Robert Goodman

The significance of mediastinal involvement in early stage Hodgkin's disease

Between April 1969, and December 1974, 111 consecutive surgically staged I A and II A patients with supradiaphragmatic Hodgkins disease were treated at the Joint Center for Radiation Therapy. Patients received 3600–4400 rad to mantle and para‐aortic‐splenic pedicle regions. Median follow‐up was 56 months (30–96). Fourteen patients developed relapsing Hodgkins disease and three patients died of possible treatment‐related causes, two with acute myocardial infarctions and one with radiation pneumonitis. Patients with mediastinal enlargement greater than one third of the chest diameter have a significantly higher risk (p < 0.01) of developing relapse (9 of 18) than patients with lesser or no mediastinal disease (5 of 93). Of the 18 patients with large mediastinal disease, six relapsed in the mediastinum and two in the lung. There continue to be no pelvic extensions in the entire group. There is a 92% relapse‐free and 97% overall survival in the 93 patients without extensive mediastinal disease. We continue to recommend mantle and para‐aortic‐splenic pedicle irradiation for these patients. In view of the large number of relapses in patients with extensive mediastinal disease, we are now treating this subgroup of patients with MOPP chemotherapy in addition to mantle and para‐aortic irradiation.

Malignant lymphoma after diphenylhydantoin (dilantin) therapy

A history of prolonged diphenylhydantoin (Dilantin) therapy was reported by 8 of 516 patients (1.6%) with Hodgkins disease or non‐Hodgkins lymphoma, as compared with 3 of 516 patients (0.6%) with other cancers, and 2 of 516 (0.4%) tumor‐free individuals. The findings, together with other published data, suggest a small excess risk of malignant lymphomas in patients receiving long‐term treatment with this drug. The immunosuppressive effects of chronic diphenylhydantoin therapy may be involved in the pathogenesis of these neoplasms.

The place of radiation therapy in the treatment of Hodgkin's disease

Between April 1969, and December 1974, 216 successive surgically‐staged IA‐IIIB Hodgkins disease patients were seen and treated at the Joint Center for Radiation Therapy. Patients with stages IA and IIA disease received mantle and para‐aortic‐splenic pedicle irradiation alone and have a probability of relapse‐free survival of 97% and 80%, respectively. Patients with stage IIIA disease were treated with total‐nodal irradiation (TNI) alone and have a 51% relapse‐free and 82% overall survival. In spite of the high relapse rate in stage IIIA patients, the majority are currently disease‐free following retreatment with MOPP chemotherapy. Stage IIB and IIIB patients received either radiation therapy alone or combined with chemotherapy. While the relapse‐free survival is similar in stage IIB patients with or without the addition of chemotherapy, combined TNI and MOPP chemotherapy in stage IIIB patients has provided a superior relapse‐free survival (74%) when compared to patients treated with TNI alone. There have been 3 mantle irradiation‐related deaths in 209 patients treated (1.5%); in contrast, there have been 6 deaths related to combined‐modality treatment in 74 patients at risk (8%). We continue to advocate the minimum therapy needed to produce uncomplicated cure. We feel that this is achieved with radiation therapy alone in stages IA and IIA disease without extensive mediastinal involvement and with combined modality therapy in stage IIIB disease. The role of combined modality therapy in place of radiation therapy alone in stage IIB and IIIA disease is less certain.

Can pelvic irradiation be omitted in patients with pathologic stages IA and IIA Hodgkin's disease?

From April 1969 to December 1973, 81 unselected laparotomy‐staged IA and IIA patients with supradiaphragmatic Hodgkins disease were treated at the Joint Center for Radiation Therapy. Mantle and para‐aortic fields alone were treated to 3600‐4000 rads. Median follow‐up was 31 months. There were six relapses including three true recurrences, two extensions, and one extra‐nodal dissemination. Relapses were not related to histologic type. There were no pelvic or inguinal extensions. Disease‐free survival was 95% in stage IA patients and 86% in stage IIA patients. Only one patient died of disease, with an overall survival of 96%. These results indicate that mantle and para‐aortic irradiation is sufficient treatment for pathologic stage I and IIA supradiaphragmatic Hodgkins disease. Such treatment obviates the need for pelvic irradiation or combination chemotherapy without compromising the success of treatment.

Combined irradiation and surgery in the treatment of stage II carcinoma of the endometrium

Between January 1969, and August 1975, 40 patients with pathologic Stage II carcinoma of the endometrium were treated at the Joint Center for Radiation Therapy. The treatment policy included external and intracavitary irradiation combined with surgery. The majority of patients received 4000 mg/hours of radium exposure using a Fletcher‐Suit applicator and 4000 rad whole pelvis external irradiation, followed by hysterectomy and bilateral salpingooophorectomy. Median age of the patients was 61 years (39–88) and the median followup of the patients still alive was 69 months (29–102). Relapse‐free 5‐year survival corrected for intercurrent disease was 83% and uncorrected, 78%. Overall survival was 80%. Five patients had relapsing disease, three patients failed at distant sites only, one patient died of treatment related complications, and two failed locally and distantly. There were no failures in the pelvis alone. Although the relationship between histologic grade and failure is not statistically significant, there were four failures among the 12 Grade III patients compared to two failures in 27 with Grades I and II. Similarly, 4 of 12 patients with gross cervical involvement developed relapsing disease, but only 2 of 28 failed with microscopic cervical involvement. This treatment policy yields excellent survival and continues to be our treatment recommendation.

Stages I--III Hodgkin's disease in children: results of staging and treatment.

Fifty‐two children with clinical stages I‐III Hodgkins disease were evaluated for disease extent between April 1969 and March 1975. All underwent laparotomy and splenectomy. Two patients with liver involvement were excluded. Thirty of 31 patients with pathologically staged IA‐IIA disease have been in continuous complete remission after mantle and para‐aortic irradiation. There have been no extensions into the untreated pelvis. Fourteen of 15 patients with pathologic stages IIB and IIIB disease show no evidence of relapse after TNI and MOPP. Three of four patients with stage IIIA disease developed nodal relapse after irradiation; all are alive without evidence of disease after re‐irradiation (3) and MOPP (2). Thus 45 of 50 patients (90%) have remained continuously free of disease after completion of the planned treatment, and overall 49 of 50 (98%) are alive without evidence of disease. Such results justify continuation of our staging and treatment philosophy in children with Hodgkins disease.

An evaluation of total nodal irradiation as treatment for stage III a Hodgkin's disease

Between April 1969 and December 1974, 37 patients with surgically staged III A Hodgkins disease were treated with total nodal irradiation (TNI). Their probability of relapse‐free survival at 7 years is 51% and overall survival 82% with the majority of patients remaining disease free after retreatment with MOPP (10 of 16). In contrast, 21 stage III B patients treated with TNI and MOPP chemotherapy over the same time period have a relapse‐free survival of 74% and overall survival of 91%. Because of superior results in treating stage III B patients with combined modality treatment, we feel that a relapse‐free survival of 51% may not justify continuation of TNI as the only modality of treatment for patients with stage III A disease, and we have initiated a trial of combined radiation therapy and MOPP chemotherapy in these patients. The most effective treatment of stage III A Hodgkins disease, however, remains uncertain and depends both on the ultimate risk of combined modality treatment and the success of retreatment following relapse after radiation.

Herpes Zoster in Children with Stage I–III Hodgkin's Disease

Herpes zoster infection developed in 12 (52%) of 23 children with Stage I-III Hodgkins disease but had no prognostic significance. Of these 23 patients, 22 are presently alive without evidence of active Hodgkins disease. The authors conclude that a combination of factors is important in the high incidence of herpes zoster, including more aggressive staging as well as more aggressive irradiation and chemotherapy, and that the results in their series would seem to justify continuation of this approach to staging and treatment in such cases.

The role of postoperative irradiation in carcinoma of the endometrium

Abstract The role of adjunctive irradiation in the management of Stage I carcinoma of the endometrium is reviewed. Primary surgical management is accepted therapy. Less certain is the use, type, and timing of adjunctive irradiation. The data indicate that irradiation decreases the incidence of vaginal recurrence and improves survival. The type and timing of irradiation is uncertain; however, we favor intracavitary irradiation primarily, with external beam therapy added for the enlarged uterus, poorly differentiated histology, and myometrial invasion. An outline of the timing of intracavitary or external irradiation in the various clinical circumstances is included.

The role of staging laparotomy in combined modality therapy of Hodgkin's disease: A new treatment plan based on a 6-year experience

From 1969 to 1974, staging laparotomy was performed on 187 consecutive patients with Hodgkins disease. Laparotomy changed the type of therapy in 59 of 187 patients (32%). Major staging revisions were: IIA to IIIA, 20 patients; IIIA to IA, 6 patients; IIIA to IIA, 12 patients; IIB to IIIB, 14 patients; and IIIB to IIB, 4 patients. Of stage II patients, 32 of 101 (32%) became stage III and of stage III patients, 24 of 61 (39%) became stage I or II. Forty-four patients with stage IIIA disease received 3,600–4,000 rad total nodal irradiation and their probability of relapse-free survival at 5 years was 52%. No relapses occurred in 11 stage IIB patients given combination of mantle and periaortic irradiation plus MOPP. Only 3 of 19 stage IIIB patients treated with total nodal irradiation and MOPP relapsed. Stage IIB patients with combined therapy had a diseasefree survival of 100%, while stage IIIB patients had a relapse-free survival of 77%. These striking results have led to a new treatment plan. Clinical stage IIA, pathological stage IIIA patients, and those with stage IIB disease now receive a combination of mantle and periaortic irradiation plus MOPP. Clinical stage IIIA, pathological stage IIIA patients, as well as those with stage IIIB disease, receive total nodal irradiation and MOPP. Surgical staging in this series has proved essential for effective and precise therapy.RésuméEntre 1969 et 1974, 187 malades atteints de maladie de Hodgkin ont subi une laparotomie pour préciser le stade de laffection. Dans 59 cas (32%), cette exploration a modifié le plan thérapeutique. Les réévaluations les plus importantes ont été: 20 cas sont passés du stade IIA au stade IIIA, 6 de IIIA à IA, 14 de IIIA à IIA, 12 de IIB à IIIB et 4 de IIIB à IIB. Sur 101 malades classés stade II, 32 (32%) sont devenus des stades III; sur 61 malades classés stade III, 24 (39%) sont passés aux stades I ou II. Quarante-quatre malades au stade IIIA ont reçu une irradiation ganglionnaire totale de 3600–4000 rad, et leur espérance de survie à 5 ans sans récidive est de 52%. Il ny a eu aucune récidive chez 11 patients au stade IIB traités par irradiation en capeline et périaortique combinée à une chimiothérapie (moutarde azotée, vincristine, procarbazine et prednisone: MOPP). Sur 19 cas au stade IIIB traités par irradiation ganglionnaire totale et MOPP, 3 seulement ont récidivé. Il y a 100% de survies sans récidive pour les malades au stade IIB traités par irradiation + MOPP, et 77% pour les stades IIIB. Ces résultats remarquables nous ont amenés à modifier les schémas thérapeutiques. Les stades IIA clinique et IIA histologique, et les stades IIB sont maintenant traités par irradiation en capeline et périaortique + MOPP. Les stades IIIA clinique et IIIA histologique, et les stades IIIB sont traités par irradiation ganglionnaire totale + MOPP. Dans notre série, la laparotomie sest donc révélée être un acte essentiel pour prescrire une thérapeutique précise et efficace.