Ajay Bhatnagar

Analysis of tumor control and toxicity in patients who have survived at least one year after radiosurgery for brain metastases.

PURPOSE To better evaluate tumor control and toxicity from radiosurgery for brain metastases, we analyzed these outcomes in patients who had survived at least 1 year after radiosurgery. METHODS AND MATERIALS We evaluated the results of gamma knife stereotactic radiosurgery (SRS) for 208 brain metastases in 137 patients who were followed for a median of 18 months (range 12-122) after radiosurgery. The median patient age was 53 years (range 3-83). Ninety-nine patients had solitary metastases. Thirty-eight had multiple tumors. Sixty-nine patients underwent initial SRS with whole brain radiotherapy (WBRT), 39 had initial SRS alone, and 27 patients had failed prior WBRT. The median treatment volume was 1.9 cm(3) (range 0.05-21.2). The median marginal tumor dose was 16 Gy (range 12-25). The most common histologic types included non-small-cell lung cancer, breast cancer, melanoma, and renal cell carcinoma, which comprised 37.0%, 22.6%, 13.0%, and 9.13% of the lesions, respectively. Forty-five tumors were associated with extensive edema. RESULTS At 1 and 5 years, the local tumor control rate was 89.6% +/- 2.1% and 62.8% +/- 6.9%, distal intracranial relapse occurred in 23% +/- 3.6% and 67.1% +/- 8.7%, and postradiosurgical sequelae developed in 2.8% +/- 1.2% and 11.4% +/- 3.5% of patients, respectively. Multivariate analysis found that local control decreased with tumor volume (p = 0.0002), SRS without WBRT (p = 0.008), and extensive edema (p = 0.024); distal intracranial recurrence correlated with younger patient age (p = 0.0018); and postradiosurgical sequelae increased with increasing tumor volume (p = 0.0085). CONCLUSION Long-term control of brain metastases and complication rates in this selective series of patients surviving >or=1 year after radiosurgery were similar to previously reported actuarial estimates. Large metastases and metastases associated with extensive edema can be difficult to control by radiosurgery, particularly without WBRT.

Nonmelanoma skin cancer treated with electronic brachytherapy: Results at 1 year

PURPOSE We report clinical outcomes at 1 year or more after high-dose-rate (HDR) electronic brachytherapy (EBT) using surface applicators for the treatment of nonmelanoma skin cancer (NMSC). METHODS AND MATERIALS From July 2009 to April 2012, 122 patients with 171 NMSC lesions were treated with EBT to a dose of 40Gy in eight fractions, delivered twice weekly. At followup, patients were assessed for acute and late toxicities, cosmesis, and local control. RESULTS Treatment of 171 lesions was completed in 122 patients with a mean age 73 years. There have been no recurrences to date with a mean followup of 10 months (range, 1-28 months). Followup data at 1 year or more were available for 46 lesions in 42 patients. Hypopigmentation (all Grade 1) was present in 5 (10.9%) of 46 lesions at 1 year. Other late effects at 1 year included dry desquamation, alopecia, and rash dermatitis, which occurred in 1 (2.2%), 1 (2.2%), and 3 (6.5%) of 46 lesions, respectively. No Grade 3 or higher adverse events were observed at any time point. Cosmesis was evaluated at 1 year for 42 of 46 lesions and was excellent for 39 (92.9%) and good for 3 (7.1%) of the 42 evaluable lesions. CONCLUSIONS Treatment of NMSC with HDR EBT using surface applicators was effective with no recurrences, good to excellent cosmesis, and acceptable toxicities at 1 year or more after treatment. HDR EBT provides a convenient nonsurgical treatment option for NMSC patients.

CyberKnife Frameless Radiosurgery for the treatment of extracranial benign tumors.

Limited data exists for the use of radiosurgery for benign extracranial tumors. The purpose of this study was to evaluate the feasibility, toxicity, and local control of patients with benign extracranial lesions treated with the CyberKnife Frameless Radiosurgery System. From September 2001 thru January 2004, 59 benign tumors in 44 patients were treated using the CyberKnife a frameless image-guided radiosurgery system. Of these tumors, there were 21 neurofibromas, ten schwannomas, eight meningiomas, eight hemangioblastomas, seven paragangliomas, two hemangiopericytomas, one pseudotumor, one ependymoma, and one arteriovenous malformation (AVM). The anatomic locations of these tumors were spinal (25 cervical, four thoracic, 14 lumbar, and two sacral), neck (eight), orbital (three), brainstem (one), and foramen magnum (one). All patients were treated in a single fraction except three lesions were treated in a fractionated manner. The median treatment delivery time per fraction was 59 minutes (range 11–194). Twenty three lesions initially underwent surgical resection. Ten lesions received prior external beam radiation with a median dose 48 Gy (range 40–54 Gy), and one lesion received two prior CyberKnife treatments for a total dose of 32 Gy to the 80% isodose line. The median follow-up was eight months (range 1–25 months). Acute and late toxicity was graded using the National Cancer Institute Common Toxicity Criteria (CTC) scale. Symptomatic response was documented as “improved,” “stable,” or “progression”. The median tumor dose delivered was 16.0 Gy to the 80% isodose line (range 10–31 Gy). The median tumor volume was 4.3 cc (range 0.14–98.6 cc). The median spinal cord volume receiving more than 8 Gy was 0.035 cc (range 0–2.5 cc) and the median maximum spinal cord dose 11.5 Gy (range 0–19.8 Gy). There were no patients that suffered a significant (Grade 3, 4, or 5) acute toxicity. There was no observed late toxicity. 78% of patients experienced an improvement of their pre-treatment symptoms while only one patient experienced symptom progression. Of the 26 patients who underwent follow-up imaging, the local control rate was 96%. This study suggests that CyberKnife Radiosurgery is a safe and efficacious treatment modality for benign tumors, even for those patients with recurrent previously irradiated lesions.

Analysis of repeat stereotactic radiosurgery for progressive primary and metastatic CNS tumors

PURPOSE To identify and evaluate the pretreatment and patient factors that would predict for complications after repeat radiosurgery. METHODS AND MATERIALS The data from 26 patients who underwent re-irradiation with Gamma Knife surgery after a previous procedure in the same or subjacent location were available for evaluation. The range of follow-up was 1-45 months (mean 10). The mean minimal and maximal initial dose and volume for all 26 patients was 16.2 Gy (range 12-22), 31.0 Gy (range 22.2-40.0), and 12.4 cm(3) (range 1.20-70.84), respectively. The mean marginal and maximal repeated radiosurgery dose and volume for all 26 patients was 14.9 Gy (range 12-22.5), 29.7 Gy (range 18.0-45.0) and 12.8 cm(3) (range 1.10-39.20), respectively. RESULTS Tumor control was significantly better statistically (p = 0.0129) for benign tumors (6 of 6, 100% actuarial rate at 4 years) compared with malignant tumors (7 of 20, 35% actuarial rate at 3 years, 3 of 4 metastatic tumors and 2 of 10 primary malignant gliomas). The retreatment volume for radiosurgery correlated significantly with the probability of neurologic decline (any cause) (p = 0.0181). CONCLUSION Repeat radiosurgery can be performed for recurrent tumors with minimal central nervous system toxicity, especially for benign tumors, with reasonable tumor control.

Intensity-modulated radiation therapy (IMRT) reduces the dose to the contralateral breast when compared to conventional tangential fields for primary breast irradiation: initial report.

PURPOSEThis study was designed to compare the dose received by the contralateral breast during primary breast irradiation using intensity-modulated radiotherapy with the dose received via conventional tangential field techniques. METHODS/MATERIALSBetween March 2003 and March 2004, 44 patients with breast carcinoma were treated using 6-, 10-, or mixed 6/18-MV photons (36 with tangential intensity-modulated radiotherapy technique and eight with three-dimensional technique using tangential fields with wedges) for primary breast irradiation after breast-conserving surgery. Paired thermoluminescent dosimeters were placed on each patients contralateral breast, 4 cm from the center of the medial border of the tangential field. The thermoluminescent dosimeters were left on the patient during a single fraction and then measured 24 hours later. RESULTSThe mean dose delivered with photons to the primary breast for all patients was 4998 cGy [SD = 52], and the mean single fraction dose was 200 cGy [SD = 9]. The mean percent of the prescribed dose to the contralateral breast was 7.74% (SD = 2.35) for patients treated with intensity-modulated radiotherapy, compared with 9.74% [SD = 2.04] for the patients treated with conventional tangential field techniques. This represented a 20% reduction in the mean dose to the contralateral breast with the use of intensity-modulated radiotherapy when compared with the dose received via the three-dimensional technique, a result that was statistically significant. CONCLUSIONPrimary breast irradiation with tangential intensity-modulated radiotherapy technique significantly reduces the dose to the contralateral breast when compared with conventional tangential techniques.

Recursive Partitioning Analysis of Prognostic Factors for Patients with Four or More Intracranial Metastases Treated with Radiosurgery

The purpose of this study was to devise a new recursive partitioning analysis (RPA) of patients with four or more intracranial metastases treated with a single radiosurgery procedure to identify a class of patients with extended survival. 205 patients underwent Gamma Knife radiosurgery for four or more intracranial metastases (median = 5, range 4–18) during one session. The median total treatment volume was 6.8 cc (range 0.6–51.0 cc). Radiosurgery was used as sole management (17% of patients), or in combination with WB-RT (46%), or after failure of WB-RT (38%). The median marginal radiosurgery dose was 16 Gy (range 12–20 Gy). RPA assessed the effects of age, Karnofsky >70, extracranial disease, visceral metastases, number of metastases, total treatment volume, history of breast and melanoma primaries on survival. The median overall survival after radiosurgery for all patients was 8 months. RPA identified a favorable subgroup of 78 patients (43% of the series) with a total treatment volume <7 cc and < 7 brain metastases (Class 1), with a median survival of 13 months. This subgroups survival was significantly better (p <0.00005) than the remaining patients (Class 2) (n=111) with a median survival of 6 months. In conclusion, RPA of multiple brain metastasis patients identified 2 distinct cohorts of patients. Class 1 patients have a total treatment volume <7 cc and < 7 metastases (4–6) with favorable survival after Radiosurgery and Class 2 patients have a total treatment volume ≥ 7 cc and/or ≥ 7 metastases and have a significantly poorer survival.

Aspects of dosimetry and clinical practice of skin brachytherapy: The American Brachytherapy Society working group report

PURPOSE Nonmelanoma skin cancers (NMSCs) are the most common type of human malignancy. Although surgical techniques are the standard treatment, radiation therapy using photons, electrons, and brachytherapy (BT) (radionuclide-based and electronic) has been an important mode of treatment in specific clinical situations. The purpose of this work is to provide a clinical and dosimetric summary of the use of BT for the treatment of NMSC and to describe the different BT approaches used in treating cutaneous malignancies. METHODS AND MATERIALS A group of experts from the fields of radiation oncology, medical physics, and dermatology, who specialize in managing cutaneous malignancies reviewed the literature and compiled their clinical experience regarding the clinical and dosimetric aspects of skin BT. RESULTS A dosimetric and clinical review of both high dose rate ((192)Ir) and electronic BT treatment including surface, interstitial, and custom mold applicators is given. Patient evaluation tools such as staging, imaging, and patient selection criteria are discussed. Guidelines for clinical and dosimetric planning, appropriate margin delineation, and applicator selection are suggested. Dose prescription and dose fractionation schedules, as well as prescription depth are discussed. Commissioning and quality assurance requirements are also outlined. CONCLUSIONS Given the limited published data for skin BT, this article is a summary of the limited literature and best practices currently in use for the treatment of NMSC.

The initial experience of electronic brachytherapy for the treatment of non-melanoma skin cancer

BackgroundMillions of people are diagnosed with non-melanoma skin cancers (NMSC) worldwide each year. While surgical approaches are the standard treatment, some patients are appropriate candidates for radiation therapy for NMSC. High dose rate (HDR) brachytherapy using surface applicators has shown efficacy in the treatment of NMSC and shortens the radiation treatment schedule by using a condensed hypofractionated approach. An electronic brachytherapy (EBT) system permits treatment of NMSC without the use of a radioactive isotope.MethodsData were collected retrospectively from patients treated from July 2009 through March 2010. Pre-treatment biopsy was performed to confirm a malignant cutaneous diagnosis. A CT scan was performed to assess lesion depth for treatment planning, and an appropriate size of surface applicator was selected to provide an acceptable margin. An HDR EBT system delivered a dose of 40.0 Gy in eight fractions twice weekly with 48 hours between fractions, prescribed to a depth of 3-7 mm. Treatment feasibility, acute safety, efficacy outcomes, and cosmetic results were assessed.ResultsThirty-seven patients (mean age 72.5 years) with 44 cutaneous malignancies were treated. Of 44 lesions treated, 39 (89%) were T1, 1 (2%) Tis, 1 (2%) T2, and 3 (7%) lesions were recurrent. Lesion locations included the nose for 16 lesions (36.4%), ear 5 (11%), scalp 5 (11%), face 14 (32%), and an extremity for 4 (9%). Median follow-up was 4.1 months. No severe toxicities occurred. Cosmesis ratings were good to excellent for 100% of the lesions at follow-up.ConclusionsThe early outcomes of EBT for the treatment of NMSC appear to show acceptable acute safety and favorable cosmetic outcomes. Using a hypofractionated approach, EBT provides a convenient treatment schedule.

Does breast size affect the scatter dose to the ipsilateral lung, heart, or contralateral breast in primary breast irradiation using intensity-modulated radiation therapy (IMRT)?

Purpose:To evaluate the relationship between the primary breast volume and dose received by the ipsilateral lung, heart (for left-breast cancers), and contralateral breast during primary breast irradiation using intensity-modulated radiation therapy (IMRT). Methods and Materials:Sixty-five patients with breast carcinoma were treated using 6-MV photons with IMRT technique using the Eclipse Planning System following breast conserving surgery. All patients had a treatment planning CT scan. The primary breast, ipsilateral lung, and heart were contoured on the axial CT slices. The primary breast volume was calculated using the Eclipse Planning System. The mean ipsilateral lung and heart doses were obtained from the dose-volume histogram. The contralateral breast dose was measured using paired thermoluminescent dosimeters (TLDs) placed on the patients contralateral breast, 4 cm from the center of the medial border of the primary breast irradiation field. Results:The mean dose delivered with photons to the primary breast for all patients was 49.97 Gy. The mean volume of the primary irradiated breast was 1167.9 cc. As a percentage, the mean ipsilateral lung, heart, and contralateral breast doses were 11.2%, 6.1%, and 7.2%, respectively. The primary breast volume positively correlated with the contralateral breast dose (P < 0.0005). There was no significant correlation between the breast volume and the ipsilateral lung or heart dose (P = 0.463 and 0.943, respectively). Conclusion:This study suggests that the primary breast size significantly affects the scatter dose to the contralateral breast but not the ipsilateral lung or heart dose when using IMRT for breast irradiation.

An analysis of the effects of smoking and other cardiovascular risk factors on obliteration rates after arteriovenous malformation radiosurgery

PURPOSE To assess the relationships of smoking and other cardiovascular disease risk factors (hypertension, diabetes, hypercholesterolemia, and gender) to rates of radiosurgery-induced obliteration of arteriovenous malformations (AVM). METHODS AND MATERIALS We evaluated follow-up imaging and clinical data in 329 AVM patients who received gamma knife radiosurgery at the University of Pittsburgh between 1987 and 1994. There were 113 smokers, 29 hypertensives, 5 diabetics, 4 hypercholesterolemics, 159 male patients, and 170 female patients. All patients had regular clinical or imaging follow-up for a minimum of 3 years after radiosurgery. RESULTS Multivariate analysis showed that smoking had no effect on AVM obliteration (p > 0.43). Hypertension, diabetes, and hypercholesterolemia had no discernible effect on AVM obliteration in this study (p > 0.78). However, females aged 12-49 had a statistically significant lower in-field obliteration rate than males (78% vs. 89%, p = 0.0102). CONCLUSION Smoking has no effect on AVM obliteration. Hypertension, diabetes, and hypercholesterolemia had no discernible effect in this study. Further study is needed to establish whether estrogen has a vascular protective effect that could partially limit radiosurgical AVM obliteration, as suggested by this study.