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Biomedical subjects

R M Linggood

Publications and source records attributed to R M Linggood.

At least 37 records · Page 2Linked to original sources

Pre-irradiation internal carotid artery BCNU in treatment of glioblastoma multiforme.

High-dose 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) infusion into the internal carotid artery following cranial irradiation in the treatment of glioblastoma multiforme is accompanied by evidence of leukoencephalopathy in a significant number of patients. In an attempt to avoid this problem, a phase I trial was performed using intracarotid BCNU infusion before irradiation. Twenty-eight patients with grade III/III astrocytoma (World Health Organization Classification, equivalent to Kernohan grade IV) received a 400-mg infusion of BCNU into the infraophthalmic carotid artery. The treatment was repeated every 4 weeks for a total of four cycles prior to cranial irradiation (5500 to 6000 cGy). The major toxic sequelae included nausea and vomiting (24%), decreased visual acuity (14%), transient cerebral ischemia (3.5%), and thrombocytopenia (3.5%). Fatal leukoencephalopathy occurred in two patients. The median survival time was 37 weeks for all evaluable patients and 56+ weeks for those completing the protocol. The tumor response to drug infusion as judged by computerized tomography (CT) was complete in 22% of patients and partial in 22%; 56% showed no CT tumor response. Pre-irradiation intracarotid artery BCNU benefits a very small group of patients with grade III/III astrocytoma. The associated severe leukoencephalopathy makes this mode of therapy unacceptable for a phase III trial.

Adult↗

The effect of the respiratory cycle on mediastinal and lung dimensions in Hodgkin's disease. Implications for radiotherapy gated to respiration.

Changes in mediastinal and lung dimensions during respiration were studied to assess the potential of radiotherapy gated to respiration to minimize normal tissue irradiation. Twelve patients with mediastinal Hodgkin's disease were assessed using chest radiographs and thoracic computed tomography (CT) scans both during quiet breathing and at maximum inspiration in the standing, supine, and prone positions. A simple measure of the bulk of mediastinal disease, the ratio of the width of mediastinal mass to thoracic diameter, was determined from posteroanterior (PA) chest radiographs. The volumes of mediastinum, irradiated and protected lung if anteroposterior (AP) and PA mantle fields were used were determined from sequential thoracic CT scans and three-dimensional treatment planning and compared at quiet breathing and deep inspiration. The mediastinal width to thoracic diameter ratio decreased from quiet breathing to deep inspiration an average of 3%, 9%, and 11% for the standing, supine, and prone positions, respectively. Lung volumes as measured from the thoracic CT scans showed that on average, 8% more lung was protected at deep inspiration than at quiet breathing, independent of treatment position. The maximum increase in the percentage of protected lung from quiet breathing to deep inspiration was seen in patients with extensive mediastinal adenopathy suggesting that radiotherapy gated to respiration may be most advantageous in the subset of patients.

Hodgkin Disease↗

Results of treatment of stage IA and IIA Hodgkin's disease.

This study analyzed the 5 year actuarial survival and disease-free survival of 122 patients with Stage IA and IIA Hodgkin's disease, (108 patients laparotomy staged) treated with mantle and paraaortic irradiation from 1975 to 1981. Prognostic subgroups and patterns of treatment failure were investigated. The 5 year actuarial survival and disease-free survival was 91% and 75% respectively for the entire group. For Stage IA patients, the 5 year survival and disease-free survival was 92% and 86% respectively, whereas for those in Stage IIA the respective figures were 86% and 65%. Individuals with greater than four sites of involvement at initial presentation; extensive mediastinal adenopathy; hilar or extramediastinal extension to lung, pleura or pericardium, had a poorer 5 year actuarial disease-free survival (43%-60%) than those without these factors (70%-85%). Of the 122 patients, there were 26 relapses: nine infield failures; two concurrent infield and systemic failures; nine marginal recurrences, and three relapses occurring systemically and three in nodal groups not irradiated. Following relapse, 17 patients were salvaged with chemotherapy. Two patients are alive with disease and seven patients died of Hodgkin's disease. Patients with less extensive mediastinal adenopathy and supradiaphragmatic nonmediastinal presentations can be satisfactorily treated with mantle and paraaortic irradiation, whereas patients with extensive mediastinal adenopathy receive six cycles of multiagent chemotherapy before irradiation.

Adolescent↗

Results of treatment of stage 3A Hodgkin's disease.

From 1975 to 1981, 38 patients with Stage 3A Hodgkin's disease (35 patients pathologically staged) underwent mantle and para-aortic irradiation, and in 36 patients this was preceded or followed by at least six cycles of multiagent chemotherapy. Both the 5-year actuarial survival and disease-free survival for all 38 patients were 83%. There have been six treatment failures: two patients have relapsed within irradiated nodal groups, one patient in apical pericardial lymph nodes as a marginal recurrence, one patient concurrently infield and in unirradiated nodal groups, and two patients systemically (concurrently in unirradiated nodal groups). Of these six relapses, three patients have died of Hodgkin's disease, one patient has been salvaged, and two patients currently are under treatment for salvage. One patient has developed acute nonlymphocytic leukemia and died of this disease. Extensive disease, as estimated by the number of sites of involvement at presentation, degree of splenic involvement, extent of intra-abdominal disease or mediastinal involvement, did not reveal statistically significant prognostic subgroups for relapse. It is currently recommended that patients with Stage 3A Hodgkin's disease receive six cycles of multiagent chemotherapy and mantle and para-aortic irradiation.

Actuarial Analysis↗

Endobronchial involvement with non-Hodgkin's lymphoma. A clinical-radiologic analysis.

Based on experience with three cases of endobronchial non-Hodgkin's lymphoma and a review of cases previously reported, two patterns of lymphomatous involvement of airways are described. The Type 1 pattern is characterized by diffuse submucosal infiltrates occurring in the presence of intra- and extrathoracic lymphoma. In Type 2 cases, central airways are involved by a solitary mass in the absence of clinically apparent systemic lymphoma. The clinical-radiologic picture is characterized by signs of pneumonitis in Type 1 cases, while in Type 2 cases, signs of airway obstruction uniformly occur.

Adult↗

Histopathologic features predicting recurrence of meningiomas following subtotal resection.

Histopathologic features that predict recurrence of meningiomas following subtotal resection were identified by reviewing the initial surgical specimens from 82 patients (38 with tumor recurrence and 44 without) treated at the Massachusetts General Hospital between 1962 and 1984. There was no correlation between histologic subtype and tendency toward tumor recurrence; however, the few examples of hemangiopericytoma, angioblastic meningioma, or sarcomatous meningioma were observed almost exclusively in patients with recurrent tumors. Seven histopathologic features were positively correlated with recurrence of meningiomas, including the following: hypervascularity of tumors, hemosiderin deposition, growth of tumor cells in sheets rather than the usual growth patterns of meningiomas, prominent nucleoli, mitotic figures, single-cell and small-group necrosis, nuclear pleomorphism, and overall atypical or malignant tumor grade (all p less than 0.005). In addition, sheeting of tumor cells, prominent nucleoli, and the presence of less than 10% meningothelial pattern were correlated with significantly abbreviated progression-free survival, i.e., more rapid progression of tumor with shorter intervals between treatment and tumor recurrence. These findings suggest that the presence of features such as large prominent nucleoli, tumor growth in sheets, individual-cell necrosis, and nuclear pleomorphism may be used to predict recurrence of subtotally resected meningiomas that would not be classified as malignant by traditional criteria.

Adolescent↗

Meningioma: analysis of recurrence and progression following neurosurgical resection.

The rates of survival, tumor recurrence, and tumor progression were analyzed in 225 patients with meningioma who underwent surgery as the only treatment modality between 1962 and 1980. Patients were considered to have a recurrence if their studies verified a mass effect in spite of a complete surgical removal, whereas they were defined as having progression if, after a subtotal excision, there was clear radiological documentation of an increase in the size of their tumor. There were 168 females and 57 males (a ratio of 2.9:1), with a peak incidence of tumor occurrence in the fifth (23%), sixth (29%), and seventh (23%) decades of life. Anatomical locations were the convexity (21%), parasagittal area (17%), sphenoid ridge (16%), posterior fossa (14%), parasellar region (12%), olfactory groove (10%), spine (8%), and orbit (2%). The absolute 5-, 10-, and 15-year survival rates were 83%, 77%, and 69%, respectively. Following a total resection, the recurrence-free rate at 5, 10, and 15 years was 93%, 80%, and 68%, respectively, at all sites. In contrast, after a subtotal resection, the progression-free rate was only 63%, 45%, and 9% during the same period (p less than 0.0001). The probability of having a second operation following a total excision after 5, 10, and 15 years was 6%, 15%, and 20%, whereas after a subtotal excision the probability was 25%, 44%, and 84%, respectively (p less than 0.0001). Tumor sites associated with a high percentage of total excisions had a low recurrence/progression rate. For example, 96% of convexity meningiomas were removed in toto, and the recurrence/progression rate at 5 years was only 3%. Parasellar meningiomas, with a 57% total excision rate, had a 5-year probability of recurrence/progression of 19%. Only 28% of sphenoid ridge meningiomas a second resection, the probability of a third operation at 5 and 10 years was 42% and 56%, respectively. There was no difference in the recurrence/progression rates according to the patients' age or sex, or the duration of symptoms. Implications for the potential role of adjunctive medical therapy or radiation therapy for meningiomas are discussed.

Adolescent↗

Breast cancer developing in four women cured of Hodgkin's disease.

Four patients developed breast cancer 11 to 17 years after treatment for Hodgkin's disease. Three patients received radiotherapy only, and one received radiation plus chemotherapy. This study is in keeping with the report by Nelson and associates that with duration of follow-up exceeding 10 years, there is an increase of breast cancer in women treated for Hodgkin's disease that is similar to or greater than the risk of breast cancer in women treated with radiation for benign breast disease and is probably independent of chemotherapy.

Adolescent↗

Radiation therapy of Waldeyer's ring lymphoma.

Forty-nine patients with biopsy-proven Waldeyer's ring lymphoma were treated with radiation therapy between 1968 and 1979; 45 to 50 Gy were given to Waldeyer's ring structures with a 5- to 10-Gy boost to the primary site. Uninvolved low cervical nodes received 40 to 50 Gy. Chemotherapy was reserved for treatment failures. Actuarial 5-year survival was 53%, disease-free survival was 48%, and local control was 98%. Patients with Stage I disease fared better than patients with Stage II disease, and unilateral adenopathy conferred a better prognosis than bilateral adenopathy. When classified by the Rappaport system, nodular lymphomas had a better prognosis than diffuse lymphomas, and of the diffuse lymphomas, histiocytic lymphoma was a more lethal disease than lymphocytic lymphoma. Patients with diffuse undifferentiated lymphomas in the Rappaport system, or high-grade lymphomas in the Working Formulation, fared poorly. Most relapses were systemic, and actuarial 5-year survival after salvage was only 20%. A logical approach to the treatment of this disease can be based on these prognostic features.

Actuarial Analysis↗

Impact of thoracic computed tomography on radiation therapy planning in Hodgkin disease.

Over 5 years, CT of the thorax was performed on 53 patients with Hodgkin disease and mediastinal lymphadenopathy prior to the institution of therapeutic irradiation. Information obtained from CT prompted major alterations in the plan of therapy in 11 of 53 (21%) of the patients. These included changes of treatment portal size, the addition of localized boost therapy, and a revision of diagnosis.

Combined Modality Therapy↗

Lymphocyte surface markers in orbital lymphoid neoplasms.

Since the malignant nature of many orbital lymphoid infiltrates is difficult to assess from pathologic examination alone, over the past four years lymphocyte surface marker studies have been added to the evaluation of 23 such cases. Only 10 of the 23 could be confidently classified as malignant lymphoma by histology alone. However, monoclonal surface immunoglobulin was found in 15, supporting the pathologic diagnosis of malignancy in eight and adding seven that could not have been diagnosed otherwise. Clinical evaluation, including a median follow-up of 18 months, revealed manifestations of systemic lymphoma in six of those 15; two had been diagnosed only by surface markers. In contrast, only one of eight cases lacking monoclonal surface immunoglobulin exhibited clinical evidence of malignancy (that case was also indeterminate by histologic criteria). The addition of surface marker analysis permits more accurate diagnosis of orbital lymphoma than is possible from pathologic study alone. This technique can suggest the subtype of lymphoma.

Adult↗

Primary gastric lymphoma. An analysis with emphasis on prognostic factors and radiation therapy.

Primary gastric lymphoma, lymphoma originating in the stomach, without involvement of peripheral or mediastinal lymph nodes, viscera, or the bloodstream, is sufficiently uncommon that the indications for radiation therapy, the dose of irradiation necessary for control of lymphoma, optimum field size, and patterns of failure have never been established. The authors identified 26 patients, and reviewed their charts and pathologic material. Their overall 5-year survival was 57%. Factors significantly influencing 5-year survival were serosal penetration (32% versus 91%), regional lymph node involvement (33% versus 81%), and location on the lesser curvature (20% versus 89%). Histologic characteristics, extent of surgery, and, provided the patient was irradiated, involvement of surgical margins did not influence survival. Overall, survival was not affected by irradiation, but in patients with poor prognostic factors there appeared to be a beneficial effect. Analysis of local control in this and other series suggests that patients should receive at least 40 Gy, and that whole abdominal irradiation is not necessary. The majority of failures were distant, indicating a need for effective systemic therapy.

Female↗

Medulloblastoma. The identification of prognostic subgroups and implications for multimodality management.

For 43 medulloblastoma patients who had five-and ten-year actuarial survival rates of 56%, prognostic factors of statistical significance included: T-stage (82% T1,2 versus 46% T3,4; P less than 0.02), M-stage (63% M0,1 versus 0% M2,3; P less than 0.03), and histopathologic tumor score (TS, based upon necrosis, desmoplasia, cytoplasmic processes, and mitoses) (81% TS less than or equal to 5 versus 41% TS greater than or equal to 6; P less than 0.05). Posterior fossa local control rates were also function of T-stage (90% T1,2 versus 38% T3,4) and TS (83% TS less than or equal to 5 versus 38% TS greater than or equal to 6). Combining TS with T-stage, patients fell into three prognostic and local control groups, which may have different future management implications: Small (T1,2) tumors of favorable (TS less than or equal to 5) histology had a 92% ten-year actuarial survival rate with 100% (8/8) local control; no change from current management is suggested. For the intermediate prognosis group (T1,2-TS greater than or equal to 6 or T3,4-TS less than or equal to 5 with 67% and 70% survival, respectively), increasing the irradiation dose alone may improve survival because these tumors exhibited an irradiation dose-response relationship. However, it is the poor prognosis group (T3,4-TS greater than or equal to 6 with 42% survival) which might be suitable for future adjuvant chemotherapy or radiosensitizer trials since there is no evidence that higher irradiation doses improve local control. This article identifies prognostic subgroups based on histologic type and TM staging in medulloblastoma patients which potentially may be utilized to improve therapeutic results, and confirms the value of staging patients with central nervous system malignancies.

Adolescent↗

Overwhelming post-splenectomy infection in Hodgkin's disease: pathogenesis and prevention.

After staging splenectomy, the risk of overwhelming sepsis in patients with Hodgkin's disease reaches 21% in certain subgroups. Youth, recent splenectomy and vigorous chemoradiotherapy predispose patients to this complication. Because of its explosive course and its known microbiology, post-splenectomy sepsis is better suited to prevention than to treatment. Since immunisation prior to treatment produces good antibody responses, all patients with Hodgkin's disease should probably be vaccinated against encapsulated bacteria at least 10 days prior to the onset of therapy.

Adolescent↗

Primary non-Hodgkin's lymphoma of the mediastinum.

Non-Hodgkin's lymphoma localized to the mediastinum and adjacent structures occurred in 12 of 215 (6+) non-Hodgkin's lymphoma patients seen at the Massachusetts General Hospital between 1975 and 1979. Lymphangiography, radionuclide scanning and whole body computerized tomography were used to exclude patients with extrathoracic disease at presentation. Eleven of the 12 patients presented with extensive contiguous extranodal disease (Stage IIE) with involvement of either the pericardium, sternum, chest wall, pulmonary parenchyma or, in four cases, with superior venacaval obstruction. Diffuse large cell lymphoma (eight cases) and diffuse poorly differentiated lymphocytic lymphoma (four cases) were the prevalent histologic subtypes; no instances of lymphoblastic lymphoma without extrathoracic spread were encountered. None of four lymphomas studied could be characterized as either B- or T-cell tumors utilizing conventional surface marker techniques. Ten of the 12 patients achieved complete remissions, either after treatment with combination chemotherapy alone (three patients) or after both chemotherapy and mediastinal irradiation (seven patients). Two of these ten have subsequently relapsed, but median survival has not been reached after a mean period of observation of 28 months. Primary nonlymphoblastic non-Hodgkin's lymphoma of the mediastinum is more common than previously realized, displays aggressive contiguous spread within the chest and responds well to combination chemotherapy with or without adjuvant mediastinal irradiation.

Adult↗

Medulloblastoma in adults: improved survival with supervoltage radiation therapy.

During the period from January 1962--June 1979, 17 adults (greater than or equal to 16 years of age) received postoperative supervoltage neuraxis radiation therapy for medulloblastoma. An actuarial five- and ten-year survival rate of 46% was achieved, and the major site of recurrence postirradiation was in the posterior fossa. Compared to previous pediatric series, adults may demonstrate more visceral metastases and fare less well after tumor recurrence. Compared to prior series of adult patients, the demonstrated improved survival is attributed to increased doses delivered to the posterior fossa.

Adult↗