A phase II trial of combined chemotherapy and surgery in stage IIIA non-small cell lung cancer.

A poor prognosis for patients with Stage IIIA clinical N2 treated by surgery alone has led clinical researchers to find a new treatment modality to improve the curative potential of surgery. Many Phas II trials have been carried out with induction chemo- or chemo-radiotherapy prior to surgery. From June 1988 to July 1991, 46 patients with non-small cell lung cancer (NSCLC) Stage IIIA clinical N2 entered a Phase II induction-chemotherapy trial. Patients received 2-3 cycles of high-dose cisplatin and etoposide. Forty-five were evaluable for response; the response rate was 82% (37/45: 3 CR, 34 PR). Toxicity was primarily hematologic. Surgical resection was performed in 35 patients; radical resection was possible in 28 patients (62%); three patients were incompletely resected and two patients were only explored. Three deaths were surgery-related. Median survival was 24.5 months with a 2-year survival of 53%. Cisplatin with etoposide is an active and safe induction chemotherapy regimen for NSCLC Stage IIIA N2 with a high response rate. The median survival seems to be prolonged and therefore, randomized trials are needed to compare this approach with other treatment modalities.

Neoadjuvant cisplatin and etoposide for stage IIIA (clinical N2) non-small cell lung cancer.

In an attempt to improve the curative potential of surgery, 46 patients with unresectable Stage IIIA (Clinical N2) non-small cell lung cancer received neoadjuvant chemotherapy with cisplatin and etoposide. After 2 or 3 cycles, 45 patients were evaluable for response; the overall response rate was 82% (37/45) with 3 complete and 34 partial responses. Toxicity was primarily hematologic. Surgical exploration was performed on 35 patients, but resection was possible in only 33 (73%). Of these, 28 resections were complete (62%). Four patients (2CR, 2PR; 9%) had no tumor in biopsy specimen. Three deaths were surgery-related. Median survival of the entire 46 patients was 24.5 months with a 2-year survival of 53%. Cisplatin and etoposide is an effective chemotherapeutic regimen for regionally advanced non-small cell lung cancer; the resection and survival rates justify further trials to compare this approach to other treatment modalities.

Radiation therapy of spinal cord compression caused by breast cancer: report of a prospective trial.

Fifty-six breast cancer patients with metastatic spinal cord compression were consecutively treated with radiation therapy alone. All patients received steroids plus chemotherapy and/or hormonal therapy. Emergency radiation therapy was administered using a split-course regimen: 5 Gy for 3 days, stopped for 4 days and, only in responders, a further 3 Gy for 5 days (time dose fractionation 68). Median follow-up was 22 months (range, 4 to 52 months). Response and survival were assessed on the basis of, pretreatment and posttreatment walking capacity, presence of vertebral body collapse or osteolysis, presence of other metastatic sites apart from bone and chemotherapy and/or hormonal therapy. In 89% of patients with back pain the pain disappeared or lessened. Four of 6 cases (67%) with urinary dysfunction responded to radiation therapy. Of 35 cases with motor dysfunction at the time of diagnosis, 21 (60%) regained the ability to walk and another five (14%) who were able to walk with support at diagnosis did not deteriorate. All 21 cases without motor deficits before treatment maintained good motor performance after radiation therapy. Response to therapy was better in pretreatment walking than in nonwalking patients (97% vs 69%; p less than 0.02). Probability of duration of response at 1 year was 59% and 10% for posttreatment walking and nonwalking patients, respectively (p less than 0.0001). One year survival probability was 66% for posttreatment walking and 10% for posttreatment nonwalking patients, respectively (p less than 0.0001). Pretreatment and posttreatment ambulatory status were the most important prognostic factors.

Interstitial pneumonitis after hyperfractionated total body irradiation in HLA-matched T-depleted bone marrow transplantation.

Interstitial pneumonia is one of the major causes of morbidity and mortality after bone-marrow transplantation. We here report a series of 58 patients suffering from hematological malignancies who received HLA-matched T-lymphocyte depleted bone-marrow transplants between July 1985 and January 1990. Interstitial pneumonia occurred in 7/58 patients (12%) and was fatal in six. Three different pre-bone-marrow transplantation conditioning regimens were employed. Total body irradiation was delivered according to a hyperfractionated scheme of 12 fractions given three per day 5 hr apart for 4 days. Twenty-three patients received 36 mg/Kg procarbazine, 1275 UL/Kg antithymocite globulin, 14.4 Gy hyperfractionated total body irradiation and 120 mg/Kg cyclophosphamide. Only one patient developed interstitial pneumonia, but two rejected the graft and 10 relapsed. As a consequence, the total hyperfractionated scheme was increased to 15,6 Gy, cyclophosphamide to 200 mg/Kg, antithymocite globulin to 3400 UL/Kg and procarbazine eliminated. There were three cases of interstitial pneumonia, no rejection and four relapses in the 17 patients who received this regimen. In the last 18 patients hyperfractionated total body irradiation was reduced to 15 Gy, cyclophosphamide to 100 mg/Kg, and 10 mg/Kg of the myeloablative agent thiothepa added to enhance the cytoreductive effect without significantly increasing extramedullary toxicity. Three cases of interstitial pneumonia, one relapse but no rejection were recorded. Our results demonstrate that the absence of graft-versus-host disease due to T-cell depletion, and radio-chemotherapy doses and schedules used for the conditioning regimen each contributed to reducing the risk of interstitial pneumonitis. Hyperfractionated total body irradiation therefore, seems to play an important role in lowering the incidence of this complication.

Lung damage following bone marrow transplantation after hyperfractionated total body irradiation.

From July 1985 to December 1989, 72 evaluable patients aged between 6 and 51 (median age 27 years) suffering from haematological malignancies received an allogeneic bone marrow transplant (BMT) depleted of T-lymphocytes to reduce the risk of graft-versus-host-disease (GvHD); 57 were matched and 15 mismatched. Three different conditioning regimens were used in an effort to enhance cytoreduction without increase extramedullary toxicity. Mismatched patients were treated with more immunosuppressive regimens. Total body irradiation (TBI) was given in three doses per day, 5 h apart, over 4 days for a total of 12 fractions. The dose to the lungs was 14.4, 15.6 and 9 Gy according to the conditioning regimen. The incidence of interstitial pneumonia (IP) was 12.3% in matched and 46.7% in mismatched patients. Our results seem to indicate that lung toxicity is correlated with the intensity of the conditioning regimen, the stage of disease and, in mismatched patients, with the degree of human leucocyte antigen (HLA) disparity and the poor post-BMT reconstitution, rather than the radiotherapy dose delivered to the lungs. On the contrary, the hyperfractionated scheme adopted, the absence of GvHD and, perhaps, the post-TBI administration of cyclophosphamide all seem to have contributed to the low incidence of IP in our matched patients.

[Surgery after neo-adjuvant therapy of non-small cell lung cancer. Preliminary results]. / Chirurgia dopo terapia neo adiuvante del cancro del polmone non a piccole cellule. Risultati preliminari.

The Authors report their personal experience of surgical treatment following neo-adjuvant therapy in NSCLC (III a N2) in order to assess: 1) the feasibility and safety of surgical treatment following major responses to neoadjuvant chemotherapy; 2) the sectile rate; and 3) the survival rate. Preliminary results show that: 1) chemotherapy using cisplatin and VP-16 gives a high rate of major responses in these patients; 2) surgery is feasible; 3) there is high radical sectile rate; 4) further research is needed to obtain statistical significance.

[Endocavitary curietherapy of tumors of the rhinopharynx after external radiotherapy]. / La curieterapia endocavitaria dei tumori della rinofaringe dopo radioterapia esterna.

We report our experience in the treatment of nasopharyngeal carcinoma with intracavitary curietherapy to cure small recurring carcinomas or residual local disease 2-6 weeks after completing external radiotherapy. Since 1984, 10 patients have received intracavitary radiotherapy with customized molds charged with Ir 192. Six of them received a boost dose because of residual disease and for local recurrence. The technique we employed to shape the molds is described, together with the mode of use and the doses to target volume. Due to both the small number of treated cases and the short follow-up, no significant conclusions could be drawn relative to survival time. However, it must be stressed that this therapeutic approach gives a high local control rate with no severe side-effects or sequelae.

[Pre- and postoperative radiotherapy of operable carcinoma of the rectum]. / Radioterapia pre- e postoperatoria del carcinoma del retto operabile.

This was a non-randomized prospective study on the "sandwich" radiosurgical treatment of resectable rectal and rectosigmoid carcinomas. From December 1984 to December 1989, 100 patients were treated 86 of them are now evaluable. Mean follow-up was 38 months (range: 9-69). Surgery was abdomino-perineal resection in 33 cases and anterior resection in 53 cases. Radiotherapy was preoperative pelvic irradiation, with a single 500-Gy fraction, the day before surgery. To stages B2, C1 and C2 patients (Astler and Coller) postoperative radiotherapy was administered for a total dose of 4500 Gy (180 Gy/fraction, 5 fractions/week), with box technique, from a Co 60 unit or Linear Accelerator (photon 18 MV). Preliminary results indicate 8% (7/86) local recurrences and 9.3% (8/86) distant metastases. Five-year actuarial disease-free survival is 63.2% +/- 8 for stage B1, 55.6% +/- 19 for stage B2, and 40.2% +/- 13 for stages C1 + C2. Overall 5-year actuarial disease-free survival is 53% +/- 10. No lethal or severe complications were observed following treatment.

Radiation therapy in metastatic spinal cord compression. A prospective analysis of 105 consecutive patients.

One hundred thirty consecutive patients with metastatic spinal cord compression (MSCC) were entered in a therapeutic protocol in which radiation therapy (RT) played the main role. When MSCC is diagnosed by clinical-radiologic methods such as myelography with or without computed tomography (CT) or magnetic resonance imaging (MRI), steroids are given and RT treatment started within 24 hours. When diagnostic doubts exist or stabilization is necessary, surgery precedes RT. Chemohormonal potentially responsive tumors are also treated with chemotherapy or hormonal therapy. Twelve patients (9.2%) underwent surgery plus RT, and 118 (90.8%) received RT alone. Thirteen (11%) early death patients were not evaluable. The 105 evaluable cases that received RT alone were analyzed. Median follow-up was 15 months (range, 4 to 38 months). Response among patients with back pain was 80%. In cases with motor dysfunction, 48.6% improved, and in 33 of 105 patients (31.4%) without motor disability there was no deterioration. Forty percent of patients with autonomic dysfunction responded to RT. Median survival time was 7 months with a 36% probability of survival for 1 year. The median duration of improvement was 8 months. The most important prognostic factor was early diagnosis. Radiosensitivity of tumor was only important in paraparetic patients in predicting response to RT. Complete myelographic block significantly diminished response to RT. Vertebral collapse did not influence response or survival.

[Role of lymphangiography and abdomino-pelvic CT in uterine tumors]. / Ruolo della linfografia pedidia e della TC addomino-pelvica nei tumori uterini.

Between January 1983 and December 1987, 77 patients with cervical and endometrial carcinoma (40 and 37 cases, respectively) were studied with a diagnostic protocol which included lymphangiography and abdomino-pelvic CT. The only administered treatment was radiation since all patients were considered inoperable or had non-resectable disease. Median age was 55 years (range 29-77). Median follow-up was 44 months-minimum 24, maximum 72 months. Subdiaphragmatic nodes were considered as pathologic even when just one of the two techniques demonstrated their involvement. Radiotherapy doses and volumes varied according to these findings (45 Gy to pelvis as a precautional dose; 6-8 Gy booster dose in N1 cases; 45 Gy to the periaortic area in N4 cases). The two diagnostic techniques agreed as to the presence/absence of pathologic nodes in 50 (64.9%) and 12 (15.6%) patients, respectively. There was disagreement between CT and lymphangiographic findings in 12 patients (15.6%) as regards the pelvic area and in 8 patients as regards the periaortic area (10.4%; 5 of the 8 also figured in the pelvic group). Actuarial 5-year disease-free survival for both groups, summing up stages I, II and III, goes as follows: cervical carcinoma patients: 47% (N0 cases 56%, N1-N4 33%, p = 0.07) and endometrial carcinoma group: 74.5% (no difference was found between N0 and N1 cases). Higher diagnostic accuracy seems to be obtained when CT is combined with lymphangiography than when either of them is performed alone. Therefore, the combined use of the two techniques could have a precise diagnostic role.

[Radiotherapy of the breast after conservative surgery for primary carcinoma. Irradiation technic with matched fields]. / La radioterapia della mammella dopo chirurgia conservativa per carcinoma iniziale. Tecnica di irradiazione con fasci collimati.

The authors report their technique for breast radiotherapy following conservative surgery (quadrantectomy + axillary dissection). The breast and chest wall are irradiated with photons from a 60Co unit through two fixed opposing tangential fields. The posterior field edges must be parallel and coplanar to the chest wall. A routine treatment plan using simulator, pantograph and computerized console is standardized by mathematical formulae elaborated from geometric breast measurement parameters. Gammagraphies acquired prior to and during therapy allow verification and control of treatment parameters. For 35 patients the therapy plan as described was compared with that obtained by CT images. Our procedure proved valid and an accurate treatment plan could be elaborated even without CT images. The use of wedges, half-field blocks and the dose scattered to the contralateral breast are also discussed.

[Diagnostic-therapeutic integration in metastatic spinal cord compression. Analysis of a prospective study]. / L'integrazione diagnostico-terapeutica nella compressione midollare metastatica. Analisi di uno studio prospettico.

Metastatic Spinal Cord Compression (MSCC), an oncologic emergency, is a frequent complication of many neoplastic diseases in an advanced stage. Our experience is reported, which was obtained with a series of 61 patients following a diagnostic-therapeutic protocol aimed at early diagnosing MSCC and at assigning the major role in therapy to radiotherapy (RT) alone. Fifty-seven patients with an average follow-up of 13 months (range 4-26) were evaluable. Diagnosis was always made by means of myelography and/or myelography plus CT. In 50 cases the treatment consisted in RT alone and the remaining 7 patients had surgery before RT because of diagnostic doubts; in 1 case the patient was operated on because stabilization was necessary. A dose of 30 Gy was delivered, over 2 weeks, (TDF = 62) to those tumors which were considered as radiation-responsive and having a better prognosis (myeloma, lymphoma), whereas all the other histologies were given a split-course regimen (5 Gy x 3 days, stop x 4 days, +/- 3 Gy x 5 days; TDF = 68). All patients received medium or high doses of steroid depending on the degree of neurologic involvement. Patients with chemo/hormone-responsive primary tumors also received chemotherapy and/or hormone therapy. The clinical parameters considered in evaluating the response to treatment were backache, motor performance, and sphincter function. Respectively 86%, 47% and 44% of patients responded. Early diagnosis was the most important prognostic factor, whereas histology of the primary tumor was important in cases with severe neurologic damage only. The results obtained are similar to those reported in literature and confirm the value of the diagnostic-therapeutic approach used, which suggests continuing this trial.

Role of radiotherapy in metastatic spinal cord compression: preliminary results from a prospective trial.

A non-randomized prospective trial in which radiotherapy (RT) alone played the major role in the treatment of metastatic spinal cord compression (MSCC) is reported. Diagnosis was formulated on myelography and/or myelography plus computed thomography (CT). Of 51 cases treated, 48 are evaluable. The therapy consisted of radiation alone (42 cases) or decompressive laminectomy followed by radiotherapy (6 cases). Surgery was performed when the site of the primary tumor was unknown. The group of patients who received radiotherapy alone (42 of 48 evaluable cases) are analysed in this report. Medium to high doses of steroids were administered to all patients depending on the gravity of the case. Patients with chemo- or hormone-responsive primary tumors also received chemotherapy and/or hormone therapy. Pain relief, assessed by comparing use of narcotics and minor analgesics before and after treatment, was achieved in 54% cases (confidence limits, CL = 38-69%). In 36% (CL = 22-51%) of patients back pain diminished to the point when only milder analgesics were necessary (partial remission). Motor performance, based on patients' ability to walk, improved in 48% cases (CL = 31-65%). The 19 patients who were ambulatory before RT, did not deteriorate after treatment. Sphincter function, evaluated by patient's need for indwelling catheter, improved in 3 of 7 automatic dysfunction cases. It was found that early diagnosis was more important than primary tumor type for predicting a good was found that early diagnosis was more important than primary tumor type for predicting a good prognosis. In fact, all ambulating patients responded to treatment independent of the radiosensitivity of the tumor histology.(ABSTRACT TRUNCATED AT 250 WORDS)

[Surgical and radiotherapeutic treatment in stage I endometrial adenocarcinoma. Retrospective analysis of 218 patients]. / Trattamento chirurgico e radioterapico dell'adenocarcinoma endometriale I stadio. Analisi retrospettiva su 218 pazienti.

From April 1977 through April 1985, 218 stage I endometrial carcinomas were treated with radiosurgery or radiotherapy alone. Postoperative irradiation was external (60Co) in 131 and curietherapy in 27 patients. Twenty patients underwent preoperative curietherapy and 40 patients radiotherapy alone. Median follow-up was 5.6 years (range 3-11). The overall 5-year actuarial survival (Kaplan-Meier method) was 86.1% +/- 2.5. The 5-year D.F. actuarial survival was 95% +/- 4.9, 93.1% +/- 4.7, 88.4% +/- 2.9, respectively, for preoperative radiotherapy, postoperative curietherapy and postoperative external irradiation groups. The 5-year actuarial survival was 69.8% +/- 7.7 in the radiotherapy alone group. There was difference in survival among patients treated with radiotherapy alone as compared to those radiosurgically treated (P less than 0.001). Local and general recurrence rate was 8.2%; vaginal recurrences 2/218 (0.9%); pelvic recurrences 7/218 (3.3%); distant metastases 9/218 (4.1%). Overall side effects were observed in 20/218 patients (9.1%): grade I and II in 8.6% of cases, grade III in 0.9% of cases. The authors conclude that good results can be achieved with adjuvant radiotherapy both in high risk cases and in low risk cases, with minimal side effects.

[Radiotherapy of testicular seminoma. Stages I and II A, B]. / Radioterapia del seminoma testicolare. Stadio I e II A, B.

From June 1977 through June 1987, 46 patients (36 evaluable) affected by stage I and II non-bulky testicular seminoma were treated with postoperative telecobaltotherapy (TCT). In stage I seminomas, radiotherapy was extended to the omolateral iliac and the para-aortic areas (total dose: 30 Gy over 4 weeks). In stage II seminomas, the subdiaphragmatic lymph nodes were irradiated with 40-45 Gy over 5-6 weeks; after an interval of one month the subdiaphragmatic lymph nodes were irradiated again with a total dose of 25 Gy over 3.5 weeks. Minimal follow-up lasted two years and maximum ten years (average: 5.5). Two (5.5%) recurrences occurred, but salvage radiotherapy and salvage chemotherapy respectively allowed a complete permanent remission. One patient died from a different neoplasia with no evidence of testicular involvement. The 5-year actuarial survival is 96.6 +/- 3.4. In 20% of the patients the side effects were nausea and/or vomiting, easily controlled. No late complications were observed.

Hyperfractionated total body irradiation for T-depleted HLA identical bone marrow transplants.

Twenty patients suffering from malignant hemopathies (mean age 31.7 years) were given hyperfractionated total body irradiation (TBI) (120 cGy/3 fractions per day: total dose = 1440 cGy/4 days) as conditioning for T-depleted HLA identical allogeneic bone marrow transplantation. At an average of 12 months (range of 4.5-22 months) follow-up there were two cases of early death and two cases (11%) of rejection. There were no cases of acute or chronic graft versus host disease (GVHD) nor cases of interstitial pneumonitis. The average time for durable engraftment was 22 days. Disease-free survival at 12 months was 65%. To improve the results and further reduce the percent of rejection, the authors propose intensifying the immunosuppressive conditioning by increasing the cyclophosphamide dose and that of TBI so that a total dose of 1560 cGy is reached.

[Combined chemotherapeutic and radiotherapeutic treatment of limited pulmonary microcytoma]. / Il trattamento integrato chemioterapico e radioterapico del microcitoma polmonare a malattia limitata.

Between 1978 and 1983, 34 patients (32 evaluable) suffering from limited small cell lung carcinoma (SCLC-L) were treated following the protocol polychemotherapy (CAV) plus thoracic cobalt teletherapy and "precautionary" cranial irradiation (30 Gy in 2 weeks). Minimum follow-up was 30 months. After induction chemotherapy there was complete remission (CR) in 20% of cases whereas at the end of induction chemo-radiotherapy there was complete remission (CR) in 44% (p less than 0.05) of cases. Median duration of the responds was 12 months. Total median survival is 15 months, median NED survival 32 months (6-90 months). Seven out of 14 CR patients received consolidated thoracic radiotherapy (Rt); 6 of these survived disease-free for over 2 years. No salvage therapy carried out has proved useful. Only in one patient (3%) brain metastasis occurred. Iatrogenic toxicity was also kept within limits of brain level. The role Rt plays in increasing the CR percentage, in drastically diminishing the incidence of brain metastasis, in improving the quality of life by increasing the disease-free interval must be emphasized. Finally it should be noted that only CR patients have the possibility to become "long survivors".