[Chemoradiation therapy optimization for stage III NSCLC].
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Publications and source records attributed to F Mornex.
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Lung cancer is the most frequent form of malignant tumours. The prognosis is poor with a 5-year cure rate which increased from approximately 6% in the sixties to only 15% in the nineties. Surgery remains the reference treatment but only a small minority of patients (about 25%) present with operable disease. The post-surgical 5-year survival is only 25%, providing the rationale for the current research on adjuvant treatments for control of both local and metastatic disease. In that context, the combination of radiotherapy and chemotherapy, commonly referred to as chemo-radiotherapy, has assumed considerable importance: either exclusively in inoperable patients (inoperable tumour or patients inoperable for medical reasons), or pre-operatively. This article reviews the results of the pivotal definitive chemoradiotherapy studies in non-metastatic non-small-cell lung cancer. With exclusive chemoradiation, the concomitant scheme seems to be the most favourable, results issued from randomised studies are expected to confirm that point. An increased toxicity is observed, and the advent of conformal therapy may allow another survival gain. Optimal treatments integration will be necessary.
The very disappointing results obtained by surgery in resectable non-small-cell lung cancer have led to a high active clinical research concerning pre- or postoperative treatment. Preoperative treatment has several distincts goals: to increase survival for patients suitable for surgery, to limit surgery or transform borderline or non resectable cancer into resectable tumors. Available datas on preoperative treatments for non-small-cell lung cancer provide from three types of therapeutics trials: 1/Some phase II studies of neoadjuvant chemotherapy have demonstrated that the neoadjuvant approach was feasible, and didn't compromise surgery. 2/Phase II trials of neoadjuvant chemoradiotherapy, performed for the majority on more extensive cancers, have demonstrated that this approach was also feasible at the expense of higher but still tolerable toxicity. 3/Phase III randomised published trials exclusively deal with preoperative chemotherapy with different results: two of them concerned a small number of patients presenting with non-small-cell lung stage IIIA cancer: they are positive. The third concerned 373 patients presenting with stage I, II, IIIA cancer: the three-year survival was increased by 11%, but this difference is not yet significant. The benefit essentially appeared for stage I and II. One trial comparing preoperative chemotherapy and radiochemotherapy has been reported, concluding to the superiority of the association. These observations suggest that the clinical research should now be different for stages I and II, and stage IIIA.
Target volume delineation remains an important medical step for conformal radiotherapy. In this general presentation are discussed: the main difficulties for evaluation of gross tumor (GTV) and clinical target volume (CTV), the main recommendations for representation according to ICRU 62 report, differences observed during inter-observer volume comparisons.
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BACKGROUND: The authors performed a specific analysis of the clinical significance of inguinal lymph nodes metastases in patients with anal canal carcinoma (ACC). METHODS: A retrospective analysis was conducted of 270 patients who were treated in Lyon between 1980 and 1996 with radiotherapy with curative intent for ACC: No elective irradiation of clinically normal inguinal areas was performed. Patients with metastatic inguinal lymph nodes were treated with inguinal dissection and postoperative irradiation with a dose of 50 grays over 5 weeks. Concomitant chemoradiation, usually with a regimen of fluorouracil and cisplatinum, was given to 159 patients. RESULTS: The median follow-up for the whole series was 72 months. Synchronous inguinal metastases were observed in 10% of patients (n = 27; the rate was 16% for patients with T3--T4 lesions), and the 5-year overall survival rate was 54.4%. Metachronous inguinal metastases were seen in 19 patients (7.8%), and the 5-year overall survival rate of these patients was 41.4%. An original finding was that, when the primary tumor clearly was located on a single lateral side of the anal canal, the inguinal lymphatic metastases was always homolateral to it (36 of 36 synchronous plus metachronous tumors). CONCLUSIONS: The data from this series of patients and a review of the literature are in favor of a selective approach in the management of inguinal lymph node involvement for patients with ACC, depending on the disease stage and the location of the primary tumors.
PURPOSE: Oxaliplatin could increase the efficacy of fluorouracil (5-FU)/folinic acid chemoradiotherapy in rectal cancer. We tested three dose levels to identify a feasible oxaliplatin dose for combination therapy. PATIENTS AND METHODS: Between February 1998 and April 2000, we included 17 rectal adenocarcinoma patients in a single-center phase I study. Patients had T4 rectal carcinoma, T1-T3 disease with colostomy refusal, or potentially operable T2/T3 M1 requiring local treatment. Pelvic radiotherapy was 45 Gy over 5 weeks, 1.8 Gy/fraction, with concomitant chemotherapy weeks 1 and 5. Chemotherapy was oxaliplatin 80, 100, or 130 mg/m2 2-hour infusion on day 1 followed by L-folinic acid 100 mg/m2/d intravenous bolus, and 5-FU 350 mg/m2/d continuous infusion on days 1 to 5 (FolfoR1). Six patients refusing surgery received additional contact radiotherapy +/- brachytherapy. Dose escalation proceeded if less than two of six patients had dose-limiting toxicity (DLT) at a given dose-level. RESULTS: All except two patients completed treatment; patients at level 1 (prolonged grade 1 thrombocytopenia) and level 3 (prolonged cold-related dysesthesia) had no second chemotherapy course. Median follow-up is 14 months (range, 2 to 28 months). One elderly patient at dose level 1 had DLT asthenia, severe diarrhea and vomiting, and more than 10% weight loss. There were no other DLTs and no severe rectitis or gastrointestinal toxicity. There were objective responses at all doses and no progressions. Eight patients underwent radical surgery after chemoradiotherapy. Two had complete pathologic responses. CONCLUSION: FolfoR1 seems feasible and effective. Dose escalation did not increase toxicity. Although the MTD was not reached in this study, we recommend oxaliplatin 130 mg/m2 for phase II studies because it is the dose determined from studies in metastatic patients with no toxicity when given concurrently with radiation.
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.
Anatomical data of pancreas, biliary tree, regional lymph nodes is required to define GTV and CTV. In case of postoperative irradiation, CTV is designed in collaboration with radiation oncologist and surgeon oncologist. For exclusive radiotherapy, endodigestive ultrasonography, CT scan and MRI could help radiation oncologist defining GTV. Although, accuracy of all the imaging techniques in past years remains poor. Currently, no available literature is published regarding security margins for the definition of CTV. Therefore, recommendations according to clinical experience are proposed.
PURPOSE: To determine if the timing of whole brain radiotherapy (WBRT) with respect to chemotherapy with cisplatin and vinorelbine would influence survival in patients with non-small-cell lung cancer (NSCLC) and concurrent brain metastasis. PATIENTS AND METHODS: One hundred seventy-six patients with brain metastasis from NSCLC were included in the study between July 1995 and October 1997. All patients received chemotherapy with cisplatin 100 mg/m2 on day 1 and vinorelbine 30 mg/m2 on days 1, 8, 15, 22. Cycles were repeated every four weeks. Evaluation of response was performed after two, four or six cycles. After two cycles, chemotherapy was administered to the responders to a maximum of six cycles. Patients were randomised to receive WBRT 30 Gy/10 fx/12 days and delayed corticosteroids. (arm A) for the intracranial nonresponders, or early on day 1 to 12 during the first cycle of chemotherapy (arm B). RESULTS: One hundred seventy-one patients were eligible: eighty-six in arm A and eighty-five in arm B; none had received prior chemotherapy; seventy-six and seventy-three, respectively, were assessable for response. There was a 21% overall objective response rate (OR) (with 1 complete response and 17 partial responses) after two cycles of chemotherapy alone (arm A) and a 20% OR (with 17 partial responses) to chemotherapy and early WBRT (arm B). The intracranial OR was 27% and 33%, respectively (P = 0.12). The six months survival rate (46% and 40%) and the median survival duration (24 and 21 weeks, respectively) were not significantly different between the two arms (P = 0.83, log-rank test). The major toxicity was severe or life-threatening neutropenia (grade 4), which occurred in 35% of arm A patients and 36% of arm B patients. There were thirteen treatment-related deaths (six in arm A and seven in arm B). There was no difference between the arms for haematological and neuro-toxicities. CONCLUSIONS: These results confirm the efficacy of chemotherapy in brain metastases of NSCLC and suggest that the timing (early or delayed) of WBRT did not influence survival of NSCLC with brain metastasis treated with concurrent chemotherapy.
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Cancer is still considered from a physiopathological point of view as a disease of the cell. This concept is underlying the idea of cure. Treatment with curative intent should aim at eradicating all the tumoral cells. Local control is mandatory and essential in cancers localized in organ with vital function. In breast cancer a complex and controversial relationship exists between local relapse and increased risk of fatal distant metastasis. In case of organ preserving treatment, a complete local control is necessary from the start. If a too high risk of local relapse is foreseable, conservative treatment should not be recommended.
The management of superior sulcus tumors with Pancoast 's syndrome is not well defined, especially in view of their low frequency. Even if surgery performed by "en bloc" resection of the tumor and the chest wall is recommended, neoadjuvant treatment could have a potential benefit on the resecability and pain control. We report five cases of Pancoast tumors (NSCLC), treated by radiotherapy and chemotherapy before surgery. Four tumors was on stage IIIb. A regimen with radiotherapy (50 Gy) and chemotherapy (cisplatinum + etoposide) was initially performed. Four tumors were resected, with 2 complete pathologic responses and good control on pain. Three patients received radiotherapy during surgery. No toxic reaction was observed. This regimen may be discussed with locally advanced tumors and poor prognosis.
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BACKGROUND: Surgery remains the treatment of choice for patients with esophageal squamous cell carcinoma (SCC), but survival rates have not improved over the past decades. The objective of this study was to evaluate the effect of multimodal therapy on resectability, on the overall and on disease free survival (DFS) rates, and on the laryngeal resection rate. METHODS: Fifty-five patients (49 men and 6 women) with a mean age of 58 +/- 8 years underwent combined modality treatment for esophageal SCC. The tumor location was in the upper one-third of the esophagus in 19 patients, the middle one-third in 22 patients, the lower one-third in 9 patients, and the upper and lower one-thirds in 5 patients. The intent of combined therapy was curative in 87.3% of patients and palliative in 12.7% of patients. Neoadjuvant treatment consisted of two courses of 5-fluorouracil and cisplatin on Days 1-5 and Days 21-25. Radiotherapy was commenced on Day 21 and consisted of 36 grays delivered in 12 fractions over 17 days. Surgery was performed on Day 60. RESULTS: Full neoadjuvant treatment was possible in 67.3% of patients and was uneventful in 56. 4% of patients. The resection rate was 96.4% (complete macroscopic resection with histologic clear margins [R0], 83.6%; complete macroscopic resection with microscopic disease at the resection margin [R1], 1.8%; and macroscopic residual disease [R2], 10.9%). The operative mortality rate was 0%, whereas the hospital mortality was 7.3%. Twenty-three patients had a complete macroscopic response, 12 of whom (21.8%) had a complete histopathologic response. The tumor stages according to the American Joint Committee on Cancer staging system were pT0N0 in 12 patients, Stage 0 in 8 patients, Stage IIa in 6 patients, Stage IIb in 6 patients, Stage III in 8 patients, and Stage IV in 13 patients. Laryngeal preservation was achieved in 8 of 12 patients in whom total pharyngolaryngoesophagectomy initially was indicated because of tumor response and an R0 resection. The overall survival rates at 1 year, 3 years, and 5 years were 61%, 39%, and 33%, respectively, and the DFS rates were 49%, 32%, and 29%, respectively. The respective survival rates for responders were 82%, 58%, and 53%, and the DFS rates were 68%, 54%, and 48%. CONCLUSIONS: Neoadjuvant treatment is tolerated well by most patients. Combination therapy increases the resectability rate and facilitates laryngeal preservation. Significant improvements in the actuarial survival rate and the DFS rate were observed in the group of patients who achieved partial and complete responses.
The prognosis of pancreatic adenocarcinoma remains poor, with a 5-year survival rate lower than 5%. Resection, the gold standard treatment, can be performed in less than 10% of patients. Following surgery, the median survival is 12 months. Concomitant chemoradiation, as an adjuvant treatment could be superior to surgery alone, in terms of survival; controlled trials are currently performed. Neoadjuvant chemoradiation is a new approach, potentially able to increase survival and resection rate. Finally, current data regarding intraoperative irradiation are exposed.
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AIM: To study retrospectively the relapse rate, the functional results and the survival rate in patients with rectal carcinoma treated with local excision and adjuvant radiotherapy. METHODS: Between 1980 and 1995, 43 patients were treated. All cancers were infiltrating tumours except 4 high grade dysplasias with positive margins. The pT classification was: pT1 (n=34), pT2 (n=4), pT3 (n=1). In 4 cases the depth of penetration of the tumor into the bowel wall was not evaluable. The endo-anal excision was performed by surgery (n=20) or by endoscopy (n=23). Only the tumor bed was irradiated in 35 cases (contact x-ray therapy: 30, interstitial iridium implant: 5) and in 8 cases the whole rectum was irradiated with external beam radiotherapy (+/- endocavitary irradiation). RESULTS: Median follow-up was 72 months. Four malignant relapses were observed (local: 1, perirectal lymphatic: 2, distant metastasis: 1). The overall 5- and 10-year survival rates were 80 and 68%, respectively. A total of 41 patients preserved a normal sphincter (95%). The anal function was evaluated as excellent or good in all the cases. No severe radiation toxicity was observed. CONCLUSION: Small rectal carcinomas T1 N0 can be effectively treated in most cases by local excision and postoperative radiation therapy. A close multidisciplinary collaboration is necessary to achieve an optimal result.