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Evaluation of First-line Radiosurgery vs Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases: The FIRE-SCLC Cohort Study

Rusthoven, Chad G; Yamamoto, Masaaki; Bernhardt, Denise; Smith, Derek E; Gao, Dexiang; Serizawa, Toru; Yomo, Shoji; Aiyama, Hitoshi; Higuchi, Yoshinori; Shuto, Takashi; Akabane, Atsuya; Sato, Yasunori; Niranjan, Ajay; Faramand, Andrew M; Lunsford, L Dade; McInerney, James; Tuanquin, Leonard C; Zacharia, Brad E; Chiang, Veronica; Singh, Charu; Yu, James B; Braunstein, Steve; Mathieu, David; Touchette, Charles J; Lee, Cheng-Chia; Yang, Huai-Che; Aizer, Ayal A; Cagney, Daniel N; Chan, Michael D; Kondziolka, Douglas; Bernstein, Kenneth; Silverman, Joshua S; Grills, Inga S; Siddiqui, Zaid A; Yuan, Justin C; Sheehan, Jason P; Cordeiro, Diogo; Nosaki, Kename; Seto, Takahashi; Deibert, Christopher P; Verma, Vivek; Day, Samuel; Halasz, Lia M; Warnick, Ronald E; Trifiletti, Daniel M; Palmer, Joshua D; Attia, Albert; Li, Benjamin; Cifarelli, Christopher P; Brown, Paul D; Vargo, John A; Combs, Stephanie; Kessel, Kerstin A; Rieken, Stefan; Patel, Samir; Guckenberger, Matthias; Andratschke, Nicolaus; Kavanagh, Brian D; Robin, Tyler P
Importance/UNASSIGNED:Although stereotactic radiosurgery (SRS) is preferred for limited brain metastases from most histologies, whole-brain radiotherapy (WBRT) has remained the standard of care for patients with small cell lung cancer. Data on SRS are limited. Objective/UNASSIGNED:To characterize and compare first-line SRS outcomes (without prior WBRT or prophylactic cranial irradiation) with those of first-line WBRT. Design, Setting, and Participants/UNASSIGNED:FIRE-SCLC (First-line Radiosurgery for Small-Cell Lung Cancer) was a multicenter cohort study that analyzed SRS outcomes from 28 centers and a single-arm trial and compared these data with outcomes from a first-line WBRT cohort. Data were collected from October 26, 2017, to August 15, 2019, and analyzed from August 16, 2019, to November 6, 2019. Interventions/UNASSIGNED:SRS and WBRT for small cell lung cancer brain metastases. Main Outcomes and Measures/UNASSIGNED:Overall survival, time to central nervous system progression (TTCP), and central nervous system (CNS) progression-free survival (PFS) after SRS were evaluated and compared with WBRT outcomes, with adjustment for performance status, number of brain metastases, synchronicity, age, sex, and treatment year in multivariable and propensity score-matched analyses. Results/UNASSIGNED:In total, 710 patients (median [interquartile range] age, 68.5 [62-74] years; 531 men [74.8%]) who received SRS between 1994 and 2018 were analyzed. The median overall survival was 8.5 months, the median TTCP was 8.1 months, and the median CNS PFS was 5.0 months. When stratified by the number of brain metastases treated, the median overall survival was 11.0 months (95% CI, 8.9-13.4) for 1 lesion, 8.7 months (95% CI, 7.7-10.4) for 2 to 4 lesions, 8.0 months (95% CI, 6.4-9.6) for 5 to 10 lesions, and 5.5 months (95% CI, 4.3-7.6) for 11 or more lesions. Competing risk estimates were 7.0% (95% CI, 4.9%-9.2%) for local failures at 12 months and 41.6% (95% CI, 37.6%-45.7%) for distant CNS failures at 12 months. Leptomeningeal progression (46 of 425 patients [10.8%] with available data) and neurological mortality (80 of 647 patients [12.4%] with available data) were uncommon. On propensity score-matched analyses comparing SRS with WBRT, WBRT was associated with improved TTCP (hazard ratio, 0.38; 95% CI, 0.26-0.55; P < .001), without an improvement in overall survival (median, 6.5 months [95% CI, 5.5-8.0] for SRS vs 5.2 months [95% CI, 4.4-6.7] for WBRT; P = .003) or CNS PFS (median, 4.0 months for SRS vs 3.8 months for WBRT; P = .79). Multivariable analyses comparing SRS and WBRT, including subset analyses controlling for extracranial metastases and extracranial disease control status, demonstrated similar results. Conclusions and Relevance/UNASSIGNED:Results of this study suggest that the primary trade-offs associated with SRS without WBRT, including a shorter TTCP without a decrease in overall survival, are similar to those observed in settings in which SRS is already established.
PMID: 32496550
ISSN: 2374-2445
CID: 4481022

Stereotactic Radiation for Treating Primary and Metastatic Neoplasms of the Spinal Cord

Liu, Elisa K; Silverman, Joshua S; Sulman, Erik P
Stereotactic radiation treatment can be used to treat spinal cord neoplasms in patients with either unresectable lesions or residual disease after surgical resection. While treatment guidelines have been suggested for epidural lesions, the utility of stereotactic radiation for intradural and intramedullary malignancies is still debated. Prior reports have suggested that stereotactic radiation approaches can be used for effective tumor control and symptom management. Treatment-related toxicity has been documented in rare subsets of patients, though the incidences of injury are not directly correlated with higher radiation doses. Further studies are needed to assess the factors that influence the risk of radiation-induced myelopathy when treating spinal cord neoplasms with stereotactic radiation, which can include, but may not be limited to, maximum dose, dose-fractionation, irradiated volume, tumor location, histology and treatment history. This review will discuss evidence for current treatment approaches.
PMID: 32582555
ISSN: 2234-943x
CID: 4493422

Endometrial adenocarcinoma presenting as a suprasellar mass: lessons to be learned [Case Report]

Granina, Evgenia; Fehniger, Julia; Kondziolka, Douglas; Silverman, Joshua; Downey, Andrea; Placantonakis, Dimitris; Muggia, Franco
A 66-year-old woman with a history of stage IA mixed endometrioid and serous endometrial cancer presented to our centre with 2 weeks of worsening headaches nearly 4 years after her initial surgery. At admission, she manifested bitemporal hemianopsia, difficulty walking and clinical and laboratory findings of panhypopituitarism, including diabetes insipidus. Magnetic resonance imaging of the brain revealed a 2.7 cm sellar/suprasellar mass compressing the optic chiasm and infiltrating the pituitary stalk. Computerised tomography documented mediastinal, lung, adrenal and liver involvement, including a 2.5 cm palpable left supraclavicular node that on excisional biopsy demonstrated metastatic endometrial adenocarcinoma. Due to the advanced stage of her cancer as well as the presence of multiple metastases, including lung and hepatic metastases causing post-obstructive pneumonia and coagulopathy, the sellar/suprasellar mass was treated with fractionated radiosurgery rather than surgical excision.
PMID: 32863877
ISSN: 1754-6605
CID: 4615322

How Many Lesions can be Treated With Radiosurgery? Whole Brain Dose from Radiosurgery of Multiple Targets [Meeting Abstract]

Becker, S. J.; Jozsef, G.; Molitoris, J. K.; Silverman, J. S.; Presser, J.; Kondziolka, D.
ISSN: 0360-3016
CID: 4686222

Hippocampal Dosimetry In Patients Receiving Radiosurgery For >= 25 Brain Metastases: Implications For HA-WBRT [Meeting Abstract]

Kavi, A.; Gurewitz, J.; Benjamin, C.; Bernstein, K.; Silverman, J. S.; Donahue, B. R.; Kondziolka, D.
ISSN: 0360-3016
CID: 4686332


Kurz, Sylvia; Zan, Elcin; Gurewitz, Jasone; Cordova, Christine; Troxel, Andrea B.; Sawaged, Zacharia; Sevillano-Torres, Hector; Silverman, Joshua S.; Snuderl, Matija; Zagzag, David; Golfinos, John; Kondziolka, Douglas; Sulman, Erik
ISSN: 1522-8517
CID: 4688132


Gurewitz, Jason; Donahue, Bernadine; Silverman, Joshua S.; Benjamin, Carolina; Bernstein, Kenneth; Kondziolka, Douglas
ISSN: 1522-8517
CID: 4688212


Silverman, Joshua S.; Gurewitz, Jason; Gunter, Courtney; Cooper, Benjamin; Palermo, Amy; Boulio, Lynda; Schafrick, Jessica; Lim, Whei Ying; Karhan, Ece; Renzullo, Stephanie; Kozhaya, Lina; Golfinos, John; Sulman, Erik; Unutmaz, Derya; Kondziolka, Douglas
ISSN: 1522-8517
CID: 4688222

Initial Experience in MRI-Based Brain Metastases Detection Using Deep Learning [Meeting Abstract]

Teruel, J.; Bernstein, K.; Galavis, P.; Spuhler, K.; Silverman, J.; Kondziolka, D.; Osterman, K.
ISSN: 0094-2405
CID: 5320872

An International Radiosurgery Research Foundation Multicenter Retrospective Study of Gamma Ventral Capsulotomy for Obsessive Compulsive Disorder

Gupta, Amitabh; Shepard, Matthew J; Xu, Zhiyuan; Maiti, Tanmoy; Martinez-Moreno, Nuria; Silverman, Joshua; Iorio-Morin, Christian; Martinez-Alvarez, Roberto; Barnett, Gene; Mathieu, David; Borghei-Razavi, Hamid; Kondziolka, Douglas; Sheehan, Jason P
BACKGROUND:Obsessive compulsive disorder (OCD) across its full spectrum of severity is a psychiatric illness affecting ∼2% to 3% of the general population and results in significant functional impairment. There are few large patient series regarding Gamma ventral capsulotomy (GVC). OBJECTIVE:To evaluate clinical outcomes of severe medically refractory OCD treated with GVC. METHODS:This is an international, multicenter, retrospective cohort study. Forty patients with pre-GVC Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores ≥ 24 (indicating severe OCD) were included. GVC was performed with 1 or 2 isocenters with a median maximum dose of 135 Gy (range, 120-180 Gy). Patients were deemed "responders" to GVC if there was ≥35% reduction of follow-up Y-BOCS scores, and considered in remission if their Y-BOCS scores were ≤16. The median follow-up was 36 mo (range, 6-96 mo). RESULTS:The median pre-SRS Y-BOCS score was 35 (range, 24-40). Eighteen patients (45%) were considered "responders," and 16 (40%) of them were in remission at their last follow-up. Nineteen patients (47.5%) remained stable with Y-BOCS of 33 (range, 26-36) following GVC, whereas 3 patients (7.5%) experienced worsening in Y-BOCS scores. Patients treated with 2 isocenters were more likely to have improvement in Y-BOCS score at 3 and 5 yr (P < .0005). Ten patients (25%) experienced post-GVC mood disturbance and neurological complications in 3 patients (7.5%). One patient developed radiation necrosis with edema that improved with steroids. CONCLUSION/CONCLUSIONS:GVC serves as a reasonable treatment strategy for severe medical refractory OCD. Patients treated with 2 isocenters were more likely to have substantial improvement in OCD.
PMID: 30476294
ISSN: 1524-4040
CID: 4246062