1 / 38

Radiotherapy in Pediatric Hodgkin Lymphoma

Radiotherapy in Pediatric Hodgkin Lymphoma. Tasha Mcdonald , MD Department of Radiation Medicine June 18, 2008. OVERVIEW. Case presentation Risk-groups Early/favorable risk Unfavorable risk Toxicities Future directions. Case presentation.

sutton
Télécharger la présentation

Radiotherapy in Pediatric Hodgkin Lymphoma

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Radiotherapy in Pediatric Hodgkin Lymphoma Tasha Mcdonald, MD Department of Radiation Medicine June 18, 2008

  2. OVERVIEW • Case presentation • Risk-groups • Early/favorable risk • Unfavorable risk • Toxicities • Future directions

  3. Case presentation • L.S.: 18 yo girl presented in 1/08 with 2 months of fatigue, fever, chills, sweats and 10 lb weight loss • Developed difficulty swallowing and enlarged neck nodes and SOB when lying down • On exam: palpable cervical LAD • Underwent US of the neck 1/3/08: irregular 2.3x2.3 x3.4cm nodule in right neck. • LN biopsy on 1/4/08 at Kaiser: nodular sclerosing Hodgkin disease

  4. Outside PET 1/22/08

  5. Outside CT Chest 1/22/08

  6. Case presentation • Stage IIB NSHD • No subdiaphragmatic disease • Bone marrow bx was negative • Started on COG AHOD 0031 protocol and received 2 cycles of ABVE-PC • Re-imaged on 3/7/08 and determined to be a slow early responder per protocol

  7. OHSU PET 3/7/08

  8. OHSU CT Chest 3/7/08

  9. Case presentation • Randomized to the augmented therapy arm to receive DECA x 2 followed by 2 more cycles of ABVE-PC • CT and PET on 4/28/08 (before the ABVE-PC) showed a 66% reduction tumor size • Finished chemotherapy and scheduled to start RT on 5/23/08.

  10. OHSU PET 4/28/08

  11. OHSU CT Chest 4/28/08

  12. RT Guidelines for AHOD0031 Protocol • IFRT for all pts except those who achieve rapid early response after 2 cycles of chemo AND CR after 4 cycles of chemo. • IFRT with 21 Gy in 14 fxs given with AP:PA fields • RT to start w/in 4 weeks of last chemo cycle • GTV = LN>1.5 cm; CTV = anatomical compartment of LN; PTV = 1.0 cm margin to CTV • RT fields adapted to response of chemo are not permitted except if treating the mediastinum

  13. RT Plan evaluation

  14. RT field with pre-chemo volume shown

  15. RT AP field with post-chemo volume

  16. History • Treated with full-dose (35-45 Gy) extended-field RT w/ excellent disease control but significant late toxicity • Chemotherapy (MOPP or ABVD) was shown to salvage relapsed disease after RT and improve DFS when used as part of initial therapy1,2 • Low-dose RT (15-25 Gy) following chemotherapy was shown to produce excellent EFS and OS3-5 • Chemotherapy followed by low-dose RT became the standard therapy • The most recent trials use risk-adapted and/or response-adapted therapy

  17. Risk groups • Division into groups based on factors shown to influence outcome • Histology • Clinical stage • B symptoms • Bulky disease

  18. Risk groups • Prognostic stratification (not uniformly agreed on): • Low-risk/favorable: Stage I or II, no B symptoms, no bulky disease and disease in fewer than 3 nodal regions • Intermediate-risk: Stage IB, IIB (or bulky disease and extranodal involvement) and sometimes IIIA • High-risk: Stage IIIB, IVA/B

  19. Early stage/favorable risk • Goal = limit treatment-related toxicity and maintain success of therapy • Efficacy of various strategies is relatively equivalent • ~90% or better EFS or PFS • ~95% OS • Treatment: 2-4 cycles of chemotherapy +/- involved field RT • Response-adapted approach: Response to the first cycles of chemotherapy determines inclusion of additional chemo or dose of RT

  20. Treatment and outcomes in early stage pediatric Hodgkin disease

  21. Early stage/favorable riskResponse-adapted approach • SDS group study6,7: single arm study; 4 cycles of VAMP followed by IFRT with RT dose determined by response to first 2 cycles • PR (53%): 25 .5 Gy IFRT • CR (47%): 15Gy IFRT • German HD958,9: OPPA or OEPA for two cycles • CR (27%): observation • PR with >75% reduction (53%): 25 Gy IFRT • <75% reduction (~5%): 20-30 Gy IFRT + 5 Gy boost to >50 ml residual • French MDH9010: 4 cycles of VBVP • >70% response (85%): 20 Gy IFRT • <70% response: 1 or 2 more cycles of OPPA and 20 or 40 Gy IFRT • Despite the differences in treatment, all these studies had a EFS or PFS of 93% or better

  22. Early stage/favorable riskExclusion of RT • POG 862511: Laparotomy-staged IA-IIIA disease • 4 cycles of MOPP/ABVD OR 2 cycles of MOPP/ABVD plus 25.5 Gy IFRT • EFS (83% vs 91%) and OS (94% vs 97%) were statistically equivalent • CCG 594212: Clinically staged I-II disease • 4 cycles of COPP/ABV • CRs randomized to observation vs. 21 Gy IFRT • Stopped early after interim analysis indicated superiority of RT arm (EFS 85% vs 93%) but OS was 100% in both arms

  23. Intermediate and advanced stage disease • More intensified regimens with a combination of diverse chemotherapeutic agents • Goal of minimizing treatment-related toxicity is still important but studies that reduced alkylating agents and anthracyclines with limited IFRT lead to decreased EFS13,14 • RT continues to be standard therapy in this risk group (unless on protocol)

  24. Treatment and outcomes in intermediate/advanced stage pediatric Hodgkin disease

  25. Intermediate and advanced stage disease • POG15: 8 cycles of MOPP/ABVD +/- total-nodal irradiation • No diff by intent-to-treat analysis • CCG 52116: 6 cycles MOPP alternating with 6 cycles of ABVD vs 6 cycles of ABVD with 21 Gy extended-field RT • Equivalent outcome • EFS 77% vs 87%, P = .09; OS 84% vs 90%, P=.45 • German HD-958,9: 2 cycles of OPPA or OEPA +2-4 cycles of COPP • >70% reduction in tumor volume: No RT • <70% reduction: IFRT • OS equivalent but EFS with RT =92% vs with chemo alone = 69%

  26. RT Planning • Historical mantle field and total nodal irradiation

  27. RT Fields

  28. IFRT • IFRT requires careful evaluation of pre- and post-chemotherapy volumes • CTV encompasses post-chemo mediastianal width laterally and pre-chemo extent in sup/inf direction • An anterior laryngeal block can be used if it does not shield involved nodes • If the axillae are to be treated humeral head blocks are used • CT based planning allows evaluation of adequate CTV coverage and normal tissue dose

  29. IFRT • Whole-heart irradiation indications: pericardial involvement/invasion • Splenic irradiation is indicated in pts with splenic involvement but renal dose must be limited to mean <10.5 Gy or keep 2/3rds of the kidney to <15 Gy • If the pelvis needs to be treated the ovaries should be relocated and the dose should be limited to <3 Gy • When treating a male, ensure on a daily basis that the scrotum is not in the pelvic field

  30. Late Toxicity of Radiotherapy • Growth abnormalities17 • Bone and soft-tissue hypoplasia in prepubertal children • Thyroid sequela18,19 • Hypothyroidism • Hyperthyroidism • Benign and malignant thyroid nodules • 17% of children treated with RT dose <26 Gy had thyroid abnormalities compared to 78% with >26 Gy

  31. Late Toxicity • Cardiovascular disease20,21 • Atherosclerotic heart disease • Valvular dysfunction • Pericardial disease • Pulmonary toxicity22 • Decrease in pulmonary function tests • Sterility/Infertility: limit dose to ovaries to 3Gy • Increase incidence of secondary cancers23-25 • Late effects study group: 30 yr cumulative incidence of SC = 26.3% in pts dx’ed before age 16 • Breast cancer was most elevated solid cancer

  32. Late Toxicity • Toxicities of higher dose RT are well documented but it is less clear what toxicities will exist with 15-25 Gy bc many toxicities are dose and volume dependent • Second solid cancer risk appears to be dose dependent with patients w/ <23 Gy mediastinal RT with lower risk of developing breast cancer26

  33. Future Directions • Improve the technique of response-adapted therapy • Incorporate functional imaging into evaluating treatment response and RT planning • Improve upon late toxicities AND determine the effects of decreased dose IFRT on late toxicities • Refine risk categories • Improve treatment regimen for high-risk disease

  34. References • Devita VT Jr et al. Combination chemotherapy in the treatment of advanced HD. Ann Intern Med 73: 881-95. 1970 • Bonadonna G et al. Combination chemotherapy of HD with adriamycin, bleomycin,vinblastine,andimidazolevs MOPP. Cancer 36: 252-9, 1975. • Donaldson SS et al. HD: Treatment with low dose radiation and chemotherapy. Front RadiatTherOncol 16: 122-33, 1981. • Hunger SP et al. ABVD/MOPP and low-dose IFRT in pediatric HD. J ClinOncol12:2160-6, 1994. • Weiner MA et al. Intensive chemotherapy and low-dose RT for the treatment of advanced-stage HD in pediatric patients: A POG study. J ClinOncol9: 1591-98, 1991. • Donaldson SS et al. VAMP and low-dose, IFRT for children and adolescents with favorable, early-stage HD: results of a prospective clinical trial. J ClinOncol 20:3081–3087, 2002. • Donaldson SS et al. Final results of a prospective clinical trial with VAMP and low-dose IFRT for children with low-risk HD. J ClinOncol25:332–337, 2007 .

  35. References • Ruhl U et al. Response adapted RT in the treatment of pediatric HD: an interim report at 5 years of the German GPOH-HD 95 trial. IJROBP, 51: 1209–1218, 2001. • Ruhl U et al. Abstract at ASTRO, 46th annual meeting: German GPOH-HD 95 trial: Treatment results and analysis of failures in pediatric HD using combination chemotherapy with and without RT. IJROBP 60:S131, 2004. • Landman-Parker Jet al. Localized childhood HD: response-adapted chemotherapy with etoposide, bleomycin, vinblastine, and prednisone before low-dose RT-results of the French MDH90. J ClinOncol18:1500–1507, 2000. • Kung FH et al. POG 8625: a randomized trial comparing chemotherapy with chemoradiotherapy for children and adolescents with stages I, IIA, IIIA1 HD: a report from the COG. J PediatrHematolOncol 28:362–368, 2006. • Nachman JB et al. Randomized comparison of IFRT and no RT for children with HD who achieve a complete response to chemotherapy. J Clin Oncol 20(18):3765–3771, 2002. • Hudson MM et al. Risk-adapted, combined-modality therapy with VAMP/COP and response-based, IFRT for unfavorable pediatric HD. J ClinOncol22:4541–4550, 2004. • Friedmann AM et al. Treatment of unfavorable childhood HD with VEPA and low-dose, involved-field radiation. J Clin Oncol 20:3088–3094, 2002.

  36. References • Weiner MA et al. Randomized study of intensive MOPP-ABVD with or without low-dose total-nodal RT in the treatment of HD in pediatric patients: a POG study. J ClinOncol15:2769–79, 1997. • Fryer CJ et al. Efficacy and toxicity of 12 courses of ABVD chemotherapy followed by low-dose regional RT in advanced HD in children: a report from the Children’s Cancer Study Group. J ClinOncol8(12):1971–1980, 1990. • Willman KY, Cox RS, Donaldson SS: Radiation induced height impairment in pediatric HD. IJROBP 28(1): 85–92, 1994. • Constine LS ,et al. Thyroid dysfunction after radiotherapy in children with Hodgkin’s disease. Cancer 53:878-883, 1984. • Sklar C, et al. Abnormalities of the thyroid in survivors of HD: Data from the Childhood Cancer Survivor Study. J ClinEndocrinolMetab85:3227-3232, 2000. • Hancock SL, et al. Factors affecting late mortality from heart disease after treatment of Hodgkin’s disease. JAMA 270: 1949-1955, 1993. • Hull MC, et al. Valvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of HD treated with RT. JAMA 290:2831-2837, 2003. • Villani F, et al. Late pulmonary effects in favorable stage I and IIA HD treated with radiotherapy alone. Am J ClinOncol 23:18-21, 2000.

  37. References • Bhatia S et al. Second cancers after pediatric Hodgkin’s disease. J ClinOncol16(7):2570–2572, 1998. • Bhatia S, et al. High risk of subsequent neoplasms continues with extended follow-up of childhood HD: Report from the Late Effects Study Group. J ClinOncol21:4386-4394, 2003. • Metayer C, et al. Second cancers among long-termsurvivors of Hodgkin’s disease diagnosed in childhood and adolescence. J Clin Oncol 18:2435-2443, 2000. • Travis LB,et al. Cumulative absolute breast cancer risk for young women treated for Hodgkin lymphoma. J NatlCancerInst97:1428-1437, 2005.

More Related