Dual-targeting CD33/CD123 NANOBODY T-cell engager with potent anti-AML activity and good safety profile.

Novel therapies are needed for effective treatment of acute myeloid leukemia (AML). Relapse is common and salvage treatment with cytotoxic chemotherapy is rarely curative. CD123 and CD33, 2 clinically validated targets in AML, are jointly expressed on blasts and leukemic stem cells in >95% of patients with AML.

Comparison between MRI and choline-PET trans-perineal target biopsies and saturation biopsies for detection and topography of intra-prostatic recurrence after primary radiation therapy for prostate cancer.

Introduction: Biochemical recurrence of prostate cancer after radiation therapy occurs in 5 to 50% of cases depending on the radiation technique used. The diagnosis of recurrence of prostate adenocarcinoma must be made accurately. The aim of this study was to compare transperineal saturation and target biopsies to index lesion (IL) as defined on MRI and 18FCholine PET-CT (PETc) for detection of intra-prostatic recurrence after primary radiation therapy for prostate cancer.

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.

An Antibody-Drug Conjugate Targeting MUC1-Associated Carbohydrate CA6 Shows Promising Antitumor Activities.

Glycosylation is a complex multienzyme-related process that is frequently deregulated in cancer. Aberrant glycosylation can lead to the generation of novel tumor surface-specific glycotopes that can be targeted by antibodies. Murine DS6 mAb (muDS6) was generated from serous ovary adenocarcinoma immunization.

Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): a 112-month follow-up of a phase 3, randomised trial.

Background: Radiotherapy is the standard salvage treatment after radical prostatectomy. To date, the role of androgen deprivation therapy has not been formally shown. In this follow-up study, we aimed to update the results of the GETUG-AFU 16 trial, which assessed the efficacy of radiotherapy plus androgen suppression versus radiotherapy alone.

Reoxygenation during radiotherapy in intermediate-risk prostate cancer.

Hypoxia is a major risk factor of prostate cancer radioresistance. We evaluated hypoxia non-invasively, using F-Misonidazole PET/CT prior to radiotherapy and after a dose of 20 Gy in intermediate-risk prostate cancer patients. Decreased hypoxic volumes were observed in all patients, suggesting that radiotherapy induces early prostate tumor reoxygenation.

Evaluation of tumor hypoxia prior to radiotherapy in intermediate-risk prostate cancer using F-fluoromisonidazole PET/CT: a pilot study.

Purpose: Hypoxia is a major factor in prostate cancer aggressiveness and radioresistance. Predicting which patients might be bad candidates for radiotherapy may help better personalize treatment decisions in intermediate-risk prostate cancer patients. We assessed spatial distribution of F-Misonidazole (FMISO) PET/CT uptake in the prostate prior to radiotherapy treatment.

Delineation of the Prostate Bed: The "Invisible Target" Is Still an Issue?

For pathological high-risk prostate cancer, adjuvant irradiation has shown a survival benefit. Phase III studies have highlighted that half men would face biochemical relapse and would be candidate for radiotherapy at adjuvant or salvage times. Despite at least four published international contouring guidelines from different collaborative groups, discrepancies remain for volumes, delineation, and margins to be considered in order to optimize radiotherapy planning.

Post-Prostatectomy Image-Guided Radiotherapy: The Invisible Target Concept.

In the era of intensity-modulated radiation therapy, image-guided radiotherapy (IGRT) appears crucial to control dose delivery and to promote dose escalation while allowing healthy tissue sparing. The place of IGRT following radical prostatectomy is poorly described in the literature. This review aims to highlight some key points on the different IGRT techniques applicable to prostatic bed radiotherapy.

[Prostate cancer brachytherapy].

Prostate brachytherapy techniques are described, concerning both Iodine 125 high dose rate brachytherapy. The following parts are presented: brachytherapy indications, technical description, immediate postoperative management and post-treatment evaluation, and 4 to 6 weeks as well as long-term follow-up.

Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial.

Background: How best to treat rising prostate-specific antigen (PSA) concentration after radical prostatectomy is an urgent clinical question. Salvage radiotherapy delays the need for more aggressive treatment such as long-term androgen suppression, but fewer than half of patients benefit from it. We aimed to establish the effect of adding short-term androgen suppression at the time of salvage radiotherapy on biochemical outcome and overall survival in men with rising PSA following radical prostatectomy.

DNA-PKcs Expression Is a Predictor of Biochemical Recurrence After Permanent Iodine 125 Interstitial Brachytherapy for Prostate Cancer.

Purpose: Predictive factors for biochemical recurrence (BCR) in localized prostate cancer (PCa) after brachytherapy are insufficient to date. Cellular radiosensitivity depends on DNA double-strand breaks, mainly repaired by the nonhomologous end-joining (NHEJ) system. We analyzed whether the expression of NHEJ proteins can predict BCR in patients treated by brachytherapy for localized PCa.

Definition of lymph node areas for radiotherapy of prostate cancer: A critical literature review by the French Genito-Urinary Group and the French Association of Urology (GETUG-AFU).

Purpose: Recommendations for pelvic lymph node (LN) contouring rely on relatively dated studies that defined the Clinical Target Volume (CTV) of interest proposed for radiotherapy. The aim of this article was to review these recommendations with a critical analysis of published data on prostate cancer drainage.

Methods: We performed a review of data on LN drainage in prostate cancer, based on anatomy texts and studies on lymphography, pelvic LN dissections, sentinel LN techniques, magnetic resonance imaging, computed tomography and functional imaging.

[Prostate cancer: what treatment techniques for which tumors? Ethical and methodological issues].

The identification of the optimal radiation technique in prostate cancer is based on the results of dosimetric and clinical studies, although there are almost no randomized studies comparing different radiation techniques. The feasibility of the techniques depends also on the technical and human resources of the radiation department, on the cost of the treatment from the points of view of the society, the patient and the radiation oncologist, and finally on the choice of the patient. The slow evolution of prostate cancer leads to consider the biochemical failure as the main judgment criteria in the majority of the studies.

[Postoperative radiotherapy of prostate cancer].

Between 10 and 40% of patients who have undergone a radical prostatectomy may have a biologic recurrence. Local or distant failure represents the possible patterns of relapse. Patients at high-risk for local relapse have extraprostatic disease, positive surgical margins or seminal vesicles infiltration or high Gleason score at pathology.

SAR405838: an optimized inhibitor of MDM2-p53 interaction that induces complete and durable tumor regression.

Blocking the oncoprotein murine double minute 2 (MDM2)-p53 protein-protein interaction has long been considered to offer a broad cancer therapeutic strategy, despite the potential risks of selecting tumors harboring p53 mutations that escape MDM2 control. In this study, we report a novel small-molecule inhibitor of the MDM2-p53 interaction, SAR405838 (MI-77301), that has been advanced into phase I clinical trials. SAR405838 binds to MDM2 with K(i) = 0.

Discovery and optimization of pyrimidone indoline amide PI3Kβ inhibitors for the treatment of phosphatase and tensin homologue (PTEN)-deficient cancers.

Compelling molecular biology publications have reported the implication of phosphoinositide kinase PI3Kβ in PTEN-deficient cell line growth and proliferation. These findings supported a scientific rationale for the development of PI3Kβ-specific inhibitors for the treatment of PTEN-deficient cancers. This paper describes the discovery of 2-[2-(2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (7) and the optimization of this new series of active and selective pyrimidone indoline amide PI3Kβ inhibitors.

[Longitudinal follow-up of the IPSS within the 5 years following treatment of a localized prostate cancer: overall analysis and by type of treatment].

Objectives: The International Prostate Score Symptom (IPSS) and the question of quality of life (QOL-Q) associated were used in this study for monitoring patients treated for localized prostate cancer (P-Ca).

Patients And Methods: Three groups treated with radical prostatectomy (RP), external beam radiotherapy (RT) or brachytherapy (BRACHY) completed the self-administered questionnaire IPSS and Q-QOL before treatment (bef-TT), after 3 months and once a year for 5 years.

Results: The study included 40 PR, 40 RT and 40 BRACHY.

Nomograms to predict late urinary toxicity after prostate cancer radiotherapy.

Objective: To analyze late urinary toxicity after prostate cancer radiotherapy (RT): symptom description and identification of patient characteristics or treatment parameters allowing for the generation of nomograms.

Methods: Nine hundred and sixty-five patients underwent RT in seventeen French centers for localized prostate cancer. Median total dose was 70 Gy (range, 65-80 Gy), using different fractionations (2 or 2.

[Hypofractionated radiotherapy in prostate cancer].

Radiotherapy plays a central role in the management of localized prostate cancer, but the total duration of treatment of nearly 2 months poses not only problems of fatigue related to repetitive transports, especially for older patients, but also increases the overall cost of treatment including linear accelerators occupancy and patient transportation. To address this problem, various teams have developed hypofractionated radiotherapy protocols seeking to maintain the same efficacy and toxicity while reducing the total duration of treatment. These hypofractionated protocols require recent techniques such as image-guided radiation therapy (IGRT) and intensity-modulated radiation therapy (IMRT).

[High dose rate prostate brachytherapy].

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.

[Home-based zoledronic acid infusion therapy in patients with solid tumours: compliance and patient-nurse satisfaction].

Purpose: To explore patient and nurse satisfaction, compliance with best practice, technical feasibility and safety of home infusion of a bisphosphonate.

Methods: Prospective 1-year survey of home zoledronic acid therapy (4 mg, 15-min intravenous, every three to four weeks) in patients with bone metastases secondary to a solid malignancy. A physician questionnaire, nurse satisfaction/feasibility questionnaire and patient satisfaction questionnaire were administered.

Home-based zoledronic acid infusion therapy in patients with solid tumours: compliance and patient-nurse satisfaction.

Purpose: This study aimed to explore patient and nurse satisfaction, compliance with best practice, technical feasibility and safety of home infusion of the bisphosphonate zoledronic acid (ZOL).

Methods: This was a prospective 1-year survey of home ZOL therapy (4 mg Zometa, 15-min i.v.