Analysis of treatment results in advanced Hodgkin's disease: the case for adjuvant radiotherapy

PURPOSE: To assess the treatment results in patients with advanced Hodgkin's disease in a single center and to evaluate the clinical and therapeutic prognostic factors, including verification of the significance of the prognostic score. METHODS AND MATERIALS: Treatment results were analyzed in 133 patients with newly diagnosed Stage IIIB and IV Hodgkin's disease. Treatment consisted of six courses of hybrid chemotherapy (mechlorethamine, vincristine, procarbazine, and prednisone [MOPP]/doxorubicin (adriamycin), bleomycin, and vincristine [ABV]) followed by irradiation (RT) in patients with an indication for RT (84 patients). Chemotherapy was then continued for another two cycles. The indications for consolidation RT included bulky disease and/or partial response after six cycles of chemotherapy. In 31 patients, extended-field RT was performed, and in 53, limited fields were irradiated. The median radiation dose was 39 Gy. RESULTS: The median follow-up was 78 months. Complete remission after whole treatment was achieved in 88.7% of patients. The actuarial overall survival rate was 78% and 71%, and relapse-free survival rate was 73% and 65% at 5 and 10 years, respectively. The independent adverse prognostic factors in multivariate analysis appeared to be older age, low serum albumin, low serum gammaglobulin, lower number of chemotherapy cycles, and no RT. The value of the prognostic score was confirmed; the higher the prognostic score, the worse the survival. CONCLUSION: In patients with advanced Hodgkin's disease, consolidation RT improved survival. The best results were achieved with the use of large-volume RT.     

Prospective trial of concurrent chemoradiotherapy with protracted infusion of 5-fluorouracil and cisplatin for T4 esophageal cancer with or without fistula

PURPOSE: A prospective trial of concurrent chemoradiotherapy (CT-RT) with a protracted infusion of 5-fluorouracil and cisplatin was performed to evaluate the safety and efficacy of this protocol for T4 esophageal cancer (UICC 1997). METHODS AND MATERIALS: Between 1998 and 2000, 28 patients with T4 esophageal squamous cell carcinomas were treated with concurrent CT-RT. Of the 28 patients, 15 had Stage III, 5 Stage IVA, and 8 Stage IV disease. Five of the T4 tumors had evidence of fistula before treatment. Patients received a protracted infusion of 5-fluorouracil 300 mg/m(2)/24 h on Days 1-14, a 1-h infusion of cisplatin 10 mg/body on Days 1-5 and 8-12, and concurrent radiation at a dose of 30 Gy in 15 fractions during 3 weeks. This schedule was repeated twice, with a 1-week split, for a total RT dose of 60 Gy during 7 weeks for 25 patients. For the remaining 3 patients, 30 Gy of preoperative CT-RT was administered. RESULTS: Of the 25 patients who were treated with the full dose of CT-RT, 14 (56%) completed the two courses of the CT-RT protocol, and 8 patients (32%) received the full dose of RT but a reduced dose of chemotherapy. Eight (32%) of the 25 tumors showed complete regression. Although Grade 3 hematologic toxicities were frequently noted, Grade 4 or more hematologic toxicities were few. Of the 5 T4 fistulous tumors, 2 demonstrated the disappearance of the fistula after CT-RT. However, the worsening or development of an esophageal fistula was noted in 5 patients. The 2-year survival rate for patients with Stage III was 27%, and the median survival time for those with Stage III and Stage IVA+IV was 12 and 5 months, respectively. CONCLUSION: Despite its significant toxicity for esophageal fistula, this concurrent CT-RT protocol of protracted 5-fluorouracil infusion and cisplatin appears feasible and effective for T4 esophageal cancer with or without fistulas.     

Analysis of in-field control and late toxicity for adults with early-stage Hodgkin's disease treated with chemotherapy followed by radiotherapy

PURPOSE: We analyzed in-field (IF) control in adults with early-stage Hodgkin's disease who received chemotherapy followed by radiotherapy (RT) in terms of the (1) chemotherapeutic regimen used and number of cycles delivered, (2) response to chemotherapy, and (3) initial tumor size. Cardiac toxicity and second malignancies, particularly the incidence of solid tumors in terms of the RT field size treated, were also examined. METHODS AND MATERIALS: From 1980 to 1995, 286 patients ranging in age from 16 to 88 years (median: 28 years) with Ann Arbor clinical Stage I or II Hodgkin's disease underwent chemotherapy followed 3 to 4 weeks later by RT. There were 516 nodal sites measuring 0.5 to 19.0 cm at the start of chemotherapy, including 134 cases of bulky mediastinal disease. NOVP, MOPP, ABVD, CVPP/ABDIC, and other chemotherapeutic regimens were given to 161, 67, 19, 18, and 21 patients, respectively. Patients received 1-8 (median: 3) cycles of induction chemotherapy. All 533 gross nodal and extranodal sites of disease were included in the RT fields. The median prescribed RT dose for gross disease was 40.0 Gy given in 20 daily 2.0-Gy fractions. There was little variation in the RT dose. Eighty-five patients were treated with involved-field or regional RT (to one side of the diaphragm), and 201 patients were treated with extended-field RT (to both sides of the diaphragm), based on the protocol on which they were enrolled. RESULTS: Follow-up of surviving patients ranged from 1.3 to 19.9 years (median: 7.4 years). Based on a review of simulation films, there were 16 IF, 8 marginal, and 15 out-of-field recurrences. The chemotherapeutic regimen used and the number of cycles of chemotherapy delivered did not significantly affect IF control. IF control also did not significantly depend on the response to induction chemotherapy. In cases where there was a confirmed or unconfirmed complete response as opposed to a partial response or stable disease in response to induction chemotherapy for bulky nodal disease, the 5-year IF control rates were 99% and 92%, respectively (p = 0.0006). The 15-year actuarial risks of coronary artery disease requiring surgical intervention and of solid tumors were 4.1% and 16.8%, respectively. There was a trend toward a greater risk of solid tumors in patients who received extended-field RT rather than involved-field or regional RT (p = 0.08). CONCLUSIONS: In patients with nonbulky disease, induction chemotherapy followed by RT to a median dose of 40.0 Gy resulted in excellent IF control, regardless of the chemotherapeutic regimen used, the fact that only 1-2 cycles of chemotherapy were delivered, and the response to chemotherapy. There was a trend toward a higher incidence of solid tumors in patients who received consolidation RT to both sides rather than only one side of the diaphragm. Ongoing Phase III trials will help clarify whether lower RT doses and smaller RT fields after chemotherapy can maintain the IF control seen in our study, but with a lower incidence of late complications in patients with Stage I or II Hodgkin's disease.     

Spontaneous pneumothorax in patients irradiated for Hodgkin's disease and other malignant lymphomas

A retrospective review of patients treated for Hodgkin's disease or other malignant lymphomas between 1953 and 1988 revealed 10 cases of spontaneous pneumothorax. Nine had Hodgkin's disease whereas one had diffuse histiocytic lymphoma. Ages of the 10 patients ranged from 11 to 54 years, although nine were less than 30-years old. Spontaneous pneumothorax was observed only in patients who had received mantle or mini-mantle radiation therapy (RT). Five patients had concurrent severe parenchymal pulmonary disease including chemotherapy-induced interstitial fibrosis, Varicella pneumonia and severe radiation pneumonitis. Pneumothorax in these patients tended to be severe, bilateral and/or recurrent. All five required chest tube placement. Three of the five also required thoracotomy. RT dose ranged from 3000-7500 cGy, exceeding 4700 cGy in three patients who required a second course of RT which included the involved lung apex. In comparison, the five who did not have concurrent severe lung disease had milder episodes of pneumothorax. Only one required chest tube placement, whereas none required thoracotomy. Pulmonary apex RT dose ranged from 3672-4257 cGy. For Hodgkin's disease patients treated by RT, the frequency of spontaneous pneumothorax in the absence of concurrent pulmonary disease was 2.2%. Limiting analysis to patients in the peak age population of 10-30 years raised the frequency to 3.0%. No RT dose-response effect could be demonstrated, although spontaneous pneumothorax was not observed in patients who received less than 3000 cGy. Spontaneous pneumothorax was not more frequent among patients who also received chemotherapy as compared to those treated only by RT. Exploratory thoracotomy in three cases with severe pulmonary disease revealed subpleural apical blebs and/or dense pleural fibrosis. Unusual aspects in the medical histories of other cases suggest the possibility that patients who develop pneumothorax may have unusually dense pulmonary and/or pleural fibrosis compared to the majority of patients who receive RT for Hodgkin's disease or other malignant lymphomas.     

Low-dose radiation therapy and reduced chemotherapy in childhood Hodgkin's disease: the experience of the French Society of Pediatric Oncology.

PURPOSE: With the aim of decreasing undesirable side effects of therapy, we investigated the reduction of both chemotherapy and radiation therapy (RT) in children with Hodgkin's disease, and compared Adriamycin (doxorubicin; Farmitalia Carlo Erba, Rueil-Malmaison, France), bleomycin, vinblastine, and dacarbazine (ABVD) alone to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and ABVD in favorable cases and assessed the effectiveness of low-dose RT (20 Gy) after good response to chemotherapy. PATIENTS AND METHODS: A French national study began in 1982 that included 238 pediatric patients with Hodgkin's disease. Initial staging was clinical and without laparotomy. In patients with localized disease (IA-IIA), an equivalence trial compared the effectiveness of four cycles of ABVD with two cycles of ABVD that were alternated with two cycles of MOPP. Patients with more advanced disease (IB-IIB-III-IV) received three courses of MOPP that was alternated with three courses of ABVD. All of the patients who achieved a good remission after chemotherapy were administered 20 Gy RT, which was limited to the initially involved areas for localized disease, and encompassed the paraaortic nodes and the spleen as well for more advanced stages. When a good remission was not obtained, 40 Gy RT was administered. RESULTS: At the completion of chemotherapy, 227 patients (97%) were considered good responders, whereas 11 did not achieve a good remission. With a median follow-up of 6 years, the 6-year actuarial survival was 92% and the disease-free survival was 86%. The relapse-free survival in favorable stages was 90% in the ABVD arm and was 87% in the MOPP and ABVD arm. In June 1987, inclusion of stage IV patients was discontinued because of poor results. CONCLUSIONS: Present findings indicate that (1) in favorable stages, ABVD alone and alternating MOPP and ABVD are equivalent, and (2) chemotherapy followed by 20 Gy RT represents a valid therapeutic approach in the vast majority of children with Hodgkin's disease.     

Combination chemotherapy for the treatment of Hodgkin's disease in relapse

Vindesine (desacetyl vinblastine amide sulfate, DVA) was used in combination with CCNU (lomustine) and melphalan (Alkeran) (CAD) to treat 15 heavily pretreated patients with Hodgkin's disease in relapse. The patients were treated with up to six cycles, depending upon their response. Two patients (13%) achieved a complete remission (CR) and five (33%) patients a partial remission (PR). The major toxicity was prolonged thrombocytopenia, which was decreased by a reduction in the initial drug doses for patients who had received extensive prior chemotherapy and radiotherapy (RT). The CAD regimen was then alternated with nitrogen mustard or cyclophosphamide, vincristine, procarbazine, and prednisone (MOPP, C-MOPP) and doxorubicin (Adriamycin), bleomycin, and vinblastine (ABV) for a total of nine cycles in 25 patients with Hodgkin's disease in relapse with somewhat more favorable prognostic features. Two patients also received low-dose RT to areas of bulky nodal disease. Eleven patients (44%) achieved a CR and seven (28%) a PR. Of the 11 CR patients, six remain in remission. The serious toxicity was comparable to that seen with other combination chemotherapy regimens. These results indicated that the CAD/MOPP/ABVD regimen is as active as other so-called 'salvage' regimens for Hodgkin's disease in relapse, and suggest that it might be useful for newly diagnosed Hodgkin's disease.     

食管鳞癌再程放疗发生食管瘘高危因素分析

目的再程放疗已经越来越多的应用于首程放疗后复发食管癌患者中,然而食管瘘是其最严重的并发症之一。本研究探索食管鳞癌患者行再程放疗伴或不伴化疗发生食管瘘的高危因素。方法回顾性分析山东省肿瘤医院2014-08-01-2019-04-30收治的71例食管鳞癌复发行再程放疗患者临床和剂量学资料,采用Logistic回归模型进行单因素和多因素分析筛选出发生食管瘘的高危因素。结果纳入研究的71例患者中有17例患者发生食管瘘(23.94%),3例患者在再程放疗过程中发生食管瘘,14例患者再程放疗结束后发生食管瘘;在本研究中食管瘘的类型包括食管气管瘘8例,食管纵隔瘘9例。中位随访时间为12.75(0.33~46.83)个月。单因素分析显示,年龄、性别、T分期、放疗总剂量、超分割放疗、肿瘤最大厚度、溃疡型食管癌和2次放疗时间差与食管瘘发生相关。多因素分析显示,T分期、放疗总剂量和两次放疗时间差为食管瘘发生的高危因素,均P<0.05。结论再程放疗食管癌患者食管瘘发生率显著增加,T4分期、放疗总剂量较高、两次放疗时间间隔较短是发生食管瘘的高危因素,超分割放疗可降低再程放疗食管瘘的发生率。     

Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results of a prospective clinical trial.

PURPOSE: To provide more mature data on the efficacy and complications of a brief, dose-intense chemotherapy regimen plus radiation therapy (RT) to bulky disease sites for locally extensive and advanced-stage Hodgkin's disease. PATIENTS AND METHODS: One hundred forty-two patients with stage III or IV or locally extensive mediastinal stage I or II Hodgkin's disease received Stanford V chemotherapy for 12 weeks followed by 36-Gy RT to initial sites of bulky (> or =5 cm) or macroscopic splenic disease. Freedom from progression (FFP), overall survival (OS), and freedom from second relapse (FF2R) were determined using life-table estimates. Outcomes were analyzed according to the international prognostic score. Late effects of treatment were recorded in follow-up. RESULTS: With a median follow-up of 5.4 years, the 5-year FFP was 89% and the OS was 96%. No patient progressed during treatment, and there were no treatment-related deaths. FFP was significantly superior among patients with a prognostic score of 0 to 2 compared with those with a score of 3 and higher (94% v 75%, P <.0001). No secondary leukemia was observed. To date, there have been 42 pregnancies after treatment. Among 16 patients who relapsed, the FF2R was 69% at 5 years. CONCLUSION: These data confirm our preliminary report that Stanford V chemotherapy with RT to bulky disease sites is highly effective in locally extensive and advanced Hodgkin's disease. It is most important to compare this approach with standard doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy in the ongoing intergroup trial (E2496) to determine whether Stanford V with or without RT represents a therapeutic advance.     

The residual mediastinal mass following radiation therapy for Hodgkin's disease

Thirty-two patients with mediastinal involvement by Hodgkin's disease (HD), treated with an isocentric technique of extended-field radiation therapy (RT) with or without chemotherapy, are described. Twenty-nine patients (91%) had a complete response to therapy and four patients subsequently relapsed, with a median follow-up of 54 months. Five of seven patients not in continuous complete remission were salvaged, with one additional salvage therapy. Ten patients had persistent mediastinal masses at 1 year, following completion of planned therapy; only one of these has had recurrent disease. Of those who achieved complete response, only one patient has had disease recurrence in the mediastinum. We conclude that extended-field RT, using an isocentric technique, provides excellent local disease control in HD; however, persistent mediastinal widening after therapy is frequent, and additional therapy should not be given in the absence of conclusive evidence of disease progression.     

Treatment of advanced Hodgkin's disease

MOPP chemotherapy was the significant breakthrough that improved the outlook for patients with advanced Hodgkin's disease. Results with alternating potentially non-cross-resistant drug combinations, including MOPP/ABVD, CAD/MOPP/ABV, and MOPP/ABV, are similar and seem to be slightly superior to those with MOPP alone. Limited adjuvant RT does not seem to add appreciably to the morbidity of chemotherapy, although its role in improving on results with chemotherapy alone has not been well studied in prospective, randomized, controlled clinical trials. There are two major challenges for the future. The first is to improve the outcome for advanced Hodgkin's disease patients, perhaps with more intensive chemotherapy and RT with use of cytokines such as the colony-stimulating factors or interleukin-1 or with rescue employing autologous bone marrow transplantation or both. The second challenge is to reduce the morbidity but not the effectiveness of treatment for advanced Hodgkin's disease patients without adverse prognostic factors.     

Prospective study of combined modality treatment or radiotherapy alone in the management of early-stage adult Hodgkin's disease

PURPOSE: To determine the efficacy and toxicity of combined modality treatment (CMT) or radiotherapy (RT) alone in the management of clinical Stage I-IIA adult Hodgkin's disease patients. METHODS AND MATERIALS: Forty-seven patients with supradiaphragmatic clinical Stage I-IIA Hodgkin's disease without bulky mediastinal lymphadenopathy were enrolled into this prospective study between September 1997 and February 2002. Patients with very favorable criteria presenting with one or two nonbulky nodal areas involved, an erythrocyte sedimentation rate of <50 mm/h, age <40 years, and either lymphocyte predominant or nodular sclerosing histologic findings were treated by RT alone. Patients missing any of these favorable criteria were classified as the other favorable group and were treated with three courses of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy followed by involved-field RT. The median age was 36 years (range, 19-53 years). Of the 47 patients, 15 were women and 32 were men. Only 3 patients were classified as the most favorable group and treated with mantle RT alone; the remaining 44 were treated with CMT. RESULTS: The median follow-up was 51 months (range, 20-74 months). Only 2 patients developed recurrence, both out of the irradiated field, one in the contralateral neck and the other in the abdomen. The 5-year relapse-free and overall survival rate was 95.4% and 97.8%, respectively. Although none of the prognostic factors were statistically significant for relapse-free survival, a trend was noted for the response to chemotherapy (p = 0.06). Only 2 patients developed treatment-related complications. One patient treated with mantle RT alone developed severe ischemic heart disease and one in the CMT arm developed subclinical hypothyroidism. CONCLUSION: Despite the short follow-up, CMT or RT alone tailored according to the clinical prognostic factors were successful in terms of disease control in clinical Stage I-IIA Hodgkin's disease. Longer follow-up is required to make definitive conclusions.     

Comparison of high-dose and low-dose radiation with and without chemotherapy for children with Hodgkin's disease: an analysis of the experience at the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania.

PURPOSE: In an effort to minimize complications related to high-dose radiotherapy (RT), children with Hodgkin's disease are often treated with low-dose RT (less than 25 Gy) plus chemotherapy. We performed a retrospective study comparing the results in these children with those from children treated with higher doses of RT (30 to 40 Gy) with or without chemotherapy. PATIENTS AND METHODS: From 1970 to 1988, 121 patients younger than 18 years of age with newly diagnosed Hodgkin's disease were treated at the Children's Hospital of Philadelphia (CHOP) and the Hospital of the University of Pennsylvania (HUP). Before 1977, most children underwent laparotomy and received high-dose RT with or without chemotherapy. Since then, high-dose RT alone has been reserved for pathologic stage IA and IIA postpubertal children without large mediastinal masses. In general, most postpubertal children with stage IIB through IVB disease or large mediastinal masses and all prepubertal children have received low-dose RT plus chemotherapy without laparotomy. RESULTS: The 10-year actuarial survival for all children was 86%, and the event-free survival (EFS) was 67% (median follow-up, 6.6 years). For 58 children treated with low-dose RT plus chemotherapy, 10-year survival and EFS (median follow-up, 6.8 years) were 88% and 67%, respectively. The corresponding figures for 10-year survival and EFS in 48 children treated with high-dose RT with or without chemotherapy were 88% and 66%, respectively. In children receiving combined modality therapy, the in-field failure rate was 7% for sites given between 17.5 and 22.5 Gy and 2% for sites given more than 32.5 Gy. In children receiving RT alone, the failure rate was 5% for sites given more than 32.5 Gy. CONCLUSION: We conclude that low-dose RT plus chemotherapy has yielded results comparable to those with higher doses of RT with or without chemotherapy.     

Occurrence of acute nonlymphocytic leukemia in a prospective randomized study of treatment for Hodgkin's disease

In a prospective randomized study of treatment with radiation therapy (RT) or RT followed by chemotherapy (CT) for patients with Hodgkin's disease stages I-III, four patients developed acute nonlymphocytic leukemia (ANLL) during post-treatment follow-up. There was a significant relationship between the intensity of the treatment and the appearance of this complication: no cases of ANLL were observed among the 128 patients treated with involved field (IF) RT, IF RT followed by CT, total nodal RT alone (TNR), or total lymphoid irradiation alone (TLI) after a follow-up from 21 to 126+ months (median follow-up 76 months). In contrast, four of 36 patients treated with extensive RT followed by CT developed ANLL at 17, 63, 72, and 91 months. Three of these patients had received TLI + CT, the fourth one TNR + CT.     

Randomized study of low‐dose versus standard‐dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303)

Low‐dose cisplatin and 5‐fluorouracil (LDPF) chemotherapy with daily radiotherapy (RT) is used as an alternative chemoradiotherapy regimen for locally advanced esophageal carcinoma. We evaluated whether RT plus LDPF chemotherapy had an advantage in terms of survival and/or toxicity over RT plus standard‐dose cisplatin and 5‐fluorouracil (SDPF) chemotherapy in this study. This multicenter trial included esophageal cancer patients with clinical T4 disease and/or unresectable regional lymph node metastasis. Patients were randomly assigned to receive RT (2 Gy/fraction, total dose of 60 Gy) with SDPF (arm A) or LDPF (arm B) chemotherapy. The primary endpoint was overall survival (OS). A total of 142 patients (arm A/B, 71/71) from 41 institutions were enrolled between April 2004 and September 2009. The OS hazard ratio in arm B versus arm A was 1.05 (80% confidence interval, 0.78–1.41). There were no differences in toxicities in either arm. Arm B was judged as not promising for further evaluation in the phase III setting. Thus, the Data and Safety Monitoring Committee recommended that the study be terminated. In the updated analyses, median OS and 3‐year OS were 13.1 months and 25.9%, respectively, for arm A and 14.4 months and 25.7%, respectively, for arm B. Daily RT plus LDPF chemotherapy did not qualify for further evaluation as a new treatment option for patients with locally advanced unresectable esophageal cancer. This study was registered at the UMIN Clinical Trials Registry as UMIN000000861.     

The usefulness of high dose (7-10mci) gallium (67Ga) scanning to diagnose Richter's transformation

Gallium (67Ga) scan was performed in 29 CLL patients with chronic lymphocytic leukemia who were suspected on clinical grounds to have Richter's transformation (RT). Of 29 patients, nine had a positive 67Ga scan; seven of these had a subsequent biopsy that verified large-cell lymphoma or Hodgkin's disease. The other two patients underwent biopsies that revealed fungal infections, a known cause of 67Ga uptake. Two patients had biopsies that were consistent with RT but showed no affinity to 67Ga. One false negative resulted five days after chemotherapy, a known cause of diminished 67Ga uptake. The other occurred within a small infraorbital mass, containing only 10% centroblasts, which is below the level of detection for 67Ga scanning. Subsequent 67Ga scans in both patients revealed 67Ga avid lesions, which demonstrated RT upon biopsy. This technique was more strongly predictive of RT than was measurement of serum B-2 microglobulin or serum lactate dehydrogenase levels. 67Ga scanning is very useful in localizing an optimal site for biopsy to document RT; it may also have the potential to help assess response to treatment, predict recurrence, and contribute to long-term follow-up in this subset of patients.     

Stage IA-IIB Hodgkin's disease: staging and treatment of patients with large mediastinal adenopathy

Ninety-two patients with clinically staged (CS) IA-IIB Hodgkin's disease (HD) with large mediastinal adenopathy (LMA) underwent three different staging and treatment approaches between April 1969 and December 1984. These approaches included: (1) staging laparotomy followed by radiation therapy (RT) alone; (2) staging laparotomy followed by combined RT and chemotherapy (CMT); or (3) clinical staging followed by CMT. Patients treated with CMT were more likely to have "B" symptoms, extension into extranodal sites, or stage III disease. Patients treated with RT alone had a significantly higher risk of relapse as compared to patients receiving CMT. No overall survival differences were seen between the three groups of patients. For patients treated with CMT without RT to the spleen or abdominal nodes, the risk of relapse in the abdomen was low (4%). These data suggest that for those CS I-II HD patients with LMA who are treated with CMT, the role for staging laparotomy and abdominal irradiation is limited. RT alone remains an option for some patients with LMA, but careful assessment of the anatomic extent of thoracic disease as well as staging laparotomy is essential if such treatment is recommended.     

Reduction of fatal complications from combined modality therapy in Hodgkin's disease

A total of 464 pathologically staged IA through IIIB Hodgkin's disease patients were evaluated for the risk of developing acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, or a fatal infection after treatment with radiation therapy (RT) alone, initial combined radiation therapy and chemotherapy (CMT), or RT with MOPP administered at relapse. Patients received a standard six cycles of MOPP, and additional maintenance chemotherapy was not administered. Patients receiving total nodal irradiation (TNI) and MOPP chemotherapy have an 11.9% actuarial risk of developing a fatal complication at ten years, as compared to a 0.8% risk for lesser field irradiation and MOPP (P = .005). The risk with RT alone is 0.6%. Patients 40 years of age or older have a greater risk for complications. These data report a low risk for fatal complication with CMT when less than TNI is administered and when maintenance chemotherapy is not used.     

Lung cancer following Hodgkin's disease: a case-control study.

It is recognized that survivors of Hodgkin's disease are at a substantially increased risk of lung cancer. A collaborative group of population-based cancer registries and major treatment centers carried out a case-control study, in which 98 cases of lung cancer were identified in patients who had survived at least 1 year following a diagnosis of Hodgkin's disease. A total of 259 matched controls were selected from patients with Hodgkin's disease who did not develop subsequent lung cancer, and for both cases and controls detailed information was abstracted from medical records concerning stage and treatment of Hodgkin's disease. Patients treated with chemotherapy alone had about twice the risk of developing lung cancer than those treated by radiotherapy alone or both modalities. There was no increase in risk with cumulative number of cycles of chemotherapy. Among patients treated with radiotherapy alone, there was an increase in risk related to estimated radiation dose to the lung. There was also a strong association between cigarette smoking and the risk of lung cancer. The finding of a higher risk following chemotherapy than following radiotherapy was unexpected, but could not be explained by any identified methodological flaws. A plausible inference from the study is that all forms of Hodgkin's disease therapy are carcinogenic to the lung and that, in particular, chemotherapy is associated with an increase in risk which is at least comparable to and perhaps higher than the risk produced by radiotherapy.     

The Role of Adjuvant Radiation Therapy for Stages III and IV Hodgkin's Disease

The treatment for advanced stage Hodgkin's disease was revolutionized approximately 30 years ago with the introduction of combination chemotherapy. This approach has resulted in the cure of approximately 50% of patients with advanced disease. In an effort to improve these results, consolidation of radiotherapy (RT) was introduced approximated 25 years ago. The rationale for adjuvant RT comes from several observations: significant numbers of patients relapse following combination chemotherapy alone, these relapses occur predominantly at initially involved sites, and successful salvage following relapse can be quite difficult to achieve. Data from numerous phase II trials have demonstrated that adjuvant RT significantly reduces the relapse rate compared with what is seen following chemotherapy alone and appears to increase survival as well. Phase III trials have confirmed the reduction in relapse but, as yet, have failed to demonstrate survival benefits. Because definitive phase II trials are lacking, the use of consolidation radiotherapy has gained only partial acceptance and remains controversial. There have been numerous methodological difficulties with the execution of the reported phase III trials, most notably the failure of a substantial portion of patients randomly allocated to the radiotherapy group to actually receive radiation. This review presents updated results of studies using chemotherapy alone including patterns of failure analyses, summarizes the available literature pertaining to both retrospective and prospective trials of combined modality therapy, discusses toxicity issues, and attempts to provide guidelines regarding patient selection, sequencing of chemotherapy and radiotherapy, and radiation dose and field size. It is our conclusion that the available evidence supports the routine use of combined modality therapy for patients with advanced stage Hodgkin's disease.     

Impact on second malignancy risk of the combined use of radiation and chemotherapy for lymphomas

The risk of a second malignancy was determined for 999 patients given primary treatment using chemotherapy only, radiation therapy only, or both for Hodgkin's Disease or a non-Hodgkin's lymphoma at Duke University Medical Center between 1970 and 1981. The incidence, 10-year actuarial risk, and relative risk of developing an acute leukemia, solid tumor, or second lymphoma were determined by treatment modality and initial lymphoma type. Among the 313 Hodgkin's disease patients, the acute leukemia actuarial risk was 2.0% after chemotherapy, 1.4% after radiation therapy, and 0.9% after combined treatment with chemotherapy and radiation therapy. Their relative risk for acute leukemia was 51.3 overall (95% confidence interval [CI] 13.8 to 131.8) and was elevated in each treatment group. Among the 686 non-Hodgkin's lymphoma patients, the acute leukemia actuarial risk was zero after radiation therapy, 4.6% after chemotherapy, and 4.5% after the combined treatment, again not significantly different between treatment groups. The leukemia relative risk was 10.6 (95% CI 3.4 to 24.8) in the chemotherapy and 11.9 (95% CI 3.2 to 30.6) in the combined treatment group. Among both the Hodgkin's disease and non-Hodgkin's lymphoma populations, the combined treatment group had a lower actuarial risk for solid tumors than either the chemotherapy or radiation therapy group (P less than 0.02). Solid tumor actuarial risk did not differ significantly between the chemotherapy and radiation therapy groups. Hodgkin's disease patients had a solid tumor relative risk that was elevated significantly after radiation therapy (6.5; 95% CI 2.4 to 14.0) and to a lesser extent after chemotherapy (2.6; 95% CI 0.8 to 6.1) or combined treatment (1.7; 95% CI 0.2 to 6.0). Solid tumor relative risk among non-Hodgkin's lymphoma patients was 0.3 for the combined treatment, 0.8 for the chemotherapy, and 1.0 for the radiation therapy group. None of the Hodgkin's disease patients developed a non-Hodgkin's lymphoma. This study found no significant difference in leukemia risk among lymphoma patients treated with chemotherapy and the combined treatment. It also found that the overall risk of a second malignancy is no higher after treatment with the combined therapy than with chemotherapy or radiation therapy alone.