/very severe dry mouth 6 months post radiotherapy had on average higher Dmean. The V16‐V28 of the combination of the contralateral glands showed the highest correlation with the clinical endpoint.

S138 ESTRO 37were randomized to control-arm or zalutumumab-arm.The control-arm was primary accelerated RT, predominantly 66-68Gy, 2Gy/fx, 6fx/wk and concomitant daily hypoxic radiosensitisation with nimorazole.Stage III-IV carcinomas received weekly cisplatinum 40 mg/m2 during RT.Elective neck-dissection was not performed.The zalutumumab-arm was identical with the control-arm plus zalutumumab 8 mg/kg.First dose was given the week before start of RT and continued weekly during irradiation.Analyses were performed as intention-totreat.Primary endpoint was Loco-Regional Control (LRC).Secondary endpoints were Disease Specific Survival (DSS) and Overall Survival (OS). ResultsMedian observation time was 59 months.608 patients were eligible for analysis.307 pts were in the controlarm and 301 in the zalutumumab-arm.Patient and tumor parameters were well balanced.The 5-year LRC rate was 70% in the zalutumumab-arm vs. 74% in the control-arm, HR: 1.10 [95% CI: 0.81-1.50].This outcome was also reflected in DSS: HR 1.12 [0.79-1.60]and in OS: HR 1.17 [0.89-1.52].There was no benefit of adding zalutumumab to C-RT nor RT alone for any of the endpoints.Treatment was generally well tolerated, but 94% of the pts in the zalutumumab-arm experienced a skin-rash (29% grade 3+4 rash), and pts treated with zalutumumab experienced significantly more frequent confluent mucositis (70% vs. 56%, p=0.001) and grade 3+4 in-field skin reaction (27% vs. 4%, p<0.0001).The 5-year update did not reveal any significant increase in late morbidity between the zalutumumab-arm and control-arm: severe dysphagia (19% vs. 16%), severe dryness of the mouth (20% vs. 18%), severe late oedema (3% vs. 5%), severe atrophia (8% vs. 6%) and severe fibrosis (20% vs. 16%). ConclusionTreatment with zalutumumab was generally well tolerated, but the addition of concomitant zalutumumab to primary C-RT or RT and nimorazole for HNSCC did not increase loco-regional control nor disease specific or overall survival at 5 years.Acute toxicities, but not late morbidity, were increased in the zalutumumab-arm.

Purpose: To compare the correlations between different dosimetric indices derived from the pharyngeal constrictor muscles and proximal esophagus with patient‐reported difficulty in swallowing 6 months post radiotherapy using a novel patient reported outcome version of CTCAE (PRO‐CTCAE). Methods: Forty‐three patients with oropharyngeal squamous cell carcinoma were treated on a prospective multi‐institutional study. All patients received de‐intensified 60 Gy intensity modulated radiotherapy. We investigated correlations of individual patient dosimetric data of the superior (SPC), middle (MPC), inferior (IPC) pharyngeal constrictor muscles, the superior esophagus (SES), and the inferior esophagus (IES) to their self‐reported 6 month post‐treatment swallowing difficulty responses. Mild (≥ Grade 1) swallowing difficulty responses were used as the clinical endpoint indicating response. The predictive efficacy of Dmean and dose‐volume (VD) points were assessed through the area under the Receiver Operating Characteristic curve (ROC) and Odds Ratio (OR). Results: The SES and SPC had more favorable area under the curves (AUC) for the Dmean (0.62 and 0.70) while the Dmean to the IPC, MPC, and IES produced suboptimal AUCs (0.42, 0.48, and 0.52). Additionally, over the range of VD, the V54 and V55 for the SES and SPC demonstrated the highest AUCs: AUC(SES) = 0.76–0.73 and AUC(SPC) = 0.72–0.69, respectively. The IES, IPC, and MPC had worse AUC results over the range of VD. An optimal OR can be found when V54 = 96% for the SPC, where OR = 3.96 (1.07–14.62). Conclusion: The V45 and V55 of the SES and SPC had the highest correlation to the clinical endpoint compared to the commonly used dosimetric index, Dmean for both the esophagus and constrictor muscles. The reported dosimetric data demonstrates that new dosimetric indices may need to be considered in the setting of dose de‐escalation and self‐reported outcomes.

Intensity Modulated radiation therapy (IMRT) for prostate cancer has been rapidly adopted over older techniques because of its potential ability to reduce treatment-related morbidity. We examined the comparative morbidity of IMRT vs. non-IMRT using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. A total of 39,662 men with non-metastatic prostate cancer diagnosed between 2000 and 2005, 66 years or older, were included. Patients with claims for any IMRT-related procedure codes were considered to have received IMRT. Patients were stratified into two cohorts for analysis: those receiving radiation (RT) only within 1 year of diagnosis (definitive RT, n = 38,159), and those receiving RT within 3 years after surgery (post-operative RT; n = 1,503). These time windows were set to minimize inclusion of palliative RT. Logistic regression models were used to examine the odds of morbidity diagnoses and procedures occurring more than 12 months after IMRT vs. non-IMRT while adjusting for year, age, race, tumor grade, SEER region, Medicaid eligibility, and education. Overall, 28% of definitive RT patients and 33% of post-operative RT patients received IMRT. In the definitive RT cohort, IMRT was associated with a lower risk of non-incontinence urinary morbidity diagnoses (OR 0.91, p = 0.003), urinary incontinence diagnoses (OR 0.86, p < 0.001) and procedures (OR 0.85, p < 0.001), and erectile dysfunction diagnoses (OR 0.92, p = 0.02). In post-operative patients, IMRT was associated with a lower risk of GI morbidity diagnoses (OR 0.68, p = 0.03) and procedures (OR 0.62, p = 0.002). In no case was IMRT associated with increased morbidity. Prostate cancer patients undergoing definitive IMRT experienced lower rates of urinary morbidity and erectile dysfunction, and those undergoing post-operative IMRT had lower rates of GI morbidity. Prostatectomy is the dominant factor causing incontinence and erectile dysfunction in the post-operative patients, likely explaining the lack of difference from radiation technique. This is a large-scale study examining the comparative outcomes of IMRT vs. non-IMRT for prostate cancer, and suggests improved morbidity outcomes for IMRT in both definitive and post-operative patients.TableSummary of multivariable analyses of morbidity outcomes for IMRT vs. non-IMRT for prostate cancerOdds ratio of IMRT vs. non-IMRT (95% CI) for definitive treatmentp valueOdds ratio of IMRT vs. non-IMRT (95% CI) for post-operative treatmentp valueGI morbidityDiagnosis1.01 (0.96 – 1.07)0.660.68 (0.48 – 0.96)0.03Procedure1.01 (0.96 – 1.07)0.710.62 (0.46 – 0.83)0.002Non-incontinence urinary morbidityDiagnosis0.91 (0.86 – 0.97)0.0030.78 (0.56 – 1.08)0.13Procedure0.93 (0.84 – 1.03)0.161.01 (0.65 – 1.56)0.98Urinary incontinenceDiagnosis0.86 (0.79 – 0.94)0.00081.03 (0.76 – 1.38)0.87Procedure0.85 (0.80 – 0.91)< 0.00010.89 (0.64 – 1.25)0.50Erectile dysfunctionDiagnosis0.92 (0.86 – 0.99)0.020.82 (0.61 – 1.12)0.21Procedure0.87 (0.74 – 1.03)0.110.63 (0.38 – 1.07)0.09Hip fractureDiagnosis1.01 (0.85 – 1.21)0.881.89 (0.70 – 5.13)0.21 Open table in a new tab

6607 Background: The National Institutes of Health prioritize adequate representation of women in medical research. Methods: We collected data on researchers & participants from clinical oncology s...