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Hematologic Malignancies: … a Guide to the ILROG Guidelines

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Hematologic Malignancies: … a Guide to the ILROG Guidelines Hematologic Malignancies: … A Guide to the ILROG Guidelines John P. Plastaras, MD, PhD Associate Professor February 27, 2020 Disclosures Steering Committee of ILROG, and chair the Education Committee Co-chair of the Lymphoma Committee for the American Board of Radiology ASTRO Scientific Committee (Heme, Vice-Chair) My wife is on ASTRO Board of Directors, ACGME, RRC I am receiving support from Merck (free drug) for a clinical trial we are doing at Penn Unfortunately, no financial disclosures 2 Outline What ILROG guidelines are out there? Solitary Plasmacytoma and Multiple Myeloma Low-Grade Lymphomas Hodgkin Lymphoma Insights into “Involved Site” Radiotherapy (ISRT) Treating the Mediastinum DLBCL 3 Who is making guidelines currently? National Comprehensive Cancer Network (NCCN) European Society for Medical Oncology (ESMO) Children’s Oncology Group (COG) American Radium Society (ARS) adopted the Appropriateness Criteria program from the American College of Radiology (ACR) International Lymphoma Radiation Oncology Group (ILROG) 4 ESMO Guidelines: Medical Oncology 5 ESMO Guidelines: Hematologic Diseases Waldenstrom's macroglobulinaemia Chronic myeloid leukaemia Newly diagnosed and relapsed mantle cell lymphoma Multiple myeloma Newly diagnosed and relapsed follicular lymphoma Extranodal diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma Acute lymphoblastic leukaemia Peripheral T-cell lymphomas Diffuse large B cell lymphoma Chronic lymphocytic leukaemia Hairy cell leukaemia Philadelphia chromosome-negative chronic myeloproliferative neoplasms Myelodysplastic syndromes Hodgkin lymphoma Primary cutaneous lymphoma Acute myeloblastic leukaemia in adult patients Gastric marginal zone lymphoma of MALT type 6 NCCN Guidelines for Hematologic Diseases Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Chronic Myeloid Leukemia Hairy Cell Leukemia Hodgkin lymphoma Multiple Myeloma Waldenström's Macroglobulinemia / Lymphoplasmacytic Lymphoma Myelodysplastic Syndromes Myeloproliferative Neoplasms B-cell Lymphomas Primary Cutaneous Lymphomas T-Cell Lymphomas 7 Guidelines for Supportive Care ESMO: • Chemotherapy and radiotherapy-induced nausea and vomiting • Oral and gastrointestinal mucosal injury • Management of refractory symptoms at the end of life and the use of palliative sedation • Advanced care planning in palliative care • Bone health in cancer patients • Cancer, fertility and pregnancy • Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy NCCN: • Survivorship • Palliative Care • others 8 Current ILROG Guidelines 2014: 2020: • Nodal non-Hodgkin lymphoma • ISRT Mini-Atlas • Hodgkin lymphoma • “Making Every Single Gray Count: Involved 2015: Site Radiation • Primary cutaneous lymphomas Therapy Delineation • Extranodal lymphomas Guidelines for • Pediatric Hodgkin lymphoma Hematological Malignancies” 2018: • Not exactly a • Lymphoblastic Lymphoma guideline, but a • Central Nervous System Leukemia supplementary • Extramedullary Leukemia/Chloroma resource • Total Body Irradiation • Solitary Plasmacytoma and Multiple Myeloma • Relapsed/Refractory Hodgkin Lymphoma • Relapsed/Refractory Diffuse Large B-Cell Lymphoma • Proton therapy for adults with mediastinal lymphomas 2019: • Optimal use of imaging 9 ILROG.org Easy Links to All the Guidelines Major Limitation of ILROG Guidelines: No current mechanism to maintain “evergreen” status, so they are aging quickly. 10 Plasma Cell Diseases: Picking Dose 61 M with newly diagnosed multiple 62 M with solitary plasmacytoma of the myeloma with a path comp fx at T11. nasopharyngeal wall, < 1 cm, resected T9 infiltrated as well. Back pain. Treatment Approach? 2.5 Gy x 8 = 20 Gy 1.8 Gy x 22 = 39.6 Gy 11 Plasma Cell Disease Guidelines Solitary BONY plasmacytomas: • SBPs <5 cm: total dose 35 to 40 Gy – for small SBPs it is acceptable to prescribe 35 Gy, which has differed from NCCN • SBPs >/= 5 cm: total dose 40 to 50 Gy Solitary EXTRAMEDULLARY plasmacytomas • SEPs: total dose 40 to 50 Gy (if small, well-defined, or post-excision with positive margins, 40 Gy is acceptable.) 12 Myeloma Palliation Doses: For bony sites, where the goal is limited to symptom relief: 8-30 Gy (8 Gy x 1, 20 Gy in 5, 30 Gy in 10). • 8 Gy x1 preferred for bone disease with poor predicted survival • 20 to 30 Gy in 10 to 15 preferred RT volumes are large or retreatment For epidural disease with spinal cord compression, or bulky mass, when durable local control is desired: 30 Gy in 10 to 15 • consider glucocorticoids to prevent pain flare Trend: lowered doses overall to mitigate marrow toxicity • Active trial (Leslie Ballas is PI) for 2 Gy x 2. • 2.5 x 10 for cord compression? • 2.5 Gy x 8, 4 Gy x 5, 8 Gy x 1. • “New Paradigm for Radiation in Multiple Myeloma: lower yet effective dose to avoid radiation toxicity.” Elhammali A, et al. Haematologica. 2020 Jan 9. 13 Limited Stage Low Grade Lymphomas 31 M with left submandibular gland mass, FNA showed “may be compatible with a CD5+ mature B Cell neoplasm” Underwent TORS excision, piecemeal resection (3 chunks). Left him with speech defect, tongue and facial numbness, but a diagnosis of marginal zone lymphoma. Margins? Treatment Approach? 14 ISRT Volumes Without Chemo? “…in clinical situations that require RT as the primary modality…the CTV should be more generous in this clinical situation and also encompass lymph nodes in the vicinity that, although of normal size, might contain microscopic disease that will not be treated when no chemotherapy is given.” RT Alone is used with CURATIVE intent in: • Stage I/II follicular lymphoma • Stage IE marginal zone lymphoma • Stage I/II Nodular Lymphocyte Predominant Hodgkin Lymphoma • Relapsed/refractory HL or NHL 15 ISRT with RT Alone: How Much Margin? British Columbia retrospective of limited stage follicular lymphoma defined “Involved Site” RT as 5 cm margin or less • Adjust according to what toxicities worry you • I will add 2-5 cm of nodal volume depending on what is adjacent (e.g. parotid) Bonus planning tip: • Bone marrow is the most important OAR given future systemic therapies once these patients relapse and need treatment 16 Non-Nodal NHL: Extranodal and Skin pCNS, Orbital, Head & Neck (incl thyroid), NK/T-cell, Breast, Lung, Testicular, bone, abdomen/Pelvis, bowel 17 Dose Considerations for Indolent NHL Indolent nodal lymphomas, stage I/II with curative intent: • 24-30 Gy in 12-15 fx Marginal zone lymphomas with curative intent: • Salivary: 24 Gy • Gastric: 30 Gy (but maybe 24 Gy?) • Orbit: 24 Gy (but maybe 4 Gy?) • Other sites (thyroid, cutaneous, pulmonary): 24-30 Gy Advanced stage or palliative intent indolent B-cell NHL: • 2 Gy x 2, but realize that local control may not be as durable Palliation of cutaneous T-cell lymphoma: • 4 Gy x 2 or 8 Gy x 1 for localized CTCL/MF • 12 Gy for total skin electron treatment 18 Basics of Hodgkin Lymphoma Treatment Early stage, favorable: EORTC H10 Style: • ABVD x 2 + 20 Gy IFRT (HD10) - 2 vs. 3 sites of disease can be F Early stage, unfavorable: - ABVD x 3 for F • ABVD x 4 + 30 Gy IFRT (HD11) - 30 Gy regardless U/F Advanced stage (IIB bulky, III/IV): - BEACOPP escalation for DS3-4 • ABVD x 6 (or BEACOPP in Europe) after PET2 • RT for partial response, bulky disease Relapsed/refractory: • 2nd line chemo +/- RT +/- transplant • Brentuximab (CD30 ADC) and PD1 inhibitors Palliation 19 Relevant Guidelines: Hodgkin Lymphoma 2019 20 Early Stage Mediastinal Hodgkin 25-year old woman received ABVD x 4 for an unfavorable risk, Stage IIA classic Hodgkin lymphoma of the mediastinum. Pre-chemotherapy PET/CT (fused to planning CT), in DIBH What ISRT Volume would you use? Post Chemo Mass 21 A B C D 22 ISRT with Combined Modality Treatment Contour the post-chemotherapy tissue volume, which contained the initially involved lymphoma tissue, taking into account tumor shrinkage, respecting normal structures that were never involved by lymphoma (lungs, chest wall, muscles, esophagus) Be a bit more generous when in doubt Connect CTV’s when nodal volumes are less than 5 cm apart 23 Minimizing Dose to OARs: Mediastinum 21 F with unfavorable risk classic Hodgkin lymphoma (per GHSG criteria – 3 sites of disease, non-bulky, ESR <50, no extranodal sites). Upper mediastinum and bilateral SCV. • ABVD x 2 → Deauville (5PS) 2. AVD x 2 more (4 cycles total) Treatment Approach? Free Breathing Deep Inspiratory Breath Hold Decreases dose to lungs and heart Requires confirmatory method to ensure breath hold position is reproducible 24 DIBH and Protons: Which has more value? Rechner LA et al. Radiother Oncol. 2017 Oct;125(1):41-47. Life years lost attributable to late effects after radiotherapy for early stage Hodgkin lymphoma: The impact of proton therapy and/or deep inspiration breath hold. 25 Minimizing Dose to OARs: Mediastinum 21 F with unfavorable risk classic Hodgkin lymphoma (per GHSG criteria – 3 sites of disease, non-bulky, ESR <50, no extranodal sites) • ABVD x 2 → Deauville (5PS) 2. AVD x 2 more (4 cycles total) Deep breath hold? 3D? IMRT? Proton? Dose constraints for substructures? 26 27 New Era: Stricter Dose Requirements Continued controversial role of RT in combination with chemo, so pressure is on to make RT safe Era of ISRT has allowed very conformal techniques to prioritize certain OAR’s over others Many new technological options to achieve lower dose constraints • 3D, IMRT (fixed/VMAT), protons • Positioning: special angle
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