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Early-Stage Hodgkin’s Disease: To Mantle or Not to Mantle?

Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

To the Editor:I read with interest the recent article by Backstrand et al¹ in the February 1, 2001, issue of the Journal of Clinical Oncology. In this single-arm prospective study of 87 selected patients with early-stage (pathologic stage IA to IIA and clinical stage IA), favorable Hodgkin’s disease, the authors sought to evaluate the efficacy of mantle irradiation alone. They reported that mantle irradiation alone in selected patients with pathologic confirmation of absence of disease below the diaphragm and in patients with low risk of occult disease in the abdomen resulted in disease control rates comparable to those with extended-field irradiation. Therefore, they concluded, those patients can be spared chemotherapy-induced toxicity and thereby benefit from a higher probability of successful salvage if a relapse were to occur.

I do not agree with their conclusion for two reasons. First, even if there is evidence that, after staging laparotomy, mantle irradiation alone could be a sufficient treatment in terms of local control or survival,² there is also evidence that without staging laparotomy, even in selected patients with very favorable disease (women younger than 40 years with clinical stage IA and elevated sedimentation rates < 50 mm with lymphocyte-predominant or nodular sclerosis histology) treated with mantle irradiation alone, relapse is still considered an important problem. The April 1997 update of the European Organization of Research and Treatment of Cancer (EORTC) H7-VF and H8-VF trials revealed a 32% relapse rate with a 97% survival rate at 6 years thanks to the efficacy of salvage treatments.^3,4 Several reports have documented the increased risk of second malignancy following salvage treatment; therefore, it is important to minimize any recurrence of Hodgkin’s disease. ^5,6 In the beginning of the millennium, staging laparotomy is no longer justified given its morbidity, despite the progress in surgery.⁷ In the article by Backstrand et al,¹ only 7% of the patients were clinically staged, and no information was given in terms of sex distribution, which is also an important prognostic factor.⁸

Second, even if we accept the efficacy of mantle irradiation alone in early-stage, nonlaparotomized Hodgkin’s disease, we do not know if the therapeutic index of mantle alone is better or worse than a combination of anthracycline-based chemotherapy and involved-field radiation therapy. In terms of disease control, it is hoped that this issue will be resolved by the ongoing EORTC H9 (20982) randomized phase III trial to assess the role of adjuvant involved-field radiation (0 v 20 v 36 Gy) in favorable patients (including the above-mentioned very favorable patients) with a complete response after chemotherapy. In terms of morbidity, anthracycline-based chemotherapy alone or combined with involved-field radiation therapy should, theoretically, induce fewer second cancers than mantle irradiation alone, especially for very favorable patients for whom involved-field irradiation includes relatively smaller normal-tissue volumes than mantle irradiation does.^9-12 Moreover, mantle irradiation–induced breast cancer is reported to be biologically more aggressive and results in worse overall survival compared with the matched control population.¹³

REFERENCES

1. Backstrand KH, Ng AK, Takvorian RW, et al: Results of a prospective trial of mantle irradiation alone for selected patients with early-stage Hodgkin’s disease. J Clin Oncol 19: 736-741, 2001[Abstract/Free Full Text]

2. Tubiana M, Henry-Amar M, Carde P, et al: Toward comprehensive management tailored to prognostic factors of patients with clinical stages of I and II in Hodgkin’s disease: The EORTC Lymphoma Group controlled clinical trials—1964-1987. Blood 73: 47-56, 1989[Abstract/Free Full Text]

3. Noordijk EM, Carde P, Hagenbeek A, et al: Combination of radiotherapy is advisable in all patients with clinical stage I-II Hodgkin’s disease: Six-year results of EORTC-GPMC controlled clinical trials H7-VF, H7-F and H7-U. Int J Radiat Oncol Biol Phys 39: 173, 1997 (suppl, abstr)[Medline]

4. Cosset JM, Fermé C, Henry-Amar M, et al: Le rôle de la radiothérapie dans les formes localisées de maladie de Hodgkin en 1999: Limitations et perspectives. Cancer Radiother 3: 112-118, 1999[Medline]

5. Doria R, Holford T, Farber L, et al: Second solid malignancies after combined modality therapy for Hodgkin’s disease. J Clin Oncol 13: 2016-2022, 1995[Abstract/Free Full Text]

6. Donaldson SS, Hancock SL, Hoppe RT: Hodgkin’s disease: Finding the balance between cure and late effects. Cancer J Sci Am 5: 325-333, 1999[Medline]

7. Carde P, Hagenbeek A, Hayat M, et al: Clinical staging versus laparotomy and combined with MOPP versus ABVD in early-stage Hodgkin’s disease: The H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol 11: 2258-2272, 1993[Abstract/Free Full Text]

8. Cosset JM, Henry-Amar M, Meerwaldt JH, et al: The EORTC trials for limited stage Hodgkin’s disease: The EORTC Lymphoma Cooperative Group. Eur J Cancer 28A: 1847-1850, 1992

9. van Leeuwen FE, Klokman WJ, Hagenbeek A, et al: Second cancer risk following Hodgkin’s disease: A 20-year follow-up study. J Clin Oncol 12: 312-325, 1994[Abstract]

10. Bhatia S, Robinson LL, Oberlin O, et al: Breast cancer and other second neoplasms after childhood Hodgkin’s disease. N Engl J Med 334: 745-751, 1996[Abstract/Free Full Text]

11. Aisenberg AC, Finkelstein DM, Doppke KP, et al: High risk of breast carcinoma after irradiation of young women with Hodgkin’s disease. Cancer 79: 1203-1210, 1997[Medline]

12. Swerdlow AJ, Barber JA, Vaughan-Hudson G, et al: Risk of second malignancy after Hodgkin’s disease in a collaborative British cohort: The relation to age at treatment. J Clin Oncol 18: 498-509, 2000[Abstract/Free Full Text]

13. Gaffney DK, Hemmersmeier J, Holden J, et al: Breast cancer after mantle irradiation for Hodgkin’s disease: Correlation of clinical, pathologic, and molecular features including loss of heterozygosity at BRCA1 and BRCA2. Int J Radiat Oncol Biol Phys 49: 539-546, 2001[Medline]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ozsahin, M. Search for Related Content PubMed PubMed Citation Articles by Ozsahin, M. Social Bookmarking                            What's this?