Publications by authors named "Sunjay Shah"

7 Publications

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Potential Clinical Significance of Overall Targeting Accuracy and Motion Management in the Treatment of Tumors That Move With Respiration: Lessons Learnt From a Quarter Century of Stereotactic Body Radiotherapy From Dose Response Models.

Front Oncol 2020 9;10:591430. Epub 2021 Feb 9.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, United States.

Objective: To determine the long-term normal tissue complication probability with stereotactic body radiation therapy (SBRT) treatments for targets that move with respiration and its relation with the type of respiratory motion management (tracking . compression or gating).

Methods: A PubMed search was performed for identifying literature regarding dose, volume, fractionation, and toxicity (grade 3 or higher) for SBRT treatments for tumors which move with respiration. From the identified papers logistic or probit dose-response models were fitted to the data using the maximum-likelihood technique and confidence intervals were based on the profile-likelihood method in the dose-volume histogram (DVH) Evaluator.

Results: Pooled logistic and probit models for grade 3 or higher toxicity for aorta, chest wall, duodenum, and small bowel suggest a significant difference when live motion tracking was used for targeting tumors with move with respiration which was on the average 10 times lower, in the high dose range.

Conclusion: Live respiratory motion management appears to have a better toxicity outcome when treating targets which move with respiration with very steep peripheral dose gradients. This analysis is however limited by sparsity of rigorous data due to poor reporting in the literature.
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http://dx.doi.org/10.3389/fonc.2020.591430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900559PMC
February 2021

Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001.

J Clin Oncol 2020 04 14;38(10):1019-1029. Epub 2020 Feb 14.

Vanderbilt University Medical Center, Ingram Cancer Center, Nashville, TN.

Purpose: Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition.

Methods: This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden.

Results: Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% 40.4%; = .01) and learning and memory at 6 months (11.5% 24.7% [ = .049] and 16.4% 33.3% [ = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue ( = .04), less difficulty with remembering things ( = .01), and less difficulty with speaking ( = .049) and using imputed data, less interference of neurologic symptoms in daily activities ( = .008) and fewer cognitive symptoms ( = .01).

Conclusion: HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.
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http://dx.doi.org/10.1200/JCO.19.02767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106984PMC
April 2020

Update on Radiotherapy for Central Nervous System Malignancies.

Surg Oncol Clin N Am 2017 07 11;26(3):347-355. Epub 2017 May 11.

Department of Radiation Oncology, Christiana Care, 4701 Ogletown-Stanton Rd, Newark, DE 19713, USA.

Malignancies arising from the central nervous system are rare. Brain metastases, in contrast, are perhaps the most common neurologic complication of cancer. Radiotherapy, as part of combined modality therapy, continues to evolve with the advancement of stereotactic radiosurgery indications, the addition of new technologies, such as alternating electric field therapy, and mounting advances in the complex biology of these entities. The explosion of new clinical trials combined with newly discovered molecular markers suggest the beginning of a paradigm shift in the management of these challenging malignancies that will allow for future risk-stratification strategies.
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http://dx.doi.org/10.1016/j.soc.2017.01.003DOI Listing
July 2017

Adult patients with supratentorial pilocytic astrocytoma: long-term follow-up of prospective multicenter clinical trial NCCTG-867251 (Alliance).

Neurooncol Pract 2015 Dec 6;2(4):199-204. Epub 2015 Aug 6.

Department of Radiation Oncology , The University of Texas MD Anderson Cancer Center , 1515 Holcombe Blvd, Unit 97, Houston, TX 77030 (P.D.B.); Department of Radiation Oncology , Mayo Clinic , 200 SW 1st St, Rochester, MN 55905 (P.D.B.); Alliance Statistics and Data Center, Department of Health Sciences Research , Mayo Clinic , 200 SW 1st St, Rochester, MN 55905 (S.K.A., X.W.C); Department of Neurology , Mayo Clinic , 200 SW 1st St, Rochester, MN 55905 (B.P.O.); Division of Anatomic Pathology , Mayo Clinic , 200 SW 1st St, Rochester, MN 55905 (C.G.); Department of Medical Oncology , Mayo Clinic , 200 SW 1st St, Rochester, MN 55905 (E.G., J.C.B.); Delaware/Christiana Care CCOP , 4701 Ogletown-Stanton Rd Ste 1109, Newark, DE 19713 (S.A.S.); Department of Radiation Oncology , Rush University Medical Center , 500 S Paulina St Atrium Bldg Ground Floor, Chicago, IL 60612 (R.A.A.); Department of Radiation Oncology , Emory University School of Medicine , 1365 Clifton Rd NE Ste A-1358, Atlanta, GA 30322 (W.J.C.); Department of Radiation Oncology , Wake Forest University Medical Center , 2000 W. First St. Ste 101, Winston-Salem, NC 27104 (E.G.S.).

Background: Pilocytic astrocytoma is a rare tumor in adults. This report is of a prospective clinical trial with long-term follow-up.

Methods: Between 1986 and 1994, 20 eligible adults with supratentorial pilocytic astrocytomas were enrolled in a prospective intergroup trial of radiotherapy (RT) after biopsy (3 patients) or observation after gross (11 patients) or subtotal (6 patients) resection.

Results: At the time of analysis (median follow-up, 20.8 years), 2 patients (10%) have died and 18 patients (90%) are alive. Neurologic and cognitive function were stable or improved over time for the majority of patients. No toxic effects of treatment or malignant transformations have been recorded at last follow-up. For the entire cohort the 20-year time to progression and overall survival rates are 95% and 90% respectively. The cause of death (2.2 and 16.1 years after enrollment) in both patients was unrelated to tumor although both were biopsy-only patients. One subtotally resected tumor progressed 1 month after enrollment requiring injection into an enlarging cyst. Because of further progression this patient required RT 18 months later. This patient is alive without evidence of progression 18 years after RT.

Conclusion: The long-term follow-up results of this prospective trial confirm that adults with pilocytic astrocytomas have a favorable prognosis with regard to survival and neurologic function. Close observation is recommended for adults with pilocytic astrocytomas, reserving RT for salvage, as the majority remain stable after gross or subtotal resection and no adjuvant therapy.
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http://dx.doi.org/10.1093/nop/npv031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669035PMC
December 2015

Phase II double-blind placebo-controlled randomized study of armodafinil for brain radiation-induced fatigue.

Neuro Oncol 2015 Oct 12;17(10):1393-401. Epub 2015 May 12.

Department of Radiation Oncology, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, North Carolina (B.R.P., E.G.S., M.D.C.); Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina (L.L., D.C.); Department of Medical Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (G.J.L.); Via Christi Cancer Center, Witchita, Kansas (D.B.); Greenville Health System Cancer Institute, Greenville, South Carolina (D.G.); Spartanburg Regional Healthcare System, Spartanburg, South Carolina (D.C.M.); Hofstra Northshore-LIJ School of Medicine, New Hyde Park, New York (S.R.S.); Christiana Care CCOP, Newark, Delaware (S.S.); Wake Forest University Department of Geriatric Medicine, Memory Assessment Clinic Counseling Center, Winston-Salem, North Carolina (E.G.S.); Department of Medicine, Ohio State University, Columbus, Ohio (M.J.N.); Department of Psychiatry, Wake Forest School of Medicine, Winston-Salem, North Carolina (S.R.R.).

Background: Common acute-term side effects of brain radiotherapy (RT) include fatigue, drowsiness, decreased physical functioning, and decreased quality of life (QOL). We hypothesized that armodafinil (a wakefulness-promoting drug known to reduce fatigue and increase cognitive function in breast cancer patients receiving chemotherapy) would result in reduced fatigue and sleepiness for patients receiving brain RT.

Methods: A phase II, multi-institutional, placebo-controlled randomized trial assessed feasibility of armodafinil 150 mg/day in participants receiving brain RT, from whom we obtained estimates of variability for fatigue, sleepiness, QOL, cognitive function, and treatment effect.

Results: From September 20, 2010, to October 20, 2012, 54 participants enrolled with 80% retention and 94% self-reported compliance. There were no grade 4-5 toxicities, and the incidence of grade 2-3 toxicities was similar between treatment arms, the most common of which were anxiety and nausea (15%), headaches (19%), and insomnia (20%). There were no statistically significant differences in end-RT or 4 week post-RT outcomes between armodafinil and placebo in any outcomes (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, Brief Fatigue Inventory, Epworth Sleepiness Scale, FACT-Brain, and FACIT-cognitive function). However, in participants with more baseline fatigue, those treated with armodafinil did better than those who received the placebo on the end-RT assessments for several outcomes.

Conclusion: Armodafinil 150 mg/day was well tolerated in primary brain tumor patients undergoing RT with good compliance. While there was no overall significant effect on fatigue, those with greater baseline fatigue experienced improved QOL and reduced fatigue when using armodafinil. These data suggest that a prospective, phase III randomized trial is warranted for patients with greater baseline fatigue.
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http://dx.doi.org/10.1093/neuonc/nov084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578583PMC
October 2015

Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial.

J Clin Oncol 2014 Dec 27;32(34):3810-6. Epub 2014 Oct 27.

Vinai Gondi, Cadence Brain Tumor Center and CDH Proton Center, Warrenville, IL; Vinai Gondi and Howard Rowley, University of Wisconsin School of Medicine and Public Health, Madison, WI; Stephanie L. Pugh, Radiation Therapy Oncology Group Statistical Center; Wenyin Shi, Thomas Jefferson University Hospital, Philadelphia; Albert DeNittis, Lankenau Medical Center, Main Line Community Clinical Oncology Program (CCOP), Wynnewood; Andre A. Konski, Chester County Hospital, West Chester; Wolfgang A. Tome, Montefiore Medical Center and Albert Einstein College of Medicine, Yeshiva University, Bronx, NY; Chip Caine, Intermountain Medical Center and University of Phoenix, Salt Lake City, UT; Ben Corn and Andrew Kanner, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Vijayananda Kundapur, Saskatoon Cancer Centre, Saskatoon, Saskatchewan; Jeffrey N. Greenspoon, McMaster University-Hamilton, Hamilton; Glenn S. Bauman, London Regional Cancer Program, London, Ontario, Canada; Sunjay Shah, Christiana Care Health Services CCOP, Newark, DE; Merideth Wendland, US Oncology-Willamette Valley Cancer Institute, Eugene, OR; Lisa Kachnic, Boston Medical Center Minority-Based CCOP, Boston, MA; and Minesh P. Mehta, University of Maryland School of Medicine, Baltimore, MD.

Purpose: Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance.

Patients And Methods: Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05.

Results: Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, -4.7% to 18.7%), significantly lower in comparison with the historical control (P < .001). No decline in QOL scores was observed. Two grade 3 toxicities and no grade 4 to 5 toxicities were reported. Median survival was 6.8 months.

Conclusion: Conformal avoidance of the hippocampus during WBRT is associated with preservation of memory and QOL as compared with historical series.
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http://dx.doi.org/10.1200/JCO.2014.57.2909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239303PMC
December 2014

A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320.

Int J Radiat Oncol Biol Phys 2013 Apr 4;85(5):1312-8. Epub 2013 Feb 4.

Metro MN CCOP, Minneapolis, Minnesota, USA.

Background: A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS.

Methods And Materials: NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy × 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m(2)/day × 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m(2)/day × 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS.

Results: After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001).

Conclusion: The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.
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http://dx.doi.org/10.1016/j.ijrobp.2012.11.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740376PMC
April 2013