Mantle Irradiation Research Articles

Radiation-induced premature menopause: A misconception

To disprove the common view that women who have undergone irradiation to fields excluding the pelvis are at risk for radiation-induced premature menopause, we reviewed menstrual function and fertility among women treated with subtotal lymphoid irradiation for Hodgkin's Disease. Treatment and follow-up records of all women less than age 50 at the time of diagnosis of Stage I or II supradiaphragmatic Hodgkin's Disease, treated with subtotal lymphoid irradiation alone and enrolled in radiotherapy trials from 1967 to 1985, were reviewed. In addition, patients were surveyed regarding their menstrual status and fertility history. Thirty-six women, aged 10 to 40 years, with normal menstrual function at the time of Hodgkin's diagnosis, were identified. Mean follow-up was 14 years, with a range of 1.25-22.75 years. The average radiation dose to mantle and paraaortic fields was 40-44 Gy; the calculated scatter radiation dose to the pelvis at the ovaries was 3.2 Gy. There were 38 pregnancies in 18 women; all offspring are normal. One of 36 women (2.7%) experienced premature menopause. The reported rate of premature menopause in women who have not undergone irradiation is 1-3%; not significantly different than the rate in our study. There is a syndrome whereby antibodies to several endocrine organs occur (including the ovary), which is associated with premature ovarian failure. This syndrome may be associated with prior radiation to the thyroid, such as that given by mantle irradiation for Hodgkin's Disease. We report such a case. There is little risk of premature menopause in women treated with radiation fields that exclude the pelvis. Women with presumed radiation-induced premature menopause warrant an evaluation to exclude other causes of ovarian failure, such as autoimmune disorders.

Serial pulmonary function studies in children treated for newly diagnosed Hodgkin's disease with mantle radiotherapy plus cycles of cyclophosphamide, vincristine, and procarbazine alternating with cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine.

The pulmonary toxicity of bleomycin-containing chemotherapy combined with mantle radiotherapy in children treated for Hodgkin's disease was longitudinally assessed. The results of serial pulmonary function studies in 37 children, newly diagnosed and treated at St. Jude Children's Research Hospital between September 23, 1983, and June 30, 1988, with cyclophosphamide, vincristine, and procarbazine (COP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus low dose mantle radiotherapy are analyzed. All patients had pulmonary function studies at least before the first bleomycin dose, after completion of radiotherapy, and serially upon discontinuation of therapy. Bleomycin therapy was withheld whenever measured carbon monoxide diffusing capacity was less than 50% of the predicted value. Vital capacity, diffusing capacity, and diffusing capacity per unit of alveolar volume declined during the first 6 months of therapy but improved there after. At 2 years postdiagnosis, diffusing capacity per unit of alveolar volume remained significantly reduced. Only one patient was symptomatic at the 2-year point. The survival rate of these patients was 95% at a median follow up of 93 months. If bleomycin is with held when diffusing capacity is diminished to 50% predicted, clinical compromise of pulmonary function appears to be minimal in pediatric patients receiving alternating cycles of COP/ ABVD in combination with low-dose mantle radiotherapy. Survival was excellent, even with reduction of the total bleomycin dose.

Mantle irradiation alone for selected patients with laparotomy-staged IA to IIA Hodgkin's disease: preliminary results of a prospective trial.

To determine the feasibility of omitting prophylactic paraaortic irradiation in selected patients with laparotomy-staged (pathologically staged [PS]) IA to IIA Hodgkin's disease. We initiated a prospective single-arm trial in October 1988 to study the role of mantle irradiation alone in selected PS IA to IIA patients with Hodgkin's disease. A total of 37 patients have been entered onto this trial. Entrance criteria included nodular sclerosis (NS) or lymphocyte predominance (LP) histology, absence of B symptoms, disease limited above the carina, and a negative laparotomy. Results of treatment of 23 patients in the prospective trial, monitored off treatment for > or = 1 year, are presented. Twenty-three additional PS IA to IIA patients, treated with mantle irradiation alone from 1970 to 1987, were analyzed as a comparison group. The median follow-up durations were 32 and 113 months, respectively, for the two groups. The 4-year actuarial rates of freedom from relapse and overall survival are 83% and 100%, respectively, for the prospective trial. The 10-year actuarial rates of freedom from relapse and overall survival are 83% and 89%, respectively, for retrospectively studied patients. There have been five recurrences among 46 patients who received mantle irradiation alone, all with a component of relapse below the diaphragm. These early results support the use of mantle irradiation alone in selected PS IA to IIA patients with NS or LP histology. Relapses, although rare, have occurred predominantly below the diaphragm. This suggests the need for continued long-term surveillance of abdominal and pelvic nodes in this group of treated patients.

Treatment of early and intermediate stages of supradiaphragmatic Hodgkin's disease: The Swedish National Care Programme Experience

Since 1985 a Swedish National Care Programme has provided tailored principles for the staging, treatment and follow-up of patients with Hodgkin's disease (HD). This report presents treatment results for all patients below 60 years of age who were diagnosed with early and intermediate stages, between 1985 and 1989. During that period, 210 patients with supradiaphragmatic HD in clinical (CS) and pathological (PS) stages IA+IIA, PS IB+IIB, and PS III1 A were diagnosed in five Health Care Regions in Sweden. In patients with CS IA, staging laparotomy was not recommended provided that the radiological assessment of the abdomen was adequate, whereas this procedure was recommended in stages CS IB, IIA and IIB in order to minimize treatment. In the absence of bulky mediastinal disease, patients with CS+PS IA and PS IIA were treated with mantle (occasionally mini-mantle) irradiation alone, while patients with bulky disease, as well as those with stages PS IB+IIB+III1 A, were treated with one cycle of MOPP/ABVD prior to mantle (PS III1 A sub-total nodal) irradiation. Full chemotherapy followed by radiotherapy to initial sites with bulky disease was recommended for patients with CS IIA who did not undergo laparotomy. After a median follow-up in excess of five years, treatment results are 'favourable' for all stages, provided the recommendations were followed. In patients with CS+PS IA treated according to the recommendations, recurrence rates were 14% (9/65) with all but one patient (64/65, 98%) remaining in continuous first or second remission. These figures were worse in patients treated inadequately (9/26 [35%] and 22/26 [85%], respectively). In PS IIA, adequately-treated patients had a recurrence rate of 13% (7/52) whereas 5/7 (71%) of those with bulky disease who received only mantle irradiation developed recurrences. Similar patterns also emerged in patients with CS IIA, PS IB+IIB and PS III1 A. The tailored principles, which usually entail less staging and/or treatment than is generally the case, produced favourable results when applied to an entirely unselected group of patients with early and intermediate stages of HD.

Acute parotitis during mantle irradiation: Incidence, onset, duration, and treatment

AbstractDetailed information, including the incidence, onset, and duration of symptoms, as well as the management of irradiation‐related sialadenitis, is not well defined in the literature. Between June 1967 and October 1993 126 patients received mantle irradiation in the treatment of Hodgkin's disease at the Fox Chase Cancer Center. All patients were treated with continuous course, once daily external beam radiotherapy (RT) using megavoltage equipment. The mantle fields extended from the level of the external acoustic meatus to the level of the insertion of the diaphragm. Seven of 126 patients (5.5%) treated with mantle irradiation developed clinical signs of parotitis during their RT treatments. Each patient described a painful sensation over the parotid gland. Palpable swelling over the parotid gland was appreciated in three patients. No systemic symptoms developed in any patient. All patients developed symptoms within the first week of treatment. Six patients were treated with aspirin and in each case the symptoms resolved within 48 hr. One patient did not receive medication and his symptoms persisted for 5 days. © 1995 Wiley‐Liss, Inc.

Conservative surgery and radiation for early-stage breast cancer.

In selected patients with early-stage breast cancer, conservative surgery and radiation represent an alternative equal to mastectomy in terms of local recurrence, distant metastasis, survival, and long-term complications. Patients with early-stage breast cancer who are candidates for conservative surgery and radiation include those whose primary tumor is less than 4 to 5 cm in size without evidence of gross multicentricity or diffuse microcalcifications. Patients with an extensive intraductal component may be appropriate candidates provided that margins of resection are negative. Young age is not a contraindication to the conservative treatment. A preexisting history of collagen vascular disease or prior mantle irradiation for Hodgkin's or non-Hodgkin's lymphoma represents a contraindication to conservative surgery and radiation because of the potential for severe complications. An additional contraindication is the pregnant woman in whom delivery cannot be accomplished before the initiation of radiation. Mammography is essential in the pretreatment evaluation and posttreatment follow-up of the conservatively treated patient. The goal of the pretreatment mammogram is to assess the extent of disease in the ipsilateral breast as well as to evaluate the contralateral breast. In patients who present with microcalcifications, a postbiopsy mammogram before radiation is essential to document complete removal of all malignant-appearing microcalcifications. Mammography is an essential part of the follow-up program in order to detect a recurrence in the treated breast as well as a cancer in the contralateral breast cancer. The optimal interval for follow-up mammography has not been determined, although programs employing mammography on a yearly basis after treatment have been associated with the detection of early recurrences and excellent survival after salvage mastectomy for these recurrences.

The management of Hodgkin's disease

A 27-year-old female school teacher originally presented in March 1987 with a six month history of painless left cervical lymphadenopathy. She had no systemic symptoms and there were no other signs of disease on clinical examination but a chest radiograph showed non-bulky mediastinal adenopathy. An abdominal CT scan was normal. Biopsy confirmed nodular sclerosing Hodgkin’s disease (HD) and a staging laparotomy with splenectomy was performed. None of the lymph nodes or the spleen or the liver contained HD and it was concluded that the disease was confined to two sites above the diaphragm (pathological stage ILA). Mantle field radiotherapy was administered during April and May 1987 and a complete remission was obtained.

Hodgkin's disease with bulky mediastinal involvement: Effective management with combined modality therapy

Purpose : To assess results, complications, treatment techniques, and patterns of failure in patients with bulky mediastinal Hodgkin's disease treated with combined modality therapy. Methods and Materials : Between 1980 and 1988, 48 patients with Hodgkin's disease who had large mediastinal masses were treated at Stanford University. All patients were staged with clinical studies which included computed tomographic scans of the chest and bipedal lymphograms. Initially, 10 patients underwent staging laporotomy and splenectomy, subsequently all patients were staged by clinical criteria alone. Mediastinal mass ratios ranged .35 to .85 (mean .46). The majority of patients had at least one site of extralymphatic extension (E-lesion) within the chest. Combined modality therapy included MOPP (prednisone deleted after mediastinal irradiation) in 15, ABVD in 14, and PAVe in 19 patients. All patients received mantle irradiation (mean dose 44 Gy) but only patients with abdominal disease received subdiaphragmatic irradiation. Results : The actuarial survival and freedom from relapse were 84% and 88% at 9 years. There was an intrathoracic component of failure in all seven patients who either failed to achieve an initial complete response or who experienced a relapse after a complete response. Both patients who experienced a relapse after a complete response achieved durable second responses with subsequent chemotherapy. Two of five patients who failed to achieve an initial complete response were treated successfully with alternative chemotherapy. Conclusions : Routine combined modality therapy is the treatment of choice for patients with Hodgkin's disease who have large mediastinal masses.

Mantle irradiation alone for selected patients with pathologically staged (PS) Ia–IIa Hodgkin's disease: Preliminary results of a prospective trial

Mantle irradiation alone for selected patients with pathologically staged (PS) Ia–IIa Hodgkin's disease: Preliminary results of a prospective trial

Symptomatic coronary artery disease after mantle irradiation for Hodgkin's disease

Symptomatic coronary artery disease after mantle irradiation for Hodgkin's disease

Breast carcinoma in women previously treated for Hodgkin disease: mammographic evaluation.

Although the risk of second malignancies occurring after curative therapy for Hodgkin disease (HD) is well known, few cases of breast carcinoma developing in this setting have been reported. The authors performed a retrospective review of institutional records and identified 27 women with 29 breast carcinomas who had previously undergone treatment of HD and for whom mammograms were available. Two of the 29 carcinomas were synchronous, bilateral tumors. Although the patients' ages ranged from 33 to 75 years, most were young; 16 patients (55%) were younger than 45 years, and nine (31%) were younger than 40 years. Time from treatment for HD to development of breast cancer ranged from 8 to 34 years (mean, 18 years). All women developed ductal carcinoma. Mammography demonstrated 26 of the 29 cancers (90%); 11 of the 29 cancers (38%) were detected only with mammography. In 26 tumors for which clinical findings were known, the results of physical examination were positive in 18 (69%). Women previously treated for HD may be at increased risk of developing breast cancer, which may be bilateral and develop at a young age. This increased risk may be due to scattered radiation to the breast during mantle irradiation. Mammographic screening of these women is indicated. In women who were treated for HD at a young age, routine screening before the age of 35 years is recommended.

Long-term effects on pulmonary function of mantle radiotherapy in patients with Hodgkin's disease.

Twenty-five patients (21-45 years old) treated for Hodgkin's disease with mantle radiotherapy but no chemotherapy underwent chest radiography and pulmonary testing with spirometry, pulmonary mechanics and exercise test combined with arterial blood gas analysis, lung scintigraphy, assessment of pulmonary artery pressure with Doppler cardiography and vector ECG 10-20 years after treatment. The doses to mediastinum ranged from 35-43 (mean 40) Gy given in 26 fractions with the split-course technique. Radiographic signs of slight to moderate pulmonary fibrosis were seen in 18 patients. Minor restrictive ventilatory defects were found with decreased VC, TLC and lung compliance and increased maximal elastic recoil. Little evidence of airflow obstruction was found. Exercise capacity was decreased in three individuals but the mean value for the study group as a whole was normal. Arterial PO2 at maximum exercise was reduced but no patient had diminished hemoglobin saturation. Lung scintigraphy showed defects in 21 patients, mostly consisting of slight abnormalities at the lung periphery and apices. The perfusion seemed to be more affected than the ventilation, suggesting primary vascular lesions. Twelve patients showed signs of right ventricular hypertrophy in vector ECG and four of these had systolic pulmonary artery pressure greater than or equal to 30 mm Hg. The observed abnormalities were mostly of a minor degree and few clinically significant long-term effects of mantle radiotherapy on pulmonary function were observed.

Late cardiopulmonary toxicity after treatment for Hodgkin's disease.

Cardiac and pulmonary functions were evaluated in 75 patients aged 50 years or under, treated for Hodgkin's disease by mantle radiotherapy at least 3 years earlier; all received the same mantle field radiotherapy: radiotherapy alone, MOPP chemotherapy plus radiotherapy, MOPP and ABVD chemotherapy plus radiotherapy. No patient had any symptom of heart disease. Only borderline abnormalities of ECG or echocardiogram were observed in 12 patients. One of them showed a moderate aortic stenosis which was known before the treatment; apical or septum hypokinesia were present in four patients and one patient had a slightly right ventricular dilatation. Twelve (16%) chest radiographs showed moderate or severe abnormalities, but there was no significant correlation between the results of pulmonary function tests and Xenon ventilation/perfusion scintigraphy, the clinical examination and the intensity of the radiological sequelae. Twenty-nine (64%) Xenon scintigraphies showed a reduction of lung perfusion in the irradiated areas without any symptom. The resting mean pulmonary function test was significantly lower for the patients than for the control group with regard to Total Capacity and Vital Capacity. The exercise tolerance, as indicated by analysis of blood gases, was below the one expected for only two patients who were dyspneic during the low level of exercise. We did not find any significant difference between the three treatment groups. We conclude that the treatment with mantle field under good technical conditions (high energy photons, moderate doses...) can result in minimal cardiopulmonary dysfunction.

Management of stage II Hodgkin's disease: 15 years experience at St. Bartholomew's Hospital.

One hundred seventy-seven consecutive patients with newly diagnosed stage II Hodgkin's disease (HD) (supradragmatic 157; infra diaphragmatic 20) were treated at St. Bartholomew's Hospital on the basis of pathologic stage (PS) in 84 (IIA 69; IIB 15) and clinical stage (CS) in 93 (IIA 33, IIB 60) between January 1968 and December 1984. The median follow up is 13 years. Overall, complete remission (CR) was achieved in 143 patients (75%) of whom 53 have had a recurrence. One hundred twenty-seven patients remain alive, the cumulative predicted survival at 15 yrs being 70%. Mantle radiotherapy was prescribed to 88 patients with supradiaphragmatic HD, of whom 75 entered CR and 9 achieved good partial remission (GPR) (95%). The duration of remission correlated strongly with ESR (greater than 50 mm/h) and mediastinal thoracic ratio (less than 33% vs. greater than 33%) in a multivariate analysis (p = 0.05 and 0.02, respectively). 46/88 patients remain in continuous first remission, the median duration of remission having not reached at 15 years. Combined modality therapy or chemotherapy alone was prescribed to 69 patients with supradiaphragmatic HD, CR being achieved in 51 patients and GPR in 8 at the completion of all therapy. 48/59 patients continue in first remission. The duration of remission of patients receiving combined modality therapy or CT alone was significantly longer (p = 0.002) than that of patients receiving RT alone, in spite of the fact that the former group comprised predominantly of patients with unfavourable features.(ABSTRACT TRUNCATED AT 250 WORDS)

Variation in mantle technique: implications for establishing priorities for quality assurance in clinical trials

74 European and American radiotherapists responded to a questionnaire investigating the treatment of a patient with stage IIA non-bulky Hodgkin's disease by mantle irradiation. A consensus was present for the dose aims to involved and uninvolved lymph nodes and the acceptable incidence of late normal tissue effects. There was less agreement as to the total dose and dose per fraction required to maintain normal tissue toxicity within the agreed acceptable incidence. Variation was found in the radiation technique employed, the amount of spinal cord shielding used, the prescription point, modifications if irradiation was given after chemotherapy, and the routine recording of dose and dose per fraction to the normal tissue at risk. This descriptive survey confirms the need for well designed quality assurance programmes and indicates the areas of particular uncertainty that currently exist.

Lymphoid irradiation results in long-term increases in natural killer cells in patients treated for Hodgkin's disease

Therapeutic lymphoid irradiation has been shown to produce profound long-term alterations in lymphocyte subpopulations and immunologic responsiveness. Dual immunofluorescence flow cytometry and functional cytolytic assays were used to investigate the effects of lymphoid irradiation either alone or in combination with chemotherapy on T-cell and natural killer (NK) cell populations in the blood of patients treated for Hodgkin's disease. Patients treated with mantle and paraaortic lymphoid irradiation show significant increases in the proportion of cells bearing the NK cell phenotypic marker Leu-11 (CD16). These patients also display proportionately increased cytotoxicity against K562 tumor targets in vitro. A sizable number of these NK cells label dimly with Leu-2 (CD8) although they lack the pan-T-cell marker Leu-4 (CD3). The emergence after lymphoid irradiation of this population of Leu-11+2+ NK cells may lead to an apparent decrease in the ratio of helper to suppressor T-cells, although the actual ratio of these T-cell subsets generally is normal. These changes persist for years after the completion of radiation therapy. It was concluded that lymphoid irradiation may produce profound changes in NK cell populations in patients treated for Hodgkin's disease; the clinical significance of these changes is unclear.

Mantle irradiation in the upright position: A technique to reduce the volume of lung irradiated in patients with bulky mediastinal hodgkin's disease

Many patients with mediastinal Hodgkin's disease radiographically show a wider horizontal width of disease in the supine or prone as compared to the upright position. Yet for most patients mantle treatment in the supine/prone position is still preferable. This position allows good patient immobilization and precise matching between the mantle and paraaortic-splenic pedicle fields that would not be possible in the sitting or upright position. Adequate blocking of the lungs and heart remains possible in the supine position since most patients do not have extensive subcarinal Hodgkin's disease. Even when more extensive disease is present, contoured blocks to protect the heart and lungs can be adjusted to protect a greater portion of normal tissues if the mediastinal nodes respond to treatment. But if sizeable mediastinal disease persists, it may be impossible to protect sufficient heart and lung. Under these circumstances, repositioning the patient upright can shift the configuration of the mass, allowing larger lung blocks to be added. We report the use of a chair to facilitate treatment with mantle irradiation in the upright position for patients whose mediastinal disease when supine is too large to allow adequate blocking of heart and lung. Blocks are made from the initial port films and daily treatment films are taken to confirm an accurate set-up. To avoid excessive dose to the spinal cord, patients who are to receive para-aortic irradiation receive a maximum of 15–20 Gy in the upright position and the remainder of the mantle is given in the supine-prone position. The use of the upright technique allows for the use of radiation in patients who would otherwise be unable to receive adequate doses due to potential lung and cardiac toxicity.

Analysis of supradiaphragmatic clinical stage I and II Hodgkin's disease treated with radiation alone

Patients with clinical Stage I and II Hodgkin's disease have been managed at the Princess Margaret Hospital for over 20 years, without the use of routine staging laparotomy. Our experience identified as adverse prognostic factors presence of a large mediastinal mass, B symptoms, and advanced age in presence of unfavorable histology (20). We had suggested previously that the use of extended field radiation therapy (XRT) was associated with a lower risk of relapse than involved field XRT or mantle XRT. There has been a trend over the past decade to select those patients with favorable prognostic factors for treatment with XRT alone and to use mantle plus upper abdominal XRT (extended field XRT) to treat them. A retrospective study of patients with clinical Stage I and II Hodgkin's disease treated at the Princess Margaret Hospital between 1978 and 1986 was conducted to determine the impact of patient selection and extended field radiation on outcome. The study involved 250 patients with supradiaphragmatic disease selected for treatment with radiation alone on the absence of adverse prognostic factors. Radiation techniques included involved field radiation in selected patients (those with upper neck involvement), mantle radiation in the earlier years, and mantle plus upper abdominal radiation in the later years of the study. Actuarial survival was 83.3% at 8 years; cause-specific survival was 90.1% and the relapse-free rate 71.6%. Local tumor control was 94.6%; only two patients had true infield failure. Multivariate analysis showed that significant prognostic factors included age, histology, and erythrocyte sedimentation rate. Extent of the radiation treatment volume was significant and influenced the risk of relapse, particularly out-of-field relapse, independently of other factors. A dose of 35 Gy was found to be sufficient for control of clinical disease. This study validated a previously developed model for the selection of clinically staged patients with Stage I and 11 Hodgkin's disease for treatment with radiation alone. Careful selection of these patients can yield excellent results without requiring that staging laparotomy be routinely performed or the use of systemic chemotherapy as the initial treatment.

Enhanced normal tissue response to radiation in a patient with discoid lupus erythematosus

We report the case of a patient with discoid lupus erythematosus who developed a severe skin reaction whilst undergoing mantle irradiation for non-Hodgkin's lymphoma. Widespread moist desquamation occurred after a skin dose of only 17 Gy and was associated with an abscopal response outside the treatment area. The case illustrates the need for extreme caution when administering radiotherapy to patients with discoid or systemic lupus erythematosus.

Radiotherapy during pregnancy for clinical stages IA–IIA Hodgkin's disease

Between 1956 and 1990, 775 women were treated for Hodgkin's disease at The University of Texas M. D. Anderson Cancer Center. Of these, 25 (3.2%) were pregnant at diagnosis. Seven of these women were in the first trimester, 10 in the second, and eight in the third. Prior to treatment, three women in the third trimester had normal deliveries, and six patients in the first trimester had abortions. Sixteen patients received radiotherapy for supradiaphragmatic presentations during their pregnancies. All these patients had nodular sclerosing Hodgkin's disease: Two had clinical stage IA presentations and 14 had clinical stage IIA. In two patients radiotherapy (35 Gy) was limited to the neck, three patients were treated definitively to the neck and mediastinum (40 Gy), and 11 patients received mantle irradiation (40 Gy). Four to five half-value layers of lead were used to shield the uterus during radiotherapy. The dose to the fetus was estimated individually in nine patients, using a combination of an Anderson-Rando and a water phantom. The estimated total dose to the mid-fetus ranged from 1.4 to 5.5 cGy for treatment with 6 MV photons, and from 10 to 13.6 cGy for Cobalt 60. All 16 patients subsequently delivered full-term, normal infants. Following delivery, all of the patients had further staging procedures; eight received additional treatment. Subsequently, the disease relapsed in four patients; two eventually died of Hodgkin's disease. The 10-year determinant and overall survival rates were 83% and 71%, respectively. Currently, all offspring are physically and mentally normal, and none has developed a malignancy. Radiotherapy is an appropriate initial treatment for supradiaphragmatic presentations of Hodgkin's disease during the second and third trimesters of pregnancy, provided special attention is paid to treatment and shielding techniques. The outcome for women treated with irradiation for clinical stage I and II Hodgkin's disease during pregnancy has not been shown to be adversely affected by pregnancy, and after the first 8 weeks of gestation, the risk to the fetus appears to be minimal.