Mantle Irradiation Research Articles

High incidence of late effects found in Hodgkin's lymphoma survivors, following recall for breast cancer screening

Assessment of late effects in a cohort of female Hodgkin's lymphoma patients treated with mantle radiotherapy, identified from the DoH breast cancer screening recall showed high mortality and frequent undiagnosed abnormalities in tissues affected by radiotherapy. With increasing age, this patient group may suffer premature cardiac and respiratory morbidity.

Long-Term Outcome after LACE (Lomustine, Ara-C, Cyclophosphamide, Etoposide) Conditioned Autologous Stem Cell Transplantation for Relapsed or Refractory Hodgkin's Lymphoma: A Single Centre Experience.

Introduction: The majority of patients with Hodgkin's lymphoma are cured with initial therapy. However, in patients with primary refractory or relapsed disease, high-dose therapy followed by autologous stem cell transplantation has been shown to be the best option. We analysed patients (pts) who underwent autologous stem cell transplantation (ASCT) following LACE (Lomustine 200 mg/m2, Ara-C 4 g/m2, Cyclophosphamide 4.8 g/m2, Etoposide 1 g/m2) conditioning for relapsed or refractory Hodgkin's lymphoma at the Hammersmith Hospital, London, between 1991 and 2004.Patients and methods: 67 pts (46 m, 21 f) initially diagnosed with Hodgkin's lymphoma (stage I; n=2, stage II; n=29, stage III; n=22 and stage IV; n=14) received first-line chemotherapy with ABVD or COP/ABVD (n=20), BEMOP-CA (n=29), COPP or similar (n=14) or mantle radiotherapy alone (n=4). High dose chemotherapy (HDC) with LACE and ASCT was undertaken in 45 of these pts in 1st relapse, 15 pts in 2nd or subsequent relapse and 7 pts with refractory disease. Median age at the time of HDC was 32 y (17 – 70 y). Prior to ASCT further chemotherapy achieved a complete or partial remission in 41 pts (chemosensitive), but 26 pts had no significant response (chemoresistant). Stem cells were mobilised with Etoposide (1.8 g/m2) and G-CSF in 56 pts, and bone marrow harvest was performed in the other 11 pts.Results: Two pts suffered a treatment-related mortality (TRM) within the first 100 days (3%). Two pts (3%) developed secondary malignancy (acute myeloid leukaemia). With a median follow-up of 43.3 months (range 0.5 – 145.5 months) the cumulative probabilities of overall survival (OS) and progression free survival (PFS) at both 5 and 10 years was 70% and 62% respectively. Pts who had chemosensitive disease at the time of ASCT had a better OS (p=0.008) and PFS (p=0.08) when compared with pts who had chemoresistant disease. Median PFS has not yet been reached for chemosensitive pts but was 23.4 months for chemoresistant pts. Median OS has not yet been reached for either group.Conclusions: The outcome for patients with relapsed or refractory Hodgkin's lymphoma following high dose chemotherapy and ASCT has been sufficiently encouraging to suggest that ASCT should be considered early in chemosensitive patients. However, new therapeutic strategies are needed to improve the clinical outcome of patients with chemoresistant disease.

Creating the Basis for a Breast Health Program for Female Survivors of Hodgkin Disease Using a Participatory Research Approach

To learn from female survivors of Hodgkin disease about their perceptions of their current health status and future health risks, self-care practices to prevent or diminish health risks, and what kind of breast health program could benefit them, including the most effective methods and optimal times for learning about breast health. Participatory research using focus groups. Urban pediatric cancer center. 1 African American and 19 Caucasian female survivors of Hodgkin disease aged 16-26 years, diagnosed at least two years before the start of the study, and treated with mantle radiation therapy. Participants were recruited during visits to an outpatient clinic. Six open-ended questions were asked during three separate focus group sessions. Transcribed data were evaluated by content analysis techniques and analyzed to identify common themes. Current health status and perceived health risks, current health practices, and effective methods and timing for breast health teaching. Survivors reported feeling damaged by their cancer and its treatment and perceived that they were at risk for breast cancer. Self-care and risky behaviors also were reported. Internal influences (e.g., fear) and external influences (e.g., family) motivated survivors to participate in health promotion activities. Effective methods identified for learning about breast health included having access to other survivors, being respected as an adult, and having one-on-one staff teaching and peer support. The preferred timing of teaching varied, but survivors generally supported a gradual provision of information. A positive listening environment is important for developing a breast health program for survivors. An essential first step is to create an opportunity for survivors to tell about their experiences with cancer, including its impact on their lives. Information regarding breast health must be provided in multiple formats during and after treatment if good practices are to be undertaken. The provision of adequate information during and after therapy as well as peer counseling in a positive listening environment are important in helping survivors participate in health promotion activities.

Screening for breast cancer in women with previous mantle radiotherapy for Hodgkin's disease

There is an established increased risk of secondary malignancy following radiation therapy for cancer in childhood or as a young adult. Breast cancer poses a particular problem as the population risk is significant and screening methods are available raising the question of possible screening interventions for women who are at high lifetime risk.

Long-Term Results of a Prospective Trial of Mantle Irradiation (RT) Alone for Early-Stage Hodgkin’s Disease (HD)

Long-Term Results of a Prospective Trial of Mantle Irradiation (RT) Alone for Early-Stage Hodgkin’s Disease (HD)

Stroke As a Late Treatment Effect of Hodgkin's Disease: A Report From the Childhood Cancer Survivor Study

The objectives of this report are to examine the incidence of and risk factors for stroke among childhood Hodgkin's disease (HD) survivors. The Childhood Cancer Survivor Study is a multi-institutional cohort study of more than 5-year cancer survivors diagnosed between 1970 and 1986 and a sibling comparison group. Incidence rates of stroke among HD survivors (n = 1,926) and siblings (n = 3,846) were calculated and compared. Cox proportional hazards models were used to estimate the hazard ratios, reported as relative risks (RR), of developing stroke between HD survivors and siblings. Nine siblings reported a stroke, for an incidence of 8.00 per 100,000 person-years (95% CI, 3.85 to 14.43 per 100,000 person-years). Twenty-four HD survivors reported a stroke. The incidence of late-occurring stroke among HD survivors was 83.6 per 100,000 person-years (95% CI, 54.5 to 121.7 per 100,000 person-years). The RR of stroke among HD survivors was 4.32 (95% CI, 2.01 to 9.29; P = .0002). All 24 survivors received mantle radiation exposure (median dose, 40 Gy). The incidence of late-occurring stroke among HD survivors treated with mantle radiation was 109.8 per 100,000 person-years (95% CI, 70.8 to 161.1 per 100,000 person-years). The RR of late-occurring stroke among HD survivors treated with mantle radiation was 5.62 (95% CI, 2.59 to 12.25; P < .0001). Survivors of childhood HD are at increased risk of stroke. Mantle radiation exposure is strongly associated with subsequent stroke. Potential mechanisms may include carotid artery disease or cardiac valvular disease.

A new option for early breast cancer patients previously irradiated for Hodgkin's disease: intraoperative radiotherapy with electrons (ELIOT)

IntroductionPatients who have undergone mantle radiotherapy for Hodgkin's disease (HD) are at increased risk of developing breast cancer. In such patients, breast conserving surgery (BCS) followed by breast irradiation is generally considered contraindicated owing to the high cumulative radiation dose. Mastectomy is therefore recommended as the first option treatment in these women.MethodsSix patients affected by early breast cancer previously treated with mantle radiation for HD underwent BCS associated with full-dose intraoperative radiotherapy with electrons (ELIOT).ResultsA total dose of 21 Gy (prescribed at 90% isodose) in five cases and 17 Gy (at 100% isodose) in one case were delivered directly to the mammary gland without acute complications and with good cosmetic results. After an average of 30.8 months of follow up, no late sequelae were observed and the patients are free of disease.ConclusionIn patients previously irradiated for HD, ELIOT can avoid repeat irradiation of the whole breast, permit BCS and decrease the number of avoidable mastectomies.

Intra‐abdominal desmoid tumor after successful treatment for Hodgkin disease

The risk of second malignancies after successful treatment for Hodgkin disease can be considerable. The most common malignancies are solid tumors arising in irradiated sites, such as the breast and thyroid gland after mantle field radiation. Sarcomas and other musculoskeletal tumors are also seen. We describe a young woman who developed an intra-abdominal desmoid tumor more than 4 years after completing therapy for Stage IIB Hodgkin disease, treated with combination chemotherapy (ABVD) and mantle irradiation. The tumor did not occur at either a surgical site or within a radiation field. She did not carry a mutation for familial adenomatosis polypoli.

Use of Conventional Radiation Therapy As Part of Breast-Conserving Treatment

Whole breast irradiation following breastconserving surgery is an integral part of breast-conserving therapy (BCT). Radiation therapy was introduced early in the development of breast-conserving surgery and techniques were based on the premise that limited surgery might leave microscopic residual disease in the breast. Early studies of mastectomy specimens demonstrated that microscopic disease could extend up to 2 to 4 cm beyond the primary site of the tumor within the breast tissue. Trials comparing mastectomy to BCT (breast-conserving surgery plus radiation) demonstrated equivalent survival confirming the effectiveness of this combined approach. Trials comparing breast-conserving surgery alone to breast-conserving surgery plus radiation confirmed a substantial decrease in the risk of local recurrence and the prevention of mastectomy with breast irradiation. Whole breast irradiation is normally delivered with two opposed tangential fields to encompass the breast, often including part of the underlying chest wall and the lower axilla. Beam modifying devices, usually lead wedges, are used to improve dose homogeneity. A dose of 45 to 50 Gy in 25 fractions (or daily doses) of 1.8 to 2 Gy, Monday to Friday for 5 weeks, is often used. Additional radiation limited to the site of the primary tumor, called boost irradiation, may be given using a variety of approaches to a dose of 10 to 16 Gy in five to eight fractions. This technique has been in existence since the early 1980s, with little changes until recently. Increasingly, centers now use computed tomography (CT) to plan radiation therapy which permits clearer definition of underlying lung and heart and avoidance of these critical structures. CT planning also permits for the correction of underlying lung density and optimization of compensation if necessary. Patient selection criteria for whole breast irradiation are based on the eligibility criteria of the original trials and include any patient with a primary tumor of less than 5 cm with clear margins of the excision following breast-conserving surgery. Absolute contraindications to breast irradiation include pregnancy and previous breast irradiation (including mantle irradiation for Hodgkin’s disease). Relative contraindications include scleroderma, systemic lupus erythematosis, severe cardiopulmonary disease, or the inability to lie supine, which would limit the ability to deliver radiotherapy. Breast irradiation is well tolerated. Common early toxicity includes fatigue, breast edema, and skin erythema and irritation, which can have a modest impact on quality of life. Mild to moderate longterm effects are relatively uncommon: 5% to 10% of patients may experience limited breast pain attributed to radiation therapy or adverse cosmetic outcome associated with breast fibrosis, scar retraction, and telangiectasia. Serious long-term adverse effects are relatively rare (less than 1%) and include radiation pneumonitis, VOLUME 23 d NUMBER 8 d MARCH 1

A randomized phase II trial of amifostine for head and neck irradiation in lymphoma

Acute and long-term oral complications occur in patients receiving mantle radiation therapy or irradiation to the head and neck region for Hodgkin's disease or non-Hodgkin's lymphoma. While considerable data are available on the effect of radiation therapy on the oral function and quality of life of patients with squamous cell carcinoma of the head and neck, such information is lacking for similarly irradiated lymphoma patients. In this article we discuss the rationale and study design of an ongoing, randomized phase II study evaluating the role of amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD) as a radiation protectant in patients receiving head and neck irradiation for lymphoma. Further investigation in this lymphoma population is needed to improve our understanding of the extent of the problem and its impact on patients' daily living and functioning. Importantly, fine-tuning the treatment and management approaches to minimize morbidity while maximizing the survival and quality of life of patients are crucial next steps.

Osteosarcoma de mama posradioterapia

We present the case of a 69 years old woman who underwent chemotherapy and mantle radiotherapy for non Hodgkin lymphoma. Fifteen years later, she underwent mastectomy for breast mass that was diagnosed as an osteosarcoma at final pathological examination. Radical surgery was the only treatment she received. Postirradiation breast sarcoma are rare and have poorer prognosis than primary breast sarcomas. Surgery is the main treatment. The use of adjuvant treatment is controversial, but there are some data that support the use of chemotherapy in these sarcomas.

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.

888 poster Thyroid dose, received after Mantle irradiation for Hodgkin's disease

888 poster Thyroid dose, received after Mantle irradiation for Hodgkin's disease

Second malignancies after pediatric Hodgkin lymphoma: Associations with radiation dose and volume

Second malignancies after pediatric Hodgkin lymphoma: Associations with radiation dose and volume

Differential attenuation of clavicle growth after asymmetric mantle radiotherapy

Purpose To determine the effects of 15 Gy on bone growth as a function of time and age by comparing clavicle length before and after asymmetric mantle irradiation in pediatric patients. Methods and materials We measured the lengths of both clavicles from radiographs made before and after radiotherapy (median follow-up, 39.6 months), in 15 children (median age, 13.3 years) with early-stage Hodgkin's disease treated with combined modality therapy. The intercepts and slopes of regression lines for individual patients were used to form an estimating regression curve for the population. Results The irradiated volume, patient age, and time elapsed after treatment influenced the measured growth. Fully irradiated clavicles grew 1.3 ± 0.3 cm, significantly less (0.5 cm; p = 0.007) than did the partially irradiated clavicles. The difference between partially and fully irradiated clavicle lengths was statistically significant, regardless of age. Also, the growth rate of partially and fully irradiated clavicles was significantly different between younger (mean age, 9.9 years) and older (mean age, 16.4 years) patients ( p = 0.036). Conclusion Clavicle growth is vulnerable to radiation doses as low as 15 Gy, and patient age at the time of irradiation influences the growth rate.

Risk of breast cancer following mantle radiotherapy for Hodgkin's disease

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Autoimmune Diabetes mellitus, Hodgkin’s Disease and Graves’ Ophthalmopathy in a Patient with 8.1 Ancestral Haplotype

In this report, we describe the case of a 43-year-old woman affected by type 1 diabetes mellitus diagnosed 8 years before, who developed Graves' disease 2 years after chemotherapy and mantle radiotherapy treatment for Hodgkin's disease. Bilateral Graves' ophthalmopathy appeared four months before our observations. Intravenous methyl-prednisolone therapy was started, but was interrupted due to severe metabolic failure. Autoantibodies (anti-islet cells, anti-thyroid, thyroid-stimulating, non-organ-specific) were positive. Since the clinical picture suggested a genetic immunological ground predisposing to autoimmunity, we evaluated her HLA haplotype. Genomic typing of the patient permitted identification of the 8.1 ancestral haplotype, a Caucasoid haplotype unique in its association with many immunopathological diseases. Moreover, we also observed a haplotype unusual in Caucasians, trans DRB1*1101, DQA1*0103, DQB1*0603. To our knowledge, HLA-related genetic risk of developing thyroid autoimmunity after neck irradiation has never been studied. Although we cannot confirm a direct association between the 8.1 ancestral haplotype or DRB1*1101, DQA1*0103, DQB1*0603 and the diseases described, we suggest considering immunological parameters and HLA typing in candidate patients for mantle radiation therapy for Hodgkin's disease or other tumors. HLA haplotype determination could be useful in identifying the patients at raised risk of developing autoimmune diseases after irradiation, thus permitting a more appropriate follow-up schedule.

The cancer screening practices of adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

The current study characterized the self-reported cancer screening practices of adult survivors of childhood cancer. A cohort of 9434 long-term survivors of childhood cancer and a comparison group of 2667 siblings completed a 289-item survey that included items regarding cancer-screening practices. Overall, 27.3% of female respondents reported performing breast self-examination (BSE) regularly, 78.2% reported undergoing a Papanicolaou smear within the previous 3 years, 62.4% underwent a clinical breast examination (CBE) within the last year, and 20.9% had gotten a mammogram at least once in their lifetime. Approximately 17.4% of male respondents reported performing regular testicular self-examination (TSE). Women age > or =30 years who had been exposed to chest or mantle radiation therapy were more likely to report undergoing CBE (odds ratio [OR], 1.59; 95% confidence interval [95% CI], 1.32-1.92) and mammography (OR, 1.92; 95% CI, 1.47-2.56). Compared with the sibling comparison group, survivors demonstrated an increased likelihood of performing TSE (OR, 1.52; 95% CI, 1.22-1.85) or BSE (OR, 1.30; 95% CI, 1.10-1.52), of having undergone a CBE within the last year (OR, 1.18; 95% CI, 1.02-1.35), and of ever having undergone a mammogram (OR, 1.82; 95% CI, 1.52-2.17). The results of the current study demonstrate that the cancer screening practices among survivors of childhood cancer are below optimal levels. Primary care physicians who include childhood cancer survivors among their patients could benefit these individuals by informing them about future cancer risks and recommending appropriate evidence-based screening.

Time interval to the development of breast carcinoma after treatment for Hodgkin disease.

Women with Hodgkin disease (HD) who received mantle irradiation had an increased risk of developing breast carcinoma. The authors examined the influence of radiotherapy on the time interval to the development of breast carcinoma. Using population, cancer incidence, and survival data from the Surveillance, Epidemiology, and End Results (SEER) registries, standardized incidence ratios (SIR) were calculated and Kaplan-Meier curves were constructed to estimate breast carcinoma-free survival in women with HD treated with and without radiotherapy. The log-rank test was utilized and multivariate proportional hazard regression analysis was performed. Multivariate analysis was also performed using the PHPH regression model. In 9 SEER registries, 8036 females were identified who were diagnosed with HD between 1973 and 1999. Of these women, 183 (2.3%) were subsequently diagnosed with breast carcinoma. The use of radiotherapy in the treatment of HD resulted in an increased risk of development of breast carcinoma (SIR = 1.90, P < 0.01). The log-rank test and proportional hazard regression model failed to detect a difference (P = 0.79) in breast carcinoma-free survival for women treated with and without radiotherapy. The PHPH regression model revealed that the use of radiotherapy had an adverse effect on long-term survival (relative risk [RR] = 1.84, P = 0.01), but was associated with a short-term survival advantage (RR = 0.45, P = 0.01). Use of the PHPH model indicated that the use of radiotherapy in the treatment of HD resulted in an increased long-term risk for the subsequent development of breast carcinoma, but conferred a short-term reduction.

Intraoperative Radiotherapy during Breast Conserving Surgery in Patients Previously Treated with Radiotherapy for Hodgkin's Disease

Women who have received radiotherapy for Hodgkin's disease have an increased risk of developing breast cancer. Breast-conserving surgery followed by breast irradiation is generally considered to be contraindicated in such patients owing to the high cumulative radiation dose to the breast. Mastectomy is therefore recommended as the preferred treatment option in these women. We report 3 patients affected by breast cancer who had previously been treated with mantle radiation for Hodgkin's disease and on whom breast-conserving surgery and full-dose intraoperative radiotherapy with electrons (ELIOT) were performed. A total dose of 17 Gy (prescribed at 100% isodose) in one case and 21 Gy (at the 90% isodose) in two cases was delivered directly to the mammary gland without acute complications and with good cosmetic results. In women previously irradiated for Hodgkin's disease, ELIOT could avoid repeat irradiation of the whole breast, thereby permitting conservative surgical treatment.