Search

The authors describe the results of 71 patients with clinical stage I A (40 patients) and II A (31 patients) primarily treated with radiotherapy alone (61 mantle fields and 10 subtotal-nodal plus spleen irradiation). All patients achieved complete remission at the end of the treatment; 31 (43.7%) patients (15 at stage I and 16 at stage II) relapsed during the follow-up, mostly for nodal or extranodal extensions (87% of relapses). In 21/31 relapsed patients chemotherapy +/- radiotherapy was utilized as salvage treatment. Three patients died for second solid tumors and 1 patient died for jatrogenic late effect (leukemia after 4 cycles of MOPP). Despite the high percent of relapses, the long term overall survival (83.4%) of these patients is quite satisfactory mostly for the efficacy of chemotherapy as salvage treatment. However the authors think that laparosplenectomy plus subtotal-nodal irradiation is the treatment of choice for patients with Hodgkin disease at stage I and II A. Chemotherapy, instead, must be primarily utilized only for patients with a worse prognosis for hilar adenopathies or "bulky" mediastinum.

During a preliminary clinical experience (1973-1977) we experimented three different sequences in associating 6 MOPP cycles (CT) with radiotherapy (RT) for the treatment of stage II and III Hodgkin's disease. A total of 55 consecutive previously untreated patients can be estimated to contribute in defining feasibility, immediate results and toxicity of the combined treatment. In this group of patients RT preceded CT in 20 cases (RT-6 MOPP), the opposite sequence (6 MOPP-RT) was preferred in 16 cases, whilst a split-course CT fitting in the RT (3 MOPP-RT-3 MOPP) was employed in 19 cases. Except for the sequence used with respect to irradiation, the CT was carried out in all the cases according to the classical scheme proposed by De Vita et al. (11). RT was effected with 60Co-teletherapy and a wide field or segmental sequential fields, having variable extension depending on the stage ("extended nodal irradiation" for stage II and III cases with lymph node involvement not below L3; "total nodal irradiation" for the remaining cases in stage III). The programmed doses were 45.0 Gy to the involved areas and 40.0 Gy to the clinically uninvolved regions for the RT-6 MOPP and 6 MOPP-RT groups. Doses of 35.0/30.0 Gy were planned for the 3 MOPP-RT-3 MOPP group. The three different groups are not homogeneous with regard to certain important clinical and pathological characteristics; in fact, a higher quota of stage III patients, with systemic symptoms and spleen positivity is present in the 6 MOPP-RT and 3 MOPP-RT-3 MOPP groups. The combined treatment has achieved a complete clinical remission in 18/20 patients in the RT-6 MOPP group (90.0%), in 12/16 patients of the 6 MOPP-RT group (75.0%), and in 17/19 cases in the 3 MOPP-RT-3 MOPP "sandwich" combination (89.5%). The average overall duration of the treatment was 48 weeks for the sandwich combination, 50 weeks for the RT-6 MOPP group, and 56 weeks for the 6 MOPP-RT association. As regards the sandwich combination, both CT and RT took a reasonable length of time to complete. On the contrary, both the medical treatment and irradiation required an excessively long time and were not well tolerated when preceded by either RT or CT in full doses. In particular, myelosuppression was less acute and prolonged in the 3 MOPP-RT-3 MOPP group, whereas the actual doses of CT and RT were higher than those which can be reached with respect to other groups. Three preliminary cycles of CT considerably reduce the target volumes and complications arising from RT. The first CT time gave an objective response greater than 50% in 9/9 cases of the 3 MOPP-RT-3-MOPP group with mediastinal involvement. In this group, rather considerable pulmonary complications were observed in 3/9 patients (33.3%) with respect to the 40% found for the 6 MOPP-RT group (2/5 cases) and the 67.7% for the RT-6 MOPP group (6/9 cases).

Thirty-three chordomas were observed at the Istituto Nazionale Tumori of Milan from 1933 to 1983: 27 sacrococcygeal, 3 spheno-occipital, and 3 vertebral. The male:female ratio was 2.7, and the median age was 63 yr for patients with sacrococcygeal and 35.2 yr for those with nonsacral chordomas. After pathologic reassessment, distinct cytologic patterns were found: physaliphorous, syncytial, and mixed subtypes, with variable degrees of cytologic atypia. However, no evident difference in survival was documented in relation to these cytohistologic features. Four cases had a prior traumatic fracture, and the pathogenetic role of trauma is stressed. Eight cases were operated with adequate surgery and only three recurred, whereas of 11 inadequate operations, 10 developed local relapse. However, follow-up for recent adequate operations is short. Radiation therapy seemed to be effective with adjuvant or palliative aims. No chemotherapeutic regimen achieved any result; one case had a short complete remission after cis-dichlorodiammineplatinum + vinblastine + bleomycin (PVB). This analysis confirms the possibility of achieving radicality with high resection of the sacrum for lesions confined below the second sacral vertebra. Nonsacral chordomas were all unresectable. The best treatment for unresectable lesions seems to be palliative surgery plus radiotherapy.

Ninety-four patients with T2 NO, N1a, N1b, MO were treated with primary radiotherapy (RT) because of old age or poor general conditions. In 32 patients (34%), younger in age and in better general conditions, Halsted radical mastectomy could be performed 5-8 months from starting RT; surgery was not done at random, but decided case by case on the basis of a good response to RT and an improvement of general status. Relapse was documented in 42 patients. Relapse rate was 50% in the group treated with RT alone (high incidence of breast recurrences) and 33% in the group operated on after RT. Distant metastases had the same incidence in the 2 groups, with a median free interval of 14 months. Overall disease-free survival rates at 5 to 10 years were 46% and 35%, respectively; these results are not particularly different from the data of historical series of T2 breast cancer treated with surgery alone. The patients operated on after RT had a significantly better survival, but the results were clearly influenced by the selection of patients. For the future, a safe policy could be a conservative combined treatment consisting of tumorectomy followed by curative RT; adjuvant medical therapy could be scheduled for high-risk patients (N1b).

Preliminary results of a randomized study (radiotherapy versus radiotherapy plus weekly low-dose cisplatin) are reported. Fifty-four patients (43 evaluable) with stage IIIa-b non small cell lung cancer were randomized. Objective responses (CR + PR) were seen in 62% of the radiotherapy-treated group and in 63% of the group treated with radiotherapy plus cisplatin. No major toxicity was seen. Patient compliance for both treatments was satisfactory.

Cumulative 5 years survival following radiotherapy for carcinoma of the nasopharynx does not exceed 30 divided by 35%. Better survival rates are reported in patients with primary lesion of limited extent (T1) or without neck lymph node involvement (N0): 5 years survival 50 divided by 60%. Reports from the most recent series and a review of 159 cases treated at National Cancer Institute of Milano indicate the prognostic significance of the histological type. The 5 years survival rate for "well differentiated carcinoma" ranges from 10 to 34%, in comparison with 25 divided by 50% for the "undifferentiated" type. Local recurrence and invasion of the base of the skull are seen more frequently in the "well differentiated" group while the "undifferentiated carcinoma" shows a stronger tendency to distant metastases (30 divided 35%). On the base of these data a more selected therapeutic approach is suggested.

From 1974 to 1982 a total of 58 patients with locoregional breast cancer, judged not suitable for demolitive surgery because of old age, bad general conditions or other reasons, were treated with simple tumorectomy followed by radiotherapy. The median age of the patients was 71 years. Two patients had synchronous bilateral breast cancer, both treated with the same conservative approach. Thirty-three tumors were classified as T1, 24 as T2, 1 as T3, and 2 as T4 of a small size. The median size of the tumor was 2 cm; mean size was 2.24 cm. Radiotherapy was given to the whole breast, followed by a conedown on the tumor bed. The median dose to the tumor bed was 64 Gy, over 7-9 weeks. Thirty-two patients received irradiation on nodal sites too, up to 45-60 Gy. The median follow-up for the whole series was 44 months. Only 4 of 60 treated breasts have presented a local recurrence (6.6%); relapse-free survival at 3 and 5 years is 85.4% and 79%, respectively. Our results confirm that tumorectomy followed by radiotherapy appears to be a very effective alternative to radiotherapy alone and to demolitive surgery. In fact, local control, survival and cosmetic results are quite satisfactory and achievable through a simple therapeutic modality.

Cis-Dichlorodiammine platinum (II) (cis-DDP) was demonstrated to be a potentiator of radiation therapy (RT) in experimental tumor models and in cultured cells. To assess the effectiveness of a combined modality treatment including RT and a weekly low-dose administration of cis-DDP, from January 1986 to June 1987, 95 patients with unresectable locally advanced non-small cell carcinoma of the lung (stage IIIa, b) were randomized for study. Fifty patients received RT alone at doses of 50 Gy; 45 patients received the same RT plus cis-DDP 15 mg/m2 IV weekly. An overall response rate of 50% and 64% was observed in the RT and RT + cis-DDP group, respectively. No statistically significant differences were detected with regard to median survival time (11 months for RT v 16 months for RT + cis-DDP) and progression-free interval (7 months in the RT arm v 9 months in the RT + cis-DDP arm), but the patterns of the first failure appeared to be affected by treatment. In fact, a lower number of intrathoracic relapses was observed in the RT + cis-DDP arm (12 in the RT + cis-DDP v 23 in the RT arm). Toxicity was mild and the feasibility of this schedule must be remarked. A better local control of disease can be obtained using cis-DDP as a radiation potentiator, but the true influence of this combined modality treatment on the length of survival, and the optimal cis-DDP timing and dosage are still to be evaluated in further clinical trials.

The aim of this paper is the analysis of the complications occurred after surgical and radiological procedures, for staging and treatment of malignant lymphomas and testicular carcinoma with an evaluation of the possible efficacy of their surgical treatment. At the Istituto Nazionale dei Tumori of Milan during the period 1970-1976, 718 patients with malignant lymphomas were staged with laparosplenectomy; 444 of them received radiotherapy on the abdominal area. Laparosplenectomy was not performed on other 123 cases that were irradiated as well on the abdominal area. Retroperitoneal lymphadenectomy or explorative laparotomy were carried out in 98 patients with carcinoma of the testis and 46 of them received adjuvant radiotherapy; other 29 were irradiated without previous surgical procedures. After surgery alone morbidity and mortality rate were 2.7% and 0.73% respectively. The mortality/morbidity ratio was 26%. The incidence of complications after radiotherapy alone was 3.3%. No deaths followed the treatment. Combined treatment had a morbidity rate of 5.5% and mortality rate of 2%. The mortality/morbidity ratio was 37%. Complications were treated mainly by surgery: out of 50 interventions, 22 were intestinal resections. New secondary complications were however frequent (more than 50% after intestinal resection) especially in patients originally treated with laparosplenectomy or retroperitoneal dissection plus radiotherapy.

In a prospective randomized study, the efficacy of two combined modality approaches (chemotherapy plus radiotherapy or chemotherapy plus mastectomy) was tested in a total of 132 women with locally advanced breast cancer. Chemotherapy consisted of Adriamycin plus vincristine (AV) administered for three cycles before either local-regional modality and subsequently for seven additional cycles. Although a higher proportion of women achieved complete remission after mastectomy (100%) compared to women given radiotherapy (60%), the total response rate at the end of combined modality was identical (75%). There was no significant difference between the two treatment groups in terms of patterns of treatment failure, median duration of response, and total survival. Treatment was not influenced by menopausal or estrogen receptor status. Two patients of the surgical group showed Adriamycin-induced cardiomyopathy after cumulative doses less than 500 mg/m2. The results of present study failed to indicate that surgery per se improved the overall results including local control, over radiotherapy in a combined modality setting.

The radiographic documentation for over 300 malignant lymphoma patients who received radiotherapy to the hilo-mediastinal regions at the National Cancer Institute of Milan is examined with a view to ascertaining the pleuroparenchymal and cardiomediastinal sequelae of irradiation in a fairly homogeneous series in respect of treatment techniques. Early and late lesions of varying severity, mild, marked and severe, were found in 60% of the patients. Only in 15% were the lesions severe; in 6% pronounced pleural effusions were found and in 1.2% exudative pericarditis. To identify the etiological factors, the lesions were correlated with several variables: patient age, disease stage, pretreatment condition of the intrathoracic organs, radiotherapeutic techniques and doses, and combined therapy with Bleomycin at the doses usually given in the treatment of lymphomas, where relevant. Of these factors only the radiotherapeutic technique (site and number of fields, division of dose) and especially the dose absorbed seem to be relatively closely related to the frequency and severity of the post-irradiation lesions. There seem to be other factors in the genesis of these lesions, probably related to individual reactivity, but for these we have no evaluation parameters.

Local surgical failures of rectal and rectosigmoidal cancer are often observed and represent a heavy clinical problem from the viewpoint of quality of life. After having referred bad results of radiotherapy in a group of 55 patients locally relapsed after radical surgery, the authors analyse causes of therapeutic failure, underlining that ineffectiveness of radiation treatment comes mainly from late and, frequently, not complete diagnosis. Computed tomography must be currently considered the best way for monitoring these patients in order to get an earlier detection and the most correct radiation treatment plan.

From 1973 to 1980, a controlled clinical trial was carried out at the National Cancer Institute of Milan to compare the Halsted mastectomy with breast quadrantectomy and axillary dissection followed by radiotherapy in patients with breast cancer of less than 2 cm in size. Cases of breast cancer classified as T1N0 were randomized into the two treatment procedures: 349 cases were treated with the Halsted mastectomy and 352 with the quadrantectomy technique. The two series were comparable with regard to age distribution, size, site of primary tumor, menopausal status and frequency of axillary metastases. Three local recurrences occurred in the Halsted group and one in the quadrantectomy group. Actuarial curves showed no difference in the two series with regard to disease-free and overall survival. In view of these results, mastectomy appears to be an unnecessary mutilation for patients with breast carcinomas less than 2 cm in size and no palpable axillary nodes.

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%.

154 cases of breast cancer (30 T1-52; 124 T3-54) treated by irradiation followed by radical mastectomy were subjected to histological revision in order to check the efficacy of radiotherapy in the local control of cancer and to seek correlations between the histological findings and the clinical course of the disease. The tumor disappeared completely only in 24% of cases, the percentage being higher in the initially smaller tumors; the axillary lymph nodes showed disappearance of the metastases in a still smaller proportion of cases, namely 15-20%. Only in 16 cases (10% of cases) were the histological findings negative both at mammary and axillary levels. X-ray therapy and cobalt therapy were of equal value in the local control of the disease, despite the higher doses of cobalt. The patients operated on after radiotherapy had a decidedly better survival rate than those treated with irradiation only, since the former were selected because of their better clinical course and operated on because of this. Of the operated patients those whose axillary histology was negative presented a higher survival rate (75% of patients living) than those whose findings were positive (53%). Factors of negligible importance prognostically were: complete sterilization at mammary and axillary level after radiotherapy, persistence of florid cancer tissue at mammary level and histiocytosis of the axillary lymph nodes. In short, the result of locoregional therapy, even when successful, was not crucial in the general control of the disease, especially in advanced locoregional breast cancer (T3-T4 with axillary metastases).

Prolonged follow-up of large series of patients treated for Hodgkin's disease with an intensive therapeutic approach has demonstrated an incidence of second tumors of around 5-10%. Acute leukemia is the most frequent second neoplasia, and treatments including alkylating agents and radiotherapy seem to be correlated with a higher risk of this fatal complication. Bone and soft tissue sarcomas have rarely been observed after treatment of Hodgkin's disease, and only a few cases are described in the literature. Four cases observed at the Istituto Nazionale Tumori of Milano in a large series of nearly 800 patients treated over the last two decades with different modalities are presented. One case of chondrosarcoma and 3 cases of soft tissue sarcomas were diagnosed after a median and mean interval of 50 and 70 months, respectively (range 49-96). Three patients had been treated with radiotherapy plus chemotherapy (MOPP, 2 cases; ABVD, 1 case), and one with radiotherapy alone. The site of the second tumor was always within an irradiated area, which had received a dose ranging from 10 to 43 Gy. Prognosis of secondary bone and soft tissue sarcomas is very poor. Three of our cases died 14, 15 and 19 months after diagnosis; only one patient is alive, 3 months after diagnosis of a chondrosarcoma. The problem of second tumors in patients treated for Hodgkin's disease requires a careful evaluation of aggressive treatment modalities to minimize the risks of this severe complication.

The clinical records of 66 patients with T4 (for skin infiltration or ulceration) breast cancer not larger than 5 cm treated with primary radiotherapy at the Istituto Nazionale Tumori of Milan from 1968 through 1977 were reviewed. The tumor measured no more than 3 cm in 19 patients and 3-5 cm in 47 patients. In the first group axillary involvement was lower (32% vs 55%) and mean age was older (68 years vs 58). Thirty-four patients were irradiated with orthovoltage and 32 with cobalt, at full doses. In 22 of 66 patients (33.3%) a Halsted radical mastectomy was carried out after completion of radiotherapy. No medical treatment was planned. The incidence of locoregional and distant metastases was the same in both groups of patients, but that of patients with smaller T4 (up to 3 cm) demonstrated a better prognosis in terms of absolute survival at 5 years (71.3% vs 34.7%). T4 breast cancer of 3-5 cm had very poor results quite similar to those of historical large series of T4 carcinomas of any size; therefore they should be treated by the same aggressive combined modality approach adopted for locally advanced breast cancer. On the contrary, small T4, up to 3 cm, in older women could be treated by tumorectomy followed by radiotherapy at full doses; systemic medical therapy (hormonal manipulation or chemotherapy) should be decided according to endocrine receptor investigation and general conditions.

From 1973 to 1980, we carried out a controlled study at the National Cancer Institute in Milan to consider the value of a conservative procedure in patients with breast cancer of small size. We randomized 701 patients with breast cancer measuring less than 2 cm in diameter and with no palpable axillary lymph nodes to Halsted radical mastectomy or to "quadrantectomy" with axillary dissection and radiotherapy to the ipsilateral residual breast tissue. We treated 349 patients with Halsted mastectomy and 352 with quadrantectomy. The two groups were comparable in age distribution, size and site of primary tumor, menopausal status, and frequency of axillary metastases. There were three local recurrences in the Halsted group and one in the quadrantectomy group. Actuarial curves showed no difference between the two groups in disease-free or overall survival. From these results, mastectomy appears to involve unnecessary mutilation in patients with breast cancer of less than 2 cm and no palpable axillary nodes.

From 1973 to 1980, 701 patients with breast cancer measuring less than 2 cm in pathological diameter and with no palpable axillary lymph nodes were randomized to Halsted mastectomy (349) or to "quadrantectomy" with axillary dissection and radiotherapy to the ipsilateral breast tissue (QUART) (352). The two groups were comparable in age distribution, size and site of primary tumor; menopausal status; and frequency of axillary metastases. At 8 years, the disease-free survival was 77% for the Halsted patients and 80% for the "quadrantectomy" patients, while overall survival was 83% and 85%, respectively. Disease-free and overall survival curves show no difference between the two groups. Breast cancer of small size (less than 2 cm) may be safely treated with conservative treatment. Mutilating operations are not justified.