[Predictive factors assessment of pathological response to neoadjuvant radiotherapy of soft tissue sarcomas]. / Évaluation de facteurs prédictifs de réponse pathologique à la radiothérapie néoadjuvante des sarcomes des tissus mous.

PURPOSE: Conserving surgery combined with radiotherapy in presence of local recurrence risk factors is standard treatment of soft tissue sarcomas, a group of rare and heterogeneous tumours. Radiotherapy is performed before or after surgery. In neoadjuvant setting, late radiation-induced toxicity is reduced and pathological response to radiotherapy could be achieved. A complete pathological response to radiotherapy has recently been shown to predict better survival. Our study aims at identifying predictive factors of pathological response to neoadjuvant radiotherapy (clinical, radiological or histological) of soft tissue sarcomas. PATIENTS AND METHODS: Clinical, imaging (MRI: perilesional oedema, necrosis, tumour heterogeneity, vasculonervous relationships) and pathological (pathological subtype, tumour grade, anticipated/obtained resection quality) data were retrospectively collected. Tumour response (imaging and pathological), patient outcome, acute and late radiation-induced toxicity, predictive factors of pathological response to neoadjuvant radiotherapy were studied. The 2-test or exact-Fisher test (qualitative variables) and by Student's t-test or Kruskal-Wallis test (quantitative variables) were used for statistical analysis. RESULTS: From April 2017 to April 2021, neoadjuvant radiotherapy (50Gy in 25 fractions) followed by surgical excision was performed to 36 consecutive patients with liposarcomas (n=17/36), or undifferentiated sarcomas (n=8/36). MRI response was complete in 1 patient, partial in 9 patients (n=9/36, 25%), stable in 21 patients (n=21/36, 58%) or in progression in 5 patients (n=5/36, 14%). Pathological response was observed in 22 patients (61%). No grade 3-4 acute radiation-induced toxicity was observed. Regarding late toxicity, 28% of patients had grade 1-2 oedema (n=10/36), 39% had a grade 1 fibrosis (n=14/36), and 30% grade 1 pain (n=11/36). No predictive factors of response to radiotherapy was statistically significant. CONCLUSIONS: Neoadjuvant radiotherapy is well-tolerated. No clinical, radiological or pathological predictive factors was identified for radiotherapy tumour response.

[Stereotactic Body Radiation Therapy for less than 3cm (stage I) and 5cm (stage II) inoperable lung tumors: 10 years experience of Montpellier Cancer Institute]. / Radiothérapie stéréotaxique (RTST) pulmonaire des tumeurs de moins de 3cm (stade I) et 5cm (stade II) non opérées : 10 ans d'expérience de l'Institut du Cancer de Montpellier (ICM).

PURPOSE: Search for predictive factors on survival and local control for less than 3 centimeters (cm) (stage I) and 5cm (stage II) inoperable lung tumors treated by Stereotactic Body Radiation Therapy (SBRT) in a retrospective monocentric study from Montpellier Cancer Institute (ICM) PATIENTS AND METHOD: Every patients treated at ICM for a stage I or II inoperable lung tumors from 2009 to 2019 were analyzed. RESULTS: One hundred and seventy nine lesions were treated in 176 patients, with a major part (82,7%) in operated due to chronic obstructive pulmonary disease. Median overall survival for all patients was 71,7 months with a 35 months follow-up and the 2 years loco-regional free survival was 94,0 months. Better associated outcomes were stage I (median overall survival 71,7 versus 29,0 months P=0,004 ; HR=2,37 P=0,005), BED≥150Gy (median time-to-progression not reached versus 76,7 months P=0,025), small size of Planning Target Volume (PTV) (HR=0,42 P=0,032 when PTV<15,6 cc). 7,3% of all patients developed radiation pneumonitis. CONCLUSION: SBRT is associated with an excellent overall survival and a high rate of local control for less than 3cm (stage I) and 5cm (stage II) lung tumors but a low rate of toxicities. For these patients with many comorbidities, BED over 150Gy seems to be associated with a better loco-regional free survival, while cause of death is often other than lung cancer.

[Results of surgical revisions for ureteral complications after renal transplantation]. / Résultats des reprises chirurgicales pour complications urétérales après transplantation rénale.

OBJECTIVE: To analyze the results of surgical revision for ureteral complication (ureteric stenosis or urinary leakage) after renal transplantation over a period of 10 years. MATERIALS AND METHODS: We performed a retrospective study on 1313 consecutive kidney transplantations carried out in a University Hospital Center between 2005 and 2014. The data of the patients who developed a ureteral stenosis or a urinary leakage secondary to a renal transplantation were analyzed. Combined organ transplantations (kidney-liver and kidney-pancreas), as well as pediatric transplantations were excluded. RESULTS: Seventy-six patients (5.8%) had ureteric stenosis or urinary leakage after renal transplantation. Forty-six patients (3.5%) underwent surgical revision: 27 for ureteral stenosis, 19 for urinary leakage. Early success was achieved in 26 patients (56.5%), including 14 ureteric stenosis (51.9%) and 12 urinary leakage (63.2%) (P=0.45). After a complementary endoscopic or surgical treatment, the final success rate was increased to 73.1% (34 patients): 20 ureteric stenosis (74.1%) and 14 urinary leakage (73.7%) (P=0.98). There were 2 graft losses (4.3%) and one death (2.2%). The mean glomerular filtration rate estimated by the MDRD was 44.58mL/min/1.73m2 (±14.7) before surgery and 45.37mL/min/1.73m2 (±16.5) 6 months after surgery (P=0.92). CONCLUSION: Although frequently challenging, surgical revisions for ureteral complications after renal transplantation give good results, with a low rate of graft loss and mortality. LEVEL OF EVIDENCE: 4.

MRI-based score to predict surgical difficulty in patients with rectal cancer.

BACKGROUND: Rectal cancer surgery is technically challenging and depends on many factors. This study evaluated the ability of clinical and anatomical factors to predict surgical difficulty in total mesorectal excision. METHODS: Consecutive patients who underwent total mesorectal excision for locally advanced rectal cancer in a laparoscopic, robotic or open procedure after neoadjuvant treatment, between 2005 and 2014, were included in this retrospective study. Preoperative clinical and MRI data were studied to develop a surgical difficulty grade. RESULTS: In total, 164 patients with a median age of 61 (range 26-86) years were considered to be at low risk (143, 87·2 per cent) or high risk (21, 12·8 per cent) of surgical difficulty. In multivariable analysis, BMI at least 30 kg/m2 (P = 0·021), coloanal anastomosis (versus colorectal) (P = 0·034), intertuberous distance less than 10·1 cm (P = 0·041) and mesorectal fat area exceeding 20·7 cm2 (P = 0·051) were associated with greater surgical difficulty. A four-item score (ranging from 0 to 4), with each item (BMI, type of surgery, intertuberous distance and mesorectal fat area) scored 0 (absence) or 1 (presence), is proposed. Patients can be considered at high risk of a difficult or challenging operation if they have a score of 3 or more. CONCLUSION: This simple morphometric score may assist surgical decision-making and comparative study by defining operative difficulty before surgery.

Nutritional assessment in overweight and obese patients with metastatic cancer: does it make sense?

BACKGROUND: Obesity is causally related with tumor development, and thus, many cancer patients are overweight or obese at diagnosis. Whether these patients need regular nutritional assessment is not known. In the present study, we evaluated the utility of Mini Nutritional Assessment (MNA), a nutritional screening/assessment questionnaire, in overweight or obese patients with metastatic tumors. PATIENTS AND METHODS: Overweight or obese patients referred for initiation of systemic therapy in three cancer centers were eligible. Basic demographics and clinical data were recorded. MNA was completed at baseline and patients were divided into three groups: A (well nourished), B (at risk), and C (malnourished). Survival data were subsequently collected. The prevalence of malnutrition and prognostic significance were evaluated. RESULTS: In total, 1469 patients with metastatic primaries were identified. Of them, 594 (41.9%) were overweight or obese and included in the analysis. According to MNA, almost 50% were at risk and around 12% were already malnourished at presentation. A significant difference in overall survival was found between groups [group A 17.8 (15.5-20.1) months, group B 8.2 (7.3-9.3) months, and group C 6.4 (3.2-9.6) months, P < 0.001]. Moreover, MNA was the only independent predictor of survival. CONCLUSIONS: Our findings support that a significant percentage of overweight or obese cancer patients may be at nutritional risk and this is moreover related with adverse prognosis. An MNA score could be used for the identification of this risk.

Sorafenib and irinotecan (NEXIRI) as second- or later-line treatment for patients with metastatic colorectal cancer and KRAS-mutated tumours: a multicentre Phase I/II trial.

BACKGROUND: This trial evaluated the feasibility and efficacy of combined sorafenib and irinotecan (NEXIRI) as second- or later-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC), who had progressed after irinotecan-based chemotherapy. METHODS: In Phase I, in a 3+3 dose escalation schedule, patients received irinotecan (125, 150 or 180 mg m(-2) every 2 weeks), in combination with 400 mg sorafenib b.d. The primary end point was the maximum-tolerated dose of irinotecan. In Phase II, the primary end point was disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: Phase I included 10 patients (median age 63 (49-73)); no dose-limiting toxicity was seen. In Phase II, 54 patients (median age 60 (43-80) years) received irinotecan 180 mg m(-)(2) every 2 weeks with sorafenib 400 mg b.d. Nine patients (17%) remained on full-dose sorafenib. The DCR was 64.9% (95% CI, 51-77). Median PFS and OS were 3.7 (95% CI, 3.2-4.7) and 8.0 (95% CI, 4.8-9.7) months, respectively. Toxicities included Grade 3 diarrhoea (37%), neutropenia (18%), hand-foot syndrome (13%) and Grade 4 neutropenia (17%). CONCLUSION: The NEXIRI regimen showed promising activity as second- or later-line treatment in this heavily pretreated mCRC population (ClinicalTrials.gov NCT00989469).

Feasibility of biweekly combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in patients with metastatic solid tumors: results of a two-step phase I trial: XELIRI and XELIRINOX.

BACKGROUND: Biweekly schedule of capecitabine combined with irinotecan (XELIRI), consecutively with irinotecan and oxaliplatin (XELIRINOX), was evaluated in patients with metastatic cancer from any solid tumors. PATIENTS AND METHODS: In this two-step phase I trial, seventeen and eleven patients were enrolled in the XELIRI and XELIRINOX stages, respectively. RESULTS: In XELIRI, a total of 136 chemotherapy cycles were administered with a median number of 8 cycles per patient (2-16). Main dose-limiting toxicities (DLT) were grade 3-4 neutropenia, with one toxicity-related death. Maximum tolerated dose (MTD) for capecitabine combined with 180 mg/m(2) of irinotecan was 3,500 mg/m(2)/day. In XELIRINOX, capecitabine starting dose was 2,500 mg/m(2)/day. Fifty-eight chemotherapy cycles were administered with a median of 4 cycles per patient (1-16). DLT included 3 grade 4 neutropenia, associated with 1 grade 3 diarrhea, and 1 grade 4 pneumopathy leading to patient death. MTD for capecitabine with 180 mg/m(2) of irinotecan and 85 mg/m(2) of oxaliplatin was 3,000 mg/m(2)/day. The recommended doses for capecitabine were 3,000 and 2,500 mg/m(2)/day D1-D7 in combination with 180 mg/m(2) of irinotecan in XELIRI, plus 85 mg/m(2) of oxaliplatin in XELIRINOX (D1 = D14), respectively. CONCLUSION: XELIRI and XELIRINOX regimens are feasible and warrant further investigation in combination with targeted therapy in metastatic colorectal cancer patients.

Efficacy of irinotecan in combination with 5-fluorouracil (FOLFIRI) for metastatic gastric or gastroesophageal junction adenocarcinomas (MGA) treatment.

OBJECTIVES: The most commonly used schedules are 5-FU in combination with CDDP with or without epirubicin (ECF) or docetaxel (TCF) in treatment of MGA patients (pts), independently of HER status. We evaluated the efficacy of FOLFIRI regimen in a large retrospective series of MGA pts. METHODS: Two hundred and twelve pts from 13 French centers were treated with at least one cycle of FOLFIRI (irinotecan 180 mg/m2 intravenous (i.v.) over 90 minutes on day 1 with folinic acid (FA) 400mg/m2 i.v. over two hours followed by 5-FU 400mg/m2 i.v. bolus then 5- FU 2400 mg/m2 continuous infusion over 46 hours on day 1, repeated every 14 days). Primary tumour sites were 120 (58%) stomach and 92 (42%) gastroesophageal junction. FOLFIRI was administered as first-line in 137 (65%) pts and as later-line in 75 (35%) pts for MGA. RESULTS: There was no difference between chemonaive and not chemonaive pts treated as firstline in terms of response rate 37% (95% CI: 25-50) vs 44% (95% CI: 21-69), median PFS, 6.7 (95% CI: 5.5-9.9) vs 5.3 months (95% CI: 3.6-6.9) (P = 0.25), and OS, 13.1 (95% CI: 11.7-18.7) vs 8.8 months (95% CI: 7.3­15.6) (P = 0.19), respectively. There was no difference between pts treated as second or later-line in terms of response rate 20% (95% CI: 8-39) vs 22% (95% CI: 6-48), median PFS, four months (95% CI: 2.8-5.4) vs 3.5 months (95% CI: 2.3-4.5) (P = 0.56), and OS, 10.4 months (95% CI: 5.4-14.4) vs 5.3 months (95% CI: 3.5-11.3) (P = 0.58), respectively. The global grade 3-4 toxicities were: diarrhea 11%, vomiting 9%, neutropenia 18%, febril neutropenia 4% (one toxic death). CONCLUSIONS: This retrospective study confirms the activity and good tolerance of FOLFIRI regimen in MGA as first-line as well as later-line.

A large-scale candidate gene approach identifies SNPs in SOD2 and IL13 as predictive markers of response to preoperative chemoradiation in rectal cancer.

Neoadjuvant radiochemotherapy followed by total mesorectal excision is now the standard treatment for locally advanced rectal cancer. However, tumor response to chemoradiation varies widely among individuals and cannot be determined before the final pathologic evaluation. The aim of this study was to identify germline genetic markers that could predict sensitivity or resistance to preoperative radiochemotherapy (RT-CT) in rectal cancer. We evaluated the predictive value of 128 single-nucleotide polymorphisms (SNPs) in 71 patients preoperatively treated by RT-CT. The selected SNPs were distributed over 76 genes that are involved in various cellular processes such as DNA repair, apoptosis, proliferation or immune response. The SNPs superoxide dismutase 2 (SOD2) rs4880 (P=0.005) and interleukin-13 (IL13) rs1800925 (P=0.0008) were significantly associated with tumor response to chemoradiation. These results reinforce the idea of using germline polymorphisms for personalized treatment.

A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer.

BACKGROUND: Studies indicate that adjuvant 5-fluorouracil (5-FU) with folinic acid (FA) in colorectal cancer patients with completely resectable liver-limited metastases (LMCRC) offers clinical benefit over surgery alone. This phase III trial compared FOLFIRI with simplified 5-FU/FA in this setting. PATIENTS AND METHODS: LMCRC patients were randomized to receive every 14 days, FA, 400 mg/m2 infused over 2 h, followed by 5-FU as a 400 mg/m2 i.v. bolus, followed by continuous 5-FU infusion, 2400 mg/m2 over 46 h (LV5FUs) with or without irinotecan: 180 mg/m2 infusion (FOLFIRI). The primary end point was disease-free survival (DFS); secondary end points included overall survival (OS) and safety. RESULTS: Treated patients (n = 306) were balanced for critical prognostic factors in each arm. Median DFS in patients receiving LV5FUs was 21.6 versus 24.7 months for FOLFIRI [hazard ratio (HR) 0.89, log-rank P = 0.44]. No significant differences were found in OS. A trend was observed for improved DFS in patients receiving FOLFIRI within 42 days of surgery (HR 0.75, P = 0.17). Grade 3/4 toxic effects were more common in patients treated with FOLFIRI versus LV5FUs (47% versus 30%) with neutropenia being most common (23% versus 7%). CONCLUSION: FOLFIRI in the adjuvant treatment of LMCRC showed no significant improvement in DFS compared with LV5FUs.

A randomized phase II trial evaluating safety and efficacy of an experimental chemotherapy regimen (irinotecan + oxaliplatin, IRINOX) and two standard arms (LV5 FU2 + irinotecan or LV5 FU2 + oxaliplatin) in first-line metastatic colorectal cancer: a study of the Digestive Group of the Fédération Nationale des Centres de Lutte Contre le Cancer.

BACKGROUND: To assess activity and safety of an experimental combination of irinotecan and oxaliplatin (IRINOX) as first-line treatment in advanced colorectal cancer. PATIENTS AND METHODS: In this randomized phase II trial, 80 patients were treated: arm A (IRINOX) in 40 patients received at day 1 oxaliplatin 85 mg/m(2) and irinotecan 180 mg/m(2) biweekly, standard arm B received a biweekly simplified folinic acid (FA) and fluorouracil (FU), FA 200 mg/m(2) in a 2-h infusion and bolus injection of 5FU 400 mg/m(2) on day 1, then a two 400 mg/m(2) continuous infusion of FU on days 1 and 2 with either oxaliplatin 85 mg/m(2) (20 patients) or irinotecan 180 mg/m(2) (20 patients). RESULTS: Twenty-one partial responses (52.5%, median duration 7.2 months) were observed with the IRINOX arm and two complete and 20 partial responses (55%, median duration 6.4 months) with arm B. Median progression-free and overall survival times were 8.4 and 19 months, respectively, in the IRINOX arm and 8.1 and 20.4 months in arm B. Main grade 3/4 toxic effects were, respectively, neutropenia 42.5% and 32.5%; febrile neutropenia 10% and 5%; diarrhea 32.5% and 7.5%; vomiting 10.0% and 5%; neurosensory toxicity 17.5% and 7.5%. CONCLUSION: The IRINOX arm has a manageable toxicity and is active.

The value of endoscopic rectal ultrasound in predicting the lateral clearance and outcome in patients with lower-third rectal adenocarcinoma.

BACKGROUND AND STUDY AIMS: The aim of this study was to assess whether preoperative endorectal ultrasound (ERUS) is able to predict histological infiltration of the external anal sphincter or the levator ani muscle in patients with a lower-third rectal neoplasm and so the possibility of treatment by sphincter-saving surgery. PATIENTS AND METHODS: Between May 1996 and May 2003, 66 patients with a lower-third rectal neoplasm that was staged as uT2 or greater were entered into a prospective evaluation of ERUS. All patients underwent neoadjuvant treatment before surgery. RESULTS: The first ERUS (ERUS 1) was performed before neoadjuvant treatment; the second ERUS (ERUS 2) was performed between the end of the radiotherapy and the surgery. An abdominoperineal resection was performed mainly when the lower extent of the tumor was within 3.5 cm from the anal verge (P = 0.011), but no correlation was observed between the lateral clearance determined by ERUS 1 and the histological clearance (P = 0.091). After neoadjuvant treatment, the ERUS 2 lateral clearance was significantly correlated with the type of surgery (P = 0.003) and the histological clearance (P < 0.001). With regard to the performance of ERUS 2 for predicting histological infiltration of the external anal sphincter or the levator ani muscle, the sensitivity was 100%, the negative predictive value was 100%, the specificity was 87%, and the positive predictive value was 53%. In a multivariate analysis, the histological clearance and tumor T stage were statistically correlated with disease-free survival (P = 0.035 and P = 0.05, respectively). CONCLUSIONS: ERUS could help oncologists and surgeons in the management of patients with lower rectal carcinomas. Moreover, ERUS is able to predict lateral histological clearance after neoadjuvant treatment.

[Sun exposure and sun protection behavior and attitudes among the French population]. / Connaissances, attitudes et comportements des adultes vis-à-vis du soleil en France.

INTRODUCTION: The number of new skin cancers has constantly increased in France over the past two decades. The role of sun exposure can partly explain this phenomenon and justifies the development of information and prevention campaigns to change peoples' attitude towards sun bathing. To be effective, we need to know how much information and what attitudes the population currently has with regard to the sun. Although several studies in France have targeted children, little data is available regarding adults. This trial was aimed at pinpointing the knowledge, attitude and behavior of adults regarding sun exposure. MATERIAL AND METHODS: Data were collected during a randomized multicenter study on the prevention and early diagnosis of cutaneous tumors, conducted in 26 Health Centers from 1998 to 2000. Standardized questionnaires were handed to those consulting to assess their knowledge, attitudes and behavior towards sun bathing. The population was composed of 41 143 adults aged over 30, consulting one of the 26 Health Check-up units. Analysis of the data was made using SAS v 6.12 and STATA 7.0 software. Logistic regression identified the explicative factors of knowledge and behavior. All the statistical analyses were considered significant above a threshold of alpha<5%. RESULTS: A total of 33 021 persons filled-in the self-questionnaire. Forty-nine percent were women and 51% were men, with a mean age of 50 years. Geographically, 25% lived in the North-East, 16% in the North-West, 25 p.cent in the South-East and 34% in the South-West. Thirty percent claimed that they tanned without burning and 2% of the population studied had often suffered from sun burn, generally when they were adult. The risks related to sun burn were known, because 92% knew that the sun increased the risk of skin aging and 89% knew that it increased the risk of skin cancer. Regarding sun screens, knowledge was not so good; 42% thought that all products were the same and 53% that they allowed one to sun bathe longer. This knowledge was better in those with fair skins, in those who had a history of sun burn, in women and in those who lived in the northern areas of France. Conversely, knowledge decreased with age and was limited in those aged over 60. Regarding behavior, those with fair skin and who reddened under the sun without tanning, protected themselves more. The women declared they protected themselves more than the men, but they used less sun protective measures (clothing, hats...), other than sun screens, than men. Subjects aged over 60 protected themselves more than younger subjects. Lastly, a personal cutaneous history increased protective behavior, and those from northern France protected themselves more than those from the South. DISCUSSION: This analysis of 33 021 adults aged over 30 shows the good global knowledge of the consequences of sun bathing, but also the lack of knowledge on the interest of using external sun protection and the role of physical means of protection. Attitudes varied depending on gender, age and phototype and also depending on the area where they lived. Despite good knowledge, the most frequent behavior of adults aged over 30 is still not appropriate with differences depending on age, gender and area, which must prompt more appropriate targeting of prevention campaigns according to the populations concerned.

p53 status and response to radiotherapy in rectal cancer: a prospective multilevel analysis.

The aim of this study was to evaluate, in a prospective study, the predictive role of p53 status analysed at four different levels in identifying the response to preoperative radiotherapy in rectal adenocarcinoma. Before treatment, 70 patients were staged and endoscopic forceps biopsies from the tumour area were taken. p53 status was assessed by total cDNA sequencing, allelic loss analysis, immunohistochemistry, and p53 antibodies. Neoadjuvant treatment was based on preoperative radiotherapy or radiochemotherapy. Response to therapy was evaluated after surgery by both pathologic downstaging and histologic tumour regression grade. In all, 35 patients (50.0%) had p53 gene mutations; 44.4% of patients had an allelic loss; nuclear p53 overexpression was observed in 39 patients (55.7%); and p53 antibodies were detected in 11 patients (16.7%). In the multilevel analysis of p53 status, gene mutations correlated with both nuclear protein overexpression (P < 0.0001) and loss of heterozygosity (P = 0.013). In all, 29 patients (41.4%) were downstaged by pathologic analysis, and 19 patients (29.2%) were classified as tumour regression grade 1. Whatever the method of evaluation of treatment response, no correlation between p53 alterations and response to radiotherapy was observed. Our results do not support the use of p53 alterations alone as a predictive marker for response to radiotherapy in rectal carcinoma.

A weekly schedule of docetaxel for metastatic hormone-refractory prostate cancer.

RATIONALE: Docetaxel has proven its efficacy in the management of hormone-refractory prostate cancer (HRPC). Schedules of docetaxel administration differ. This prospective phase II study was designed to reevaluate the activity and toxicity of docetaxel administered weekly at an optimal dose to a large cohort of HRPC patients. PATIENTS AND METHODS: Sixty-four patients were treated with docetaxel 40 mg/m(2) i.v., administered weekly for 6 consecutive weeks followed by a 2-week recovery period. Three treatment cycles were planned in the absence of progression or toxicity. The principal end point was the biochemical response based on the prostate-specific antigen (PSA) level (a decline of more than 50% for at least 4 weeks). Secondary end points were objective response to measurable disease, survival and toxicity. RESULTS: Toxicity was assessed in 64 patients. Toxicity was acceptable, with no toxicity-related deaths. Twenty-one percent of the patients developed grade 3-4 hematological toxicity. Sixty-four patients were evaluable for the PSA response. Forty-one patients (64%) achieved a decrease in PSA of >50%, 13 of whom had a PSA <4 ng/ml. Two out of 12 patients with measurable disease exhibited an objective response. With respect to PSA, the median progression-free survival was 29 weeks (95% confidence interval: 18-46 weeks). The global 1-year survival rate was 58%. CONCLUSION: Weekly docetaxel at a dosage of 40 mg/m(2) is a well-tolerated treatment, which has very promising activity on the reduction of PSA in metastatic HRPC. A large phase III study is underway.

Five-year change in statistical designs of phase II trials published in leading cancer journals.

This study compares the evolution in statistical design reporting for phase II cancer clinical trials published in the six following leading journals: American Journal of Clinical Oncology, Annals of Oncology, British Journal of Cancer, Cancer, European Journal of Cancer and Journal of Clinical Oncology. Only articles where tumour response was considered as the primary endpoint were selected. A total of 393 phase II trials published in 1995 (n=185) and 2000 (n=208) were reviewed. Neither sample size nor design parameters were specified in 157 (85%) and 113 (46%) papers in 1995 and 2000, respectively. 28 (15%) and 95 (46%) papers included at least some information on the statistical designs used: Gehan (4.3% and 3.3%), Fleming (2.2% and 4.3%), and Simon (2.7% and 11.0%). Ad hoc, non-referenced methods were used in 5.9% and 27.3% articles in 1995 and 2000, respectively. Although there is an increase in the mention of at least some statistical design parameters in phase II cancer clinical trials over a 5-year period in these selected cancer journals, the use of referenced methods is still short or often inadequate.

[Pilot study of conformal intensity modulated radiation therapy for localized prostate cancer].

PURPOSE: - To report our experience on treatment planning and acute toxicity in 16 patients suffering from clinically localized prostate cancer treated with high-dose intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: - Between March 2001 and October 2002, 16 patients with clinically localized prostate cancer were treated with IMRT. Treatment planning included an inverse-planning approach, and the desired beam intensity profiles were delivered by dynamic multileaf collimation. All patients received the entire treatment course with IMRT to a prescribed dose of 78 Gy. All IMRT treatment plans were compared with a theoretical conventional three-dimensional conformal radiation therapy (3D-CRT). Acute lower gastro-intestinal (GI) and genito-urinary (GU) toxicity was evaluated in all patients and graded according to the Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE v. 3.0). A relationship between dose volume and clinical toxicity was evaluated. RESULTS: - Ninety-five percent of the PTV2 received more than 76 Gy using IMRT or 3D-CRT with no difference between both methods. The dose-volume histogram mean obtained for the PTV2 was not different between IMRT and 3D-CRT. IMRT improved homogeneity of the delivered dose to the PTV2 as compared with 3D-CRT (7.5 vs 9%, respectively). Ninety-five percent of the PTV1 received 5 Gy more using IMRT with protection of the bladder and the rectum walls. The benefit was considered below 75 and 70 Gy for the wall of the bladder and the rectum, respectively. Grade 2 GI and GU toxicity was observed in four (25%) and five (31%) patients, respectively. No grade 3 toxicity was observed. There was a trend towards a relationship between the mean rectal dose and acute rectal toxicity but without statistical significant difference (P =0.09). CONCLUSION: - Dose escalation with IMRT is feasible with no grade 3 or higher acute GI or GU toxicity. Examination of a larger cohort and longer-term follow-up are warranted in the future.

Changing estrogen and progesterone receptor patterns in breast carcinoma during the menstrual cycle and menopause.

BACKGROUND: Estrogen receptor (ER) and progesterone receptor (PgR) status at the time of breast carcinoma surgery is used as a marker of both prognosis and hormone dependency to guide adjuvant therapy. The authors studied the influence of hormonal milieu at the time of surgery on ER and PgR levels. METHODS: A population of 2020 patients with breast carcinoma, including 575 premenopausal women, was analyzed. ER and PgR levels were determined by radioligand binding assays (cutoff values, 10 fmol/mg). Serum estradiol (E2), progesterone (Pg), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels obtained on the day of surgery were used to define the menstrual cycle phase in premenopause. RESULTS: In premenopause, there was a higher proportion of ER positive (ER+) tumors in the follicular phase (62%, n = 316) than in the ovulatory phase (51%, n = 59) and the luteal phase (53%, n = 200, P = 0.03). The mean ER level was also higher in the follicular phase (30 fmol/mg) than in the ovulatory phase (20 fmol/ mg) and the luteal phase (25 fmol/mg, P < 0.001). The percentage of PgR positive (PgR+) tumors tended to be higher in the ovulatory phase (85%) than in the follicular (78%) and luteal (72%) phases (P = 0.11). The mean PgR was also higher in the ovulatory phase (177 fmol/mg) than in the follicular and luteal phases (134 and 92 fmol/mg, respectively; P < 0.001). The percentage of ER+ tumors was higher among menopausal women than among premenopausal women (67% vs. 59%, respectively; P < 0.001). Conversely, the percentage of PgR+ tumors was lower among menopausal women than among premenopausal women (65% vs. 78%, respectively; P < 0.001). In premenopause, there was a weak negative correlation between ER and E2 levels. No correlations were found between levels of ER and Pg and levels of FSH and LH or among levels of PgR and E2, Pg, and FSH and LH in premenopausal and menopausal women. CONCLUSIONS: Changes in ER and PgR levels in breast carcinoma during the menstrual cycle and menopause suggest that interpretations of hormone dependency on the basis of steroid receptor values should take into account hormonal status at the time of surgery.