The influence of radiation dose on taste impairment in a prospective observational study cohort of oropharyngeal cancer patients.

BACKGROUND: To analyze the influence of radiation dose on late radiation-associated taste impairment in oropharyngeal cancer (OPC) patients treated with intensity-modulated radiotherapy (IMRT) using the taste bud bearing tongue mucosa as organ at risk. MATERIAL AND METHODS: This study is part of an ongoing, prospective observational study. Cancer-free OPC survivors with at least 24 months from IMRT were included in this analysis. Scores for taste impairment and dry mouth were extracted from the MD Anderson Symptom Inventory Head and Neck module (MDASI-HN) with scores of ≥5 considered as moderate-to-severe symptoms. The mean dose, minimum and maximum dose to the taste bud bearing tongue mucosa, the ipsi- and contralateral parotid and submandibular glands were extracted and analyzed for correlation with moderate-to-severe taste impairment. RESULTS: One hundred sixteen T1-4 OPC patients were included (81% males, median age: 55). The primary tumor was in the tonsil in 92 cases (79%) and in the base of tongue in 21 cases (18%). Patients were treated with 64.2-72.0 Gy; 37 patients (32%) received concurrent chemotherapy and 22 (19%) concurrent targeted therapy. After a median of 58 months from RT (IQR: 43-68) 38 patients (33%) suffered from moderate-to-severe long-term radiation-associated taste impairment. No dose volume parameter of the taste bud bearing tongue mucosa and the salivary glands was significantly associated with moderate-to-severe taste impairment for the whole patient cohort. For patients without concurrent chemotherapy, the minimum and mean dose to the ipsilateral parotid gland, and the maximum dose to the submandibular gland was significantly associated with late taste impairment (all p < 0.05). A significant correlation was found between taste impairment and dry mouth (p < 0.001). CONCLUSION: The dose to the ipsilateral parotid gland seems to play an important role in the development of late taste impairment. The influence of dose to the taste bud bearing tongue mucosa remains unclear and needs further investigation.

Normal tissue complication probability models in plan evaluation of children with brain tumors referred to proton therapy.

Background: Children with brain tumors undergoing radiotherapy are at particular risk of radiation-induced morbidity and are therefore routinely considered for proton therapy (PT) to reduce the dose to healthy tissues. The aim of this study was to apply pediatric constraints and normal tissue complication probability (NTCP) models when evaluating the differences between PT and contemporary photon-based radiotherapy, volumetric modulated arc therapy (VMAT). Methods: Forty patients (aged 1-17 years) referred from Norwegian institutions to cranial PT abroad during 2014-2016 were selected for VMAT re-planning using the original CT sets and target volumes. The VMAT and delivered PT plans were compared by dose/volume metrics and NTCP models related to growth hormone deficiency, auditory toxicity, visual impairment, xerostomia, neurocognitive outcome and secondary brain and parotid gland cancers. Results: The supratentorial brain, temporal lobes, hippocampi, hypothalamus, pituitary glands, cochleas, salivary glands, optic nerves and chiasm received lower mean doses from PT. Reductions in population median NTCP were significant for auditory toxicity (VMAT: 3.8%; PT: 0.3%), neurocognitive outcome (VMAT: 3.0 IQ points decline at 5 years post RT; PT: 2.5 IQ points), xerostomia (VMAT: 2.0%; PT: 0.6%), excess absolute risk of secondary cancer of the brain (VMAT: 9.2%; PT: 6.7%) and salivary glands (VMAT: 2.8%; PT:0.5%). Across all patients, 23/38 PT plans had better or comparable estimated risks for all endpoints (within ±10% of the risk relative to VMAT), whereas for 1/38 patients all estimates were better or comparable with VMAT. Conclusions: PT reduced the volumes of normal tissues exposed to radiation, particularly low-to-intermediate dose levels, and this was reflected in lower NTCP. Of the included endpoints, substantial reductions in population medians were seen from the delivered PT plans for auditory complications, xerostomia, and risk of secondary cancers of the brain and salivary glands.

Risk of radiation-induced secondary rectal and bladder cancer following radiotherapy of prostate cancer.

BACKGROUND: An elevated risk of radiation-induced secondary cancer (SC) has been observed in prostate cancer patients after radiotherapy (RT), rising to as high as one in 70 patients with more than 10 years follow-up. In this study we have estimated SC risks following RT with both previous and contemporary techniques, including proton therapy, using risk models based on different dose-response relationships. MATERIAL AND METHODS: RT plans treating the prostate and seminal vesicles with either conformal radiotherapy (CRT), volumetric modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) were created for 10 patients. The risks of radiation-induced cancer were estimated for the bladder and rectum using dose-response models reflecting varying degrees of cell sterilisation: a linear model, a linear-plateau model and a bell-shaped model also accounting for fractionated RT. RESULTS: The choice of risk models was found to rank the plans quite differently, with the CRT plans having the lowest SC risk using the bell-shaped model, while resulting in the highest risk applying the linear model. Considering all dose-response scenarios, median relative risks of VMAT versus IMPT were 1.1-1.7 for the bladder and 0.9-1.8 for the rectum. Risks of radiation-induced bladder and rectal cancers were lower from VMAT if exposed at 80 years versus IMPT if exposed at 50 years. CONCLUSIONS: The SC risk estimations for the bladder and rectum revealed no clear relative relationship between the contemporary techniques and CRT, with divergent results depending on choice of model. However, the SC risks for these organs when using IMPT were lower or comparable to VMAT. SC risks could be assessed when considering referral of prostate cancer patients to proton therapy, taking also general patient characteristics, such as age, into account.