Anne Ducassou

αvβ3 Integrin and Fibroblast growth factor receptor 1 (FGFR1): Prognostic factors in a phase I–II clinical trial associating continuous administration of Tipifarnib with radiotherapy for patients with newly diagnosed glioblastoma

BACKGROUNDnBased on our previous results showing the involvement of the farnesylated form of RhoB in glioblastoma radioresistance, we designed a phase II trial associating the farnesyltransferase inhibitor Tipifarnib with radiotherapy in patients with glioblastoma and studied the prognostic values of the proteins which we have previously shown control this pathway.nnnPATIENTS AND METHODSnPatients were treated with 200mg Tipifarnib (recommended dose (RD)) given continuously during radiotherapy. Twenty-seven patients were included in the phase II whose primary end-point was time to progression (TTP). Overall survival (OS) and biomarker analysis were secondary end-points. Expressions of αvβ3, αvβ5 integrins, FAK, ILK, fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor 1 (FGFR1) were studied by immuno-histochemistry in the tumour of the nine patients treated at the RD during the previously performed phase I and on those of the phase II patients. We evaluated the correlation of the expressions of these proteins with the clinical outcome.nnnRESULTSnFor the phase II patients median TTP was 23.1 weeks (95%CI = [15.4; 28.2]) while the median OS was 80.3 weeks (95%CI = [57.8; 102.7]). In the pooled phase I and II population, median OS was 60.4 w (95%CI = [47.3; 97.6]) while median TTP was 18.1 w (95%CI = [16.9; 25.6]). FGFR1 over-expression (HR = 4.65; 95%CI = [1.02; 21.21], p = 0.047) was correlated with shorter TTP while FGFR1 (HR = 4.1 (95% CI = [1.09-15.4]; p = 0.036)) and αvβ3 (HR = 10.38 (95%CI = [2.70; 39.87], p = 0.001)) over-expressions were associated with reduced OS.nnnCONCLUSIONnAssociation of 200mg Tipifarnib with radiotherapy shows promising OS but no increase in TTP compared to historical data. FGFR1 and αvβ3 integrin are independent bad prognostic factors of OS and TTP.

Retrospective Analysis of Local Control and Cosmetic Outcome of 147 Periorificial Carcinomas of the Face Treated With Low–Dose Rate Interstitial Brachytherapy

PURPOSEnSkin cancer is the most common malignancy in white populations. We evaluated the local cure rate and cosmetic outcome of patients with basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the face treated with low-dose rate brachytherapy.nnnMETHODS AND MATERIALSnBetween February 1990 and May 2000, 147 facial carcinomas in 132 patients were treated by (192)Ir wire implantation. Side effects of brachytherapy were noted. Follow-up was 2 years or more. Locoregional recurrence-free survival (LRFS) and overall survival were recorded. Group A included patients treated by primary brachytherapy, and Group B included those treated after recurrence.nnnRESULTSnA total of 121 carcinomas were BCCs (82.3%) and 26 were SCCs (17.7%); the median tumor size was 10 mm. Of the tumors, 86 (58.5%) were in men and 61 (41.5%) were in women; the median age was 71 years. Group A comprised 116 lesions (78.9%), and Group B, 31 (21.1%). There were 17 relapses (11.6%) after a median follow-up of 72 months: 12 local, 4 nodal, and 1 local and nodal. Locoregional-free survival was 96.6% at 2 years and 87.3% at 5 years. Five-year LRFS was 82.6% in men and 93.3% in women (p = 0.027). After adjustment for gender, LRFS was better after primary treatment than after recurrence (hasard ratio HR, 2.91; 95% confidence interval, 1.06-8.03; pxa0= 0.039). Five-year LRFS was 90.4% for BCC and 70.8% for SCC (p = 0.03). There were no Grade 3 complications.nnnCONCLUSIONSnLow-dose rate brachytherapy offers good local control and cosmetic outcome in patients with periorificial skin carcinomas, with no Grade 3 complications. Brchytherapy is more efficient when used as primary treatment.

Patterns of failure after radiotherapy for pediatric patients with intracranial ependymoma

PURPOSEnTo investigate the patterns of failure after radiotherapy for pediatric intracranial ependymoma and their correlation with dose parameters.nnnMETHODSnBetween 2000 and 2013, 206 patients were treated in France. MRI scans at relapse were registered to the original planning CTs for topographic analysis of failure patterns. To compare relapse patients (RP) with non relapse patients (NRP), several dose parameters were derived from dose volume histograms.nnnRESULTSnOver a median follow-up of 53.8months, 84 patients presented with relapse. Topographic analysis showed 50 patients with local relapse in the radiation field, 6 in the edge of field, 6 locoregional outside the field, 10 in the spine, 5 supratentorial and 7 local and distant. The median coverage, target coverage and homogeneity indices did not differ significantly between RP and NRP. The median volume of in-field relapse was 1.25cc [0.11, 27], with a median dose of 57.83Gy [50.04, 61.69].nnnCONCLUSIONSnLocal relapse in the tumor bed and the higher dose regions was the predominant pattern of failure. Improving coverage of the target volume and increasing the dose to the high radioresistant regions, taking into consideration other clinical and biological pronostic factors, may be an effective way of reducing local failures.

Impact of dosimetric parameters on local control for patients treated with three-dimensional pulsed dose-rate brachytherapy for cervical cancer

PURPOSEnTo investigate the impact of dose-volume histograms parameters on local control of three-dimensional (3D) image-based pulsed dose-rate brachytherapy (BT).nnnMETHODS AND MATERIALSnWithin a French multicentric prospective study, the data of the 110 patients treated for cervical cancer with external beam radiotherapy followed by 3D image-based and optimized pulsed dose-rate BT were analyzed. Delineation procedures were performed on magnetic resonance imaging in a minority of cases and on CT for the majority of cases, adapted from the Gynaecological Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology recommendations. Optimization procedure was left to the discretion of the treating center.nnnRESULTSnAt 2xa0years, local control rate reached 78%. Dose to Point A, total reference air kerma, and intermediate-risk clinical target volume (IR-CTV) V60 were predictive factors for local control (pxa0=xa00.001, pxa0=xa00.001, and pxa0=xa00.013, respectively). Patients with IR-CTV V60 <75% had a relative risk of local recurrence of 3.8 (95% confidence interval, 1.4-11.1). There was no correlation found between the high-risk clinical target volume dosimetric parameters and local control.nnnCONCLUSIONSnThis multicentric study has shown that 3D image-based BT provides a high local control rate for cervical cancer patients. The V60 for IR-CTV was identified as an important predictive factor for local control.

Prognostic and predictive values of diffusion and perfusion MRI in paediatric intracranial ependymomas in a large national study

OBJECTIVEnTo assess the relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) derived, respectively, from perfusion and diffusion pre-operative MRI of intracranial ependymomas and their predictive and prognostic values.nnnMETHODSnPre-operative MRI and clinical data for intracranial ependymomas diagnosed between January 2000 and December 2013 were retrospectively retrieved from a web-based national database. MRI data included diffusion (62 patients) and perfusion (20 patients) MRI. Patient age, histopathological diagnosis, tumour location, ADC, relative ADC (rADC) and rCBV were considered as potential factors in a survival analysis. Survival rates were estimated using the Kaplan-Meier method. Univariate analyses were performed using the log-rank test to compare groups. We also performed a multivariate analysis, applying the Cox proportional hazards model.nnnRESULTSnADC and rADC values within hypointense regions differed significantly between grades II and III (pu2009=u20090.01). The 75th percentile of ADC within hypointense regions and the 25th percentile of rCBV within non-enhancing lesions were prognostic of disease-free survival (pu2009=u20090.004, pu2009=u20090.05). A significant correlation was found between the 75th percentile of rCBV and the 25th percentile of rADC (pu2009=u20090.01) in enhancing regions of grade-III tumours.nnnCONCLUSIONnPre-operative rADC and rCBV could be used as prognostic factors for clinical outcome and to predict histological grade in paediatric ependymomas.nnnADVANCES IN KNOWLEDGEnPrognostic value of diffusion and perfusion MRI in paediatric ependymoma was found and may play a role in the prognostic classification of patients in order to design more tailored treatment strategies.

Imaging biomarkers of outcome after radiotherapy for pediatric ependymoma

BACKGROUND AND PURPOSEnEpendymoma is the third most common brain tumor in children. Radiation therapy (RT) is systematically administered after maximum surgical resection, utilizing recent advances in radiation delivery. Imaging can make a significant contribution to improving treatment outcome. This prompted us to look for significant preoperative and postoperative imaging markers for survival.nnnMATERIAL AND METHODSnWe undertook a national retrospective review of 121 patients who had undergone resection followed by RT. Preoperative tumor volumes on T1 and FLAIR images were delineated, together with postoperative hyperintense volumes on FLAIR images. Overall survival (OS) and disease-free survival (DFS) analyses included clinical data and volumes extracted from images.nnnRESULTSnAfter a median follow-up of 38.5u202fmonths, 80.2% of patients were alive, but 39.7% had experienced at least one event. Statistically significant differences between patients with and without postoperative FLAIR abnormalities were found for both DFS (71.9% vs. 40.3%; pu202f=u202f0.006) and OS (93.7% vs. 72.4%; pu202f=u202f0.023) in the univariate analyses, and for OS (pu202f=u202f0.049) in the multivariate analyses.nnnCONCLUSIONSnPostoperative FLAIR hyperintensities are a negative prognostic factor for intracranial ependymoma and may be a surrogate for residual disease. They could therefore prove helpful in patients surgical and radiotherapeutic management.

Sexual Quality of Life and Needs for Sexology Care of Cancer Patients Admitted for Radiotherapy: A 3-Month Cross-Sectional Study in a Regional Comprehensive Reference Cancer Center

BACKGROUNDnProviding early and better care in onco-sexuality and a better understanding of the sexual health care needs of patients before they start treatment is required.nnnOBJECTIVEnTo assess sexual quality of life and need for sexology care of patients when they are starting radiotherapy.nnnDESIGNnWe performed a cross-sectional study of adult patients with cancer admitted for radiotherapy treatment in a regional comprehensive cancer center.nnnMETHODSnWe selected all consecutive adult patients scheduled to start radiotherapy within a 3-month period and excluded patients who could not complete the questionnaires. Patients were asked to complete the Sexual Quality of Life Questionnaire (SQoL) and a needs-assessment questionnaire.nnnOUTCOMESnTotal score on the SQoL and willingness (yes or no) to get help for a sexual problem.nnnRESULTSnThe study sample was composed of 77 men and 123 women. The average SQoL scores were 68.4xa0±xa020.9 and 47.1 ± 13.0 for men and women, respectively (P < .001). Of sexually active patients, 58% had decreased frequency of intercourse or had completely stopped sexual activity after their cancer diagnosis. Half the participants wanted care for their sexual concerns. The proportion desiring specific types of care varied from 28.5% (couple counseling) to 54.5% (sexual physician) with variation by sex or type of cancer. Furthermore, 11.5% of participants declared their willingness to join support groups.nnnCLINICAL IMPLICATIONSnEarly interventions before radiotherapy could improve sexual quality of life, particularly in women.nnnSTRENGTHS AND LIMITATIONSnStrengths are the SQoL validated in men and women, the original window for assessment, and the study location. Limitations are the monocentric design, the potential recall bias for data before cancer diagnosis, and the fact that some patients had treatments before radiotherapy.nnnCONCLUSIONnOur data suggest the need to examine the sexual health trajectory in a prospective fashion from diagnosis to survivorship. Almont T, Delannes M, Ducasson A, etxa0al. Sexual Quality of Life and Needs for Sexology Care of Cancer Patients Admitted for Radiotherapy: A 3-Month Cross-Sectional Study in a Regional Comprehensive Reference Cancer Center. J Sex Med 2017;14:566-576.

Clinical and histological features of second breast cancers following radiotherapy for childhood and young adult malignancy

OBJECTIVEnThe purpose of this study was to determine the characteristics of early second breast cancer (SBC) among survivors of childhood and young adult malignancy treated with irradiation.nnnMETHODSnWe conducted a multicenter retrospective study of women who presented with breast cancer aged 50 years or younger in nine French centers.nnnRESULTSn121 patients and 141 SBC were analyzed (invasive = 130; non-invasive = 11). The mean age at first cancer diagnosis was 15 years and at initial SBC diagnosis was 38 years. Bilateral disease before the age of 51 years was diagnosed in 16% of the females. The majority of SBC were invasive carcinomas (92%). Among the invasive carcinomas, 39% had a histoprognostic score of III, 3.1% overexpressed HER2 and 29% were triple negative. The proportion of triple negative phenotype SBC was higher in patients older at first cancer diagnosis [RR = 1.2, 95%u2009CIxa0(1.1-1.3)]. 94% of triple negative SBCs developed in breast tissue which had receivedxa0>20u2009Gy.nnnCONCLUSIONnWe found a high proportion of aggressive SBC following thoracic radiotherapy in childhood or early adulthood. Advances in knowledge: SBC screening is recommended by scientific societies for these child/young-adulthood cancer survivors in the same way as the one for high risk women because of constitutional mutations. Our results support these recommendations, not only because of a similar cumulative risk, but also because of the aggressive histological characteristics.

Clinical and diagnosis characteristics of breast cancers in women with a history of radiotherapy in the first 30 years of life: A French multicentre cohort study

PURPOSEnIrradiation (>3Gy) to the breast or axillae before 30years of age increases the risk of secondary breast cancer (SBC). The purpose of this article is to describe the clinical characteristics of SBC and the way of diagnosis in young women (before the age of national screening) in France who had received previous radiotherapy for a childhood or a young adulthood cancer.nnnPATIENTS AND METHODSnThis retrospective, multicentre study reviewed the medical records of women with SBC before the age of the national screening who had received irradiation (≥3Gy) on part or all of the breast before 30years of age, for any type of tumour except BC.nnnRESULTSnA total of 121 SBC were detected in 104 women with previous radiotherapy. Twenty percent of SBC were detected during regular breast screening and 16% of the women had a regular radiological follow-up.nnnCONCLUSIONnOur results points out that the main proportion of childhood cancer survivors did not benefit from the recommended breast cancer screening. This result is comparable to other previously published studies in other countries. A national screening programme is necessary and should take into account the patients age, family history, personal medical history and previous radiotherapy to reduce the number of SBC diagnosed at an advanced stage.

OC-0308: Identification of significant biological subvolumes from MRI in pediatric ependymoma related to treatment outcome

Despite late complications related to radiation therapy, RT remains a standard component of treatment among pediatric patients. The current aim of many pediatric clinical trials is to reduce dose and volume of irradiation to decrease side effects without affecting the rate of local control using multimodality treatment. Recent advances in radiotherapy technology contribute also to improve therapeutic ratio thanks to better conformal dose distribution and avoidance of surrounding critical structures. Integration of multimodal imaging in target delineation, use of CT for treatment planning (3D conformal radiation therapy) and immobilization devices have significantly decreased clinical and planning target volume margins. Intensity modulated radiation therapy could be particularly useful in cases of complex and large volume closed to critical structures. While high dose to neighboring structures can be selectively decreased by the means of IMRT, low dose is raised in the rest of the body with theoretical increased risk of secondary malignancies or unexpected toxicities related to irradiation of very sensitive organs at risk located at distance of target volume. Number of prospective studies comparing IMRT to 3D CRT is low. However available data suggest that IMRT provided local control equivalent to 3D CRT with favorable short term toxicity profile and reduction of some sequelae. No excess of second tumor is described but followup is still limited. Concerning strategies for management of internal target movement due to respiratory motion, the more widespread modality in pediatric radiotherapy is 4-dimensional CT for radiation. Other techniques such as active breathing control or respiratory gating is not widely widespread because their use is conditioned by collaboration ability and patient age. Up to now stereotactic radiation therapy has been mainly used in childhood for intracranial benign disease by neurosurgeon. However development of non-invasive repositioning system and LINAC dedicated to stereotactic irradiation gives the opportunity of hypofractionated treatment of metastasis or recurrence in previously irradiated field with minimal impact of quality of live in palliative setting. With high precision techniques, reproducibility in daily set-up becomes more critical to prevent geographic misses and image-guided RT (IGRT) has become a common practice of care for children as for the adults. One of the most applied IGRT technique is cone-beam computed tomography (CBCT). A limitation in use of CBCT among pediatric population is the extra dose deposit to critical structures witch is higher in children than in adults. Because of potential of yielding a secondary cancer at long term, it is essential to adapt scanning protocol when CBCT is applied to pediatric cancer patients routinely.