Person: Mahadevan, Anand
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Mahadevan
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Anand
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Mahadevan, Anand
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Publication The RSSearch™ Registry: patterns of care and outcomes research on patients treated with stereotactic radiosurgery and stereotactic body radiotherapy(BioMed Central, 2013) Davis, Joanne N; Medbery III, Clinton; Sharma, Sanjeev; Danish, Adnan; Mahadevan, AnandBackground: The RSSearch™ Registry is a multi-institutional, observational, ongoing registry established to standardize data collection from patients treated with stereotactic radiosurgery (SRS) and/or stereotactic body radiotherapy (SBRT). This report describes the design, patient demographics, lesion characteristics, and SRS/SBRT treatment patterns in RSSearch™. Illustrative patient-related outcomes are also presented for two common treatment sites – brain metastases and liver metastases. Materials and methods Thirty-nine US centers participated in RSSearch™. Patients screened for SRS/SBRT were eligible to be enrolled. Descriptive analyses were performed to assess patient characteristics, physician treatment practices, and clinical outcomes. Kaplan-Meier analysis was used to determine overall survival (OS), local progression-free (LPFS), and distant disease-free survival (DDFS). Results: From January, 2008 – January, 2013, 11,457 patients were enrolled. The median age was 67 years (range 7–100 years); 51% male and 49% female. Forty-six percent had no prior treatment, 22% had received chemotherapy, 19% radiation therapy and 17% surgery. There were 11,820 lesions from 65 treatment locations; 54% extracranial and 46% intracranial. The most common treatment locations were brain/cranial nerve/spinal cord, lung, prostate and liver. Metastatic lesions accounted for the majority of cases (41.6%), followed by primary malignant (32.9%), benign (10.9%), recurrent (9.4%), and functional diseases (4.3%). SRS/SBRT was used with a curative intent in 39.8% and palliative care in 44.8% of cases. The median dose for all lesions was 30 Gy (range < 1 – 96.7 Gy) delivered in a median number of 3 fractions. The median dose for lesions in the brain/cranial nerve/spinal cord, lung, liver, pancreas and prostate was 24, 54, 45, 29 and 36.25 Gy, respectively. In a subset analysis of 799 patients with 952 brain metastases, median OS was 8 months. For patients with a Karnofsky performance score (KPS) > 70, OS was 11 months vs. 4 months for KPS ≤ 70. Six-month and 12-month local control was 79% and 61%, respectively for patients with KPS ≤ 70, and 85% and 74%, respectively for patients with KPS > 70. In a second subset analysis including 174 patients with 204 liver metastases, median OS was 22 months. At 1-year, LPFS and DDFS rates were 74% and 53%, respectively. LPFS. Conclusion: This study demonstrates that collective patterns of care and outcomes research for SRS/SBRT can be performed and reported from data entered by users in a common database. The RSSearch™ dataset represents SRS/SBRT practices in a real world setting, providing a useful resource for expanding knowledge of SRS/SBRT treatment patterns and outcomes and generating robust hypotheses for randomzed clinical studies.Publication The role of whole brain radiation therapy in the management of melanoma brain metastases(BioMed Central, 2014) Dyer, Michael A.; Arvold, Nils; Chen, Yu-Hui; Pinnell, Nancy E; Mitin, Timur; Lee, Eudocia; Hodi, F Stephen; Ibrahim, Nageatte; Weiss, Stephanie E; Kelly, Paul J; Floyd, Scott R.; Mahadevan, Anand; Alexander, BrianBackground: Brain metastases are common in patients with melanoma, and optimal management is not well defined. As melanoma has traditionally been thought of as “radioresistant,” the role of whole brain radiation therapy (WBRT) in particular is unclear. We conducted this retrospective study to identify prognostic factors for patients treated with stereotactic radiosurgery (SRS) for melanoma brain metastases and to investigate the role of additional up-front treatment with whole brain radiation therapy (WBRT). Methods: We reviewed records of 147 patients who received SRS as part of initial management of their melanoma brain metastases from January 2000 through June 2010. Overall survival (OS) and time to distant intracranial progression were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results: WBRT was employed with SRS in 27% of patients and as salvage in an additional 22%. Age at SRS > 60 years (hazard ratio [HR] 0.64, p = 0.05), multiple brain metastases (HR 1.90, p = 0.008), and omission of up-front WBRT (HR 2.24, p = 0.005) were associated with distant intracranial progression on multivariate analysis. Extensive extracranial metastases (HR 1.86, p = 0.0006), Karnofsky Performance Status (KPS) ≤ 80% (HR 1.58, p = 0.01), and multiple brain metastases (HR 1.40, p = 0.06) were associated with worse OS on univariate analysis. Extensive extracranial metastases (HR 1.78, p = 0.001) and KPS (HR 1.52, p = 0.02) remained significantly associated with OS on multivariate analysis. In patients with absent or stable extracranial disease, multiple brain metastases were associated with worse OS (multivariate HR 5.89, p = 0.004), and there was a trend toward an association with worse OS when up-front WBRT was omitted (multivariate HR 2.56, p = 0.08). Conclusions: Multiple brain metastases and omission of up-front WBRT (particularly in combination) are associated with distant intracranial progression. Improvement in intracranial disease control may be especially important in the subset of patients with absent or stable extracranial disease, where the competing risk of death from extracranial disease is low. These results are hypothesis generating and require confirmation from ongoing randomized trials.Publication Stereotactic radiosurgery for brain metastasis from gynecological malignancies(D.A. Spandidos, 2017) Kasper, Ekkehard; Ippen, Franziska; Wong, Eric; Uhlmann, Eric; Floyd, Scott; Mahadevan, AnandBrain metastases are relatively uncommon in gynecological malignancies, and there is limited available data on their management. The present study reports the outcomes of patients with brain metastasis from gynecological malignancies who were treated with stereotactic radiosurgery (SRS). Patients with brain metastasis from a gynecological primary site were treated with SRS using the Cyberknife™ frameless SRS system. Primary lesions were treated with a single fraction of 16–22 Gy. A total of 3 resection cavities were treated with 8 Gy 3 times, meaning a total of 24 Gy, and 1 recurrent lesion was re-irradiated with 5 Gy 5 times, meaning a total of 25 Gy. All patients were followed up with regular magnetic resonance imaging and clinical examinations 1 month after treatment and every 2 months thereafter. A total of 20 lesions in 8 patients were included in this study; 1 patient presented with metastatic endometrial cancer and the remaining 7 presented with metastatic ovarian cancer. The median age was 61 years (range, 48–78 years). All patients had received systemic therapy prior to developing brain metastasis. A total of 3 patients underwent surgical resection and 1 patient was administered re-irradiation for recurrence. There were 3 local failures in 2 patients. The actuarial 1-, 2- and 3-year local control rates were 91, 91 and 76%, respectively. The median overall survival time was 29 months. No SRS-associated toxicities or neurological mortalities were observed. In conclusion, brain metastasis from gynecological malignancies is uncommon, however, SRS is a safe and effective treatment modality for local control as a primary or adjuvant treatment in patients with this disease.Publication Stereotactic Radiosurgery for Renal Cancer Brain Metastasis: Prognostic Factors and the Role of Whole-Brain Radiation and Surgical Resection(Hindawi Publishing Corporation, 2015) Ippen, Franziska M.; Mahadevan, Anand; Wong, Eric; Uhlmann, Erik; Sengupta, Soma; Kasper, EkkehardBackground:. Renal cell carcinoma is a frequent source of brain metastasis. We present our consecutive series of patients treated with Stereotactic Radiosurgery (SRS) and analyse prognostic factors and the interplay of WBRT and surgical resection. Methods. This is a retrospective study of 66 patients with 207 lesions treated with the Cyberknife radiosurgery system in our institution. The patients were followed up with imaging and clinical examination 1 month and 2-3 months thereafter for the brain metastasis. Patient, treatment, and outcomes characteristics were analysed. Results. 51 male (77.3%) and 15 female (22.7%) patients, with a mean age of 58.9 years (range of 31–85 years) and a median Karnofsky Performance Status (KPS) of 90 (range of 60–100), were included in the study. The overall survival was 13.9 months, 21.9 months, and 5.9 months for the patients treated with SRS only, additional surgery, and WBRT, respectively. The actuarial 1-year Local Control rates were 84%, 94%, and 88% for SRS only, for surgery and SRS, and for WBRT and additional SRS, respectively. Conclusions. Stereotactic radiosurgery is a safe and effective treatment option in patients with brain metastases from RCC. In case of a limited number of brain metastases, surgery and SRS might be appropriate.Publication Stereotactic body radiotherapy for centrally located early-stage non-small cell lung cancer or lung metastases from the RSSearch® patient registry(BioMed Central, 2015) Davis, Joanne N.; Medbery, Clinton; Sharma, Sanjeev; Pablo, John; Kimsey, Frank; Perry, David; Muacevic, Alexander; Mahadevan, AnandBackground: The purpose of this study was to evaluate treatment patterns and outcomes of stereotactic body radiotherapy (SBRT) for centrally located primary non-small cell lung cancer (NSCLC) or lung metastases from the RSSearch® Patient Registry, an international, multi-center patient registry dedicated to radiosurgery and SBRT. Methods: Eligible patients included those with centrally located lung tumors clinically staged T1-T2 N0, M0, biopsy-confirmed NSCLC or lung metastases treated with SBRT between November 2004 and January 2014. Descriptive analysis was used to report patient demographics and treatment patterns. Overall survival (OS) and local control (LC) were determined using Kaplan-Meier method. Toxicity was reported using the Common Terminology Criteria for Adverse Events version 3.0. Results: In total, 111 patients with 114 centrally located lung tumors (48 T1-T2,N0,M0 NSCLC and 66 lung metastases) were treated with SBRT at 19 academic and community-based radiotherapy centers in the US and Germany. Median follow-up was 17 months (range, 1–72). Median age was 74 years for primary NSCLC patients and 65 years for lung metastases patients (p < 0.001). SBRT dose varied from 16 – 60 Gy (median 48 Gy) delivered in 1–5 fractions (median 4 fractions). Median dose to centrally located primary NSCLC was 48 Gy compared to 37.5 Gy for lung metastases (p = 0.0001) and median BED10 was 105.6 Gy for primary NSCLC and 93.6 Gy for lung metastases (p = 0.0005). Two-year OS for T1N0M0 and T2N0M0 NSCLC was 79 and 32.1 %, respectively (p = 0.009) and 2-year OS for lung metastases was 49.6 %. Two-year LC was 76.4 and 69.8 % for primary NSCLC and lung metastases, respectively. Toxicity was low with no Grade 3 or higher acute or late toxicities. Conclusion: Overall, patients with centrally located primary NSCLC were older and received higher doses of SBRT than those with lung metastases. Despite these differences, LC and OS was favorable for patients with central lung tumors treated with SBRT. Reported toxicity was low, although low grade toxicities were observed in patients where dose tolerances approached or exceeded published guidelines. Prospective studies are needed to further define the optimal SBRT dose for this cohort of patients. Trial registration Clinicaltrials.gov Identifier: NCT01885299Publication Stereotactic Body Radiotherapy (SBRT) for Intrahepatic and Hilar Cholangiocarcinoma(Ivyspring International Publisher, 2015) Mahadevan, Anand; Dagoglu, Nergiz; Mancias, Joseph; Raven, Kristin; Khwaja, Khalid; Tseng, Jennifer F; Ng, Kimmie; Enzinger, Peter; Miksad, Rebecca; Bullock, Andrea; Evenson, AmyBackground: Unresectable intrahepatic and hilar cholangiocarcinomas carry a dismal prognosis. Systemic chemotherapy and conventional external beam radiation and brachytherapy have been used with limited success. We explored the use of stereotactic body radiotherapy (SBRT) for these patients. Methods: Patients with unresectable intrahepatic or hilar cholangiocarcinoma or those with positive margins were included in this study. Systemic therapy was used at the discretion of the medical oncologist. The CyberknifeTM stereotactic body radiotherapy system used to treat these patients. Patients were treated with three daily fractions. Clinical and radiological follow-up were performed every three months. Results: 34 patients (16 male and 18 female) with 42 lesions were included in this study. There were 32 unresectable tumors and two patients with resected tumors with positive margins. The median SBRT dose was 30Gy in three fractions. The median follow-up was 38 months (range 8-71 months). The actuarial local control rate was 79%. The median overall survival was 17 months and the median progression free survival was ten months. There were four Grade III toxicities (12%), including duodenal ulceration, cholangitis and liver abscess. Conclusions: SBRT is an effective and reasonably safe local therapy option for unresectable intrahepatic or hilar cholangiocarcinoma.Publication Dosimetric analysis of the alopecia preventing effect of hippocampus sparing whole brain radiation therapy(BioMed Central, 2015) Mahadevan, Anand; Sampson, Carrie; LaRosa, Salvatore; Floyd, Scott R.; Wong, Eric; Uhlmann, Erik; Sengupta, Soma; Kasper, EkkehardBackground: Whole brain radiation therapy (WBRT) is widely used for the treatment of brain metastases. Cognitive decline and alopecia are recognized adverse effects of WBRT. Recently hippocampus sparing whole brain radiation therapy (HS-WBRT) has been shown to reduce the incidence of memory loss. In this study, we found that multi-field intensity modulated radiation therapy (IMRT), with strict constraints to the brain parenchyma and to the hippocampus, reduces follicular scalp dose and prevents alopecia. Methods: Suitable patients befitting the inclusion criteria of the RTOG 0933 trial received Hippocampus sparing whole brain radiation. On follow up, they were noticed to have full scalp hair preservation. 5 mm thickness of follicle bearing scalp in the radiation field was outlined in the planning CT scans. Conventional opposed lateral WBRT radiation fields were applied to these patient-specific image sets and planned with the same nominal dose of 30 Gy in 10 fractions. The mean and maximum dose to follicle bearing skin and Dose Volume Histogram (DVH) data were analyzed for conventional and HS-WBRT. Paired t-test was used to compare the means. Results: All six patients had fully preserved scalp hair and remained clinically cognitively intact 1–3 months after HS-WBRT. Compared to conventional WBRT, in addition to the intended sparing of the Hippocampus, HS-WBRT delivered significantly lower mean dose (22.42 cGy vs. 16.33 cGy, p < 0.0001), V24 (9 cc vs. 44 cc, p < 0.0000) and V30 (9 cc vs. 0.096 cc, p = 0.0106) to follicle hair bearing scalp and prevented alopecia. There were no recurrences in the Hippocampus area. Conclusions: HS-WBRT, with an 11-field set up as described, while attempting to conserve hippocampus radiation and maintain radiation dose to brain inadvertently spares follicle-bearing scalp and prevents alopecia.Publication Stereotactic body radiotherapy for early-stage non-small cell lung cancer: clinical outcomes from a National Patient Registry(Springer Berlin Heidelberg, 2015) Davis, Joanne N.; Medbery, Clinton; Sharma, Sanjeev; Perry, David; Pablo, John; D’Ambrosio, David J.; McKellar, Heidi; Kimsey, Frank C.; Chomiak, Paul N.; Mahadevan, AnandObjectives: Stereotactic body radiotherapy (SBRT) is a definitive local treatment option for patients with stage I non-small cell lung cancer (NSCLC) who are not surgical candidates and patients who refuse surgery. The purpose of this study was to assess the impact of SBRT on T1–T2 NSCLC from a national registry, reflecting practices and outcomes in a real-world setting. Methods: The RSSearch® Patient Registry was screened for T1–T2N0M0 NSCLC patients treated from May 2004 to May 2013 with SBRT. Descriptive analyses were used for patient, tumor, and treatment characteristics. Overall survival (OS) and local control (LC) were calculated using the Kaplan-Meier method. Results: In total, 723 patients with 517 T1 and 224 T2 lesions were treated with SBRT. Median follow-up was 12 months (1–87 months) with a median age of 76 years. Median SBRT dose was 54 Gy (range 10–80 Gy) delivered in a median of 3 fractions (range 1–5), and median biological equivalent dose (BED10) was 151.2 Gy (range 20–240 Gy). Median OS was 30 and 26 months for T1 and T2 tumors, respectively (p = 0.019). LC was associated with higher BED10 for T2 tumors, but not in T1 tumors at a median follow-up of 17 months. Seventeen-month LC for T2 tumors treated with BED10 < 105 Gy, BED10 105-149, and BED10 ≥ 150 Gy was 43, 74, and 95 %, respectively (p = 0.011). Local failure rates for T2 tumors treated with BED10 < 105 Gy, 105–149 Gy, and ≥150 Gy were 32, 21, and 8 % (p = 0.029), respectively. Median OS for patients with T2 tumors treated with BED10 < 105 Gy was 17 vs. 32 months for T2 tumors treated with BED10 105–149 Gy (p = 0.062). Conclusion: SBRT for T1–T2 NSCLC is feasible and effective in the community setting. OS was greater for patients with T1 lesions compared to T2 lesions. An improvement in LC was observed in patients with T2 lesions treated with BED10 > 105 Gy.Publication Hypofractionated Radiotherapy and Stereotactic Boost with Concurrent and Adjuvant Temozolamide for Glioblastoma in Good Performance Status Elderly Patients – Early Results of a Phase II Trial(Frontiers Media S.A., 2012) Floyd, Scott R.; Kasper, Ekkehard; Uhlmann, Erik; Fonkem, Ekokobe; Wong, Eric; Mahadevan, AnandGlioblastoma Multiforme (GBM) is an aggressive primary brain neoplasm with dismal prognosis. Based on successful phase III trials, 60 Gy involved-field radiotherapy in 30 fractions over 6 weeks [Standard radiation therapy (RT)] with concurrent and adjuvant temozolomide is currently the standard of care. In this disease, age and Karnofsky Performance Status (KPS) are the most important prognostic factors. For elderly patients, clinical trials comparing standard RT with radiotherapy abbreviated to 40 Gy in 15 fractions over 3 weeks demonstrated similar outcomes, indicating shortened radiotherapy may be an appropriate option for elderly patients. However, these trials did not include temozolomide chemotherapy, and included patients with poor KPS, possibly obscuring benefits of more aggressive treatment for some elderly patients. We conducted a prospective Phase II trial to examine the efficacy of a hypofractionated radiation course followed by a stereotactic boost with concurrent and adjuvant temozolomide chemotherapy in elderly patients with good performance status. In this study, patients 65 years and older with a KPS > 70 and histologically confirmed GBM received 40 Gy in 15 fractions with 3D conformal technique followed by a 1–3 fraction stereotactic boost to the enhancing tumor. All patients also received concurrent and adjuvant temozolomide. Patients were evaluated 1 month post-treatment and every 2 months thereafter. Between 2007 and 2010, 20 patients (9 males and 11 females) were enrolled in this study. The median age was 75.4 years (range 65–87 years). At a median follow-up of 11 months (range 7–32 months), 12 patients progressed and 5 are alive. The median progression free survival was 11 months and the median overall survival was 13 months. There was no additional toxicity. These results indicate that elderly patients with good KPS can achieve outcomes comparable to the current standard of care using an abbreviated radiotherapy course, radiosurgery boost, and temozolomide.Publication Gefitinib and High-Dose Fractionated Radiotherapy for Carcinomatous Encephalitis from Non-Small Cell Lung Carcinoma(Dove Medical Press, 2007) Wong, Eric; Wu, Julian K.; Mahadevan, AnandCarcinomatous encephalitis is a rapidly fatal form of metastasis caused by miliary spread of systemic cancer into the brain parenchyma. The diagnostic criteria and optimal treatment for this disease are not well defined. We report a patient with rapid neurologic deterioration from carcinomatous encephalitis from lung adenocarcinoma. She was treated with gefitinib and high-dose fractionated whole brain radiotherapy, and eventually improved neurologically and was discharged home on hospital day 48. Gefitinib and high-dose fractionated radiotherapy may have synergistic activity in patients with carcinomatous encephalitis from non-small cell lung cancer having favorable prognostic factors. More importantly, timely recognition of this disease and the use of large fraction radiation therapy are necessary to control rapid neurologic deterioration.