Breast cancer care compared with clinical Guidelines: an observational study in France.

BACKGROUND: Great variability in breast cancer (BC) treatment practices according to patient, tumour or organisation of care characteristics has been reported but the relation between these factors is not well known. In two French regions, we measured compliance with Clinical Practice Guidelines for non-metastatic BC care management and identified factors associated with non-compliance at clinical and organisational levels. METHODS: Eligible patients had invasive unilateral BC without distant metastases and at least two contacts with one of the two regional healthcare systems (2003-2004) in the first year after diagnosis. Medical data were collected from patient medical records in all public and private hospitals (99 hospitals).The care process was defined by 20 criteria: clinical decisions for treatment and therapeutic procedures. Each criterion was classified according to level of compliance ("Compliant", "Justifiable" and "Not Compliant") and factors of non-compliance were identified (mixed effect logistic regression). RESULTS: 926 women were included. Non-compliance with clinical decisions for treatment was associated with older patient age (OR 2.1; 95%CI: 1.3-3.6) and region (OR 3.0; 95%CI: 1.2-7.4). Non-compliance with clinical decisions for radiotherapy was associated with lymph node involvement or the presence of peritumoural vascular invasion (OR 1.5; 95%CI: 1.01-2.3) and non-compliance with overall treatment (clinical decisions for treatment + therapeutic procedures) was associated with the presence of positive lymph nodes (OR 2.0; 95%CI: 1.2-3.3), grade III versus grade I (OR 2.9; 95%CI: 1.4-6.2), and one region of care versus another (OR 3.5; 95%CI: 1.7-7.1). Finally, heterogeneity of compliance in overall treatment sequence was identified between local cancer units (p < 0.05). CONCLUSION: This study provides interesting insights into factors of non-compliance in non-metastatic BC management and could lead to quality care improvements.

Quality of surgery in T3-4 rectal cancer: involvement of circumferential resection margin not influenced by preoperative treatment. Results from EORTC trial 22921.

PURPOSE: The present analyses aimed to determine risk factors for rectal cancer patients associated with circumferential resection margin (CRM) and number of examined lymph nodes (LN) and to correlate these parameters of surgical quality with local recurrence (LR), disease-free and overall survival (DFS and OS). MATERIALS AND METHODS: Data of 884 eligible patients, who underwent a resection and had no metastases at time of surgery, were analysed. RESULTS: Age, period of treatment, distance and pT-stage were associated with surgical quality. CRM involvement, but not the number of examined LN, was associated with a higher risk of an LR, reduced DFS and OS. An abdomino-perineal resection (APR) was a risk factor for adverse outcome. CONCLUSION: Surgical quality is an important predictor of outcome, also for patients treated with conventional RT or chemoradiotherapy (CRT). Preoperative CRT results in downstaging and downsizing of the tumour, but not in less CRM involvement.

Chemotherapy with preoperative radiotherapy in rectal cancer.

BACKGROUND: Preoperative radiotherapy is recommended for selected patients with rectal cancer. We evaluated the addition of chemotherapy to preoperative radiotherapy and the use of postoperative chemotherapy in the treatment of rectal cancer. METHODS: We randomly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy, preoperative chemoradiotherapy, preoperative radiotherapy and postoperative chemotherapy, or preoperative chemoradiotherapy and postoperative chemotherapy. Radiotherapy consisted of 45 Gy delivered over a period of 5 weeks. One course of chemotherapy consisted of 350 mg of fluorouracil per square meter of body-surface area per day and 20 mg of leucovorin per square meter per day, both given for 5 days. Two courses were combined with preoperative radiotherapy in the group receiving preoperative chemoradiotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy; four courses were planned postoperatively in the group receiving preoperative radiotherapy and postoperative chemotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy. The primary end point was overall survival. RESULTS: We enrolled 1011 patients in the trial. There was no significant difference in overall survival between the groups that received chemotherapy preoperatively (P=0.84) and those that received it postoperatively (P=0.12). The combined 5-year overall survival rate for all four groups was 65.2%. The 5-year cumulative incidence rates for local recurrences were 8.7%, 9.6%, and 7.6% in the groups that received chemotherapy preoperatively, postoperatively, or both, respectively, and 17.1% in the group that did not receive chemotherapy (P=0.002). The rate of adherence to preoperative chemotherapy was 82.0%, and to postoperative chemotherapy was 42.9%. CONCLUSIONS: In patients with rectal cancer who receive preoperative radiotherapy, adding fluorouracil-based chemotherapy preoperatively or postoperatively has no significant effect on survival. Chemotherapy, regardless of whether it is administered before or after surgery, confers a significant benefit with respect to local control. (ClinicalTrials.gov number, NCT00002523 [ClinicalTrials.gov].).

Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results--EORTC 22921.

PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) trial evaluated the addition of chemotherapy (CT) to preoperative radiation (preop RT) and the value of postoperative CT for improving the survival in patients with T3-4 resectable rectal cancer. Patients were allocated to the following four arms: arm 1, preop RT 45 Gy in 5 weeks; arm 2, preop RT plus two 5-day CT courses (fluorouracil 350 mg/m2/d and leucovorin 20 mg/m2/d) in the first and fifth week of RT; arm 3, preop RT plus four postoperative CT courses; and arm 4, preop RT and CT plus postoperative CT. We investigated the effect of adding CT on the pathologic parameters. PATIENTS AND METHODS: One thousand eleven patients were entered onto the trial; 505 received preop RT (arms 1 and 3), and 506 received preop RT-CT (arms 2 and 4). We analyzed the differences in tumor size, tumor node stage, number of retrieved nodes, and histologic features such as lymphatic, venous, and perineural invasions, tumor differentiation, and tumor type. RESULTS: After preop RT-CT, tumors were smaller (P < .0001), had less advanced pT (P < .001) and pN stages (P < .001), had small numbers of examined nodes (P = .046), and less frequent LVN invasions (P < or = .008). Mucinous tumors increased after preop RT-CT (P < .001). CONCLUSION: In patients with rectal cancer, preliminary results of EORTC Trial 22921 indicate that the addition of CT to preop RT induces down-sizing, downstaging, and significant changes in histologic characteristics. Longer follow-up is needed to assess the impact on local control and survival.

Phase I study with dose escalation of gemcitabine and cisplatin in combination with ifosfamide (GIP) in patients with non-small-cell lung carcinoma.

Gemcitabine (G) and cisplatin (P) are active reference agents in patients with non-small-cell lung cancer (NSCLC). Ifosfamide (I) has also been approved for NSCLC treatment. This phase I trial aimed to determine the dose-limiting toxicity (DLT), maximum tolerated dose [maximum tolerated dosage (MTD)], and recommended dose (RD) of a GIP combination in patients with advanced/metastatic NSCLC. In this study, one cycle of chemotherapy combined the following: ifosfamide: 3 g/m2 fixed dose (24-hour intravenous infusion) combined with mesna, day 1; gemcitabine: starting dose 1,000 mg/m2/d, escalating by 250 mg/m2 increments, days 1 and 15; cisplatin: starting dose 80 mg/m2, subsequently 100 mg/m2, day 15; in cohorts of at least 3 patients. Cycles were repeated every 28 days and no hematopoietic growth factors were administered. DLT was evaluated after the first chemotherapy cycle. Thirty-three patients (30 men, 3 women) with stage III (14 patients)/IV (19 patients) NSCLC were treated at eight dose levels, receiving 109 cycles of chemotherapy. Neutropenia was the only DLT reported. Although the MTD was not reached at the highest tested dose level, the RD chosen corresponds to the full doses of the GP3000 doublet standard (G: 3,000 mg/m2; P: 100 mg/m2 per cycle) every 28 days. Nonhematologic toxicities were mainly grade I-II. Relative dose intensities of G, I, and P at the RD were 96%, 98%, and 96%, respectively. Sixteen of 33 patients with measurable/evaluable disease had an objective response including two complete responses. In conclusion, GIP chemotherapy is safe and appears to be active in patients with NSCLC. The RD is gemcitabine: 1,500 mg/m2 days 1 and 15; ifosfamide: 3 g/m2 day 1; cisplatin: 100 mg/m2 day 15. A confirmatory phase II study is currently under way, before a phase III trial of GIP versus GP.