- Email: [email protected]
Response to Konski and Pellegrin
826
I. J. Radiation Oncology 0 Biology 0 Physics
medical and surgical colleagues, to name a few, contribute to the success and failure rates achieved among various centers. And until causes and mechanisms underlying the disease are understood, treatment remains a quantitative art which ultimately focuses on a careful evaluation of the patient, weighing the benefits and risks which may result from different approaches. To compare different treatment approaches properly, a clinical trial is needed. Nonetheless, the University of Minnesota experience should provide valuable insights for those pondering the subtleties of current schools of thought for Hodgkin’s disease radiotherapy. Our analysis is limited to a retrospective, sequential evaluation of a select group of patients who underwent surgical staging. Improved outcomes were observed only in those “high risk” patients who received radical radiotherapy, without sacrificing salvage treatment options or increasing long-term complications (using meticulous field design and optimal daily and total doses to reduce lung complications). Previously poor risk factors were no longer significant after radical radiotherapy, and were indeed treatment-dependent. Certainly, better imaging with CT and better staging may lead to improved outcomes and are a determining factor regarding field modification for high risk patients; however, whole-lung and hilar tomography were used in our patients previously and the advent of CT did not influence the treatment fields. Perhaps the most most challenging group of Hodgkin’s disease patients to treat and achieve complete and lasting remission are those with large mediastinal masses (LMM). Recently, combined modality therapy has become a common approach for early-stage Hodgkin’s disease with mediastinal, hilar, or spleen involvement, with some reporting these characteristics lose significance as poor risk factors in RFS (3, 8). However, some have reported that chemotherapy alone (10) or chemotherapy + radiotherapy were insufficient in controlling disease in patients with LMM, with poor salvage treatment outcomes among those who failed after chemotherapy as a primary modality (6, 9, I 1).It is generally agreed that radiotherapy is necessary regardless of whether or not chemotherapy is used, especially for bulky disease. Looking at benefits versus risks, the development of second malignant neoplasms and cardiovascular complications are the most serious delayed sequellae. It has been widely reported that patients treated with combined modality showed a higher incidence of second malignant neoplasms than patients treated with radiotherapy alone (1, 4, 12, 13) and we have yet to evaluate the late effects of aggressive combined modality regimens. Despite regional variations in the guidelines surrounding good practice and staging techniques for high risk Hodgkin’s disease patients, our experience and that of others (5, 7) leads us to recommend whole-lung irradiation for those with LMM. Our results are comparable to the results of others using chemotherapy alone or aggressive combined modality treatment without the more serious complications associated with these regimens. We feel that combined modality treatment using limited cycles of chemotherapy and low-dose lung irradiation within the mantle field deserves further study (2). CHUNG K. K. LEE, M.D.
University of Minnesota Mpls, MN 55455 1. Boivin, J. F.; Hutchison, Cl. B. Leukemia and other cancers after radiotherapy and chemotherapy for Hodgkin’s disease. JNCI 67(4): 751-759; 1981. 2. Fuller, L. M.; Hagemeister, F. B.; North, L. B.; McLaughlin, P.; Velasquez, W. S.; Cabanillas, F. The adjuvant role of two cycles of MOPP and low-dose lung irradiation in stage IA through IIIB Hodgkin’s disease: preliminary results. Int. J. Radiat. Oncol. Biol. Phys. 14:683-692; 1988. 3. Hagemeister, F. B.; Fuller, L. M.; Velasquez, W. S.; Sullivan, J. A.; North, L.; Butler, J. J.; Johnston, D. A.; Schullenberger, C. C. Treatment of Stage I and II mediastinal Hodgkin’s disease. A comparison of involved fields, extended fields, and involved fields followed by MOPP in patients staged by laparotomy. Radiology 14 1:783-789; 1981. 4. Henry-Amar, M. Quantitative risk of second cancer in patients in first remission from early stages of Hodgkin’s disease. NC1 Monog. 6~65-72; 1988. 5. Hoppe, R. T. The management of stage II Hodgkin’s disease with a large mediastinal mass: a prospective program emphasizing irradiation. Int. J. Radiat. Oncol. Biol. Phy. 11:349-355; 1985. 6. Khmo, P.; Connors, J. M. An update on the Vancouver experience
September 1990, Volume 19, Number 3
7
8
9.
IO.
II
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13.
in the management of advanced Hodgkin’s disease treated with the MOPP/ABV hybrid program. Sem. Hematol. 25(2):34-40; 1988. Lee, C. K. K.; Aeppli, D. M.; Bloomfield, C. D.; Levitt, S. H. Curative radiotherapy for laparotomy-staged IA, IIA, IIIA Hodgkin’s disease: an evaluation of the gains achieved with radical radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 19:000-000; 1990. Mauch, P.; Hellman, S. Supradiaphragmatic Hodgkin’s disease: is there a role for MOPP chemotherapy in patients with bulky mediastinal disease? Int. J. Radiat. Biol. Phys. 6:947-949; 1980. Mazza, P.; Lauria, F.; Sciascia, R.; Emiliani, E.; Fiacchini, M.; Baccarani, M.; Frezza, G.; Dominici, Cl.; Cantore, M.; Feadi, M.; Gherlinzoni, F.; Tura, S. Prognostic significance of large mediastinal involvement in Hodgkin’s disease. Scan J. Haematol. 31:315-32 I; 1983. Pavlofsky, S.; Maschio, M.; Santarelli, M. T.; Muriel, F. S.; Caorrado, C.: Garcia, 1.; Schwartz, L.; Montero, C.; Sanahuja, F. L.; Magnasuo, 0. Randomized trial of chemotherapy vs. chemotherapy plus radiotherapy for Stage I-II Hodgkin’s disease. M. Nat. Cancer Inst. 2323:1466-1473; i988. Sutcliffe, S. B.; Gospodarowicz, M. K.; Bergsagel, D. E.; Bush, R. S.; Alison, R. E.; Bean, H. A.; Brown, T. C.; Chua, T.; Clark, R. M.; Curtis, A. J.; Dembo, A. J.; Fitzpatrick, P. J.; Hasselback, R. H.; Rideout, D. F.; Sturgeon, J. F. G.; Quirt, 1.; Yeoh, L.; Peters, M. V. Prognostic groups for management of localized Hodgkin’s disease. JOC 3(3):393-401; 1985. Tester, W. J.; Kinsella, T. J.; Wailer, B.; Makuch, R. W.; Kelley, R. A.; Glatstein, E.; DeVita, V. T. Second malignant neoplasms complicating Hodgkin’s disease: the National Cancer Institute Experience. J. Clin. Oncol. 2(7):762-769; 1984. Tucker, M. A.; Coleman, C. N.; Cox, R. S.; Varghese, A.; Rosenberg, S. A. Risk of second cancers after treatment for Hodgkin’s disease. N. Engl. J. Med. 318(2):76-81; 1988.
RESPONSE
TO KONSKI AND PELLEGRIN
To the Editor: We appreciate the comments of Drs. Konski and Pellegrini regarding our experience with radiation therapy and agree that their results have roughly paralleled ours as documented in the current article’ and previous publication? We agree, as documented in this article, that there is no longer a role for the use of five- and ten-fraction protocols. The one remaining significant discrepancy concerns the issue of shielding the trochanteric osteotomy site. The trochanteric migration rate in the unshielded group of hips was much higher than the expected incidence seen in our nonirradiated historical controls. This cannot be explained by the incidence of revisions in the group, as three of the five trochanteric migrations occurred following primary total hip arthroplasty. In addition, a significant number of revision operations were done in the group of hips with shielded trochanteric osteotomies, yet all these hips showed union. In conclusion, we prefer the use of larger fields to assure adequate coverage of the high risk areas with custom shielding of porous components and the trochanteric osteotomy (if present). LINDSAY H. BLOUNT, M.D. Department of Radiation Oncology BERTJ. THOMAS,M.D. Department of Orthopaedics UCLA School of Medicine 10833 LeConte Ave. Los Angeles, CA 90024- 17I4
Sylvester, J. E.; Greenberg, P.; Selch, M. T.; Thomas, B. J.; Amstutz, H. C. Irradiation for the prevention of heterotropic bone formation after total hip replacement. Int. J. Radiat. Oncol. Biol. Phys. 14: 47 l-476; 1988. Konski, A.; Pellegrini, V. D. Postoperative irradiation for prevention of heterotopic bone after total hip arthroplasty. Int. J. Radiat. Oncol. Biol. Phys. 19:809-8 I 1; 1990. Konski, A.; Pellegrini, V. D.; Poulter, C.; DeVanny, J.; Rosier, R.; Evarts, C. M.; Henzler, M.; Rubin, P. Randomized trial comparing single dose vs. fractioned irradiation for prevention of heterotropic bone: a preliminary report. Int. J. Radiat. Oncol. Biol. Phys. 18: 1139-1142; 1990.
I. J. Radiation Oncology 0 Biology 0 Physics
medical and surgical colleagues, to name a few, contribute to the success and failure rates achieved among various centers. And until causes and mechanisms underlying the disease are understood, treatment remains a quantitative art which ultimately focuses on a careful evaluation of the patient, weighing the benefits and risks which may result from different approaches. To compare different treatment approaches properly, a clinical trial is needed. Nonetheless, the University of Minnesota experience should provide valuable insights for those pondering the subtleties of current schools of thought for Hodgkin’s disease radiotherapy. Our analysis is limited to a retrospective, sequential evaluation of a select group of patients who underwent surgical staging. Improved outcomes were observed only in those “high risk” patients who received radical radiotherapy, without sacrificing salvage treatment options or increasing long-term complications (using meticulous field design and optimal daily and total doses to reduce lung complications). Previously poor risk factors were no longer significant after radical radiotherapy, and were indeed treatment-dependent. Certainly, better imaging with CT and better staging may lead to improved outcomes and are a determining factor regarding field modification for high risk patients; however, whole-lung and hilar tomography were used in our patients previously and the advent of CT did not influence the treatment fields. Perhaps the most most challenging group of Hodgkin’s disease patients to treat and achieve complete and lasting remission are those with large mediastinal masses (LMM). Recently, combined modality therapy has become a common approach for early-stage Hodgkin’s disease with mediastinal, hilar, or spleen involvement, with some reporting these characteristics lose significance as poor risk factors in RFS (3, 8). However, some have reported that chemotherapy alone (10) or chemotherapy + radiotherapy were insufficient in controlling disease in patients with LMM, with poor salvage treatment outcomes among those who failed after chemotherapy as a primary modality (6, 9, I 1).It is generally agreed that radiotherapy is necessary regardless of whether or not chemotherapy is used, especially for bulky disease. Looking at benefits versus risks, the development of second malignant neoplasms and cardiovascular complications are the most serious delayed sequellae. It has been widely reported that patients treated with combined modality showed a higher incidence of second malignant neoplasms than patients treated with radiotherapy alone (1, 4, 12, 13) and we have yet to evaluate the late effects of aggressive combined modality regimens. Despite regional variations in the guidelines surrounding good practice and staging techniques for high risk Hodgkin’s disease patients, our experience and that of others (5, 7) leads us to recommend whole-lung irradiation for those with LMM. Our results are comparable to the results of others using chemotherapy alone or aggressive combined modality treatment without the more serious complications associated with these regimens. We feel that combined modality treatment using limited cycles of chemotherapy and low-dose lung irradiation within the mantle field deserves further study (2). CHUNG K. K. LEE, M.D.
University of Minnesota Mpls, MN 55455 1. Boivin, J. F.; Hutchison, Cl. B. Leukemia and other cancers after radiotherapy and chemotherapy for Hodgkin’s disease. JNCI 67(4): 751-759; 1981. 2. Fuller, L. M.; Hagemeister, F. B.; North, L. B.; McLaughlin, P.; Velasquez, W. S.; Cabanillas, F. The adjuvant role of two cycles of MOPP and low-dose lung irradiation in stage IA through IIIB Hodgkin’s disease: preliminary results. Int. J. Radiat. Oncol. Biol. Phys. 14:683-692; 1988. 3. Hagemeister, F. B.; Fuller, L. M.; Velasquez, W. S.; Sullivan, J. A.; North, L.; Butler, J. J.; Johnston, D. A.; Schullenberger, C. C. Treatment of Stage I and II mediastinal Hodgkin’s disease. A comparison of involved fields, extended fields, and involved fields followed by MOPP in patients staged by laparotomy. Radiology 14 1:783-789; 1981. 4. Henry-Amar, M. Quantitative risk of second cancer in patients in first remission from early stages of Hodgkin’s disease. NC1 Monog. 6~65-72; 1988. 5. Hoppe, R. T. The management of stage II Hodgkin’s disease with a large mediastinal mass: a prospective program emphasizing irradiation. Int. J. Radiat. Oncol. Biol. Phy. 11:349-355; 1985. 6. Khmo, P.; Connors, J. M. An update on the Vancouver experience
September 1990, Volume 19, Number 3
7
8
9.
IO.
II
12.
13.
in the management of advanced Hodgkin’s disease treated with the MOPP/ABV hybrid program. Sem. Hematol. 25(2):34-40; 1988. Lee, C. K. K.; Aeppli, D. M.; Bloomfield, C. D.; Levitt, S. H. Curative radiotherapy for laparotomy-staged IA, IIA, IIIA Hodgkin’s disease: an evaluation of the gains achieved with radical radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 19:000-000; 1990. Mauch, P.; Hellman, S. Supradiaphragmatic Hodgkin’s disease: is there a role for MOPP chemotherapy in patients with bulky mediastinal disease? Int. J. Radiat. Biol. Phys. 6:947-949; 1980. Mazza, P.; Lauria, F.; Sciascia, R.; Emiliani, E.; Fiacchini, M.; Baccarani, M.; Frezza, G.; Dominici, Cl.; Cantore, M.; Feadi, M.; Gherlinzoni, F.; Tura, S. Prognostic significance of large mediastinal involvement in Hodgkin’s disease. Scan J. Haematol. 31:315-32 I; 1983. Pavlofsky, S.; Maschio, M.; Santarelli, M. T.; Muriel, F. S.; Caorrado, C.: Garcia, 1.; Schwartz, L.; Montero, C.; Sanahuja, F. L.; Magnasuo, 0. Randomized trial of chemotherapy vs. chemotherapy plus radiotherapy for Stage I-II Hodgkin’s disease. M. Nat. Cancer Inst. 2323:1466-1473; i988. Sutcliffe, S. B.; Gospodarowicz, M. K.; Bergsagel, D. E.; Bush, R. S.; Alison, R. E.; Bean, H. A.; Brown, T. C.; Chua, T.; Clark, R. M.; Curtis, A. J.; Dembo, A. J.; Fitzpatrick, P. J.; Hasselback, R. H.; Rideout, D. F.; Sturgeon, J. F. G.; Quirt, 1.; Yeoh, L.; Peters, M. V. Prognostic groups for management of localized Hodgkin’s disease. JOC 3(3):393-401; 1985. Tester, W. J.; Kinsella, T. J.; Wailer, B.; Makuch, R. W.; Kelley, R. A.; Glatstein, E.; DeVita, V. T. Second malignant neoplasms complicating Hodgkin’s disease: the National Cancer Institute Experience. J. Clin. Oncol. 2(7):762-769; 1984. Tucker, M. A.; Coleman, C. N.; Cox, R. S.; Varghese, A.; Rosenberg, S. A. Risk of second cancers after treatment for Hodgkin’s disease. N. Engl. J. Med. 318(2):76-81; 1988.
RESPONSE
TO KONSKI AND PELLEGRIN
To the Editor: We appreciate the comments of Drs. Konski and Pellegrini regarding our experience with radiation therapy and agree that their results have roughly paralleled ours as documented in the current article’ and previous publication? We agree, as documented in this article, that there is no longer a role for the use of five- and ten-fraction protocols. The one remaining significant discrepancy concerns the issue of shielding the trochanteric osteotomy site. The trochanteric migration rate in the unshielded group of hips was much higher than the expected incidence seen in our nonirradiated historical controls. This cannot be explained by the incidence of revisions in the group, as three of the five trochanteric migrations occurred following primary total hip arthroplasty. In addition, a significant number of revision operations were done in the group of hips with shielded trochanteric osteotomies, yet all these hips showed union. In conclusion, we prefer the use of larger fields to assure adequate coverage of the high risk areas with custom shielding of porous components and the trochanteric osteotomy (if present). LINDSAY H. BLOUNT, M.D. Department of Radiation Oncology BERTJ. THOMAS,M.D. Department of Orthopaedics UCLA School of Medicine 10833 LeConte Ave. Los Angeles, CA 90024- 17I4
Sylvester, J. E.; Greenberg, P.; Selch, M. T.; Thomas, B. J.; Amstutz, H. C. Irradiation for the prevention of heterotropic bone formation after total hip replacement. Int. J. Radiat. Oncol. Biol. Phys. 14: 47 l-476; 1988. Konski, A.; Pellegrini, V. D. Postoperative irradiation for prevention of heterotopic bone after total hip arthroplasty. Int. J. Radiat. Oncol. Biol. Phys. 19:809-8 I 1; 1990. Konski, A.; Pellegrini, V. D.; Poulter, C.; DeVanny, J.; Rosier, R.; Evarts, C. M.; Henzler, M.; Rubin, P. Randomized trial comparing single dose vs. fractioned irradiation for prevention of heterotropic bone: a preliminary report. Int. J. Radiat. Oncol. Biol. Phys. 18: 1139-1142; 1990.