Brief Introduction
Dr. Anand Mahadevan is Director of Stereotactic Radiation and Co-Lead of the GI Cancer Disease Group at NYU Perlmutter Cancer Center, with an academic appointment as Professor of Radiation Oncology at NYU Grossman School of Medicine. Trained in surgery and radiation oncology in India and the UK (FRCS, FRCR) and fellowship-trained at the Harvard Joint Center for Radiation Therapy, he previously served as System Director and Chairman of Radiation Oncology at Geisinger Health System and as Associate Professor at Harvard Medical School / Beth Israel Deaconess Medical Center. He is internationally recognized for pioneering stereotactic body radiotherapy (SBRT) techniques — particularly for pancreatic and liver cancers — and has authored over 80 peer-reviewed publications.
Specialty
- Stereotactic Body Radiotherapy (SBRT) and Stereotactic Radiosurgery (SRS)
- GI malignancies: pancreatic, liver, and hepatobiliary cancer
- Reirradiation and adaptive radiotherapy
- Global oncology / radiotherapy capacity-building
Education
- Board Certified, American Board of Radiology, 2004 (recertified 2014)
- Radiation Oncology Fellowship, Harvard Joint Center for Radiation Therapy, Boston, MA, 2003
- FRCR, Royal College of Radiologists, UK, 1998
- FRCS, Royal College of Surgeons, UK, 1997
- Master of Surgery, Pondicherry University, India, 1992
- MBBS, Madras Medical College, Chennai, India, 1988
Experience
- 2022 – Present: Director of Stereotactic Radiation & Co-Lead, GI Cancer Disease Group, NYU Perlmutter Cancer Center
- 2022 – Present: Professor of Radiation Oncology, NYU Grossman School of Medicine
- 2017 – 2022: System Director, Professor & Chairman of Radiation Oncology, Geisinger Health System
- 2011 – 2016: Associate Professor, Harvard Medical School; Director, Stereotactic Radiation, Beth Israel Deaconess Medical Center
- 2003 – 2010: Instructor, Harvard Medical School; Clinical Fellow, Harvard Joint Center for Radiation Therapy
Professional Leadership & Service
- Past President & Chairman of the Board, The Radiosurgery Society (President 2013–2015, Chairman 2015–2017)
- Founding Member, Ibero-Latin American Radiosurgery Society
- Member, International Committee, ASTRO (2023–present)
- Deputy Editor, Cureus — Electronic Medical Journal (2015–present)
- Expert Peer Reviewer: Int J Radiat Oncol Biol Phys, Head & Neck, Cancer Medicine
- Grant Reviewer: Dutch Cancer Society; Cancer Research Council, UK
Grants & Funding
- 2022: NYU Radiation Oncology Seed Grant — Detection of Volatile Organic Compounds in Aerodigestive Cancers
- 2018 – 2022: NCI NCORP Grant, Co-PI — Geisinger Cancer Institute
- 2015: Harvard Joint Center for Radiation Therapy Foundation Grant, Sole PI — Danger Signal Modulation in Radio-Immunotherapy
- 2008: Cyberknife Society Registry Grant, Sole PI
Selected Publications
- Mahadevan A, Moningi S, Grimm J, et al. Maximizing Tumor Control and Limiting Complications With Stereotactic Body Radiation Therapy for Pancreatic Cancer. Int J Radiat Oncol Biol Phys. 2021;110(1):206–216.
- Mahadevan A, Miksad R, Goldstein M, et al. Induction Gemcitabine and Stereotactic Body Radiotherapy for Locally Advanced Nonmetastatic Pancreas Cancer. Int J Radiat Oncol Biol Phys. 2011;81(4):e615–e622.
- Mahadevan A, Goldstein M, Jain S, et al. Stereotactic Body Radiotherapy and Gemcitabine for Locally Advanced Pancreas Cancer. Int J Radiat Oncol Biol Phys. 2010;78(3):735–742.
BACKGROUND:
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a 5-year overall survival under 13%. Locally advanced pancreatic cancer (LAPC) accounts for 30–40% of presentations and has historically represented an area of therapeutic futility for radiotherapy (RT). The failure of the Alliance A021501 trial — largely attributable to RT quality deficiencies and institutional heterogeneity — reinforced a misconception that RT adds little to systemic therapy. This talk argues that the failure was one of dose and precision, not modality, and that three converging advances now define a new paradigm: image-guided dose escalation, biologically rationalized fractionation, and biology-driven patient selection.
DISCUSSION:
Precision — MR-Guided Adaptive RT: MR-Linac platforms (ViewRay MRIdian 0.35T; Elekta Unity 1.5T) provide diagnostic-quality real-time MRI during beam delivery, enabling direct tumor tracking and gating at PTV margins of 3–5 mm versus 8–15 mm with conventional CBCT. Daily Adapt-to-Shape (ATS) re-optimization reduces duodenal constraint violations from ~40% to <5% of fractions. The SMART phase II trial (Chuong et al., Lancet Gastroenterol 2023) demonstrated MR-guided SBRT at 40–50 Gy/5 fx yields 1-year local control of 85%, median OS of 17.5 months, and grade ≥3 GI toxicity <5% — outcomes that substantially reframe expectations in unresectable LAPC.
Dose Intensity — BED10 Threshold and Ablative Intent: Dose-response analyses in LAPC identify a BED₁₀ inflection point of ~70–100 Gy beyond which local control gains become clinically meaningful. Conventional fractionation (45–54 Gy at 1.8 Gy/fx; BED₁₀ ~57–65 Gy) consistently underperforms this threshold. NRG-GI011 (LAP100; NCT06958328) is the first phase III trial testing dose-escalated RT (28 fx conventional or 5 fx ablative) in biochemically selected LAPC — requiring CA 19-9 response or normalization after induction chemotherapy. Complementing photon-based approaches, an investigational Phase I/II protocol (NYU Langone Health / Taipei Veterans General Hospital; PI: Mahadevan) is systematically escalating single-fraction carbon ion RT (CIRT) from 10 to 25 GyRBE as an upfront GTV boost, exploiting the Bragg peak and RBE of 2–3× for radioresistant PDAC cells.
Biology — Patient Selection and the Oligometastatic Frontier: CA 19-9 kinetics after induction chemotherapy serve as a practical surrogate for systemic control and identify patients most likely to benefit from local intensification. The EXTEND randomized phase II basket trial (Ludmir et al., JCO 2024) demonstrated a PFS hazard ratio of 0.43 (95% CI 0.20–0.94; p=0.03) favoring metastasis-directed therapy (MDT) in the pancreatic cohort. EXPAND (NCT06593431; PI: Ludmir), a phase III trial enrolling patients with ≤5 metastatic sites to MDT plus systemic therapy versus systemic therapy alone, now tests whether local consolidation can delay systemic progression in oligometastatic PDAC, with translational correlatives including ctDNA and peripheral immune profiling.
CLINICAL IMPLICATIONS:
These three pillars are synergistic. Precision delivery enables dose escalation that would otherwise violate OAR constraints; ablative doses are most impactful in patients whose systemic disease is controlled; and biological characterization of the tumor informs both local and systemic sequencing. The emerging paradigm positions LAPC management as a precision oncology problem: modern induction chemotherapy followed by biomarker-stratified, MR-guided ablative RT — with active enrollment in NRG-GI011, EXPAND, and investigational CIRT protocols — alongside prospective collection of translational correlatives to decode the determinants of durable local control. Radiation oncologists, medical oncologists, and surgeons must be conversant with this landscape to identify candidates for enrollment, optimize multidisciplinary sequencing, and appropriately counsel patients on the evolving role of local therapy intensity in PDAC.