M. Kostich

Dosimetric feasibility of sparing the primary site for oropharyngeal squamous cell carcinoma after transoral laser microsurgery in patients with unilateral positive neck nodes

PURPOSE To quantify the effect of sparing the primary site after transoral laser microsurgery (TLM) for oropharyngeal squamous cell carcinoma (OPSCC). METHODS AND MATERIALS We reviewed 4 patients with OPSCC who were treated with TLM and postoperative radiation. All patients had T1 base of tongue primaries with the following N stages: 1 N1; 2 N2a; and 1 N2b. Three were lateralized to the right and 1 lateralized to the left. The primary site was not spared initially. We created new intensity modulated radiation treatment (IMRT) plans that spared the primary site. The prescribed dose to the high-risk (HR) and standard-risk (SR) planning target volumes (PTVs) was 60 Gy and 46 Gy at 2 Gy/fraction. PTV-SR and PTV-HR were adjusted to exclude the primary site. The primary site was maximally spared while maintaining similar PTV coverage and normal tissue avoidance as the initial plan. Dosimetric comparisons were made between the initial and primary-site sparing IMRT plans. RESULTS Dosimetric coverage of the PTVs and normal tissues (pharyngeal constrictors, contralateral parotid, etc) were comparable. The mean dose to the primary site was reduced by 20 Gy. The mean dose to the oral cavity was reduced by 25 Gy. CONCLUSIONS This study suggests that omitting the primary site from the radiation therapy target volume is unlikely to reduce long-term swallowing function to a meaningful degree in patients who receive radiation therapy following TLM for base of tongue cancer.

SU-D-204-04: Correlations Between Dosimetric Indices and Follow-Up Data for Salivary Glands Six Months After Radiation Therapy for Head and Neck Cancer

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 VDs 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.

SU-D-204-05: Fitting Four NTCP Models to Treatment Outcome Data of Salivary Glands Recorded Six Months After Radiation Therapy for Head and Neck Tumors

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.

SU-F-T-104: Determining the NTCP Parameters of Pharyngeal Constrictors and Proximal Esophagus for Radiation Induced Swallowing Problems Recorded Six Months After Radiation Therapy for Head and Neck Tumors.

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.

SU-F-T-107: Correlations Between Dosimetric Indices of Pharyngeal Constrictors and Proximal Esophagus with Associated Patient-Reported Outcomes Six Months After Radiation Therapy for Head and Neck Cancer

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.

SU-F-T-523: Radiobiological Comparison of Helical Tomotherapy and VMAT in the Treatment of Head and Neck Tumors

PURPOSE This study aims at comparing the efficacy of Helical Tomotherapy (TOMO) and Volumetric Modulated Arc Therapy (VMAT) in producing highly conformal dose distributions in challenging head & neck cancer patients. Furthermore, to interpret the dosimetric findings into expected tissue response rates in order to estimate their clinical impact. METHODS Seven patients were studied and for each patient two treatment plans (one TOMO and one VMAT) were created. Structures used for optimization were: high risk PTV, standard risk PTV, brainstem, spinal cord, parotid gland, larynx, mandible and surrounding tissue. The prescription varied between 60 - 74.4Gy to the HR. The same dosimetric constraints were used for both pairs of plans. Additionally, the TCP and NTCP values of the different targets and organs at risk (OAR) were calculated and compared together with the P+, which is the probability of achieving tumor control without normal tissue complications. RESULTS The proposed plan evaluation shows that the VMAT gives better results than TOMO in terms of expected clinical outcome. Specifically, the average difference in P+ = 3.3±1.8%, TCP = 3.3±1.8%, NTCP = 0.0±0.0%. The difference observed mainly stems from the lower TCP with TOMO (average difference of 2.9% for the high risk PTV and 3.1% for the standard risk PTV). The NTCP differences between the two modalities are very small even though their average differences in BEUD can be large (e.g. -21.9 Gy in brainstem, 27.2 Gy in larynx). CONCLUSION The findings of the analysis indicate that VMAT achieves better coverage to the targets with lower doses to the OARs compared to TOMO for the patients tested. However, the dosimetric differences appear to have a measurable impact only in the expected TCP rates of the targets. Radiobiological evaluation of treatment plans should provide a closer association of the delivered treatment with the clinical outcome.

Dosimetric evaluation of an ipsilateral intensity modulated radiotherapy beam arrangement for parotid malignancies

Abstract Background. We conducted a dosimetric comparison of an ipsilateral beam arrangement for intensity modulated radiotherapy (IMRT) with off-axis beams. Patients and methods. Six patients who received post-operative radiotherapy (RT) for parotid malignancies were used in this dosimetric study. Four treatment plans were created for each CT data set (24 plans): 1) ipsilateral 4-field off-axis IMRT (4fld-OA), 2) conventional wedge pair (WP), 3) 7 field co-planar IMRT (7fld), and 4) ipsilateral co-planar 4-field quartet IMRT (4fld-CP). Dose, volume statistics for the planning target volumes (PTVs) and planning risk volumes (PRVs) were compared for the four treatment techniques. Results. Wedge pair plans inadequately covered the deep aspect of the PTV. The 7-field IMRT plans delivered the largest low dose volumes to normal tissues. Mean dose to the contralateral parotid was highest for 7 field IMRT. Mean dose to the contralateral submandibular gland was highest for 7 field IMRT and WP. 7 field IMRT plans had the highest dose to the oral cavity. The mean doses to the brainstem, spinal cord, ipsilateral temporal lobe, cerrebellum and ipsilateral cochlea were similar among the four techniques. Conclusions. For postoperative treatment of the parotid bed, 4-field ipsilateral IMRT techniques provided excellent coverage while maximally sparing the contralateral parotid gland and submandibular gland.