Dose-volume toxicity modeling for de-intensified chemo-radiation therapy for HPV-positive oropharynx cancer.

BACKGROUND AND PURPOSE: The aim is to determine the radiobiological parameters of four popular normal tissue complication probability (NTCP) models that describe the dose-response relations of salivary glands and pharyngeal constrictors to the severity of patient reported xerostomia and dysphagia, respectively 6 and 12months post chemo-radiotherapy, furthermore, to evaluate the goodness-of-fit of the NTCP models for different combinations of glands and constrictors. MATERIAL AND METHODS: Forty-three patients were treated on a prospective multi-institutional phase II study (ClinicalTrials.gov, NCT01530997) assessing the efficacy of de-intensified chemoradiotherapy in patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma. All patients received 60Gy intensity modulated radiotherapy with concurrent weekly intravenous cisplatinum. All patients reported severity of their xerostomia and dysphagia (pre- and post-treatment) using the patient reported outcome version of the CTCAE (PRO-CTCAE). A change in severity (from baseline) of ≥2 was considered clinically meaningful. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS), Logit, and Relative Seriality Logit (RSL) NTCP models were used to fit the patients' dose/volume data to changes in PRO-CTCAE severity of xerostomia and dysphagia (from baseline to 6 and 12months post-treatment). The correlation of the models with the patient outcomes was performed for different combinations of salivary glands and different sections of pharyngeal constrictors. The goodness-of-fit of the different models was assessed through the area under the receiver operating characteristic curve (AUC), maximum of the log-likelihood function, normal error distribution and Akaike information criterion (AIC). RESULTS: The dose/volume metrics of the combined contralateral (parotid+submandibular) glands appear to correlate best with xerostomia, at both 6- and 12-months. Among the different sections of pharyngeal constrictors, the dose/volume metrics of the superior pharyngeal constrictors appear to correlate best with dysphagia at 6months. The AUC values ranged from 0.72 to 0.85 in the case of xerostomia and 0.73 to 0.74 in the case of dysphagia over the different models. The four NTCP models showed similar goodness-of-fit. The differences in AIC between the different models were less than 2 and ranged within 0.7 and 0.8 in the cases of xerostomia and dysphagia, respectively. The calculated parameters of the LKB model were D50=26.9Gy, m=0.63, n=1.0 for the combined contralateral glands at 12months and D50=62.0Gy, m=0.10, n=0.49 for the superior pharyngeal constrictors at 6months. CONCLUSIONS: The values of the parameters of four NTCP models were determined for salivary glands and pharyngeal constrictors. All four models could fit the clinical data equally well. The NTCP predictions of the combined contralateral glands and superior pharyngeal constrictors showed the best correlation with the patient reported outcomes of xerostomia and dysphagia, respectively.

Helical tomotherapy for bilateral breast cancer: Clinical experience.

We report our initial clinical experience with using Helical tomotherapy to irradiate the bilateral breasts/chest-wall and regional nodes. METHODS: The records of patients who received bilateral irradiation of the breast/chest-wall and regional nodes with tomotherapy were retrospectively reviewed. Clinical outcomes for tumor and normal tissues were assessed. RESULTS: From August 2011 to January 2016, nine women were identified; median age 52 years (range 37-74), mean follow up was 10.3 months (range 0.3-34). In two patients, tomotherapy represented re-irradiation to one side. All received regional nodal irradiation. The average lung V20 was 29% (range 25-35), average lung V5 was 66% (range 51-75). Average heart mean dose was 20 Gy (range 13-28). NORMAL TISSUE OUTCOMES: Acute toxicity during radiation included dysphagia (5/9), fatigue (4/9), nausea and weight loss (1/9) and skin desquamation (9/9). Two patients were lost to long follow-up and one patient recently completed treatment. Longer-term toxicity included: pneumonitis (1/6), elevated liver function tests (1/6) and sternal osteonecrosis (1/6; in patient with prior sternal surgery). CONCLUSIONS: Despite the small numbers of patients and relatively short follow-up, significant clinical toxicities were observed. Given the rarity of this situation and relatively high rate of complications in this small series, considerable care should be taken in minimizing dose to normal structures. Longer follow up with larger numbers of patients will be needed to establish safe dosimetric parameters for bilateral breasts/chest wall and nodal irradiation with tomotherapy.

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

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.

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.