Genotoxic effects of radiotherapy and chemotherapy on the circulating lymphocytes of breast cancer patients. II. Alteration of DNA repair and chromosome radiosensitivity

Lymphocytes from 43 breast cancer patients were tested for their DNA-repair ability and in vitro chromosomal radiosensitivity. Lymphocytes were collected before and after treatment with radiotherapy or chemotherapy or both, and then irradiated in vitro. The aim was to detect alterations of these 2 indicators of radiosensitivity, in relation to cancer status or medical treatment. Patients before treatment were significantly deficient in DNA-repair ability but had a normal chromosomal radiosensitivity as compared to healthy donors. When assessed after treatment, DNA-repair ability and the frequency of in vitro-induced chromosome anomalies were modified according to the type of treatment. A reduced DNA-repair ability was observed for patients after radiotherapy but not after chemotherapy. In vitro-induced dicentrics and acentrics were not modified to the same extent according to the treatment. A decreased number of acentrics (the most frequently observed alteration) was preferentially associated with a more reduced DNA-repair ability. Interindividual differences of response to in vitro irradiation tested by both assays were observed between patients who had undergone similar treatments. The possibility that these assays could be used for predicting individual susceptibility to radiation or chemotherapy drug exposure is discussed.     

Retrospective Analysis of 234 Nasopharyngeal Carcinoma Patients with Distant Metastasis at Initial Diagnosis: Therapeutic Approaches and Prognostic Factors

Purpose

The purpose of this retrospective study was to identify the independent prognostic factors and optimize the treatment for nasopharyngeal carcinoma (NPC) patients with distant metastasis at initial diagnosis.

Methods

A total of 234 patients referred between January 2001 and December 2010 were retrospectively analyzed. Among the 234 patients, 94 patients received chemotherapy alone (CT), and 140 patients received chemoradiotherapy (CRT). Clinical features, laboratory parameters and treatment modality were examined with univariate and multivariate analyses.

Results

The median overall survival (OS) time was 22 months (range, 2-125 months), and the 1-year, 2-year, 3-year overall survival rates were 82.2%, 51.3% and 34.1%. The overall response and disease control rates of metastatic lesions after chemotherapy were 56.0% and 89.8%. The factors associated with poor response were karnofsky performance score (KPS) <80, liver metastasis, lactate dehydrogenase (LDH)>245 IU/L, and number of chemotherapy cycles <4. The 3-year OS of patients receiving CRT was higher than those receiving CT alone (48.2% vs. 12.4%, p<0.001). Subgroup analysis showed that significantly improved survival was also achieved by radiotherapy of the primary tumor in patients who achieved complete remission (CR)/partial remission (PR) or stable disease (SD) of metastatic lesions after chemotherapy. Significant independent prognostic factors of OS were KPS, liver metastasis, levels of LDH, and multiple metastases. Treatment modality, response to chemotherapy and chemotherapy cycles were also associated with OS.

Conclusion

A combination of radiotherapy and chemotherapy seems to have survival benefits for selected patients with distant metastases at initial diagnosis. Clinical and laboratory characteristics can help to guide treatment selection. Prospective randomized studies are needed to confirm the result.     

Multimodality Treatment May Improve the Survival Rate of Patients with Metastatic Nasopharyngeal Carcinoma with Good Performance Status

The aim of the present study was to evaluate the benefit of chemotherapy, combined with palliative radiotherapy (PRT) and other local treatments to the metastatic sites, for patients with metastatic nasopharyngeal carcinoma (NPC) who had a performance status 0–2. We conducted a retrospective review of available data from 197 biopsy-proven NPC patients who developed metastasis after their initial definitive treatment. These patients were grouped into three categories according to the different treatment paths that were followed: the best supportive care (64 patients), chemotherapy alone (55 patients), and multimodality treatment with chemotherapy combined with PRT and other local treatments to metastatic sites (78 patients). The 2-year metastatic survival rate of patients in the multimodality treatment group was 57.7%, which was significantly better than that of the patients in both the chemotherapy alone group and the best supportive care group (32.7% and 1.6%, respectively). The independent significant factors affecting survival were the disease-free interval prior to the detection of metastatic disease, the number of metastases, the number of chemotherapy cycles and the biological effective dose of PRT. In conclusion, multimodality treatment may improve survival of select patients with recurrent NPC with distant metastases.     

Primary malignant non-Hodgkin's lymphoma of the breast: a study of seven cases and literature review

ABSTRACT: INTRODUCTION: Primary breast lymphoma is an uncommon disease with poor clinical outcome. Breast lymphomas present less than 0.5% of malignant breast neoplasms and 2.2% of extranodal lymphomas. This study investigated the clinicopathological features and optimal treatment of PBL. Case presentations Clinical records of seven Moroccan PBL patients, treated at the National Institute of Oncology, Rabat, Morocco, from 2002 to 2010, were reviewed. Six of the patients were women and one a man, with ages ranging from 32 to 76. Five patients had stage IE and two stage IIE. All of the patients were classified with DLBCL. Of seven patients, one received a mastectomy and three excision of the breast lesion. Axillary dissection was performed in three patients. Two patients received chemotherapy followed by radiotherapy, while four received chemotherapy alone. Complete remission (CR) following primary treatment for all patients with PBL except in two cases was obtained. In one patient, recurrence occurred. CONCLUSIONS: There is no consensus on the question of how to best treat PBL: Mastectomy offers no benefit in the treatment of PBL. The combined therapy approach, with chemotherapy and radiotherapy, is the most successful treatment. PBL is poorly represented in rituximab-containing trials in DLBCL patients; there is not much experience with this agent in breast DLBCL. Because of the high incidence of central nervous system (CNS) involvement in PBL patients, many authors strongly believe that patients with aggressive forms of PBL should receive CNS infiltration prophylaxis.     

Combination Chemotherapy in Generalized Hodgkin's Disease

Fifty-two patients with generalized Hodgkin''s disease were treated with a combination of mustine hydrochloride, vinblastine, procarbazine, and prednisolone. Complete remissions were obtained initially in six out of seven patients (86%) who had previously received no treatment, in 15 out of 19 (79%) who had had only radiotherapy in the past, and in 9 out of 26 (35%) who had previously been given chemotherapy with or without radiotherapy. Of these 30 patients in whom a complete remission was obtained 22 have been free of any symptoms or signs of disease for periods ranging from 4 to 22 months. The response to treatment was rapid, and toxicity was not a major problem, except in those who had previously been treated with cytotoxic drugs used continuously and not in courses. A comparative trial of radiotherapy and combination therapy in the treatment of Stage III Hodgkin''s disease is strongly recommended.     

Nephroblastoma in infants, 1969-75: variations in treatment and survival.

In a series of 79 infants aged under 1 year with nephroblastoma diagnosed during 1969-75 all the patients underwent nephrectomy, 33 (42%) received a course of radiotherapy, and 49 (62%) received chemotherapy. The overall three-year survival rate for patients who survived at least one week after diagnosis was 65%. The corresponding rate for infants with stage I tumours was 76%. The survival rate in children with early-stage tumours was significantly higher in those who were treated by nephrectomy and chemotherapy alone compared with those who also received radiotherapy. In a large proportion of cases nephrectomy and chemotherapy together constituted sufficient treatment for the cure of infants with nephroblastoma, and in some instances nephrectomy alone proved adequate. There was no general tendency for children under 1 year old to be unable to withstand chemotherapy.     

Low-dose Taxol radiosensitization in locally advanced head and neck cancers

INTRODUCTION: Combined modality treatment with chemotherapy and radiotherapy in locally advanced head and neck cancers is an effective and often the only treatment with a chance of cure. An alternative is to use chemotherapeutic agents at low doses as radiosensitizers. In this study we examined the radiosensitizing effect of low dose Taxol in locally advanced head and neck cancer. Patients and methods: 26 patients with locally advanced squamous cell carcinoma of the oral cavity and the oropharynx were treated with external beam radiotherapy up to doses of 66-70 Gy and received concomitantly 2 mg/m(2) Taxol intravenously three times a week. Response rates according to WHO criteria, side effects according to the National Cancer Institute Common Toxicity Criteria, overall and progression-free survival were evaluated. RESULTS: All patients completed the therapy. Median radiation dose was 66 Gy, Taxol dose 40 mg/m(2) and treatment duration 54 days. 8 weeks after completion of therapy complete response was 30.8%, partial response 34.6%, stable disease 11.5% and progressive disease 23.1%. The median follow-up time was 25 months (9-36). At the cloes- out date 12 (46,1%) of the patients were alive, 9 without evidence of disease. The estimated median overall survival was 22 months (CI 14.2-34.6), the median progression-free survival 12 months (CI 5.2-18.8). We observed four grade 4, fourteen grade 3 and numerous grade 1-2 side effects. There was no treatment related death. DISCUSSION: Our regimen resulted in a worse response rate than the aggressive chemoradiation protocols treating the same disease. However, the two-year survival was comparable with the results of other studies. The advantages of our schedule are that it is well tolerated, easy to perform on an outpatient basis, resource effective and does not deteriorate the general condition of the patients, therefore successive therapy can be carried out immediately if necessary. We intend to evaluate the effectivity of this treatment in a study comparing radiotherapy with Taxol sensitization versus radiotherapy alone.     

Comparison of combined and single-agent chemotherapy in non-Hodgkin's lymphoma of favourable histological type.

Sixty-six untreated patients with advanced non-Hodgkin''s lymphoma of favourable histological type were allocated alternately to initial treatment with cyclophosphamide, vincristine, and prednisolone or with chlorambucil. The complete remission rate was higher in the group receiving combination chemotherapy, but the overall response rate was the same for both groups. The mean duration of complete remission was the same as that of good partial remission, and was the same for both treatments. The duration of remission was influenced by histological type and extent of disease at presentation, but not age. Those who responded to the initial treatment (whether with complete or with good partial remission) survived significantly longer than did non-responders. It is concluded that neither treatment is satisfactory and that new treatment programmes are needed for patients with a favourable prognosis, especially young patients with extensive disease.     

Neoadjuvant chemotherapy in head and neck cancer

BACKGROUND: Neoadjuvant chemotherapy has an increasing role in multimodality treatment of advanced head and neck cancer. In this paper we summarize our first results with this treatment. METHOD: Thirty-five, previously untreated, mostly inoperable head and neck cancer patients were given two cycles of Cisplatin and 5FU chemotherapy. We continued the therapy only in case of regression until four cycles, then the patients received surgical and/or radiotherapy according to their status. After the treatment patients' status was regularly evaluated. RESULTS: We detected 4 complete and 20 partial responses after the chemotherapy. Three patients became eligible for a radical operation. At this moment 10 patients are free of tumor, 8 patients died in consequence of the tumor, we have no data in 3 cases, 3 patients are given palliative therapy because of progression, 4 patients are receiving radiotherapy and 7 patients with partial response are candidates for further active oncotherapy. CONCLUSIONS: Although the number of the patients we treated is too small for a statistical analysis, our results are similar to the conclusion of the large randomized studies: after neoadjuvant chemotherapy of advanced head and neck cancer partial response can improve the result of surgical or radiological treatment. Neoadjuvant chemotherapy does not improve survival in advanced head and neck cancer, but it is of great importance because of better quality of life of patients, especially those who had organ preserving therapy.     

Long-term follow-up after relapses in children with Hodgkin's disease

In the years 1969-1980, 68 children with Hodgkin's disease were subjected to a combined MVPP and radiotherapy. Remissions were obtained in 64 patients, and relapses occurred in 11 children. The treatment of relapse consisted in administration of B-DOPA alone or alternatively with MVPP combined with radiotherapy (in 7 out of 11 patients). The patients were recycled every 2-3 weeks which, with other modifications of chemotherapy, allowed for the completion of the six first cycles within the period of 4,5 to 7 months. A relapse caused death of one child, and two others demonstrated further relapses. At present eight children have been showing disease-free survival following a relapse for the period of 29+ to 152+ (median, 94.5 months). The authors concluded that in patients with relapses of Hodgkin's disease the decisive role rests upon aggressive chemotherapy (high frequency of cycles).     

Malignant cerebral glioma--I: Survival,disability, and morbidity after radiotherapy.

OBJECTIVE: To describe survival, disability, and morbidity after radiotherapy for malignant glioma. DESIGN: Two year prospective study with home interviews with patients and relatives. SETTING: Seven neurosurgical and radiotherapy centres in London. SUBJECTS: 105 patients aged 21 to 75: 59 had biopsy; 46 had partial macroscopic resection; 92 received radiotherapy; and 13 received steroids alone. MAIN OUTCOME MEASURES: Survival, time free from disability, and changes in disability after treatment. RESULTS: Six and 12 month survival for radiotherapy patients was 70% and 39%, respectively. Age, World Health Organisation clinical performance status, extent of surgery, and history of seizures before diagnosis each influenced survival. The Medical Research Council prognostic index was also significantly related to survival. Multivariate analysis showed that initial clinical performance status was the most important component of the index. Most (80%; 49/61) patients with a clinical performance status of 0, 1, or 2 lived at least six months before becoming permanently disabled. Most patients who had initially had a good clinical performance status (0-2) and who were alive six months after radiotherapy (68%; 36/52), however, had experienced either clinical deterioration or severe tiredness after treatment. In 17% (9/52) of these some permanent loss of function remained. These adverse effects were associated with increasing radiotherapy dose. Severely disabled patients (clinical performance status 3 or 4) gained little benefit. CONCLUSION: Severely disabled patients gain little physical benefit from radiotherapy, whereas those not so disabled may experience considerable adverse effects.     

Rôle de la TEP au 18F-FDG dans l’évaluation des volumes cibles chez des patients atteints de CBNPC traités par radiochimiothérapie

Currently ¹⁸F-FDG-PET is the gold standard to evaluate tumor response after chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC). PET can also determine the volumes to be treated by radiotherapy, in inoperable patients. The aim of our mixed (prospective and retrospective) study concerned 28 patients with NSCLC, was to quantify the variation of the metabolic activity of lesions and their volumes after chemotherapy. We also studied the impact of change of these volumes on the definition of radiotherapy target volumes. Patients with stage II–IV and inoperable NSCLC were included. Two PET scans were performed: before treatment (PET1), then after two to six courses of chemotherapy (PET2). Of the 28 patients included, we observed complete metabolic response in six patients (21%), partial metabolic response in 13 patients (46%), stable disease in seven patients (25%), and progressive metabolic disease in two patients (7%), according to the PERCIST criteria. We observed significant variation (P < 0.001) of metabolic activity (estimated by SULpeak or SUVmax) for primary tumor as well as for overall lesions between the two PET scans. Thus, the target volumes of radiotherapy decreased significantly (P < 0.01) in PET2. Our results confirm that ¹⁸F-FDG-PET is not only a powerful technique for treatment evaluation but also a useful tool for radiotherapy planning after chemotherapy, in the context of personalized treatments.     

MVPP chemotherapy regimen for advanced Hodgkin's disease

During January 1968 to December 1972, 133 patients with advanced Hodgkin''s disease (HD) were admitted to hospital for combination chemotherapy with mustine, vinblastine, procarbazine, and prednisolone (MVPP regimen). Remission rates were 76% among 49 untreated patients and 90% among 42 patients who had relapsed after radiotherapy. The corresponding five-year survival rates were 65% and 86% respectively. Provided the observed yearly mortality (6%) remains unchanged 75% of patients who had previously received no treatment or irradiation and achieved remission are expected to continue in first remission after five years. Forty-two patients had received prior chemotherapy. They had lower remission and five-year survival rates (40% and 33% respectively), and fewer than half of those achieving remission were still in first remission after five years. There were several reasons for the poor prognosis in this group, including advanced-stage disease (stage IVB), age over 40, and achievement of remission.Chemotherapy was administered on an outpatient basis. Haematological toxicity and immediate drug-related side effects were similar to those of other regimens but there was no appreciable neurotoxicity. Most deaths were due to either HD itself or complications of advanced disease. Five malignancies other than HD occurred in patients who had received both single-agent chemotherapy and radiotherapy before MVPP chemotherapy. Two patients developed osteonecrosis of the femoral heads.Combination chemotherapy has a profound effect on the prognosis of advanced HD. The MVPP regimen yields results comparable to those of other regimens but with perhaps less toxicity.     

Prednisone in MOPP chemotherapy for Hodgkin's disease.

High remission rates have been produced by MOPP (mustine, vincristine, procarbazine, and prednisone) chemotherapy in patients with advanced Hodgkin''s disease, but the prednisone component has caused adverse effects in patients who have undergone radiotherapy. The remission rates and length of remission were reviewed in 211 patients with Hodgkin''s disease who received chemotherapy either with or without prednisone. In contrast to the findings of a British study, there were no significant differences in remission rates or length of remission between patients who had received prednisone and patients who had not. There were differences between the British prospective study and this retrospective one, but it is difficult to know what accounted for the substantial differences in the findings.     

CyberKnife radiosurgery for inoperable stage IA non-small cell lung cancer: 18F-fluorodeoxyglucose positron emission tomography/computed tomography serial tumor response assessment

Abstract

Management of localized primary gastric B lymphoma (PGL) remains controversial. The aim of this study is to compare two treatments: chemotherapy alone and surgery plus chemotherapy.

Materials

Records of all patients with a diagnosis of gastric lymphoma and which were treated in the National Institute of Oncology, between 1999 and 2006, were reviewed and patients fulfilling the following criteria were included in this study: histologically proven large-cell B lymphoma of the stomach; complete clinical information stage I/II disease according to the Musshoff staging; patients who received surgery followed by chemotherapy (group I) or chemotherapy alone (group II).

Results

This study included 82 patients who were treated for cancer in our Institute. All clinical and pathological features were similar between the two groups, except that patients of group-I had significantly more stage II disease (P = 0.023) than that of group II. Among the 52 patients who could be evaluated for response to chemotherapy, there were 45 who had complete response to treatment, 3 had partial response to the treatment and 4 had progressive disease. The projected 5-year relapse-free survival (RFS) and overall survival (OS) of group I were 86.69% (95% CI, 57.9 - 97.7%) and 90.0% (95% CI, 58.0 - 97.8%), respectively. And the projected 5-year relapse-free survival RFS and OS of group II were 86.67% (95% CI, 57.0 - 88.2%) and 93.33% (95% CI, 73.3 - 98.7%) respectively. There were no statistically significant differences in RFS (P = 0.485) and OS (P = 0.551) between the two groups.

Conclusion

Our data suggest that chemotherapy alone may be a reasonable alternative treatment for stage I/II gastric large-cell lymphoma but this result must be confirmed by prospective randomized clinical trials.     

Prognostic risk factors in advanced Hodgkin's lymphoma. Report of the German Hodgkin Study Group

In a national multicentre trial in the FRG patients with Hodgkin's lymphoma in stages CS/PS III B/IV were entered into the HD 3 protocol and received induction chemotherapy with 3 x (COPP + ABVD). Patients in complete remission (CR) received consolidation therapy by either radiotherapy (20 Gy IF) or chemotherapy (COPP + ABVD). Patients not in CR received salvage therapy (40 Gy in case of persisting nodal disease, else 4 x CEVD chemotherapy). Between July 1983 and May 1987 230 untreated patients aged 15 to 60 qualified for this HD 3 protocol. This analysis is based on the first 137 patients evaluable for response. Of these, 86 (63%) achieved CR after induction chemotherapy. Including salvage therapy a total of 104 patients (76%) achieved CR. Univariate and multivariate prognostic risk factor analyses were performed using freedom from treatment failure (FFTF) as endpoint. Sex, age, splenectomy, bone marrow, liver and bone involvement had no prognostic impact nor had stage according to the Ann Arbor classification. In contrast, a pretreatment erythrocyte sedimentation rate (ESR) above 80 mm/h and a serum alkaline phosphatase (AP) above 230 IU/ml appeared as significant risk factors (p less than 0.01, relative risk 2.3). The two parameters were not independent. Comparing a group A (ESR less than or equal to 80 and AP less than or equal to 230) versus a pooled group B (ESR greater than 80 and/or AP greater than 230) increased the difference (p less than 0.001, relative risk of 2.8) which was also significant for survival (p less than 0.04).     

Leukaemia complicating treatment for Hodgkin's disease: the experience of the British National Lymphoma Investigation.

OBJECTIVE--To determine the incidence of and risk factors for the development of secondary acute leukaemia and myelodysplasia in patients treated in British National Lymphoma Investigation''s studies of Hodgkin''s disease since 1970. PATIENTS--2676 Patients entered into Hodgkin''s disease studies between February 1970 and November 1986. Data accrued up to November 1988 were analysed, ensuring a minimum follow up period of two years. DESIGN--Retrospective analysis of multicentre trial data by case-control and life table methods. RESULTS--17 Cases of secondary leukaemia were recorded in this group of 2676 patients, giving an overall risk at 15 years of 1.7%. The risks of leukaemia after chemotherapy alone and chemotherapy with radiotherapy were not significantly different. The risk of leukaemia increased sharply with the amount of treatment given as measured by the number of attempts at treatment. The 15 year risks of leukaemia were 0.2%, 2.3%, and 8.1% for patients receiving one, two, or three or more attempts at treatment. The highest risk, 22.8% at 15 years, was observed in patients treated with lomustine (CCNU), and a case-control study suggested that this was an independent risk factor. The risk of secondary leukaemia was largely related to the overall quantity of treatment, although exposure to lomustine seemed to be an important risk factor. Treatment with both drugs and radiation was not more leukaemogenic than treatment with drugs alone. The greatest risk of secondary leukaemia was seen in multiply treated patients who were unlikely to be cured of Hodgkin''s disease. CONCLUSIONS--Avoidance of secondary leukaemia should be a minor factor in the choice of treatment for Hodgkin''s disease.     

PF方案同步放化疗治疗中晚期宫颈癌的疗效及毒性反应研究

目的：探究PF 方案同步放化疗治疗中晚期宫颈癌患者的疗效和毒性反应。方法：回顾性分析我院在2014 年6 月～2015 年6 月期间收治的ⅡB～Ⅲ期宫颈癌患者,共152 例,根据治疗方法将其分为单纯放疗组和同步放化疗组,比较两组患者治疗的疗效 和毒性反应。结果：单纯放疗组和同步放化疗组近期疗效总有效率无显著差异,差异不具有统计学意义(P>0.05),但分别对ⅡB 和 Ⅲ期患者进行分析,Ⅲ期患者同步放疗组总有效率显著高于单纯放疗组,差异具有统计学意义(P<0.05);同步放化疗组患者治疗 后骨髓抑制白细胞下降和消化道反应发生率显著高于单纯放疗组,差异具有统计学意义(P<0.05),两组患者皮肤反应的发生情况 比较无显著差异(P>0.05)。结论：PF方案同步放化疗治疗Ⅲ期宫颈癌的临床疗效显著优于单纯放疗治疗,可有效提高近期总有效 率,毒性反应虽较单纯放疗组有所增加,但经临床支持治疗患者均可耐受。     

Risk of second primary cancers after Hodgkin's disease by type of treatment: analysis of 2846 patients in the British National Lymphoma Investigation.

OBJECTIVE--To analyse the risk of second primary cancers during long term follow up of patients with Hodgkin''s disease. DESIGN--Cohort study. SETTING--The British National Lymphoma Investigation (a collaborative group of over 60 participating centres in Britain treating lymphomas). PATIENTS--2846 patients first treated for Hodgkin''s disease during 1970-87, for whom follow up was complete in 99.8%. MAIN OUTCOME MEASURES--Second primary cancers; uniform pathology reviews confirmed the diagnosis of Hodgkin''s disease and of second primary non-Hodgkin''s lymphomas. RESULTS--113 second primary cancers occurred. Relative risk of cancer other than Hodgkin''s disease was 2.7 (95% confidence interval 2.3 to 3.3) compared with the general population, with significant risk of leukaemia (16.0(9.1 to 26.0)); non-Hodgkin''s lymphoma (16.8(9.8 to 26.9)); and cancers of the colon (3.2 (1.4 to 6.2)), lung (3.8 (2.6 to 5.4)), bone (15.1 (1.8 to 54.7)), and thyroid (9.4 (1.1 to 33.9)). Absolute excess risk associated with treatment was greater for solid tumours than for leukaemia and lymphomas. Relative risk of leukaemia increased soon after treatment, reaching a peak after five to nine years. It was increased substantially after chemotherapy (27.9 (12.7 to 52.9)), combined treatment with radiotherapy and chemotherapy (21.5 (7.9 to 46.8)), and relative to number of courses of chemotherapy but was not significantly increased after radiotherapy (2.5 (0.1 to 14.1)). Relative risk of non-Hodgkin''s lymphoma increased in the first five years after treatment and remained high but showed no clear relation with type or extent of treatment. Relative risk of solid tumours was less raised initially but increased throughout follow up and for lung cancer 10 years or more after entry was 8.3 (4.0 to 15.3). The risk of solid tumours increased after treatments including radiotherapy and after chemotherapy alone. The risk after chemotherapy increased significantly with time since first treatment. CONCLUSION--The risk of solid cancer, not of leukaemia, is the major long term hazard of treatment for Hodgkin''s disease, and this seemed to apply after chemotherapy as well as after radiotherapy. These risks of second cancers are important in choice of treatment and in follow up of patients, but they are small compared with the great improvements in survival which have been brought about by modern therapeutic methods for Hodgkin''s disease.     

Second malignancies in Hodgkin's disease: a complication of certain forms of treatment.

A total of 764 patients with Hodgkin''s disease treated with radiotherapy (RT) or chemotherapy or both were reviewed 3-186 months (median 43 months) after initial treatment to assess the incidence of second malignancies. Incidence of solid tumours and acute non-lymphoblastic leukaemia (ANLL) were calculated by a life-table method and percentages of patients affected derived from life-table plots. Within 10 years after initial treatment the overall incidence of second solid tumours was 7.3%, and over a comparable period 2.4% of patients developed ANLL. Solid tumours occurred only in patients given RT with or without adjuvant chemotherapy, and ANLL occurred only after treatment with MOPP (mustine, vincristine, procarbazine, and prednisolone) or modified MOPP regimens. Neither solid tumours nor ANLL occurred in patients given ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine). The highest incidence of leukaemia (5.4%) occurred after treatment with extensive RT plus (5.4%) occurred after treatment with extensive RT plus MOPP; hence the benefits of this approach in Hodgkin''s disease must be weighed against its carcinogenic potential.