Prostate-specific antigen decline: a major prognostic factor for prostate cancer treated with radiation therapy.

PURPOSE: To assess the prognostic significance of serum prostate-specific antigen (PSA) in the monitoring of patients with localized prostate cancer treated with primary radiation therapy, we analyzed the data from 179 patients treated at our institution between 1987 and 1990. PATIENTS AND METHODS: One hundred seventy-nine previously untreated patients received radiation at 69 Gy to the prostate with curative intent for prostate adenocarcinoma. The median follow-up duration is now 41 months. PSA levels were measured before radiotherapy and then evaluated periodically. RESULTS: Baseline levels were greater than 4 ng/mL in 83% of cases and were significantly correlated with clinical tumor stage (P = .002). Six months after completion of therapy, PSA values had returned to normal in 53% of the patients with initially elevated values. At the time of analysis, 32 patients have relapsed, including three of 30 patients (10%) with normal initial and 6-month values, five of 79 patients (6%) with initially elevated but normal 6-month values, and 24 of 69 patients (35%) with persistently elevated PSA levels at 6 months. Actuarial 4-year relapse-free survival was significantly correlated with initial and 6-month PSA values (84% in patients with normal 6-month values v 60% in patients with persistently elevated levels). Furthermore, when the relative decline between initial and 6-month PSA values exceeded 50%, the crude rate of recurrence was 14% as opposed to 34% when it failed to exceed 50%. The 4-year relapse-free survival rates were 77% and 59%, respectively (P = .008). By multivariate analysis restricted to the patients with elevated baseline PSA levels, the rate of decline of PSA values reached the highest prognostic significance (P < .0001). Age at diagnosis, clinical tumor stage, and Gleason score only reached statistical significance in univariate analysis. CONCLUSION: PSA values are of major prognostic significance in assessing the 4-year results of radical radiation therapy for localized prostate cancer. The rate of decline of PSA values is the strongest predictor of outcome and might help to identify a subset of patients with poorer prognosis who may benefit from early hormonal therapy.

Outpatient treatment with subcutaneous interleukin-2 and interferon alfa administration in combination with fluorouracil in patients with metastatic renal cell carcinoma: results of a sequential nonrandomized phase II study. Subcutaneous Administration Propeukin Program Cooperative Group.

PURPOSE: We report the results of the Subcutaneous Administration Propeukin Program (SCAPP) II trial of an outpatient treatment in renal cell carcinoma using interleukin-2 (IL-2) and interferon alfa-2a (IFN-alpha) administered subcutaneously in combination with fluorouracil (5-FU). The objective of this multicenter trial was to confirm that the combination of IL-2, IFN-alpha, and 5-FU leads to a response rate greater than 20%. PATIENTS AND METHODS: Patients with metastatic renal cell carcinoma were included in this study. During the induction phase of the treatment, which lasted 10 weeks, IL-2 and IFN-alpha were administered subcutaneously three times a week for 8 weeks at doses of 18 MIU and 9 MIU, respectively. During these 8 weeks, every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes. After evaluation, responding patients or patients with stable disease (SD) were given maintenance treatment, until disease progression (PD) or the appearance of unacceptable toxicity. Each maintenance cycle consisted of a 2-week treatment followed by a three-week rest period. During treatment, IL-2 and IFN-alpha were administered subcutaneously three times a week at doses of 18 MIU and 9 MIU, respectively. Every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes. RESULTS: This trial was closed when the sixth sequential analysis showed the lack of benefit from this combination. At the end of the induction period, of 62 patients, 12 (19%; 95% confidence interval [CI], 10% to 31%) reached an objective response, including one complete response (CR), 16 presented with SD, and 27 showed PD. Twenty-seven patients (43%) developed severe toxicity that required reduction of the planned doses (13 patients), delayed treatment (eight patients), or treatment termination (six patients). Seventeen patients were given maintenance treatment. One- and 2-year survival rates were estimated at 55% and 33%, respectively. The 2-year survival rate was 15% in 11 patients who presented with three poor-prognosis factors and 41% in 51 patients who initially presented with no, one, or two poor-prognosis factors (P = .04). CONCLUSION: As in other recently published studies that used 5-FU, IL-2, and IFN-alpha, the multicenter SCAPP II trial in patients with metastatic renal cell carcinoma generated severe toxicity. This sequential trial failed to confirm the favorable results previously obtained by Atzpodien and Sella with this combination of three drugs. Its efficacy, assessed on the response and survival rates, is near to the results observed in programs that used IL-2 alone given subcutaneously.

Bazex syndrome (acrokeratosis paraneoplastica). An analytic review.

Bazex syndrome (acrokeratosis paraneoplastica) is characterized by a psoriasiform eruption that favors acral sites and has been associated with an underlying malignancy in all reported cases. Of the 93 patients in this series, 89 were male with a mean age of 60 +/- 8.5 years. Squamous cell carcinomas of the head and neck and squamous cell tumors of unknown primary with cervical lymph node metastases were the most commonly associated neoplasms, suggesting that the factor(s) responsible for the development of the syndrome are relatively specific for tumors of the upper aerodigestive tract. The cutaneous lesions were erythematous to violaceous in color and had associated scale; the most frequently observed sites of involvement were the ears, nose, hands, and feet, including the nails. In 63% of the cases, the cutaneous lesions preceded the initial symptoms or diagnosis of the tumor by an average of 11 months (range, 1-72) and, in general, the eruption was resistant to a variety of topical treatments. Occasionally, a reappearance of the papulosquamous lesions signaled the recurrence of the tumor (6 cases) or the appearance of skin lesions coincided with the development of metastatic disease (3 cases). In 91% (64/70) of the patients, the skin eruption either improved significantly following treatment of the underlying malignancy or did not improve in the setting of persistent tumor. However, even when all of the skin lesions cleared, the nail dystrophy often persisted. Fifteen of the patients developed vesicles, bullae, and crusts in addition to papulosquamous lesions. Possible explanations include the formation of an epidermal-dermal split via a bullous lichen planus-like mechanism, or the coexistence of two diseases; i.e., acrokeratosis paraneoplastica plus either porphyria cutanea tarda, bullous pemphigoid, or epidermolysis bullosa acquisita. One possible explanation for the development of the characteristic cutaneous eruption is an immune reaction, humoral or cellular, directed against a common antigen present on the tumor and the normal skin. Alternatively, tumor production of a keratinocyte growth factor such as TGF-alpha may be involved in the induction of the psoriasiform skin lesions.

Radiation therapy with concomitant continuous infusion cisplatin for unresectable nonsmall cell lung carcinoma.

PURPOSE: This pilot study was designed to test the tolerance and effectiveness of concurrent continuous infusion cisplatin and radiotherapy in the treatment of unresectable nonsmall cell lung (NSCL) cancer. METHODS AND MATERIALS: Between July 1989 and July 1991, 92 consecutive patients with either medically or technically inoperable NSCL cancer were treated with thoracic radiotherapy and concomitant chemotherapy. Radiotherapy consisted of a total dose of 70 Gy delivered in 2 Gy daily fractions over 9 weeks with a planned 2-week break after 40 Gy. During the second week of each cycle of radiotherapy, cisplatin was administered, 20 mg/m2/day for 5 days as a continuous infusion. Eighty-five patients were evaluable. RESULTS: Overall response rate was 81.7% (65.9% complete response). Medically operable patients were considered for curative surgical resection following 40 Gy and one cycle of chemotherapy; 11 patients underwent resection with 3/11 having no pathologic evidence of tumor. Median survival for all 85 patients was 11.4 months with a median follow-up of 27 months. Overall survival was 48.2%, 27.5%, and 25% at 12, 24, and 36 months, respectively. Survival was independent of tumor stage, histology and grade, and patient age and gender. Patients having a complete response (n = 54) had a 2-year survival of 42.1% compared to 3.2% for partial-responders and nonresponders (n = 31; p < 0.0001). Patients undergoing surgical resection (n = 11) had a 2-year survival of 75.8% compared to 20.6% for those treated with chemoradiotherapy alone (n = 74). Forty-eight patients have died of their disease. There were two treatment-related deaths, seven deaths of intercurrent disease and three of unknown causes. Eighteen of 25 patients alive at the time of analysis were without evidence of disease. Actuarial local control was 50.6% at 1 year, and 33.3% at 2 years. The distant failure rate was 47.8% at 2 years. Major acute toxicities, mainly hematologic or gastrointestinal, occurred in less than 10% of patients. Esophagitis was mild and infrequent (8.4%). Severe late pulmonary fibrosis occurred in 5.2% of patients and resulted in two treatment-related deaths. CONCLUSION: Concomitant chemoradiotherapy was well tolerated, resulted in a high rate of local control, and in a survival benefit for patients demonstrating a complete response or going on to surgical resection. The incidence of distant metastases continues to be high and future strategies should be directed at improving systemic therapy.

Concurrent cisplatin, etoposide, and radiotherapy for unresectable stage III nonsmall cell lung cancer: a phase II study.

PURPOSE: Prognosis of unresectable Stage III nonsmall cell lung cancer (NSCLC) treated with thoracic radiotherapy alone has been disappointing. In recent years, several Phase III trials have demonstrated encouraging results with induction chemotherapy, but with poor long-term local control. Concurrent cisplatin alone during the radiation therapy course has resulted in improved local control, but without efficacy on occult metastatic disease. Intensification of chemotherapy during radiation has the potential of improving both local control and metastasis-free survival. This Phase II study was undertaken to determine the feasibility, toxicity, response rate, local control, and survival of concurrent chemotherapy with cisplatin-etoposide and radiotherapy in unresectable Stage IIIA and IIIB nonsmall cell lung cancer. METHODS AND MATERIALS: Between February 1992 and April 1993, 50 patients with either medically or technically inoperable Stage III NSCLC were treated with concurrent chemoradiotherapy. Thoracic radiotherapy was administered to a total dose of 60 Gy. Concurrent chemotherapy consisted of cisplatin 20 mg/m2/day plus etoposide 50 mg/m2/day, from day 1 through day 5, every 4 weeks for four cycles. Medically operable patients were evaluated for surgical resection after 45 Gy and two cycles of concurrent chemotherapy. All patients received an esophagitis preventive regimen. RESULTS: Response rate was 84%, including 68% complete response. With a minimum follow-up of 23 months, overall survival was 70% at 1 year, 39.7% at 2 years, and 34.7% at 3 years. Median survival was 18 months. Age, performance status, histologic type and grade, and stage and tumor size, did not influence survival, with the exception of contralateral nodal involvement (p = 0.0055). Patients achieving a complete response (n = 34) had a 2-year survival of 58.4% compared to 0% for nonresponders (p < 0.0001). Patients who could benefit from surgery (n = 9) had a 2-year survival of 77.8% compared to 31.2% for nonoperated patients (p < 0.013). Seventeen patients (34%) are currently alive and free of disease. Actuarial local control was 63.4% at 1 year, and 58.5% at 2 and 3 years, respectively. Major hematologic toxicity occurred in 24% of the patients. CONCLUSIONS: Concomitant chemoradiotherapy with cisplatin and etoposide at this dose level is a well tolerated outpatient regimen, which resulted in a high local control rate, and an encouraging survival at 1, 2, and 3 years. A direct comparison of this treatment schedule to induction chemotherapy followed by radiotherapy, or concurrent chemoradiation therapy using cisplatin alone, appears warranted.

[Localized small-cell lung cancers: prospects of concomitant radiochemotherapy]. / Cancers bronchiques á petites cellules localisés: perspectives de la radio-chimiothérapie concomitante.

Concurrent chemoradiotherapy in the treatment of small-cell lung cancer: current results and future prospects. The prognosis of small cell carcinoma of the lung is reportedly poor, even in limited disease. However, new modalities of combined chemotherapy and radiotherapy may actually result in improved survival in these patients. First-line chemotherapy regimens with cisplatin and etoposide are effective and allow early and concurrent administration of thoracic radiotherapy, without overwhelming toxicity. Radiosensitizing properties of cisplatin and etoposide have been demonstrated, and concurrent delivery of radiotherapy results in a high complete response rate on the primary tumor, and improved long-term local control, which is a prerequisite for cure. In addition, a reduction of the irradiated volume, restricted to the macroscopic tumor, appears feasible without compromising local control and results in a reduced long-term complication rate of the combined treatment. Acute toxicities of these concurrent regimens are mainly hematological and esophageal, but are reversible and without late effect in the majority of the patients. The potential benefit of a twice-daily over standard once-daily irradiation has not been conclusively demonstrated in recent trials. However, these trials have demonstrated excellent outcome after short duration chemotherapy (four courses) with early concurrent radiotherapy (45 Gy), resulting in a 40% survival at 2 years, which appears substantially higher than that obtained with the sequential or alternating regimens. The benefit of prophylactic cranial irradiation has also been confirmed in a large trial in terms of reduction of brain relapses, but with only marginal benefit upon survival. Further improvement of the prognosis of these patients may result form an early intensification of chemotherapy with the support of hematopoietic growth factors and from a dose escalation of radiotherapy with the support of three dimensional computerized dosimetry.

[Axillary lymph node and bone marrow micrometastases of breast cancer]. / Les micrométastases ganglionnaires et osseuses des cancers du sein.

Micrometastatic disease from breast cancer is a major concern both for clinicians and pathologists. Histologically, they can be defined as potentially invasive microfoci of tumoral cancer cells located in the vicinity of blood vessels and are a distinct entity from residual disease. They are mainly looked for in bone marrow and lymph nodes specimens and their diagnosis is currently easier thanks to immunohistochemistry. Provided a standard definition of micrometastatic disease and standard screening procedures can be met, the presence of micrometastases at the time of diagnosis could represent a major parameter in therapeutic decision-making. Although controversial, the presence of medullary and axillary lymph node micrometastases appears to be a major prognostic factor in terms of survival. Recognition of this entity could help in better defining the high-risk subset of patients who would potentially benefit from adjuvant chemotherapy.

[Radiotherapy and concomitant cisplatin in stage III non-small cell bronchial cancer: results of a pilot study]. / Radiothérapie et cisplatine concomitant dans les cancers bronchiques inopérables non à petites cellules stade III: résultats d'une étude pilote.

From July 1989 to July 1991, 73 previously untreated patients with histologically proven stage III inoperable non-small cell lung cancer have been treated with standard fractionation radiation therapy and concomitant cisplatin by continuous infusion. Thoracic irradiation was delivered at a dose of 40 grays in 20 fractions over 4 weeks to the entire mediastinum, ans was followed after a two-week rest by a boost of 30 grays in 15 fractions over 3 weeks with oblique fields sparing the spinal cord. Continuous infusion cisplatin was given during the second week or each radiation therapy sequence at a dose of 20 mg/sqm/24 hours during five days (120 hours) with usual hyperhydratation and antiemetic measures. Toxicity was essentially hematologic and gastro-intestinal but there was only 4.1% grade 3 or grade 4 complications. Radical surgery became feasible after the first cycle of treatment in 10 patients (13.7%). Complete response rate as determined by CT-scan and fiberoptic bronchoscopy was 61.6%. At a median follow-up of 26 months, actuarial overall survival at 1, 2 and 3 years was 46.6%, 27.7% and 24.5%, respectively. There were no local recurrence or distant relapses after 3 years, which will hopefully result in long-term survival in one quarter of these patients. These results compare favorably with other studies combining radiation therapy and concomitant cisplatin with different dosage and schedule. Local control appears substantially improved by this combined modality treatment over radiation therapy alone. However, the incidence of distant metastasis remains significant, especially during the first year of follow-up. Further improvement of early and long-term survival could possibly result from the incorporation in this protocol of a second drug active against subclinical dissemination.

[Preoperative radio-chemotherapy of stage III unresectable non-small cell lung cancer: results of a pilot study]. / Radio-chimiothérapie préopératoire des cancers bronchiques non à petites cellules au stade III inopérables d'emblée: résultats d'une étude pilote.

Prognosis of Stage III NSCLC remains dismal, particularly when mediastinal nodal involvement is present. In order to improve local control and to reduce early distant failures, we have treated Stage III patients with concurrent chemoradiotherapy since 1989. From September 1989 to February 1994, 140 patients were treated with concurrent chemoradiotherapy. Among these, 24 initially inoperable patients became operable after induction chemoradiotherapy. Characteristics: median age 51 years (35-70); squamous: 45.8%; non squamous: 41.7%; median tumor size: 8 cm; T3 (79.2%); T4a (12.5%); N2 (62.5%) and N3 (8.3%). Preoperative radiotherapy was delivered at a dose of 45 Gy (25 f) over 5 weeks to the mediastinum. Concurrent chemotherapy was continuous infusion cisplatin (n = 10) or cisplatin plus etoposide (n = 14). Five weeks later, radical surgery was carried out (lobectomy n = 14, pneumonectomy n = 10), followed by additional chemotherapy (n = 12) and/or radiotherapy (n = 6), according to histological response. Pathological CR rate was 29.2%. Grade III toxicities were digestive (12.5%), hematologic (8.3%) and infectious (4.2%). Three patients had severe non-lethal postoperative complications with one hemorrhage and two pneumothorax (12.5%). With a median follow-up of 41 months, overall survival at 2 and 5 years was 77.5%, and 72%, respectively. Actuarial local control at 5 years was 82.4%. Nine patients presented with distant metastases, including six with isolated brain metastases. This preoperative chemoradiotherapy regimen appears feasible without overwhelming toxicity and with an acceptable rate of postoperative complications. Despite a significant incidence of isolated brain metastases (25%), 5-year survival is highly encouraging since and appears substantially better than primary surgery.

[Adjuvant combined radiochemotherapy: a feasibility study of a new strategy in stages I and II]. / Traitement adjuvant des cancers du sein par radiochimiothérapie concomitante: étude de faisabilité d'une nouvelle alternative stratégique dans les stades I et II.

Adjuvant radiotherapy is the rule after conservative surgery for breast cancer. Furthermore, an anthracycline-based chemotherapy is recommended in node-positive patients and in poor prognosis tumors. The optimal schedule of treatment has yet to be determined, but ideally, none of these therapeutic modalities should be delayed. We have therefore conducted a feasibility trial using post-operative concurrent chemoradiation therapy with an anthracenedione. Between May 1990 and October 1994, 154 patients with stage I or II breast cancer who had benefited of either limited or radical surgery were treated with adjuvant concurrent chemoradiotherapy. Radiotherapy consisted of 50 Gy in 25 fractions over 5 weeks to the chest wall or the breast, and to the supraclavicular and internal mammary lymph nodes. When indicated, a boost of 15 Gy was then delivered to the primary tumor bed (n = 75). Starting on the first week of radiotherapy, combined chemotherapy with 5-fluorouracil, mitoxantrone, and cyclophosphamide was administered at 21-day intervals, for 4 to 6 cycles. Compliance to therapy was excellent. Median radiotherapy dose was 49.5 Gy to the chest wall or breast, and to the lymph nodes, and 14.2 Gy to the tumor bed. Chemotherapy was given at full dose in over 80% of the cases and the 21-day interval between cycles was respected in 31%. In 45% of the cases, a 28-day interval was required due to toxicity, and at least one interval longer than 28 days was necessary in the remainder of the patients. Main toxicities were nausea and vomiting (20.8%) and grade 3-4 neutropenia (12.3%). Grade 1 cutaneous toxicity occurred in 62.3% of the cases, and severe grade 3 radiation dermatitis requiring temporary interruptions of therapy in 4.5%. With the exception of one case of grade 3 acute cardiac toxicity, there was no other severe side-effects. In conclusion, this pilot study demonstrates the feasibility of concurrent chemoradiation therapy with an anthracenedione for stage I and II breast cancer in the adjuvant setting. Whether this approach compares favorably with standard sequential therapy in terms of long-term results remains to be determined and should be assessed in a phase III trial.

[Concomitant radiochemotherapy for locally advanced bronchial cancers: current results and prospects]. / Radio-chimiothérapie concomitante dans les cancers bronchiques localement évolués: résultats actuels et perspectives.

The prognosis of locally advanced lung cancer is reportedly poor in all histologic types. In non-small cell lung cancer, radiation therapy alone results in disappointing long-term survival. Three recent randomized trials, however, have shown a limited but significant improvement of survival with induction chemotherapy, though local control remained poor in these studies as well as in small-cell lung cancer treated with chemotherapy and late radiotherapy. Two randomized trials focusing on small-cell lung cancer have recently shown significant benefit due to the combination of early concurrent mediastinal irradiation and chemotherapy, with major improvement in local control and a more than 40% 2-year survival rate. The concept of concurrent chemoradiotherapy has also been studied in non-small cell carcinoma with several pilot studies leading to both encouraging results and improved survival rate (up to 40% at 2 years). Ongoing phase III trials are comparing sequential versus concurrent chemoradiotherapy and will define the role of radical surgery after chemoradiotherapy in locally advanced non-small cell lung cancer.

[Concomitant radiochemotherapy with cisplatin-etoposide with or without surgery in stage III non-small cell lung cancers: results of a pilot study in 67 patients]. / Radio-chimiothérapie concomitante avec cisplatine-étoposide avec ou sans chirurgie dans les cancers bronchiques non à petites cellules au stade III: résultats d'une étude pilote chez 67 patients.

PURPOSE: This pilot phase II study was aimed at determining the feasibility, toxicity, response rate, local control, and survival of concomitant chemotherapy with cisplatin-etoposide and radiotherapy in stage IIIA or IIIB non small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between February 1992 and February 1994, 67 patients with either medically or technically inoperable stage III NSCLC were treated with concomitant chemoradiotherapy. Thoracic radiotherapy was administered to a median dose of 60 Gy over 6 weeks. Concomitant chemotherapy consisted of cisplatin 20 mg/m2/day plus etoposide 50 mg/m2/day from day 1 to day 5, every 4 weeks over four cycles. Medically operable patients were evaluated for surgical resection after a 45-Gy irradiation and two cycles of concomitant chemotherapy. Only 14 patients could undergo subsequent surgery. RESULTS: With a median 49-month and a minimum 34-month follow-up, the overall survival rate was 42% at 2 years, and 34% at 4 years. The median survival was 19 months and the actuarial local control rate was 57% at 3 years. Toxicity was mainly associated with myelosuppression and esophagitis, but could be treated and was of short duration. CONCLUSION: Concomitant chemoradiotherapy with cisplatin and etoposide at this dose level provides a well tolerated outpatient regimen that results in high local control rate and encouraging survival at 2.4 years. A similar regimen is being compared in a phase III trial including induction chemotherapy followed by radiotherapy.

[Preoperative concurrent radiochemotherapy for cancer of the rectum]. / Radiochimiothérapie concomitante préopératoire pour cancer du rectum.

PURPOSE: To evaluate retrospectively treatment-related morbidity of concurrent radiotherapy and chemotherapy for rectal cancer. PATIENTS AND METHODS: Between 1992 and 1995, 38 patients (median age: 60) were treated for locally advanced resectable rectal cancer. Median dose of radiotherapy was 45 Gy/25 fractions/5 weeks. Chemotherapy consisted of two courses of 5-fluorouracil and leucovorin administered during the first and the fifth weeks of radiotherapy. Median dose of 5-fluorouracil was 350 mg/m2/day, and median dose of leucovorin was 20 mg/m2/day, day 1 to day 5. Surgery was performed 5 weeks after completion of radiotherapy. RESULTS: Before surgery, one patient died of febrile neutropenia and sepsis after two cycles of chemotherapy and 45 Gy. Main pre-operative grade 3-4 toxicities were respectively: neutropenia: 3%; nausea/vomiting: 3%; diarrhea: 3%; proctitis: 5%; radiation dermatitis: 8%. Twenty-six patients underwent a low anterior resection and 11 an abdomino-perineal resection. A temporary colostomy was performed in 12 patients. Pathologic complete response rate was 27%. There was one post-operative death due to thromboembolic disease. Major post-operative grade 3-4 complications were: pelvic infection: 14%; abdominal infection: 5%; perineal sepsis: 8%; anastomotic dehiscence: 8%; cardiac failure: 5%. Delayed perineal wound healing was observed in six patients. No significant prognosic factor of post-operative complications has been observed. Median duration of hospitalization was 22 days. With a median follow-up of 24 months, 2-year overall and disease-free survival rates were 82 and 64%. CONCLUSION: Tolerance of preoperative concurrent chemoradiotherapy was acceptable. Ongoing controlled studies will assess the impact of this combined treatment on survival.

[Treatment of obstructive bronchial cancers with high dose, endobronchial curietherapy. Technical aspects and clinical results]. / Traitement des cancers bronchiques obstructifs par curiethérapie endobronchique à haut débit. Aspects techniques et résultats cliniques.

Between September 1990 and September 1991, 35 patients with mainly recurrent or residual endobronchial carcinoma were treated with 91 high-dose-rate endobronchial brachytherapy applications. Treatment technique was fairly simple and could easily be performed on an outpatient basis. Endoscopic placement of one or two applicators is followed by computerized dosimetry and irradiation during a median time of 10 minutes. Treatment included 3 sessions of 10 grays measured at 10 mm from the center of the radioactive source at 2-week intervals. Response rate was 81.8% including 51.5% complete clinical response. There were 12 microscopically complete response out of 14 patients biopsied. Immediate tolerance was excellent in 90% of cases. However, late complications were severe in 25% of cases. Ongoing radiobiological research should determine an optimal therapeutic approach in term of efficacy and long term toxicity before using endobronchial brachytherapy as a part of the initial management of unresectable lung cancers.

[Stage III non-small cell lung cancers: prospects of concomitant radiochemotherapy]. / Cancers bronchiques non à petites cellules stade III: perspectives de la radiochimiothérapie concomitante.

The prognosis of stage III non small cell lung cancer is reportedly poor, particularly in patients with mediastinal lymph node involvement. These patients may be either good surgical candidates, marginally resectable, or inoperable for technical or medical reasons, but, in any case, surgery and/or radiotherapy are curative in only a minority of them. The high incidence of early distant failures underscores the need for early and effective systemic therapy in association with local treatment, since occult metastatic disease is present in most patients at the time of diagnosis. Recent phase III trials have demonstrated significant benefit to induction chemotherapy prior to irradiation or surgery in reducing the distant metastasis rate. However, poor local control remains a major issue in these locally advanced tumors. In patients with inoperable disease, the concomitant use of chemotherapy along with radiotherapy substantially improves local control. For operable patients, induction chemotherapy with concomitant moderate-dose radiotherapy improves local control as well, and may facilitate surgical resection in marginally operable cases. Currently, a number of phase II clinical trials report encouraging results with concomitant chemoradiotherapy used either prior to surgery or with curative intent in locally advanced non small cell lung cancer.

Combined radiation therapy and cisplatin for locally advanced carcinoma of the urinary bladder.

BACKGROUND: This study evaluates feasibility and results of combined treatment of cisplatin and radiation therapy for patients with inoperable invasive bladder carcinoma. METHODS: From January 1988 to October 1991, 69 patients received radiation therapy and concomitant cisplatin. Median age was 71 years. Most tumors were locally advanced and high grade. A macroscopically complete transurethral resection was performed initially in 18 patients. Dose of pelvic radiation ranged from 40 Gy to 45 Gy, and total dose to the bladder ranged from 55 Gy to 60 Gy. Concomitant continuous cisplatin infusion at a dose of 20-25 mg/m2/day for 5 days was delivered during the 2nd and 5th weeks of radiation. RESULTS: As of April 1993, the median follow-up time was 36.4 months (range, 18-70 months). Ninety-one percent of the patients completed radiation therapy as planned, and 78.3% completed two courses of chemotherapy. Despite one treatment-related death due to renal failure, toxicity was generally mild and acceptable. Sixty-three patients were evaluable for response. Forty-eight patients (76.2%) achieved a complete response. Actuarial overall 3-year survival rate was 37.1% for all patients. Among the patients who experienced complete response, the 3-year actuarial local control and disease-free survival rates were 65.4% and 56.3%, respectively. Twenty-six patients (37.7%) are alive and disease-free with bladder preservation. One patient is alive and disease-free after salvage cystectomy. CONCLUSIONS: Concomitant cisplatin and radiation therapy offers high probability of complete response and local control in patients with invasive bladder cancer unsuitable for surgery. These results provide a basis for randomized studies comparing this approach with conventional therapy for patients with operable carcinoma.

Concurrent cisplatin and radiotherapy for patients with muscle invasive bladder cancer who are not candidates for radical cystectomy.

PURPOSE: We assessed the results and prognostic factors in patients with bladder cancer treated conservatively with concurrent cisplatin and radiotherapy. MATERIALS AND METHODS: A total of 109 patients with localized muscle invasive bladder cancer who were not candidates for radical cystectomy underwent concomitant chemotherapy and radiation. Median patient age was 70 years. Of the patients 36% had stages T3B and 4 tumors, and 37% had benefited from prior macroscopically complete transurethral resection. Pelvic irradiation consisted of 40 to 45 Gy., and was followed by a boost to the bladder to a total dose of 55 to 60 Gy. Continuous infusion cisplatin (20 to 25 mg./m.2 daily for 5 days) was delivered during weeks 2 and 5 of radiation therapy. RESULTS: Median followup was 54.8 months. The projected 4-year locoregional control rate was 47.6% for the 109 patients and 61.2% for 76 with a complete response. Projected overall 4-year survival was 41.9% for all patients and 51.4% for complete responders. Univariate analysis of prognostic factors was done for local control and survival. Local control was statistically better in patients with a good performance status, stages T2 and 3A disease, complete initial transurethral resection and without hydronephrosis. In terms of overall survival 4 factors were significant: 1) performance status, 2) T stage, 3) absence of hydronephrosis and 4) complete response. By multivariate analysis performance status, hydronephrosis and T stage were significant factors for local control, while T stage and complete response were the strongest determinants for survival. CONCLUSIONS: Concurrent cisplatin and radiation therapy is a potentially curative and conservative treatment for patients with localized muscle invasive bladder cancer who are not candidates for radical surgery, particularly those with intravesical stages T2 and T3A tumors.