Angelo Lattuada

Improved five year survival after combined radiotherapy-chemotherapy for stage I-II non-hodgkin's lymphoma

Abstract In order to improve the prognosis of patients with localized non-Hodgkins lymphomas (NHL) who are treated with radiotherapy (RT), a prospective controlled study utilizing a combined modality approach was carried out in patients with pathologic Stage 1[-II NHL. After treatment with regional RT, patients in complete remission were randomized to receive either no further therapy or 6 cycles of cyclophosphamide, vincristine and prednisolone (CVP). At 5 years from completion of irradiation, the relapse-free survival was 46.3% after RT and 72.1% after RT plus CVP ( P = 0.005). The corresponding findings for the overall survival calculated from the beginning of irradiation were 55.8 and 82.8% respectively ( P = 0.03). The favorable effects of adjuvant chemotherapy on relapse-free survival were statistically significant only in the subgroup with diffuse histology. In patients who relapsed after RT alone, the salvage therapy failed to induce a high incidence of second durable remission. Adjuvant chemotherapy is indicated to improve the cure rate in pathologic stage I-II NHL with diffuse histology when regional RT is utilized.

Natural history of dysgerminoma

Data on 56 patients with pure dysgerminoma are discussed. Forty-nine patients were classified as having new disease or were to have reassessment of disease, and seven cases were to be restaged (one with and six without clinical evidence of disease). Of new and reassessment cases, 44 patients underwent lymphography, 16 underwent peritoneoscopy with diaphragmatic inspection and 30 had peritoneal cytologic testing performed. Positive lymphography resulted in restaging in 31.6% of patients. Diaphragmatic inspection was always negative. Peritoneal cytologic testing was positive for malignant cells in three patients and worsened the stage in one. Pathologic staging of disease was as follows: Stage IA, 24; Stage IB, one Stage IC, one; Stage III peritoneal disease, two. Stage III retroperitoneal disease, 12; Stage III peritoneal and retroperitoneal disease; four. The 5-year relapse-free survival rates were 91% in patients with pathologic Stages IA, IB, and IC; 74% in those with Stage III retroperitoneal disease, and 24% in patients with Stage III peritoneal disease or peritoneal plus retroperitoneal disease. The results indicate that the prognosis is excellent for patients with Stage I and Stage III retroperitoneal disease whereas peritoneal involvement is associated with a poor prognosis.

Recent trends in the treatment of non-Hodgkin's lymphomas.

Abstract The results of new effective therapies as well as of new treatment approaches for non-Hodgkins lymphomas are reviewed. Despite the limitation of a broad spectrum of obstacles precluding effective comparisons of case series, recent data allow to draw some practical therapeutic considerations. In early stages classified on pathological bases, megavoltage radiotherapy still represents the treatment of choice, and the cure rate after adequate doses and fields is achieved in about 60% of patients. One controlled study showed a significant improvement in the disease-free survival by adding chemotherapy to the irradiation. In advanced disease, a number of multiple drug treatments has produced a definite increase in the incidence of complete remission as well as a longer median survival compared to single agent therapy. Childhood lymphomas were shown to be controlled only by aggressive combined modalities. After either radiotherapy or chemotherapy patients free of disease at two years from the end of treatment can be considered cured if their primary disease was a diffuse histiocytic lymphoma. This definition of cure is less applicable to patients with lymphocytic lymphomas because of their pattern of continuous late relapse. Although the Rappaport histopathologic classification has demonstrated the prognostic importance of nodular and diffuse lymphomas, new functional classifications, if found applicable and reproducible, might improve in future the correlation between morphology and clinical findings. However, the progress is expected to be slow and difficult.

Lymphangiography in patients with ovarian epithelial cancer: an evaluation of 289 consecutive cases.

From January, 1973, to June, 1976, 226 patients with palpable ovarian masses were evaluated preoperatively by lymphography. Histology showed 166 cases of malignant epithelial tumors, 26 benign tumors, and 34 malignant special tumors (not included in this report). Furthermore, the group of patients included 99 recurrences of ovarian epithelial cancer and 24 patients who underwent restaging diagnostic procedures without clinical evidence of disease. Lymphography was negative in all patients with benign tumors. In the 289 cases of epithelial cancer, lymphangiography gave evidence of nodal metastases in 88 (30%). When the histological subtype was considered, the highest incidence of metastases was in undifferentiated carcinoma (50%) and the lowest, in mesonephroid carcinoma (14%). According to the stage before lymphography, nodal metastases were found in 8% of Stage I, 0% of Stage II, 29% of Stage II, and 53% of Stage IV cases. The incidence of metastases was 46% in patients studied for recurrent disease and 17% in patients studied for restaging. Fifty‐four percent of patients had metastases only in the pelvic nodes and 18% only in the para‐aortic chains; in 28% both chains were involved simultaneously. Bilateral involvement was found in 63% of the positive cases. Retroperitoneal node biopsies were performed in 68 patients (36%). The radiologic/histologic correlation was 100% in the lymphangiographically positive cases; 81% in the negative cases, with nine false‐negative reports; and 87% in all cases.

Combined modality treatment for stage I–II non-hodgkin's lymphomas: CVP versus BACOP chemotherapy

This paper reports the 5-year results of a prospective randomized study beginning in 1976 on 177 evaluable patients with pathologic Stage I-IE and II-IIE non-Hodgkins lymphomas with diffuse histology according to the Rappaport classification. Treatment consisted of either CVP or BACOP chemotherapy (3 cycles) followed by regional radiotherapy (40 to 50 Gy) and further cycles of either combination. In both arms, complete remission at the end of combined treatment was high (CVP 93%, BACOP 98%) regardless of age, stage or bulky disease. At 5 years, the comparative freedom from first progression was 62% for CVP vs 78% for BACOP (p = 0.02), respectively. Clinically relevant differences favoring BACOP chemotherapy were essentially documented in patients with large cell lymphomas (International Working Formulation), those with Stage II having more than three involved anatomical sites, bulky disease and age over 60 years. Recurrence within radiation fields was documented in only 5% of complete responders. Combined treatment was, in general, well tolerated particularly when BACOP was used. In only 2 patients given CVP post radiation cutaneous fibrosis was documented. Second solid tumors were detected in 4 patients. One patient started on CVP died because of brain stem necrosis after 45 Gy. We conclude that in Stage I-II patients with nodal and extranodal diffuse non-Hodgkins lymphomas, particularly large cell lymphomas, combined modality approach with primary Adriamycin and bleomycin containing regimen, such as BACOP, followed by adjuvant radiotherapy offers high chances of cure with minimal toxicity.

Germ cell tumors of the ovary: The experience of the national cancer institute of milan. I. Dysgerminoma

The experience of the Istituto Nazionale Tumori of Milan on dysgerminoma is presented. Between 1970 and December of 1982, 25 patients were treated with a unique protocol which considered surgery and radiotherapy with different schedules according to the extension of the disease. With this treatment protocol all 13 patients at Stage I were alive and free of disease with a median follow-up of 77 months. Of 12 patients at Stage III (10 retroperitoneal and 2 retroperitoneal and peritoneal) 4 relapsed. The 5-year relapse-free survival of Stage III patients was 61.4% and the overall survival 89.5%. Amenorrhea due to radiation dose absorbed by the contralateral shielded ovary was found in 7.7%. The excellent results in Stage I patients were balanced by the unsatisfactory results in Stage III patients. A more aggressive treatment and the knowledge of other prognostic factors seem necessary.

Sequential half-body irradiation as systemic treatment of progressive ewing sarcoma

Sequential half-body irradiation (HBI) to be delivered in two sessions was used in 18 consecutive patients with metastatic Ewing sarcoma who relapsed after radiotherapy and multidrug chemotherapy. The HBI program to both upper and lower hemi body was completed in 11 patients (61%). The remaining 7 patients received only one single treatment of HBI because of relapse before the completion of the treatment program. In 20 of the 29 sessions HBI was employed to treat overt metastases. The overall objective response rate was 50%. Six of 18 patients (33%) are alive from 4 to 27 months, 3 of them without evidence of disease. No severe toxicity was observed. HBI as systemic treatment was more effective in patients who relapsed while off chemotherapy, with metastases confined to the lungs or to one single bone segment.

Ten years experience with Ewing's sarcoma.

The series comprises 57 consecutive patients with Ewings sarcoma admitted to the National Cancer Institute of Milan from 1965 to 1976. In 75 % the disease was confined to one bone, while in 25 % multiple bone and/or visceral lesions were present. Patients with clinically localized tumor treated before 1971 with local therapy, showed a median disease-free survival of 5 months. After 1971, radiotherapy and/or surgery to local tumor was combined with multiple drug chemotherapy (ADM, VCR, CTX) and the projected median disease-free survival increased to 24+ months. In previously untreated patients with advanced tumor adriamycin, used as single drug, achieved an overall response rate of 73 %. This is comparable to that achieved by a new combination including ADM, VCR, CTX, CCNU (75%). This multiple drug regimen is, however, expected to prolong the duration of response.

Non-Hodgkin's lymphomas of Waldeyer's ring.

From 1970 to 1980, 171 consecutive cases with non-Hodgkins lymphomas (NHL) of Waldeyers ring were admitted to this Institute. The cases were reviewed to evaluate whether involvement of Waldeyers ring might represent a distinct clinicopathologic entity. Adequate pathologic staging was performed in 86% of cases. All slides were reviewed, and the histologic diagnosis given according to the Rappaport classification, the Kiel classification, and the recent Working Formulation of NHL for Clinical Usage. Waldeyers ring alone was involved in 12.3% of the cases at presentation; regional nodes were positive in one-third (35.7%), and distant involvement was detected in half of the patients (52%). The tonsils represented the most frequent site of involvement by NHL within Waldeyers ring. Treatments employed were heterogeneous, but most of the patients with stage I-II received radiotherapy alone. The present series shows that the association of involvement of Waldeyers ring and the stomach by NHL occurs in less than 10% of the cases. Treatment results and patterns of recurrence fail to differentiate NHL involving Waldeyers ring from those of other sites. Prognosis remains related to the classical variables and is independent of the site of onset.

Adjuvant irradiation after radical surgery of cancer of the rectum and rectosigmoid

From January 1975 through December 1983, 74 consecutive patients were given adjuvant radiotherapy on the whole pelvis after radical surgery for locally advanced rectal (44 cases) and rectosigmoidal (30 cases) cancer. Most patients received 45 Gy to the whole pelvis in 5-7 weeks through AP, PA opposed fields. Fourteen patients were also given adjuvant chemotherapy. Minimum follow-up time of the series is 24 months and median follow-up is 36 months. First relapse was evaluated. Pelvic failures occurred in 17.5% of patients, while distant metastases rate was 32%; median time to relapse was 18 and 10 months respectively. Thirty patients (40.5%) never relapsed and are alive and well, while five additional patients are alive with disease. Four patients died of treatment toxicity. Thirty-one patients died of cancer (41.9%); 8 of them from pelvic failure only. Actuarial relapse-free survival at 3 and 5 years was 51.7% and 46.8%, while actuarial overall survival was 63% and 49%.