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Fatherhood issues in the country of Lebanon remain largely unexplored and undocumented. This review serves as a basis for fatherhood issues and presents a snapshot of the current situation with a background of some of the most related challenges affecting the issue of parenting in Lebanon. In addition, this review lays the background of how these challenges affect women of childbearing age who often end up raising their families on their own. Cultural and religious beliefs as well as factors relating to political influences in the Middle East region are discussed. The author concludes with a set of lessons learned. [ABSTRACT FROM AUTHOR]

The 2 × 2 PEACE-1 study showed that combining androgen-deprivation therapy with docetaxel and abiraterone improved overall and radiographic progression-free survival in patients with de novo metastatic castration-sensitive prostate cancer. We aimed to examine the efficacy and safety of adding radiotherapy in this population. We conducted an open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Europe. Eligible participants were male patients (aged ≥18 years) with de novo metastatic castration-sensitive prostate cancer confirmed by bone scan, CT, or MRI, and an Eastern Cooperative Oncology Group performance status of 0–1 (or 2 in the case of bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen-deprivation therapy alone or with six cycles of intravenous docetaxel 75 mg/m2 every 3 weeks), standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), standard of care plus radiotherapy (74 Gy in 37 fractions to the prostate), or standard of care plus radiotherapy and abiraterone. Participants and investigators were not masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival, analysed by intention to treat in patients with low-volume metastatic disease and in the overall study population. This ongoing study is registered with EudraCT, 2012-000142-35. Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled and 1172 were randomly assigned to receive standard of care (n=296 [25·3%]), standard of care plus abiraterone (n=292 [24·9%]), standard of care plus radiotherapy (n=293 [25·0%]), and standard of care plus abiraterone and radiotherapy (n=291 [24·8%]). Median follow-up was 6·0 years (IQR 5·1–7·0) at the time of radiographic progression-free survival and overall survival analysis. A qualitative interaction between radiotherapy and abiraterone for radiographic progression-free survival in the population of patients with low-volume disease prevented the pooling of intervention groups for analysis (p=0·026). Adding radiotherapy to standard of care improved radiographic progression-free survival in patients with low-volume disease treated with abiraterone (median 4·4 years [99·9% CI 2·5–7·3] in the standard of care plus abiraterone group vs 7·5 years [4·0–not reached] in the standard of care plus abiraterone and radiotherapy group; adjusted hazard ratio [HR] 0·65 [99·9% CI 0·36–1·19]; p=0·019), but not in patients not treated with abiraterone (median 3·0 years [99·9% CI 2·3–4·8] in the standard of care group vs 2·6 years [1·7–4·6] in the standard of care plus radiotherapy group; 1·08 [0·65–1·80]; p=0·61). For overall survival, the predefined threshold for a statistical interaction was not reached (p=0·12); therefore, the two intervention groups receiving radiotherapy were pooled together for analysis. In patients with low-volume disease, the overall survival was not influenced by radiotherapy (median 6·9 years [95·1% CI 5·9–7·5] for standard of care with or without abiraterone vs 7·5 years [6·0–not reached] for standard of care plus radiotherapy with or without abiraterone; HR 0·98 [95·1% CI 0·74–1·28]; p=0·86). In the overall safety population, 339 (56·1%) of 604 patients who did not receive radiotherapy and 329 (58·8%) of 560 patients who received radiotherapy developed at least one severe adverse event (grade ≥3), the most common being hypertension (110 [18·2%] patients in the standard of care with or without abiraterone group and 127 [22·7%] in the standard of care plus radiotherapy with or without abiraterone group) and neutropenia (40 [6·6%] and 29 [5·2%]). Combining radiotherapy with standard of care plus abiraterone improves radiographic progression-free survival and castration resistance-free survival, but not overall survival in patients with low-volume de novo metastatic castration-sensitive prostate cancer. Radiotherapy reduces the occurrence of serious genitourinary events, regardless of metastatic burden and without increasing the overall toxicity, and could become a component of standard of care in patients with both high-volume and low-volume de novo metastatic castration-sensitive prostate cancer. Janssen-Cilag, Ipsen, Sanofi, and Institut National du Cancer. [ABSTRACT FROM AUTHOR]

Background: Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care.Methods: We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland. Eligible patients were male, aged 18 years or older, with histologically confirmed or cytologically confirmed de novo metastatic prostate adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0-1 (or 2 due to bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen deprivation therapy alone or with intravenous docetaxel 75 mg/m2 once every 3 weeks), standard of care plus radiotherapy, standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), or standard of care plus radiotherapy plus abiraterone. Neither the investigators nor the patients were masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival. Abiraterone efficacy was first assessed in the overall population and then in the population who received androgen deprivation therapy with docetaxel as standard of care (population of interest). This study is ongoing and is registered with ClinicalTrials.gov, NCT01957436.Findings: Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled (one patient subsequently withdrew consent for analysis of his data) and assigned to receive standard of care (n=296), standard of care plus radiotherapy (n=293), standard of care plus abiraterone (n=292), or standard of care plus radiotherapy plus abiraterone (n=291). Median follow-up was 3·5 years (IQR 2·8-4·6) for radiographic progression-free survival and 4·4 years (3·5-5·4) for overall survival. Adjusted Cox regression modelling revealed no interaction between abiraterone and radiotherapy, enabling the pooled analysis of abiraterone efficacy. In the overall population, patients assigned to receive abiraterone (n=583) had longer radiographic progression-free survival (hazard ratio [HR] 0·54, 99·9% CI 0·41-0·71; p<0·0001) and overall survival (0·82, 95·1% CI 0·69-0·98; p=0·030) than patients who did not receive abiraterone (n=589). In the androgen deprivation therapy with docetaxel population (n=355 in both with abiraterone and without abiraterone groups), the HRs were consistent (radiographic progression-free survival 0·50, 99·9% CI 0·34-0·71; p<0·0001; overall survival 0·75, 95·1% CI 0·59-0·95; p=0·017). In the androgen deprivation therapy with docetaxel population, grade 3 or worse adverse events occurred in 217 (63%) of 347 patients who received abiraterone and 181 (52%) of 350 who did not; hypertension had the largest difference in occurrence (76 [22%] patients and 45 [13%], respectively). Addition of abiraterone to androgen deprivation therapy plus docetaxel did not increase the rates of neutropenia, febrile neutropenia, fatigue, or neuropathy compared with androgen deprivation therapy plus docetaxel alone.Interpretation: Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard of care for these patients.Funding: Janssen-Cilag, Ipsen, Sanofi, and the French Government. [ABSTRACT FROM AUTHOR]

Oligorecurrent pelvic nodal relapse in prostatic cancer is a challenge for regional salvage treatments. Androgen depriving therapies (ADTs) are a mainstay in metastatic prostate cancer, and salvage pelvic radiotherapy may offer long ADT-free intervals for patients harboring regional nodal relapses. To assess the efficacy of the combination of ADT and salvage radiotherapy in men with oligorecurrent pelvic node relapses of prostate cancer. We performed an open-label, phase II trial of combined high-dose intensity-modulated radiotherapy and ADT (6 mo) in oligorecurrent (five or fewer) pelvic node relapses in prostate cancer, detected by fluorocholine positron-emission tomography computed tomography imaging. The primary endpoint was 2-yr progression-free survival defined as two consecutive prostate-specific antigen levels above the level at inclusion and/or clinical evidence of progression as per RECIST 1.1 and/or death from any cause. Between August 2014 and July 2016, 67 patients were recruited in 15 centers. Half of the patients had received prior prostatic irradiation. The median age was 67.7 yr. After a median follow-up of 49.4 mo, 2- and 3-yr progression-free survival rates were 81% and 58%, respectively. Median progression-free survival was 45.3 mo. The median biochemical relapse–free survival (BRFS) was 25.9 mo. At 2 and 3 yr, the BRFS rates were 58% and 46%, respectively. Grade 2 + 2-yr genitourinary and gastrointestinal toxicities were 10% and 2%, respectively. Combined high-dose salvage pelvic radiotherapy and ADT appeared to prolong tumor control in oligorecurrent pelvic node relapses in prostate cancer with limited toxicity. After 3 yr, nearly half of patients were in complete remission. Our study showed initial evidence of benefit, but a randomized trial is required to confirm this result. In this report, we looked at the outcomes of combined high-dose salvage pelvic radiotherapy and 6-mo-long hormone therapy in oligorecurrent pelvic nodal relapse in prostatic cancer. We found that 46% of patients presenting with oligorecurrent pelvic node relapses in prostate cancer were in complete remission after 3 yr following combined treatment at the cost of limited toxicity. Combined high-dose elective salvage pelvic radiotherapy and androgen depriving therapy appeared to prolong tumor control in oligorecurrent pelvic node relapses in prostate cancer, with a significant proportion of patients still in complete remission 3 yr after the procedure, at the cost of only limited toxicity. [ABSTRACT FROM AUTHOR]

Objectives: Urinary tract infection (UTI) is the most common bacterial infection to complicate pregnancy. Medical authorities recommend screening for asymptomatic bacteriuria (ASB) in pregnancy; albeit there is no consensus on ideal timing and frequency for testing. Due to the persistent physiologic changes of pregnancy postpartum, a recent trend to perform urinalysis upon presentation for delivery has been adopted at our institution and various satellite hospitals to putatively minimize cases of postpartum pyelonephritis. The aim of this study is to examine whether routine testing with urinalysis and screening for ASB following suspicious urinalysis with treatment can decrease the incidence of postpartum pyelonephritis, and to determine whether certain urinalysis parameters are more predictive of a positive urine culture.Study Design: A retrospective chart review study of all term deliveries was conducted over two years at the American University of Beirut Medical Center, a university teaching hospital. A total of 2359 deliveries of women with no increased susceptibility to UTIs were reviewed. None had urinary symptoms upon presentation. Urinary parameters including time of urinalysis and urine culture collection with respect to time of delivery, corresponding results and mode of urine collection were correlated to intrapartum course, incidence of ASB and of postpartum pyelonephritis.Results: The incidence of ASB among women presenting for delivery was 4.83 %, with Escherichia coli as the most commonly detected pathogen. The presence of nitrite on urinalysis was significantly associated with a positive urine culture (p-value<0.001). Women with history of antenatal ASB or UTI were more likely to have ASB intrapartum with an odds ratio of 3.14 (95 % CI 1.71-5.75, p-value <0.001). Intrapartum urinalysis with subsequent diagnosis and treatment of ASB did not significantly affect the incidence of postpartum pyelonephritis (p-value 0.280). Similarly, intrapartum urinalysis in the setting of positive history of antenatal ASB or UTI did not increase the incidence of postpartum pyelonephritis compared to women with no such history (p-value 0.659).Conclusions: Urinalysis screening intrapartum does not decrease the incidence of postpartum pyelonephritis. Universal urinalysis screening intrapartum is not warranted and should be reserved for women reporting urinary symptoms and/or women at high risk of UTI. [ABSTRACT FROM AUTHOR]

• To the best of our knowledge, this is the first study to evaluate the cost-effectiveness of replanning ART and the present study adds to the still limited body of cost-effectiveness of IMRT in head and neck cancer. • The cost-effectiveness analysis was designed alongside the ARTIX phase-III trial which was linked to the French national health data system (SNDS). To the best of our knowledge, this is the first cost-effectiveness analysis based on a randomized clinical trial matched to the SNDS. • ICERs were €162,444 and €194,529 per xerostomia avoided at 12 and 24 months, respectively. The ICER are too high to consider that ART is a cost-effective technique. Replanning ART was slightly behind when progression-free and overall survival were taken into account. We performed a cost-effectiveness analysis (CEA) comparing an adaptive radiotherapy (ART) strategy, based on weekly replanning, aiming to correct the parotid gland overdose during treatment and expecting therefore to decrease xerostomia, when compared to a standard IMRT. We conducted the ARTIX trial, a randomized, parallel-group, multicentric study comparing a systematic weekly replanning ART to a standard IMRT. The primary endpoint was the frequency of xerostomia at 12 months, measured by stimulating salivary flow with paraffin. The CEA was designed alongside the ARTIX trial which was linked to the French national health data system (SNDS). For each patient, healthcare consumptions and costs were provided by the SNDS. The reference case analysis was based on the primary endpoint of the trial. Sensitivity and scenario analyses were performed. Of the 129 patients randomly assigned between 2013 and 2018, only 2 records were not linked to the SNDS, which provides a linkage proportion of 98.4%. All of the other 127 records were linked with good to very good robustness. On the intent-to-treat population at 12 months, mean total costs per patient were €41,564 (SD 23,624) and €33,063 (SD 16,886) for ART and standard IMRT arms, respectively (p = 0.033). Incremental cost effectiveness ratio (ICER) was €162,444 per xerostomia avoided. At 24 months, ICER was €194,521 per xerostomia avoided. For both progression-free and overall survival, ART was dominated by standard IMRT. The ART strategy was deemed to be not cost-effective compared with standard IMRT for patients with locally advanced oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

The article offers information on the author's experience of working in a primary health-care centre (PHCC). It mentions PHCC assumed an important role in the relief efforts by helping to implement several international health and medical aid projects for Syrian refugees; and also mentions partnership with International Medical Corps (IMC) and the United Nations Population Fund (UNFPA) allowed us to offer a wide array of health-care services to Syrian refugees.

Le cancer de la prostate est un adénocarcinome sensible, dans plus de 80 % des cas, à la castration chimique, en raison de son hormonodépendance. Le cancer localement évolué et/ou à haut risque est défini en fonction du stade clinique, de la valeur initiale de la concentration sérique d'antigène spécifique de la prostate ou du score de Gleason élevé. L'hormonothérapie associée à la radiothérapie est le standard de la prise en charge et améliore le contrôle local, diminue le risque de métastase à distance et améliore les probabilités de survie spécifique et globale. La durée d'hormonothérapie, le niveau de dose de radiothérapie seule ou associée à la curiethérapie sont des données controversées dans la littérature. Le choix thérapeutique, pluridisciplinaire, dépend de l'âge et des maladies associées du patient, des critères pronostiques de la pathologie et de la fonction urinaire du patient. La recherche actuelle est orientée sur l'optimisation du contrôle local et à distance de ces formes agressives et intègre la chimiothérapie néoadjuvante ou adjuvante de même que les nouvelles hormonothérapies. Prostate cancer is a sensitive adenocarcinoma, in more than 80% of cases, to chemical castration, due to its hormone dependence. Locally advanced and/or high-risk cancer is defined based on clinical stage, initial prostate specific antigen serum concentration value or high Gleason score. Hormone therapy associated with radiation therapy is the standard of management and improves local control, reduces the risk of distant metastasis and improves specific and overall survival. Duration of hormone therapy, dose level of radiation therapy alone or associated with brachytherapy are controversial data in the literature. The therapeutic choice, multidisciplinary, depends on the age and comorbidity of the patient, the prognostic criteria of the pathology and the urinary function of the patient. Current research focuses on optimizing local and distant control of these aggressive forms and incorporates neoadjuvant or adjuvant chemotherapy and also new hormone therapies. [ABSTRACT FROM AUTHOR]

Our goal was to evaluate the impact of progression type (prostate-specific antigen [PSA] only, radiological or clinical) at initiation of first-, second- and third life-extending therapy (LET) on treatment outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients, by performing a post-hoc analysis using data from the CATS international registry. The 669 consecutive mCRPC patients of the CATS registry were classified according to their type of progression at initiation of each LET: PSA only (PSA-p), radiological (±PSA) (Radio-p); or clinical (±PSA, ±radiological) progression (Clin-p). Overall survival (OS), the primary endpoint, was calculated from initiation of the first-, second- and third-LET to death for each sequence. Median OS was shorter in the Clin-p group compared with the PSA-p group (14-month difference in first line; around 7-month difference in second- and third line). Shorter progression-free survival (PFS) was also observed in Clin-p patients, whatever the treatment is. Clinical progression seemed to be associated with a shorter duration of therapy with androgen receptor-targeted therapy (ART) compared with taxanes. Clinical progression at initiation of a LET is associated with poor outcomes including shorter PFS and OS as well as clinical and biological features of aggressive disease. Stratifying patients in clinical trials according to disease progression type may prevent selection bias and data heterogeneity. In daily practice, first signs of clinical progression may prompt physicians to consider starting a new LET, independently of PSA levels. • Metastatic castration-resistant prostate cancer (mCRPC) is treated by using several drugs. • Prognostic factors are useful to determine optimal treatment sequences in mCRPC. • Data were collected in 661 real-life patients over three successive treatment lines. • Post-hoc analysis showed that clinical progression was associated with poor outcomes. • Type of disease progression at the start of each line is a useful prognostic factor. [ABSTRACT FROM AUTHOR]

Purpose: Limited pelvic nodal relapse of prostatic cancer is a paramount challenge for locoregional salvage treatments. Salvage whole pelvis radiation therapy as considered in the BLINDED trial is an attractive option, but there are concerns about its toxicity. This article describes early toxicity with the technique.Methods and Materials: BLINDED was a prospective multicenter phase 2 trial investigating high-dose salvage pelvic irradiation with an additional dose to the fluorocholine-based positron emission tomography-positive pelvic lymph nodes, combined with 6-month androgen blockade. The prescribed dose was 54 Gy in 1.8 Gy fractions with up to 66 Gy in 2.2 Gy fractions to the pathologic pelvic lymph nodes. Early toxicity was defined as toxicity until 1 year after radiation therapy. Patients quality of life was assessed using the European Organisation for Research and Treatment of Cancer questionnaires (QLQ-C30 and QLQ-PR25).Results: Seventy-four patients were recruited in 15 French radiation oncology departments between August 2014 and July 2016. Seven were excluded before treatment because of violation of the inclusion criteria. The intention-to-treat analysis therefore included 67 patients. Half had received prior prostatic irradiation. Median age was 67.7 ± 6.5 years. Grade 2 acute urinary toxicity was observed in 9 of 67 patients (13.4%), and grade 2 1-year toxicity occurred in 4 of 67 patients (6%). Three patients (4.4%) had grade 3 urinary toxicity. Grade 2 acute digestive toxicity was observed in 10 of 67 patients (14.9%), and grade 2 1-year toxicity occurred in 4 of 67 patients (6%). Patients with prior prostate bed irradiation did not exhibit increased urinary or digestive toxicity. The European Organisation for Research and Treatment of Cancer questionnaire scores at 1 year did not worsen significantly.Conclusions: The acute and 1-year toxicity of the BLINDED protocol was satisfactory, even in patients with a history of prostatic irradiation. [ABSTRACT FROM AUTHOR]

Background: According to the Catalogue of Transmission Genetics in Arabs, less than half of diseases reported in Lebanese patients are mapped. In the recent years, Next Generation Sequencing (NGS) techniques have significantly improved clinical diagnosis, compared to traditional sequencing methods. Methods: A total of 213 analyses by NGS (167 by whole exome sequencing (WES) and 46 by multigene panels tests) were performed on pediatric patients across different regions of Lebanon over a period of two years (December 2015–December 2017). Results: Neurological disorders were the most frequent referral demand for both WES and gene panels (122/213). Pathogenic, likely pathogenic, or variants of unknown significance were identified in 69.5% of the WES and panel patients combined. Over half of the patients with such variants had an autosomal recessive disorder. A definite molecular diagnosis (pathogenic or likely pathogenic variants) was achieved in 34.1% and 47.8% of the patients studied by WES and the multigene panels, respectively. Thirty‐three novel variants were found in the cases that were molecularly solved; 26 of these being identified by WES and seven by the multigene panels. In three consanguineous families, autosomal recessive inheritance of genes previously reported as showing dominant inheritance patterns were found. Biallelism was found in six cases, digenism in four cases, and one case was trigenic. Conclusion: Our study thus suggests that NGS tools are valuable for an improved clinical diagnosis, and highlights that the increased adoption of such techniques will significantly further improve our understanding of the genetic basis of inherited diseases in Lebanon. We present the results of a study which included a total of 213 analyses by NGS. Thirty‐three novel variants were found in the cases that were molecularly solved; and autosomal recessive inheritance of genes previously reported as showing dominant inheritance patterns were found. [ABSTRACT FROM AUTHOR]

Background Treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (DOC), cabazitaxel (CABA) and new hormone therapy (NHT) is limited. Rechallenge with DOC is limited because of cumulative toxicities. This study investigated the activity and safety of CABA rechallenge in mCRPC. Patients and methods Clinical data were collected retrospectively in 17 centres in Europe. Eligible patients had undergone rechallenge with cabazitaxel after three previous lines of treatment (DOC, NHT and CABA, in any order). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan–Meier method. Data on toxicities were collected. Results A total of 69 of 562 patients (Eastern Cooperative Oncology Group performance status 0–1 69%) were rechallenged with CABA (25 mg/m 2 q3w, 58%; 20 mg/m 2 q3w, 27.5%; other, 14.5%) for 1–10 (median 6) cycles; 76.8% received prophylactic granulocyte colony-stimulating factor. Median radiological or clinical PFS with CABA rechallenge was 7.8 months and 11.9 months with initial CABA therapy. OS was 13.7 months (95% confidence interval [CI]: 9.3–15.7) from the first CABA rechallenge cycle, 59.9 months (47.8–67.1) from the first life-extending therapy in mCRPC and 78.3 months (66.4–90.7) from mCRPC diagnosis. Best clinical benefit was improved (34.3%) or stable (47.8%). Lack of response to rechallenge occurred in 17.9% of patients (3.1% with initial CABA). The level of prostate-specific antigen decreased by ≥ 50% in 24% of patients at rechallenge (71% with initial CABA). There was no grade ≥III peripheral neuropathy or nail disorders. Conclusions CABA rechallenge may be a treatment option without cumulative toxicity in heavily pretreated patients with mCRPC who are still fit and had a progression >3 months after the last CABA injections. [ABSTRACT FROM AUTHOR]