Is Radiation Therapy Cost-Effective in the Positron Emission Tomography/Computed Tomography Era for Early-Stage Favorable Hodgkin Lymphoma With Alternative Payment Models?

PURPOSE: Despite multiple randomized trials, variation in practice remains regarding the most effective treatment for early-stage, favorable-risk Hodgkin lymphoma. With increasing emphasis on alternative payment models, we investigate the cost-effectiveness of chemotherapy alone versus combined modality therapy (CMT). METHODS AND MATERIALS: A Markov model was formed to compared 2 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) to 2 cycles of ABVD followed by 20 Gy in 10 fractions involved-site radiation therapy. Modalities were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs) and evaluated with a willingness to pay a threshold of $100,000 per QALY gained. RESULTS: The base case analysis showed that CMT is cost-effective compared with ABVD alone, with an incremental cost-effectiveness ratio of $8028 per QALY gained and an incremental cost of $236 gaining 0.029 QALYs. On sensitivity analyses, the results were the most sensitive to changes in recurrence rates. If the recurrence rate differences were ≥6%, CMT was cost-effective. CONCLUSIONS: CMT is a cost-effective strategy for early-stage, favorable-risk Hodgkin lymphoma based on currently available evidence. However, small variations in recurrence-rate estimates dramatically affect strategy cost-effectiveness.

How to choose first salvage therapy in Hodgkin lymphoma: traditional chemotherapy vs novel agents.

Approximately 10% to 30% of patients with classical Hodgkin lymphoma (cHL) develop relapsed or refractory (R/R) disease. Of those patients, 50% to 60% show long-term progression-free survival after standard salvage chemotherapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). In the past decade, novel therapies have been developed, such as the CD30-directed antibody-drug conjugate brentuximab vedotin and immune checkpoint inhibitors, which have greatly extended the treatment possibilities for patients with R/R cHL. Several phase 1/2 clinical trials have shown promising results of these new drugs as monotherapy or in combination with chemotherapy, but unfortunately, very few randomized phase 3 trials have been performed in this setting, making it difficult to give evidence-based recommendations for optimal treatment sequencing. Two important goals for the improvement in the treatment of R/R cHL can be identified: (1) increasing long-term progression-free and overall survival by optimizing risk-adapted treatment and (2) decreasing toxicity in patients with a low risk of relapse of disease by evaluating the need for HDCT/ASCT in these patients. In this review, we discuss treatment options for patients with R/R cHL in different settings: patients with a first relapse, primary refractory disease, and in patients who are ineligible or unfit for ASCT. Results of clinical trials investigating novel therapies or strategies published over the past 5 years are summarized.

Assessment of Radiation Doses Delivered to Organs at Risk Among Patients With Early-Stage Favorable Hodgkin Lymphoma Treated With Contemporary Radiation Therapy.

Importance: Response-adapted randomized trials have used positron emission tomography-computed tomography to attempt to identify patients with early-stage favorable Hodgkin lymphoma (ESFHL) who could be treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) without radiation therapy (RT). While maximal efficacy is demonstrated with combined modality therapy, RT is often omitted in fear of late adverse effects; however, the application of modern RT could limit these toxic effects. Objective: To determine the radiation doses delivered to organs at risk with modern involved-site RT among patients with ESFHL treated with 20 Gy after 2 cycles of ABVD. Design, Setting, and Participants: This case series included 42 adult patients with ESFHL (according to the German Hodgkin Study Group criteria) who were treated between 2010 and 2019, achieved complete response by positron emission tomography-computed tomography (1-3 on 5-point scale) following 2 cycles of ABVD, and then received consolidative RT. The study was conducted at a single comprehensive cancer center. Exposures: 2 cycles of chemotherapy followed by 20-Gy involved-site RT. Main Outcomes and Measures: The medical records of patients with ESFHL were examined. Organs at risk were contoured, and doses were calculated. Progression-free survival, defined from date of diagnosis to disease progression, relapse, or death, and overall survival were estimated using the Kaplan-Meier method. Results: The cohort comprised 42 patients with ESFHL (median [range] age at diagnosis, 35 [18-74] years; 18 [43%] women; 24 [57%] with stage II disease). At a median follow-up of 44.6 (95% CI, 27.6-61.6) months, the 3-year progression-free survival and overall survival rates were 91.2% (95% CI, 74.9%-97.1%) and 97.0% (95% CI, 80.4%-99.6%), respectively. The mean heart dose was less than 5 Gy (mean, 0.8 Gy; SD, 1.5 Gy; range, 0-4.8 Gy) in all patients. The mean (SD) breast dose for both breasts was 0.1 (0.2) Gy (left breast range, 0-1.0 Gy; right breast range, 0-0.9 Gy). Conclusions and Relevance: In this study, combined modality therapy with 2 cycles of ABVD and 20 Gy for ESFHL was highly effective and avoided excess doses to organs at risk, which may limit long-term toxic effects.

Association of intensity-modulated radiation therapy on overall survival for patients with Hodgkin lymphoma.

PURPOSE: The purpose of this study was to compare outcomes with Hodgkin lymphoma (HL) patients receiving IMRT (intensity-modulated radiation therapy), versus those receiving 2D/3D-CRT (3-dimensional conformal RT) in a large observational cohort. PATIENTS AND METHODS: We evaluated patients diagnosed with stage I-IV HL from 1998 to 2011 from the National Cancer Database (NCDB). The association between IMRT use vs. 2D/3D-CRT, co-variables, and outcome was assessed in a Cox proportional hazards model. Propensity score (PS) matching was performed to balance known confounding factors. Survival was estimated using the Kaplan-Meier method. RESULTS: Of the 76,672 patients with HL within the NCDB, 12,393 patients with stage I-IV HL received RT (median dose=30.6 Gy) and were eligible for this study, and 6013 patients analyzed for overall survival. The cohort had a median follow-up of 6.2 years and median age of 37 years (range: 18-90). The RT modalities used were: 2D/3D-CRT (n=11,491, 92.7%) or IMRT (n=902, 7.3%). Patients were more likely to receive IMRT if they were of male gender, early stage, no "B" symptoms, and treated at comprehensive cancer programs (all p<0.05). During this time period, there was a significant decrease in use of 2D/3D-CRT from 100% to 81.5%, with a subsequent increase in IMRT utilization from 0% to 18.5%. Five-year overall survival for patients receiving 2D/3D-CRT (n=5844) was 89.9% versus 95.2% for those receiving IMRT (n=169; HR=0.45; 95% CI, 0.23-0.91, p=0.02). After PS-matching based on clinicopathologic characteristics, IMRT use remained associated with improved overall survival (HR=0.40; 95% CI, 0.16-0.97, p=0.04). CONCLUSIONS: Our study reveals that HL patients receiving modern RT techniques were associated with an improvement in overall survival. This may have been related to patient selection, access to improved staging and management, or improvements in treatment technology. This represents the only study examining survival outcomes of advanced RT modalities, which may be considered on a case-by-case basis for highly selected patients with HL.

Involved node radiation therapy: an effective alternative in early-stage hodgkin lymphoma.

PURPOSE: The involved node radiation therapy (INRT) strategy was introduced for patients with Hodgkin lymphoma (HL) to reduce the risk of late effects. With INRT, only the originally involved lymph nodes are irradiated. We present treatment outcome in a retrospective analysis using this strategy in a cohort of 97 clinical stage I-II HL patients. METHODS AND MATERIALS: Patients were staged with positron emission tomography/computed tomography scans, treated with adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy, and given INRT (prechemotherapy involved nodes to 30 Gy, residual masses to 36 Gy). Patients attended regular follow-up visits until 5 years after therapy. RESULTS: The 4-year freedom from disease progression was 96.4% (95% confidence interval: 92.4%-100.4%), median follow-up of 50 months (range: 4-71 months). Three relapses occurred: 2 within the previous radiation field, and 1 in a previously uninvolved region. The 4-year overall survival was 94% (95% confidence interval: 88.8%-99.1%), median follow-up of 58 months (range: 4-91 months). Early radiation therapy toxicity was limited to grade 1 (23.4%) and grade 2 (13.8%). During follow-up, 8 patients died, none from HL, 7 malignancies were diagnosed, and 5 patients developed heart disease. CONCLUSIONS: INRT offers excellent tumor control and represents an effective alternative to more extended radiation therapy in the combined modality treatment for early-stage HL.

Salvage therapy in Hodgkin's lymphoma.

Hodgkin's lymphoma (HL) is a commonly cured malignancy. Unfortunately, patients who are refractory to or relapse after first-line treatment pose a significant therapeutic challenge. There is evidence that these patients are best treated with an approach involving salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT). This approach may result in cure, with better results in patients with low-risk relapse. In patients with high-risk relapse and refractory disease, HDCT/ASCT is rarely curative. More aggressive transplant approaches have shown promising results in this group and are currently under active investigation. For those relapsing after HDCT/ASCT, there exists a range of therapeutic options, including further salvage chemotherapy, reduced-intensity allogeneic transplantation, monoclonal antibody therapy, and novel agents. All patients in this category should be considered for enrollment in clinical trials. This review discusses the evidence behind the current practice in patients with relapsed or refractory HL. Specifically, the efficacy of various salvage chemotherapy regimens, the risk factors influencing outcome with HDCT/ASCT, and the results with alternative transplant approaches, monoclonal antibody therapies, and novel agents are addressed. We conclude by providing our approach to these patients, with the hope that this will serve as a framework for the practicing oncologist.

Multimodality surgical and hyperbaric management of mandibular osteoradionecrosis.

PURPOSE: To elucidate long-term outcomes in 65 consecutive patients meeting a uniform definition of mandibular osteoradionecrosis (ORN) treated with multimodality therapy including hyperbaric oxygen (HBO). METHODS AND MATERIALS: Pretreatment, post-treatment and long-term follow-up of mandibular lesions with exposed bone were ranked by a systematic review of medical records and patient telephone calls. The ranking system was based on lesion diameter and number plus disease progression. Changes from pretreatment to post-treatment and follow-up were analyzed by Wilcoxon signed-rank tests. Improved wound survival, measured by time to relapse, defined as any less favorable rank after HBO treatment, was assessed by Kaplan-Meier analysis. RESULTS: In all, 57 cases (88%) resolved or improved by lesion grade or progression and evolution criteria after HBO (p < 0.001). Four patients healed before surgery after HBO alone. Of 57 patients who experienced improvement, 41 had failed previous nonmultimodality therapy for 3 months and 26 for 6 months or more. A total of 43 patients were eligible for time-to-relapse survival analysis. Healing or improvement lasted a mean duration of 86.1 months (95% confidence interval [95% CI], 64.0-108.2) in nonsmokers (n = 20) vs. 15.8 months (95% CI, 8.4-23.2) in smokers (n = 14) versus 24.2 months (95% CI, 15.2-33.2) in patients with recurrent cancer (n = 9) (p = 0.002 by the log-rank method). CONCLUSIONS: Multimodality therapy using HBO is effective for ORN when less intensive therapies have failed. Although the healing rate in similarly affected patients not treated with HBO is unknown, the improvements seen with peri-operative HBO were durable provided that the patients remained cancer free and abstained from smoking.

Coronary artery disease after radiation therapy for Hodgkin's lymphoma: coronary CT angiography findings and calcium scores in nine asymptomatic patients.

OBJECTIVE: Long-term survivors of Hodgkin's lymphoma treated with radiation therapy have an increased incidence of coronary artery disease. The purpose of this study is to describe the coronary CT angiography findings and calcium scores of asymptomatic patients who had mediastinal irradiation for Hodgkin's lymphoma and to evaluate the impact of coronary CT angiography on patient management. MATERIALS AND METHODS: We evaluated nine consecutive patients, age range 35-60 years, who had been treated for Hodgkin's lymphoma by radiation therapy between the ages of 11 and 27 years. The total mediastinal dose ranged from 34 to 45 Gy. All patients were evaluated with 64-MDCT with calcium scoring followed by CT angiography of the coronary arteries. Imaging findings and clinical follow-up were analyzed. RESULTS: Eight of nine patients had coronary artery disease. CT showed long segments of diffuse disease; areas of stenosis from soft plaque; and calcification in the proximal right coronary, left anterior descending, and left circumflex arteries. Calcium scores were significantly higher than in other patients of this age group. Additional tests, including selective coronary angiography, were necessary in patients with diffuse disease with calcifications. CT evaluation led to bypass surgery and angioplasty in two patients. CONCLUSION: Coronary CT angiography and calcium scores are useful tools for evaluation of irradiation-related coronary artery disease. Complementary tests might be necessary in selected patients. Prospective larger studies are needed to better define the role of coronary CT angiography and calcium scores and to establish an algorithm for evaluation and treatment of these patients.

[Thyroid function after external irradiation of the neck in patients with Hodgkin's disease--long-term observation]. / Czynnosc tarczycy po radioterapii okolicy szyi u pacjentów z choroba Hodgkina--dlugoletnia obserwacja.

INTRODUCTION: The modern therapy of Hodgkin's disease (HD): chemotherapy (CT) or/and radiotherapy (RT) gives a chance of a long time survival but it brings a possibility of early and late complications including thyroid gland function disorders (post-radiotherapy thyroiditis, thyroid hypofunction, Graves disease, thyroid nodules, thyroid cancer). AIM: Evaluation of thyroid gland function in patients with total HD remission status from 6 to 16 years after the treatment. MATERIAL AND METHODS: The study included 29 patients suffering from HD (9 women, 20 men, mean age 22.8 years), treated with CT (cycles MVPP and B-DOPA) and with RT (cervical region; 18-40 Gy) in their childhood. The patients were examined by palpation, ultrasound, fine-needle aspiration biopsy. The thyroid gland on the average 6 (1st examination) and 16 years (2nd examination) after the treatment as well as thyroid hormones (TSH, fT3, fT4), thyroglobulin (Tg) and anti-thyroid antibodies in blood serum were estimated. The results were analyzed statistically; the percentage of abnormal results of estimated hormones with reference range was calculated. RESULTS: There were no abnormalities in thyroid palpation examination in any patient. The mean thyroid volume in ultrasound in 2nd examination cor-responded to 66.3% of healthy individuals thyroid volume. In 8 patients thyroid nodules were found, in one thyroid papillary carcinoma was diagnosed. In one patient (3.4%) the features of subclinical thyroid hypofunction and in 17.2% the increased level of Tg in blood serum with normal thyroid hormone levels were found. In two patients (6.8%) the raised titre of a-TG and a-TPO was observed. CONCLUSIONS: 1. In majority of patients with HD after RT in cervical region in long term remission period the normal thyroid function was observed. 2. Due to thyroid cancer hazard even many years after radiotherapy regular morphological thyroid evaluation is necessary.

Is the treatment of Hodgkin's disease detrimental to the parathyroid gland?

The thyroid gland is often injured by supradiaphragmatic irradiation for Hodgkin's lymphoma. The aim of the present study was to examine whether the parathyroid gland gets injured by the treatment for Hodgkin's disease. Calcium, phosphorus and parathormone levels of 143 patients with primary treatment for Hodgkin's disease and in complete remission for 2 years were measured as well as the presence of antiparathyroid antibody in patients having antithyroid antibody. Out of the 143 patients studied, 104 received neck irradiation (with or without chemotherapy); among them laboratory alterations were observed in 7 cases. 39 patients received only chemotherapy; 3 of them had alterations. In contrast to the injury of the thyroid gland, no damage to the parathyroid glands associated with the treatment for Hodgkin's disease was noted. It has been concluded that the use of high-dose external radiotherapy does not mean a higher risk as regards the parathyroid gland but further follow-up studies of the patients may result in the revelation of the development of parathyroid lesions.

[Preliminary results of thyroid function assessment in children and adolescents with Hodgkin's disease (HD) treated according to PGP-HD-97 protocol]. / Wstepne wyniki badania czynnosci tarczycy u dzieci i mlodziezy z choroba Hodgkina (HD) leczonych wedlug programu PGP-HD-97.

The intensive treatment of HD (multidrug chemotherapy combined with radiotherapy) carries the risk of early and late complications. One of the late effects is thyroid dysfunction which may occur after radiotherapy of the cervical region. In this report preliminary results of thyroid function assessment in children with HD in correlation with time after cessation of therapy are presented. Between January 1, 1997 and December 31, 2002, 58 children with HD (age: 2.6-18.3 years, median, 14.9 years) were treated in Department of Pediatric Oncology and Hematology PAIP CMUJ in Kraków, according to PGP-HD-97 protocol and these patients were included in the study. Multidrug chemotherapy combined with low-dose involved-field radiotherapy (15-25 Gy) was used in treatment of these children. Therapy was completed in all of analysed patients and in 38 of them (65.5%) at least 24 months before the end of observation. Physical and ultrasound examination of thyroid gland, and plasma levels of T3, T4, fT3, fT4, and TSH were measured before treatment of HD, before the treatment cessation, and every 6-12 months after the completion of therapy. The observation was completed on December 31, 2003. Six hundred and twelve measurements were performed in all of patients. At least one abnormal result of thyroid hormones or TSH levels was found in 50% of children. The most frequent abnormality was the increased level of TSH which occurred in 27.6% of patients. The rates of abnormal results of TSH concentration before HD treatment, and 1 year, 2 years, and later than 2 years after the cessation of therapy were: 8.3%, 8.8%, 21,4%, and 10.2%, respectively. These differences were not statistically significant. Seven patients (12%) require endocrinological treatment due to thyroid dysfunction. These patients as well as other analysed children are clinically euthyreotic. Initial results of thyroid function assessment presented in this report indicate that longer follow up and further thyroid function tests, physical and ultrasound examination of thyroid gland in patients after HD therapy cessation are needed. These studies are essential to early detection and adequate treatment of early and late complications of HD therapy.

[Total irradiation of the liver in treating patients with lymphogranulomatosis]. / Total'noe obluchenie pecheni v lechenii bol'nykh limfogranulematozom.

AIM: The study of efficiency of radiation in specific affection of the liver in lymphogranulomatosis (LGM). MATERIALS AND METHODS: 212 LGM patients were examined for hepatic lesions using x-ray, radiological, cytochemical and histological investigations of the biopsies. Coagulation, alkaline phosphatase, copper and ceruloplasmin in the serum were measured to evaluation the disease activity. All the patients received polychemotherapy (PCT). Irradiation of the liver in the total focal dose 36-44 Gy was performed in confirmed involvement of the liver as adjuvant to PCT. RESULTS: Specific liver lesions were detected in 6.1% of patients at primary examination and in 15.6%--at follow-up. Liver lesions occurred most frequently in mixed-cell variant of LGM and lymphoid depletion. Eradication of liver lesion after PCT was achieved in 15.4%. Subsequent radiation produced a complete remission in 100% of patients with diffuse and 80% of patients with large-focal liver lesion. In detection of liver involvement at the time of LGM progression eradication and remission were achieved in 70 and 50% of patients, respectively. From 30% of patients with liver lesions resistant to PCT and radiation, 15% had stable disease. The survival did not depend on eradication of liver lesion. CONCLUSION: In involvement of the liver its radiation is indicated for all the patients with new-onset LGM. In the recurrence, liver radiation is recommended for those in whom the liver is the only extranodal lesion.

High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) and autologous transplantation for patients with Hodgkin's disease who fail to enter a complete remission after combination chemotherapy.

Patients with Hodgkin's disease (HD) who fail to enter a complete remission after an initial course of combination chemotherapy are usually considered to have an induction failure (IF); this subset of patients has an extremely poor outcome with further conventional therapy. Since 1985, we have entered 30 IF patients into protocols using conditioning with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) followed by autologous stem cell transplantation (ASCT) with bone marrow (19 patients), peripheral blood stem cells (PBSCs; 8 patients), or both (3 patients). All except 2 patients had previously received chemotherapy regimens for HD that contained at least 7 drugs, and 9 had received prior radiotherapy (RT). After documentation of IF, the majority of patients received some cytoreductive therapy as specified by protocol (local RT in 9, two cycles of conventional chemotherapy in 2, both modalities in 2, or high-dose cyclophosphamide to enhance PBSC collection in 11) before CBV +/- P. Five treatment-related deaths occurred, all before day 150 posttransplant. Eleven patients have had progressive HD at a median of 6 months (range, 0.1 to 45 months) after ASCT. The actuarial progression-free survival (PFS) at a median follow-up of 3.6 years (range, 0.2 to 8.2 years) is 42% (95% confidence intervals, 21% to 61%). The statistical analysis identified only prior clinical bleomycin lung toxicity as an adverse risk factor for PFS, mainly because of the increased nonrelapse mortality seen in these patients. CBV +/- P and ASCT can produce durable remission in a substantial proportion of IF HD patients who otherwise have a poor survival, and we believed ASCT approaches represent the best therapy currently available for these patients. Additional measures are needed to reduce the primary problem of disease progression despite high-dose chemotherapy and stem cell transplantation.

Pediatric radiotherapy.

The perils of radiotherapy in pediatric oncology are well advertised and, justifiably, alternative treatment strategies have been sought. However, radiotherapy can be a highly effective antitumor agent and results with alternative therapies, in terms of survival and quality of life, need to be carefully scrutinized. In addition, biologic and technical innovations in radiotherapy are increasing its versatility and providing means of more adequately protecting adjacent normal tissues.

El papel de la radioterapia en las etapas tempranas de la enfermedad de Hodgkin / The role of radiotherapy in the early stages of Hodgkin's disease

Con el fin de evaluar el papel de la radioterapia, usada como primer intento curativo en pacientes con enfermedad de Hodgkin en estadio temprano, se efectuó un análisis retrospectivo de 86 pacientes en los cuales se usó radioterapia ganglionar total (RGT) como enfoque terapéutico primario. El grupo tiene un seguimiento de 13.1 años como mediana y la duración de la supervivencia fue el punto más importante en el presente análisis. El 60 porciento de los pacientes con estadio IA permanecen en primera remisión, mientras que sólo el 39 porciento de los casos en estadio IIA están en dicha condición (p<.01). La mediana de la supervivencia a 10 años también fue significativamente diferente: 78 porciento para los pacientes en estadio IA comparado con el 55 porciento para los casos en estadio IIA (p<.01). En el análisis de los factores pronósticos se encontró que la presencia de estadio IIA y enfermedad voluminosa (adenomegalia > 7 cm) fueron asociados a un mal pronóstico. Se puede considerar que la RGT sólo puede considerarse como curativa en los pacientes en estadio IA de la enfermedad de Hodgkin, pero siempre y cuando no tengan enfermedad voluminosa.

Autologous peripheral blood stem cell transplantation after high dose therapy in patients with advanced lymphomas.

Thirty-eight patients with refractory or relapsed non-Hodgkin's lymphoma (19 patients) or Hodgkin's disease (19 patients) were treated with salvage therapy. The peripheral stem cell collection was performed during hematologic recovery after myeloablative chemotherapy. In eight patients with Hodgkin's disease the number of CFU-GM collected was less than 0.5 x 10(4)/kg and these patients were excluded for stem cell transplantation. In the remaining 30 patients, a median of 4 x 10(4) CFU-GM/kg was collected (range 0.8-100 x 10(4)/kg) by three leukaphereses in 25 patients and six to 11 leukaphereses in five patients. Conditioning regimens were CBV (eight), BEAM (six), BEAC (10) and cyclophosphamide + total body irradiation (TBI) (six). Without TBI, the mean time for reaching a granulocyte count greater than 0.5 x 10(9)/l was 18 days and for a platelet count greater than 50 x 10(9)/l was 19 days in 23 out of 24 patients. With TBI, in five patients the mean time for reaching a granulocyte count greater tahn 0.5 x 10(9)/l was 37 days and for a platelet count greater than 50 x 10(9)/l was greater than 100 days. Complications were minor. There was only one toxic death. The outcome in these patients was similar to that observed in patients who received autologous bone marrow transplantation for advanced lymphomas. In conclusion, we observed good hematologic recovery except when TBI was used in the conditioning regimen.

Local hyperthermia and radiation therapy in the retreatment of superficially located recurrences in Hodgkin's disease.

Five patients with Hodgkin's disease, nodular sclerosing subtype, who had multiple failures after chemotherapy and radiation therapy were treated for palliation with low-dose radiation therapy and hyperthermia to seven superficially located sites of recurrence. Six of the seven areas were in previously irradiated fields and one was at the margin of the prior radiation therapy field. Local control was obtained for all lesions and was maintained for the duration of the patients survival (5 to 27 months). Four of the five patients expired with no relapse in the area of treatment. One patient remains alive and free of recurrence in his treatment fields. Temperatures were monitored using thermistors, fluoroptic systems or thermocouples manually mapped through closed-end catheters inserted into the tumor and thermal parameters and temperature distributions were calculated. Excellent heating was obtained with 46.4% of monitored intratumoral temperatures greater than or equal to 43 degrees C. The average of the monitored intratumoral temperatures for all treatments (Tave) was 43.2 degrees C; the average of the monitored intratumoral minimal temperatures for all treatments (T min) was 40.1 degrees C, and the average of all monitored intratumoral maximum temperatures (T max) was 46.7 degrees C. In comparison with temperatures obtained in 277 superficially located tumors of other histologies, Tmax was significantly higher in Hodgkin's disease lesions (p = 0.007). The difference in Tave approached significance (p = 0.058). These initial results support the role of radiation therapy and hyperthermia for palliation of isolated superficial recurrences in patients with Hodgkin's disease who have failed conventional therapies. In addition, this approach may aid in cytoreduction prior to bone marrow transplant in patients with superficially located bulky recurrent disease. Hyperthermia may also be considered in combination with chemotherapeutic agents for palliative treatment of recurrences.