Pattern of failures in gastric cancer patients with lymph node involvement treated by surgery, intraoperative and external beam radiotherapy.

AIMS: High local failure rates in gastric cancer have been reported, up to 67%. To achieve a better local control, we evaluated intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT) in association with surgery for gastric cancer patients with lymph node involvement. We report here the analysis of the patterns of failure for patients involved in this IORT protocol. MATERIAL AND METHODS: Forty-two positive lymph node (N+) gastric cancer patients were operated on (31 total, three subtotal and eight extended gastrectomies) with IORT procedure between 1985 and 1997 (33 males, nine females, mean age 61.3 years). IORT was focused on coeliac area (mean dose 15 Gy), followed by EBRT (46 Gy) in 36 patients. Ten patients were pN1 and 32 were pN2. A concurrent systemic chemotherapy (five Fluoro-Uracil and Cisplatinum) was performed in 14 patients. RESULTS: One patient died postoperatively. Actuarial pN+ 10 year survival rate was 44.8%. The 5 year actuarial local control and disease-free survival rates were 78.8 and 47.5%, respectively. As far as patterns of failure were explored, 5 patients have a local coeliac recurrence (12%) and 12 have distant metastases with no evidence of coeliac recurrence. CONCLUSION: This retrospective analysis suggests a potential effect of IORT and/or EBRT in promoting local control and long-term survival in gastric cancer patients with lymph node involvement.

[Gross tumor volume and clinical target volume in radiotherapy: lung cancer]. / Volume tumoral macroscopique et volume-cible anatomoclinique en radiothérapie: cancer bronchique.

Radiotherapy plays a major role as a curative treatment of various stages non-small cell lung cancers (NSCLC): as an exclusive treatment in curative attempt for patients with unresectable stages I and II; as a preoperative treatment, which is often associated with chemotherapy, for patients with surgically stage IIIA NSCLC in clinical trials; in association with chemotherapy for unresectable stages IIIA and IIIB patients. Currently, three-dimensional conformal radiotherapy allows for some dose escalation, increasing radiation quality. However, the high inherent conformality of this radiotherapy technique requires a rigorous approach and an optimal quality of the preparation throughout the treatment procedure and specifically of the accurate definition of the safety margins (GTV, CTV...). Different questions remain specific to lung cancers: 1) Despite the absence of randomized trials, the irradiated lymph nodes volume should be only, for the majority of the authors, the visible macroscopically involved lymph nodal regions. However, local control remains low and solid arguments suggest the poor local control is due to an insufficient delivered dose. Therefore the goal of radiotherapy, in this particular location, is to improve local control by increasing the dose until the maximum normal tissue tolerance is achieved, which essentially depends on the dose to the organs at risk (OAR) and specifically for the lung, the esophagus and the spinal cord. For this reason, the irradiated volume should be as tiny as possible, leading to not including the macroscopically uninvolved lymph nodes regions in prophylactic view in the target volume; 2) The lung is one of the rare organs with extensive motion within the body, making lung tumors difficult to treat. This particular point is not specifically considered in the GTV and CTV definitions but it is important enough to be noted; 3) When radiation therapy starts after a good response to chemotherapy, the residual tumoral volume should be defined as the target volume in place of the initial tumor volume. These different elements are discussed in this paper.

Intraoperative radiotherapy and external beam radiation therapy in gastric adenocarcinoma with R0-R1 surgical resection.

INTRODUCTION: The aims of this study were to evaluate the results of intraoperative radiotherapy (IORT) and external beam therapy (EBRT) in the treatment of gastric adenocarcinoma. METHODS: From 1986 to 1999, 87 patients who underwent surgical resection for gastric adenocarcinoma combined with IORT were reviewed. A R0 surgical resection was performed in 82 patients and five underwent R1 resection. The stage was: pT1 in 12, pT2 in 19, pT3 in 44 and pT4 in seven. Thirteen patients were pN1 and 43 were pN2, The IORT dose ranged from 12 to 23 Gy. Patients with pT3 and/or pN tumours underwent EBRT with a standard dose of 44-46 Gy. RESULTS: The post-operative mortality and morbidity rates were 2.3 and 6.8%, respectively. The 5-year survival rate for R0 patients was 60%, for R0-pN0 was 90% and for R0-pN+ patients was 55%. The local failure rate in the 19 pN+ patients was 21%. CONCLUSION: IORT and EBRT combined with surgical resection may provide overall survival, improving the local control after gastrectomy.

Intra-operative electron radiotherapy as a conservative treatment for infiltrating bladder cancer.

The intent of this feasibility study was to evaluate the use of intra-operative electron radiotherapy (IOERT), after transurethral resection (TUR), combined with external beam radiation with concurrent chemotherapy for the conservative treatment of infiltrating bladder cancer. From November 1988 to June 1998, 27 patients with histologically proven non-metastatic infiltrating bladder cancer were included in this protocol. The treatment consisted of: TUR, external beam irradiation (x18 MV:48 Grays (Gy)/24 fractions/5 weeks), with concurrent chemotherapy (cisplatin 30 mg/day for 3 days-two cycles during irradiation), followed by control cystoscopy and cystotomy with IOERT (e 9 MeV:15 Gy). 14 patients received two cycles of neoadjuvant methotrexate, vinblastine and cisplatin (MVC) and folinic acid chemotherapy. Patients were evaluated for toxicity, local control and survival. The 5-year overall and cystectomy-free survival rates were 53.3% +/-11.1% and 48.1%+/-11.4%, respectively. 4 patients developed infiltrating intravesicular recurrence (3 were treated by salvage cystectomy), and an additional patient developed a superficial recurrence. 2 patients subsequently developed regional recurrence in pelvic nodes and 10 patients were found to have distant metastases. The protocol was found to be feasible and associated with acceptable toxicity. Early and late toxicities consisted of 3 cases of bladder mucosal necrosis or ureteral stenosis which resolved with medical management. These preliminary results indicate that IOERT combined with TUR and neoadjuvant external beam radiation with concurrent chemotherapy is feasible. It could be considered as an alternative therapy for infiltrating carcinoma of the bladder, especially in patients unfit for radical surgery, and is well adapted to treat lesions of the fixed portion of the bladder.

Curative external beam radiotherapy for prostate carcinoma: results in 231 patients treated in Lyon.

BACKGROUND: Radical prostatectomy and external beam radiation therapy (EBRT) are the mainstays of treatment of prostate cancer with curative intent. The possible development of radiation proctitis and rectal bleeding are major concerns when using EBRT. Recently, conformal radiotherapy has been introduced in an attempt to improve the results of EBRT. This paper presents an overview of the Lyon experience using standard EBRT with doses of 68 Gy, and reports the preliminary results of a study of conformal radiotherapy with dose escalation. METHODS: From 1981 to 1995, EBRT was used to treat 231 patients with localized adenocarcinomas of the prostate. The dose of EBRT was 68 Gy/34 fractions/7 weeks using a four-field box technique with 18-MeV photons. A feasibility study of conformal radiotherapy was commenced in 1996. To date, 145 patients have been treated with doses escalating from 68 to 80 Gy. RESULTS: In the EBRT group of 231 patients, the 5-year overall survival was 80.3%. Anorectal function was scored as excellent in 90% of patients. Rectal bleeding was seen in 14.3% of patients and required local treatment in only seven. In the group treated with conformal radiotherapy, the preliminary results indicate good early tolerance. CONCLUSION: The curative treatment of patients with prostate cancer using EBRT gives good long-term survival with low rectal toxicity. Conformal radiotherapy appears to be an interesting approach to improve local control and perhaps survival.

Intraoperative radiation therapy combined with limited lymph node resection in gastric cancer: an alternative to extended dissection?

PURPOSE: To describe the results of a series of 63 Western patients presenting with gastric adenocarcinoma and treated with surgery and intraoperative radiation therapy (IORT) over a 8-year period and to discuss the role of IORT when combined with limited lymph node dissection. METHODS AND MATERIALS: From 1986 to 1993, 63 patients with gastric adenocarcinoma have been operated in the department of radiation oncology of the Hospices Civils de Lyon. The stage was: I in 17, II in 11, IIIA in 9, IIIB in 20, and IV in 6. The lymph node dissection was considered to be limited in 56 patients and extended in 7. The IORT dose ranged from 12 to 23 Gy (median: 15). Thirty patients also underwent a postoperative external beam irradiation with a standard dose of 44-46 Gy. RESULTS: The postoperative mortality rate was 4.8%. The 5-year overall survival in the entire series was 47% and was 82, 55, 78, 20, and 0% in Stages I, II, IIIA, IIIB, and IV, respectively. Loco-regional relapse occurred in 15 of 63 patients and metastases in 15 of 63. CONCLUSION: In Western patients treated by gastrectomy for adenocarcinoma of the stomach, IORT combined with limited lymph node dissection may provide overall survival similar to that observed after gastrectomy with extended lymph node dissection but with less postoperative mortality.

Intraoperative radiotherapy in resected pancreatic cancer: feasibility and results.

BACKGROUND AND PURPOSE: To evaluate the impact of intraoperative radiotherapy (IORT) combined with postoperative external beam irradiation in patients with pancreatic cancer treated with curative surgical resection. MATERIALS AND METHODS: From January 1986 to April 1995 25 patients (11 male and 14 female, median age 61 years) underwent a curative resection with IORT for pancreatic adenocarcinoma. The tumour was located in the head of the pancreatic gland in 22 patients, in the body in two patients and in the tail in one patient. The pathological stage was pT1 in nine patients, pT2 in nine patients, pT3 in seven patients, pN0 in 14 patients and pN1 in 11 patients. All the patients were pM0. A pancreaticoduodenectomy was performed in 22 patients, a distal pancreatectomy was performed in two patients and a total pancreatectomy was performed in one patient. The resection was considered to be complete in 20 patients. One patient had microscopic residual disease and gross residual disease was present in four patients. IORT using electrons with a median energy of 12 MeV was performed in all the patients with doses ranging from 12 to 25 Gy. Postoperative EBRT was delivered to 20 patients (median dose 44 Gy). Concurrent chemotherapy with 5-fluorouracil was given to seven patients. RESULTS: The overall survival was 56% at 1 year, 20% at 2 years and 10% at 5 years. Nine local failures were observed. Twelve patients developed metastases without local recurrence. Twenty patients died from tumour progression and two patients died from early postoperative complications. Three patients are still alive; two patients in complete response at 17 and 94 months and one patient with hepatic metastases at 13 months. CONCLUSION: IORT after complete resection combined with postoperative external beam irradiation is feasible and well tolerated in patients with pancreatic adenocarcinoma.

[Stereotaxic radiotherapy: status in France in January 1997]. / La radiothérapie stéreotaxique: situation en France en Janvier 1997.

Stereotactic radiosurgery has been used in France since 1986 in the treatment of arteriovenous malformations and brain neoplasms, and has been performed in 23 public and private centres. We briefly describe the techniques used in these centres and review the results of French teams, which are comparable to those reported in the world literature.

Adenocarcinoma of the body and tail of the pancreas: is there room for adjuvant radiotherapy?

AIMS AND BACKGROUND: Adenocarcinoma of the body and tail of the pancreas is a rare malignancy with a poor prognosis. Few long-term survivors have been reported in the literature. The role of adjuvant treatment after curative resection has not yet been assessed. This retrospective study aims to describe the patterns of failure and the survival of 10 patients treated with resection and adjuvant radiotherapy. MATERIALS AND METHODS: From 1982 to June 1994, 10 patients with adenocarcinoma of the body and tail of the pancreas received adjuvant radiotherapy in our department. There were 4 females and 6 males, with a median age of 63 years (range, 45-77). The pT distribution was 2 pT1, 4 pT2, 4 pT3 and for pN it was 7 pN0 and 3 pN1. Four patients had stage I, 3 stage II and 3 stage III disease. All the patients underwent a resection: distal pancreatectomy in 7, partial resection of the body in 1, and total pancreatectomy in 2. Gross residual disease was present in 2 cases. Three patients received intraoperative radiotherapy up to a dose of 12-15 Gy. Postoperative radiotherapy was given in 9 patients with a dose ranging from 40 to 50 Gy (median, 45). One patient who received intraoperative radiotherapy had no postoperative radiotherapy. In 4 patients, chemotherapy with 5-fluorouracil was given during the first week of irradiation. RESULTS: Six patients experienced a local-regional relapse and 3 developed metastases. The median survival was 21 months. The 5-year overall survival was 15%. Eight patients died of progressive disease. One patient who presented with stage I disease was alive and free of disease at 24 months from diagnosis and, interestingly, one with stage III disease was alive at 111 months. No severe treatment-related complications were observed. CONCLUSIONS: As in carcinoma of the head of the pancreas, adjuvant radiotherapy should be considered as an adjuvant treatment of resected adenocarcinoma of the body and tail of the pancreas. Further evaluation is necessary to assess the role of intraoperative radiotherapy.

[Uterine sarcoma treated by surgery and postoperative radiation therapy. Patterns of relapse, prognostic factors and role of radiation therapy]. / Les sarcomes utérins traités par chirurgie et irradiation postopératoire. Modes de rechute, facteurs pronostiques, rôle de la radiothérapie.

The objective was to evaluate the results of a combination of surgery and postoperative radiotherapy in patients with uterine sarcoma, to describe the patterns of relapse and to define prognostic factors. From 1980 to 1993, 29 patients (median age: 56 years) presenting with uterine sarcoma have been treated with surgery and postoperative irradiation. The histology was: leiomyosarcoma: 11; carcinosarcoma: 12; stromal sarcoma: 6. The distribution by stage was: pT1: 18; pT2: 5; pT3: 3; pT4: 3; pNO: 27; pN1: 2. Gross residual disease was present in 4 patients. External beam irradiation was performed in all the cases and brachytherapy in 19. Chemotherapy was given in 3 patients. The overall survival rate was 66% at 2 years and 57% at 5 years with a disease free survival of 54% at 2 years and 50% at 5 years. Seven patients relapsed locally and 8 developed metastases. One patient died of ileitis. In a multivariate analysis, the disease free survival was strongly influenced by the menopausal status. The survival in this study is higher than that described in series of patients treated with surgery alone. This study confirms the worse prognosis of uterine sarcoma in postmenopausal women.

[Peroperative radiotherapy in the conservative treatment of infiltrating bladder cancers]. / La radiothérapie per-opératoire dans le traitement conservateur des cancers infiltrants de la vessie.

OBJECTIVE: Descriptive analysis of an intraoperative radiotherapy protocol (IOR) in the context of conservative management of invasive bladder cancer. METHOD: From November 1988 to September 1994, 24 patients with invasive bladder carcinoma (20 T2, 3 T3) were included in this protocol consisting of: transurethral resection (TUR), neoadjuvant chemotherapy (M.V.C.) in 14 patients, external irradiation (x 18 MV: 48 Gy/24 F/5 weeks) with concomitant chemotherapy (cisplatin 30 mg/day-3 days-2 cycles during irradiation)-follow-up cystoscopy then surgery with IOR (E 9 MeV: 15 Gy). RESULTS: The global 3-year survival was 69%. An invasive intravesical relapse developed in 3 patients (1 salvaged by cystectomy) and a superficial relapse occurred in 1 patient. One patient developed pelvic lymph node progression and 7 developed distant metastases. The early and late toxicity was acceptable with 3 cases of ureteric necrosis or stenoses resolving after medical treatment. CONCLUSION: This series shows encouraging preliminary results. IOR appears to be a technique well adapted to lesions of the fixed portion of the bladder.

[Radiotherapy of macular lesions in age-related macular degeneration (AMD): initial results of a study inducted in Lyon, France]. / Radiothérapie des dégénérescences maculaires liées à l'âge (DMLA): résultats préliminaires d'une étude lyonnaise.

PURPOSE: To evaluate irradiation effects on functional signs and choroidal neovascular lesions in age-related macular degeneration (AMD) that does not respond to laser therapy. MATERIALS AND METHODS: Since 1994, 250 consecutive AMD patients were treated by two radiotherapy teams for subfoveal neovascular lesions. At the end of September 1996, 52 patients were evaluable with a 1-year follow-up. Group 1 (Département de Radiothérapie Oncologie, Centre Hospitalo-Universitaire Lyon Sud) included 26 patients who were treated with a lateral beam of 6 MV photons. The irradiation doses were 20 Gy in five fractions for small lesions and 28.8 Gy in eight fractions for larger lesions. Group 2 (Centre Oncologie Radiothérapie Saint-Jean) was composed of 26 patients treated with a mini-beam of 25 MV photons via lateral arc-therapy. Beam diameters (14 and 18 mm) were adapted to the lesion size. The total dose was 16 Gy in four fractions or 20 Gy in five fractions. RESULTS: Functional and anatomical results were assessed at 3, 6, 9 months and 1 year after radiation therapy. Stable visual acuity was observed in 44% (23/52) of the patients and visual acuity was improved in 35% (18/52) of the patients at 6 months. Good functional results reached 79% (41/52) at 6 months and 74% (17/23) at 12 months. A significant decrease (> 10%) of the membrane was present in 46% (16/52) of the cases at 6 months and in 65% (15/23) of the cases at 12 months. There was no statistical difference between the two groups and dose levels. All severe complications (1 cataract, 3 dilated choridal vessels, and 2 papillitis) occurred in group 1. CONCLUSION: Though it is too early to conclude on the best dose level, radiotherapy of subfoveal neovascular lesions of AMD that cannot be treated via laser therapy provides encouraging results. The technique used must be very precise to adequately irradiate the fovea and spare surrounding sensitive areas. Further studies and trials involving patients' randomization are necessary to confirm these preliminary results.

[Intraoperative radiotherapy in 1997]. / La radiothérapie peropératoire en 1997.

Intra Operative Radiation Therapy (IORT) has been routinely used for the past 20 years. It is a feasible treatment, with a reasonable cost and an acceptable acute and late toxicity. There is so far no strong randomized trial demonstrating that IORT can improve overall survival. Nevertheless, in many institutions it is recognized as an efficient treatment in selected patients. In case of locally recurrent disease an incomplete gross resection is often the only choice; IORT in such a situation has led to very encouraging results. For locally advanced deep seated primary tumors IORT seems to improve local control. In the near future IORT should be used on a larger and stronger basis. The manufacturing of new mobile linac should allow more surgeons to perform IORT and to conduct clinical trials to confirm the present indications in cancers with high local malignancy.

Stereotactic radiosurgery for arteriovenous malformations of the brain using a standard linear accelerator: the Lyon experience.

Radiosurgery (RS) was initiated in Lyon in October 1989. The technique was adapted from that described by Lutz and Saunders in Boston (BRW stereotactic frame). Irradiation is delivered with 18-MV photons produced by a LINAC. From December 1989 to December 1992, 41 patients with arteriovenous malformations were treated by RS; the median age was 33 years. The largest lesion diameter was 11.2-38.5 mm. Fifteen to 20 Gy were delivered on the 70% isodose line. Angiography was performed at 2 years post-treatment in 32 patients demonstrating an overall complete thrombosis rate of 81.3%. This incidence was significantly correlated with the Spetzler and Martin grade before RS (P = 0.0055). Two patients (4.9%) experienced haemorrhage after radiosurgical treatment and one died from an intracerebral-intraventricular haemorrhage. Four patients (9.7%) experienced permanent radiation-induced neurological complications.

Prevention of radiation related complications in the treatment of rectal adenocarcinoma. The importance of the dose volume relationship.

AIM: To illustrate and stress the role of the dose volume relationship in the risk of radiation induced rectal complications. METHODS: With different techniques of irradiation like contact x ray therapy, Iridium implant, external beam irradiation, intra operative electrontherapy, it is possible to irradiate different volumes from few centicubes to liters. RESULTS: The data from the literature clearly demonstrate that high doses can be given safely in small volumes, but that doses of 50 Gy or more in large volumes are dangerous. The irradiation of the whole pelvis through two antero posterior (AP - PA) fields ecompassing more than 4 liters should not be recommended. Other classical risk factors must be taken into account when planning the treatment. Previous surgery, obesity, diabetus, collagen disease, combined chemotherapy, all these factors can lead to a modification of the irradiation technique. CONCLUSIONS: A perfect technique of irradiation is mandatory to achieve the best therapeutic ratio when treating rectal cancer. To avoid severe complications the dose must be closely adapted to the irradiated volume.

Stereotactic radiosurgery: the Lyon experience.

From 10/1989 to 12/1992, 135 patients were treated, in Lyon, by Stereotactic Radiosurgery (RS) +/- External beam Radiotherapy (EBRT). Indications were AVMs or tumours that could not be cured by embolisation or/and surgery and are not larger than 30 to 35 mm. Lesions received 15 to 20 Gy (70% isodose) in one course. Among the 42 AVMs, only one rebled 6 months after RS and 9/15 had clinical improvement. Thirty-one had a radiological follow-up of 4 to 29 months after RS. Ten were totally obliterated, seven regressed more than 80% and six had a reduction of 50 to 80% of their AVM. Three grade 3 radio necrosis occurred for a cerebral trunk AVM and two large lesions. Three of the 15 treated meningiomas progressed after RS, 2 of them were controlled by conventional surgery. Four out of nine presenting symptoms had clinical improvement and, with a radiological follow-up of 4 to 24 months, 5 were stabilised and 6 regressed. Two grade three complications occurred for large lesions. The biological and radiological results of RS were good for the 42 treated pituitary adenomas but the high visual complication rate (12/42 with 8 grade 3) was too important and we stopped RS for these tumours except for small (less than 2 cm) adenoma at some distance from the optic chiasma. The visual complications were related to the tumour volume, the distance between the adenoma and the visual tract and pre-existent visual alterations.(ABSTRACT TRUNCATED AT 250 WORDS)