[The combined radiochemotherapy of inoperable esophageal neoplasms: a feasibility study]. / Radio-chemioterapia combinata delle neoplasie esofagee inoperabili: studio di fattibilità.

January, 1994, through January, 1995, eighteen patients (17 men; median age: 59.9, range: 32-73) with biopsy-proved squamous cell carcinoma (n = 15), adenocarcinoma (n = 2) or undifferentiated carcinoma (n = 1) of the esophagus were treated with concurrent chemo-radiotherapy. All patients had inoperable lesions for unresectable disease (11 patients) or concomitant illness (7 patients); median Karnofsky score was 70 (range: 60-80). According to the 1988 American Joint Committee on Cancer Staging system, one patient was graded as Stage IIA (T2N0 + oropharyngeal cancer T4N1), two Stage IIB (T2N1), twelve Stage III (8 T3N1, 1 T4N0, 3 T4N1) and three Stage IV (2 T3N0M1, 1 T4N0M1). Treatment consisted of two courses of chemotherapy by cisplatin (75 mg/m2 i.v. on days 1 and 29) and 5-FU (1000 mg/m2/24 hours by continuous infusion from days 1 to 4 and from days 29 to 32) along with one course of concomitant radiotherapy at 45 Gy (1.8 Gy per fraction, one fraction per day and 5 fractions a week). After 15-30 days, the patients were treated with a boost dose of 7 Gy by high-dose-rate intraluminal brachytherapy. All patients are assessable for toxicity and seventeen for response. The combined treatment was generally well tolerated, with only one case of WHO grade III toxicity (thrombocytopenia). Eight of the eighteen patients had a complete response (47%); four a partial response (24%); four a minimal response (24%) and one showed stable disease (5%). Only one patient developed local progression, and four distant metastases. All the eight patients with CR are alive without local recurrence (two distant metastases) with a mean follow-up of 6 months. This treatment regimen provides good local tumor resolution with no major toxicity. The value of this study protocol will be determined by the rate of long-term survivors.

[The results of sandwich adjuvant radiotherapy in 2nd- and 3rd-stage rectal adenocarcinoma. The authors' personal experience]. / Risultati della radioterapia adiuvante a "sandwich" nell'adenocarcinoma del retto negli stadi II e III. Esperienza personale.

From January, 1985, to June, 1993, 125 patients with stages B2-C adenocarcinomas of the rectum were submitted to pre- and postoperative irradiation according to Thomas Jefferson University protocol guidelines. Five hundred cGy were administered as a single preoperative dose 24 hours before surgery using parallel opposed (AP-PA) treatment fields including the whole pelvis. Pathologic samples were classified following the Astler-Coller staging criteria. Forty-seven patients had no postoperative treatment because their disease stage was A, B1 or D, 11 for refused consent and 9 postoperative complications preventing any further therapy. Seventy-eight patients concluded the treatment schedule and are assessable for response. Radiotherapy total dose consisted of 4400-5000 cGy administered over 5-6 weeks: the patients were treated with megavoltage photons (15-MeV photons) and one dose fraction of 2 Gy was delivered daily, 5 days a week, with the "box" or the "three-field" technique. Median follow-up time was 50.2 months from the beginning of treatment for all the patients in our series (range: 18-120 months). Radiation therapy was well tolerated: 5 patients had severe diarrhea and 2 had small bowel obstruction which required surgery. Local recurrences were observed in 13 of 78 patients (16.7%). Overall actuarial survival at 5 years was 66.8%. Our results confirm the efficacy of this treatment, which is in agreement with international literature data. However, no difference was seen relative to the results obtained with postoperative irradiation alone. We conclude that sandwich radiotherapy can be an effective tool for the local control of rectal adenocarcinoma, with acceptable morbidity, even though it fails to prevent metastases.

Preoperative concurrent radiation therapy and cisplatinum continuous infusion in IIIa (N2) non small cell lung cancer. A pilot study.

From April 1991 to September 1993, 18 patients affected by a presumed operable IIIa (N2) non small cell lung cancer (NSCLC) with histologically confirmed bulky mediastinal metastases, received preoperative concurrent radiation therapy and continuous infusion of cisplatinum (CDDP). The radiotherapy consisted of 2 Gy given 5 days a week for a total dose of 50 Gy; CDDP was administered by means of a central catheter and a portable pump at the daily dose of 6 mg/m2 given on the same days as the radiation therapy (total dose: 150 mg/m2). Two weeks after the end of the treatment, the patients were reevaluated: 5 patients had either local or distant disease progression, the other 13 were submitted to thoracotomy: 12 received a complete resection and 1 patient underwent only a mediastinal lymphadenectomy, because pneumonectomy was impossible due to lack of respiratory function. No histological evidence of cancer cells was observed in the specimens of 6 patients (33%). Radiological response rate was 61% (11/18); resection rate was 66% (12/18) and complete resection rate was 61% (11/18). There was one postoperative death (5%). The 3 year actuarial survival rate is 63.6% for the patients who received a resection with a median survival time of 18 months. All non operated patients died within one year. Combined preoperative treatment was well tolerated. Better results were achieved in patients with squamous cell carcinoma who had a complete resection following a total tumor sterilization with radio-chemotherapy.

[RAdio-chemo-surgical combined treatment of non-small cell lung carcinoma N2]. / Trattamento integrato radio-chemio-chirurgico nel carcinoma polmonare non a piccole cellule N2.

As yet, no optimal treatment for stage-IIIA non-small-cell lung cancer (NSCLC) has been established. Particularly, in the patients with stage-IIIA N2 disease, surgical resection for cure is limited to few selected patients. Of late, a number of studies have suggested that such treatment modalities as chemotherapy, radiotherapy and surgery might be combined to improve treatment efficacy. Based on these conclusions, a cooperative study for N2 NSCLC patients was performed. Treatment included continuous CDDP infusion (6 mg/m2/day) and concomitant irradiation. Fifteen patients were examined. After neoadjuvant treatment, 4 patients were found to have unresectable lesions for local disease progression or metastasis. Eleven patients underwent complete resection (73% resectability). Follow-up ranged 6 to 32 months: 6 patients are now free from relapse (respectively at 31, 28, 23, 14, 12 and 3 months) and 1 is alive with adrenal gland metastasis. Overall and disease-free survival rates are 40.6% and 31.5%, respectively. Our preliminary results indicated that this protocol is well tolerated. Resectability was good and tumor sterilization rate was satisfying (complete T and N sterilization in 6 cases, sterilization of either T or N in 3 cases). The patients with non-adenocarcinoma histology exhibited better local control and prognosis than those with histologic diagnosis of adenocarcinoma.

[The use of cisplatin as radiosensitizing agent in advanced tumors of the head and neck. Randomized study]. / Utilizzazione del cisplatino come radiosensibilizzante nei tumori avanzati della regione testa-collo. Studio randomizzato.

This study was aimed at assessing whether c-DDP administration immediately before radiotherapy could increase frequency and duration of objective responses, as well as survival, in patients affected with locally advanced stages of squamous carcinomas of the head and neck. All patients had already undergone two induction cycles according to the CABO schedule. Ninety-six of 108 treated patients could be evaluated. Treatment schedule consisted in: 1) randomized distribution of patients into two groups before induction chemotherapy; 2) two cycles of induction chemotherapy according to the CABO schedule in all patients; 3) radiation therapy: the patients in group A were given 5 mg/mq of i.v. cisplatin, 30-60 minutes before each session. The results from the two groups were compared and no significant differences were observed regarding objective response (82.5% in group A vs. 86% in group B), response duration and overall survival rates. Even though toxicity was higher in the patients in group A, therapeutic protocol never needed be modified.

[Treatment of N2-3 pulmonary carcinoma. Preoperative radio-chemotherapy]. / Trattamento del carcinoma polmonare N2-3. Radio-chemioterapia preoperatoria.

Preoperative integrated neo-adjuvant radio-chemotherapy was performed in 8 patients suffering from NSCLC bronchial carcinoma at stages IIIA-IIIB (N3 mediastinal). After treatment, 7 patients underwent apparently radical pulmonary exeresis, whereas the patient with adenocarcinoma (T2 N2 M0) was not operated due to the recurrence of disease following supraclavicular lymph node metastasis. Preoperative radio-chemotherapy allows the sub-staging of the disease and the insertion of these patients into the operating programme.

[The use of electrons in oncologic radiotherapy: our experience]. / L'uso degli elettroni nella radioterapia oncologica: nostra esperienza.

The authors describe the interaction of electrons with tissues, the characteristics of depth isodose curves with sharp dose fall-off. These characteristics reduce the utilization of electron therapy only for tumors situated some 5 cm depth below the skin surface and with regular surface. The authors report their experience from 1978 in the treatment of vulvar carcinoma, chest-wall recurrences from breast carcinoma, and cutaneous lymphomas. All these neoplastic diseases were treated with electron beam of adequate energy. Initially betatron was used, successively a linear accelerator (Siemens) about for two years. Results obtained in the treatment of vulvar carcinoma are reported. Two and five years disease free survival rates was respectively 33% and 19% (it is remarked the importance of prophylactic treatment on inguinal lymphnodes). Local control observed in 44 patients with cutaneous lymphomas was 85% until three years; a greater number of recurrences was observed in centrocytic-centroblastic lymphomas. Moreover, local control of breast recurrences was 65% with 5 years survival rate of 22% (34% in patients with only one skin recurrence). Only 22% of the further local failures appear within the treatment field while 78% appear out of field.

Late cytokinetic abnormalities in irradiated rectal mucosa.

Late cytokinetic changes of the colonic crypt epithelium after radiation therapy were investigated. A monoclonal antibody to bromodeoxyuridine (anti-BrdU MAb) was used in tissue specimens previously incubated with BrdU to show S-phase cells by immunohistochemical technique. Endoscopic rectal biopsies were taken from 30 patients previously treated with radiotherapy for gynaecological cancer and from 50 patients with comparable but untreated neoplasms, as controls. Number and height distribution of S-phase cells were evaluated by dividing each crypt column into 5 equal longitudinal compartments. No statistically significant differences were found in total Labelling Index (LI) between controls and irradiated mucosa, whereas LI per crypt compartment, percentage of labelled compartments and percentage of BrdU-positive cells in the middle and superficial portions of the crypt were significantly higher in patients submitted to radiation therapy. This kinetic abnormality corresponds to a progressive shift of the major zone of DNA synthesis to the upper third of the crypt as a late reaction to radiation and represents an early step in the histogenesis of colorectal cancer. These results lend support to the view that there is a higher risk of colorectal carcinoma after pelvic irradiation.

[Preoperative endocavitary curietherapy of stage Ib-IIa-IIb cervical carcinoma. Personal observations]. / Curieterapia endocavitaria pre-operatoria nel carcinoma della cervice uterina agli stadi Ib-IIa-IIb. Osservazioni personali.

From 1980 through 1984, 41 patients with squamous cell cervix carcinoma and 1 with adenosquamous carcinoma were treated with preoperative irradiation. Clinical stages were Ib in 6 patients, IIa in 24, and IIb in 12. At surgery, lymph node metastases were found in 5 cases, and residual tumors in 8. The latter risk patients were given further external radiotherapy after surgery. Overall three-year survival rates for FIGO stage Ib was 100%; 91.6% for stage IIa, and 83% for stage IIb (minimum follow-up: 3 years). Two patients died from locoregional recurrence of the disease 12-24 months after the treatment, and 2 from distant metastases; 5 patients have showed signs of local improvement. Our results seem to point to pelvic lymph node involvement as the major prognostic factor: in fact, 40% only of the patients with involved lymph nodes is alive. Actuarial survival rates show 90.4% of patients to be alive at 5 years. Tolerance to the combined use radiotherapy and surgery was fair: no severe side-effects were observed. Even though our results are encouraging, a randomized study is still recommended to verify the actual value of this treatment versus combined surgery and radiotherapy or radiotherapy alone.

[Radiotherapy in the treatment of carcinoma of the major salivary glands]. / La radioterapia nel trattamento dei carcinomi delle ghiandole salivari maggiori.

The authors conducted a retrospective study on 99 patients with malignant tumors of the major salivary glands, who had been treated by radiotherapy between 1976 and 1986: 86 cases of parotid tumors and 13 cases of submandibular gland tumors. Only 28 tumors (28%) were T1-T2, N0-N1. Local control, 3-5 and 8-year survival rates, and complications were considered. Radiation therapy alone was performed on 19 patients (19%), while combined surgical and radiation therapy was performed on 80 patients (80%). The results of radiation therapy alone and combined with surgery are discussed. Loco-regional disease control was obtained in 9 out of 19 patients (47%) by irradiation alone, and by combined irradiation and surgery in 60 out of 80 cases (75%). Distant metastases developed in 23 out of 99 patients (23%). Loco-regional metastases were the most frequent cause of death (20 out of 55 cases: 36%). Severe complications were extremely rare. The results demonstrate not only the advantages of combined treatment but also the value of radiotherapy alone in the treatment of tumors of the major salivary glands.

[Post-actinic pulmonary fibrosis. Longitudinal study of 279 cases]. / La fibrosi polmonare post-attinica. Indagine longitudinale su 279 casi.

The incidence and extent of postactinic pulmonary fibrosis was investigated in relation to the different types of radiation therapy. For this purpose, 131 patients treated with fast electron (for breast cancer) and 148 patients treated with TCT (for breast cancer and cancer of other nature) observed in the period 1976-1987 were followed up (from 13 months to 7 years). The frequency of postactinic fibrosis was much less in the first group of patients than the second (6.61% vs 18.99%); further, the functional damage in these patients proved less and developed in a less unfavourable way.

Radical vulvectomy and inguinal lymphadenectomy versus inguino-pelvic lymphadenectomy combined with radical vulvectomy and the role of radiotherapy.

We studied 39 patients with stromal invasion exceeding 1 mm. Among them 3 underwent emivulvectomy and 8 simple vulvectomy; all had selective inguinal lymphadenectomy of one side the first and bilaterally the others. 17 women underwent radical vulvectomy and inguinal lymphadenectomy while 11 had radical vulvectomy and inguino-pelvic lymphadenectomy. Out of 21 patients with lymph nodal metastases, 11 had one side inguinal metastases, 2 had a single metastasis, 2 had double metastases, 1 had three metastases and 2 multiple ones. Survival rate decreased from 54.5% to 20.0% when patients had more than 3 monolateral inguinal metastases or bilateral ones, with increase of pelvic lymph nodal metastases; therefore, in those cases, pelvic lymphadenectomy can be associated to inguinal lymphadenectomy or, when the carcinoma is situated in the clitoridis, Bartolino's gland or vagina (the same could be done for melanoma of the vulva). The usefulness of radiotherapy is limited by the small response of vulvar tissue. In a series of 45 patients with clinical diagnosis of inguinal metastases, who could not undergo operation, only therapy, with electron beam therapy (9 meV) associated to inguinal fields (15 meV), had positive influence in 27% of the cases.

[Quadrantectomy and adjuvant radiotherapy in carcinoma of the breast. Initial results of our cases]. / Quadrantectomia e radioterapia adiuvante nel carcinoma della mammella. Primi risultati della nostra casistica.

The conservative treatment of early breast cancer always requires irradiation of residual mammary tissue. The preliminary results obtained in 45 early breast cancer patients, who received quadrantectomy plus axillary dissection, followed by radiation of residual breast are reported. Radiation was performed by the two opposed field technique. In some cases the residual breast tissue was compressed using a special accessory provided with the Theratron 780. In addition to the tumor dose of 50 GY, 10 GY boots was added to the surgical scar using 7 MeV electrons. The 6 patients with positive axillary nodes received 6 courses of adjuvant chemotherapy (CMF) after radiotherapy. All patients are currently alive and free of disease. The 64% (29 patients) were followed up for at least 5 years, and 36% (16 patients) for at least 3 years. Only 2 cases of local recurrence were encountered (4.4%). The esthetic result was satisfactory in all cases. No side effects due to treatment were noted.

Chest irradiation as an attempt to improve the response after induction chemotherapy in small cell lung carcinoma.

Forty-six patients with small cell lung carcinoma received cyclic chemotherapy with cisplatin-VP 16 and vincristine, doxorubicin, and cyclophosphamide. The responding patients were given prophylactic cranial irradiation. Patients without metastases not achieving a complete response (CR) following induction chemotherapy were given chest irradiation. The response rate was 73.9 per cent. Response was improved by radiation therapy in only 9 per cent of the patients with limited disease. Median survival was 39 weeks, with 2 patients surviving for longer than 24 months. The duration of response and survival in complete and partial responders was similar; absence of radiation therapy in the patients with CR might explain this finding.