Role of Radiotherapy in Early Hodgkin's Lymphoma (HL)
•Download as PPT, PDF•
1 like•70 views
Deescalation of therapy is becoming the rule of the game in cancer management. Radiotherapy is known to cause serious side effects. Can we avoid using it in early HL.
Recommended
Recommended
More Related Content
What's hot
What's hot (20)
Similar to Role of Radiotherapy in Early Hodgkin's Lymphoma (HL)
Similar to Role of Radiotherapy in Early Hodgkin's Lymphoma (HL) (20)
More from Prof. Shad Salim Akhtar
More from Prof. Shad Salim Akhtar (20)
Recently uploaded
Recently uploaded (20)
Role of Radiotherapy in Early Hodgkin's Lymphoma (HL)
- 1. NO Radiotherapy in Early Stage Classical Hodgkin’s Lymphoma Prof. Shad Salim Akhtar MBBS, MD, MRCP(UK), FRCP (Edin), FICA (USA), FACP(USA) Member AUICC Fellows, ESMO, ASCO Member Breast Cancer Screening Network, NIH USA Overseas Advisor Royal College of Physicians UK Member Global Cancer Control Community UICC Consultant Medical Oncologist Chairman Board of Directors Hakim Sanaullah Cancer Centre Sopore, Kashmir, J & K
- 2. Science is simply common sense at its best…that is, rigidly accurate in observation and merciless to fallacy in logic Thomas H Huxley
- 3. Stage III/IV Stage I/II I/II Bulky, B symptoms I/II Not Bulky, No B symptoms N America Advanced Stage Early stage GHDSG Advanced stage Early stage unfavorable Early stage favorable Early Stage Confusion Younes A: J Clin Oncol 2012; 30:895-6 Some II B with risk factors considered advanced stage Engert A et al: N Engl J Med 2010; 363:640-52 Suppl App
- 5. German HD7 Trial EFRT VS CT+EFRT Engert A et al. J Clin Oncol 2007; 25:3495-3502 FFTF Overall Surv
- 6. EORTC GELA H8 Trial CT + IFRT Better than STLNI Ferme C et al. N Engl J Med 2007;357:1916-27.
- 7. Median age 35 yrs+ 90% pts 16-65 yrs of age 85% Long term survival Treatment related toxicity Balance Benefit vs. Side Effects
- 8. Late Effects of Radiotherapy • Second malignant neoplasm – 26-28% at 25-30 yrs • Fibrosis – Neuromuscular: Neck muscle wasting (neck drop) – Cardiovascular • Cardiac – 2 to 7 fold increase in MI, angina, CHF – Cardiac valve fibrosis, conduction abnormalities – Restrictive cardiomyopathy • Carotid intimal thickening, stenosis, stroke – Lymphedema – Pulmonary & pericardial fibrosis – Brachial plexopathy Straus DJ. J Int Med 2011;270:197-205
- 9. Age 20 yrs 40 yrs 0-9 0.0 0.0 10-14 6.8 34.5 15-19 6.4 36.1 20-24 3.5 29.2 25-29 7.4 17.4 30-35 9.8 27.5 Age at supra-diaphragmatic RT and Cumulative Risk of breast cancer Swerdlow AJ et al: J Clin Oncol 2012; 30:2746-52 Cumulative risk, based on 5002 of 7612 females <36 yrs age (25% <20) at the diagnosis of HL and received supra-diaphragmatic RT in England & Wales 1956-2003
- 10. Morton LS et al. J Clin Oncol 2013; 31:3369-77 2013 Sep 20;31(27):3369-77.
- 11. Hodgson DC et al. J Clin Oncol 2007; 25:1489-97 Long Term Solid Cancer Risk Among 10000, 5 yr Male Survivors of HL in Population Based Cancer Registries of N America & Europe
- 12. Hodgson DC et al. J Clin Oncol 2007; 25:1489-97 Long Term Solid Cancer Risk Among 8000 5 yr Female Survivors of HL- Population Based Registry Data
- 13. Galper SL et al Blood 2011; 117:412-418 Cumulative incidence of cardiac diagnoses and cardiac procedures among 1279 HL patients treated from 1969- 1989 with RT (Dana Farber) Sudden deaths not included
- 14. Cumulative Risk In Early Stage HL Receiving Both RT & CT Armitage JO: NEJM 2010; 363:653
- 15. Engert A et al: N Engl J Med 2010; 363:640-52ç German HD 10 Trial 4 vs 2 ABVD & 30 vs 20 G IFRT
- 16. Site/Type 30Gy IFRT+2 or 4 X ABVD 20Gy IFRT+2 or 4 X ABVD AML/MDS 2 (0.3) 0 NHL 7 (1.2) 8 (1.3) Solid tumors 22 (3.8) 16 (2.7) Total 31 (5.4) 24 (4.1) Engert A et al: N Engl J Med 2010; 363:640-52 Incidence of Second Cancers in GHSG HD 10 Trial F Up 7.5 yrs
- 18. 60% Combined CT & RT
- 23. 405 pts with stage I-IIA non bulky HL Favorable cohort (31%) Unfavorable cohort (69%) Randomize Randomize ABVD X 4-6 ABVD X 4-6STLI ABVD X 2 +STLI Meyer RM et al. N Engl J Med 2012;366:399-408. ABVD Alone vs. RT based therapy in limited stage HL: NCIC CTG/ECOG HD.6 ABVD Only Arm 196 Patients
- 24. ABVD alone RT + - ABVD HR ABVD (95% CI) P Value No 196 203 OS 94 87 0.50(0.25-0.99) 0.04 FFDP 87 92 1.91(0.99-3.69) 0.05 EFS 85 80 0.88(0.54-1.43) 0.60 Meyer RM et al. N Engl J Med 2012;366:399-408.
- 25. Causes of Death, According to Treatment Strategy and Risk Profile. Cause of death ABVD Alone RT +-ABVD Any 12 24 HL 6 4 SMN 4 10 Cardiac events 2 2 Infection 0 3 Others 0 5 Meyer RM et al. N Engl J Med 2012;366:399-408 Causes of Death HD.6 NCIC CTG/ECOG Trial
- 26. GHSG HD10 & HD11 CMT and NCIC HD.6 ABVD Alone for non bulky Stage I-IIA HL PFS OS HD.6 87% 94% HD 10 87% 94% HD 11 84% 94% HD.6 = ABVD X 4-6 12 year FUP HD 10 = ABVD X 2 + IFRT 8 year F UP HD 11 = ABVD X 4 + IFRT 8 year F UP Engert A et al. N Engl J Med 2010; 363:640 Meyer RM et al. NEJM 2012; 366:399 Eich HT et al. J Clin Oncol 2010; 28:4199
- 27. GHSG HD10 & HD11 CMT & NCIC HD.6 ABVD Alone for non bulky Stage I-II A HL • Eligible patients – 2 cycles of ABVD + 20 Gy IFRT on GHSG HD 10 – 4 cycles of ABVD + 30 Gy IFRT on GHSG HD 11 – 4-6 cycles of ABVD alone on NCIC CTG HD.6 • Eligibility of – HD.6 for HD 10/11 (determined by GHSG) – HD 10/11 for HD.6 (determined by NCIC CTG) • Stratification by propensity score – Age, Gender, Stage, ESR, disease sites Hay AE et al. ASH 2012 Abstract 548
- 28. GHSG HD10 & HD11 CMT & NCIC HD.6 ABVD Alone for non bulky Stage I-IIA HL:All Eligible Patients End point HD10/11 N=406 HD.6 N=182 HR PFS 89% 86% 0.71 CR after C2 87% 95% 2.8 Non CR after C2 88% 74% 0.35 OS 95% 95% 1.09 TTP 93% 87% 0.44 Hay AE et al. ASH 2012 Abstract 548 HD10/11 exclusion causes= B symptoms=127; large mediastinal mass=80 14 pts of HD.6 not included in HD10/11, 1 was not assignable
- 29. They strapped the fair young maiden to the table as needles painfully pierced the soft flesh between her tender young toes. As if vivisection were not punishment enough for sins unknown, her spleen is stolen, her liver is assaulted, she is impaled, her skin is repeatedly burned, and her body is filled with poison while she is left to await an uncertain fate. If she still survives she is sprayed with the invisible rays to give her heart aches, pouring wounds and lumps for all times to come. Sounds like something from H.P. Lovecraft, does it not? But indeed, that was the ghost of Hodgkin past. Cheson B: J Clin Oncol 2012; 30:4456
- 30. HD.6 Progression Free Survival 92% vs 87%
- 31. HD.6 Overall Survival 94% vs 87%
- 32. Myeloid leukemia Ovarian tumors • All forms of ionizing radiation are carcinogenic • Tumors of any histology may be induced in a susceptible individual under appropriate conditions • Incidence of some tumors is increased by relatively small amount of radiation Thyroid tumors
- 33. Only dose of RT NOTassociated with increased risk of Cancer Zero Longo DL. J Natl Cancer Inst 2003; 95:928-9
- 34. PLEASE PROTECT THE VICTIM OF OUR SUCCESS A Patient of Early Stage Hodgkin’s Lymphoma Cheson B: J Clin Oncol 2012; 30:4456
- 35. THANKS FOR YOUR ATTENTION
- 36. Schaapveld M et al NEJM 2015;273:2499
- 37. Schaapveld M et al NEJM 2015;273:2499
- 38. Schaapveld M et al NEJM 2015;273:2499
- 39. Schaapveld M et al NEJM 2015;273:2499
- 40. Schaapveld M et al NEJM 2015;273:2499
- 41. Schaapveld M et al NEJM 2015;273:2499
- 43. Borchmann P etal: Nat Rev Clin Oncol 2012;9:450-9
- 44. Changes in RT fields over time. Hodgson D C Hematology 2011;2011:323-329
- 45. p<0.01 EFS HR NS Death due to BC HR NS Metachronous Contralateral BC HR 4.3 Death due to any cause HR 1.9 HL with breast Ca =253 Rxed 1980-2006 Sporadic Breast Ca=741 Elkin EB et al. J Clin Oncol 2011; 29:2466-2473
Editor's Notes
- Quoted by Dan L Longo in his editorial in J Nat Canc Institute
- Tabular List 3. Early, Intermediate and Advanced Stages of Hodgkin Lymphoma On the basis of the Ann Arbor staging criteria, the GHSG subdivides Hodgkin lymphoma patients into the following risk groups: Early stages – Stage IA (involvement of a single lymph node region or a single extra-nodal focus, no B-symptoms ｧ) without risk factors – Stage IB (involvement of a single lymph node region or a single extra-nodal focus, one or more B-symptoms) without risk factors – Stage IIA (involvement of two or more lymph node regions or extra-nodal structures on the same side of the diaphragm, no B-symptoms) without risk factors – Stage IIB (involvement of two or more lymph node regions or extra-nodal structures on the same side of the diaphragm, one or more B-symptoms) without risk factors Intermediate stages – Stage IA or IB and stage IIA with one or more risk factors – Stage IIB, only if the risk factors ‘high ESR’ and/or ‘involvement of ≥ 3 lymph node areas’ are present * Extra-nodal involvement is defined as localized involvement of an extra-lymphatic tissue (by continuous growth from an involved lymph node or in close anatomic relation) that is treatable by irradiation. � Lymph node areas are defined in Tabular List 2 � Please note: The definition of lymph node areas for the definition of risk factors does not correspond to the Ann Arbor definition of lymph node regions. ｧ B-symptoms include: fever with no other explanation, drenching sweats at night without any other explanation, weight loss of more than 10% of body weight within the last 6 months without any other explanation Supplementary Appendix, Page 3 of 17 GHSG HD10 Study for Patients with Early-Stage Hodgkin Lymphoma Advanced stages – Stage IIB with risk factors, extra-nodal involvement and/or large mediastinal mass – Stage IIIA (involvement of lymph node regions on both sides of the diaphragm or extra-nodal involvement with or without nodal involvement, no B-symptoms) – Stage IIIB (involvement of lymph node regions on both sides of the diaphragm or extra-nodal involvement with or without nodal involvement, with one or more B-symptoms) – Stage IVA (disseminated involvement of one or more extra-lymphatic organs with or without nodal involvement, no B-symptoms) – Stage IVB (disseminated involvement of one or more extra-lymphatic organs with or without nodal involvement, with one or more B-symptoms)
- he 2 clinical trials described herein were initiated in 1962 with the following objectives: (a) to determine whether intensive prophylactic irradiation of apparently uninvolved lymph node regions adjacent to clinically involved regions in patients with regionally localized Hodgkin's disease increases the duration of remission and of survival; (b) to determine whether potentially curative doses of radiation given to patients with generalized Hodgkin's disease are more effective than palliative doses, as measured by length of remission and/or survival; (c) to accumulate additional information on the natural history of Hodgkin's disease in patients whose clinical stage was, in all instances, determined with the aid of lymphangiography and other special diagnostic procedures; (d) to evaluate the tolerance of normal tissues in patients treated with extended-field, high-dose radiations.Patients who met the defined eligibility criteria were assigned to alternative treatment groups at random after an extensive diagnostic evealuation, which included lymphangiography, open bone marrow biopsy, and a battery of liver function tests, as well as other, more routine procedures in all cases. All patients were carefully examined at serial intervals, following completion of the defined radiotherapeutic program. Follow-up intervals are not yet long enough to permit evaluation of comparative survival in the various treatment groups. However, it is clear that extended-field megavoltage radiotherapy to doses in the range of 4000 rads, given at the rate of about 1000 rads/week, is surprisingly well tolerated; there have been virtually no major complications, and most of the observed hematologic, respiratory, neurologic, and endocrine complications have been relatively mild and transient in nature.
- Background Treatment of early-stage Hodgkin’s disease is usually tailored in line with prognostic factors that allow for reductions in the amount of chemotherapy and extent of radiotherapy required for a possible cure. Methods From 1993 to 1999, we identified 1538 patients (age, 15 to 70 years) who had untreated stage I or II supradiaphragmatic Hodgkin’s disease with favorable prognostic features (the H8-F trial) or unfavorable features (the H8-U trial). In the H8-F trial, we compared three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) combined with doxorubicin, bleomycin, and vinblastine (ABV) plus involved-field radiotherapy with subtotal nodal radiotherapy alone (reference group). In the H8-U trial, we compared three regimens: six cycles of MOPP-ABV plus involved- field radiotherapy (reference group), four cycles of MOPP-ABV plus involvedfield radiotherapy, and four cycles of MOPP-ABV plus subtotal nodal radiotherapy. Results The median follow-up was 92 months. In the H8-F trial, the estimated 5-year eventfree survival rate was significantly higher after three cycles of MOPP-ABV plus involvedfield radiotherapy than after subtotal nodal radiotherapy alone (98% vs. 74%, P<0.001). The 10-year overall survival estimates were 97% and 92%, respectively (P = 0.001). In the H8-U trial, the estimated 5-year event-free survival rates were similar in the three treatment groups: 84% after six cycles of MOPP-ABV plus involvedfield radiotherapy, 88% after four cycles of MOPP-ABV plus involved-field radiotherapy, and 87% after four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The 10-year overall survival estimates were 88%, 85%, and 84%, respectively. Conclusions Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin’s disease with favorable prognostic features. In patients with unfavorable features, four courses of chemotherapy plus involved-field radiotherapy should be the standard treatment. (ClinicalTrials.gov number, NCT00379041.)
- To investigate breast cancer risk after supradiaphragmatic radiotherapy administered to young women with Hodgkin’s lymphoma (HL) in a much larger cohort than previously to provide data for patient follow-up and screening individualized according to treatment type, age, and time point during follow-up. Patients and Methods Breast cancer risk was assessed in 5,002 women in England and Wales treated for HL with supradiaphragmatic radiotherapy at age _ 36 years from 1956 to 2003, who underwent follow-up with 97% completeness until December 31, 2008. Results Breast cancer or ductal carcinoma in situ developed in 373 patients, with a standardized incidence ratio (SIR) of 5.0 (95% CI, 4.5 to 5.5). SIRs were greatest for those treated at age 14 years (47.2;95% CI, 28.0 to 79.8) and continued to remain high for at least 40 years. The maximum absolute excess risk was at attained ages 50 to 59 years. Alkylating chemotherapy or pelvic radiotherapy diminished the risk, but only for women treated at age _ 20 years, not for those treated when younger. Cumulative risks were tabulated in detail; for 40-year follow-up, the risk for patients receiving _ 40 Gy mantle radiotherapy at young ages was 48%. Conclusion This article provides individualized risk estimates based on large numbers for patients with HL undergoing follow-up after radiotherapy at young ages. Follow-up of such women needs to continue for 40 years or longer and may require more-intensive screening regimens than those in national general population programs. Special consideration is needed of potential measures to reduce breast cancer risk for girls treated with supradiaphragmatic radiotherapy at pubertal ages.
- Purpose Treatment-related stomach cancer is an important cause of morbidity and mortality among the growing number of Hodgkin lymphoma (HL) survivors, but risks associated with specific HL treatments are unclear. Patients and Methods We conducted an international case-control study of stomach cancer nested in a cohort of 19,882 HL survivors diagnosed from 1953 to 2003, including 89 cases and 190 matched controls. For each patient, we quantified cumulative doses of specific alkylating agents (AAs) and reconstructed radiation dose to the stomach tumor location. Results Stomach cancer risk increased with increasing radiation dose to the stomach (Ptrend _ .001) and with increasing number of AA-containing chemotherapy cycles (Ptrend _ .02). Patients who received both radiation to the stomach _ 25 Gy and high-dose procarbazine (_ 5,600 mg/m2) had strikingly elevated stomach cancer risk (25 cases, two controls; odds ratio [OR], 77.5; 95% CI, 14.7 to 1452) compared with those who received radiation _ 25 Gy and procarbazine _ 5,600 mg/m2 (Pinteraction _ .001). Risk was also elevated (OR, 2.8; 95% CI, 1.3 to 6.4) among patients who received radiation to the stomach _ 25 Gy but procarbazine _ 5,600 mg/m2; however, no procarbazine-related risk was evident with radiation _ 25 Gy. Treatment with dacarbazine also increased stomach cancer risk (12 cases, nine controls; OR, 8.8; 95% CI, 2.1 to 46.6), after adjustment for radiation and procarbazine doses. Conclusion Patients with HL who received subdiaphragmatic radiotherapy had dose-dependent increased risk of stomach cancer, with marked risks for patients who also received chemotherapy containing high-dose procarbazine. For current patients, risks and benefits of exposure to both procarbazine and subdiaphragmatic radiotherapy should be weighed carefully. For patients treated previously, GI symptoms should be evaluated promptly.
- (A) Cumulative incidence of all solid cancers among 10,619 male 5-year survivors of Hodgkin’s lymphoma (HL) compared with men of the same age in the general population (GP). (B) Cumulative incidence for8,243 female 5-year survivors compared with women of the same age in the GP. Purpose Hodgkin’s lymphoma (HL) survivors are known to be at substantially increased risk of solid cancers (SC). However, no investigation has used multivariate modeling to estimate the relative risk (RR), excess absolute risk (EAR), and cumulative incidence for specific attained ages and ages at HL diagnosis. Patients and Methods We identified 18,862 5-year HL survivors from 13 population-based cancer registries in North America and Europe. Poisson regression was used to evaluate the effects of age at diagnosis, attained age, latency, sex, treatment, and year of diagnosis on the RR and EAR of SC. Results Among 1,490 identified SC, 850 were estimated to be in excess. For most cancer sites, both RR and EAR decreased with age at HL diagnosis and showed strong dependencies on attained age. For a patient diagnosed at age 30 years and survived to _ 40 years, modeled risks were significantly elevated for cancers of the breast (RR _ 6.1), other supradiaphragmatic sites (RR _ 6.0), and infradiaphragmatic sites (RR _ 3.7); the largest RR (20-fold) was observed for malignant mesothelioma. Thirty-year cumulative risks of SC for men and women diagnosed at 30 years were 18% and 26%, respectively, compared with 7% and 9%, respectively, in the general population. For young HL patients, risks of breast and colorectal cancers were elevated 10 to 25 years before the age when routine screening would be recommended in the general population. Conclusion Multivariable modeling demonstrates for the first time temporal changes in SC risk not evident in unadjusted analyses, and can facilitate the development of individualized risk assessment and the creation of screening strategies for early detection. Cumulative incidence of solid cancers among 5-year survivors of HL compared with controls of the same age in the general population. (A) Males (n = 10 619 survivors). (B) Females (n = 8243 survivors). (From Hodgson et al.8 Reprinted with permission. Copyright 2007, American Society of Clinical Oncology. All rights reserved.)
- Fig 2. (A) Cumulative incidence of all solid cancers among 10,619 male 5-year survivors of Hodgkin’s lymphoma (HL) compared with men of the same age in the general population (GP). (B) Cumulative incidence for 8,243 female 5-year survivors compared with women of the same age in the GP. Cumulative incidence of solid cancers among 5-year survivors of HL compared with controls of the same age in the general population. (A) Males (n = 10 619 survivors) Purpose Hodgkin’s lymphoma (HL) survivors are known to be at substantially increased risk of solid cancers (SC). However, no investigation has used multivariate modeling to estimate the relative risk (RR), excess absolute risk (EAR), and cumulative incidence for specific attained ages and ages at HL diagnosis. Patients and Methods We identified 18,862 5-year HL survivors from 13 population-based cancer registries in North America and Europe. Poisson regression was used to evaluate the effects of age at diagnosis, attained age, latency, sex, treatment, and year of diagnosis on the RR and EAR of SC. Results Among 1,490 identified SC, 850 were estimated to be in excess. For most cancer sites, both RR and EAR decreased with age at HL diagnosis and showed strong dependencies on attained age. For a patient diagnosed at age 30 years and survived to _ 40 years, modeled risks were significantly elevated for cancers of the breast (RR _ 6.1), other supradiaphragmatic sites (RR _ 6.0), and infradiaphragmatic sites (RR _ 3.7); the largest RR (20-fold) was observed for malignant mesothelioma. Thirty-year cumulative risks of SC for men and women diagnosed at 30 years were 18% and 26%, respectively, compared with 7% and 9%, respectively, in the general population. For young HL patients, risks of breast and colorectal cancers were elevated 10 to 25 years before the age when routine screening would be recommended in the general population. Conclusion Multivariable modeling demonstrates for the first time temporal changes in SC risk not evident in unadjusted analyses, and can facilitate the development of individualized risk assessment and the creation of screening strategies for early detection. . (B) Females (n = 8243 survivors). (From Hodgson et al.8 Reprinted with permission. Copyright 2007, American Society of Clinical Oncology. All rights reserved.)
- This study assessed the cumulative incidence of clinically significant cardiac disease in 1279 Hodgkin lymphoma patients treated with mediastinal irradiation and quantified the standard incidence ratios (SIRs) and absolute excess risks of cardiac procedures compared with a normal matched population. Cox regression analysis was used to explore factors associated with cardiac complications. Poisson regression analysis of SIRs was used to estimate the excess risk of cardiac interventions from mediastinal irradiation. After a median follow-up of 14.7 years, 187 patients experienced 636 cardiac events and 89 patients required a cardiac procedure. 5-, 10-, 15-, and 20-year cumulative incidence rates of cardiac events were 2.2%, 4.5%, 9.6%, and 16%. SIRs for cardiac procedures were increased for coronary artery bypass graft (3.19), percutaneous intervention (1.55), implantable cardioverter defibrillator or pacemaker placement (1.9), valve surgery (9.19), and pericardial surgery (12.91). Absolute excess risks were 18.2, 19.3, 9.4, 14.1, and 4.7 per 10 000 person-years, respectively. Older age at diagnosis and male sex were predictors for cardiac events. However, younger age at diagnosis was associated with excess risk specifically from radiation therapy compared with the general population. These results may help guideline development for both the types and timing of cardiac surveillance in survivors of Hodgkin lymphoma. (Blood. 2011; 117(2):412-418) Dana Farber Cancer Centre
- Figure 1. Approximate Cumulative Risk of Recurrent Hodgkin’s Lymphoma, Second Malignant Conditions, and Cardiovascular Events among Patients Receiving Both Radiotherapy and Chemotherapy for Early-Stage Hodgkin’s Lymphoma.
- GHSG HD 10 data of second malignant neoplasm. Total number in Group 1+3=575 and 2+4=588. Follow up only 7.5 yrs.
- Unfavorable any of the following characteristics=Age >40, ESR >50, Mixed Cell/LD histology, >4 nodal sites
- Figure 1. Kaplan–Meier Estimates of Overall Survival and Freedom from Disease Progression. A total of 405 patients with stage IA or IIA nonbulky Hodgkin's lymphoma were randomly assigned to receive treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or to treatment that included subtotal nodal radiation therapy; 399 of the patients were included in the analyses. Among the 203 patients assigned to subtotal nodal radiation therapy, 64 had a favorable risk profile and received subtotal nodal radiation therapy alone and 139 had an unfavorable risk profile and received two cycles of ABVD plus subtotal nodal radiation therapy. At 12 years, the rate of overall survival (Panel A) was 94% among patients in the ABVD-only group and 87% among patients in the radiation-therapy group, and the rate of freedom from disease progression (Panel B) was 87% and 92% in the two groups, respectively.
- Background Chemotherapy plus radiation treatment is effective in controlling stage IA or IIA nonbulky Hodgkin’s lymphoma in 90% of patients but is associated with late treatment- related deaths. Chemotherapy alone may improve survival because it is associated with fewer late deaths. Methods We randomly assigned 405 patients with previously untreated stage IA or IIA nonbulky Hodgkin’s lymphoma to treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or to treatment with subtotal nodal radiation therapy, with or without ABVD therapy. Patients in the ABVD-only group, both those with a favorable risk profile and those with an unfavorable risk profile, received four to six cycles of ABVD. Among those assigned to subtotal nodal radiation therapy, patients who had a favorable risk profile received subtotal nodal radiation therapy alone and patients with an unfavorable risk profile received two cycles of ABVD plus subtotal nodal radiation therapy. The primary end point was 12-year overall survival. Results The median length of follow-up was 11.3 years. At 12 years, the rate of overall survival was 94% among those receiving ABVD alone, as compared with 87% among those receiving subtotal nodal radiation therapy (hazard ratio for death with ABVD alone, 0.50; 95% confidence interval [CI], 0.25 to 0.99; P = 0.04); the rates of freedom from disease progression were 87% and 92% in the two groups, respectively (hazard ratio for disease progression, 1.91; 95% CI, 0.99 to 3.69; P = 0.05); and the rates of event-free survival were 85% and 80%, respectively (hazard ratio for event, 0.88; 95% CI, 0.54 to 1.43; P = 0.60). Among the patients randomly assigned to ABVD alone, 6 patients died from Hodgkin’s lymphoma or an early treatment complication and 6 died from another cause; among those receiving radiation therapy, 4 deaths were related to Hodgkin’s lymphoma or early toxic effects from the treatment and 20 were related to another cause. Conclusions Among patients with Hodgkin’s lymphoma, ABVD therapy alone, as compared with treatment that included subtotal nodal radiation therapy, was associated with a higher rate of overall survival owing to a lower rate of death from other causes. (Funded by the Canadian Cancer Society and the National Cancer Institute; HD.6 ClinicalTrials.gov number, NCT00002561.)
- There were differences in eligibility, staging, end points and follow up duration of these three trials.
- Even diagnostic levels of radiation like simple chest xray done frequently have been found to increase the incidence of breast cancer
- Figure 2. Cumulative Incidence of Subsequent Malignant Neoplasms, According to Treatment Period, with Death as a Competing Risk. Solid lines represent the observed incidence, and dashed lines the expected incidence in the general population. The insets show the same data on enlarged y axes.
- Figure 2. Cumulative Incidence of Subsequent Malignant Neoplasms, According to Treatment Period, with Death as a Competing Risk. Solid lines represent the observed incidence, and dashed lines the expected incidence in the general population. The insets show the same data on enlarged y axes.
- Figure 2. Cumulative Incidence of Subsequent Malignant Neoplasms, According to Treatment Period, with Death as a Competing Risk. Solid lines represent the observed incidence, and dashed lines the expected incidence in the general population. The insets show the same data on enlarged y axes.
- Figure 2. Cumulative Incidence of Subsequent Malignant Neoplasms, According to Treatment Period, with Death as a Competing Risk. Solid lines represent the observed incidence, and dashed lines the expected incidence in the general population. The insets show the same data on enlarged y axes.
- Figure 1. Standardized Incidence Ratios and Absolute Excess Risks of Any Subsequent Malignant Neoplasm after Treatment for Hodgkin’s Lymphoma, According to Follow-up Interval. The standardized incidence ratio is a comparison of the incidence of second cancer observed in the study cohort with the expected incidence in the general population. Vertical lines indicate 95% confidence intervals.
- Figure 1. Standardized Incidence Ratios and Absolute Excess Risks of Any Subsequent Malignant Neoplasm after Treatment for Hodgkin’s Lymphoma, According to Follow-up Interval. The standardized incidence ratio is a comparison of the incidence of second cancer observed in the study cohort with the expected incidence in the general population. Vertical lines indicate 95% confidence intervals.
- NCIC ECOG trial excluded pts with mediastinal mass
- Changes in RT fields over time. Figures are 3-dimensional reconstructions of RT fields based on computed tomography imaging. Light green illustrates irradiated field. The true heart position is shown. (A) Mantle and upper abdomen (“spade”) field. Note the large volume of heart and left breast irradiated. (B) Mantle field. (C) IFRT for mediastinal disease without axillary disease. Less breast tissue is treated, although inclusion of the subcarinal nodes encompasses the proximal coronary arteries. (D) INRT for a patient with mediastinal, low neck, and high axillary disease. The patient was also treated with active breath hold to decrease heart dose.
- Characteristics and Outcomes of Breast Cancer in Women With and Without a History of Radiation for Hodgkin’s Lymphoma: A Multi-Institutional, Matched Cohort Study 8 medical centres from North America. Elena B. Elkin, Michelle L. Klem, Anne Marie Gonzales, Nicole M. Ishill, David Hodgson, Andrea K. Ng, Lawrence B. Marks, Joanne Weidhaas, Gary M. Freedman, Robert C. Miller, Louis S. Constine, Sten Myrehaug, and Joachim Yahalom DOI: 10.1200/JCO.2010.32.4079 A B S T R A C T Purpose To compare characteristics and outcomes of breast cancer in women with and without a history of radiation therapy (RT) for Hodgkin’s lymphoma (HL). Patients and Methods Women with breast cancer diagnosed from 1980 to 2006 after RT for HL were identified from eight North American hospitals and were matched three-to-one with patients with sporadic breast cancer by age, race, and year of breast cancer diagnosis. Information on patient, tumor and treatment characteristics, and clinical outcomes was abstracted from medical records. Results A total of 253 patients with breast cancer with a history of RT for HL were matched with 741 patients with sporadic breast cancer. Median time from HL to breast cancer diagnosis was 18 years. Median age at breast cancer diagnosis was 42 years. Breast cancer after RT for HL was more likely to be detected by screening, was more likely to be diagnosed at an earlier stage, and was more likely to be bilateral at diagnosis. HL survivors had an increased risk of metachronous contralateral breast cancer (adjusted hazard ratio [HR], 4.3; 95% CI, 1.7 to 11.0) and death as a result of any cause (adjusted HR, 1.9; 95% CI, 1.1 to 3.3). Breast cancer–specific mortality was also elevated, but this difference was not statistically significant (adjusted HR, 1.6; 95% CI, 0.7 to 3.4). Conclusion In women with a history of RT for HL, breast cancer is diagnosed at an earlier stage, but these women are at greater risk for bilateral disease and are more likely to die as a result of causes other than breast cancer. Our findings support close follow-up for contralateral tumors in these patients and ongoing primary care to manage comorbid conditions. J Clin Oncol 29:2466-2473. ｩ 2011 by American Society of Clinical Oncology From Dana Farber Cancer Istitute