[Dosimetric evaluation of conformal radiotherapy: conformity factor]. / Evaluation dosimétrique d'une radiothérapie conformationnelle: le facteur de conformation.

The aim of three-dimensional conformal therapy (3DCRT) is to treat the Planning Target Volume (PTV) to the prescribed dose while reducing doses to normal tissues and critical structures, in order to increase local control and reduce toxicity. The evaluation tools used for optimizing treatment techniques are three-dimensional visualization of dose distributions, dose-volume histograms, tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP). These tools, however, do not fully quantify the conformity of dose distributions to the PTV. Specific tools were introduced to measure this conformity for a given dose level. We have extended those definitions to different dose levels, using a conformity index (CI). CI is based on the relative volumes of PTV and outside the PTV receiving more than a given dose. This parameter has been evaluated by a clinical study including 82 patients treated for lung cancer and 82 patients treated for prostate cancer. The CI was low for lung dosimetric studies (0.35 at the prescribed dose 66 Gy) due to build-up around the GTV and to spinal cord sparing. For prostate dosimetric studies, the CI was higher (0.57 at the prescribed dose 70 Gy). The CI has been used to compare treatment plans for lung 3DCRT (2 vs 3 beams) and prostate 3DCRT (4 vs 7 beams). The variation of CI with dose can be used to optimize dose prescription.

[Definition of prostatic contours using tomodensitometric slices: study of differences among radiotherapists and between examinations]. / Définition des contours prostatiques sur coupes tomodensitométriques: étude des discordances entre radiothérapeutes et entre examens.

Accuracy of conformal treatment planning for prostatic radiotherapy is based on the contours of target volumes (prostate +/- seminal vesicles) and normal tissues (rectum and bladder), drawn on CT (computed tomography) images by radiation oncologists. The interpretation of a given CT image can be different from one radiation oncologist to another, and may change in time with the state of filling of the bladder and of the rectum during the treatment. In order to quantify these variations, 12 patients treated with conformal radiotherapy for prostate carcinoma (pelvis 40 Gy/20 sessions + prostate 30 Gy/15 sessions) had two series of CT at one month intervals. Contouring of prostate, rectum and bladder were performed independently on each CT by two radiation oncologists. The first CT scan (planning CT) and the first series of contours (planning contours) were used for treatment planning. The contours of the second scan were compared to the planning contours after image fusion based on manual superimposition of bony anatomy of the two sets of CT images. Coherence ratio were defined to measure discrepancies in prostate volumes between radiation oncologists (RCE) and between scans (RCT). The mean RCE was 38 +/- 7% (1 standard deviation). Those discrepancies were primarily located at the prostate apex and at the interface between bladder and prostate and between rectum and prostate. The mean RCT was 42 +/- 8% (1 sigma). Those discrepancies were due to the prostate motion related to the state of filling of the rectum and bladder. For bladder and rectal walls, less important differences were observed between the two radiation oncologists for the same CT (4.5% for rectal volume receiving 65 Gy or more, 3% for bladder volume receiving 65 Gy or more). However, important differences in bladder and rectal volumes receiving 65 Gy or more (16% and 7% respectively) were noted for the same patient from a CT to another due to the variation in bladder or rectal filling. New techniques for planning CT acquisition are needed to decrease the discrepancies due to contouring. The treatment must, as far as possible, be delivered with an empty bladder and rectum in order to ensure a good reproduction of the initially planned treatment.

[Endobronchial brachytherapy]. / Curiethérapie endobronchique.

Endobronchial brachytherapy was developed following the miniaturization of radio-active sources enabling the use of fiberoptic techniques to deliver treatment at high dose yet substantially reducing the duration of treatment. Endobronchial brachytherapy has been used in patients presenting with symptomatic obstruction of the proximal bronchial tree in association with laser therapy. The level of responses in these palliative indications is around 80 per cent. Currently, other investigations are undergoing evaluation to test the method in association with conventional treatment to determine whether brachytherapy can augment local control. In the treatment of small tumours when other conventional treatments are not possible brachytherapy employed alone has shown undoubted efficacy. However there remain numerous problems to resolve: what is the ideal protocol in terms of total dose, dose per fraction, the order of dosing and fractions? How can secondary complications to endoluminal irradiation be limited in particular for curative therapy. An answer should be found for all these questions before this technique is eventually integrated into the primary treatment regimes for bronchial cancer.

[Conservative treatment of anal canal carcinoma with external radiotherapy and interstitial brachytherapy, with or without chemotherapy: long-term results]. / Traitement conservateur des cancers du canal anal par irradiation suivie de curiethérapie interstitielle, avec ou sans chimiothérapie: résultats à long terme.

PURPOSE: A retrospective analysis of conservative treatment of anal canal cancers with external radiation therapy and interstitial brachytherapy with or without chemotherapy. PATIENTS AND METHODS: From 1986 to 1996, 69 patients were treated with external radiotherapy (40 Gy/20 fractions) and interstitial brachytherapy (20 Gy) after a mean interval of six weeks for a localized epidermoid carcinoma of the anal canal. Patients who did not complete the whole therapeutic sequence were not included. Forty-five patients received additional 5-fluorouracil- and/or mitomycin C-based chemotherapy regimen. RESULTS: Acute toxicity was acceptable. Complete response rate was 81%. Actuarial local control rate was at two and five years, 65% and 59% respectively (median follow-up: eight years). At two, five and ten years, actuarial colostomy rate was 26%, 33% and 33% respectively, and colostomy-free survival rates 61%, 47% and 37%. Overall survival at two, five and ten years was 81%, 65% and 53% respectively. Distant metastases occurred in 11 patients (16%). Prognostic factors for overall survival were performance status (PS) (79% survival at five years for patients with PS 0 versus 50% for patients with PS 1-3, P = 0.04) and tumor stage (80% at five years for T1-T2 versus 53% for T3-T4, P = 0.03). Overall treatment time less than 12 weeks and time interval between external radiotherapy and brachytherapy inferior than six weeks were associated with a better local control (P = 0.05). In multivariate analysis, these prognostic factors were not significant. CONCLUSION: These results confirm the efficacy of external radiotherapy and brachytherapy in the treatment of small anal canal cancers, and point out the need for improving treatment outcome of larger tumors.

[Treatment of infiltrating cancer of the bladder with cisplatin, fluorouracil, and concurrent radiotherapy: results of a pilot study]. / Traitement des cancers infiltrants de vessie par cisplatine, fluoro-uracile et radiothérapie concomitante: résultats d'une étude pilote.

PURPOSE: Pilot study to assess treatment feasibility and results of a 2-drug chemotherapy (CT) regimen administered concurrently with radiotherapy (RT) for muscle-invasive bladder cancer. MATERIALS AND METHODS: Fourty-six patients were included into a prospective study from December 1992 to April 1996. The median age was 66 years. Thirty-seven percent of the patients had T3B-T4 tumors, and 46% had benefited from prior macroscopically complete transurethral resection (TUR). Pelvic irradiation consisted of 50.4 Gy in 28 fractions over 39 days. Concurrent CT consisting of cisplatin (80 mg/m2/d1) and 5-fluorouracil (800 mg/m2/d2 to 5) by continuous infusions (5-FU) was delivered during the first and fifth weeks of radiation therapy. Twenty-three patients received two additional courses of adjuvant CT with cisplatin, methotrexate and vinblastin (MCV). RESULTS: The median follow-up was 38 months. The feasibility of concurrent CT-RT was excellent: 96% of the patients completed radiotherapy and 100% of them received the two courses of P-FU. The acute toxicity was mild: no hematological toxicity or renal toxicity over grade II, 4 cases of bowel or rectal reversible grade III toxicity and 2 cases of reversible grade III cystitis. A complete response was achieved in 30 out of the 42 evaluable patients (65.2%). Nine patients received an immediate salvage treatment (3 TUR, 3 additional radiotherapy and 3 cystectomies). Ten patients had local failure. Projected 3-year locoregional control was 49% for the 46 patients. Projected overall 3-year survival was 53%. Functional results were good for disease-free patients with preserved bladder: 1 grade I, 3 grade II, and no grade III cystitis. CONCLUSION: Concurrent 2-drug chemoradiotherapy with cisplatin and 5-fluorouracil is feasible without major toxicity and offers a potentially curative and conservative treatment for patients with localized muscle-invasive bladder cancer.

[Results of long-term treatment of inoperable cancer of the bladder with cisplatin and concurrent irradiation: prognostic factors of local control and survival]. / Résultats à long terme du traitement des cancers de vessie inopérables par cisplatine et irradiation concomitante: facteurs pronostiques du contrôle local et de la survie.

PURPOSE: Therapeutic strategies for muscle invasive bladder cancer are currently evolving. A recent European randomized study has shown that neoadjuvant chemotherapy does not improve the chance of cure or and radiotherapy would provide better results but there is a need to identify by prognostic factors patients who may benefit from such a conservative strategy. MATERIAL AND METHODS: One hundred and nine patients with localized muscle-invasive bladder cancer, who were not candidates for radical cystectomy, were treated with concomitant cisplatin and radiation therapy. Their mean age was 71. Thirty-six percent of the patients had T3B-4 tumors, and 37% had benefited from prior macroscopically complete transurethral resection (TUR). 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/m2/d for 5 days) was delivered during the second and fifth weeks of radiation therapy. RESULTS: Median follow-up was 73 months. The projected 5-year locoregional control rate was 43% for the 109 patients and 55% for the 86 patients with complete response. The projected overall 5-year survival rate was 36% for all patients and 44% for complete responders. Univariate analysis of prognostic factors was carried out for local control, and survival. The local control was statistically better in patients with good performance status, T2-3A, complete initial TUR, and in patients without hydronephrosis. In terms of overall survival, four factors were significant: the performance status, T-stage, absence of hydronephrosis, and 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. CONCLUSION: Concurrent cisplatin and radiation therapy is a potentially locally curative treatment for 43% of patients with muscle-invasive bladder cancer not candidates for radical surgery. Clinical T-stage and hydronephrosis have a significant and independent prognostic value on local control but appears not discriminant enough to select patients for conservative treatment.

[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.

High dose rate endobronchial brachytherapy: results and complications in 189 patients.

The purpose of this study was to determine the benefit of high dose rate endobronchial brachytherapy in the treatment of obstructive lung cancer. Between September 1990 and March 1995, 189 patients with bronchogenic carcinoma were treated with high dose rate endobronchial brachytherapy. Most patients (69.3%) had received prior treatment and presented with symptomatic bronchial obstruction due to either recurrent or residual endobronchial disease. A small group (12%) was medically unfit for either surgical resection or thoracic radiotherapy and benefited from endobronchial brachytherapy alone for small endobronchial tumours. The remainder of the patients had not been treated previously and endobronchial brachytherapy was performed for life-threatening symptoms requiring emergency obstruction relief before other therapy. Treatment was performed weekly and consisted of three to four 8 to 10 Gy fractions at a radius of 10 mm from the centre of the source. Major symptomatic relief was obtained for haemoptysis (74%), dyspnoea (54%), and cough (54%). Complete endoscopic response was observed in 54% of cases. Median survival was 7 months for the entire group. For small, strictly endobronchial tumours, complete response rate was 96%, median survival 17 months, and 30 month survival 46%, with a plateau starting at 18 months. Grade 3 to 4 toxicities occurred at a rate of 17% and included massive haemoptysis (n=13), bronchial stenosis (n=12), soft tissue necrosis (n=8), and bronchial fistula (n=3). By univariate analysis, no factor was found to be predictive of late pulmonary toxicity. The present study confirms the usefulness of endobronchial brachytherapy in alleviating symptoms caused by endobronchial recurrence of bronchogenic carcinoma. In addition, this therapy can be tried with curative intent in patients who present with small endobronchial tumours and are not candidates for other forms of therapy.

[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.

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.

[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.

[High-dose rate endobronchial brachytherapy: results and complications in 189 patients]. / Curiethérapie endobronchique à haut débit de dose: résultats et complications chez 189 patients.

Between September 1990 and March 1995, 189 patients were treated with high-dose-rate endobronchial brachytherapy. Most patients (70%) presented with either recurrent or persistent symptomatic endobronchial tumor after standard therapy. A minority of the patients (12%) had small endobronchial tumor and were unfit for surgical resection or radiotherapy. Treatment was delivered weekly and consisted of three to four 8- to 10-Gy radiotherapy fractions applied at 10 mm from the source. Major symptomatic improvement was obtained on hemoptysis (74%), dyspnea (54%), and cough (54%). Complete endoscopic response occurred in 54.5% of the cases. Median survival was 7 months for the entire group. For small strictly endobronchial tumors, complete response rate was 95.5%, median survival was 17 months, and 30-month survival was 46%, with a plateau starting at 18 months. The rate of late grade 3 to 4 toxicity was 17%, including hemoptysis (n = 13), stenosis (n = 12), local necrosis (n = 8), and bronchial fistula (n = 3). By univariate analysis, no factor was found to be predictive of late toxicity. Our study confirms the benefit of endobronchial brachytherapy in the palliative treatment of endobronchial recurrences and in the curative intent treatment of small endobronchial tumors in patients not suitable for other forms of therapy.

[Lymphoscintigraphic aspects of the effects of manual lymphatic drainage]. / Aspects lymphoscintigraphiques des effets du drainage lymphatique manuel.

Manual lymphatic drainage is used in physiotherapy of limb lymphedema in combination with other physical techniques. In order to assess the effectiveness of the method, 47 patients with upper limb lymphedema after radiosurgical therapy for breast cancer underwent lymphoscintigraphy. The examination was performed after subcutaneous injection of technetium-labeled colloid via the fourth and first interdigital space on the hand of the limb with lymphedema. The level of the technetium label was compared on scintigraphies performed before and after manual lymph drainage. Results were analyzed as a function of the clinical characteristics of the edema. Manual lymphatic drainage produced an effective progression of the label in 25 cases (53.2%), independent of radiotherapy. Contralateral lymph nodes were reached in 5 cases and the homolateral internal mammary nodes in 2. These nodes were visualized only after manual lymphatic drainage. The visualization of the drainage routes in unexpected areas demonstrated the effectiveness of the technique in stimulating accessory routes useful for resorption of lymphedema. The use of two injection sites on the hand is also discussed. This study demonstrated the effect on a single session of manual lymphatic drainage and should be completed with an assessment of a complete series of manual lymphatic drainages.

[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.

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.

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.

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.

[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.

Serum prostate-specific antigen in monitoring the response of carcinoma of the prostate to radiation therapy.

In order to assess the value of serum prostate-specific antigen (PSA) levels in the monitoring of patients with localized prostatic carcinoma undergoing radical radiation therapy, 146 previously untreated patients were entered into this study. Sixty to 70 Gy were administered to the prostate over 8 to 9 weeks. Serum PSA levels were measured prior to radiotherapy, every 3 months during the first year and every 6 months thereafter. Median follow-up was 28 months. Pretreatment PSA values exceeded 10 ng/ml in 62% (91/146). Initial PSA values were correlated with tumor size and Gleason score. Six months after completion of radiation therapy, PSA levels decreased as compared to initial value in 88.3% of the patients. It had fallen to 10 ng/ml or less in 54 (59%) out of the 91 patients with initial abnormal PSA levels. Patients whose initial PSA exceeded 50 ng/ml attained levels of 10 ng/ml or less in only 19% of the cases (6/32). Only 3 of the 55 patients (5.5%) with both initial and 6-month PSA values less than or equal to 10 ng/ml developed metastasis. Out of the 91 patients with initial PSA values over 10 ng/ml, 54 (59.6%) had a 6-month PSA level of 10 ng/ml or less, and only 4/54 (7.4%) relapsed. By contrast, 13 of the 37 patients (35.1%) with a 6-month PSA value persistently above 10 ng/ml relapsed. The 3-year relapse-free survival is 85.1% for patients with a 6-month PSA level less than or equal to 10 ng/ml, and 50.2% for patients with persistently elevated PSA values.(ABSTRACT TRUNCATED AT 250 WORDS)