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Treatment of nonlaparotomized (clinical) stage I and II Hodgkin’s disease patients by extended field and splenic irradiation
Int. J. Radiation Oncology Biol. Phys., Vol. 46, No. 5, pp. 1235–1238, 2000 Copyright © 2000 Elsevier Science Inc. Printed in the USA. All rights reserved 0360-3016/00/$–see front matter
PII S0360-3016(99)00511-8
CLINICAL INVESTIGATION
Hodgkin’s Disease
TREATMENT OF NONLAPAROTOMIZED (CLINICAL) STAGE I AND II HODGKIN’S DISEASE PATIENTS BY EXTENDED FIELD AND SPLENIC IRRADIATION MORTON COLEMAN, M.D.,* THOMAS KAUFMANN, M.D.,†1 LOURDES Z. NISCE, M.D.,† JOHN P. LEONARD, M.D.*
AND
*The Center for Lymphoma and Myeloma, Division of Hematology–Oncology, Department of Medicine, and †Department of Radiation Oncology, The New York Presbyterian Hospital and the Weill Medical College of Cornell University, New York, NY Purpose: At the New York Presbyterian Hospital–Cornell Medical Center, patients with unequivocal clinical stage I and IIA Hodgkin’s disease (HD) have been treated with mantle, splenic, and extended field radiation therapy (EFRT) (without surgical staging). A 24-year retrospective review was conducted to determine the effectiveness of our patient selection on the outcome of patients treated with this modality. Methods and Materials: During the period 1971 to 1994, 94 patients with clinically staged HD, with favorable prognostic factors, were retrospectively reviewed. Patients with pathological or equivocal staging, “B” symptoms, bulk disease, history of previous chemotherapy, and/or Stage III or IV disease were excluded from our analysis. There were 27 Stage IA and 67 Stage IIA patients. All patients were treated to 3600 cGy with a 400 cGy boost to the involved field. The median follow-up was 52 months, mean of 62.1 months. Results: Ten of 94 patients (10.5%) relapsed. Seven of the relapses were in the pelvis, one submandibularily, one in the tonsil, and one in the axilla. Nine of the relapses had nodular sclerosis histology, one had lymphocyte predominance, and none had mixed cellularity. The median time to relapse was 38 months; mean time 42.3 months. All patients are alive, well and free of disease, including nine who received subsequent chemotherapy and one who underwent autotransplantation. Conclusions: Careful clinical staging of early, asymptomatic HD patients treated with mantle, splenic, and EFRT may obviate the need for exploratory laparotomy. © 2000 Elsevier Science Inc. Hodgkin’s disease, Clinical staging, Radiation therapy.
INTRODUCTION
by clinical staging are already committed to extended field and splenic radiation therapy (6, 7). At the New York Presbyterian Hospital–Cornell Medical Center, our approach has been to treat unequivocally staged, early HD, without adverse prognostic factors, with splenic and EFRT, without the routine use of laparotomy. To examine the effectiveness of our current treatment approach, we have retrospectively reviewed our more than 20-year experience in clinically staged IA and IIA HD patients.
Exploratory laparotomy and splenectomy have revolutionized our understanding of Hodgkin’s disease (HD). These surgical procedures have resulted in a clearer grasp of both the natural history and pathophysiology of the disease. While many therapeutic options are available for the treatment of early-stage HD, laparotomy and extended field radiation therapy (EFRT) remain one of the more common treatment approaches in the United States (1). Clinical staging alone has often been shown, following exploration, to be inaccurate. At Stanford, 43% of patients had a change in their stage following laparotomy (2). The Joint Center in Boston noted a discrepancy of 28% between surgical and clinical staging (3). Overall, approximately 25% of patients are upstaged, while 10% are downstaged at laparotomy (4, 5). Despite these findings, it is still not clear that surgical staging is truly necessary for most patients who
METHODS AND MATERIALS Patient selection During the period 1971 through 1994, 94 patients with clinically staged IA and IIA HD were retrospectively reviewed. The Ann Arbor and Rye nomenclature were employed for staging (8) and classifying (9) the disease.
Reprint requests to: John P. Leonard, M.D., Center for Lymphoma and Myeloma, The New York Presbyterian Hospital–Cornell Medical Center, 520 East 70th Street, Starr 341, New York, NY 10021. E-mail [email protected] Supported in part by the National Institutes of Health Grant CA
07968 and by grants from the Malvin Sevin Memorial Fund and the Fund for Blood and Cancer Research. 1 Deceased. Accepted for publication 15 November 1999. 1235
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Patients with laparotomy, “B” symptoms, large mediastinal mass (more than one-third of the chest diameter), history of previous chemotherapy, clinical stage III or IV, or equivocal clinical stage were excluded from our analysis. Specifically, these latter patients, mostly with an equivocal lymphangiogram (LAG) and/or computed transaxial tomography (CAT) scan, were either explored or given chemotherapy. All patients studied required a detailed history; clinical examination; chest roentgenogram; CAT scan of the neck, chest, abdomen, and pelvis; and bipedal lymphangiography. Gallium scan, bone scan, metastatic survey, liver/spleen scan, and bone marrow biopsy were performed as indicated. Routine evaluation included complete blood counts with differential, sedimentation rate, chemistry profile, and serum electrolytes. There were 27 Stage IA and 67 Stage IIA patients. Nine had lymphocyte predominance (LP), 64 nodular sclerosis (NS), and 21 mixed cellularity (MC) HD. The median age was 31, mean of 33.5 years (range of 17 to 66 years). The median follow-up was 52 months, mean of 62.1 months (range 5 to 265 months). Treatment plan All patients were treated with curative intent, using 10 MV photons at 120 c.m. source-skin distance. All patients had custom-shaped blocks to protect the lung, kidneys, heart, and bowel. In order to immobilize the patient and assure daily reproducibility, the “mantle board” was employed. Splenic localization was performed by CT scanning and simulation. The 2 and 2 technique was used (10). Treatment was divided into two phases. Phase 1: mantle RT, 2000 cGy in 10 equal fractions over 2 weeks, followed by paraaortic and splenic RT, 2000 cGy in 10 fractions, over 2 weeks. Phase 2: mantle RT for a total dose of 1600 cGy in 8 fractions over 11⁄2 weeks, followed by paraaortic and splenic RT in 11⁄2 weeks to a dose of 1600 cGy. A boost dose was given in the involved field totaling 400 cGy in 2 days. The mantle, paraaortic and splenic fields received a total dose of 3600 cGy, and the involved areas 4000 cGy.
RESULTS Only 10 of 94 patients (10.5%) relapsed. Of the 10 relapses, seven recurred nodally in the pelvis, one in the axilla, one submandibularly, and one in the tonsil. There were no relapses among patients with MC disease; nine were with NS, and one with LP. Two were Stage I and eight were Stage II. There were three males and seven females. The median age was 30 and the mean age was 27.4 years (range 17 to 45 years). The median time to relapse was 38 months, mean of 42.3 months (range of 24 to 67 months). All relapsed patients are alive and in complete remission, nine with conventional chemotherapy, and one following autologous bone marrow transplant. No correlation with the erythrocyte sedimentation
Volume 46, Number 5, 2000
rate, lactate dehydrogenase (LDH), or sites of presentation could be established in patients who recurred. DISCUSSION Overall, between a quarter and a third of clinically staged I and II patients will be found to have abdominal disease on exploratory laparotomy (4, 5, 11–13). While these 30% of clinically staged patients will then be upstaged to at least Stage III disease, at exploratory laparotomy, only rarely will asymptomatic clinically staged I and II (A category) patients have lower abdominal node (PSIII) or organ involvement. Virtually all of these nonsymptomatic (A) patients will be upstaged, because of the presence of splenic or upper abdominal node involvement, to pathologic stage III1A (12). Although chemotherapy is generally employed for PSIII1A disease, radiation alone may be adequate (14, 15) since prognosis following RT is roughly comparable to Stage II disease. Powlis and coworkers (16) have shown also that patients with minimal splenic involvement may be adequately treated with mantle, splenic and extended field RT. Thus the finding of III1A disease at exploratory laparotomy would have little impact theoretically on prognosis if the intent is to apply splenic and EFRT on a clinical basis alone. There are now a number of retrospective reports in the treatment of early, clinically staged, nonexplored HD patients treated solely with splenic and EFRT. All reports, including ours, exclude patients with bulky disease and B symptoms, since they conventionally are given chemotherapy either with or without radiation. Some reports have also used other selective criteria for exclusion of certain Stage IIA patients, whereas others, as we, have been more inclusive. A total of more than 300 patients, exclusive of our study (13, 17–21), have now received splenic and EFRT for clinical stage I and II disease. The overall results are virtually identical to our results where no exclusion other than B symptoms or bulk are permitted. Prior data, as well as our own, compare favorably to pathologic stage (PS) I and II (explored) patients who have been treated with EFRT (19, 22). Since approximately 30% of nonexplored clinically stage IIA patients will be presumed to have Stage III1A disease, the inclusion of these patients does not appear to have had an impact on survival or freedom from the disease. Only 10% of patients in our series have relapsed, all of whom are alive following retreatment. A reason adduced for laparotomy is that its use reduces the morbidity of radiation by precluding the need for abdominal and splenic treatment. However, the concern that renal function is compromised by splenic RT is exaggerated because any spleen sufficiently large to overlap substantial amounts of kidney would upstage the patients to CS III, precluding RT as the mainstay modality. In general practice, very few explored patients are treated with mantle field (thorax) RT alone because there is always concern for false-negative explorations. Indeed an exploratory laparot-
Treatment of early-stage Hodgkin’s disease
omy may yield an isolated involved node, which if undetected would have rendered the patient a higher stage (23, 24). This notion is buttressed by a report from the Royal Marsden Hospital, where surgically staged patients were administered mantle radiation alone (25). Most of the relapses occurred in the paraaortic nodes. Mauch et al., from the Harvard Collaborative Oncology Group, reported on 46 laparotomized patients with PS I and II disease, all of whom were treated solely with mantle radiation (26). Half of the patients were retrospectively analyzed. The 4-year actuarial rate of relapse was 17%, almost exclusively below the diaphragm. Although comparisons between our study and the Harvard study are always subject to the criticisms of retrospective analysis, is the 7% difference the result of “false-negative” explorations? The European Organization for Research and Treatment of Cancer (EORTC) H5 trial in PS I and II patients noted an 11% relapse below the diaphragm in mantle treated patients as compared to 4% relapse in EFRT patients (27, 28). Staging laparotomy is associated with potential operative and postoperative complications. Patients who undergo exploratory laparotomy may be subject to a greater incidence of small bowel adhesions and obstruction and other potential complications as a result of radiation (21, 27, 29). There are a number of studies addressing the morbidity of surgical staging. Brogadir and colleagues noted that 37% of patients sustained complications related to this procedure (30). Meeker and associates related a 27% morbidity rate and 6.6% mortality (31). Smith et al. noted that most of the clinically staged I and II patients who were upstaged at surgery had splenic, splenic hilar, or paraaortic involvement, areas covered when patients receive EFRT (6). Although laparoscopy may be useful in certain instances as an alternative to laparotomy for determining the liver status of HD patients (32), there is little need to use the procedure in limited asymptomatic clinically staged disease since the incidence of liver involvement is so rare. While we are not advocates of the routine use of exploratory laparotomy, it still may have utility in the staging of
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certain HD patients, if avoidance of chemotherapy is considered a priority. If such a priority is entertained, laparotomy would be indicated for those patients whose clinical staging is uncertain as may be encountered with an equivocal LAG or CAT scan. Adjuvant chemotherapy, however, would in most circumstances be an alternative. We acknowledge the pitfalls of retrospective analysis. Our data, though, are sufficiently compelling for a general rethinking of the approach to the staging of early HD. Indeed, the EORTC has reported a trial (H6F) which randomized limited clinical stage HD to exploration or directly to EFRT, as in this report. The data indicate that there was no advantage to exploratory laparotomy (19). Patients clinically staged and treated with splenic and EFRT, had a similar rate of freedom from relapse as those explored and treated with EFRT. The Princess Margaret Hospital, in a review of their 20-year experience, concluded that carefully selected patients can be adequately treated with clinical staging and with EFRT (13). Wasserman and coworkers reported that the relapse rate of the clinically staged patients to those staged with laparotomy was similar. Most of their patients, similar to our results, relapsed in the pelvic nodes (21). It is interesting to note that of the 10 patients who relapsed in our study, none had the more aggressive MC histology. Eight had NS and one had LP. Whether this finding represents a chance occurrence or a unique reflection of disease biology remains to be clarified. RT for now remains the mainstay treatment for earlystage HD. If clinically selected and staged patients with limited disease can undergo splenic and EFRT with results comparable to those who have undergone staging surgery, is there truly a place for the routine use of the procedure when it may have little impact on therapeutic decision making? Is the procedure worth the morbidity, potential morbidity, and increased fiscal and physical cost? Perhaps Lacher’s prophecy will prove correct when surgical staging will be recalled as a milestone in the history of HD management, important at one time, but abandoned because it was no longer needed (33).
REFERENCES 1. Mauch P, Tarbell N, Weinstein H, et al. Stage IA and IIA supradiaphragmatic Hodgkin’s disease: Prognostic factors in surgically staged patients treated with mantle and paraaortic irradiation. J Clin Oncol 1988;6:1576 –1583. 2. Taylor MA, Kaplan HS, Nelsen TS. Staging laparotomy with splenectomy for Hodgkin’s disease: The Stanford experience. World J Surg 1985;9:449 – 460. 3. Hellman S. Current studies in Hodgkin’s disease: What laparotomy has wrought. N Engl J Med 1994;290:894 – 898. 4. Scott JS, Dawson AA, Proctor SJ, Allan SC. The place of staging laparotomy in the management of Hodgkin’s disease. Clin Radiol 1984;35:261–263. 5. Wobbes T, Lubbers EJC, DePaw BE. Results and complications of staging laparotomy in Hodgkin’s disease. J Surg Oncol 1984;26:135–137. 6. Smith J, Pasmantier MW, Silver RT, Cornell G, Coleman M,
7. 8.
9. 10.
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Cortese A. The staging of Hodgkin’s disease: Selective vs routine laparotomy. JAMA 1973;224:1026 –1028. Johnson RE. Is staging laparotomy routinely indicated in Hodgkin’s disease? Ann Intern Med 1971;75:459 – 462. Carbone PP, Kaplan HS, Mussoff K, et al. Report of the Committee on Hodgkin’s Disease Staging Classification. Cancer Res 1971;31:1860 –1861. Lukes RJ, Carver, Hall TC, Rappaport H, Ruben P. Report of the nomenclature committee. Cancer Res 1966;26:1063–1083. Nisce LZ, D’Angio GJ. Radiotherapy of Hodgkin’s disease. In: Lacher MJ, editors. Hodgkin’s disease. 1st ed. New York: Wiley; 1976. Aragon De La Cruz G, Cardenes H, Otero J, et al. Individual risk of abdominal disease in patients with stages I and II supradiaphragmatic Hodgkin’s disease: A rule index based on 341 laparotomized patients. Cancer 1989;63:1799 –1803.
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12. Glatstein E, Guernsey JM, Rosenberg SA, Kaplan HS. The value of laparotomy and splenectomy in the staging of Hodgkin’s disease. Cancer 1969;24:709 –718. 13. Gospodarowicz MK, Sutcliffe SB, Clark RM, et al. Analysis of supradiaphragmatic clinical stage I and II Hodgkin’s disease treated with radiation alone. Int J Radiat Oncol Biol Phys 1992;22:859 – 865. 14. Farah R, Golomb HM, Hallahan DE, et al. Radiation therapy for pathologic stage III Hodgkin’s disease with and without chemotherapy. Int J Radiat Oncol Biol Phys 1989;17:761– 766. 15. Desser RK, Golomb HM, Ultmann JE, et al. Prognostic classification of Hodgkin’s disease in pathologic stage III, based on anatomic considerations. Blood 1977;49:883– 893. 16. Powlis WD, Mauch P, Goffman T, Goodman RL. Treatment of patients with “minimal” stage IIIA Hodgkin’s disease. Int J Radiat Oncol Biol Phys 1987;13:1437–1442. 17. Tubiana M, Henry-Amar M, Hayat M, et al. The EORTC treatment of early stages of Hodgkin’s disease: The role of radiotherapy. Int J Radiat Oncol Biol Phys 1984;10:197–210. 18. Somers R, Tubiana M, Henry-Amar M. EORTC lymphoma cooperative group studies in Hodgkin’s disease. In: Diehl V, editor. Proceedings of the First International Symposium on Hodgkin’s Lymphoma. Koln, FRG, October 1–3, 1987. 19. Carde P, Hagenbeek A, Hayat M, et al. Clinical staging versus laparotomy and combined modality 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 1993;11:2258 –2272. 20. Glenn LD, Kumar P. Radiation therapy alone versus radiation therapy and chemotherapy in the management of Hodgkin’s disease. J Nat Med Assoc 1990;82:101–107. 21. Wasserman TH, Trenkner DA, Fineberg B, Kucik N. Cure of early stage Hodgkin’s disease with subtotal nodal irradiation. Cancer 1991;68:1208 –1215. 22. Bergsagel DE, Alison RE, Bean HL, et al. Results of treatment of Hodgkin’s disease without a policy of laparotomy staging. Cancer Treat Rep 1982;66:717–731.
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23. Fuller LM, Hutchinson GB. The collaborative clinical trials for stage I and II Hodgkin’s disease: Significance of mediastinal and non-mediastinal disease in laparotomy and nonlaparotomy staged patients. Cancer Treat Rep 1982;66:775– 787. 24. Specht L, Nordentoft AM, Cold S. Tumor burden in early Hodgkin’s disease: The single most important prognostic factor for outcome after radiotherapy. Br J Cancer 1987;55:535– 539. 25. Verger E, Easton D, Brada M, Duchesne G, Horwich A. Radiotherapy results in laparotomy staged Hodgkin’s disease. Clin Radiol 1988;39:428 – 431. 26. Mauch P, Canellos GP, Shulman LN, et al. Mantle irradiation alone for selected patients with laparotomy-staged IA to IIA Hodgkin’s disease: Preliminary results of a prospective trial. J Clin Oncol 1995;13:947–952. 27. Carde P, Burgers J, Henry-Amar M, et al. Clinical stage I and II Hodgkin’s disease: A specifically tailored therapy according to prognostic factors. J Clin Oncol 1988;6:239 –252. 28. Tubiana M, Henry-Amar M, Carde P, et al. Toward comprehensive management tailored to prognostic factors of patients with clinical stages I and II in Hodgkin’s disease. The EORTC Lymphoma Group controlled clinical trials: 1964 –1987. Blood 1989;73:47–56. 29. Cornbleet MA, Vitolo U, Ultmann JE, et al. Pathologic stage I and IIA Hodgkin’s disease: Results of treatment with radiotherapy alone (1968 –1980). J Clin Oncol 1985;3:758 –768. 30. Brogadir S, Fialk MA, Coleman M, et al. Morbidity of staging laparotomy in Hodgkin’s disease. Am J Med 1978;64:429 – 433. 31. Meeker WR, Richard JD, West WO, et al. Critical evaluation of laparotomy and splenectomy in Hodgkin’s disease. Arch Surg 1972;105:222–229. 32. Coleman M, Lightdale CJ, Vinciguerra VP, et al. Peritoneoscopy in Hodgkin’s disease: Confirmation of results by laparotomy. JAMA 1976;236:2634 –2636. 33. Lacher MJ. Staging laparotomy in patients with Hodgkin’s disease. In: Lacher MJ, editor. Hodgkin’s disease. 1st ed. New York, Wiley; 1976.
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CLINICAL INVESTIGATION
Hodgkin’s Disease
TREATMENT OF NONLAPAROTOMIZED (CLINICAL) STAGE I AND II HODGKIN’S DISEASE PATIENTS BY EXTENDED FIELD AND SPLENIC IRRADIATION MORTON COLEMAN, M.D.,* THOMAS KAUFMANN, M.D.,†1 LOURDES Z. NISCE, M.D.,† JOHN P. LEONARD, M.D.*
AND
*The Center for Lymphoma and Myeloma, Division of Hematology–Oncology, Department of Medicine, and †Department of Radiation Oncology, The New York Presbyterian Hospital and the Weill Medical College of Cornell University, New York, NY Purpose: At the New York Presbyterian Hospital–Cornell Medical Center, patients with unequivocal clinical stage I and IIA Hodgkin’s disease (HD) have been treated with mantle, splenic, and extended field radiation therapy (EFRT) (without surgical staging). A 24-year retrospective review was conducted to determine the effectiveness of our patient selection on the outcome of patients treated with this modality. Methods and Materials: During the period 1971 to 1994, 94 patients with clinically staged HD, with favorable prognostic factors, were retrospectively reviewed. Patients with pathological or equivocal staging, “B” symptoms, bulk disease, history of previous chemotherapy, and/or Stage III or IV disease were excluded from our analysis. There were 27 Stage IA and 67 Stage IIA patients. All patients were treated to 3600 cGy with a 400 cGy boost to the involved field. The median follow-up was 52 months, mean of 62.1 months. Results: Ten of 94 patients (10.5%) relapsed. Seven of the relapses were in the pelvis, one submandibularily, one in the tonsil, and one in the axilla. Nine of the relapses had nodular sclerosis histology, one had lymphocyte predominance, and none had mixed cellularity. The median time to relapse was 38 months; mean time 42.3 months. All patients are alive, well and free of disease, including nine who received subsequent chemotherapy and one who underwent autotransplantation. Conclusions: Careful clinical staging of early, asymptomatic HD patients treated with mantle, splenic, and EFRT may obviate the need for exploratory laparotomy. © 2000 Elsevier Science Inc. Hodgkin’s disease, Clinical staging, Radiation therapy.
INTRODUCTION
by clinical staging are already committed to extended field and splenic radiation therapy (6, 7). At the New York Presbyterian Hospital–Cornell Medical Center, our approach has been to treat unequivocally staged, early HD, without adverse prognostic factors, with splenic and EFRT, without the routine use of laparotomy. To examine the effectiveness of our current treatment approach, we have retrospectively reviewed our more than 20-year experience in clinically staged IA and IIA HD patients.
Exploratory laparotomy and splenectomy have revolutionized our understanding of Hodgkin’s disease (HD). These surgical procedures have resulted in a clearer grasp of both the natural history and pathophysiology of the disease. While many therapeutic options are available for the treatment of early-stage HD, laparotomy and extended field radiation therapy (EFRT) remain one of the more common treatment approaches in the United States (1). Clinical staging alone has often been shown, following exploration, to be inaccurate. At Stanford, 43% of patients had a change in their stage following laparotomy (2). The Joint Center in Boston noted a discrepancy of 28% between surgical and clinical staging (3). Overall, approximately 25% of patients are upstaged, while 10% are downstaged at laparotomy (4, 5). Despite these findings, it is still not clear that surgical staging is truly necessary for most patients who
METHODS AND MATERIALS Patient selection During the period 1971 through 1994, 94 patients with clinically staged IA and IIA HD were retrospectively reviewed. The Ann Arbor and Rye nomenclature were employed for staging (8) and classifying (9) the disease.
Reprint requests to: John P. Leonard, M.D., Center for Lymphoma and Myeloma, The New York Presbyterian Hospital–Cornell Medical Center, 520 East 70th Street, Starr 341, New York, NY 10021. E-mail [email protected] Supported in part by the National Institutes of Health Grant CA
07968 and by grants from the Malvin Sevin Memorial Fund and the Fund for Blood and Cancer Research. 1 Deceased. Accepted for publication 15 November 1999. 1235
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I. J. Radiation Oncology
●
Biology
●
Physics
Patients with laparotomy, “B” symptoms, large mediastinal mass (more than one-third of the chest diameter), history of previous chemotherapy, clinical stage III or IV, or equivocal clinical stage were excluded from our analysis. Specifically, these latter patients, mostly with an equivocal lymphangiogram (LAG) and/or computed transaxial tomography (CAT) scan, were either explored or given chemotherapy. All patients studied required a detailed history; clinical examination; chest roentgenogram; CAT scan of the neck, chest, abdomen, and pelvis; and bipedal lymphangiography. Gallium scan, bone scan, metastatic survey, liver/spleen scan, and bone marrow biopsy were performed as indicated. Routine evaluation included complete blood counts with differential, sedimentation rate, chemistry profile, and serum electrolytes. There were 27 Stage IA and 67 Stage IIA patients. Nine had lymphocyte predominance (LP), 64 nodular sclerosis (NS), and 21 mixed cellularity (MC) HD. The median age was 31, mean of 33.5 years (range of 17 to 66 years). The median follow-up was 52 months, mean of 62.1 months (range 5 to 265 months). Treatment plan All patients were treated with curative intent, using 10 MV photons at 120 c.m. source-skin distance. All patients had custom-shaped blocks to protect the lung, kidneys, heart, and bowel. In order to immobilize the patient and assure daily reproducibility, the “mantle board” was employed. Splenic localization was performed by CT scanning and simulation. The 2 and 2 technique was used (10). Treatment was divided into two phases. Phase 1: mantle RT, 2000 cGy in 10 equal fractions over 2 weeks, followed by paraaortic and splenic RT, 2000 cGy in 10 fractions, over 2 weeks. Phase 2: mantle RT for a total dose of 1600 cGy in 8 fractions over 11⁄2 weeks, followed by paraaortic and splenic RT in 11⁄2 weeks to a dose of 1600 cGy. A boost dose was given in the involved field totaling 400 cGy in 2 days. The mantle, paraaortic and splenic fields received a total dose of 3600 cGy, and the involved areas 4000 cGy.
RESULTS Only 10 of 94 patients (10.5%) relapsed. Of the 10 relapses, seven recurred nodally in the pelvis, one in the axilla, one submandibularly, and one in the tonsil. There were no relapses among patients with MC disease; nine were with NS, and one with LP. Two were Stage I and eight were Stage II. There were three males and seven females. The median age was 30 and the mean age was 27.4 years (range 17 to 45 years). The median time to relapse was 38 months, mean of 42.3 months (range of 24 to 67 months). All relapsed patients are alive and in complete remission, nine with conventional chemotherapy, and one following autologous bone marrow transplant. No correlation with the erythrocyte sedimentation
Volume 46, Number 5, 2000
rate, lactate dehydrogenase (LDH), or sites of presentation could be established in patients who recurred. DISCUSSION Overall, between a quarter and a third of clinically staged I and II patients will be found to have abdominal disease on exploratory laparotomy (4, 5, 11–13). While these 30% of clinically staged patients will then be upstaged to at least Stage III disease, at exploratory laparotomy, only rarely will asymptomatic clinically staged I and II (A category) patients have lower abdominal node (PSIII) or organ involvement. Virtually all of these nonsymptomatic (A) patients will be upstaged, because of the presence of splenic or upper abdominal node involvement, to pathologic stage III1A (12). Although chemotherapy is generally employed for PSIII1A disease, radiation alone may be adequate (14, 15) since prognosis following RT is roughly comparable to Stage II disease. Powlis and coworkers (16) have shown also that patients with minimal splenic involvement may be adequately treated with mantle, splenic and extended field RT. Thus the finding of III1A disease at exploratory laparotomy would have little impact theoretically on prognosis if the intent is to apply splenic and EFRT on a clinical basis alone. There are now a number of retrospective reports in the treatment of early, clinically staged, nonexplored HD patients treated solely with splenic and EFRT. All reports, including ours, exclude patients with bulky disease and B symptoms, since they conventionally are given chemotherapy either with or without radiation. Some reports have also used other selective criteria for exclusion of certain Stage IIA patients, whereas others, as we, have been more inclusive. A total of more than 300 patients, exclusive of our study (13, 17–21), have now received splenic and EFRT for clinical stage I and II disease. The overall results are virtually identical to our results where no exclusion other than B symptoms or bulk are permitted. Prior data, as well as our own, compare favorably to pathologic stage (PS) I and II (explored) patients who have been treated with EFRT (19, 22). Since approximately 30% of nonexplored clinically stage IIA patients will be presumed to have Stage III1A disease, the inclusion of these patients does not appear to have had an impact on survival or freedom from the disease. Only 10% of patients in our series have relapsed, all of whom are alive following retreatment. A reason adduced for laparotomy is that its use reduces the morbidity of radiation by precluding the need for abdominal and splenic treatment. However, the concern that renal function is compromised by splenic RT is exaggerated because any spleen sufficiently large to overlap substantial amounts of kidney would upstage the patients to CS III, precluding RT as the mainstay modality. In general practice, very few explored patients are treated with mantle field (thorax) RT alone because there is always concern for false-negative explorations. Indeed an exploratory laparot-
Treatment of early-stage Hodgkin’s disease
omy may yield an isolated involved node, which if undetected would have rendered the patient a higher stage (23, 24). This notion is buttressed by a report from the Royal Marsden Hospital, where surgically staged patients were administered mantle radiation alone (25). Most of the relapses occurred in the paraaortic nodes. Mauch et al., from the Harvard Collaborative Oncology Group, reported on 46 laparotomized patients with PS I and II disease, all of whom were treated solely with mantle radiation (26). Half of the patients were retrospectively analyzed. The 4-year actuarial rate of relapse was 17%, almost exclusively below the diaphragm. Although comparisons between our study and the Harvard study are always subject to the criticisms of retrospective analysis, is the 7% difference the result of “false-negative” explorations? The European Organization for Research and Treatment of Cancer (EORTC) H5 trial in PS I and II patients noted an 11% relapse below the diaphragm in mantle treated patients as compared to 4% relapse in EFRT patients (27, 28). Staging laparotomy is associated with potential operative and postoperative complications. Patients who undergo exploratory laparotomy may be subject to a greater incidence of small bowel adhesions and obstruction and other potential complications as a result of radiation (21, 27, 29). There are a number of studies addressing the morbidity of surgical staging. Brogadir and colleagues noted that 37% of patients sustained complications related to this procedure (30). Meeker and associates related a 27% morbidity rate and 6.6% mortality (31). Smith et al. noted that most of the clinically staged I and II patients who were upstaged at surgery had splenic, splenic hilar, or paraaortic involvement, areas covered when patients receive EFRT (6). Although laparoscopy may be useful in certain instances as an alternative to laparotomy for determining the liver status of HD patients (32), there is little need to use the procedure in limited asymptomatic clinically staged disease since the incidence of liver involvement is so rare. While we are not advocates of the routine use of exploratory laparotomy, it still may have utility in the staging of
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certain HD patients, if avoidance of chemotherapy is considered a priority. If such a priority is entertained, laparotomy would be indicated for those patients whose clinical staging is uncertain as may be encountered with an equivocal LAG or CAT scan. Adjuvant chemotherapy, however, would in most circumstances be an alternative. We acknowledge the pitfalls of retrospective analysis. Our data, though, are sufficiently compelling for a general rethinking of the approach to the staging of early HD. Indeed, the EORTC has reported a trial (H6F) which randomized limited clinical stage HD to exploration or directly to EFRT, as in this report. The data indicate that there was no advantage to exploratory laparotomy (19). Patients clinically staged and treated with splenic and EFRT, had a similar rate of freedom from relapse as those explored and treated with EFRT. The Princess Margaret Hospital, in a review of their 20-year experience, concluded that carefully selected patients can be adequately treated with clinical staging and with EFRT (13). Wasserman and coworkers reported that the relapse rate of the clinically staged patients to those staged with laparotomy was similar. Most of their patients, similar to our results, relapsed in the pelvic nodes (21). It is interesting to note that of the 10 patients who relapsed in our study, none had the more aggressive MC histology. Eight had NS and one had LP. Whether this finding represents a chance occurrence or a unique reflection of disease biology remains to be clarified. RT for now remains the mainstay treatment for earlystage HD. If clinically selected and staged patients with limited disease can undergo splenic and EFRT with results comparable to those who have undergone staging surgery, is there truly a place for the routine use of the procedure when it may have little impact on therapeutic decision making? Is the procedure worth the morbidity, potential morbidity, and increased fiscal and physical cost? Perhaps Lacher’s prophecy will prove correct when surgical staging will be recalled as a milestone in the history of HD management, important at one time, but abandoned because it was no longer needed (33).
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