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To present the feasibility study of optimal dose coverage in ultra-focal brachytherapy (UFB) with multiparametric MRI for low- and intermediate-risk prostate cancer.UFB provisional dose plans for small target volumes (7 cc) were calculated on a prostate training phantom to optimize the seeds number and strength. Clinical UFB consisted in a contour-based nonrigid registration (MRI/Ultrasound) to implant a fiducial marker at the location of the tumor focus. Dosimetry was performed with iodine-125 seeds and a prescribed dose of 160 Gy. On CT scans acquired at 1 month, dose coverage of 152 Gy to the ultra-focal gross tumor volume was evaluated. Registrations between magnetic resonance and CT scans were assessed on the first 8 patients with three software solutions: VariSeed, 3D Slicer, and Mirada, and quantitative evaluations of the registrations were performed. Impact of these registrations on the initial dose matrix was performed.Mean differences between simulated dose plans and extrapolated Bard nomogram for UFB volumes were 36.3% (26-56) for the total activity, 18.3% (10-30) for seed strength, and 22.5% (16-38) for number of seeds. Registration method implemented in Mirada performed significantly better than VariSeed and 3D Slicer (p = 0.0117 and p = 0.0357, respectively). For dose plan evaluation between Mirada and VariSeed, DThis UFB study confirmed the possibility to treat with optimal dose coverage target volumes smaller than 7 cc.

International audience; Purpose - The optimal frequency of prostate cancer image guided radiation therapy (IGRT) has not yet been clearly identified. This study sought to compare the safety and efficacy of daily versus weekly IGRT. Materials and methods - This phase 3 randomized trial recruited patients with N0 localized prostate cancer. The total IGRT doses in the prostate ranged from 70 Gy to 80 Gy, sparing the lymph nodes. Patients were randomly assigned (1:1) to 2 prostate IGRT frequency groups: daily and weekly (ie, on days 1, 2, and 3 and then weekly). The primary outcome was 5-year recurrence-free survival. Secondary outcomes included overall survival and toxicity. Post hoc analyses included biochemical progression-free interval, clinical progression-free interval, and other cancer-free interval. Results - Between June 2007 and November 2012, 470 men from 21 centers were randomized into the 2 groups. Median follow-up was 4.1 years. There was no statistically significant difference in recurrence-free survival between the groups (hazard ratio [HR] = 0.81; P = .330). Overall survival was worse in the daily group than in the weekly group (HR = 2.12 [95% confidence interval (CI), 1.03-4.37]; P = .042). Acute rectal bleeding (grade ≥1) was significantly lower in the daily group (6%) (n = 14) than in the weekly group (11%) (n = 26) (P = .014). Late rectal toxicity (grade ≥1) was significantly lower in the daily group (HR = 0.71 [95% CI, 0.53-0.96]; P = .027). Biochemical progression-free interval (HR = 0.45 [95% CI, 0.25 - 0.80]; P = .007) and clinical progression-free interval (HR = 0.50 [95% CI, 0.24-1.02]; P = .057) were better in the daily group, whereas other cancer-free interval was worse in the daily group (HR = 2.21 [95% CI, 1.10-4.44]; P = .026). Conclusions - Compared with weekly control, daily IGRT control in prostate cancer significantly improves biochemical progression-free and clinical progression-free interval, and rectal toxicity.

Focal therapy of prostate cancer requires precise positioning of therapeutic agents within well-characterized index tumors (ITs). We assessed the feasibility of low-dose-rate ultrafocal brachytherapy.The present study was an institutional review board-approved European Clinical Trials Database-registered phase II protocol. Patients referred (October 2013 to August 2016) for active surveillance (prostate-specific antigen10 ng/mL, cT1c-cT2a, Gleason score on referring biopsy specimens ≤6 (3+3), ≤3 positive biopsy cores, ≤50% of cancer) were preselected. Inclusion was confirmed when complementary image-guided biopsy findings informed a single Prostate Imaging Reporting and Data System (PI-RADS) ≥3, Gleason score ≤7a (3+4) lesion. A ultrasound-visible ancillary marker was positioned within the IT using a magnetic resonance imaging (MRI)/3-dimensional transrectal ultrasound (TRUS) elastic fusion-guided system (Koelis). Ultrafocal transperineal delivery ofOf the 44 preselected patients, 27 did not meet the inclusion criteria. Of the 17 ultrafocal brachytherapy-treated patients, 16 met the primary objective (per protocol success). The prescription dose was delivered to 14.5% ± 6.4% of the prostate volume, resulting in negligible urethral and rectal irradiation and toxicity. No recurrence was evidenced on the 1-year follow-up MRI studies or IT biopsy specimens. Seven nonclinically significant cancers and one Gleason score 7a (3+4) cancer (salvage prostatectomy) were observed in the untreated parenchyma.Recent technology has allowed for selective and effective brachytherapy of small MRI targets.

BACKGROUND Oncology involves complex care and multidisciplinary management of patients; however, misinformation and ineffective communication remain problematic. OBJECTIVE The educational objective of our study was to develop a new teaching method to improve cancer treatment and management by emphasizing the link between hospitals (inpatients) and their surrounding communities (outpatients). METHODS A team of 22 professionals from public and private institutions developed a small private online course (SPOC). Each offering of the course lasted 6 weeks and covered 6 topics: individual health care plans, cancer surgery, ionizing radiation, cancer medicines, clinical research, and oncological supportive care. For participants in the course, we targeted people working in the cancer field. The SPOC used an active teaching method with collaborative and multidisciplinary learning. A final examination was offered in each session. We evaluated participants’ satisfaction rate through a questionnaire and the success of the SPOC by participants’ completion, success, and commitment rates. RESULTS Of the total participants (N=1574), 446 completed the evaluation form. Most participants were aged 31 to 45 years. Participants included 56 nurses, 131 pharmacists, 80 from the medical field (including 26 physicians), 53 from patients’ associations, 28 health teachers, and 13 students (medical and paramedical). Among the participants, 24.7% (90/446) had an independent medical practice, 38.5% (140/446) worked in a public institution, and 36.8% (134/446) worked in a private institution. After completing the SPOC sessions, 85.9% (384/446) thought they had learned new information, 90.8% (405/446) felt their expectations were met, and 90.4% (403/446) considered that the information had a positive impact on their professional practice. The completion rate was 35.51% (559/1574), the success rate was 71.47% (1025/1574), and the commitment rate was 64.67% (1018/1574). Concerning the cost effectiveness of SPOC compared with a traditional classroom of 25 students, online education became more effective when there were more than 950 participants. CONCLUSIONS SPOCs improved the management of oncology patients. This new digital learning technique is an attractive concept to integrate into teaching practice. It offered optimal propagation of information and met the students’ expectations.

To review the clinical outcome of I-125 permanent prostate brachytherapy (PPB) for low-risk and intermediate-risk prostate cancer and to compare 2 techniques of loose-seed implantation.574 consecutive patients underwent I-125 PPB for low-risk and intermediate-risk prostate cancer between 2000 and 2008. Two successive techniques were used: conventional implantation from 2000 to 2004 and automated implantation (Nucletron, FIRST system) from 2004 to 2008. Dosimetric and biochemical recurrence-free (bNED) survival results were reported and compared for the 2 techniques. Univariate and multivariate analysis researched independent predictors for bNED survival.419 (73%) and 155 (27%) patients with low-risk and intermediate-risk disease, respectively, were treated (median follow-up time, 69.3 months). The 60-month bNED survival rates were 95.2% and 85.7%, respectively, for patients with low-risk and intermediate-risk disease (P=.04). In univariate analysis, patients treated with automated implantation had worse bNED survival rates than did those treated with conventional implantation (P.0001). By day 30, patients treated with automated implantation showed lower values of dose delivered to 90% of prostate volume (D90) and volume of prostate receiving 100% of prescribed dose (V100). In multivariate analysis, implantation technique, Gleason score, and V100 on day 30 were independent predictors of recurrence-free status. Grade 3 urethritis and urinary incontinence were observed in 2.6% and 1.6% of the cohort, respectively, with no significant differences between the 2 techniques. No grade 3 proctitis was observed.Satisfactory 60-month bNED survival rates (93.1%) and acceptable toxicity (grade 3 urethritis3%) were achieved by loose-seed implantation. Automated implantation was associated with worse dosimetric and bNED survival outcomes.

Resume Objectif Comparer la radiotherapie conformationnelle asservie a la respiration et la radiotherapie conformationnelle classique pour l’irradiation des cancers du poumon non a petites cellules et des cancers du sein. Patients et methodes Le projet du programme de Soutien aux techniques innovantes couteuses (Stic) de 2003 etait une etude comparative, non randomisee, multicentrique et prospective qui a inclus entre avril 2004 et juin 2008 dans 20 centres francais, un total de 634 patients, 401 atteints de cancer du poumon non a petites cellules et 233 de cancer du sein. Resultats L’analyse des resultats definitifs a confirme la faisabilite et la bonne reproductibilite des differents systemes de radiotherapie asservie a la respiration. Il a ete observe dans le groupe traite par irradiation asservie a la respiration une diminution des parametres dosimetriques predictifs d’une toxicite pulmonaire, cardiaque et œsophagienne, notamment pour les cancers du poumon non a petites cellules. Ces benefices dosimetriques ont ete surtout rapportes avec les techniques de blocage proche de l’inspiration maximum actif Active Breath Control (ABC, Eleckta™) ou volontaire SDX (Dyn’R™) par rapport au systeme de synchronisation respiratoire (RPM). Pour les cancers du poumon non a petites cellules, ces benefices dosimetriques theoriques etaient correles avec une diminution significative de la toxicite clinique aigue et tardive, notamment pulmonaire. Pour les cancers du sein, bien que moins evident compte tenu de la plus faible dose totale, il a ete retrouve une reduction de la dose au cœur diminuant potentiellement le risque de toxicite cardiaque a long terme, particulierement lors de l’irradiation du sein gauche, et une reduction de la dose delivree au sein controlateral. Conclusion La radiotherapie asservie a la respiration apparait essentielle pour reduire le risque de toxicite aigue et tardive, notamment pulmonaire et cardiaque, lors des irradiations des cancers du poumon non a petites cellules et des cancers mammaires.

Resume Objectifs La preservation de la fertilite de l’homme d’âge moyen est une problematique qui connait un interet croissant. Le cancer de la prostate est le second cancer chez l’homme et est diagnostique plus tot qu’auparavant. La curietherapie est un traitement du cancer de la prostate qui conserve l’ejaculation. Notre objectif etait d’etudier la fertilite des hommes traites par curietherapie de la prostate dans un but d’amelioration de l’information au patient. Patients et methodes Sur une serie de 122 hommes traites dans notre institution entre 2000 et 2006 par curietherapie (implants permanents d’Iode 125) pour un cancer localise de la prostate, ayant moins de 65 ans au moment du diagnostic (43–65), quatre patients ont manifeste spontanement leur interet pour la preservation d’une fertilite et ont eu une evaluation andrologique. Resultats Les quatre patients etaient âges de 43, 48, 57 et 61 ans, tous en activite professionnelle (dont deux chefs d’entreprise), leur partenaire etait âgee respectivement de 42, 37, 47 et 38 ans. Tous les quatre avaient un spermogramme posttraitement (realise plus d’un an apres la curietherapie) riche en spermatozoides, avec une asthenospermie moderee, la principale anomalie etant une hypospermie severe. Ces spermogrammes etaient neanmoins compatibles avec la survenue d’une grossesse spontanee (survenue d’une fausse couche chez le patient 1). Conclusion Il existe un interet a demander aux hommes atteints d’un cancer de la prostate leur position concernant la fertilite afin de pouvoir les informer de la morbidite des differents traitements, des possibilites de preservation de la fertilite, et de la necessite de continuer une contraception apres curietherapie si la partenaire n’est pas menopausee et qu’ils n’ont pas de projet d’enfant.

Purpose This study aims to determine prognostic factors for patients who have non–small-cell lung cancer (NSCLC) that is treated with definitive chemoradiation therapy. Materials and Methods Seventy-eight patients has been treated with radiation therapy and concomitant or sequential chemotherapy between 2000 and 2005. Paraffin-embedded biopsy specimens were obtained before treatment from 73 patients and reviewed by two independent pathologists. Complete follow-up data were collected. The impact of clinical and pathological factors and treatment modality on survival was studied using the χ 2 and Fisher exact tests. A multivariate analysis was performed using the Cox proportional hazard model. Results Seventy-three patients were evaluated, 58 men and 15 women. Median age was 62 years. Most had locally advanced disease (42 stage IIIB and 24 stage IIIA), whereas 7 were medically inoperable stage I-II patients. Lymphovascular invasion (LVI) was identified in 20 biopsy specimens (27.4 %). Radiotherapy delivered a median dose of 66 Gy (range, 60 to 70 Gy). The median overall survival was 20.5 months. Relapse-free and overall survival were significantly higher in the concomitant arm than in the sequential arm ( P = .025 and P = .031, respectively). We found an independent association between the presence of LVI and both the risk of death with an adjusted hazard ratio (HR) of 2.69 (95% confidence interval [CI] 1.50-4.83) and the risk of metastatic progression (adjusted HR=3.01; 95% CI 1.58-5.72). Conclusion The presence of LVI on stage III NSCLC biopsy specimens was the only independent prognostic factor for poor outcome and may, therefore, be helpful in identifying patients at high risk of metastatic disease.

Resume Objectifs L’orgasme est un domaine peu etudie de la sexualite masculine. Notre but etait de realiser la premiere analyse detaillee sur la fonction orgasmique chez les patients traites par implants permanents d’iode 125 pour cancer localise de la prostate. Patients et methodes Sur une serie de 270 hommes sexuellement actifs traites par curietherapie de prostate (implants permanents d’iode 125), 241 (89 %), de moyenne d’âge 65 ans (43–80), ont participe a une enquete par courrier sur la fonction sexuelle en moyenne 36 mois apres implantation (9–70). Les fonctions erectiles et ejaculatoires et l’orgasme ont ete explores par questionnaire courrier. Deux questions concernaient l’orgasme. La premiere portait sur la qualite de l’orgasme (rapide/intense/tardif, difficile/emousse/absent) et la seconde sur la presence de douleurs lors de l’orgasme (toujours/parfois/souvent). Resultats Apres curietherapie de prostate, 81,3 % des hommes sexuellement actifs avaient conserve une ejaculation et 90 % un orgasme. On observait une degradation de l’orgasme apres curietherapie ( p = 0,0001). Plus de 50 % des patients avaient des orgasmes alteres (emousse, difficile, absent) apres curietherapie, contre 16 % avant implantation ( p = 0,001). Les hommes ayant une diminution du volume de l’ejaculat avaient plus frequemment un orgasme emousse/difficile ( p = 0,007). L’antecedent d’hormonotherapie neoadjuvante ne semblait pas modifier a long terme le volume de l’ejaculat, la qualite de l’orgasme, ni la frequence des ejaculations douloureuses. Les patients avec un score IIEF-5 superieur a 12 avaient plus frequemment un orgasme intense (26,7 % vs 2,7 % ; p n = 31) avant CP ( p = 0,0001). Conclusion La plupart des patients traites par curietherapie de prostate conservaient un orgasme apres traitement. Cependant, une majorite decrivait une deterioration de la qualite de l’orgasme.

Purpose To evaluate bladder preservation and functional quality after concurrent chemoradiotherapy for muscle-invasive cancer in 53 patients included in a Phase II trial. Patient and Methods Pelvic irradiation delivered 45Gy, followed by an 18-Gy boost. Concurrent chemotherapy with cisplatin and 5-fluorouracil by continuous infusion was performed at Weeks 1, 4, and 7 during radiotherapy. Patients initially suitable for surgery were evaluated with macroscopically complete transurethral resection after 45Gy, followed by radical cystectomy in case of incomplete response. The European Organization for Research and Treatment of Cancer quality of life questionnaire QLQ-C30, specific items on bladder function, and the Late Effects in Normal Tissues–Subjective, Objective, Management, and Analytic (LENT-SOMA) symptoms scale were used to evaluate quality of life before treatment and 6, 12, 24, and 36 months after treatment. Results Median age was 68 years for 51 evaluable patients. Thirty-two percent of patients had T2a tumors, 46% T2b, 16% T3, and 6% T4. A visibly complete transurethral resection was possible in 66%. Median follow-up was 8 years. Bladder was preserved in 67% (95% confidence interval, 52–79%) of patients. Overall survival was 36% (95% confidence interval, 23–49%) at 8 years for all patients, and 45% (28–61%) for the 36 patients suitable for surgery. Satisfactory bladder function, according to LENT-SOMA, was reported for 100% of patients with preserved bladder and locally controlled disease 6–36 months after the beginning of treatment. Satisfactory bladder function was reported for 35% of patients before treatment and for 43%, 57%, and 29%, respectively, at 6, 18, and 36 months. Conclusions Concurrent chemoradiation therapy allowed bladder preservation with tumor control for 67% patients at 8 years. Quality of life and quality of bladder function were satisfactory for 67% of patients.

Resume Objectifs La curietherapie et la radiotherapie externe sont deux traitements du cancer de la prostate localise. La sexualite etant un important determinant de la qualite de vie, et son maintien pouvant entrer en jeu dans le choix du traitement du cancer de la prostate, nous avons souhaite faire le point concernant les effets sexuels de la radiotherapie externe et de la curietherapie de la prostate. Methode Une recherche sur PubMed a ete realisee en utilisant les mots-cles : prostate cancer, erectile dysfunction, radiotherapy, brachytherapy, ejaculation et orgasm. Resultats Apres curietherapie comme apres radiotherapie de la prostate, des troubles sexuels apparaissent progressivement, la dysfonction erectile survenant generalement 12 a 18 mois apres traitement. Bien que les mecanismes physiopathologiques aboutissant a la dysfonction erectile apres curietherapie et radiotherapie de la prostate ne soient pas clairement identifies, l’atteinte vasculaire et des bandelettes neurovasculaires, et l’irradiation des corps erectiles semblent les principaux mecanismes a l’origine de la dysfonction erectile. Encore peu de donnees existent concernant l’ejaculation et l’orgasme apres traitement radiotherapique du cancer de la prostate. Des donnees recentes montrent que les hommes traites par curietherapie conservent generalement une ejaculation et un orgasme, mais qu’ils decrivent souvent une reduction du volume de sperme et une deterioration de l’orgasme. Les patients ayant un cancer de la prostate localise devraient etre informes des consequences possibles de la radiotherapie et de la curietherapie de la prostate sur leurs fonctions sexuelles avant qu’ils ne fassent le choix du traitement de leur maladie. Ils devraient egalement etre informes des possibilites de traitement de la dysfonction erectile.

Resume Objectif Determiner la survie et les criteres pronostiques predictifs des tumeurs pT3NxM0 (TMN 2002) apres prostatectomie totale retropubienne (PT). Materiels et methode Entre 1988 et 2000, 606 PT consecutives ont ete effectuees pour des tumeurs T1-3 clinique, dont 246 (40,6 %) ont ete classees pT3, suivies dans 53 cas d’une radiotherapie adjuvante, et dans 71 cas d’une radiotherapie de rattrapage. Cinquante-cinq patients ont eu une hormonotherapie complementaire. La recidive biologique a ete definie par deux valeurs consecutives du PSA superieur a 0,2 ng/ml. Resultats L’âge median etait de 65 ans, le suivi moyen de 91,4 mois, le PSA preoperatoire median de 12,8 ng/ml. La population etait composee de 170 pT3a (69,1 %) et 76 pT3b (30,9 %). A dix ans, les survies sans recidive biologique, sans metastase, specifique et globale etaient respectivement de 54, 86, 92 et 75 %. Les facteurs pronostiques statistiquement associes a la recidive biologique etaient l’envahissement ganglionnaire, le score de Gleason, le PSA preoperatoire, l’atteinte des vesicules seminales, le statut des marges chirurgicales et l’absence de radiotherapie adjuvante. Conclusion Cette etude montre que les tumeurs pT3, traitees par des associations therapeutiques comprenant une prostatectomie totale presentent une excellente survie specifique a dix ans. La determination des facteurs de mauvais pronostic devrait aider a la selection des patients necessitant un traitement complementaire a la chirurgie.

To investigate the association between magnetic resonance spectroscopic imaging (MRSI)-defined, metabolically abnormal tumor regions and subsequent sites of relapse in data from patients treated with radiotherapy (RT) in a prospective clinical trial.Twenty-three examinations were performed prospectively for 9 patients with newly diagnosed glioblastoma multiforme studied in a Phase I trial combining Tipifarnib and RT. The patients underwent magnetic resonance imaging (MRI) and MRSI before treatment and every 2 months until relapse. The MRSI data were categorized by the choline (Cho)/N-acetyl-aspartate (NAA) ratio (CNR) as a measure of spectroscopic abnormality. CNRs corresponding to T1 and T2 MRI for 1,207 voxels were evaluated before RT and at recurrence.Before treatment, areas of CNR2 (CNRor =2) represented 25% of the contrast-enhancing (T1CE) regions and 10% of abnormal T2 regions outside T1CE (HyperT2). The presence of CNR2 was often an early indicator of the site of relapse after therapy. In fact, 75% of the voxels within the T1CE+CNR2 before therapy continued to exhibit CNR2 at relapse, compared with 22% of the voxels within the T1CE with normal CNR (p0.05). The location of new contrast enhancement with CNR2 corresponded in 80% of the initial HyperT2+CNR2 vs. 20.7% of the HyperT2 voxels with normal CNR (p0.05).Metabolically active regions represented a small percentage of pretreatment MRI abnormalities and were predictive for the site of post-RT relapse. The incorporation of MRSI data in the definition of RT target volumes for selective boosting may be a promising avenue leading to increased local control of glioblastomas.

Le cancer du testicule est le premier cancer de l’adulte jeune et son incidence augmente dans la quasi-totalite des pays industrialises. Le taux de survie apres cancer du testicule est de 95%, tous stades confondus, cependant un groupe de patients a mauvais pronostic continue a echapper aux therapeutiques. Le delai diagnostique est defini comme le temps en mois entre la perception du premier symptome de cancer du testicule par le patient et le diagnostic par le medecin de la maladie. L’objectif de cette etude est de determiner si le delai diagnostique a une valuer pronostique, en particulier s’il est correle avec le stade de la maladie et la survie. Le delai diagnostique a ete etudie chez 542 patients ayant eu un diagnostic de cancer du testicule entre 1983 et 2002 dans la region Midi-Pyrenees. L’information concernant la maladie et les traitements contenus dans les dossiers medicaux a ete colligee sur un document synthetique. Le delai diagnostique a ete correle avec les parametres pronostiques, dont le stade et la survie. Le delai diagnostique etait de 3,7±5,1 mois et etait plus long pour les seminomes (4,9±6,1 mois) que pour les tumeurs germinales non seminomateuses (TGNS) (2,8±4,0 mois). La duree du delai diagnostique etait correlee avec le stade de la maladie et la survie a 5 ans, sur l’ensemble de la population et dans le groupe des TGNS, mais non dans le groupe des seminomes. La precocite du diagnostic conserve une valeur pronostique (correlation avec le stade de la maladie et le taux de survie a 5 ans). Les mesures de sensibilisation et d’information du cancer du testicule sont donc a considerer.

Background. This is the first report of graft function and prostate cancer control in renal transplant recipients subjected to modern conformal radiotherapy. Methods. Eight kidney transplant recipients were treated with three-dimensional conformal radiotherapy. All patients but one were subjected to transitory hormonal deprivation. A three-dimensional radiotherapy-planning system (Pinnacle, Philips Medical System, Bothell, WA) was used to delineate anatomic contours on pretreatment computed tomography and for dose computation. The clinical target volume encompassed the prostate and was expanded with a 10-mm wide margin in all directions to obtain the planning target volume. The irradiation technique consisted of a nine-field arrangement delivering 70 Gy in 2-Gy fractions, with 18-MV photon beams. Biochemical recurrence was defined as two consecutive increases in prostate-specific antigen (>1.5 ng/mL). Graft function was monitored by creatinine clearance. Excretory profiles were assessed by furosemide-stimulated diethylenetriaminepentaacetic acid renography. All patients were subjected to hip magnetic resonance imaging to assess for avascular hip necrosis. Results. After a mean follow-up of 28 months, two patients showed isolated biochemical recurrence and six patients remained free of recurrence. In seven patients with functional allografts, the creatinine clearance was unimpaired by treatment. However, significant obstruction of the terminal ureter was revealed in two patients by furosemide-stimulated diethylenetriaminepentaacetic acid renograms. The doses delivered to the uretero-neocystostomy were calculated to range from less than 20 Gy to more than 45 Gy depending on bladder repletion. Conclusions. Adequate cancer control was achieved at the expense of infraclinical ureteral obstruction. The doses delivered to the uretero-neocystostomy may be reduced by having a full bladder at the time of irradiation. No avascular hip necrosis was observed.

Objectives: To report the long-term impact of two cycles of adjuvant chemotherapy on relapse rates and treatment-related morbidity in high-risk stage I nonseminomatous testicular germ cell tumors (NSGCTT I). Material and Methods: From April 1987 to September 1997, 40 stage I NSGCTT patients with evidence of vascular invasion and/or embryonal carcinoma (EC) in the orchidectomy specimen were treated with two courses of bleomycin, cisplatin, and etoposide (BEP). Results: All patients but one (incidental death) were alive after an extended follow-up (median 113.2 months, range 63–189). No patients relapsed but two patients presented a second cancer in the remaining testis. Short-term toxicity was minimal and no long-term toxicity was observed. Conclusion: The present series, with extensive follow-up, demonstrated that the efficacy and toxicity of two cycles of BEP compared well with the results of surveillance strategies or RPLND in high-risk stage I NSGCTT.

Objectifs La fusion entre IRM multiparametrique et echographie transrectale facilite le diagnostic biopsique du CaP tout en archivant la position des biopsies positives dans le volume de la glande, presentant un avantage decisif dans le developpement des traitements focaux. On sait cependant que le volume tumoral estime dur l’IRM differe du volume histologique (Baco, Eur Urol 2016) posant le probleme des marges de securite necessaires. Methodes A partir d’une BDD prospective, nous avons calcule, par reference a la carotte index definie comme positive et prelevee dans la cible IRM : – la distance la separant du risque de base d’obtenir une carotte positive en un autre lieu de la glande ; – la courbe de decroissance du risque en fonction de la distance. Parmi 961 patients biopsies par fusion elastique (Koelis, La Tronche, France) de 1/2012 a 9/2015, 672 patients ont montre des carottes positives. Les carottes ont ete caracterisees en termes de resultats (positif/negatif) et de distance (mm) mesuree par reference a la carotte index. Resultats Au total, 5285 carottes ont ete prelevees, dont 1811 (34,3 %) etaient positives. On observe une decroissance lineaire de la proportion des biopsies positives jusqu’a un plateau de 20 % a partir de 20 mm. Par regression lineaire, on obtient que dans ce volume le risque decroit selon la formule suivante : 80 % moins 3,5 fois la distance en mm (p Fig. 1 , Fig. 2 ). Conclusion Cette premiere etude biopsique, independante du biais de verification des series chirurgicales, montre l’existence d’un risque residuel (20 % a partir de 20 mm) et apporte une contribution originale sur le debat existant sur les marges de securite. Cette methodologie pourrait etre utilisee dans une population cible de therapie focale.

4 Background: The optimal frequency of prostate cancer image-guided radiation therapy (IGRT) has not yet been clearly identified. This study sought to compare the safety and efficacy of daily versus weekly IGRT. Methods: This Phase III randomized trial recruited 470 patients with N0 localized prostate cancer, from 21 centers between June 2007 and November 2012. Total IGRT doses ranged from 70 to 80 Gy. Patients were randomly assigned (1:1) to two prostate IGRT control frequency groups: daily or weekly (Days 1, 2, and 3, then weekly). The primary outcome was 5-year recurrence-free survival (RFS). Secondary outcomes included overall survival (OS) and toxicity (CTCAE V.3.0). Post-hoc analyses included biochemical progression-free interval (BPFI), clinical progression-free interval (CPFI) and second cancer-free interval (SCFI). Results: Median follow-up was 4.1 years (Q1 – Q3 = 3.1 – 5.1).There was no statistically-significant difference in RFS between the groups (hazard ratio [HR] = 0.81 [95% CI: 0.52 – 1.25]; p = 0.330). OS was worse in the daily control group versus the weekly control group (HR = 2.12 [95% CI: 1.03 – 4.37]; p = 0.042). Late rectal toxicity (Grade ≥1) incidence was significantly lower in the daily control group (HR = 0.71 [95% CI: 0.53 – 0.96]; p = 0.027). BPFI was better in the daily control group versus the weekly control group (HR = 0.45 [95% CI: 0.25 – 0.80]; p = 0.007). CPFI was better in the daily control group (HR = 0.50 [95% CI: 0.24 – 1.02]; p = 0.057). SCFI was worse in the daily control group versus the weekly control group (HR = 2.21 [95% CI: 1.10 – 4.44]; p = 0.026). Conclusions: Compared to weekly control, daily IGRT control in prostate cancer significantly decreases the risks of recurrence and late rectal toxicity but is associated with an increased risk of second cancer. Clinical trial information: NCT00433706.

Purpose : To evaluate reliability of Trans-rectal ultra-sonography (TRUS) guidance with lipiodol injection for prostate localization before radiotherapy planning. Material and methods : From October 1997 to March 2000, 31 patients with prostatic adenocarcinoma and six patients with anastomotic recurrence after radical prostatectomy had TRUS-guided injection of lipiodol. Two milliliters of lipiodol were injected into each side of the prostate and 1 ml into both seminal vesicles with a 22 Gauge CHIBA needle and US probe guide before radiotherapy planning.We had established a contrast quality index (0 for no prostate enhancement to 5 for efficient pacification without any diffusion).On simulation films, we had performed anatomic measurements for comparison with other anatomic studies. Results : For all 37 patients, TRUS-guided injection was well tolerated. Among 31 patients with the prostate in situ, three had no apex opacification and 15 had no vesicle enhancement or peri-vesicle space diffusion. However, in 19 patients there was good contrast quality with an index score of ≥3. The majority of patients had prostatic apex between 1.5 and 3.5 cm from ischial tuberosities ligne (27 from 28 evaluable for apex). Among 19 evaluable patients, 15 had seminal vesicles 2–4 cm above the top of pubis.For six patients with anastomotic recurrence after radical prostatectomy, lipiodol was precious aid to locate it. We had only one failure because of a precocious bladder absorption relating to a delay which is too long between rectal probe locating and portal films. Conclusion : TRUS injection of lipiodol is a simple, inexpensive, relatively safe technique for localization of prostatic apex, but not appropriate for seminal vesicles enhancement. This is also an interesting method to locate anastomotic recurrence.

Objectives. We assessed magnetic resonance imaging (MRI) performance in the prediction of positive surgical margins (PSMs) before radical prostatectomy in a prospective study correlating the MRI results and pathologic findings. Methods. Between January 1995 and December 1999, 176 patients (mean age 64.2 years, range 49 to 75), with localized prostate cancer (49 with Stage T1 and 127 with Stage T2) underwent preoperative MRI with a pelvic phased-array coil (Tesla-1, Siemens) at a mean interval of 35 days after randomized transrectal biopsies. The mean preoperative prostate-specific antigen level was 10.9 ng/mL (range 1.2 to 39). The MRI studies and specimen analysis were performed by one radiologist unaware of the clinical and biopsy findings and by one pathologist, respectively. Multivariate analysis was performed to compare the predictive value of MRI staging, prostate-specific antigen value, and preoperative Gleason score to identify the PSM rate. Results. Of the 176 patients, 131 (74%) had Stage T2 disease by MRI and 45 (26%) Stage T3 disease by MRI. Pathologic staging showed 103 with pT2 and 73 with pT3. Overall, the PSM rate of the series was 18%. The PSM rate was 13.7% and 31% for patients with T2 and T3 disease by MRI, respectively. For the T3 MRI cases, the PSM rate was 2.32-fold higher. MRI staging, like the prostate-specific antigen value, was a predictive factor of PSMs ( P = 0.05). Conclusions. The results of this study show that preoperative MRI staging with the phased-array coil may be helpful in predicting the PSM risk in radical prostatectomy candidates with clinically localized prostate cancer.

Objective: This study was undertaken in order to evaluate the impact of pharmacokinetics on the toxicity of oral etoposide administered daily for 21 days. Methods: The daily dose was 50 mg/m2. Thirty-two patients 24 males and eight females, 36–76 years old, treated for various tumour types), were evaluated. Blood samples were obtained on day 1 for all patients, and on day 21 for 16 patients. Plasma etoposide concentrations were determined by high-performance liquid chromatography, and etoposide plasma protein binding by equilibrium dialysis. Results: On day 1, the mean value (with coefficient of variation for interindividual variability) for the unbound fraction (fu), area under the concentration versus time curve (AUC), and unbound AUC was 9.8% (59%), 34 mg · h/l (39%), and 3.5 mg · h/l (92%), respectively. The ratio between AUC on day 1 and day 21 ranged between 0.5 and 1.8 (mean 0.9, with CV 33%). The plasma trough unbound concentrations and the unbound AUCs both corresponding to the first administration were significantly higher in the 11 patients who had a severe neutropenia than in the 21 patients who had no or moderate toxicity. However, total etoposide concentrations did not differ between these two groups. A limited sampling strategy using the NONMEM program and a database of 89 patients previously studied was performed. The optimal sampling schedule (i.e. 1, 4, and 24 h after oral etoposide administration) allowed to obtain the AUC accurately on day 1. Conclusion: Individual adjustment of oral etoposide based on unbound pharmacokinetics after the first administration appears relevant and feasible.

To analyze erectile function in men treated by prostate brachytherapy (PB) for localized prostate cancer.Of a series of 270 sexually active men treated by PB, 241 (89%), mean age 65 yr (range, 43-80 yr), participated in a study on erectile function that was evaluated using the International Index of Erectile Function 5-item (IIEF-5) questionnaire before implantation and by postal survey after a mean follow-up of 36 months (range, 6-70 months).After PB, 27 patients (11%) had no erectile dysfunction (ED), 36 (15%) had mild ED, 58 (24%) had mild to moderate ED, 24 (10%) had moderate ED, 53 (22%) had severe ED and 43 (18%) were not sexually active. In patients with a preimplant IIEF score12 (cut-off for intercourse with penetration), 73% had a deterioration of erectile function by at least one class after PB. Risk factors for ED after PB were age, preimplant IIEF score and prostate volume. Median time to ED onset was 16 months and was shorter with androgen deprivation (p = 0.007), diabetes (p = 0.03) and age over 55 (p = 0.01).Following PB, the majority of patients progressively develop or major ED after a free interval that may last several months.Ligue Nationale contre le Cancer, France.Etude de la fonction érectile chez les hommes traités par curiethérapie pour un cancer localisé de la prostate.A partir de 270 hommes sexuellement actifs, traités par curiethérapie, 241 (89%), moyenne d’âge 65 ans (entre, 43–80 ans), acceptaient de participer à l’étude de la fonction érectile après curiethérapie. Cette étude menée par le questionnaire validé IIEF 5 (International Index of Erectile Function 5-item), évaluait la fonction érectile avant curiethérapie, et en moyenne 36 mois (entre 6-70mois) après la curiethérapie de prostate. L’enquête était faite par envoi postal.Après la curiethérapie, 27 patients (11%) n’avaient pas de dysfonction érectile, 36 (15%) avaient une dysfonction très modérée, 58 (24%) entre très modérée et modérée, 24 (10%) modérée, 53 (22%) avaient une dysfonction érectile sévère et 43 (18%) n’étaient plus sexuellement actifs. Parmi les patients ayant un score IIEF avant curiethérapie12 (score moyen permettant une pénétration pendant l’acte sexuelle), 73% avait une détérioration de leur fonction érectile d’au moins une classe IIEF. Les facteurs de risque de la dysfonction érectile après curiethérapie étaient: l’âge, le score IIEF avant curiethérapie et le volume de la prostate. La période moyenne pour déclencher une dysfonction érectile après curiethérapie était de 16 mois. Cette période se réduisait lorsque les patients étaient sous hormonothérapie (p = 0.007), avaient du diabète (p = 0.03) et étaient âgés de plus de 55 ans (p = 0.01).Après curiethérapie, la majorité des patients développaient progressivement une dysfonction érectile plusieurs mois après la curiethérapie.Ligue Nationale contre le Cancer, France.

Purpose: To report the final results of a prospective randomized trial that aimed to evaluate efficacy and toxicity of concomitant postoperative radiotherapy and Cisplatin infusion in patients with Stage III or IV squamous cell carcinoma of the head and neck histological evidence of extracapsular spread of tumor in lymph node metastases(s). Methods and Materials: Radiotherapy was delivered using a daily dose of 1.7 Gy for the first 54 Gy and 1.8 to 2 Gy until the completion of the treatment. Cisplatin 50 mg i.v. with forced hydratation was given or not every week (i.e., seven to nine cycles) concurrently with radiotherapy. A total of 44 patients were treated by irradiation only (RT group) and 39 by irradiation with chemotherapy (CM group). Results: The RT group displayed a higher rate of loco-regional failures as compared to CM group (41 vs. 23%; p = 0.08). The overall survival, the survival corrected for deaths by intercurrent disease, and the disease-free survival were better in CM group as compared to RT group with statistically significant differences. Survival without loco-regional treatment failure was better in the CM group, the difference being close to the level of significance ( p = 0.05). Survival without distant metastases were comparable in the two therapeutic groups. Ten severe late complications were observed, four in the RT group (17%) and six in the CM group (22%). Cox univariate analysis comfirned the importance of the therapeutic modality in predicting the overall surviva, the survival corrected for deaths by intercurrent disease, and the disease-free survival. Conclusions: The present final report of this phase III study confirms preliminary results. The concomitant use of 50 mg weekly Cisplatin infusion and postoperative radiation improved loc-regional control and survival. No significant increase of laet radiation complications was observed in the CM group.

From 1981 to 1985, 428 patients presenting with an epidermoid carcinoma of the hypopharynx and/or larynx were treated with a curative intent by surgical resection and postoperative irradiation. Two-thirds of the tumours were T3 and 60% of patients presented with a clinical node involvement. The rates of local failure were 8%, 18% and 13%, respectively, for cancers of the larynx, of the piriform sinus and of the posterior wall; the rates of regional failure were 8%, 23% and 13%, respectively. There is no head and neck site with either a high or low risk of recurrence after resection, but the capsular rupture remains a factor of poor prognosis. The survival rate at 5 years of the whole series is 38%, for laryngeal localisation it reaches 62%. The risk of metastases is related to the node involvement and the interval between surgery and irradiation.

124 Background: Biology suggests that the most significant focus drives the natural history of prostate cancer. We assessed the feasibility of ultrafocal brachytherapy (BT) of the index tumor. Methods: In a 2-step Simon’s design (&=0.1, ß=0.1), 17 patients were needed to assess that 100% of clinical target volume (CTV) - gross tumor volume on T2-MRI plus 2mm margin - received ≥95% of the prescribed dose (primary objective: D100≥152Gy). Pre-inclusion:EAU guidelines for Surveillance [PSA 10yr life expectancy]. Inclusion:when mpMRI detected a PIRADS≥3 focal lesion, confirmed as Gleason sum ≤7a (3+4) cancer on elastic fusion registration (EFR) biopsies (Koelis). Procedure:EFR was used to insert trans-rectally a US-visible marker (Bard SourceLink) within CTV before biplanar TRUS for BT. Dose distribution was optimized by inverse planning (Variseed v7.2) before ultrafocal implantation of I-125 seeds (Bard Pro-Link). 1ary objective:Doses delivered within the first 30d to CTV were assessed by Variseed rigid registration between pre-implant MRI and d30 CT-Scan. 2ary objectives: GI, GU CTCAE toxicity & QoL (IPSS, IIEF5, QLQc30) were prospectively accrued. Protocol biopsies of GTV and rest of the gland were obtained by EFR 1yr post-implantation. Results: 27 patients failed confirmatory biopsies (multifocal n=10; aggressive 11; no cancer 6). Of 17 included (10/2013-8/2016), only 3 did not meet the primary objective (D100: 76, 105, 132 Gy) and the trial was deemed successful. Mean CTV was 0.74±0.31mL that is 1.9±1.1% of the gland. Prescribed dose was delivered to 14.5±6.4% of the gland, in line with the ultrafocal nature of the treatment. To date 11 patients, including the previous 3, received 1yr biopsies. No in-field recurrences (GTV) were observed, 5 non-clinically significant cancers were found in the contralateral lobe. No grade>2 toxicity was observed. QoL evaluation is in process. Conclusions: As shown by optimal dosimetry in 14/17(82.4%), minimal toxicity in all, and no in-field recurrences (0/11), ultrafocal BT is a promising avenue in focal treatment. Clinical trial information: NCT01902680.

e555 Background: Focal brachytherapy is proposed in our institute as an alternative treatment to active surveillance for low-grade prostate cancer (PCa). This study aims at characterizing the tumor focus and its margin with multiparametric Magnetic Resonance Imaging (mpMRI). Methods: Patients pre-qualified for this study were positive for PCa (Gleason 3+3) on a previous standard biopsy series. New series of mp-MRI-guided and ultrasound-targeted biopsies were performed and in total, 17 patients with confirmed tumor and diameter < 20mm were included in this phase II clinical trial (NCT01902680). mpMRI were acquired on a 1.5T Magnetom Aera Siemens scan. Anatomic imaging consists in Fast Spin Echo T2-weighted MRI (T2-MRI) and functional Diffusion Weighted MRI (DWI-MRI) and Dynamic Contrast Enhanced MRI (DCE-MRI) were also performed. After mpMRI registration, tumor volumes of interest (VOI) were drawn on anatomic T2-MRI. VOI and VOI+2mm were reported on functional DWI-MRI and DCE-MRI. Extracted parameters were Apparent Diffusion Coefficient (ADC) and KTrans. All parameters distributions were analyzed with Olea Sphere v3.0 and compared to contralateral normal appearing tissue. Focal brachytherapy was then delivered to all patients with linked 125I seeds with a dose prescription of 152 Gy on the Planning Target Volume (PTV = VOI+2mm). Results: ADC parameters (mean, meadian, 25th and 75th percentiles) are found to be significantly lower in tumor volume (VOI) compared to contralateral normal tissue (p < 0.012 for all ADC parameters), confirming diffusion tumor mass restriction. Different distributions of ADC and KTrans were observed among patients: majority (66.66%) of low ADC and abnormal KTrans values were included in the VOI but interestingly, the 2mm margin allows us to treat additional abnormal ADC and KTrans volumes on 1/3 of the patients. Conclusions: This study confirms that mpMRI is a non-invasive technique able to characterize tumor margin for focal brachytherapy in low-grade PCa. Target volume margin definition is a hot topic when focal treatments (e.g. cryotherapy or HIFU) are considered and mpMRI can bring quantitative answers. Clinical trial information: NCT01902680.

Resume Deux cent quarante-huit cas de cancers epidermoides du sinus piriforme (SP), traites de janvier 1980 a decembre 1985 par association radiochirurgicale, ont ete analyses retrospectivement. Les criteres d'inclusion ont ete les suivants: carcinome epidermoide invasif, origine dans le sinus piriforme, absence de traitement anterieur, pharyngolaryngectomie totale et radiotherapie postoperatoire. La duree moyenne de surveillance etait de 5 ans et la duree minimale, de 3 ans. Soixante et onze malades ont presente une rechute locoregionale (27,4%). Le stade tumoral initial et la presence de residus au niveau des marges ont ete des facteurs predictifs statistiquement significatifs de la rechute muqueuse. La survie actuarielle a 5 ans a ete de 33%, la survie mediane de 32 mois (plateau apres la 6 e annee). Parmi les complications severes, la plus frequente a ete la stenose pharyngee (six cas). L'etude presentee confirme le mediocre pronostic des cancers epidermoides du sinus piriforme malgre l'association radiochirurgicale.

International audience; PURPOSE: This cost analysis aimed to quantify the cost of IGRT in relation to IGRT frequency and modality with Cone Beam Computed Tomography (CBCT) or orthogonal electronic portal imaging with fiducial markers (EPI-FM). MATERIAL AND METHODS: Patients undergoing IGRT for localized prostate cancer were randomized into two prostate control frequencies (daily or weekly). Costs were calculated based on the micro-costing results according to hospitals' perspectives (in Euros, 2009) and the time horizon was radiation therapy. RESULTS: A total of 208 patients were enrolled in seven French cancer centers. A total of 6865 fractions were individually analyzed. The mean total treatment fraction duration was 21.0 min for daily CBCT and 18.3 min for daily EPI-FM. Increasing the control frequency from weekly to daily increased the mean treatment fraction duration by 7.3 min (+53%) for CBCT and 1.7 min (+10%) for EPI-FM (p ≤ 0.01). The mean additional cost per patient of daily controls compared with weekly controls was €679 and €187 for CBCT and EPI-FM, respectively (p

International audience; Purpose: The primary objective of the STIC 2003 project was to compare the clinical and economic aspects of respiratory-gated conformal radiotherapy (RGRT), an innovative technique proposed to limit the impact of respiratory movements during irradiation, versus conventional conformal radiotherapy, the reference radiation therapy for lung cancer.Methods and Materials: A comparative, nonrandomized, multicenter, and prospective cost toxicity analysis was performed in the context of this project between April 2004 and June 2008 in 20 French centers. Only the results of the clinical study are presented here, as the results of the economic assessment have been published previously.Results: The final results based on 401 evaluable patients confirm the feasibility and good reproducibility of the various RGRT systems. The results of this study demonstrated a marked reduction of dosimetric parameters predictive of pulmonary, cardiac and esophageal toxicity as a result of the various respiratory gating techniques. These dosimetric benefits were mainly observed with deep inspiration breath-hold (DIBH) techniques (ABC and SDX systems), which markedly increased the total lung volume compared with the inspiration-synchronized system based on tidal volume (Real-time Position Management). These theoretical dosimetric benefits were correlated clinically with a significant reduction of pulmonary acute toxicity, and the pulmonary, cardiac, and esophageal late toxicities, especially with DIBH techniques. Pulmonary function parameters, although more heterogeneous, especially DLCO, showed a tendency to reduction of pulmonary toxicity in the RGRT group.Conclusions: RGRT seems to be essential to reduce toxicities, especially the pulmonary, cardiac, and esophageal late toxicities with the DIBH methods.

Purpose To perform a randomized trial comparing 70 and 80 Gy radiotherapy for prostate cancer. Patients and Methods A total of 306 patients with localized prostate cancer were randomized. No androgen deprivation was allowed. The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions. Toxicity was graded using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective, objective, management, analytic scales (LENT-SOMA) scales. The patients' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item cancer-specific and 25-item prostate-specific modules. Results The median follow-up was 61 months. According to the 1997-American Society for Therapeutic Radiology and Oncology definition, the 5-year biochemical relapse rate was 39% and 28% in the 70- and 80-Gy arms, respectively ( p = .036). Using the Phoenix definition, the 5-year biochemical relapse rate was 32% and 23.5%, respectively ( p = .09). The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level >15 ng/mL. At the last follow-up date, 26 patients had died, 10 of their disease and none of toxicity, with no differences between the two arms. According to the Radiation Therapy Oncology Group scale, the Grade 2 or greater rectal toxicity rate was 14% and 19.5% for the 70- and 80-Gy arms ( p = .22), respectively. The Grade 2 or greater urinary toxicity was 10% at 70 Gy and 17.5% at 80 Gy ( p = .046). Similar results were observed using the LENT-SOMA scale. Bladder toxicity was more frequent at 80 Gy than at 70 Gy ( p = .039). The quality-of-life questionnaire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms. Conclusion High-dose radiotherapy provided a better 5-year biochemical outcome with slightly greater toxicity.

Purpose No biologic signature of chemoradiotherapy sensitivity has been reported for patients with locally advanced non–small-cell lung cancer (NSCLC). We have previously demonstrated that basic fibroblast growth factor (FGF-2) and αvβ3 integrin pathways control tumor radioresistance. We investigated whether the expression of the proteins involved in these pathways might be associated with the response to treatment and, therefore, the clinical outcome. Methods and Materials FGF-2, β3 integrin, angiopoietin-2, and syndecan-1 expression was studied using immunohistochemistry performed on biopsies obtained, before any treatment, from 65 patients exclusively treated with chemoradiotherapy for locally advanced NSCLC. The response to treatment was evaluated according to the Response Evaluation Criteria in Solid Tumors criteria using computed tomography at least 6 weeks after the end of the chemoradiotherapy. Local progression-free survival, metastasis-free survival, and disease-free survival were studied using the log–rank test and Cox proportional hazard analysis. Results Among this NSCLC biopsy population, 43.7% overexpressed β3 integrin (β3 + ), 43% FGF-2 (FGF-2 + ), 41.5% syndecan-1, and 59.4% angiopoietin-2. Our results showed a strong association between FGF-2 and β3 integrin expression ( p = .001). The adjusted hazard ratio of local recurrence for FGF-2 + /β3 + tumors compared with FGF-2 − /β3 − tumors was 6.1 (95% confidence interval, 2.6–14.6, p = .005). However, the risk of local recurrence was not increased when tumors overexpressed β3 integrin or FGF-2 alone. Moreover, the co-expression of these two proteins was marginally associated with the response to chemoradiotherapy and metastasis-free survival. Conclusion The results of this study have identified the combined profile FGF-2/β3 integrin expression as a signature of local control in patients treated with chemoradiotherapy for locally advanced NSCLC.

Ejaculatory function is an underreported aspect of male sexuality in men treated for prostate cancer. We conducted the first detailed analysis of ejaculatory function in patients treated with permanent (125)I prostate brachytherapy for localized prostate cancer.Of 270 sexually active men with localized prostate cancer treated with permanent (125)I prostate brachytherapy, 241 (89%), with a mean age of 65 years (range, 43-80), responded to a mailed questionnaire derived from the Male Sexual Health Questionnaire regarding ejaculatory function. Five aspects of ejaculatory function were examined: frequency, volume, dry ejaculation, pleasure, and pain.Of the 241 sexually active men, 81.3% had conserved ejaculatory function after prostate brachytherapy; however, the number of patients with rare/absent ejaculatory function was double the pretreatment number (p.0001). The latter finding was correlated with age (p.001) and the preimplant International Index of Erectile Function score (p.001). However, 84.9% of patients with maintained ejaculatory function after implantation reported a reduced volume of ejaculate compared with 26.9% before (p.001), with dry ejaculation accounting for 18.7% of these cases. After treatment, 30.3% of the patients experienced painful ejaculation compared with 12.9% before (p = .0001), and this was associated with a greater number of implanted needles (p = .021) and the existence of painful ejaculation before implantation (p.0001). After implantation, 10% of patients who continued to be sexually active experienced no orgasm compared with only 1% before treatment. in addition, more patients experienced late/difficult or weak orgasms (p = .001).Most men treated with brachytherapy have conserved ejaculatory function after prostate brachytherapy. However, most of these men experience a reduction in volume and a deterioration in orgasm.

This is a report of a nonrandomized comparison of treatment results of 139 patients with stage IB, IIA and proximal IIB carcinoma of the uterine cervix treated by radiation alone and 113 treated with a combination of radiation and surgery. The five-year tumor free acturial survival for the patients with stage IB either with irradiation alone (RT) or combined with surgery (RS) was approximately 87%. For stage II the tumor free actuarial five-year survival 79% with patients of RS, and 76% with RT. In the 113 patients treated with RS there were 18 (16%). In the 139 patients treated by RT there were 18 (13%) recurrences of pelvic, 4 local recurrences, 11 combined with parametrial, and free parametrial recurrences. There was no significant difference in the survival and recurrence rate of the patients treated with either method. Major complications were comparable in both groups (RT approximately 25% and RS approximately 10%), but 2/3 of those complications recovered without sequelae. The most frequent minor complication in the patients treated with RT was rectosigmoiditis.

In recent decades, testicular cancer incidence has considerably increased in a majority of industrialized countries. In France, short reports suggested that the testicular cancer incidence rate has also risen, especially in north-eastern regions. In Europe, geographical variation of incidence rates has been observed in Baltic countries and a clear birth cohort effect has been revealed. This study aimed to assess temporal trends in testicular cancer incidence in southern France. We examined incidence rates over a 20-year time period in a series of 506 consecutive cases of testicular cancer recorded from 1980 to 1999 in the Midi-Pyrenees region of France. Age, calendar period, and birth cohort effects were examined simultaneously using Poisson regression models. Our analysis found a significant rise in the overall incidence rate of testicular germ cell tumors from 1.27 to 3.04 per 100,000 between 1980–1984 and 1995–1999, an annual increase of 5.70%. These results, the first obtained in a large series in southern Europe, show a twofold increase in incidence rate of testicular cancer in the Midi-Pyrenees region, which is very similar to that observed in all European countries, more or less doubling in the last 20 years. Interestingly, this major jump and the apparent testicular cancer gradient between northern and southern Europe suggest considerable geographical heterogeneity in incidence, but low geographical variation in temporal trends.

Objective Testis cancer is the most common cancer in young men, and its incidence continues to rise. Even if prognosis is considered as good, a group with bad prognosis still remains. Diagnostic delay (DD), defined as the time elapsing from the onset of tumour symptoms to the day of diagnosis, is a way to evaluate the rapidity of diagnosis. We assessed the relationship between DD, disease stage, and survival rate. Methods A series of 542 patients diagnosed with a germ cell tumour between 1983 and 2002 at health facilities in the Midi-Pyrenees region, southwest France, were asked about DD. We analysed DD together with data regarding the disease (histologic type, stage), its treatments, and prognosis (impact on survival). Results Mean DD was longer in seminoma (4.9±6.1 mo) than in non-seminomatous germ cell tumour (NSGCT; 2.8±4.0 mo). DD was correlated with disease stage for the whole population ( p =0.014) and for NSGCT ( p =0.0009), but not for seminoma. DD had a significant impact on the 5-yr survival rate in the overall population ( p =0.001) and in the NSGCT group ( p =0.001), but not in the seminoma group. Global trends in mean DD did not change over the 20-yr study period, but we observed a slight decrease during the last decade. Conclusions DD is highly correlated with stage and survival in NSGCT. Urologists should promote programmes to enhance awareness and knowledge of testis cancer, so the diagnosis can be made more rapidly.

Study of the incidence of severe long-term gastrointestinal (GI) and genitourinary (GU) complications of conformal radiotherapy after total prostatectomy for localized prostatic adenocarcinoma.From 1991 to 2000, 114 patients with a mean age of 62 years (range: 45-82 years) were treated by total prostatectomy followed by adjuvant radiotherapy. The mean dose of radiotherapy was 65 Gy (range: 58-72 Gy). The mean interval between prostatectomy and radiotherapy was 10 months (range: 2-28 months). Patients were reviewed every 6 months. We studied severe complications (RTOG grade 3 or 4) occurring after treatment. The mean follow-up was 74 months (range: 32-132 months).Eight patients (7%) treated by adjuvant radiotherapy with a mean dose of 65.5 Gy (range: 59-70 Gy) developed long-term severe complications. The mean time to onset of complications was 25 months (range: 5-72 months). Three patients developed gastrointestinal complications (2 cases of radiation proctitis and 1 anal stricture). Five patients developed genitourinary complications (4 cases of radiation cystitis and 1 urethral stricture). These eight patients received multiple transfusions and required surgical or endoscopic procedures. Most patients were hospitalized on several occasions for periods ranging between 3 days and 1 month.Adjuvant radiotherapy after total prostatectomy is associated with severe long-term complications in 7% of cases. When they occur, these complications generally require repeated major urological and gastrointestinal surgery.

To report the long-term impact of two cycles of adjuvant chemotherapy on relapse rates and treatment-related morbidity in high-risk stage I nonseminomatous testicular germ cell tumors (NSGCTT I).From April 1987 to September 1997, 40 stage I NSGCTT patients with evidence of vascular invasion and/or embryonal carcinoma (EC) in the orchidectomy specimen were treated with two courses of bleomycin, cisplatin, and etoposide (BEP).All patients but one (incidental death) were alive after an extended follow-up (median 113.2 months, range 63-189). No patients relapsed but two patients presented a second cancer in the remaining testis. Short-term toxicity was minimal and no long-term toxicity was observed.The present series, with extensive follow-up, demonstrated that the efficacy and toxicity of two cycles of BEP compared well with the results of surveillance strategies or RPLND in high-risk stage I NSGCTT.

BACKGROUND Patients with testicular cancer have an excellent survival rate, and fertility is one of the main concerns of survivors. The authors investigated fertility status after treatment for testis cancer in long-term survivors. METHODS Four hundred fifty-one consecutive patients with testicular cancer (1979–1999) from health facilities in the French Midi-Pyrenees region were enrolled. Testis tumors were classified according to the Royal Marsden Hospital Classification. Fertility status was assessed by means of a mailed, standardized questionnaire focused on reproductive events that occurred before and after treatment. Of 451 patients with germ-cell tumors, information concerning fertility was obtained in 446 patients (98.9%). The follow-up was at least 3 years. RESULTS Before they were diagnosed with testicular cancer, 91.2% of patients who had tried to get their partners pregnant had succeeded, compared with 67.1% of patients after treatment. Radiotherapy had a much more deleterious effect on fertility compared with chemotherapy alone. Furthermore, cumulative conception rates (log-rank test) for patients who received radiotherapy were significantly lower compared with the rates for patients who received chemotherapy. CONCLUSIONS The outcome of this study, which included the largest series reported to date, showed that fertility in patients with testicular cancer decreased by 30% after treatments and that radiotherapy seemed to have the most deleterious effect on fertility. Cancer 2004;100:732–7. © 2004 American Cancer Society.

Purpose To describe treatments and acute tolerance in a randomized trial comparing 70 Gy and 80 Gy to the prostate in patients with localized prostate cancer. Methods and materials Between September 1999 and February 2002, 306 patients were randomized to receive 70 Gy (153 patients) or 80 Gy (153 patients) in 17 institutions. Patients exhibited intermediate-prognosis tumors. If the risk of node involvement was greater than 10%, surgical staging was required. Previous prostatectomy was excluded, and androgen deprivation was not admitted. The treatment was delivered in two steps. PTV1—including seminal vesicles, prostate, and a 1–0.5-cm margin—received 46 Gy given with a 4-field conformal technique. PTV2, reduced to prostate with the same margins, irradiated with at least 5 fields. Dose was prescribed according to ICRU recommendations in the 70 Gy group, but adapted at the 80 Gy level. Results All patients but one in the 80 Gy arm completed the treatment. In the 70 Gy arm, the mean dose to the PTV2 was 69.5 Gy. In the 80 Gy arm, the mean dose in the PTV2 was 78.5 Gy. Acute toxicity according to Radiation Therapy Oncology Group scale during treatment was reported in 306 patients. There was no statistically significant difference between the two arms: 12% had no toxicity, 80% complained of bladder toxicity, and 70% complained of rectal symptoms. Two months after the end of treatment, 43% of the 70 Gy level and 48% of the 80 Gy level complained of side effects, including 24% and 20% of sexual disorders. There was 6% and 2% of Grade 3 urinary and rectal toxicity. Five patients required a 10–29-day suspension of the treatment. Acute Grade 2 and 3 side effects were related to PTV and CTV1 size, which was the only independent predictive factor in multivariate analysis. Toxicity was not related to the center, age, arm of treatment, or selected data from dose–volume histogram of organ at risk. Conclusion Treatments were completed in respect to constraints. Acute toxicity was acceptable. Intensity of toxicity depended on target volumes.

Electrochemotherapy is a new anticancer therapy in which transient permeabilization of cells by an electric field induces a significant increase in the bleomycin concentration and toxicity in tumour cells. We report a clinical study of electrochemotherapy in malignant melanoma. The main issues addressed were the effect of the size of the nodules, the optimization of the electrical parameters, and posttreatment clinical observations. Four patients were enrolled in the study. They received a 10 mg/m2 dose of bleomycin administered intravenously, followed by short, intense electric pulses applied directly to the skin at the tumour sites. Antitumour effects were obtained, especially in the smallest nodules. Objective responses were obtained in more than 90% of the 55 nodules treated, with a complete response rate of 9%. All patients tolerated the treatment well. No residual effects from the electric pulses were observed, even when a high number of pulses were required or when two consecutive treatments were applied. These results are encouraging and the study should be continued.

To measure the incidence of second non-germ cell malignancies (SNGCM) in patients treated for a stage I-II testicular seminoma.From 1970 to 1992, 131 evaluable patients received in the Institut Claudius Regaud a post-orchiectomy treatment for a stage I-II testicular seminoma. The therapeutic modalities, including salvage treatment for six recurrences, were as follows: infradiaphragmatic radiotherapy (IDRT) (n = 55); infra- and supradiaphragmatic radiotherapy (IDRT + SDRT) (n = 64); IDRT + SDRT with chemotherapy (n = 12). The mean follow-up was 11 years. The cumulative incidence of SNGCM was compared to the overall cancer incidence in the general male population on the basis of the Tarn Cancer Registry; the relative risk was expressed as a standardized incidence ratio (SIR).Overall, the cumulative incidence of SNGCM was 10.7% (14/131 cases). The SIR was equal to 2.81 (95% confidence interval (CI) 1.54-4.72; P0.001) and increased with follow-up duration. The SIR was significantly increased in 64 patients treated with IDRT + SDRT (SIR = 3.08; 95% CI 1.47-5.66; P = 0.002) but not in 55 patients treated with IDRT alone (SIR = 0.62; 95% CI 0.01-3.43; P = 0.8). The 12 patients who received chemotherapy had an SIR of 26.2 (95% CI 5.48-77.69; P0.001), while the SIR was 2.26 in the 119 patients who did not receive any chemotherapy (95% CI 1.13-4.04; P = 0.01 ). Of four hematologic malignancies, three appeared in the 12 patients who received chemotherapy.An increased risk of SNGCM after SDRT + IDRT has been demonstrated. After IDRT alone, the risk of second cancer is not incremented after a median follow-up of 6 years, but further observation of the patients is necessary to achieve final conclusions. Our results suggest that the risk of second cancer and especially of hematologic malignancy is increased by the association of chemotherapy and radiation.

A population pharmacokinetics study using the NONMEM program was undertaken to determine the effects of different covariates on the pharmacokinetic parameters of etoposide. A total of 1,044 plasma etoposide concentrations were determined by high-performance liquid chromatography (HPLC) in 100 patients (pts; 75 men and 25 women aged 25–85 years) treated for various tumor types with i.v. (57 pts) or oral (43 pts) etoposide. For 67 pts, etoposide plasma protein binding was determined by equilibrium dialysis; the unbound fraction ranged from 4% to 24%. A linear two-compartment model with first-order absorption (for oral dosing) accurately described the concentration versus time data. The central and peripheral volumes of distribution were significantly correlated with the body surface area [Vc (L) = 5.5 × BSA (m2) and Vp = 4.1 × BSA], but even after BSA had been taken into account, the interindividual variability of the two volumes remained high (34% and 57%, respectively). The clearance (CL) was not correlated with the following covariates: age, BSA, sex, height, and levels of serum bilirubin and liver enzymes. The final regression model for CL was CL (ml/min) = 49.8 × (1 − 0.009 × PRO) × WT/Scr + 33.8 × (1 − 0.29 × META) × (1− (1 − 0.012 × ALB), where ALB , PRO , WT ,and Scr, respectively, were albuminemia, proteinemia (g/l), weight (kg), and serum creatinine (μM ) and META = 1 if the patient had liver metastases (otherwise, META = 0). The interindividual variability in CL (mean value 30 ml/min) decreased only from 32% to 26% when these covariates were taken into account. The mean oral bioavailability was 66%, showing an interindividual variability of 37%. The plasma clearance of the unbound fraction was strongly and negatively correlated with Scr but was not dependent on either PRO or ALB. These data show that modifications in PRO levels do not directly affect plasma exposure to unbound etoposide. This analysis makes possible the rational consideration of modifications of covariates such as Scr in etoposide dosing. This population data base will constitute the prerequisite for adaptative control with feedback dosing for continuous oral administration of etoposide.

A phase I-II study was initiated in February 1991 of concomitant radiation and cisplatin (CDDP) in the treatment of unresectable head and neck squamous cell carcinomas (n = 12). The first patient was treated palliatively for a cervical recurrence of laryngeal cancer. The 11 other patients had locally advanced (stage IV) previously untreated carcinomas of the oropharynx (n = 9), hypopharynx (n = 1), or cervical node with unknown primary site (n = 1). Standard external radiation was carried out up to a total dose of 60 Gy/6 weeks (7 MeV electron beam) for the first patient and 72 Gy/8 weeks (Co 60 beam) for the other 11 patients. CDDP was infused continuously during the entire radiation treatment, 5 days/week. The starting dose was 4 mg/m 2 /day and was escalated by increments of 1 mg/m 2 /day; dose-limiting toxicity was observed at 7 mg/m 2 /day. Neutropenia (grade 4, one patient; grade 3, three patients) and thrombocytopenia (grade 3, one patient; grade 2, one patient) were the limiting factors. Therefore, the recommended dose of CDDP is 6 mg/m 2 /day. All patients but one completed the scheduled radiation. For the entire group, mucositis was not more severe than that observed with radiotherapy alone. There was no nephro-, oto-, or neurotoxicity. A complete response was obtained in eight (66%) patients. Ofthese, four were free of disease 12-34 months after completion of treatment and one had a total glossectomy for a tongue necrosis. For the whole series, the mean overall survival was 16 months posttreatment. Pharmacokinetic analysis indicated the total cisplatin accumulation at the end of treatment to be 743-1551 ng/ml. Accumulation of ultrafilterable platin was noted in only one patient (137 ng/ml at the end of treatment).