Wide-field Radiation Research Articles

Management of the patient with large cell lymphoma

Lymphomas are neoplasms of B-lymphocytic (75% of cases) or T-lymphocytic (20% of cases) origin. It is now appreciated that the various sub-types of disease represent counterparts of the normal pathways of lymphoid differentiation and transformation, from resting cells to fully transformed and activated lymphoid cells. The large cell lymphomas represent a group of neoplasms, formerly grouped together and termed ‘histiocytic lymphoma’ which represent transformed lymphocytes, of T- or B-cell derivation. Within the Working Formulation for Clinical Usage, a recently proposed translational tool, these lymphomas fall within the ‘Intermediate’ or ‘High-grade’ disease categories. The initial evaluation of a patient with large-cell lymphoma must include a formal staging procedure, in order to ascertain the precise extent of disease, so that appropriate therapeutic decisions may be made. This evaluation is also useful for defining all sites of lymphomatous disease, so that the results of any given therapeutic intervention can be accurately assessed. For the patient with localized, stage I disease, one option would be to take the patient to formal staging laparotomy, in order to attempt to prove the presence of pathologic Stage I disease. In this instance, wide-field radiotherapy may be employed, with the chance of achieving long-term, disease-free survival of approximately 70%. Alternatively, the patient may be staged less aggressively, and given combination chemotherapy, which is also effective in low-stage disease. In patients with Stage II, III or IV large-cell lymphoma, multi-agent chemotherapy is the expected treatment modality, although some controversy currently exists regarding the optimal regimen(s). The regimens commonly employed in the 1970s, including CHOP (cyclophosphamide, hydroxyldaunamycin, vincristine, prednisone) have resulted in long-term, disease-free survival in approximately 30% of all treated patients, with 10-year follow-up data available. Although newer regimens have recently been proposed which are, for the most part more intensive, these studies have only recently been reported, and large-scale studies which seek to prospectively compare the various regimens are currently in progress. Until these studies have been completed, the true regimen(s) of choice remains undefined. Although various regimens have been reported as effective in the minority of patients who relapse after chemotherapy, the use of autologous and/or allogeneic bone marrow transplantation may provide the best possibility of long-term disease-free survival, especially in younger patients, with low tumor burden, who are not refractory to chemotherapy.

Sequential wide field irradiation and systemic chemotherapy as part of the induction treatment of small cell lung cancer.

Sequential wide field irradiation and systemic chemotherapy as part of the induction treatment of small cell lung cancer.

Merkel cell carcinoma: a review of behaviour patterns and management strategies.

Eleven patients with Merkel cell carcinoma of the skin were reviewed retrospectively. The aggressive nature of this tumour is reflected by the incidence of local recurrence, regional nodal metastases and systemic dissemination, which is 36%, 55%, and 18% respectively. This high frequency of local recurrence and metastases is confirmed in the literature. Management strategies should be planned accordingly, following accurate assessment of the extent of disease. Wide excision, with or without nodal dissection, together with adjuvant wide field irradiation is necessary for loco-regional control of this radiosensitive tumour. Radiotherapy alone may be appropriate treatment for extensive loco-regional tumours or in those that have already metastasized. Although the role of chemotherapy is unclear, there are an increasing number of reports of chemosensitivity and further investigation in this area is required.

Salvage therapy of advanced hodgkin's disease: Critical appraisal of curative potential

The therapeutic outcome in patients with advanced Hodgkin's disease has improved considerably since the advent of MOPP chemotherapy (mechlorethamine, vincristine, procarbazine, and prednisone) and MOPP-like regimens. Still, failure will eventually occur in approximately 50 percent of these patients. The optimal approach to treating these patients is not well established. Currently, the six major salvage approaches available are: (1) chemotherapy reinduction with the same initial regimen: (2) chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine); (3) non-ABVD second-line regimens; (4) third-line chemotherapy regimens; (5) wide-field radiation therapy alone or combined with second-line chemotherapy; and (6) autologous and allogeneic bone marrow transplantation. This review provides a critical evaluation of the curative potential of each therapeutic modality and outlines recommendations for the best current therapeutic approach and for future clinical study.

Wide-field radiation therapy alone or with chemotherapy for Hodgkin's disease in relapse from combination chemotherapy.

Nineteen patients with Hodgkin's disease who relapsed primarily in nodal sites after intensive combination chemotherapy were retreated with wide-field radiation therapy alone or with additional chemotherapy between January 1971 and December 1984. Six patients presented in second relapse and 13 patients in first relapse. Seven patients were treated with combination chemotherapy and radiation therapy and twelve patients were treated with radiation therapy alone. Radiation therapy field sizes and doses were similar to those recommended for early-stage Hodgkin's disease patients treated with radiation therapy alone. The 5-year actuarial freedom from relapse (FFR) and survival following retreatment were 48% and 69%, respectively. Twelve patients are currently disease-free 12 to 172 months following retreatment. Wide-field radiation therapy alone or with additional chemotherapy should be considered for patients with advanced Hodgkin's disease who relapse in nodal sites after initial combination chemotherapy.

Radiation therapy salvage of Hodgkin's disease following chemotherapy failure.

Between 1972 and 1984, 17 patients with advanced Hodgkin's disease failing intensive combination chemotherapy in previously unirradiated nodal and/or pulmonary sites were treated with salvage radiotherapy. Treatment consisted of comprehensive wide field radiotherapy to all known areas of disease. Doses administered to these fields ranged from 1,700 to 5,000 rad, with only three patients (18%) receiving less than 3,000 rad to any field. With a median follow-up of over 4 years, 88% achieved a complete response, with median actuarial disease-free survival (DFS) of 19 months (range, 4 to 61+). Actuarial median survival was 64 months, with a range of 4 to 134+ months. Nine patients (53%) are currently alive with three (18%) in continuous complete remission (CR) for 24, 30, and 61 months. In addition, four patients relapsing after salvage radiotherapy are now in CR following additional therapy. Patients younger than 35 years of age had a significantly increased overall survival when compared with older patients (P less than .005). An initial complete response to chemotherapy lasting 12 or more months appeared to be a favorable prognostic factor, although small patient numbers preclude statistical significance. Comprehensive salvage radiotherapy is of significant benefit in patients with advanced Hodgkin's disease relapsing after combination chemotherapy in nodal and/or pulmonary sites.

Radiation therapy in the management of neuroblastoma: The Duke University medical center experience 1967–1984

We have evaluated the role of radiotherapy in providing local control of primary tumors and to palliate metastases from neuroblastoma (NB). Fifty-five children with histologically verified NB were evaluated and treated from 1967 to 1984. In univariate analysis, the actuarial survival of eight children with thoracic primaries (85%) was significantly better than the survival of 39 children with intra-abdominal primaries (35%, p = 0.0287). The survival of 28 children less than or equal to 18 months of age at diagnoses was 73%, whereas 27 children older than 18 months had a survival probability of 10% ( p = 0.0001). The survival by Evans stage was: I 100% (2 patients), II 85% (7), III 60% (13), IV 4% (27) and IV-S 100% (6). According to the Pediatric Oncology Group (POG) staging system, the survival was: A 100% (3), B 66% (9), C 66% (9), D 23% (34). A multivariable analysis indicated that the Evans staging system was a more powerful indicator of prognosis than the POG system. The analysis also indicated that Evans stage and patient age were independent determinants of survival. The primary tumor site did not add significant prognostic information beyond these two factors. Children with Stage I disease were treated with surgery alone. Most children with Stages II and III disease were treated with surgery, irradiation, and Cyclophosphamide or Cyclophosphamide plus Vincristine. All seven patients with Stage 11 disease received post-operative irradiation to the primary tumor and were locally controlled with doses of 4.8 to 26.5 Gy. Eleven of the 13 patients with Stage III disease were irradiated post-operatively. Seven of these 11 patients were locally controlled with doses of 12 to 48.4 Gy. The four Stage III patients with in-field recurrences were older children with large radiotherapy fields and/or low doses administered. The Radiation Therapy Oncology Group pain score system was used to evaluate response of painful bony metastases to irradiation. A response was observed in 65% of the sites irradiated. A response was observed at 67% of the soft tissue metastases irradiated. Hepatomegaly causing respiratory embarrassment or inferior vena cava obstruction was treated with irradiation in seven patients. All patients responded with doses ranging from 5 to 24.4 Gy. Five of the 17 children who survived for more than 5 years following treatment had significant scoliosis or kyphosis secondary to vertebral body abnormalities in irradiated bones. All five children were irradiated at a young age with megavoltage equipment. Three of the five were irradiated to the full width of the vertebral body. We conclude that (a) the experience at Duke confirms previous reports that young age and early Evans stage are favorable prognostic signs in NB. (b) Stage III disease was not uniformly controlled locally by irradiation. It is not clear if this was caused by low doses or tumor biology (failures occurring in older children). (c) Post-operative wide-field irradiation and chemotherapy were used in almost all node positive (POG C) and node negative (POG B) patients. Survival in Stages B and C were equivalent. The lack of influence of nodal involvement on survival in irradiated patients is discussed.

Advances in pediatric radiotherapy in the last ten years and future proposals.

Advances made can be divided into five main categories. Firstly, the problem of geographic miss which has been reduced by delivering effective radiation doses with greater precision. This has been accomplished with more sophisticated diagnostic and therapeutic equipment, immobilization techniques and computerized treatment planning. Second is the recognition of the interplay of radiation and chemotherapy on normal tissue tolerance and local tumor control. This interaction has necessitated reduction in both dose and volume of irradiation. Third is the use of wide field irradiation as a systemic treatment. Fourthly, the utilization of cooperative group trials to define the role of irradiation. Finally, with the improvement in survival has come the recognition of late effects of irradiation in the growing child and the means of reducing such effects. The current role of radiation therapy in childhood malignancies is summarized, controversies are identified, and future prospects explored.

Influence of local-regional lymph node metastases on prognosis in neuroblastoma.

Data relative to the prognostic and therapeutic significance of lymph node metastases in regionally confined neuroblastoma (Evans stages II-III) are scant. We have analyzed lymph node status in order to assess the significance of nodal involvement. Disease-free survival (minimum follow-up of 2 years) was 84% (21/25) among node-positive patients compared with 95% (18/19) for node-negative patients (P greater than 0.1, two-tailed test). These results contrast with the results from two other centers in which lymph node involvement was a significant adverse prognostic indicator. The use of intensive multimodal therapy including surgical resection of the primary tumor, wide-field radiation therapy to the tumor bed and regional lymph nodes, and chemotherapy may have accounted for the better survival in our node-positive patients.

The place of radiotherapy in the management of localised Hodgkin's disease (report no 11)

This report reviews the experience of the BNLI in managing localised Hodgkin's disease, since the BNLI began in February 1970. The original problem investigated by this study was the evaluation of 'prophylactic' irradiation treating adjacent apparently unaffected regions, as opposed to radiation directed to only the affected regions of the body. Because lower half Hodgkin's disease is uncommon, the study was confined to patients presenting with upper half disease, without 'B' symptoms. Diagnostic laparotomy and splenectomy was not considered to be a mandatory investigation and at the commencement of the study was recommended by only two collaborators. By the completion of the study the majority of collaborators were recommending this procedure routinely. This study therefore includes two additional subgroups of patients with Stages I, IIA (upper half) Hodgkin's disease. In the laparotomised group of patients a 10-year survival rate of almost 95% with either 'local' or 'prophylactic' irradiation suggests that wide field irradiation (including total nodal irradiation) is not essential in the cure of apparently localised Stages I, IIA (upper half) Hodgkin's disease, provided the extent of the disease has been accurately determined by previous investigation. In those patients treated with strictly 'localised' (as opposed to 'prophylactic') irradiation, relapses in adjacent unirradiated regions have been completely controlled by additional treatment, usually irradiation, and none have died of Hodgkin's disease.

Prophylactic neck irradiation.

Treatment of subclinical cervical metastases from advanced squamous carcinomas of the nasopharynx, oropharynx, oral cavity, hypopharynx, and larynx remains contentious. Watchful waiting, elective neck surgery, and, more recently neck irradiation all have their advocates. The possibility of "sterilization" of the neck showing no clinical signs of metastasis has been especially appealing in concept. Wth this in mind, and by use of an external high-dose megavoltage technique, radiation therapy was used in 152 patients with clinically negative necks at the Upstate Medical Center from 1968 to 1977. Lymph node failures were extremely low (4%) when wide-field radiation ports were used and the primary lesion controlled.

Malignant Lymphoma of the Testis: Review of 17 Cases in British Columbia with Survival Related to Pathological Subclassification

We reviewed 17 patients in whom malignant lymphoma appeared to arise primarily in the testis without evidence of widespread dissemination. Malignant lymphoma of the testis occurring as part of a generalized disorder was not included. That the disease may be localized to the testis and can be cured (or long-term survival without evidence of dissemination) are supported by the results reported. The clinical features were reviewed and compared to those recorded in the literature. The 16 tumors in adults were all classified as diffuse histiocytic lymphoma. They were further classified as large cleaved cell, large non-cleaved cell and large non-cleaved cell (? immunoblastic) lymphoma. Survival was correlated with this classification and none of the patients with large cleaved cell tumors has died of malignancy. Prognosis also was related to clinical presentation and initial treatment. All surviving patients underwent orchiectomy and wide-field radiotherapy.

Results of a pilot study of wide field radiotherapy in the treatment of oat cell carcinoma of the bronchus

Twenty-two patients suffering from oat-cell carcinoma of the bronchus were treated by various forms of wide field radiation. Ten patients were treated with high dose upper half body radiation, followed by lower half body radiation and radiation to the primary. Four patients were given high dose half body radiation for metastases. Two patients received low dose total body radiation after radiotherapy to the primary. Two patients received fractionated total body radiation for metastatic disease. The median survival was 20 weeks for all cases. For those receiving radical therapy, the median survival was 22 weeks. The median survival was 10 weeks in those cases treated for metastatic disease. Major toxicity included dryness of the mouth in one case, anaemia, acute pulmonary distress following high dose upper half body radiation and acute radiation pneumonitis. There was inadequate local control in nine cases which could be improved by increasing the radiation dose to the primary. High dose half body radiation may well delay the onset of metastases. Low dose total body radiation has some palliative effect.

The radiation pneumonitis syndrome in half-body radiation therapy.

Further understanding is required of the pathological processes underlying the acute radiation pneumonitis syndrome occurring at about 4 months after irradiation. Until enough is known to be able to modify it reliably, wide field irradiation of the whole lungs, which can be useful in the treatment of cancer, needs to be done using doses carefully corrected for the low density of lung and kept below a threshold of 600 to 700 rad single dose.

Effect of wide field irradiation on unirradiated tumors in the same host

The immune system is believed to influence tumor growth; and, ionizing radiation has an immunosuppressive potential. However, investigators have come to conflicting conclusions regarding the effect of localized radiation therapy on both the immune system and on distant tumor growth. This report describes two murine models. In the first, B-16 malignant melanoma was implanted simultaneously into the left groin and right axilla. In the second model, in order to immunize the mouse, B-16 melanoma was implanted into the left groin 1 week before implanting melanoma into the right axilla. In both models, 600 rad caudal hemibody irradiation was given in a single fraction with a 4 MeV linear accelerator. Significant decrease in the growth of irradiated groin tumors occurred. Unirradiated axillary tumors did not demonstrate increased growth. We conclude that, at least in these models, high dose, wide-field irradiation does not augment the growth of unirradiated tumors in the same host.

The long-term effect of radiotherapy on the immune status of patients cured of a gynecologic malignancy.

The long-term effect of radiotherapy on the immune system were evaluated in 52 patients cured for a gynecologic malignancy from 3 to 15 years. Eighty-seven percent of the patients had no depression in cell-mediated immunity as determined by delayed hypersensitivity reaction to DNCB. The absolute lymphocyte count, as well as the circulating immunoglobulins (IgA, IgG, IgM), were within the normal range. Thus, there were no significant changes in cell-mediated immunity and circulating immunoglobulins several years after radical wide-field radiotherapy.

Fibrosarcoma of the head and neck: a clinical analysis of forty cases.

This paper is a clinical analysis of 40 patients with fibrosarcoma of the head and neck treated at the Washington University Medical School, St. Louis, Missouri. Follow-up ranged from 6 to 25 years in 31 patients. Treatment consisted of widefield surgical excision, surgery and irradiation, narrowfield surgery, and irradiation alone. Histological classification of the tumors correlates well with the prognosis. In the well differentiated tumor group 12 out of 16 patients treated for a cure were free of tumor. In the poorly differentiated group only one out of five treated for a cure was free of tumor. Widefield surgical excision is the treatment of choice. Prophylactic radical neck dissection is not indicated. Narrowfield surgical excision resulted in a high recurrence rate although the salvage rate was excellent with subsequent widefield resection. Irradiation therapy produced good palliative results in those patients treated by irradiation alone and has a definite role in the management of this disease.

Hodgkin's disease: a review of changes over 40 years.

Abstract Many changes have taken place in the past 40 years in our approach to Hodgkin's disease. The advance achieved has been largely due to the work of a succession of radiotherapists whose efforts have resulted not only in more successful treatment, but also in more acute clinical assessment and more thorough investigation. International collaboration in clinical, immunological and epidemiological studies has promoted a better understanding of the nature of Hodgkin's disease and has given us a new view of its possible aetiology. Co-operation has also resulted in agreement on histological and staging classifications and thus in the establishment of a more secure basis for the assessment of prognosis which has vastly improved in recent years following the introduction of wide-field irradiation and spaced combination chemotherapy. Survival-rates are rising steadily: 75 per cent of patients treated five years ago are still alive today. Moreover, realistic estimates of cure-rates can now be made by compari...

Immobilization of patients during wide-field radiotherapy.

Abstract A whole-body patient immobilization method is described consisting of a cast system employing a lightweight plaster mix poured around the patient, who is enclosed in removable shuttering. The separate portions of the immobilization casts are located on dowels inserted into the formica table used for making the casts. The patient may be irradiated on the formica table which can be transported on a trolley and slid on to the treatment couch or the separate portions of the casts can be positioned over identical dowels inserted into the treatment table top. In use, the system has functioned well for head and neck cases and for whole-body immobilization for the mantle technique. Whole-body immobilization is a basic necessity for automated treatment systems.

I. Radiotherapy of the Reticuloses

It is fortunate that the malignant reticuloses are highly sensitive to radiotherapy with a fair degree of consistency. Unfortunately the majority of patients presenting with malignant reticuloses have generalised metastases or systematised disease at that time. Nevertheless where the disease is apparently still localised to one lymph node area or to the site of origin and adjacent nodes, the survival rate following radiotherapy is of the same order as that obtained in carcinomata of accessible sites (Table I). The guiding principle in the treatment of these localised lymphoreticular sarcomas has been to include within the irradiated volume the lymph nodes reached by the lymphatics draining the area and any probable line of extension from the primary tumour. It follows that the fields must be large—for example the irradiated volume has extended from the base of the skull to below the clavicles—and doses of the order of 3,000 r in four weeks must be given. The discomfort to the patient which arises from this type of treatment should not be minimised and must be justified by the results. Taste and smell may be lost and the secretion of the salivary glands reduced and some cases develop radiation caries. Treatment of this type when pressed to the limits of immediate local tolerance can be followed by radiation myelitis. The lungs, kidneys, bowel and bone may also suffer late effects from radical wide field irradiation.