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Radiotherapy Lymphomas

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Radiotherapy Lymphomas

  1. 1. Radiotherapy L R di th Lymphomas h Mary Gospodarowicz MD Princess Margaret Hospital University of Toronto, Toronto, Canada
  2. 2. Changing Landscape in Lymphoma • 90% of cases in adults • median age - 64 yrs • 2008 Statistics US Canada • 66 120 new cases 7 000 • 19 160 deaths 3 100 • @ 500 000 people living with lymphoma • 90% B-cell B- • @ 40% DLBCL • 10% T-cell T-
  3. 3. RT in Non-Hodgkin L mphoma Non- Lymphoma • Challenges – Only 4 - 6% of all cancers – Numerous distinct disease entities • Mycosis fungoides • Primary brain lymphoma y yp • Gastric MALT • Burkitt’s – Changing outcomes – Little level 1 evidence to guide practice
  4. 4. Radiation Therapy in Cancer • Local therapy – Proven most effective agent in providing l idi local t l tumour control tl – Proven capable of curing localized disease in most cancers – Compensates for diagnostic ambiguity p g gy • ‘histology agnostic’ – Few contraindications
  5. 5. Radiation Therapy in Cancer • Local therapy • Proven most effective agent in providing local tumour control • Proven capable of curing localized disease in most cancers • Compensates for diagnostic ambiguity • ‘histology agnostic’ histology agnostic • Few contraindications
  6. 6. RT in Lymphomas L mphomas • Objective of RT Obj ti f – Almost always to achieve local control • Outcomes of interest – Pattern of failure • Local control • Overall failure rate – Survival – Toxicity
  7. 7. Stage I&II Follicular Lymphoma 1967-99 1967- Stage I-II I- - 668 pts • Stage I-II RT alone I- - 460 pts – median follow-up ed a follow- oo - 12.5 y s 5 yrs • range - up to 32 yrs • Treatment – IF RT 30-35 Gy 30- • Relapse • distant - 89 % • distant + local - 6% • isolated local relapse - 5%
  8. 8. PMH 1968 – 1999 Stage I-II Follicular Lymphoma RT Alone I- 460 patients
  9. 9. PMH 1968 – 1999 Stage I-II Follicular L St I- F lli l Lymphoma RT Al h Alone No relapse 80 Relapse 70 60 Age 50 40 30 20 0 5 10 15 20 25 30 35 Time to relapse or f ll Ti l follow-up
  10. 10. Stage I-II MZL PMH 1989-2004 MALT 1989 - 2004 • 166 pts treated with RT t t t d ith • median follow-up 7.6 yrs (0.6 – 16.2) follow- • median age 60 yrs (23-93) (23- • F:M=2:1 • stage I 148 (89%) • stage II t 18 (11%)
  11. 11. Stage I-II MZL PMH 1989-2004 Presenting Sites Orbit and adnexa 70 (42%) Skin & soft tissues 4 Salivary gland 28 (17%) Breast 4 Stomach St h 22 (13%) Rectum Rt 1 Thyroid 21 (13%) Meninges 1 Other head & neck* 6 neck Thymus 1 Lung 4 Bladder 4 *nasopharynx - 3, maxillary sinus - 1 larynx - 1, Hypopharynx - 1
  12. 12. Stage I/II MALT lymphoma - Relapse g yp p Stomach/Thyroid (n=43) Relapse 2 yrs: 13/31 (52%) 5 yrs: 25/31 (81%) Other sites (n=123) > 5 yrs: 6/31 (19%) y ( ) 10-year RFR Thyroid 95% Stomach 100% Salivary gland 68% Orbit 67%
  13. 13. Stage I/IIE MALT lymphoma - Survival --- 10 yr CSS - 98% — 10 yr OS - 87% …. 10 yr RFR 77% RFR-
  14. 14. Limited- g mantle- Limited-stage mantle-cell lymphoma yp Leitch et al Annals of Oncology 14: 1555 1561 2003 al. 1555–1561,
  15. 15. Int J Radiat Oncol Biol Phys 65: 1185 91 2006 1185–91,
  16. 16. Localized DLBCL Heterogeneous disease Phenotypic, molecular characteristics Nodal vs. extranodal presentations vs Stage I vs. II (II localized vs.. extensive) B-symptoms LDH Age d A and performance status f tt Comorbidity
  17. 17. Spectrum of Localized DLBL
  18. 18. PMH Experience 1984 -2003 600 patients with stage I-II I- Age 15 - 91 median - 57 yrs Follow- Follow-up 0.4 – 22 yrs y median - 10.1 yrs y Stage I - 317 B-symptoms - 64 Stage II - 283 g Extranodal - 354 Chemo 3/4 courses - 233 Chemo 5/6 courses - 336 median RT dose – 35 Gy pre- pre-rituximab
  19. 19. Overall Survival PMH DLBCL – CMT 1984-2003 1984-
  20. 20. Survival by age PMH DLBCL – CMT 1984-2003 1984-
  21. 21. Probability of Local Relapse PMH DLBCL – CMT 1984-2003 1984-
  22. 22. CHOP non-responders non- p Probability of Death from Lymphoma PMH DLBCL – CMT 1984-2003 1984-
  23. 23. Rituximab Era Rituximab Rit i b gradually i t d d ll introduced t th d to the management of all DLBCL Outcomes improved Role of RT questioned q No level 1 evidence For the benefit of RT For the lack of benefit of RT
  24. 24. Practice Guidelines G id li
  25. 25. T/NK- T/NK-cell Nasal Lymphoma Note: Non-randomized comparison Non randomized RT n=18 CMT n=61 Cheung et al, IJRBOP 2002; 54: 182-90
  26. 26. IELSG Testis Lymphoma Kaplan-Meier survival estimates 1.00 Actuarial risk of contralateral testicular failure by prophylactic scrotal RT (log (l rank t t p=0.0027) k test, 0 0027) 0.75 No scrotal XRT 0.50 0 50 0.25 Prophylactic XRT 0.00 0 10 20 30 PFS
  27. 27. RT - Refractory-Recurrent DLBCL Refractory- Martens et al, IJROBP 64: 1183-7, 2006 1183-
  28. 28. Int J Radiat Oncol Biol Phys, 51:148–155, 2001
  29. 29. Austral Radiol 50:222–7, 2006
  30. 30. RO Practice in Lymphomas • Change in radiation oncology p g gy practice – Target volume rather than nodal region treated – GTV, CTB, PTV defined and treated – Most practice in adjuvant setting • N GTV CTV non-standard No GTV, non- dd – Need to monitor and report RT relevant outcomes • Local control • Patterns of relapse
  31. 31. RT Planning Requires optimal R i ti l pre-chemotherapy imaging
  32. 32. Current Standard • Target - post chemotherapy CTV • Dose and fractionation – 30 – 35 Gy in 15-20 fractions 15- • 3D CRT / IMRT – protect normal tissues • CT planning • Image guidance as required
  33. 33. Role of RT All trials show improved local control Very safe treatment Minimal acute and late severe toxicity Modern techniques – lower acute toxicity Best local therapy cannot improve distant disease control If systemic therapy results in 100% local control – no need for RT
  34. 34. Current contro ersies C rrent controversies •L Localized f lli l l li d follicular lymphoma h – Curable with RT or just very slow natural history hi t • MALT – Role of RT in rare presentations – Need to learn more about the natural history
  35. 35. Current contro ersies C rrent controversies • Localized DLBCL L li d – Is RT needed in R-CHOP era R- • Does it add to the chemotherapy – Must conduct studies that include optimal chemotherapy and ask RT question • Extranodal lymphomas – Differences btwn EN and N presentations
  36. 36. Current contro ersies C rrent controversies • R l of RT i FDG PET era Role f in – Assessment of response to chemotherapy using mid-treatment FDG PET i mid-t t id t – Post chemotherapy PET assessed response as selection factor for RT • Role of RT in PET +ve and PET –ve cases • Patterns of failures in above situations
  37. 37. Future • Biologic imaging g gg • Disease extent • Response p • Selection for adjuvant treatment • Role of precision RT • Molecular disease characteristics • D fi iti of di Definition f disease entities titi • Impact on the management

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