Microsecond time-resolved X-ray diffraction for the investigation of fatigue behavior during ultrasonic fatigue loading.

A new method based on time-resolved X-ray diffraction is proposed in order to measure the elastic strain and stress during ultrasonic fatigue loading experiments. Pure Cu was chosen as an example material for the experiments using a 20 kHz ultrasonic fatigue machine mounted on the six-circle diffractometer available at the DiffAbs beamline on the SOLEIL synchrotron facility in France. A two-dimensional hybrid pixel X-ray detector (XPAD3.2) was triggered by the strain gage signal in a synchronous data acquisition scheme (pump-probe-like). The method enables studying loading cycles with a period of 50 µs, achieving a temporal resolution of 1 µs. This allows a precise reconstruction of the diffraction patterns during the loading cycles. From the diffraction patterns, the position of the peaks, their shifts and their respective broadening can be deduced. The diffraction peak shift allows the elastic lattice strain to be estimated with a resolution of ∼10-5. Stress is calculated by the self-consistent scale-transition model through which the elastic response of the material is estimated. The amplitudes of the cyclic stresses range from 40 to 120 MPa and vary linearly with respect to the displacement applied by the ultrasonic machine. Moreover, the experimental results highlight an increase of the diffraction peak broadening with the number of applied cycles.

Accuracy of stress measurement by Laue microdiffraction (Laue-DIC method): the influence of image noise, calibration errors and spot number.

Laue microdiffraction, available at several synchrotron radiation facilities, is well suited for measuring the intragranular stress field in deformed materials thanks to the achievable submicrometer beam size. The traditional method for extracting elastic strain (and hence stress) and lattice orientation from a microdiffraction image relies on fitting each Laue spot with an analytical function to estimate the peak position on the detector screen. The method is thus limited to spots exhibiting ellipsoidal shapes, thereby impeding the study of specimens plastically deformed. To overcome this difficulty, the so-called Laue-DIC method introduces digital image correlation (DIC) for the evaluation of the relative positions of spots, which can thus be of any shape. This paper is dedicated to evaluating the accuracy of this Laue-DIC method. First, a simple image noise model is established and verified on the data acquired at beamline BM32 of the European Synchrotron Radiation Facility. Then, the effect of image noise on errors on spot displacement measured by DIC is evaluated by Monte Carlo simulation. Finally, the combined effect of the image noise, calibration errors and the number of Laue spots used for data treatment is investigated. Results in terms of the uncertainty of stress measurement are provided, and various error regimes are identified.

Laue-DIC: a new method for improved stress field measurements at the micrometer scale.

A better understanding of the effective mechanical behavior of polycrystalline materials requires an accurate knowledge of the behavior at a scale smaller than the grain size. The X-ray Laue microdiffraction technique available at beamline BM32 at the European Synchrotron Radiation Facility is ideally suited for probing elastic strains (and associated stresses) in deformed polycrystalline materials with a spatial resolution smaller than a micrometer. However, the standard technique used to evaluate local stresses from the distortion of Laue patterns lacks accuracy for many micromechanical applications, mostly due to (i) the fitting of Laue spots by analytical functions, and (ii) the necessary comparison of the measured pattern with the theoretical one from an unstrained reference specimen. In the present paper, a new method for the analysis of Laue images is presented. A Digital Image Correlation (DIC) technique, which is essentially insensitive to the shape of Laue spots, is applied to measure the relative distortion of Laue patterns acquired at two different positions on the specimen. The new method is tested on an in situ deformed Si single-crystal, for which the prescribed stress distribution has been calculated by finite-element analysis. It is shown that the new Laue-DIC method allows determination of local stresses with a strain resolution of the order of 10(-5).

From randomized trials to the clinic: is it time to implement individual lung-cancer screening in clinical practice? A multidisciplinary statement from French experts on behalf of the French intergroup (IFCT) and the groupe d'Oncologie de langue francaise (GOLF).

BACKGROUND: Despite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France. METHODS: A literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article. RESULTS: The multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55-74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given. CONCLUSIONS: Individual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.

Cisplatin-docetaxel induction plus concurrent 3-D conformal radiotherapy and weekly chemotherapy for locally advanced non-small cell lung cancer patients: a phase II trial.

Concurrent chemoradiotherapy (CHRT) is the standard of care for unresectable locally advanced stage III non-small cell lung cancer. However, the optimal combination remains unclear. The aim of this study was to evaluate the efficacy of 2 induction chemotherapy cycles (days 1 and 22) with docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) followed by concurrent chemotherapy (weekly docetaxel-cisplatin, 20 mg/m(2)) and 3-D conformal radiotherapy for 6 weeks (66 Gy/5 fractions per week/2 Gy per fraction). The primary endpoint was the response rate. Secondary objectives were toxicity, time to progression, and overall survival. Forty-four patients were included and 40 were eligible. The mean age was 60.5 years (range 40.7-72.1), and 75% had stage IIIB disease. Six patients underwent complete R0 resection including 2 pathologic complete responses after a planned intermediate evaluation. Thirty-three patients completed CHRT. The objective response rate was 65% (95% CI 50.2-79.8). Grade 3-4 hematologic and digestive toxicities were observed mainly during the induction phase. Grade 3 esophagitis (5%) was experienced during CHRT. With a median follow-up of 38.7 months, the median progression-free survival was 28.3 months (95% CI 11.0-35.0) and the median survival rate was 31.4 months. Cisplatin-docetaxel induction followed by concurrent 3-D conformal radiotherapy and weekly chemotherapy is a feasible protocol associated with a promising response rate and acceptable toxicity.

Development of a synchrotron biaxial tensile device for in situ characterization of thin films mechanical response.

We have developed on the DIFFABS-SOLEIL beamline a biaxial tensile machine working in the synchrotron environment for in situ diffraction characterization of thin polycrystalline films mechanical response. The machine has been designed to test compliant substrates coated by the studied films under controlled, applied strain field. Technological challenges comprise the sample design including fixation of the substrate ends, the related generation of a uniform strain field in the studied (central) volume, and the operations from the beamline pilot. Preliminary tests on 150 nm thick W films deposited onto polyimide cruciform substrates are presented. The obtained results for applied strains using x-ray diffraction and digital image correlation methods clearly show the full potentialities of this new setup.

Oral vinorelbine given as monotherapy to advanced, elderly NSCLC patients: a multicentre phase II trial.

Vinorelbine intravenously (i.v.) demonstrated its efficacy and tolerability in advanced non-small cell lung cancer (NSCLC) patients, including elderly subjects. Since vinorelbine is now available as an oral formulation this phase II open study was designed to evaluate its activity and tolerability in advanced, elderly NSCLC patients. A total of 56 chemonaive patients were recruited from April 2001 through to March 2002. The dosage schedule, already tested in younger NSCLC patients, was 60 mg/m(2)once a week for three weeks (first cycle), followed by 80 mg/m(2) once a week until disease progression or development of unacceptable toxicity. A limited sampling scheme was used for performing pharmacokinetic analysis on 52 of 56 patients enrolled in the study. Treatment was well tolerated with grade 3/4 neutropenia in 11/17 patients (20/30%) and febrile neutropenia in 1 (2%). Six partial responses (11%) and 25 stable disease responses were recorded, with a disease control rate of 55%. Median overall survival was 8.2 months (95% Confidence Interval (CI) [6.2-11.3]). The clinical benefit response rate was 31% on 32 evaluable patients. Pharmacokinetic profiles appeared quite similar to the historical profiles recorded following i.v. administration. Oral vinorelbine appears to be a reasonable alternative to i.v. vinorelbine, both in terms of activity and tolerability, in advanced, elderly NSCLC patients.

Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: a Groupe Français de Pneumo-Cancérologie study.

PURPOSE: To evaluate the efficacy and safety of paclitaxel and carboplatin in the treatment of previously untreated patients with metastatic small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eligible patients were aged 18 to 75 years with an Eastern Cooperative Oncology Group (ECOG) score < or = 2 and life expectancy > or = 12 weeks. Paclitaxel (200 mg/m(2)) was infused over 3 hours, before carboplatin (area under the curve [AUC] 6; Calvert formula) infused over 1 hour, once every 3 weeks for six cycles maximum. Prednisolone, dexchlorpheniramine, and ranitidine were standard premedication. Response to treatment was assessed every two cycles, and nonresponding patients were withdrawn from the trial to receive standard chemotherapy. RESULTS: Of the 50 patients entering the study, 48 and 46 patients were assessable for toxicity and response, respectively. The overall response rate was 65%, with complete responses in three patients. Five patients had stable disease (11%) and 11 patients experienced progressive disease (24%). Median survival was 38 weeks, and median duration of response was 20 weeks. One-year survival was 22.5%. For a total of 232 cycles, grade 3 and 4 toxicity was 33% for neutropenia, 3.5% for thrombocytopenia, and 4% for anemia. Four patients had neutropenic fever (one toxic death). Nonhematologic toxicity was mainly grade 1 and 2 paresthesia (21% of patients); grade 3 myalgia/arthralgia was observed in 6.5% of patients. CONCLUSION: First-line chemotherapy with paclitaxel and carboplatin in metastatic SCLC achieved a response rate and survival similar to standard regimens. With 1-day administration and a tolerable toxicity profile, this combination merits further investigation.

[Pleural effusion]. / L'épanchement pleural.

Bronchial cancer associated with a homolateral malignant pleurisy is classed as T4 whether the pleural disease is a direct extension or metastatic. Effusions without neoplastic cells do not enter into the TNM classification. Investigations of pleural disease consist initially of needle biopsies, completed sometimes by a thoracoscopy, which enable a precise staging and also the achievement of a pleurodesis. A review of the literature does not currently establish the value of a pleurectomy in cases of a homolateral effusion in bronchial carcinoma. Surgical excision may be carried out in a case of neoplastic pleurisy where no pleural invasion is found without knowing the benefits in terms of survival. The inverse exists, with local or diffuse pleural invasion without pleurisy, which are difficult to evaluate by imagery techniques. Thus certain authors recommend pleural lavage during surgical operations for bronchial cancer even without pleural disease: positive cytology seems to be a poor prognostic feature and would justify adjuvant treatment. Thoracoscopy should be carried out when the neoplastic nature of a pleurisy has not been established by needle biopsy in order to evaluate the resectability of the tumour in the absence of surgical contra-indication. In the case of a disabling neoplastic pleurisy a pleurodesis carried out at the time of pleuroscopy may avoid the recurrence of the effusion. Talc is most often employed for pleurodesis but Bleomycin or Tetracycline are also used. In the case of failure to re-expand a shrunken lung the failure of the pleurodesis may lead to a pleuroperitoneal shunt. The type of homolateral pleural disease in bronchial cancer with local invasion by contiguity as against pleural metastases should appear in the TNM classification because there are different treatments and also a different prognosis.

Usefulness of longitudinal evaluation of Cyfra 21-1 variations in advanced lung cancer monitoring.

To investigate the usefulness of Cyfra 21-1 as an indicator of therapy effectiveness and prognosis in advanced primary lung cancer, sixty-three patients were selected on the basis of a high Cyfra 21-1 serum level (> 3.3 ng/ml) at the time of diagnosis. Serial assays of Cyfra 21-1 were performed during the first three courses of chemotherapy among 63 patients. The serial-values were analysed according to response to treatment and overall survival. After three courses of chemotherapy, a 70% reduction under the initial marker's value or a return to normal was observed for 36 patients. Twenty-two (61%) of these patients presented an objective response to therapy, making Cyfra 21-1 a moderate indicator in terms of positive predictive value (PPV). However, a significant decrease of Cyfra 21-1 was observed in 88% (sensitivity) of the 25 objective responders. Cyfra 21-1 changes after one course of chemotherapy (61 patients) were not sufficient to predict the future response after three courses (sensitivity 52%, specificity 56%, PPV 45%). Among 30 clinical or radiological relapses, a 10% increase or a return upper reference limit in Cyfra 21-1 level was observed in 18 cases (sensitivity 60%, specificity 100%, PPV 100%). Survival data were available for 61 patients. No significant statistical difference (P > 0.05) was found between survival curves depending on a significant decrease of Cyfra 21-1 after the first course of chemotherapy. We can conclude that the only interest of serial Cyfra 21-1 assays may be the detection of relapse, where one observes a significant decrease of the marker correlated with an objective response to first treatment.

[Detection of human papillomavirus by polymerase chain reaction in primary lung carcinoma]. / Détection de papillomavirus humain par amplification génique dans les cancers bronchiques primitifs.

Human papillomaviruses (HPV) have been implicated in the pathogenesis of human squamous cell carcinoma, specially of cervical carcinomas. In previous studies concerning primary lung cancer, DNA of HPV subtypes was detected by in situ hybridization or polymerase chain reaction (PCR), up to 30% of the cases, namely in squamous cell carcinomas. A series of 31 frozen biopsies of lung carcinomas (surgical biopsies or through fiber optic bronchoscopy) were examined for the presence of HPV DNA by nested PCR. Primers for the two steps were type-specific primers (6/11-16 and 18; kit Amplicis-HPV) for the transforming region of HPV. HPV-DNA was found in five tumors: in two of 18 cases of squamous cell carcinoma (11%), in one of four cases of adenocarcinoma, in one of six cases of small cell carcinomas and in the unic case of neuro-endocrin carcinoma. No case of the two large cell undifferentiated carcinomas was positive. There were three cases of HPV 6/11, one case of HPV 16, and one sample positive for HPV 6/11 and HPV 18. No morphologic changes consistent with HPV lesions were observed. The frequency of 11% among the squamous cell carcinomas is near those found by previous studies (9 to 20% for HPV 6-11-16-18). For the first time, HPVs have been detected in neuro-endocrin tumors, and this have to be confirmed by studies of many more cases. So HPV might play a role as promoter in carcinogenesis of any types of lung carcinoma, although at a low frequency.

[Prognostic value of pre-therapeutic levels of carcino-embryonic antigen in primary bronchial carcinoma]. / Valeur pronostique du taux préthérapeutique de l'antigene carcinoembryonnaire dans les cancers bronchiques primitifs.

To evaluate the pronostic value of an elevated seric carcinoembryonic antigen (CEA > 10 ng/ml) at diagnosis, in patients with lung cancer, a pair study was done: couples of patients with same staging and histologic type were established, one patient with high CEA level compared to one patient with normal CEA level (< 5.5 ng/ml). Other markers were measured: neuron specific enolase (NSE), squamous cell carcinoma (SCC) or Cyfra 21-1. Survival was the end point of comparison. For 89 couples created, patients with low CEA level had a better survival rate at one year ( p = 0.02), this prognosis advantage was confirmed by a comparison of survival curves with Mantel-Cox and Breslow test (p = 0.01), but not by the signs test. These differences were also observed for the 71 couples of squamous cell carcinomas and adenocarcinomas, and the apparied signs test was still not significant. The poor prognosis persisted for patients with high CEA level, when one another marker's level (NSE or SCC or Cyfra 21-1) was increased, in comparison with patients with any marker increased. On 29 couples of all histological subtypes or on the 25 couples of non small cell lung cancer, the signs test and the comparison of survival curves were significant, but not the 1 year survival rate. This study shows that a CEA level greater than 10 ng/ml at diagnosis is a poor pronostic factor in patients with lung carcinoma, independent of the stage of disease and of the histologic type.

[Carboplatin-VP16 combination in non small cell lung cancers in the aged patient. A study of the French group in pneumology (GFPC)]. / Association carboplatine-VP16 per os dans les cancers bronchiques non à petites cellules du sujet âgé. Etude du groupe français de pneumocancérologie (GFPC).

UNLABELLED: Between February 1992 and May 1993, 22 patients older than 75 years, with non small cell lung cancer, were treated with carboplatin and oral etoposide. There were 18 men and four women with a median age of 79 years. Fourteen patients had an epidermoid carcinoma: four had an adenocarcinoma and four had an undifferentiated carcinoma. Carboplatin was administered intravenously on day 1 at a dose of 300 mg/m2; oral etoposide was administered at a dose of 600 mg/m2 (two capsules daily) for 9, 10, 11, or 12 days according to body surface. Courses were repeated every 28 days for a total of three courses. TOXICITY: 15 patients (68%) had received previous chemotherapy. Myelosuppression was the main problem with one grade IV and five grade III hematologic toxicities. We observed one mild neurologic toxicity. RESULTS: 19 patients were evaluable for response. We observed one complete response (5%), five disease stabilizations (26%) and 13 disease progressions. Median survival was 5 months. These results led to discontinue this study.