Bone-Active Drugs in Pre-Menopausal Women with Breast Cancer Under Hormone Deprivation Therapies.

BACKGROUND: Bone health management in pre-menopausal women with breast cancer (BC) under hormone-deprivation therapies (HDTs) is often challenging, and the effectiveness of bone-active drugs is still unknown. METHODS: This retrospective multicenter study included 306 premenopausal women with early BC undergoing HDTs. Bone mineral density (BMD) and morphometric vertebral fractures (VFs) were assessed 12 months after HDTs initiation and then after at least 24 months. RESULTS: After initial assessment, bone-active drugs were prescribed in 77.5% of women (151 denosumab 60 mg/6 months, 86 bisphosphonates). After 47.0±20.1 months, new VFs were found in 16 women (5.2%). VFs risk was significantly associated with obesity [OR 3.87, p=0.028], family history of hip fractures or VFs (OR 3.21, p=0.040], chemotherapy-induced menopause (OR 6.48, p<0.001), pre-existing VFs (OR 25.36, p<0.001), baseline T-score ≤-2.5 SD at any skeletal site (OR 4.14, p=0.036) and changes at lumbar and total hip BMD (OR 0.94, p=0.038 and OR 0.88, p<0.001, respectively). New VFs occurred more frequently in women untreated compared to those treated with bone-active drugs (14/69, 20.8% vs. 2/237, 0.8%; p<0.001) and the anti-fracture effectiveness remained significant after correction for BMI (OR 0.033; p<0.001), family history of fractures (OR 0.030; p<0.001), chemotherapy-induced menopause (OR 0.04; p<0.001) and pre-existing VFs (OR 0.014; p<0.001). CONCLUSIONS: Pre-menopausal women under HDTs are at high risk of VFs in relationship with high BMI, densitometric diagnosis of osteoporosis, pre-existing VFs and family history of osteoporotic fractures. VFs in this setting might be effectively prevented by bisphosphonates or denosumab.

Denosumab improves trabecular bone score in relationship with decrease in fracture risk of women exposed to aromatase inhibitors.

PURPOSE: Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs. METHODS: 241 consecutive women (median age 58 years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18-24 months of follow-up. During the study period, 139 women (57.7%) received denosumab 60 mg every 6 months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs. RESULTS: Denosumab significantly increased TBS values (from 1.270 to 1.323; P < 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282; P = 0.021). During treatment with BPs, TBS did not significantly change (P = 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs (P = 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women (P = 0.003), without significant differences in changes of BMD at any skeletal site. CONCLUSIONS: TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs.

Serum testosterone mirrors inflammation parameters in females hospitalized with COVID-19.

BACKGROUND: While low testosterone (T) was described as a predictor of unfavorable coronavirus-disease 19 (COVID-19) outcome in men, data concerning the role of T in women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are scant and limited to small cohorts. This study investigated the relationship between serum T values and outcomes of COVID-19 in a large female hospitalized cohort. METHODS: One-hundred-sixty-eight adult women (median age 77, range 18-100 years; 154 in post-menopause) hospitalized for COVID-19 were assessed for PaO2/Fio2 ratio, serum T and inflammatory parameters. RESULTS: Median duration for hospital stay was 14.2 days (range 1-115) with overall mortality of 26% (n = 44). Subjects who died were significantly older (p < 0.001), had significantly more comorbidities (p = 0.015) and higher serum T (p = 0.040), white blood cells (p = 0.007), c-reactive protein (CRP; p < 0.001), interleukin-6 (IL-6; p < 0.001), procalcitonin (PCT; p < 0.001), lactate dehydrogenase (LDH; p = 0.001), D-dimer (p = 0.035), fibrinogen (p = 0.038) and lower serum free-triiodothyronine (FT3; p < 0.001) and luteinizing hormone (LH; p = 0.024) values. In post-menopausal women, significant associations were observed between T levels and serum CRP (rho: 0.23; p = 0.002), IL-6 (rho: 0.41; p < 0.001), LDH (rho: 0.34; p < 0.001), D-Dimer (rho: 0.21; p = 0.008), PCT (rho: 0.26; p = 0.001) and HDL cholesterol (rho: - 0,22, p = 0.008). In multivariate regression analyses, serum T maintained the significant association with mortality after correction for age, coexistent comorbidities and serum LH and FT3, whereas it was lost after correction for inflammatory parameters. CONCLUSION: In females, high serum T levels might be a mirror of inflammatory phenotype and worse COVID-19 course.

[Dosimetric impact of hydrogel spacer use for stereotactic body radiotherapy of localised prostate cancer]. / Impact dosimétrique de la pose d'un espaceur rectal dans le traitement de cancer de la prostate localisé par irradiation en conditions stéréotaxiques.

PURPOSE: Stereotactic body radiotherapy (SBRT) of prostate cancer is associated with rectal toxicities, which can be reduced by using a hydrogel spacer. The object of this retrospective study was to show the feasibility of spacer placement under local anesthesia and utility of hydrogel spacer to reduce the dose to the rectal wall. MATERIAL AND METHODS: We collected data from all patients with localised prostate cancer treated with SBRT (40Gy in 5 fractions) between 2018 and 2020. A hydrogel spacer (SpaceOAR®) was placed depending on the availability of the product. We collected dosimetric data for target volumes and organs at risk. We calculated mean values, which were compared using non-parametric tests. RESULTS: Among 35 patients, mean age was 75 years. Seventeen had a spacer placed, with a mean space created of 10mm. No complication was reported during the intervention. High doses to the rectal wall were significantly lower in spacer group (V38: 0.39 cm3 vs. 0.72 cm3; P=0.02). PTV were better covered in spacer group (P=0.07). Doses to the bladder wall were similar in both groups. CONCLUSION: Spacer procedure under local anesthesia was well tolerated. Hydrogel spacer allowed to reduce doses to the rectum while improving PTV coverage.

Patterns of practice of androgen deprivation therapy combined to radiotherapy in favorable and unfavorable intermediate risk prostate cancer. Results of The PROACT Survey from the French GETUG Radiation Oncology group.

PURPOSE: The intermediate-risk (IR) prostate cancer (PCa) group is heterogeneous in terms of prognosis. For unfavorable or favorable IR PCa treated by radiotherapy, the optimal strategy remains to be defined. In routine practice, the physician's decision to propose hormonal therapy (HT) is controversial. The PROACT survey aimed to evaluate pattern and preferences of daily practice in France in this IR population. MATERIALS AND METHODS: A web questionnaire was distributed to French radiotherapy members of 91 centers of the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG). The questionnaire included four sections concerning: (i) the specialists who prescribe treatments and multidisciplinary decisions (MTD) validation; (ii) the definition of IR subsets of patients; (iii) radiotherapy parameters; (iv) the pattern of practice regarding cardiovascular (CV) and (iv) metabolic evaluation. A descriptive presentation of the results was used. RESULTS: Among the 82 responses (90% of the centers), HT schedules and irradiation techniques were validated by specific board meetings in 54% and 45% of the centers, respectively. Three-fourths (76%) of the centers identified a subset of IR patients for a dedicated strategy. The majority of centers consider PSA>15 (77%) and/or Gleason 7 (4+3) (87%) for an unfavorable IR definition. Overall, 41% of the centers performed systematically a CV evaluation before HT prescription while 61% consider only CV history/status in defining the type of HT. LHRH agonists are more frequently prescribed in both favorable (70%) and unfavorable (98%) IR patients. Finally, weight (80%), metabolic profile (70%) and CV status (77%) of patients are considered for follow-up under HT. CONCLUSION: To the best of our knowledge, this is the first survey on HT practice in IR PCa. The PROACT survey indicates that three-quarters of the respondents identify subsets of IR-patients in tailoring therapy. The CV status of the patient is considered in guiding the HT decision, its duration and type of drug.

[Retrospective study on the intensification of hypofractionated radiotherapy: The organizational change]. / Étude rétrospective sur l'intensification des pratiques de radiothérapie hypofractionnée : le virage organisationnel.

PURPOSE: External radiotherapy process is a chain of steps in which each of them is carried out only if the previous one has been completed. The development of hypofractionation practices in recent years tends to increase the workload of the stages of preparation for irradiation and to decrease the number of fractions per patient. The purpose of this retrospective study is to analyze the evolution of these practices in a single centre and to assess the organizational issues involved. MATERIAL AND METHODS: All radiation therapy records management data were extracted from the Radiation Therapy Information System. Radiotherapy sessions were identified by patient and by ICD (International Classification of Diseases) code. The filling rate of the treatment equipment was calculated using actual data from the radiotherapy department. RESULTS: From 2015 to 2019, there was an increase in the number of scans (+16%), the number of patients treated (+11.6%) and the volume of hours available for treatment (+12%). Also, there was a decrease in the total number of fractions (-5%), in the average number of fractions performed per treatment sequence (-19%), in the occupancy rate of the machines (-7%) and in the average number of fractions performed per patient treated for malignant tumours of the bronchi and lung (-38%), digestive organs (-37%), secondary (-19%) breast (-15%) and prostate (-15%). The number of fractions administered per treatment sequence between 2015 and 2019 decreased significantly for patients in age groups [20-69] (P<0.001) and [>70] (P<0.001). CONCLUSION: A paradox appears between the increase in the total number of patients treated and the decrease in the loading rate of linacs. This shift of workload has an impact on the quality and safety of care and on the organizational and investment strategies. It also has an economic impact where the model of reimbursement is based on per fraction pricing. A reorganization of radiotherapy services is inevitable.

EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

[Prostate brachytherapy: New techniques, new indications]. / Curiethérapie de la prostate : évolutions des indications et des techniques.

Prostate brachytherapy has been for a long time one of the standard treatments for low risk prostate cancer, with high rates of biochemical control and low levels of urinary and sexual late toxicity compared to other available techniques, namely external beam radiotherapy and radical prostatectomy. The aim of this article is to review the recent innovations of prostate brachytherapy, which suggest a bright future for the technique. We will discuss the extension of indications of permanent implant brachytherapy to favorable intermediate-risk patients, the use of novel isotopes such as Palladium 103 and Cesium 131, and the benefit of brachytherapy as a boost following external beam radiotherapy for intermediate and high-risk patients. We will also discuss the rise of high dose rate brachytherapy, as a boost or monotherapy, the increasing use of MRI for patient selection and treatment planning, as well as the development of brachytherapy as a means of focal therapy.

Combined interventional sialendoscopy and intraductal steroid therapy for recurrent sialadenitis in Sjögren's syndrome: Results of a pilot monocentric trial.

OBJECTIVES: To evaluate the effectiveness of interventional sialendoscopy alone or combined with outpatient intraductal steroid irrigations in patients with sialadenitis due to Sjögren's syndrome (SS). DESIGN: A pilot therapeutic study. SETTING: ENT Clinics, Universities of Milan and Pavia. STUDY POPULATION: We included 22 patients with SS of whom 12 underwent interventional sialendoscopy followed by intraductal steroid irrigations (group A), and 10 interventional sialendoscopy alone (group B). OUTCOMES MEASURES: The following outcome measures were considered and recorded before and after the therapeutic intervention: (i) number of episodes of glandular swelling, (ii) cumulative prevalence of patients with glandular swelling assessed by the specific domain, the EULAR SS Disease Activity Index (ESSDAI), (iii) severity of pain by means of a 0-10 pain visual analogue scale (VAS), (iv) severity of xerostomia and other disease symptoms assessed by the EULAR SS Patient Reported Index (ESSPRI) and the Xerostomia Inventory questionnaire. RESULTS: The postoperative reduction in the mean number of episodes of glandular swelling was 87% (95% CI: 77-93) and 75% (95% CI: 47%-88%) in the groups A and B, respectively. The percentage of patients with glandular swelling decreased from 41.7% to 0.0% in the group A and from 30.0% to 0.0% in the group B, respectively. Most of the patients experienced a subjective clinical improvement documented by the statistically significant reductions in the postoperative mean pain VAS (group A P<.001; group B P=.004), Xerostomia Inventory (P<.001 and P=.003) and ESSPRI scores (P<.001 and P=.008). Interventional sialendoscopy followed by outpatient intraductal steroid irrigations was more effective than interventional sialendoscopy alone, when pain VAS, Xerostomia Inventory and ESSPRI scores before and after treatment were analysed together using the multivariate Hotelling T2 test (P=.0173). CONCLUSIONS: This pilot study confirms that interventional sialendoscopy with steroid duct irrigation significantly reduces the number of painful episodes of sialadenitis and improves the subjective sensation of oral dryness and other disease symptoms in patients with SS. The study results also suggest that the improvement is greater when interventional sialendoscopy is combined with a cycle of outpatient steroid ductal irrigations. Larger controlled randomised studies are certainly needed to confirm these preliminary data.

[Combination external beam radiation and brachytherapy boost for prostate cancer]. / Association de radiothérapie externe et de curiethérapie pour les cancers de la prostate.

Brachytherapy as sole treatment is standard of care for D'Amico classification low-risk prostate cancer. For intermediate and high-risk patients, brachytherapy can be associated to external beam radiation therapy to better take into account the risk of extracapsular effraction and/or seminal vesicle involvement. Three randomized studies have shown that this association increases freedom from relapse survival compared to exclusive external beam radiation therapy. This benefit is not shown for overall survival. The addition of a hormonal therapy to this association is most likely mandatory for high-risk patients, and needs to be confirmed for intermediate risk patients. Both high-dose rate and low-dose rate brachytherapy are suitable with similar biochemical disease free survival rates. High-dose rate brachytherapy seems to have a better genitourinary tolerance profile, while low-dose rate brachytherapy is an easier process and has a more widespread expertise.

The survival impact of neoadjuvant hormonal therapy before radical prostatectomy for treatment of high-risk prostate cancer.

BACKGROUND: Several randomized controlled trials assessed the outcomes of patients treated with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP). The majority of them included mainly low and intermediate risk prostate cancer (PCa) without specifically assessing PCa-related death (PCRD). Thus, there is a lack of knowledge regarding a possible effect of NHT on PCRD in the high-risk PCa population. We aimed to analyze the effect of NHT on PCRD in a multicenter high-risk PCa population treated with RP, using a propensity-score adjustment. METHODS: This is a retrospective multi-institutional study including patients with high-risk PCa defined as: clinical stage T3-4, PSA >20 ng ml-1 or biopsy Gleason score 8-10. We compared PCRD between RP and NHT+RP using competing risks analysis. Correction for group differences was performed by propensity-score adjustment. RESULTS: After application of the inclusion/exclusion criteria, 1573 patients remained for analysis; 1170 patients received RP and 403 NHT+RP. Median follow-up was 56 months (interquartile range 29-88). Eighty-six patients died of PCa and 106 of other causes. NHT decreased the risk of PCRD (hazard ratio (HR) 0.5; 95% confidence interval (CI) 0.32-0.80; P=0.0014). An interaction effect between NHT and radiotherapy (RT) was observed (HR 0.3; 95% CI 0.21-0.43; P<0.0008). More specifically, of patients who received adjuvant RT, those who underwent NHT+RP had decreased PCRD rates (2.3% at 5 year) compared to RP (7.5% at 5 year). The retrospective design and lack of specific information about NHT are possible limitations. CONCLUSIONS: In this propensity-score adjusted analysis from a large high-risk PCa population, NHT before surgery significantly decreased PCRD. This effect appeared to be mainly driven by the early addition of RT post-surgery. The specific sequence of NHT+RP and adjuvant RT merits further study in the high-risk PCa population.

Guided folding takes a start from the molecular imprinting of structured epitopes.

A biomimetic route towards assisted folding was explored. Molecularly imprinted polymeric nanoparticles (MIP NPs), i.e. biomimetics with entailed molecular recognition properties made by a template assisted synthesis, were prepared to target a structured epitope: the cystine containing peptide CC9ox, which corresponds to the apical portion of the ß-hairpin hormone Hepcidin-25. The structural selection was achieved by the MIP NPs; moreover, the MIP NPs demonstrated favouring the folding of the linear random peptide (CC9red) into the structured one (CC9ox), anticipating the future role of the MIP NPs as in situ nanomachines to counteract folding defects.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project†.

BACKGROUND: In clinical trials, the use of intermediate time-to-event end points (TEEs) is increasingly common, yet their choice and definitions are not standardized. This limits the usefulness for comparing treatment effects between studies. The aim of the DATECAN Kidney project is to clarify and recommend definitions of TEE in renal cell cancer (RCC) through a formal consensus method for end point definitions. MATERIALS AND METHODS: A formal modified Delphi method was used for establishing consensus. From a 2006-2009 literature review, the Steering Committee (SC) selected 9 TEE and 15 events in the nonmetastatic (NM) and metastatic/advanced (MA) RCC disease settings. Events were scored on the range of 1 (totally disagree to include) to 9 (totally agree to include) in the definition of each end point. Rating Committee (RC) experts were contacted for the scoring rounds. From these results, final recommendations were established for selecting pertinent end points and the associated events. RESULTS: Thirty-four experts scored 121 events for 9 end points. Consensus was reached for 31%, 43% and 85% events during the first, second and third rounds, respectively. The expert recommend the use of three and two endpoints in NM and MA setting, respectively. In the NM setting: disease-free survival (contralateral RCC, appearance of metastases, local or regional recurrence, death from RCC or protocol treatment), metastasis-free survival (appearance of metastases, regional recurrence, death from RCC); and local-regional-free survival (local or regional recurrence, death from RCC). In the MA setting: kidney cancer-specific survival (death from RCC or protocol treatment) and progression-free survival (death from RCC, local, regional, or metastatic progression). CONCLUSIONS: The consensus method revealed that intermediate end points have not been well defined, because all of the selected end points had at least one event definition for which no consensus was obtained. These clarified definitions of TEE should become standard practice in all RCC clinical trials, thus facilitating reporting and increasing precision in between trial comparisons.

[High dose rate prostate brachytherapy]. / Curiethérapie prostatique de haut débit de dose.

This article aims at presenting the interest of high dose rate brachytherapy in the radiation treatment of prostatic adenocarcinoma. We will discuss successively the biological and dosimetric specificity of brachytherapy for this particular cancer. Afterwards, we will review the main phase II and III studies, the therapeutic indications in the daily practice from the evidence based medicine as well as the techniques of external beam radiation therapy for the same indications. Finally, the principal avenues of development will be discussed.

[Contribution of 3D imaging in brachytherapy: which kind of imaging for which localization?]. / Apport de l'imagerie 3D en curiethérapie : quel type d'imagerie pour quelle localisation ?

The use of image-guided brachytherapy has led to a significant change in application techniques and improvements in treatment planning. Today, 3D imaging has replaced orthogonal radiographs for a large number of treatments, providing a possibility of an optimization adapted to the anatomy of each patient. When properly selected and implemented, this imaging provides accurate 3D information of volumes and brachytherapy device, allowing moving from a dose to points assessment to a dose/volume evaluation. This article describes the contribution of different imaging modalities for the different brachytherapy techniques: gynecological brachytherapy, interstitial brachytherapy (breast, penis, etc.) and prostate brachytherapy. It reminds recommendations for the establishment of protocols of images acquisition and 3D reconstruction of brachytherapy devices (applicators, plastic tubes, needles, etc.).

[Prospective economic evaluation of image-guided radiation therapy for prostate cancer in the framework of the national programme for innovative and costly therapies assessment]. / Évaluation économique prospective de la radiothérapie guidée par l'image des cancers de la prostate dans le cadre du programme national de soutien aux thérapeutiques innovantes et coûteuses.

PURPOSE: The main objective of the economical study was to prospectively and randomly assess the additional costs of daily versus weekly patient positioning quality control in image-guided radiotherapy (IGRT), taking into account the modalities of the 3D-imaging: tomography (CBCT) or gold seeds implants. A secondary objective was to prospectively assess the additional costs of 3D versus 2D imaging with portal imaging for patient positioning controls. PATIENTS AND METHODS: Economics data are issued from a multicenter randomized medico-economics trial comparing the two frequencies of patient positioning control during prostate IGRT. A prospective cohort with patient positioning control with PI (control group) was constituted for the cost comparison between 3D (IGRT) versus 2D imaging. The economical evaluation was focused to the radiotherapy direct costs, adopting the hospital's point of view and using a microcosting method applied to the parameters that may lead to cost differences between evaluated strategies. RESULTS: The economical analysis included a total of 241 patients enrolled between 2007 and 2011 in seven centres, 183 in the randomized study (128 with CBCT and 55 with fiducial markers) and 58 in the control group. Compared to weekly controls, the average additional cost per patient of daily controls was €847 (CBCT) and €179 (markers). Compared to PI, the average additional cost per patient was €1392 (CBCT) and €997 (fiducial markers) for daily controls; €545 (CBCT) and €818 (markers) in case of weekly controls. CONCLUSION: A daily frequency for image control in IGRT and 3D images patient positioning control (IGRT) for prostate cancer lead to significant additional cost compared to weekly control and 2D imaging (PI). Long-term clinical assessment will permit to assess the medico-economical ratio of these innovative radiotherapy modalities.

[Which modality for prostate brachytherapy?]. / Quelle modalité de curiethérapie prostatique?

Brachytherapy techniques by permanent implant of radioactive sources or by temporary high-dose-rate (HDR) fractions are nowadays extensively used for the treatment of prostatic carcinoma. Long-term results (at 20 years) concerning large amount of patients have been published by major centers confirming both in terms of efficacy and toxicities that permanent implant of radioactive iodine-125 seeds yields at least the same good results of surgery and of external beam irradiation when proposed to patients affected by low-risk disease. For intermediate to high-risk tumors, HDR temporary implants are proposed as a boost for dose escalation. For both techniques, several topics still need to be clarified dealing with a recent enlargement of indications (HDR alone for low-risk, iodine-125 seeds boost for intermediate-high-risk cancers), or with technical aspects (loose seeds versus linked ones, number of fractions and dose for HDR protocols), while dosimetric issues have only recently been addressed by cooperatives groups. Last but not least, there is a real need to address and clearly characterize the correct definition of biochemical disease control both for iodine permanent implant and for HDR implant. New challenges are facing the prostate-brachytherapy community in the near future: local relapse after external beam radiotherapy are currently managed by several salvage treatments (prostatectomy, cryo, high intensity focused ultrasounds [HIFU]) but the role of reirradiation by brachytherapy is also actively investigated. Focal therapy has gained considerable interest in the last 5 years aiming at treating only the area of cancer foci inside the prostate and preserving nearby healthy tissues. Encouraging results have been obtained with the so-called "minimally invasive" approaches and both permanent seed implantation and HDR brachytherapy techniques may be worthwhile testing in this setting because of their capability of exactly sculpting the dose inside the prostatic gland.

[Combined hormonotherapy with external beam radiotherapy in locally advanced prostate cancer: do side effects overlap the advantages?]. / Hormonothérapie combinée à la radiothérapie externe dans le cancer de prostate localement avancé: les effets secondaires contrecarrent-ils les bénéfices?

Used for more than 60 years in metastatic prostate cancers, hormone therapy is nowadays also an option for the treatment of locally advanced prostate cancer. Adjuvant androgen deprivation combined with external beam radiotherapy has become the gold standard treatment in locally advanced prostate cancer. Combined therapy has been extensively investigated and has shown to improve oncologic outcomes. However, its toxicity is not negligible. Several side effects can be encountered: cardiovascular, bone depletion, metabolic changes and neuropsychologic effects. They may overlap treatment benefits and be responsible of a specific mortality. Nevertheless, randomized studies have demonstrated that there was no increase of specific mortality from combined treatments compared to patients treated by radiotherapy alone. Therefore, these side effects might not be a barrier to adjuvant androgenic deprivation. However, long-term results are still needed and also accurate morbidity studies. In addition, the debate is still ongoing regarding the appropriate duration of hormone therapy.