First-line palliative radiotherapy for painful bone metastases is an effective treatment whatever its fractionation (single or multiple fractions). It is also indicated after failure or insufficient ...effect of a first irradiation, or the appearance of new painful site. Other indications are spinal cord compression, either as an adjuvant to surgery or as sole treatment, and after surgery for long bone metastases. The development of high precision techniques (stereotactic conditions) widens the possibility of re-irradiation when tolerance doses to normal tissues have already been delivered. Local control and possibly overall survival could be improved in oligometastatic patients.
DTS-108 is a hydrosoluble prodrug, where the SN-38 moiety is covalently linked to a 20-amino acid vector peptide by a specific esterase-sensitive cross-linker, releasing ...7-ethyl-10-hydroxycampthotecin (SN-38) by esterase bond cleavage.
The pharmacokinetics of DTS-108, adverse events graded according to NCI-CTCv3.1, dose-limiting toxicities at cycle 1, the maximum tolerated dose (MTD), and the recommended Phase II dose (RP2D) of intravenous DTS-108 (1-2 hours) every 2 weeks were evaluated in a first-in-human Phase I study in patients with advanced/metastatic carcinomas, according to an accelerated dose escalation design. SN-38 and SN-38 glucuronide (SN-38G) levels were evaluated with fluorescence high-performance liquid chromatography (HPLC) test, then liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods.
Forty-two patients received DTS-108 across 14 dosing cohorts (range 3-416 mg/m
). At 416 mg/m
, three out of six patients had grade 4 neutropenia thereby defining the MTD and the RP2D at 313 mg/m
. Fluorescence HPLC was inaccurate to quantify DTS-108 and its metabolites (SN-38 and SN-38G). New processes and analytical LC/MS/MS methods for testing SN-38 were implemented. At a dose of 313 mg/m
, mean DTS-108, SN-38, and SN-38G area under the plasma concentration-time curve to infinity (coefficients of variation %) were 439,293 (24%), 1,992 (34%), and 4,538 (46%) h·ng/mL. Stable disease (according to Response Evaluation Criteria in Solid Tumors) was observed in nine patients.
Assessing SN-38 concentration using fluorescence HPLC is questionable since this method failed to monitor dose escalation of DTS-108, a new topoisomerase I inhibitor, due to ex vivo degradation. LC/MS/MS methods were consistent in evaluating SN-38 exposures allowing drug monitoring. The maximum tolerated dose of DTS-108 was 416 mg/m
. The RP2D for intravenous DTS-108 was 313 mg/m
every 2 weeks in patients with advanced/metastatic solid tumors.
The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting ...in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint expert consensus guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group.
After a comprehensive literature review, 97 recommendation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65-74 % agreements. Any statement without consensus at round one was re-submitted in round two.
Twenty-one out of 29 (72.4%) surveyed experts responded to both rounds. Seventy-five statements achieved consensus at round one leaving 22 statements needing a revote of which 16 achieved consensus and 5 a trend to consensus. The final rate of consensus was 91/97 (93.8%). Statements with no consensus concerned patient selection (3/19), dose and fractionation (1/11), prescription and dose objectives (1/9) and organs at risk delineation (1/15). The voting resulted in the writing of step-by-step consensus guidelines.
Consensus guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocole recommendations in ongoing and further GETUG clinical trials.
The definition of nodal and/or mucosal target volumes for radiation therapy for lymphadenopathies of unknown primary is controversial. Target volumes may include all nodal areas bilaterraly and be ...pan-mucosal or unilateral, selective, including the sole oropharyngeal mucosa. This review presents current recommendations in light of changes in the TNM classification, Human papillomavirus status and therapeutic advances. We conducted a systematic review of the literature with the following keywords: lymphadenopathy; head and neck; unknown primary and radiation therapy. There are no direct comparative studies between unilateral or bilateral nodal irradiation or pan-mucosal and selective mucosal irradiation. Contralateral lymph node failure rates range from 0 to 6% after unilateral nodal irradiation and 0 and 31% after bilateral irradiation. Occurrence of a mucosal primary varies between 0 and 19.2%. Initial clinical presentation and Human papillomavirus status are critical to define mucosal target volumes. Intensity-modulated radiotherapy is recommended (rather than three-dimensional irradiation) to avoid toxicities. Systemic treatments have similar indications as for identified primary head and neck cancers. Failures do not appear superior in case of unilateral nodal irradiation but comparative studies are warranted due to major biases hampering direct comparisons. Human papillomavirus status should be incorporated into the therapeutic strategy and practice-changing TNM staging changes will need to be evaluated.
To assess the point of view of young physicians training in pediatrics in France on their theoretical courses during residency.
A free-access electronic anonymous survey was sent three times by ...e-mail to the 1215 residents in pediatrics, from July to October 2015.
Fifty-seven percent of French residents in pediatrics responded to the survey. It was established that they took part in six (range, 3-10) half-days of specific theoretical teaching in pediatrics from November 2014 to mid-April 2015. Only 54% participated in more than 75% of regional theoretical training. The main self-declared reason for their absence was that they could not leave their clinical activities. Fifty-three per cent of the residents took part in additional training, 45% of them because they found the primary theoretical training insufficient. The overall quality of the theoretical teaching was rated 5 (range, 3-7) out of 10. Eighty-five percent of residents expected to be evaluated on their knowledge during their residency.
In pediatrics, additional training is individually undertaken because they deemed their initial training insufficient during their residency. An evaluation of knowledge is requested by residents. The reform of the national residency program must take into account these results in redesigning the theoretical training in pediatrics, integrating innovative teaching techniques to daily practice, for example.
Abstract Aim of the Study To describe trends in survival of non-resectable metastatic colorectal cancer (MCRC) over a 34-year period in a French population-based registry taking into account major ...advances in medical therapy. Patients and Methods 3804 patients with non-resectable metastatic colorectal cancer diagnosed between 1976 and 2009 were included. Three periods (1976–96, 1997–2004 and 2005–09) were considered. Results The proportion of patients receiving chemotherapy dramatically increased from 19% to 57% between the first two periods, then increased steadily thereafter reaching 59% during the last period ( p < 0.001). Median relative survival increased from 5.9 months during the 1976–96 period to 10.2 months during the 1997–2004 period but, despite the availability of targeted therapies, remained at 9.5 months during the 2005–09 period. During the last study period, less than 10% of elderly patients received targeted therapies compared to more than 40% for younger patients. Their median relative survival was 5.0 months compared to 15.6 months in younger patients. Conclusion There was an improvement in survival in relation with the increased use of more effective medical treatment. However, at a population-based level, patients are not all treated equally and most of them, especially the elderly, do not benefit from the most up-to-date treatment options.
Abstract Background Quantitative immunochemical faecal occult blood tests have become the recommended tests for colorectal cancer screening. The aim of this study was to complete our knowledge on the ...performance of one of the quantitative immunochemical tests available, FOB-Gold, and to propose a possible strategy for an organised screening programme. Patients and methods Within the French organised screening programme, 23,231 average-risk individuals, aged 50–74 performed both a 3-day Hemoccult test and a 1-day FOB-Gold test. Performances of the immunochemical test were evaluated at different cut-off levels. Results The positivity rate for the Hemoccult was 2.1% and for the FOB-Gold varied between 4.6% (cut-off value of 100 ng/mL, the lowest studied cut-off) and 2.1% (cut-off value of 352 ng/mL). The number of colonoscopies decreased with increasing cut-off values by 21.5% (150 ng/mL), 35.4% (200 ng/mL) and 53.3% (352 ng/mL). The corresponding miss rate for CRC was respectively 6.4%, 11.1% and 22.2%, and for advanced adenoma respectively 16.3%, 29.2% and 43.6%. Compared with the reference cut-off for the FOB-Gold (100 ng/mL) the miss rate for Hemoccult was 53% for CRC and 77% for advanced adenoma. Conclusion The study suggests that in countries with colonoscopy facilities compatible with a screening test positivity rate of up to 5%, use of a 1-day test with a cut-off value between 100 and 150 ng/mL could be the recommended strategy. Further increasing the cut-off value up to the same positivity rate as Hemoccult could be used in areas with limited access to colonoscopy.
To establish the radiation dose level for single- and dual-source thoracic CT scans in daily practice.
The dose levels delivered during 634 consecutive examinations over a period of 2 months were ...recorded. The CT scans were performed using: (a) a standard protocol (single source, single energy group 1: n=266; dual source, single energy group 2: n=276; (b) with prospective ECG synchronisation group 3: n=13; or (c) with dual energy group 4: n=79. All the acquisitions included kilovoltage selection depending on the weight and automatic milliamperage modulation.
The mean DLP of the standard protocols was 97.12 mGycm (group 2; BMI=23.1kg/m2) and 211.1 mGycm (group 1; BMI=27.3kg/m2), the choice of protocol depending on the diameter of the thorax relative to the diameter of the field of the second source, and therefore on the patient's morphotype. When imaging included examination of the proximal and middle coronary arteries (group 3), the mean DLP was 105.5 mGycm. Morphological and functional imaging (group 4) was obtained with a mean DLP of 404.3 mGycm.
Depending on the objective of the protocol, the mean DLP varied from 97.12 to 404.3 mGycm.
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