|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 1999 American Society for Clinical Oncology Laparotomy Versus No Laparotomy in the Management of Early-Stage, Favorable-Prognosis Hodgkin's Disease: A Decision AnalysisFrom the Joint Center for Radiation Therapy and Dana-Farber Cancer Institute, Harvard Medical School; and the Department of Health Policy and Management, Harvard School of Public Health, Boston, MA. Address reprint requests to Karen M. Kuntz, ScD, Center for Risk Analysis, Harvard School of Public Health, 718 Huntington Ave, Boston, MA 02115–5924; Email kmk{at}hsph.harvard.edu
PURPOSE: To perform a decision analysis that compared the life expectancy and quality-adjusted life expectancy of early-stage, favorable-prognosis Hodgkin's disease (HD) managed with and without staging laparotomy, incorporating data on treatment outcomes of HD in the modern era. METHODS: We constructed a decision-analytic model to compare laparotomy versus no laparotomy staging for a hypothetical cohort of 25-year-old patients with clinical stages I and II, favorable-prognosis HD. Markov models were used to simulate the lifetime clinical course of patients, whose prognosis depended on the true pathologic stage and initial treatment. The baseline probability estimates used in the model were derived from results of published studies. Quality-of-life adjustments for procedures and treatments, as well as the various long-term health states, were incorporated. RESULTS: The life expectancy was 36.67 years for the laparotomy strategy and 35.92 years for no laparotomy, yielding a net expected benefit of 0.75 years for laparotomy staging. The corresponding quality-adjusted life expectancies for the two strategies were 35.97 and 35.38 quality-adjusted life years (QALYs), respectively, resulting in a net expected benefit of laparotomy staging of 0.59 QALYs. Sensitivity analysis showed that the decision of laparotomy versus no laparotomy was most heavily influenced by the quality-of-life weight assigned to the postlaparotomy state. CONCLUSION: Our model predicted that on average, for a 25-year-old patient, proceeding with staging laparotomy resulted in a gain in life expectancy of 9 months, or 7 quality-adjusted months. These results suggest that a role remains for surgical staging in the management of early-stage HD.
THE ROLE OF STAGING LAPAROTOMY in the management of early-stage Hodgkin's disease (HD) patients is controversial.1-4 Surgical staging allows treatment to be tailored to the precise pathologic stage (PS). Therefore, the detrimental effects of undertreatment, which increases the risk of relapse, and overtreatment, which increases the risk of short-term and long-term treatment toxicity, are minimized. In addition, the radiation treatment field is smaller after a laparotomy and splenectomy because it is only necessary to treat the splenic pedicle rather than the entire spleen, and in some patients the abdominal field can be omitted altogether. However, laparotomy is associated with a certain degree of surgical morbidity and mortality,5-7 and patients are at increased risk for infections after a splenectomy.8-11 Although in many parts of the world, staging laparotomy is no longer performed and the use of combined modality therapy (CMT) has increased, surgical staging remains the best way to minimize initial therapy. Whether the short-term and long-term disadvantages associated with staging laparotomy are outweighed by the benefits of pathologic staging continues to be an area of debate, as evidenced by wide variations in practice patterns. The question of whether laparotomy should be used for pathologic staging for patients with early-stage HD has been addressed by a number of investigators, using methods of decision analysis to assess the value of staging laparotomy compared with no laparotomy.12-16 Almost all of the studies (now over 15 years old) advocated the use of staging laparotomy. However, most of these studies did not adjust for quality of life, and in the interim there have been some important changes in the management of HD patients. The routine use of computed tomography scans and gallium scans as part of initial staging work-ups helps to identify patients with unfavorable prognostic features— such as large mediastinal adenopathy; hilar, subcarinal, or cardiac nodal involvement; pulmonary parenchymal disease; chest wall or pericardial invasion; or a large number of sites of involvement—in whom upfront CMT is indicated. Laparotomy is now safer, and postsplenectomy overwhelming sepsis has become extremely uncommon with the use of less myelosuppressive chemotherapy and the availability of newer vaccinations given prior to laparotomy.17-21 Less-toxic treatments have been introduced, and with the replacement of mechlorethamine, vincristine, procarbazine, and prednisone therapy by doxorubicin, bleomycin, vinblastine, and decarbazine therapy, problems with infertility have been virtually eliminated and concerns for secondary leukemia substantially reduced. As patients are observed for longer periods of time, more long-term treatment outcome data are becoming available. Delayed treatment toxicities are increasingly recognized, with cardiac complications and secondary malignancies now accounting for the majority of mortality in HD survivors.22-24 We constructed a decision-analytic model that incorporated recent data on the long-term treatment outcomes of HD and took into account quality of life, as well as the morbidity and mortality associated with surgical staging and different treatments received, to determine the optimal management strategy in early-stage, favorable-prognosis HD patients.
Structure of the Model We constructed a decision-analytic model to compare laparotomy versus no laparotomy staging for a hypothetical cohort of 25-year-old patients with clinical stages (CS) I and II, favorable-prognosis HD. Favorable prognosis, for the purpose of this study, was defined as lack of large mediastinal adenopathy and B symptoms. If a laparotomy was performed and PS I or II disease was found, the treatment options were mantle and para-aortic (MPA) radiation therapy, mantle radiation therapy alone, chemotherapy alone, or CMT. If the patient was found to have PS III or IV disease, the treatment alternatives were chemotherapy alone or CMT. The therapeutic options for the clinically staged patient included MPA-splenic radiation therapy, chemotherapy alone, or CMT. Figure 1 shows the decision tree that illustrates the primary decision of laparotomy versus no laparotomy and the secondary treatment decisions.
Markov state-transition models25 were used to project the lifetime prognosis of patients on the basis of their PSs and treatments. Each model consisted of a number of health states, including remission, refractory disease, relapse, secondary leukemia, secondary solid tumor, and secondary non–Hodgkin's lymphoma. The annual probabilities of transition from one state to another were conditional upon the PS and initial treatment. In each cycle (year), depending on their health states, patients were at risk of dying from HD, secondary malignancies, cardiac causes, or natural causes. Figure 2 illustrates a simplified version of the transitions among the different Markov states. The models also allowed for multiple events within one cycle (eg, a patient could have a relapse and develop a secondary malignancy in the same year). Outcomes for the baseline analysis were life expectancy and quality-adjusted life expectancy, with or without time discounting at a rate of 3% per year. Threshold analyses and sensitivity analyses were performed using the discounted, quality-adjusted model. For the treatment-related variables, the ranges used in the analysis were such that the lower and upper bounds were within clinically plausible ranges (eg, for the sensitivity analysis on the relapse rate after mantle radiation therapy alone, the ranges were set such that the relapse-free rate after mantle alone would never be better than that after MPA radiation therapy). The analysis was considered to be "sensitive" to a variable if its threshold value was within 30% of the baseline estimate. For other variables, such as the probability of upstaging, discount rate, and utilities associated with different health states, a range of 0 to 1 was used. The DATA software package (TreeAge Software, Inc., Williamstown, MA) was used to construct the model and perform the analyses.
Key Assumptions Patients who relapsed after radiation therapy underwent salvage treatment with CMT. For patients who relapsed after chemotherapy, one quarter of the patients had limited relapses and underwent salvage treatment with conventional-dose CMT. For patients who had more a extensive relapse after chemotherapy alone, had a relapse after initial CMT, or had refractory disease, three quarters received bone marrow transplants, whereas the remaining patients were deemed ineligible for transplant (eg, due to progressive disease during cytoreduction, presence of comorbid disease, poor performance status, or advanced age) and were treated with chemotherapy alone. It should be noted that most studies on transplant salvage treatment for HD do not report the proportion of patients who were considered for transplant but were subsequently rejected as transplant candidates. One study reported that one third of the original cohort of patients ultimately did not undergo transplants. After nonmedical reasons such as lack of insurance coverage and patient refusal were excluded, one quarter of the patients were denied transplants for medical reasons.30
Baseline Estimates
Pathologic staging.
Refractory disease and relapse. Because there were no data in the literature on treatment outcome with chemotherapy alone in patients with PS III1A HD, we assigned the same estimate of relapse rate as that for patients with PS I or II disease treated with chemotherapy alone.39,40 This was probably a reasonable assumption, since there was unlikely to be large differences in tumor burden between PS I or II patients and PS III1A patients, and both should have a similar likelihood of responding to systemic treatment. This appeared to be the case in PS I or II and PS III1A patients receiving CMT,41,42 in that their probabilities of refractory disease and relapse rates were similar after adjustment for B symptoms and large mediastinal adenopathy.
Secondary malignancies.
Mortality. The literature suggests that patients who relapse after radiation therapy are more successfully treated with salvage regimens than are patients who relapsed after chemotherapy or CMT. The estimated 5-year cause-specific survival rate after radiation-therapy failure was 79.8%,34,53,54 whereas that after chemotherapy or CMT failure was 63.8% with transplant salvage.30,55-62 Because there is a downward trend in the peritransplant mortality rate over time, we used a 9% peritransplant mortality rate, which was on the low end of the range of reported estimates. The annual probability of dying of natural causes in a 25-year-old was derived from the U.S. life tables.73
Quality-of-life adjustments.
Baseline Analysis The life expectancy was 36.67 years for patients undergoing staging laparotomy and 35.92 years for patients who did not have laparotomy, yielding a net expected benefit of 0.75 years, or 9 months, for laparotomy staging. Figure 3 displays the 20-year survival rates of patients who underwent staging laparotomy versus no laparotomy, as predicted by the model.
With quality-of-life adjustment, the laparotomy staging strategy led to a quality-adjusted life expectancy of 35.97 quality-adjusted life years (QALYs), whereas direct treatment without surgical staging yielded 35.38 QALYs. Thus the net expected benefit of laparotomy staging was 0.59 QALYs, or 7 quality-adjusted months. Results of the baseline analysis of laparotomy versus no laparotomy are summarized in Table 2.
Among the pathologically staged patients, the optimal treatment was MPA radiation therapy for PS I or II patients, CMT for PS III1A patients, and chemotherapy alone for PS III2 or IVA patients. If staging laparotomy was not performed, treatment with CMT and MPA radiation therapy yielded very similar life expectancy results, and the optimal treatment strategy for the clinically staged patients was highly dependent on the assigned values of a number of baseline estimates. The baseline analysis results of the secondary decision on therapeutic approaches for pathologically and clinically staged early-stage patients with HD are listed in Table 3. Details of the decision-analysis results on the various treatment alternatives for early-stage HD will be reported and discussed in a separate article.
Sensitivity Analysis
The analysis was highly sensitive to the utility of the postlaparotomy state, with the no-laparotomy strategy preferred over laparotomy if the utility was decreased to 0.98 from our baseline estimate of 0.99. A utility of 0.98, when the standard gamble approach is used, suggests that a patient would be willing to accept a 2% risk of death to avoid the postlaparotomy health state (and the potential increased morbidity and mortality that is implied). With the time trade-off approach, a utility of 0.98 suggests that a patient would be willing to give up 2% of his or her remaining life expectancy to avoid living the rest of his or her life without a spleen after a laparotomy.74,75 The finding that performance of staging laparotomy led to better quality-adjusted survival than did no laparotomy was insensitive to changes in the remaining variables. In particular, performance of staging laparotomy remained the optimal strategy as the probabilities of the following were varied over clinically plausible ranges: refractory disease, relapse, and development of secondary leukemia after various treatments; development of secondary solid tumor after chemotherapy alone or radiotherapy alone; mortality after relapses or development of secondary malignancies; cardiac mortality after various treatments; and short-term utility weights associated with treatments and long-term utility weights associated with health states of refractory disease, relapse or secondary malignancies. The estimates of the secondary leukemia risks after chemotherapy alone or CMT, when modern-era chemotherapy regimens are used, are not yet clearly defined and may have been overestimated in our model. Although there is clear evidence that secondary leukemia risk after HD is directly linked to the cumulative dose of alkylating agents,76 there has been no formal documentation of the risks of secondary leukemia with the more recent, predominantly nonalkylating chemotherapeutic regimens. The risk estimation is further complicated by the fact that the type and number of cycles of combination chemotherapy used are not uniform, with some oncologists continuing to include mechlorethamine in either a hybrid form or alternating with other chemotherapeutic agents. Although secondary leukemia risks did not affect the decision of laparotomy versus no laparotomy in our one-way sensitivity analysis, we simultaneously explored the effects of varying the secondary leukemia risks after chemotherapy alone and after CMT on the benefit of performing staging laparotomy. Figure 4 is a threshold graph that displays the two-way sensitivity analysis results. Variation of the AR for leukemia after chemotherapy alone had little impact on the results of the analysis. When the AR for leukemia after CMT was decreased to 8/10,000 person-years or lower, which is less than one quarter of the value of its baseline estimate, no laparotomy became the favored strategy.
Validation of the Model
We used a decision-analytic model to compare the life expectancy of patients with early-stage HD evaluated with staging laparotomy with those evaluated without staging laparotomy. Our model suggested that for a 25-year-old patient, proceeding with staging laparotomy resulted in a gain in life expectancy of 9 months, or 7 quality-adjusted months. The results of previous decision-analytic models on the management of HD, all performed over 15 years ago, almost uniformly favored the strategy of laparotomy over that of no laparotomy. However, their end points were primarily overall survival or disease-free survival without quality-of-life adjustments. In our model, the decrease in net benefit of laparotomy with quality-of-life adjustments (from 9 months to 7 quality-adjusted months) suggests that the diminished quality of life of the postlaparotomy state applied over the entire cohort of pathologically staged patients outweighs the effect of additional relapses in the inadequately treated, or toxicities in the overtreated, clinically staged patients. In the European Organization for Research and Treatment of Cancer H6 trial, conducted from 1982 to 1987, 232 early-stage, favorable-prognosis HD patients were randomized to laparotomy (laparotomy-negative patients were treated with mantle alone or MPA radiation therapy, depending on histology; laparotomy-positive patients were treated with CMT), and no laparotomy (all treated with MPA and splenic radiation therapy).76 Results at 6 years showed no survival differences, although there was a trend toward lower relapse rates among patients who underwent staging laparotomy. However, recently updated results at 10 years of median follow-up (Dr. J.M. Cosset, written communication, October 1997) revealed a significant difference in overall survival between the two treatment arms, favoring the no-laparotomy arm. The poorer survival results found in the laparotomy arm were attributed to laparotomy-related toxicity. The findings in the H6 trial, which are contrary to our results, should be considered with caution. Postlaparotomy death has become exceedingly rare in the current era. With the decreased use of myelosuppressive agents and the availability of newer vaccines, overwhelming sepsis has become very uncommon.17-21 Our finding that the performance of staging laparotomy, compared with no laparotomy, resulted in a survival gain is quite robust. The decision of laparotomy versus no laparotomy is unaffected by most of the variables in the model and is dependent on only a few variables on which there are relatively solid data. The main exception is the considerable influence of the utility of the postlaparotomy state on the optimal decision. However, although the threshold utility value of 0.98 for the postlaparotomy state is very close to its estimated baseline value of 0.99, it is rather unlikely that a patient would be willing to give up 2% of his or her remaining life expectancy to avoid being in a postlaparotomy state. This is because even though surgical staging involves removal of the spleen for pathologic evaluation, overwhelming sepsis in asplenic patients, as discussed, is now very rare. The main inconvenience faced by a postlaparotomy patient is that fevers cannot be taken lightly, and antibiotics need to be taken when a fever develops. There are several limitations in our model. First, the analysis was performed on a cohort of 25-year-old patients, and the implications of the results on patients of other ages is not clear. However, our model predicted that when the risk of perioperative mortality is above 1.5%, the no-laparotomy strategy became the favored strategy, suggesting that older patients with significant comorbid disease may not benefit from staging laparotomy. Second, only the mortality, but not the morbidity, of treatment-related cardiac complications was included in the model. It is very difficult to quantify the risks of cardiac complications after treatment, which may range from asymptomatic valvular disease or transient pericarditis to coronary artery disease,70,71 each of which may have different effects on quality of life. However, although pathologic-staging results affect the type of treatment received, cardiac complications occur in patients managed with and without staging laparotomy. Moreover, the risks are small and therefore are not expected to be influential. Third, we assumed that patients were at constant risk of dying with refractory disease, relapse, or secondary malignancy. In reality, the risks of dying of recurrent disease or a secondary malignancy decrease with time from the relapse or development of the secondary tumor. However, to model varying mortality rates after relapse or second malignancy would require the use of substantially more complex modeling techniques. Nevertheless, in validating the model, we found that the survival outcomes and distribution of mortality at various time periods after diagnosis that were predicted by the model closely agreed with the observed data, suggesting that our model is a sound one. The perioperative mortality rate for staging laparotomy of 0.5% was likely an overestimation, compared with the more recent surgical series.8,9 For patients who did not undergo staging laparotomy, we did not incorporate into the model the fact that MPA radiation therapy for the clinically staged patients, unlike that for the pathologically staged patients, involved a larger radiation field with inclusion of the entire spleen. The volume of lung and heart that were irradiated increased substantially, leading to more acute side effects as well as potentially increased long-term complications. It may also produce functional hyposplenism78 and place patients at risk for infections. Despite these biases against the laparotomy strategy, we still found laparotomy to be the favored strategy. In the management of early-stage, favorable-prognosis HD patients, there is no consensus yet on whether staging laparotomy should be performed and which, if any, is the optimal treatment approach. When faced with a disease in which there are multiple alternative management approaches, without clear advantages of one over another, physicians must consider the short-term and long-term morbidity and mortality associated with each strategy. Decision analysis offers a useful tool for the assessment of the different alternatives, weighing their benefits against risks over time. It also allows formal incorporation of individual preferences into the decision-making process. However, the need to make simplifying assumptions and the uncertainties associated with some of the baseline estimates are inherent to this type of analysis. Our results suggest that in discussing with patients the option of laparotomy as part of the staging workup, it is important to clearly communicate to them the long-term clinical implications of the procedure and that trade-offs need to be made between the potential survival gain and the nuisances associated with life after laparotomy and splenectomy. In addition, when the results of this model are applied to individual patients, it would be appropriate to incorporate their individual risk levels on the basis of their clinical characteristics because the greater life expectancy found in the laparotomy strategy reflects the average benefits for a cohort of 25-year-old patients with defined risks. Specifically, patients with low upstaging risks, such as CS IA female patients or CS IA male patients with lymphocyte-predominant histology, or patients who are at increased risk for surgery due to, for instance, comorbid diseases, should be considered for direct treatment on the basis of clinical staging results instead of surgical staging. Finally, our results indicate that there is a need for close observation of patients treated with modern-era chemotherapy regimens either alone or in combination with radiotherapy and better quantification of their secondary leukemia risks, particularly because it may alter the decision of laparotomy versus no laparotomy. Although the survival benefit of staging laparotomy predicted by our model may seem somewhat modest, consistent with the observed excellent clinical outcomes of patients with early-stage HD regardless of management approaches, it is of comparable magnitude to the gains in life expectancy reported in decision analyses for well-accepted interventions used in other types of cancer.79-81 For instance, Hillner et al79 found an 11-month gain in life expectancy with use of adjuvant chemotherapy in early-stage breast cancer patients. Therefore, our results suggest that there may remain a role for surgical staging in the management of early-stage, favorable-prognosis HD.
A.K.N. is a recipient of the American Society for Therapeutic Radiology and Oncology Outcomes Research Fellowship for 1997–1998.
1. Mauch PM: Controversies in the management of early stage Hodgkin's disease. Blood 83:318-329, 1994
2.
Mauch PM, Somers R: Controversies in the use of diagnostic staging laparotomy and splenectomy in the management of Hodgkin's disease. Ann Oncol 4:41-43, 1992 3. Rosenberg SA: Laparotomy and splenectomy in Hodgkin's disease: A reappraisal after 20 years. Scand J Haematol 34:289-292, 1985[Medline] 4. Carde P, Burgers JM, Henry-Amar M, et al: Clinical stages I and II Hodgkin's disease: A specifically tailored therapy according to prognostic factors. J Clin Oncol 6:239-252, 1988[Abstract] 5. Taylor M, Kaplan H, Nelson T, et al: Staging laparotomy with splenectomy from Hodgkin's disease: The Stanford experience. World J Surg 9:449-452, 1985[Medline] 6. Brogadir S, Fialk M, Coleman M, et al: Morbidity of staging laparotomy in Hodgkin's disease. Am J Med 65:429-453, 1978 7. Kaiser C: Complications from staging laparotomy for Hodgkin's disease. J Surg Oncol 16:319-323, 1981[Medline] 8. Leibenhaut M, Hoppe R, Efron B, et al: Prognostic indicators of laparotomy findings in clinical stage I-II supradiaphragmatic Hodgkin's disease. J Clin Oncol 7:81-85, 1989[Abstract] 9. Mauch PM, Larson D, Osteen R, et al: Prognostic factors for positive surgical staging in patients with Hodgkin's disease. J Clin Oncol 8:257-262, 1990[Abstract] 10. Donaldson SS, Moore MR, Rosenberg SA, et al: Characteristics of post-splenectomy bacteremia among patients with and without lymphoma. N Engl J Med 287:69-71, 1972 11. Chelcote RR, Baehner RL, Hammond D, et al: Septicemia and meningitis in children splenectomized for Hodgkin's disease. N Engl J Med 295:798-800, 1976[Abstract] 12. Safran C, Tsichlis PN, Bluming AZ, et al: Diagnostic planning using computer assisted decision-making for patients with Hodgkin's disease. Cancer 39:2426-2434, 1977[Medline] 13. Fineberg HV: Decision trees: Construction, uses, and limits. Bull Cancer 67:395-404, 1980[Medline] 14. Deforges JF: Diagnostic planning using computer-assisted decision-making for the patients with Hodgkin's disease. Bull Cancer 67:418-423, 1980[Medline] 15. Rutherford CJ, Deforges JF, Davies B, et al: The decision to perform staging laparotomy in symptomatic Hodgkin's disease. Br J Haematol 44:347-358, 1980[Medline] 16. Corder MP, Ellwein LB: A decision-analysis methodology for consideration of morbidity factors in clinical decision-making. Am J Clin Oncol 6:19-32, 1984 17. Jockovich M, Mendenhall NP, Sombeck MD, et al: Long-term complications of laparotomy in Hodgkin's disease. Ann Surg 219:615-624, 1994[Medline] 18. Chan CY, Molrine DC, George S, et al: Pneumococcal conjugate vaccine primes for antibody response to polysaccharide pneumococcal vaccine following treatment of Hodgkin's disease. J Infect Disease 173:256-258, 1996[Medline] 19. Molrine D, George S, Tarbell N, et al: Antibody responses to polysaccharide and polysaccharide-conjugate vaccines following treatment for Hodgkin's disease. Ann Intern Med 123:824-828, 1995 20. Grimfors G, Soderquist M, Holar G, et al: A longitudinal study of class and subclass of antibody response to pneumococcal vaccination in splenectomized individuals with special reference to patients with Hodgkin's disease. Eur J Haematol 45:101-108, 1990[Medline] 21. Siber GR, Gorham C, Martin P, et al: Antibody response to pretreatment immunization and post-treatment boosting with bacterial polysaccharide vaccines in patients with Hodgkin's disease. Ann Intern Med 104:467-475, 1986 22. Hancock SL, Hoppe RT: Long-term complications of treatment and causes of mortality after Hodgkin's disease. Semin Radiat Oncol 6:225-242, 1996[Medline]
23.
Cosset JM, Henry-Amar M, Meerwaldt JH, et al: Long-term toxicity of early stages of Hodgkin's disease therapy: The EORTC experience. Ann Oncol 2:77-82, 1991 (suppl 2) 24. Mauch PM, Kalish LA, Marcus KC, et al: Long-term survival in Hodgkin's disease: Relative impact of mortality, second tumors, infection and cardiovascular disease. Cancer J Sci Am 1:33-42, 1995[Medline] 25. Sonnenberg FA, Beck JR: Markov models in medical decision making: A practical guide. Med Decis Making 13:322-338, 1993
26.
Bodis S, Henry-Amar M, Bosq J, et al: Late relapse in early-stage Hodgkin's disease patients enrolled on European Organization for Research and Treatment of Cancer Protocols. J Clin Oncol 11:225-232, 1993 27. Weller SA, Gladstein E, Kaplan HS, et al: Initial relapses in previously treated Hodgkin's disease. Cancer 37:2840-2846, 1976[Medline] 28. Tucker MA, Coleman CN, Cox RS, et al: Risk of second cancer after treatment for Hodgkin's disease. N Engl J Med 318:76-81, 1988[Abstract]
29.
Mauch PM, Kalish LA, Marcus KC, et al: Second malignancies after treatment for laparotomy-staged IA-IIIB Hodgkin's disease: Long-term analysis of risk factors and outcome. Blood 87:3625-3632, 1996
30.
Horning SJ, Chao NJ, Negrin RS, et al: High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: Analysis of the Stanford University results and prognostic indices. Blood 89:801-813, 1997
31.
Mauch PM, 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 6:1576-1583, 1988 32. Jones E, Mauch P: Limited radiation therapy for selected patients with pathological stages IA and IIA Hodgkin's disease. Semin Radiat Oncol 6:162-171, 1996[Medline]
33.
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 34. Rosenberg SA, Kaplan HS: The evolution and summary results of the Stanford randomized clinical trials of the management of Hodgkin's disease. Int J Rad Oncol Biol Phys 11:5-11, 1985[Medline] 35. Anderson H, Crowther D, Deakin DP, et al: A randomised study of adjuvant MVPP chemotherapy after mantle radiotherapy in pathologically staged IA-IIB Hodgkin's disease: 10-year follow-up. Ann Oncol 2:49-51, 1991 (suppl 2) 36. Nissen NI, Nordentoft AM: Radiotherapy versus combined modality therapy of stages I and II Hodgkin's disease. Cancer Treat Rep 66:799-803, 1982[Medline] 37. Jones SE, Coltman CA, Grozea PN, et al: Conclusions from clinical trials of the Southwest Oncology Group. Cancer Treat Rep 66:847-853, 1982[Medline] 38. Horning SJ, Hoppe RT, Hancock SL, et al: Vinblastine, bleomycin, methotrexate: An effective adjuvant in favorable Hodgkin's disease. J Clin Oncol 6:1822-1831, 1988[Abstract] 39. Longo DL, Glatstein E, Duffey PL, et al.: Radiation therapy versus combination chemotherapy in the treatment of early-stage Hodgkin's disease: 7-Year results of a prospective randomized trial. J Clin Oncol 9:906-917, 1991[Abstract]
40.
Biti GP, Cimino G, Cartoni C, et al: Extended-field radiotherapy is superior to MOPP chemotherapy for the treatment of pathological-stage I-IIA Hodgkin's disease: 8-Year update of an Italian prospective randomized study. J Clin Oncol 10:378-382, 1992
41.
Farah R, Ultmann J, Griem M, et al: Extended mantle radiation therapy for pathological stage I and II Hodgkin's disease. J Clin Oncol 6:1047-1052, 1988
42.
Marcus KC, Kalish LA, Coleman CN, et al: Improved survival in patients with limited stage IIIA Hodgkin's disease treated with combined radiation therapy and chemotherapy. J Clin Oncol 12:2567-2572, 1994
43.
Mauch P, Goffman T, Rosenthal D, et al: Stage III Hodgkin's disease: Improved survival with combined modality therapy as compared with radiation therapy alone. J Clin Oncol 3:1166-1173, 1985
44.
Fabian CJ, Mansfield CM, Dahlberg S, et al: Low-dose involved field radiation after chemotherapy in advanced Hodgkin's disease: A Southwest Oncology Group Randomized Study. Ann Intern Med 120:903-912, 1994
45.
Crnkovich MJ, Leopold K, Hoppe RT, et al: Stage I to IIB Hodgkin's disease: The combined experience at Stanford University and the Joint Center for Radiation Therapy. J Clin Oncol 5:1041-1049, 1987 46. Canellos GP, Anderson JR, Propert KJ, et al.: Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 327:1478-1484, 1992[Abstract] 47. Yahalom J, Ryu J, Straus DJ, et al: Impact of adjuvant radiation in the patterns and rate of relapse in advanced-stage Hodgkin's disease treated with alternating chemotherapy combinations. J Clin Oncol 9:2193-2201, 1991[Abstract] 48. Santoro A, Bonadonna G, Valagussa P, et al: Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: Superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol 5:27-37, 1987[Abstract] 49. Rodgers RW, Fuller LM, Hagemeister FB, et al: Reassessment of prognostic factors in stage IIIA and IIIB Hodgkin's disease treated with MOPP and radiotherapy. Cancer 47:2196-2203, 1981[Medline] 50. Bonadonna G, Valagussa P, Santoro A, et al: Prognosis of bulky Hodgkin's disease treated with chemotherapy alone or combined with radiotherapy. Cancer Surv 4:439-457, 1985[Medline] 51. Biti G, Cellai E, Magrini SM, et al: Second solid tumors and leukemia after treatment for Hodgkin's disease: An analysis of 1126 patients from a single institution. Int J Radiat Oncol Biol Phys 29:25-31, 1994[Medline]
52.
Gobbi P, Pieresca C, Frassoldati A, et al: Vinblastine, bleomycin and methotrexate chemotherapy plus extended-field radiotherapy in early, favorably presenting, clinically staged Hodgkin's patients: The Gruppo Italiano per lo Studio dei Linfomi Experience. J Clin Oncol 14:527-533, 1996 53. Healey EA, Tarbell NJ, Kalish LA: Prognostic factors for patients with Hodgkin's disease in first relapse. Cancer 71:2613-2620, 1993[Medline] 54. Roach M III Brophy N, Cox R, et al: Prognostic factors for patients relapsing after radiotherapy for early-stage Hodgkin's disease. J Clin Oncol 8:623-639, 1990[Abstract]
55.
Yahalom J, Gulati SC, Toia M, et al: Accelerated hyperfractionated total lymphoid irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for refractory and relapsing patients with Hodgkin's disease. J Clin Oncol 11:1062-1070, 1993
56.
Anderson JE, Litzow MR, Appelbaum FR, et al: Allogeneic, synergistic, and autologous marrow transplantation for Hodgkin's disease: The 21-year Seattle experience. J Clin Oncol 11:2342-2350, 1993
57.
Reece DE, Barnett MJ, Shephard JD, et al: High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16–213) with or without cisplatin (CBV+/-P) and autologous transplantation for patients with Hodgkin's disease who fail to enter a complete remission after combination chemotherapy. Blood 86:451-456, 1985
58.
Bierman PJ, Bagin RG, Jagannath S, et al: High-dose chemotherapy followed by autologous hematopoietic rescue in Hodgkin's disease. Ann Oncol 4:767-773, 1993
59.
Chopra R, McMillan AK, Linch DC, et al: The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease: A single-center eight-year study of 155 patients. Blood 81:1137-1145, 1993 60. Linch DC, Winfield D, Goldstone AH, et al: Dose intensification with autologous bone marrow transplantation in relapsed and resistant Hodgkin's disease: Results of a BNLI randomised trial. Lancet 341:1051-1054, 1993[Medline] 61. Crump M, Smith AM, Brandwein J, et al: High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: Importance of disease status at transplant. J Clin Oncol 11:704-711, 1993[Abstract] 62. Jones RJ, Piantadosi S, Mann RB, et al: High-dose cytotoxic therapy and bone marrow transplantation for relapsed Hodgkin's disease. J Clin Oncol 8:527-537, 1990[Abstract] 63. Uematsu M, Tarbell NJ, Silver B, et al: Wide-field radiation therapy with or without chemotherapy for patients with Hodgkin's disease in relapse after initial combination chemotherapy. Cancer 72:207-212, 1993[Medline] 64. Fox KA, Lippman SM, Cassady R, et al: Radiation therapy salvage of Hodgkin's disease following chemotherapy failure. J Clin Oncol 5:38-45, 1987[Abstract] 65. Leigh BR, Fox KA, Mack CF, et al: Radiation therapy salvage of Hodgkin's disease following chemotherapy failure. Int J Radiat Oncol Bio Phys 27:855-862, 1993[Medline]
66.
Brada M, Eeles R, Ashley S: Salvage radiotherapy in recurrent Hodgkin's disease. Ann Oncol 3:131-135, 1992
67.
Roach M III Kapp DS, Rosenberg SA, et al: Radiotherapy with curative intent: An option in selected patients relapsing after chemotherapy for advanced Hodgkin's disease. J Clin Oncol 5:550-555, 1987 68. Wirth A, Corry J, Laidlow C, et al: Salvage radiotherapy for Hodgkin's disease following chemotherapy failure. Int J Radiat Oncol Bio Phys 39:599-607, 1997[Medline] 69. 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]
70.
Hancock SL, Donaldson SS, Hoppe RT: Cardiac disease following treatment of Hodgkin's disease. J Clin Oncol 11:1208-1215, 1993
71.
Hancock SL, Tucker MA, Hoppe RT: Factors affecting late mortality from heart disease after treatment of Hodgkin's disease. JAMA 270:1949-1955, 1993 72. Hoppe RT: Hodgkin's disease: Complications of therapy and excess mortality. Ann Oncol 8:115-118, 1997 (suppl 1) 73. National Center for Health Statistics: Monthly Vital Statistics Report: Annual Summary of Births, Marriages, Divorces and Deaths—United States, 1994. Washington, DC, US Public Health Service, 1995 74. Tsevat J, Weeks JC, Guadagnoli E, et al: Using health-related quality-of-life information: Clinical encounters, clinical trials, and health policy. J Gen Intern Med 9:576-582, 1994[Medline] 75. Torrance GW: Measurement of health state utility for economic appraisal: A review. J Health Econ 5:1-30, 1986[Medline]
76.
van Leeuwen FE, Chorus AMJ, van den Belt-Dusebout AW, et al: Leukemia risk following Hodgkin's disease: Relation to cumulative dose of alkylating agents, treatment with teniposide combination, number of episodes of chemotherapy and bone marrow damage. J Clin Oncol 12:1063-1073, 1994
77.
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 for the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol 11:2258-2272, 1993 78. Coleman CN, Dailey M, MacDougall IR, et al: Functional asplenia after splenic irradiation for Hodgkin's disease. Ann Intern Med 96:44-77, 1982 79. Hillner BE, Smith TJ: Efficacy and cost-effectiveness of adjuvant chemotherapy in women with node-negative breast cancer: A decision analysis model. N Engl J Med 324:160-168, 1991[Abstract] 80. Smith TJ, Hillner BE: The efficacy and cost-effectiveness of adjuvant therapy of early breast cancer in premenopausal women. J Clin Oncol 11:771-776, 1993[Abstract] 81. Hayman JA, Hillner BE, Harris JR, et al: Cost-effectiveness of routine radiation therapy following conservative surgery for early-stage breast cancer. J Clin Oncol 16:1022-1029, 1998[Abstract] Submitted May 1, 1998; accepted September 10, 1998.
This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 1999 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
