Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group.

PURPOSE: To compare (1) clinical staging and irradiation alone versus staging laparotomy and treatment adaptation in patients with a favorable prognosis (H6F); (2) two combined modalities in patients with an unfavorable prognosis (H6U). PATIENTS AND METHODS: The H6F trial (n = 262) consisted of randomization to clinical staging plus subtotal nodal irradiation (STNI) or to staging laparotomy plus treatment adaptation (adjuvant chemotherapy [CT] only in the 33% with negative laparotomy). The H6U trial (n = 316) consisted of no laparotomy, randomization to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), and mantle irradiation. RESULTS: In the H6F trial, 6-year freedom from progression (FFP) rates (78% v 83%; P = .27) were similar in clinical and laparotomy stagings, respectively. Survival rates were 93% and 89%, due to laparotomy-related deaths. In the H6U trial, the ABVD arm had superior results (6-year FFP rate, 88% v 76%; P = .01), but they were not significant for survival (91% v 85%; P = .22). CT discontinuation due to hematologic intolerance occurred more often with MOPP (14.5% v 7.3%). Decrease of the pulmonary vital capacity ([VC] < 70% of the theoretic value) was observed more frequently after ABVD than after MOPP (12% v 2%; P = .08), with two lethal pulmonary insufficiencies occurring in the ABVD arm. No modification of the isotopic left ventricular ejection fraction (LVEF) occurred. Gonadal toxicity was less in the ABVD arm. CONCLUSION: Early-stage patients benefit from treatment adaptation to initial characteristics in terms of tumor control and late toxicities. Staging laparotomy before STNI may be deleted even in favorable patients at no cost to survival or FFP. In unfavorable patients, ABVD achieved better results than MOPP, at lower hematologic and gonadal cost. Therefore, despite its pulmonary toxicity, ABVD is the best choice to design improved CT regimens associated with mantle irradiation.

Efficacy of four different regimens in 64 mantle-cell lymphoma cases: clinicopathologic comparison with 498 other non-Hodgkin's lymphoma subtypes. European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group.

PURPOSE: Before recognizing mantle-cell lymphoma (MCL) as a distinct entity, these patients were grouped into low-grade (LG) or intermediate-/high-grade categories (IGHG) according to the Working Formulation and received various therapies. This was a unique opportunity to evaluate characteristics, behavior, response to treatment, and outcome of patients with MCL from two phase III trials conducted by the European Organization for the Research and Treatment of Cancer (EORTC): EORTC 20855 IGHG and EORTC 20856 LG. PATIENTS AND METHODS: After histologic review, 64 diagnosed MCL patients (29 IGHG and 35 LG) were compared with other patients in their respective trials. In the IGHG group, patients received cyclophosphamide, doxorubicin, teniposide (VM26), prednisone, vincristine, and bleomycin (CHVmP-VB) or modified doxorubicin, cyclophosphamide, etoposide (VP 16), mechlorethamine, vincristine, procarbazine, and prednisone (ProMACE-MOPP). In the LG group, after receiving cyclophosphamide, vincristine, and prednisone (CVP) induction, patients were randomized between maintenance treatment with interferon alfa-2a (IFN) or no further treatment. RESULTS: MCL patients compared with IGHG subtypes showed a similar overall survival and response rate, but shorter duration of response and progression-free survival. Comparing with LG patients, their response rate, duration of response, and progression-free survival showed no difference, while their overall survival was nearly twice shorter. MCL patients treated with CHVmP-VB had the longest survival. No treatment showed any significant improvement in terms of progression-free survival. CONCLUSION: These data confirm that MCL represents a clinicopathologic entity. In terms of survival, it behaves like IGHG subtypes, while in terms of progression-free survival, it behaves like LG lymphoma. It is still not clear which first-line treatment offers patients with MCL the best chance to obtain both a complete response (CR) and a long-term survival.

Maintenance of remission with human recombinant interferon alfa-2a in patients with stages III and IV low-grade malignant non-Hodgkin's lymphoma. European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group.

PURPOSE: Interferon alfa has shown significant activity in patients with low-grade malignant non-Hodgkin's lymphoma (NHL). In 1985, we initiated a prospective randomized study in which the potential benefit of interferon alfa given as maintenance treatment was investigated after tumor load reduction was achieved with chemoradiotherapy in patients with advanced low-grade malignant non-Hodgkin's lymphoma. PATIENTS AND METHODS: The study involved 347 patients with stage III or IV disease, 315 satisfying the eligibility criteria. All were treated with a regimen of cyclophosphamide, vincristine, and prednisone (CVP) given every 3 weeks for eight cycles. Thereafter, patients were eligible for iceberg irradiation. Finally, all patients were completely restaged, and responding and stable-disease patients were then randomized, 122 to interferon alfa-2a maintenance, 3 million U three times weekly for 1 year; and 120 to no further treatment. RESULTS: Seventy-nine percent of the patients response to CVP, ie, 45% complete remissions (CR) and 34% partial remissions (PR). In the group of randomized patients, the response rate after CVP plus or minus radiotherapy was 90%. As compared with control patients, patients in the interferon (IFN) maintenance group had a tendency toward a prolonged time to progression (TTP) (median, 132 v 87 weeks; P = .054, adjusted for response to CVP). However, overall survival was similar in both groups. Interferon was well tolerated. The median dose of IFN actually received corresponded to 90% of the planned cumulative dose. The treatment had to be stopped because of toxicity in 16 patients (15% of the patients in whom IFN was started). CONCLUSION: Interferon maintenance treatment in the phase of minimal residual disease of patients with advanced low-grade malignant NHL increased TTP at the borderline of statistical significance, without remarkable toxicity. However, overall survival was not influenced.

The impact of age on local control in women with pT1 breast cancer treated with conservative surgery and radiation therapy.

The aim of the study was to evaluate the importance of young age with regard to local control in a prospective cohort of 1085 women with pathological T1 tumours treated with breast conservative treatment (BCT). Patients were divided into two age groups: 40 years or younger, 7.8%, and older than 40 years, 92.2%. With a median follow-up of 71 months, the local recurrence rate was 10.6% in women < or =40 years, and 3.7% in older women. The local recurrence-free survival (LRFS) was significantly different for the two age groups, respectively 89%, < or =40 years, and 97.6%, >40 years (P=0.0046). A separate analysis showed a significantly decreased LRFS for young women with a positive family history, 75.4% versus 98.4% 5-year LRFS for older women. A worse LRFS for young women with a negative lymph node status was also observed, respectively 84% versus 98% 5-year LRFS (both P<0.001). In a multivariate analysis, taking into account the pre-treatment and treatment factors, age < or =40 years, was the only significant predictor of a decreased LRFS. Thus, young age is an important factor in relation to local control. In a subset analysis, this significant adverse effect of young age on outcome appears to be limited to the node-negative patients and those with a positive family history. To date, there is no evidence that young women with pT1 breast cancer, treated by mastectomy have an improved outcome when compared with those treated with conservative surgery and radiotherapy. Taking into account results from a subset analysis suggests that giving systemic therapy to a subgroup of women who are < or =40 years, node-negative and/or have a positive family history might give a better local control.

Long-term results of low dose total body irradiation for advanced non-Hodgkin lymphoma.

Sixty-eight patients received fractionated low dose total body irradiation (LTBI) as treatment for non-Hodgkin lymphoma (NHL) at the Rotterdamsch Radio-Therapeutisch Instituut (RRTI) in the period 1973-1979. Ninety percent (61/68) of these patients had advanced disease (Stage III + IV). According to current malignancy grade classifications, 34 patients had low grade NHL, 10 intermediate, and 19 high grade. In 5 cases no exact grading was possible. LTBI was given 3 times a week, midline dose 0.1 Gy, using 6 or 25 MeV photons to a mean total dose of 1.78 Gy. Initial response rate for low, intermediate, and high grade NHL was resp. 84, 42, and 40%. The main prognostic factor for survival and recurrence-free survival (RFS) was malignancy grade. Probability of uncorrected survival at 10 years for low, intermediate, and high grade was resp. 34, 0 and 0%. Probability of RFS at 10 years was resp. 19, 0, and 0%. Neither stage nor sex had any influence on survival. Age was reversely correlated with survival, but was not correlated with RFS. Influence of prior therapy (18 patients) on survival and RFS was separately analyzed. Neither survival nor RFS of unfavorable histologic type NHL (high and intermediate grade) was influenced. On the other hand patients with a favorable histologic type NHL (low grade) had a significantly (p less than 0.05) better RFS if they received LTBI as initial treatment, but survival was not significantly influenced. RFS at 5 and 10 years of patients who received LTBI as first treatment was respectively 32% and 27%. No treatment related complications were noted. Subsequent chemotherapy in case of relapse was not hampered by previous LTBI. The high response rate and extended RFS, without maintenance therapy, makes LTBI a preferable first line treatment for patients with advanced stage low grade NHL.

Endometrial adenocarcinoma, adjuvant radiotherapy tailored to prognostic factors.

The optimal adjuvant radiotherapy for surgically treated endometrial cancer has not yet been defined. We report on 389 patients treated between 1970 and 1985 with adjuvant radiotherapy. The treatment was tailored to the known prognostic factors: myometrial invasion and grade of differentiation of the tumor. Ten-year overall survival was 67%, 10-year relapse-free survival 77%; 23% relapse, of which 21% distant and 6% locoregional relapse. In a multivariate analysis, stage (pT), grade, and myometrial invasion were prognostic factors. The number of locoregional failures was very small (n = 23). This small number, the fact that radiation treatment was tailored to prognostic factors, and the absence of a nontreated control group precluded an analysis of the effect of the adjuvant irradiation. Large randomized studies with a control (no treatment) arm should be performed to determine the value of adjuvant radiotherapy.

Low-dose total body irradiation versus combination chemotherapy for lymphomas with follicular growth pattern.

The treatment of Non-Hodgkin's lymphomas with follicular growth pattern and advanced stage of disease remains controversial. Treatments varying from no initial treatment up to aggressive combination chemotherapy have been advocated. The EORTC Lymphoma Cooperative Group has performed a randomized prospective trial comparing short duration low dose total body irradiation (TBI) vs combination chemotherapy (CHVmP) + consolidation radiotherapy. Ninety-three patients were entered; of 84 evaluable patients, 44 received TBI and 40 CHVmP. Complete remission (CR) rates were 36%--TBI and 55%--CHVmP, but overall response rates were identical, 76 versus 69%. No significant difference in freedom from progression or survival was observed. No unexpected toxicity was seen. Although numbers are small, we cannot conclude that aggressive combination chemo-radiotherapy resulted in a better survival. Our analysis confirms that there is a constant risk of relapse. Other approaches should be explored if survival benefit is the ultimate goal in treatment of this patient population.

Causes of death after therapy for early stage Hodgkin's disease entered on EORTC protocols. EORTC Lymphoma Cooperative Group.

The risk of dying from different causes after Hodgkin's disease (HD) therapy has been quantified from a series of 1,449 patients with early stages included in four successive clinical trials conducted by the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Cooperative Group since 1963. Overall, 240 patients died and the 15-year survival rate was 69% whereas the expected rate was 95%. The standardized mortality ratio (SMR) technique was used to quantify excess deaths as a function of time since first therapy. At each interval, SMR was significantly increased, giving: 0-3 year, 8.86 (p less than 0.001); 4-6 year, 9.25 (p less than 0.001); 7-9 year, 7.08 (p less than 0.001); 10-12 year, 9.53 (p less than 0.001); 13-15 year, 4.37 (p less than 0.01); and 16+ years, 3.80 (p less than 0.05). While the proportion of deaths as a consequence of HD progression, treatment side-effect, and intercurrent disease decreased with time, that of second cancer and cardiac failure peaked during the 10-12 year post-treatment interval. After 15 years of follow-up, the risk of dying from causes other than HD continued to increase. These findings indicate that although probably cured from HD, patients are at higher risk for death than expected, a risk that might be a consequence of therapy.

The role of radiotherapy in the treatment of bile duct carcinoma.

Forty-two patients with irresectable bile duct carcinoma (n = 31) or with microscopic evidence of tumor rest after aggressive surgery for bile duct carcinoma (n = 11) were given radiotherapy consisting intentionally of external-beam therapy and intraluminal 192Iridium (192Ir) wire application(s) following bile drainage procedures. The treatment was well tolerated; complications were mainly infectious and related to the success of the drainage. A median survival of 10 months was achieved for the group as a whole. Patients treated following microscopically incomplete resection survived longer than patients with an irresectable tumor (15 vs 8 months median survival, p = 0.06). Gross lymph node involvement also proved to be a prognostic factor.

Low dose reirradiation in combination with hyperthermia: a palliative treatment for patients with breast cancer recurring in previously irradiated areas.

Ninety-seven patients with breast cancer recurring in a previously irradiated area (mean dose 44 Gy) were reirradiated in combination with hyperthermia and had evaluable tumor responses. In the reirradiation series, radiotherapy was given twice weekly in most patients, with a fraction size varying from 200 to 400 cGy, the total dose varying from 8 to 32 Gy. Hyperthermia was given following the radiotherapy fractions. The combined treatment resulted in 35% complete and 55% partial responses. Duration of response was median 4 months for partial response and 26 months for complete response, respectively. The median survival time for all patients was 12 months. Acute skin reaction was mild, with more than moderate erythema in only 14/97 patients. Thermal burns occurred in 44/97 patients, generally at sites where pain sensation was decreased, and therefore they did not cause much inconvenience. In the 19 patients who survived more than 2 years, no late radiation damage was observed. When patients who received a "high dose" (greater than 29 Gy and hyperthermia) were compared with those who received a "low dose" (less than 29 Gy and hyperthermia), a higher complete response rate was observed in the high dose group (58% vs. 24%), whereas no difference in acute toxicity was found. We conclude that reirradiation with 8 x 4 Gy in combination with hyperthermia twice weekly is a safe, effective and well tolerated method for palliative treatment of patients with breast cancer recurring in previously irradiated areas.

Age as a prognostic factor in carcinoma of the cervix.

To investigate whether age is a prognostic factor in patients with carcinoma of the cervix, a retrospective study was undertaken of 261 patients, aged 45 years or less, who were referred to the Rotterdamsch Radio-Therapeutisch Instituut (RRTI) between 1973 and 1982. Patients were referred for either primary treatment--surgery or radiotherapy--or for adjuvant radiotherapy. Overall 5-year survival figures were rather low, which may be explained by negative patient selection as the RRTI is a referral hospital: stage IB, 72%; stage IIA; 61%; stage IIB; 52%; stage III; 29%. A particular poor survival was noted for patients (n = 22) aged 28 or less. Overall 5-year survival of these patients was only 39% in contrast to 67% 5-year survival of older patients. This difference was highly significant (p less than 0.002). Even if corrected for stage, very young patients had a poorer prognosis (stage IB: 45% versus 75% 5-year survival of older patients). Within the older age group, no trend towards a better prognosis with increasing age could be identified. As a treatment was similar for all patients, no explanation is available for this observation.

Peroperative brachytherapy with the use of a vicryl mat in advanced or recurrent pelvic tumors.

UNLABELLED: Uncontrolled tumor growth of pelvic tumors is a very serious problem. To test the possibility of combining intra-operative placement of brachytherapy catheters fixed in a vicryl mat, patients with pelvic tumors were subjected to surgery followed by brachytherapy plus external radiotherapy. IN CONCLUSION: the procedure is feasible.

Combined modality treatment is the treatment of choice for stage I/IE intermediate and high grade non-Hodgkin's lymphomas.

BACKGROUND AND PURPOSE: In a retrospective study, the efficacy of radiotherapy alone was compared with combined modality treatment in patients with stage I/IE non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between 1980 and 1994, 296 patients with stage I/IE non-Hodgkin's lymphoma of intermediate or high grade malignancy (according to the Working Formulation) were treated in four different institutions. All patients were included except patients that presented with NHLs localized in the central nervous system, testis or skin. Two hundred two patients were treated with radiation therapy alone and 94 patients were treated with combined modality treatment. RESULTS: Increasing age and radiation as a single treatment (versus combined modality treatment) were highly significant adverse prognostic factors by multivariate analysis. The actuarial 10-year rates for progression-free and overall survival were 83 and 70%, respectively, for the patients treated with combined modality treatment and 47 and 43%, respectively, for the patients treated with radiation therapy alone. CONCLUSION: Combined modality treatment is the treatment of choice for patients with stage I/IE intermediate and high grade non-Hodgkin's lymphomas.

Adjuvant postoperative radiotherapy for gastric carcinoma with poor prognostic signs.

Fifty-seven patients with poor prognostic factors following resection with curative intent for gastric adenocarcinoma (T3 or T4, positive lymph nodes, positive resection line) received adjuvant radiotherapy. A dose of 30.0-50.0 Gy was given in 10-25 fractions in one course or with a split of 2 weeks after 15 fractions. This was combined with 5-fluorouracil (5-FU) (375 mg/m2) given i.v. as a bolus during the first 4 days of radiation (n = 49). The 5-year survival was 26%; this rate is higher than the figures mentioned in the literature after surgery alone. The only way to prove the role of adjuvant radiotherapy for gastric carcinoma is a prospective randomized trial.

Radiation-induced lung damage after thoracic irradiation for Hodgkin's disease: the role of fractionation.

PURPOSE: to estimate the alpha/beta ratio for damage to human lung after thoracic irradiation for Hodgkin's disease. PATIENTS AND METHODS: The criterion for lung injury was the presence of radiological changes in the vicinity of the mediastinum as assessed on regular follow-up chest X-ray examinations. Patients with supradiaphragmatic stage I-II Hodgkin's disease received mantle field irradiation as part of their treatment between 1964 and 1981 (E.O.R.T.C. protocols H1, H2, and H5). The total mediastinal doses fixed by the protocols were 35-40 Gy. The fractional doses were left to the decision of the physicians in charge: the most frequent regimens were 5 x 1.8, 5 x 2.0, 4 x 2.5 and 3 x 3.3 Gy per week. The data were fit to the linear-quadratic (L.Q.) model using time-to-injury as endpoint. RESULTS: 1048 (97%) of 1082 patients were evaluable. The mean follow-up duration was 8 years. One hundred and ninety-five cases of radiologically-visible lung damage were observed after a median interval of 6 months (range: 0-101). The 3-year actuarial probability of lung damage was 19% (95% confidence limits: 17, 21). Multivariate analysis (Cox model, stratified by protocol) showed an increased risk of damage with dose per fraction (relative risk, R.R. = 2.22 per Gy (1.75, 2.82)), the presence of systemic symptoms (R.R. = 1.53 (1.09, 2.15)), and total mediastinal dose (R.R. = 1.06 per Gy (1.01, 1.12)). Age, sex, histological type, number of involved nodal sites and radiotherapy duration did not significantly modify the risk of lung damage. The L.Q. model parameters were: alpha = 0.031 Gy-1 (0.003, 0.059), beta = 0.010 Gy-2 (0.007, 0.013), alpha/beta = 3.07 Gy (-0.23, 8.46). CONCLUSION: this low alpha/beta ratio is consistent with late effects values from animals and humans, and illustrates the influence of large fraction sizes on the occurrence of late pulmonary complications.

Accuracy of patient positioning in mantle field irradiation.

A prospective study of the accuracy of patient positioning in mantle field irradiation was carried out in 13 lymphoma patients treated with curative radiotherapy. Patients were treated in the supine and prone position for anterior and posterior fields, respectively. Individually shaped divergent shielding blocks were placed in a fixed position in a template which was positioned on a tray above the patient. A total number of 94 megavoltage portal films (MV) was analysed and compared to 26 simulation films (SIM). MV-SIM differences were larger for posterior fields than for anterior fields. Regarding the position of the lung shielding blocks, mean MV-SIM differences ranged from 1.3 to 4.4 mm and errors exceeding 1 cm were found in 7.2% of cases. Most discrepancies appeared to be randomly distributed. A 4-5 mm systematic cranial shift of patients in the posterior treatment position was noted. Discrepancies in the position of the laryngeal block, spinal cord shielding block and humerus blocks were small with mean MV-SIM differences ranging from 0.3 to 2.7 mm. Differences between simulation set-up and treatment set-up were modest as compared to error rates reported in the literature. Shielding of tumour-bearing areas did not occur. It was concluded that the present standardised technique of patient positioning and the design of treatment fields results in acceptable error rates. Attention should be directed towards increasing the stability of patients in the prone treatment position in order to further reduce both systematic and random error rates.

Late radiation injuries of the gastrointestinal tract in the H2 and H5 EORTC Hodgkin's disease trials: emphasis on the role of exploratory laparotomy and fractionation.

Out of 516 patients who entered in the two successive EORTC trials H2 and H5 for supra-diaphragmatic stages I and II Hodgkin's disease (HD), and who received an infra-diaphragmatic irradiation, 36 (7%) developed late radiation injuries of the gastrointestinal tract (GIT). Twenty-five patients presented with ulcers (stomach or duodenum), 2 with severe gastritis, 6 with small bowel obstruction or perforation and 3 patients had both an ulcer and bowel obstruction. A previous laparotomy played an important role. While the complication rate was 2.7% without any previous abdominal surgery, it was 11.5% after laparotomy (p less than 0.001). Fractionation was also found to be of importance in the occurrence of complications: three different weekly schedules were used -5 x 2 Gy, 4 x 2.5 Gy and 3 x 3.3 Gy; the GIT complication rates were 4, 9 and 22%, respectively (p less than 0.001). When combining laparotomy and fractionation, we found that the patients who were treated using 5 weekly fractions of 2 Gy without any prior laparotomy had a very low rate of late digestive complications (1%), whereas the patients who received 3 weekly fractions of 3.3 Gy after laparotomy presented a 39% complication rate. The other subgroups of patients were at an intermediate risk (from 5 to 13%) of late digestive injuries. Since most patients received 40 Gy with only very small variations, the influence of the radiation dose could not be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Family history in breast cancer is not a prognostic factor?

The aim of this study is to determine if breast conservative treatment is justified for patients with a positive family history of breast cancer and to investigate whether they have a worse prognosis. We performed a prospective cohort study of breast cancer patients, treated with breast conservative treatment with radiotherapy at the Radiotherapy Department of the Medisch Spectrum Twente. Between 1984 and 1996, 1204 patients with T1 and T2 < or =3 cm were treated. Family history (FH) was recorded according to first degree relative (FDR). Treatment consisted of lumpectomy with axillary dissection followed by radiotherapy to the whole breast with a boost to the primary area. Adjuvant systemic therapy was given to patients with positive nodes. A positive FH was noted in 243 (20.5%) patients, of whom 208 (17.6%) had one FDR, and 35 (3.0%) > or =2 FDRs. The local recurrence rate was 4.1%, with similar rates for all groups. In young patients, < or =40 years, a significant relation between local recurrence and FH was found. The distant metastasis rate was 15.5%, with the lowest rate (5.7%) among patients with > or =2 FDRs. Patients with a positive FH had significantly more contralateral tumours. The 5-year corrected survival was 91.3%. Among patients with a positive FH, a 5-year corrected survival of 91% was observed and the survival 100% among patients with one and > or =2 FDR. Family history is not a contraindication for breast conservative treatment and is not associated with a worse prognosis. Family history is not a prognostic factor for local recurrence rate in patients older than 40 years.

Synchronous, bilateral breast cancer: prognostic value and incidence.

The purpose of this study was to address the question whether patients with bilateral breast cancer (BBC) have a worse prognosis in terms of recurrence and survival than patients with primarily unilateral breast cancer (UBC) following breast-conserving treatment (BCT). From 1983 to 2000, a total of 1760 BCT were registered in the Radiotherapy Department of the Medisch Spectrum Twente. We defined synchronous a BBC as cancer diagnosed in both breasts at the same time or within a period of 3 months of diagnosis of the first tumor. One thousand seven hundred and sixty BCT were performed on 1705 patients, 26 of whom presented with BBC. Of these 26 patients, 18 had BCT for both breasts. A higher proportion of patients with BBC showed more tubular carcinoma (P=0.029) and medially located tumors (P=0.076) than those with UBC did. The 5- and 10-year local recurrence rates (LRRs) were 4.5% and 9.1%, respectively, in BBC patients, as against 3.3% and 7.6% for UBC after BCT. The 5- and 10-year distant metastasis rates were 26.9% and 50.7%, respectively, for BBC as against 13.4% and 21.1% for UBC after BCT (P=0.065 and P=0.014, respectively). The 5- and 10-year disease-specific survival (DSS) rates for the 1705 patients were 82.1% and 41%, respectively, after BBC, and 91.4% and 84% after UBC (P=0.086 and P=0.0045, respectively). Patients with BBC have a higher rate of distant metastasis and a worse DSS than those with UBC. As the LRR is similar for BBC and UBC, BCT is not contraindicated in BBC. The incidence of BBC is low, at 1.5% which makes it difficult to reach any more definitive conclusions on outcome and treatment.

Low-dose total body irradiation in non-Hodgkin lymphoma: short- and long-term toxicity and prognostic factor.

The toxicity of low-dose total body irradiation (LTBI), the prognostic factors related to survival and relapse-free survival, and the efficacy of treatment given for relapse after LTBI were analyzed in 68 patients with non-Hodgkin lymphoma (NHL) treated at the Rotterdamsch Radiotherapeutisch Instituut. All patients received LTBI between 1973 and 1979. The patient material was heterogeneous with respect to malignancy grade, stage, age, and therapy given before or after LTBI; the unifying principle was that all patients received LTBI and had symptomatic NHL. Analysis of prognostic variables with Cox's model revealed grade (p less than 0.001) and age (p = 0.004) as predictors for survival and grade (p less than 0.001) and dose of LTBI (p = 0.056) as predictors for relapse-free survival after LTBI. No subjective toxicity was observed during or after LTBI treatment. Hematologic toxicity was dose-limiting and was increased if patients had received cytotoxic treatment before LTBI. LTBI-related hematologic toxicity was lower in patients with low-grade NHL than in those with intermediate or high-grade NHL, was limited in time, and recovered in all patients. Patients relapsing after LTBI received a variety of therapies. Response rates were high, but of short duration, especially in intermediate or high-grade NHL. Duration of response was progressively shorter after multiple relapses.