Rado Kenda

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.

Natural history and survival of inoperable breast cancer treated with radiotherapy and radiotherapy followed by radical mastectomy.

This retrospective study evaluates the time and site of relapse as well as the median survival of 454 consecutive patients with T3‐T4 Nx Mo breast cancer treated with radiation therapy from 1968 to 1972. Radiotherapy was delivered with kilovoltage to the first 221 patients and with cobalt to 233 patients, respectively. A group of 133 selected patients was subjected to radical mastectomy 6–8 weeks after completion of the irradiation. The incidence of first relapse was 45% within the first 18 months from starting radiotherapy. The incidence of relapse was higher in presence than in absence of regional adenopathy, with no statistical difference between T3 and T4. Inflammatory carcinoma showed the highest percent of relapse during the first 12 months (48%). The relapse rate appeared independent from type of irradiation. The site of first relapse occurred more often (68%) in areas distant from irradiation fields. Sterilization of both primary tumor and regional nodes was obtained only in 10% of patients. The median survival for the whole series was 2.5 years, with no significant difference between roentgen therapy (3 years) and cobalt (2.5 years). Unfavorable survival was directly related to the presence of regional adenopathies (2.3 years), especially in the supraclavicular fossa (1.4 years) and of inflammatory carcinoma (1.2 years). Patients treated with radiotherapy followed by surgery showed a median survival of 3.9 years compared to 2.1 years for those given only irradiation. The importance of sequentially combining chemotherapy with radiotherapy is discussed.

Early breast cancer: evaluation of the prognostic role of the site of the primary tumor.

PURPOSE The prognostic role of the site of the primary breast cancer has not been clarified. This study aimed to gather more information about this issue from a large series of patients with long-term follow-up data. PATIENTS AND METHODS Data from 2,396 patients treated for early breast cancer with a conservative approach were reviewed (1973 to 1989). In 1,619 patients, the tumor had a lateral site, while in 777 cases, it was situated in the internal/central quadrants. The characteristics of the two groups were well balanced, apart from axillary nodal metastases, which were more frequent for lateral tumors (38.1% v 26.3%). RESULTS Analysis of distant metastases indicated that the regression coefficient associated with tumor site was significant and the hazards ratio estimate was 1.291, which indicates the risk of distant metastases was increased by approximately 30% for internal/central tumors. The analysis of overall survival yielded a significant coefficient and a hazards ratio of 1.192, which indicates an approximately 20% increase of mortality for internal/central tumors. CONCLUSION Early breast cancers situated in central/ internal quadrants have a worse prognosis compared with those in lateral quadrants, in terms of distant metastases and survival. Irradiation of the internal mammary chain for internal/medial tumors could be suggested, but, to date, the therapeutic strategy is still controversial.

Combined preoperative chemoradiotherapy followed by radical surgery in locally advanced vulvar carcinoma: A pilot study

Although for decades exenterative surgery has represented the standard treatment for patients with locally advanced vulvar cancer, combined approaches, including preoperative radiation with or without chemotherapy, are now considered the treatment of choice. We report the results of a pilot study on concurrent chemoradiotherapy followed by radical surgery for patients with locally advanced squamous cell carcinoma of the vulva.

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.

Analysis of risk factors for mandibular bone radionecrosis after exclusive low dose-rate brachytherapy for oral cancer.

BACKGROUND Brachytherapy is widely adopted as an exclusive treatment of T1/T2 oral cancer with a high probability of definitive cure. Therefore, any major complication, like mandibular bone necrosis, should be avoided. Many risk factors, either clinical or technical, have been considered in the literature. MATERIALS AND METHODS One hundred consecutive interstitial iridium LDR treatments for early cancers of the tongue and floor of the mouth performed from January 1989 to November 1993 were reviewed. An analysis of some simple technical parameters (total dose, dose-rate, reference volume, linear activity, total reference kerma) was performed in order to identify the main physical risk factors. Moreover, total dose was recalculated as extrapolated responsive dose for normal tissue complications. RESULTS Bone necrosis was observed in 10 out of 100 patients with a median follow-up of 38 months. No significant incidence of this complication was observed when tumor site (mobile tongue versus floor of the mouth), dental status or total physical dose were considered. A significant correlation between the incidence of bone necrosis and two main parameters was found, i.e. dose-rate (P < 0.02) and reference volume (P < 0.05). CONCLUSIONS A threshold value may be suggested both for dose-rate (50 cGy/h) and reference volume (25,000 mm3). Bone necrosis is clearly related to both these parameters since most cases (i.e. 80%) were observed in the subgroup over the volume and dose-rate threshold.

Adult granulosa cell tumor of the ovary: a clinico pathologic study of 35 cases.

Aims and background Adult granulosa cell tumor has a low malignant potential but requires an extensive follow-up of more than 5 years to accurately assess tumor activity. The aim of the present study was to evaluate the clinical characteristics, the treatment and the outcome of this rare ovarian tumor. Study design A retrospective review of 35 cases treated at primary onset of disease during a 23-year period from 1971 to 1993. Results The disease-free survival rate for stages IA-B-C at 5 and 10 years was 90% and 84%, respectively; for stages III-IV the 5-year freedom from progression rate was 16%. Conclusions The most important prognostic factor appears to be the extent of tumor involvement outside of the ovary.

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.

Nondysgerminomatous tumors of the ovary treated with cisplatin, vinblastine, and bleomycin: Long-term results

Twenty-four consecutive patients with nondysgerminomatous germ cell tumor of the ovary were treated after surgery with cisplatin, vinblastine, and bleomycin (PVB regimen). The cycle was repeated every 3 weeks for three to five courses. Fourteen patients had endodermal sinus tumor, and 10 had mixed germ cell tumors. Stage of disease (FIGO, 1986) was as follows: stage I, 6; stage IIc-IV, 17; and recurrence, 1 patient. All patients were monitored by alpha-fetoprotein and human chorionic gonadotropin. Only 1 patient had received previous chemotherapy. All 5 patients without residual disease and with negative marker levels in which PVB was used as adjuvant treatment were free of disease for a median duration of 59 months from the start of PVB. Of the 19 patients with measurable disease (evident disease or positive marker levels), complete remission was obtained in 16 (84%), but 5 of these relapsed. Therefore, treatment with PVB failed in 8 out of 19 patients (42%) with measurable disease. Toxicity was evident, but no patient died of it. Menses were regular in 11 patients whose initial surgery was conservative. PVB regimen is an effective but not a satisfactory treatment. The considerable failure rate of PVB treatment suggests the investigation of other regimens.

Are retroperitoneal lymph node metastases a major problem in endometrial adenocarcinoma? Diagnostic and prognostic assessment with lymphography

The results of foot lymphography in 295 patients with endometrial carcinoma observed from 1968 to 1978 at two institutions are reported. One hundred and eighty‐two were new cases, 61 were recurrences, and 52 were patients who underwent restaging diagnostic procedures without clinical evidence of disease. The incidence of lymphatic spread was correlated with the clinical stage, the pathologic stage, and the extent of recurrent disease. In fact, in the 182 new cases, at clinical stage, lymphography was positive in 8.9% of patients at Stage I, 28.6% at Stage II, 57.1% at Stage III, and 66.6% at Stage IV disease; at pathological stage, lymphography was positive in 8% of patients at Stage I, 14.8% at Stage II, 39.3% at Stage III, and 53.3% at Stage IV disease. There was lymph node involvement in 47.5% of the 61 pretreated patients. Finally, in 52 pretreated patients with no evidence of disease, the incidence of lymph node involvement was 7.7%. In new cases, metastases were found only in the pelvic nodes in 56.2% of the patients and only in the para‐aortic nodes in 9.5%; in 34.3%, both chains were simultaneously involved. The five‐year survival rate for patients at Stage I, II, and III disease with positive lymphography was 35% as compared with 73% for negative cases. In patients at Stage I and II, the difference of survival was equal to 24%. The reliability of the results is confirmed by the concordance with the data of the literature on histologic involvement, by the first radiologic‐pathologic comparison, and by the clinical course of the positive cases. Lymphography is of unquestionable value for an appropriate staging and for a correct plan of treatment.