Niranjan Bhandare

Radiation therapy and hearing loss.

A review of literature on the development of sensorineural hearing loss after high-dose radiation therapy for head-and-neck tumors and stereotactic radiosurgery or fractionated stereotactic radiotherapy for the treatment of vestibular schwannoma is presented. Because of the small volume of the cochlea a dose-volume analysis is not feasible. Instead, the current literature on the effect of the mean dose received by the cochlea and other treatment- and patient-related factors on outcome are evaluated. Based on the data, a specific threshold dose to cochlea for sensorineural hearing loss cannot be determined; therefore, dose-prescription limits are suggested. A standard for evaluating radiation therapy-associated ototoxicity as well as a detailed approach for scoring toxicity is presented.

Severe dry eye syndrome after radiotherapy for head-and-neck tumors.

PURPOSE To investigate the incidence of severe dry eye syndrome (DES) after external beam radiotherapy for head-and-neck cancer and its dependence on the parameters relevant to external beam radiotherapy. METHODS AND MATERIALS The present retrospective study included 78 patients treated for primary extracranial head-and-neck tumors between 1965 and 2000, whose lacrimal apparatus/entire globe was exposed to fractionated external beam radiotherapy. The dose received by the major lacrimal gland was used for analysis. The end point of the present study was the ophthalmologic diagnosis of severe DES leading to vision compromise. RESULTS Of the 78 patients, 40 developed severe DES leading to visual compromise. The incidence of DES increased steadily from 6% at 35-39.99 Gy to 50% at 45-49.99 Gy and 90% at 60-64.99 Gy. With a mean of 0.9 years (range, 1 month to 3 years), the latency of DES was observed to be a function of the total dose and the dose per fraction. On univariate and multivariate analysis, the total dose (p < .0001 and p < .0001, respectively) and dose per fraction (p ≤ .0001 and p = .0044, respectively) were significant. However, age, gender, and the use of chemoradiotherapy were not. The actuarial analysis indicated a 5-year probability of freedom from DES of 93% for doses <45 Gy, 29% for 45-59.9 Gy, and 3% doses ≥60 Gy. A logistic normal tissue complication probability model fit to our data obtained a dose of 34 and 38 Gy corresponding to a 5% and 10% incidence of DES. CONCLUSION With a dose of 34 Gy corresponding to a 5% incidence of DES, the risk of severe DES increased, and the latency decreased with an increase in the total dose and dose per fraction to the lacrimal gland. The effect of chemoradiotherapy and hyperfractionation on the risk of DES needs additional investigation.

Low-kilovoltage, single-dose intraoperative radiation therapy for breast cancer: results and impact on a multidisciplinary breast cancer program.

BACKGROUND The Intrabeam (Carl Zeiss) brachytherapy device (IB) is an electronic brachytherapy device that can be used to deliver low energy x-rays (50 kV) to a lumpectomy cavity at the time of lumpectomy for breast cancer. Reported experience with IB for breast cancer in the United States has been extremely limited. Here we describe our experience and analyze the impact of IB on our multidisciplinary breast cancer program. STUDY DESIGN This is a retrospective review of a prospectively collected breast cancer database. Patient characteristics, treatment characteristics, recurrence, and cosmesis were analyzed. Cost data were also analyzed to determine the impact of IB on the breast cancer program. RESULTS Seventy-eight patients underwent 80 IB treatments in this series between November 2010 and October 2012. Most patients had invasive ductal carcinoma. Mean total operative time for patients receiving lumpectomy, sentinel node biopsy, and IB was 132 minutes (range 79 to 243 minutes). Intrabeam brachytherapy was the only adjuvant radiation required in 81% of patients, and only 15% of patients required additional operation after the index lumpectomy procedure. At 12 months of follow-up, cosmesis was good to excellent in 92% of patients. There have been no local recurrences in patients treated in this series. Intrabeam brachytherapy is associated with considerably lower costs (

Hypopituitarism after radiotherapy for extracranial head and neck cancers

1,857) than conventional whole breast radiation therapy (

Radiation Effects on the Auditory and Vestibular Systems

9,653). CONCLUSIONS Implementation of IB impacts treatment planning and operating room use in a multidisciplinary breast cancer program. The safety profile, ease of administration, and reduced costs of IB favor its more widespread use in selected patients with early-stage breast cancer.

Hypopituitarism After Radiotherapy for Extracranial Head and Neck Cancers in Pediatric Patients

The purpose of this study was to investigate the incidence of radiotherapy‐induced primary and secondary hypopituitarism.

A comparison of dose-response characteristics of four NTCP models using outcomes of radiation-induced optic neuropathy and retinopathy.

Definitive or postoperative radiation therapy (RT) is commonly used for the management of intracranial and extracranial head and neck tumors. Because of the variability of tumor location and dimensions, sparing of nontarget normal tissue and organs may not be possible. Treatment modalities that deliver the highest doses of radiation to the auditory system include stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) for the treatment of vestibular schwannomas (VS), and fractionated radiotherapy (FRT) or intensity-modulated radiation therapy (IMRT) for the treatment of head and neck malignancies. Radiation therapy for VS is unique because of its involvement of the inner ear and preexisting auditory and vestibular dysfunction. Auditory and vestibular dysfunction following RT for VS may be limited by limiting the total dose of cranial nerve VIII irradiation and by fractionation.

WE-C-AUD B-06: Dose Response Analysis of Radiation-Induced Retinopathy (RIRP) Single-Institution Data Using the Lyman NTCP Model

Objectives:To investigate the incidence of postradiation therapy (postRT) hypopituitarism (hp-pit) in pediatric patients treated for extracranial head and neck tumors. Methods:We retrospectively reviewed 30 pediatric patients treated with RT for extracranial head and neck tumors between 1970 and 2000. RT doses to the hypothalamic-pituitary axis were estimated by re-evaluating the treatment plans. Results:Clinical hp-pit was observed in 16 (53.3%) patients; the median detection latency was 3.3 years and the median dose to the pituitary was 40.7 Gy. Univariate analysis of clinical hp-pit revealed that the total dose to the pituitary was significant (P = 0.034) as was the patients age at the time of RT (P = 0.018) showing higher susceptibility and more damage in younger patients. Though fractionation (P = 0.018) and adjuvant chemotherapy (P = 0.016) were significant in univariate analysis, the total dose received by patients in these 2 groups was higher than the median dose for all patients. A limited multivariate analysis with 3 variables indicated that the total dose to the pituitary was significant, but chemoradiation and fractionation were not. The 5- and 10-year rates of freedom from clinical hp-pit were 42% and 37%, respectively. Conclusions:Clinical manifestations of late radiation toxicity to the hypothalamic–pituitary axis were observed among the pediatric patients with hormone deficiencies. The development of hp-pit depends on the total dose received by the hypothalamic-pituitary axis and the age of the patient. Dependence on chemoradiation and fractionation were inconclusive. Relatively long latency before clinical manifestations indicates that periodic testing after RT in pediatric patients is necessary for early detection and management of hormonal deficiencies.

Temporal Bone Osteoradionecrosis after External Beam Radiation Therapy for Head and Neck Cancer

BackgroundBiological models are used to relate the outcome of radiation therapy to dose distribution. As use of biological models in treatment planning expands, uncertainties associated with the use of specific models for predicting outcomes should be understood and quantified. In particular, the question to what extent model predictions are data-driven or dependent on the choice of the model has to be explored.MethodsFour dose-response models--logistic, log-logistic, Poisson-based and probit--were tested for their ability and consistency in describing dose-response data for radiation-induced optic neuropathy (RION) and retinopathy (RIRP). Dose to the optic nerves was specified as the minimum dose, Dmin , received by any segment of the organ to which the damage was diagnosed by ophthalmologic evaluation. For retinopathy, the dose to the retina was specified as the highest isodose covering at least 1/3 of the retinal surface (D33% ) that geometrically covered the observed retinal damage. Data on both complications were modeled separately for patients treated once daily and twice daily. Model parameters D50 and γ and corresponding confidence intervals were obtained using maximum-likelihood method.ResultsModel parameters were reasonably consistent for RION data for patients treated once daily, D50 ranging from 94.2 to 104.7 Gy and γ from 0.88 to 1.41. Similar consistency was seen for RIRP data which span a broad range of complication incidence, with D50 from 72.2 to 75.0 Gy and γ from 1.51 to 2.16 for patients treated twice daily; 72.2-74.0 Gy and 0.84-1.20 for patients treated once daily. However, large variations were observed for RION in patients treated twice daily, D50 from 96.3 to 125.2 Gy and γ from 0.80 to 1.56. Complication incidence in this dataset in any dose group did not exceed 20%.ConclusionsFor the considered data sets, the log-logistic model tends to lead to larger D50 and lower γ compared to other models for all datasets. Statements regarding normal tissue radiosensitivity and steepness of dose-response, based on model parameters, should be made with caution as the latter are not only model-dependent but also sensitive to the range of complication incidence exhibited by clinical data.

Radiation-Induced Ototoxicity

Purpose: To analyze the dose‐response characteristics of radiation‐induced retinopathy (RIRP) to high‐dose radiation therapy using the Lyman NTCP model. Method and Materials: A retrospective analysis of 108 patients treatedQD (23 RIRPs observed) and 78 patients treated BID (7 RIRPs observed) in the head‐and‐neck sites were performed. Using the α/β ratio determined with the QD group (2.65 Gy; [−1.06,∞] 95% CI), the total dose for each patient was converted to the normalized “2 Gy/fraction” total dose (NTD) before analysis. Subsequently, the Lyman NTCP parameters were estimated using the maximum‐likelihood method with asymmetric confidence intervals determined using the profile‐likelihood analysis (68% CI). The chi‐square goodness‐of‐fit test was performed to evaluate the modeling. Results: Due to the minute thickness and volume of the organ a DVH analysis was not performed. Instead, the dose to the retina was specified as the highest isodose covering at least 1/3 of the retinal surface that geometrically covered the observed retinal damage. Therefore, the volume effect parameter, n, was not investigated. The estimated values of NTD50 , and m were 72.4 Gy [67.5,79.5] and 0.356 [0.29,0.44], respectively, for QD dataset and 73.0 Gy [67.0,85.5] and 0.209 [0.15,0.30], respectively, for BID dataset. While the NTD50 was generally in good agreement between the two groups, the BID group showed steeper slope resulting in lower incidence at clinical dose range (∼ 30 to 60 Gy). The chi‐square test showed that the model was adequate (p = 1.00) for both the QD and BID groups. Conclusion: The Lyman NTCP model was used to describe the RIRP data. Results show that QD and BID groups give comparable NTD50 values when NTD conversion is made. However, the BID group showed steeper slope. If the validity of the linear‐quadratic formalism is assumed, then hyperfractionation may be beneficial for RIRP given the small α/β ratio estimated.