Alberto Banfi

Breast conservation is the treatment of choice in small breast cancer: Long-term results of a randomized trial

From 1973 to 1980, 701 women with small breast cancer (less than 2 cm in diameter) were randomized into two different treatments. 349 patients received classic Halsted mastectomy and 352 patients received quadrantectomy, axillary dissection and radiotherapy on the ipsilateral breast. 24.6% of the patients in the mastectomy group and 27.0% of the patients in the conservation group had axillary metastases. Overall 10 year survival was 76% in the Halsted patients and 79% in the quadrantectomy patients; 13 year survival was 69% and 71%, respectively. No differences were observed after analysis by site and size of the primary tumour and age of the patients. Patients with positive axillary nodes had consistently better survival curves in the quadrantectomy group compared with the Halsted group (not significant). Among the quadrantectomy patients there were 11 local recurrences (with 4 deaths) while among the Halsted patients, 7 had local recurrences (5 deaths). There were 19 cases of contralateral breast carcinomas in the quadrantectomy group and 20 in the Halsted group. At 16 years from the beginning of the trial no evidence of oncogenic radiation risk was observed. In patients with small size carcinomas total mastectomy should have no role.

The CMF program for operable breast cancer with positive axillary nodes: Updated analysis on the disease-free interval, site of relapse and drug tolerance

In a prospective randomized study adjuvant combination chemotherapy with CMF was administered for 12 monthly cycles to 207 patients subjected to radical mastectomy (Halsted or extended) and treatment failure was compared to that observed in 179 patients whose primary therapy consisted only of radical surgery (control group). All patients of both groups had histologically positive axillary lymph nodes. At three years from mastectomy the total failure time distribution was 45.7% in control patients compared to 26.3% in women given CMF (P < 0.0001). New disease manifestations were higher in the subgroup with four or more nodes (64.9% vs 41.5%) compared to that with one to three nodes (37.9% vs 19.1%). Premenopausal controls showed a progressively higher incidence of treatment failure compared to CMF patients (P = 0.00001). The decreased recurrence rate in postmenopausal women given CMF was appreciable only during the first 12 months. From this time on, the difference no longer existed. The cumulative percent of recurrence in patients without or with drug‐induced amenorrhea (27.2% vs 9.2%) was not statistically significant. At three years 21.4% of control patients have died of progressive cancer compared to 10.4% of CMF patients. The difference in the survival curves was not significant (P = 0.08). Toxicity was moderate and reversible. No drug induced neoplasm was observed. Present results confirm the efficacy of 12 CMF cycles in premenopausal patients. Postmenopausal women probably require a more intensive and prolonged adjuvant chemotherapy.

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.

Second malignancies in Hodgkin's disease: A complication of certain forms of treatment

A total of 764 patients with Hodgkins disease treated with radiotherapy (RT) or chemotherapy or both were reviewed 3-186 months (median 43 months) after initial treatment to assess the incidence of second malignancies. Incidence of solid tumours and acute non-lymphoblastic leukaemia (ANLL) were calculated by a life-table method and percentages of patients affected derived from life-table plots. Within 10 years after initial treatment the overall incidence of second solid tumours was 7.3%, and over a comparable period 2.4% of patients developed ANLL. Solid tumours occurred only in patients given RT with or without adjuvant chemotherapy, and ANLL occurred only after treatment with MOPP (mustine, vincristine, procarbazine, and prednisolone) or modified MOPP regimens. Neither solid tumours nor ANLL occurred in patients given ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine). The highest incidence of leukaemia (5.4%) occurred after treatment with extensive RT plus (5.4%) occurred after treatment with extensive RT plus MOPP; hence the benefits of this approach in Hodgkins disease must be weighed against its carcinogenic potential.

Malignant Lymphomas of Waldeyer's Ring: Natural History and Survival after Radiotherapy

The natural history of 292 consecutive cases of reticulum cell sarcoma and lymphosarcoma of Waldeyers ring and the survival rate after radiotherapy are reported. In our institute since 1928 from 30 to 35% of pharyngeal neoplasms have been lymphomas, and of these 55% have been reticulum cell sarcomas, 21% lymphosarcomas, and 1% Hodgkins disease. This high incidence may probably be ascribed to the fact that in all malignant lymphomas, irrespective of the clinical presentation, a systematic biopsy of the whole Waldeyers ring was carried out. Pharyngeal lymphomas were confined to Waldeyers ring in 19·6% of cases, with initial spread to contiguous cervical nodes in 43·8%, to distant nodes in 24·2%, and to extranodal tissues in 12·4%. Lymphography showed abnormal retroperitoneal lymph nodes in 38·3% of cases. There was gastrointestinal involvement either initially or later in 17·6% of cases. High-energy radiation therapy to both sides of the neck was the treatment of choice for local and regional disease. It achieved a five-year survival rate of 41·9% in the group of 97 patients treated during the past decade. The incidence of relapse (recurrence and new manifestations) was highest in the first year after treatment.

LYMPHORETICULAR SARCOMAS WITH PRIMARY INVOLVEMENT OF WALDEYER'S RING. CLINICAL EVALUATION OF 225 CASES.

A total of 225 consecutive untreated patients with lymphoreticular sarcomas with primary involvement of Waldeyers ring was evaluated (151 without lymphography and 74 with lymphography). On admission, the anatomical distribution of the primary growth within Waldeyers ring was as follows: tonsil, 40%; nasopharynx, 27.5%; base of tongue, 2.7%; soft palate, 2.7%; oropharynx, 0.9%; other sites, 26.2%. In the group studied without lymphography, the disease was confined to Waldeyers ring in 22.5% of cases and had spread to the cervical nodes in 62.3% and to distant nodes in 15.2%. In the group studied more recently with lymphography, these figures were 13.5%, 41.9%, and 44.6%, respectively. At the time of initial evaluation, the lymphoma involved extranodal sites in only 24 of 225. In the 74 cases evaluated with lymphography, the mode of spread was studied by observing the first site of recurrence after radiotherapy. New manifestations occurred in most patients within 2 years from the end of treatment and preferentially in extranodal sites. The involvement of the gastointestinal tract, either at the time of admission or early in the follow‐up, was 20% in the group studied with lymphography. The possibility that a certain number of lymphoreticular sarcomas could arise concomitantly in Waldeyers ring and in the gastrointestinal tract is discussed.

Adjuvant CMF effect on site of first recurrence, and appropriate follow-up intervals, in operable breast cancer with positive axillary nodes

SummaryFrom June 1973 to May 1978 a total of 845 patients with operable breast cancer were entered into different adjuvant programs. The medical records of the 278 patients showing relapse were carefully re-evaluated to assess the pattern(s) of first recurrence and the consistency of follow-up modulation. Ninety-one of 179 patients treated with surgery alone, 130 of 414 given 12 cycles of adjuvant CMF and 57 of 252 treated with 6 cycles of CMF showed treatment failure within 5 years from radical mastectomy. Thefrequency of new disease manifestations was significantly affected by primary treatment, since patients given adjuvant CMF showed a lower tendency to recur in local-regional area(s) and in bone(s). However, in relapsed patients,patterns of new lesions were not substantially altered by type of primary treatment. The most frequently involved sites were soft tissues (37.8%) and bones (37%) followed by viscera (34.2%). Retrospective evaluation of X-rays revealed that in 26.2% of osseous metastases, diagnosis could have been assessed earlier, with a median delay of 4 months (range 1–8). Present analysis also revealed that short-term repeated X-ray examinations yielded findings more controversial than reliable for assessing the exact time of relapse, thus preventing firm conclusions in the presence of suspicious recurrence. A new follow-up schedule after completion of adjuvant chemotherapy is proposed, since on the basis of our experience, in asymptomatic patients frequently repeated examinations are not necessary and some can safely be omitted.

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.