Pembrolizumab in patients with advanced upper tract urothelial carcinoma: a real-world study from ARON-2 project.

Upper tract urothelial carcinoma (UTUC) accounts for the 5-10% of all urothelial carcinomas (UCs). In this analysis, we reported the real-world data from the ARON-2 study (NCT05290038) on the efficacy of pembrolizumab in patients with UTUC who recurred or progressed after platinum-based chemotherapy. Medical records of patients with metastatic UTUC treated with pembrolizumab as second-line therapy were reviewed from 34 institutions in 14 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 235 patients were included in our analysis. Median OS was 8.6 months (95% CI 6.6-12.1), the 1 year OS rate was 43% while the 2 years OS rate 29%. The median PFS was 5.1 months (95% CI 3.9-6.9); 46% of patients were alive at 6 months, 34% at 12 months and 25% at 24 months. According to RECIST 1.1, 18 patients (8%) experienced complete response (CR), 57 (24%) partial response (PR), 44 (19%) stable disease (SD), and 116 (49%) progressive disease (PD), with an ORR of 32%. Our study confirms the effectiveness of pembrolizumab in patients pretreated with a platinum-based combination, irrespective of their sensitivity to the first-line treatment and of their histology. In addition, we emphasized the limited benefit of the treatment with pembrolizumab in patients with hepatic metastases and poor ECOG performance status.

Impact of CBE-based screening program on care pathway, stage at diagnosis, nature of treatment, and overall survival among breast cancer patients in Morocco.

BACKGROUND: This study aimed to indirectly examine whether the implementation of clinical breast examination-based screening program in Morocco has been successful in downstaging and improving survival rates. Breast cancer patients detected through the screening pathway were compared with those detected through self-referral over the same period in terms of cancer stage at diagnosis, tumor characteristics, care delays, and survival. METHODS: A prospective observational study was conducted between April 2019 and August 2020 at two major public oncology centers. RESULTS: A total of 896 women with confirmed breast cancer were recruited (483 were program-referred and 413 were self-referred). The authors did not report any significant difference between the two groups in terms of stage at diagnosis, molecular profile, or histopathological grade. Early-stage cancer (stage I-II) was detected in 55.7% of self-referred participants compared to 55.5% of program-referred participants. Median intervals between symptom recognition, pathological diagnosis, and treatment initiation were not significantly different between the two groups. Similarly, survival after treatment showed no significant difference between patients screened by the program and self-referred patients. The 3-year survival rate after treatment was 94.5% for patients referred through the program and 88.6% for patients not referred through the program (p = .16). CONCLUSIONS: This study highlights the importance of equitable and timely access to high-quality diagnosis and treatment facilities, leading to substantial downstaging and enhanced survival rates. Continued efforts to improve quality and expand coverage to include asymptomatic women will consolidate the health infrastructure gains achieved by the Moroccan breast cancer screening program.

Bone targeting agents, but not radiation therapy, improves survival in patients with bone metastases from advanced urothelial carcinoma receiving pembrolizumab: results from the ARON-2 study.

The ARON-2 study (NCT05290038) aimed to assess the real-world efficacy of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. This retrospective analysis reports the outcomes of urothelial carcinoma (UC) patients with bone metastases (BM). Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were reviewed from60 institutions in 20 countries. Patients were assessed for Overall Response Rate (ORR), Progression-Free Survival (PFS), and Overall Survival (OS). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 881 patients were included; of them, 263 (30%) presented BM. Median follow-up time was 22.7 months. Patients with BM showed both shorter median OS (5.9 months vs 13.1 months, p < 0.001) and PFS (3.5 months, vs 7.3 months, p < 0.001) compared to patients without BM. Patients who received bone targeted agents (BTAs) showed a significantly longer median OS (8.5 months vs 4.6 months, p = 0.003) and PFS (6.1 months vs 3.2 months, p = 0.003), while no survival benefits were observed among patients who received radiation therapy for BM during pembrolizumab treatment compared to those who did not. In multivariate analysis, performance status, concomitant liver metastases, and the lack of use of BTAs were significantly associated with worse OS and PFS. Bone involvement in UC patients treated with pembrolizumab predicts inferior survival. Poor performance status and liver metastases may further worsen outcomes, while the use of BTAs is associated with improved outcomes.

Statins and renal cell carcinoma: Antitumor activity and influence on cancer risk and survival.

Statins are commonly prescribed to reduce plasma cholesterol levels and risk of cardiovascular events and mortality. Statin exposure may have cancer-preventive properties in some solid tumors, including Renal Cell Carcinoma (RCC). Emerging evidences show that statins can inhibit RCC cell growth by inducing cell cycle arrest and apoptosis in a dose- and time-dependent manner. In addition, statins inhibit the phosphorylation of AKT, mammalian target of rapamycin (mTOR), and ERK leading to reduced motility of RCC cells. Interestingly, the potential impact of concomitant statin intake has been recently evaluated in RCC patients treated by targeted therapy or immunotherapy. In this review, we illustrate the most recent data on the preclinical activity of statins in Renal Cell Carcinoma models and discuss the impact of their use on the prevention and survival of patients affected by this tumor.

Impact of clinical pharmacy services in a hematology/oncology ward in Morocco.

BACKGROUND: Clinical pharmacists are contributing to safe medication use by providing comprehensive management to patients and medical staff. The aim of this study is to document and evaluate the role of clinical pharmacy services in oncology department. PATIENTS AND METHODS: A prospective, descriptive, observational study was carried out from July 2018 through June 2019 at the Department of Medical Oncology at the National Institute of Oncology, Morocco. Medication reviews concerning hospitalized adult cancer patients were performed every day by the clinical pharmacist assigned to the department. RESULTS: A total of 3542 prescriptions of 526 adult cancer patients were analyzed. The pharmacist identified 450 drug-related problems (12.7% of the prescriptions) primarily related to the analgesics (31.5%). Medication problems included mostly untreated indications (31.3%), overdosing (17.1%), drug-drug interactions (12.4%), underdosing (11.1%), administration omissions (6.7%), drug not indicated (6.0%), and contraindication (5.3%). Interventions (n = 450) led to drug additions (30.7%), drug dosing adjustments (27.1%), treatment discontinuations (20.0%), recall of the treatment (6.2%), replacement of a drug with another one (5.1%), administration optimization (4.0%), therapeutic drug monitoring (3.1%), alternate routes of administration (2.5%), and extension of treatment duration (1.3%). Most (98%) of the interventions were accepted and implemented by the medical staff-172 (38.2%) having a significant clinical impact on the patient, 88 (19.6%) as having a very significant clinical impact, and 71(15.8%) as having a potential vital impact. CONCLUSION: This work highlights the positive clinical relevance of pharmacists' interventions in oncology and the importance of medicopharmaceutical collaboration to prevent medication error.

Methylene blue and ifosfamide-induced encephalopathy: Myth or reality?

BACKGROUND: Ifosfamide-induced encephalopathy (IIE) is a rare and serious adverse reaction. Thus far, no standard medication has been documentedto be efficient in the reversal of IIE, and while ifosfamide infusion interruption and hydration are recommended, methylene blue (MB) administration remains controversial. METHODS: We retrospectively reviewed medical records to assess cases with IIE after ifosfamide infusion. We included all patients having received an ifosfamide infusion during their hospitalization in the medical oncology unit of the National Institute of Oncology in Rabat, Morocco, between September 2016 and September 2017. We subsequently conducted a literature review to determine the role of MB in IIE by searching PubMed using the terms "Methylene Blue" and "Ifosfamide". RESULTS: A total of 88 patients received ifosfamide, and four patients had IIE. Ifosfamide infusion was stopped immediately after the IIE occurrence, and patients underwent renal function correction with hydration. All patients received MB infusion, and three patients had an improvement of their neurological status. As regards the literature review, 34 articles were reviewed and 16 items were included in the review. Overall, 38 (65.5%) patients received MB infusion and 28 (75.6%) patients responded favorably to the treatment. CONCLUSIONS: Methylene blue can be used as a treatment for IIE owing to the severity of the IIE as well as absence of standard medication. Nonetheless, side effects such as serotonergic syndrome should be investigated. More broadly, prospective studies and controlled trials are needed to explore the contribution of MB in IIE management and encourage its use.

Frequency and types of EGFR mutations in Moroccan patients with non-small cell lung cancer.

BACKGROUND: Mutations in the epidermal growth factor receptor (EGFR) gene are commonly observed in non-small cell lung cancer (NSCLC), particularly in adenocarcinoma histology. The frequency of EGFR mutations is ethnicity-dependent, with a higher proportion reported in Asian populations than Caucasian populations. There is a lack of data on these mutations in north Africa. METHODS: Tumor specimens from Moroccan patients with NSCLC were collected from five pathology laboratories between November 2010 and December 2017 to determine frequency and types of EGFR mutations. Tumors were tested in a reference center for EGFR by polymerase chain reaction and sequencing of exons 18, 19, 20, and 21. RESULTS: A total of 334 patients were enrolled: 242 (72.5%) males and 92 females (27.5%). A total of 56.9% had a history of smoking. EGFR testing of the 334 lung adenocarcinoma samples demonstrated a wild-type EGFR in 261 (78.1%) and mutated EGFR in 73 (21.9%). Mutations were mainly detected in the exon 19 deletion (65.8%), followed by exon 21 L858 (17.8%) and other exon 21 codon mutations (5.5%) and exon 18 (6.8%), whereas primary mutations of exon 20 were less frequent (4.1%). In patients with advanced NSCLC, the detection of EGFR mutation was independently associated with sex (41.3% female vs 14.5% male; p < 0.001) and smoking status (34.8% nonsmokers vs 12.9% active smokers; p < 0.001). The mean age was significantly different between the two groups (p = 0.041). CONCLUSION: Our findings confirm the genetic heterogeneity of NSCLC worldwide, reporting frequency of EGFR mutations in Moroccan patients with NSCLC between those of Asian and Caucasian populations.

Cancer management challenge in a developing country in COVID-19 pandemic: reflection of a group of Moroccan oncologists.

Management of cancer patients during the COVID-19 pandemic is a worldwide challenge - in particular in developing countries where the risk of saturation of health facilities and intensive care beds must be minimized. The first case of COVID-19 was declared in Morocco on 2 March 2020, after which a panel of Moroccan experts, consisting of medical oncologists from universities and regional and private oncology centers, was promptly assembled to conduct a group reflection on cancer patient's management. The main objective is to protect the immunocompromised population from the risk of COVID-19, while maintaining an adequate management of cancer, which can quickly compromise their prognosis. Recommendations are provided according to each clinical situation: patients undergoing treatment, new cases, hospitalized patients, palliative care and surveillance.

Quality of life of early stage colorectal cancer patients in Morocco.

BACKGROUND: A multicentre cohort study was held in Morocco, designed to evaluate the quality of life of cancer patients. The aim of this paper is to report the assessment of the quality of life of early colorectal cancer patients, before and after cancer treatment, to identify other factors which are related to this quality of life. METHODS: We used the third version of the QLQ-C30 questionnaire of the European organization for Research and treatment of Cancer (EORTC) after a transcultural validation. The Data collection was done at inclusion and then every twelve weeks to achieve one year of follow up. RESULTS: Overall 294 patients presented with early colorectal cancer, the median age was 56 years (range: 21-88). The male-female sex ratio was 1.17. At inclusion, the global health status was the most affected functional dimension. For symptoms: financial difficulties and fatigue scores were the highest ones. Emotional and social functions were significantly worse in rectal cancer. Most symptoms were more present in rectal cancer. At inclusion, global health status score was significantly worse in stage III. Anorexia was significantly more important among colorectal female patients. For Patients over 70 years-old, the difference was statistically significant for the physical function item which was lower. Overall, Functional dimensions scores were improved after chemotherapy. The symptoms scores did not differ significantly for patients treated by radiotherapy, between inclusion and at one year. CONCLUSION: Our EORTC QLQ C30 scores are overall comparable to the reference values. Neither chemotherapy, nor radiotherapy worsened the quality of life at one year.

Breast and splenic metastases of squamous cell carcinoma from the uterine cervix: a case report.

INTRODUCTION: Metastases to the breast from extramammary malignancies are infrequent, the most common primary sites are malignant melanoma, leukemia, lymphoma, and cancer of the lung, stomach, prostate and ovary. The cervical origin is exceptional. Splenic metastasis from squamous cell carcinoma of the cervix is also rare. To the best of our knowledge, only three cases of isolated splenic metastasis have been reported in the literature. CASE PRESENTATION: We describe the case of a 55-year-old North African woman who presented with a nodule in her left breast eight months after treatment for stage IIB squamous cell uterine cervical carcinoma. The excisional biopsy with histological study demonstrated a poorly differentiated squamous cell carcinoma. A computed tomography scan revealed a splenic secondary location. CONCLUSIONS: We report here a case of two unusual metastatic sites of uterine cervical carcinoma, the breast and spleen. It is the first case of this association without widespread disease.

A rare case of nephrotic syndrome revealing mycosis fungoide managed successfully with chemotherapy.

The occurrence of the nephrotic syndrome during mycosis fungoide is very unusual. We report a rare case of mycosis fungoide revealed by hydrops related to nephrotic syndrom in a 37-year old male patient. He has been admitted to intensive care unit because of a breathing distress and a hydrophobs. Whole body computed tomography scan revealed bilateral axillary, cervical lymph nodes, tumoral infiltration of the subcutaneous tissue in the cervicothoracic and abdominal regions, multiples bilateral pulmonary metastasis, bilateral pleural effusion, and abdominal effusion; the kidneys were normal. The patient was staged IVb (T3N3M1). He was treated with CHOP (cyclophosphamide, Doxorubicin, Vincristin and prednisone). Evolution after eight cycles of chemotherapy was spectacular. The development of nephrotic syndrom secondary to mycosis fungoide is rare. It requires a multidisciplinary approach with nephrologists and oncologists.

Triple negative breast cancer in Moroccan women: clinicopathological and therapeutic study at the National Institute of Oncology.

BACKGROUND: Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. This is an aggressive malignancy with a poor prognosis despite the high rates of response to chemotherapy. The aim of this study is to determine the clinicopathological, therapeutic features and outcomes associated with this type of breast cancer. METHODS: This is a retrospective study of confirmed triple negative breast cancer females collected at the National institute of oncology of Rabat in Morocco, between January 2007 and December 2008. Epidemiological, clinical, histological, therapeutic and evolutive data were analyzed. OS and DFS rates were estimated by Kaplan-Meier analysis. RESULTS: A total of one 152 patients with breast cancer, were identified as having triple-negative breast cancer (16,5%). The median age at diagnosis was 46 years. 130 patients (86%) had infiltrating ductal carcinoma and thirteen had medullar carcinoma (9%). 84 cases (55%) were grade III Scarff-Bloom-Richardson (SBR). 48 % had positive lymph nodes, and 5 % had distant metastases at diagnosis. According TNM staging, 12 patients (8%) had stage I, 90 patients (60%) had stage II and the 43(28%) had stage III. 145 patients received surgery. 41 (28%) had conservative surgery and 104 (72%) received radical mastectomy with axillary lymph nodes dissection. 14 patients with advanced tumors or inflammatory breast cancer have received neoadjuvant chemotherapy and four patients (28%) had complete pathologic response. From 131 patients how received adjuvant chemotherapy, 99 patients (75,5%) had Anthracycline based chemotherapy) and 27 patients (20,6%) had sequential Anthracycline and docetaxel,. Seven patients with metastatic disease received anthracycline-based regimen in the first line metastatic chemotherapy. The median follow-up time was 46 months (range 6,1 -60 months). Overall survival at 5 years for all patients was 76,5%. CONCLUSION: These results suggest that most TNBC characteristics in Moroccan patients are in accordance with literature data, especially concerning young age at diagnosis high grade tumors, advanced stage at diagnosis, and short time to relapse. Although the high response rate to chemotherapy, the overall prognosis of this subset of tumors remains poor.

[Gastrointestinal stromal tumors]. / Tumeurs stromales gastro-intestinales.

Gastrointestinal stromal tumors (GIST) are the most common sarcomas of the gastrointestinal tract. They affect all segments of the digestive tract. They develop from the interstitial cells of Cajal. Mutations in the Kit gene is present in 86% of cases and in PDGFR gene in 15% of cases. The marker CD 117 is present in 95% of cases. Surgery is the standard treatment in localized forms. The tyrosine kinase inhibitor, imatinib is standard in first-line metastatic gastrointestinal stromal tumors, as well as adjuvant treatment after surgery. Sunitinib is the standard in second line.

Minimally differentiated acute myeloid leukemia (FAB AML-M0): prognostic factors and treatment effects on survival--a retrospective study of 42 adult cases.

Data from 42 adult patients with newly diagnosed minimally differentiated (M0) acute myeloid leukemia (AML) were reported. Clinical and biological characteristics at diagnosis were heterogenous. All patients received induction chemotherapy combining an anthracycline with cytarabine. Complete remission (CR) was achieved in 22 cases (52%). Most patients received continuation chemotherapy. Median disease-free survival (DFS) was 13.6 months with a 2-year survival rate of 28%. As post-remission therapy, 7 patients could be allografted and showed an encouraging outcome. Overall, 14 patients have relapsed (63%) after a median time of 10.2 months. Median overall survival (OS) was 20.5 months with a 5-year survival rate of 18%. This retrospective analysis points to a somewhat heterogenous group of AML in terms of biological features and outcome, and warrants a larger multicenter study with study in molecular biology to clarify treatment effects further.

[Chemotherapy in gallbladder carcinoma]. / Chimiothérapie dans le cancer de la vésicule biliaire.

Gallbladder cancer is an aggressive tumor. Its incidence varies according to geography. Surgery is the standard treatment for localized stage but there is no standard treatment in metastatic or locally advanced disease. Because of the rarity of bile tract cancer (BTC) and gallblader carcinoma (GBC), most studies have grouped all BTC and GBC together, and there are very few GBC-specific studies. In addition, there is a paucity of randomized controlled studies in this disease with small numbers of patients and inclusion bias. One randomized trial ABC-02 was well conducted and showed a survival benefit in favor of gemcitabine (GEM)+cisplatin (CDDP), which can be regarded as the standard in locally advanced BTC. Adjuvant therapy after surgical resection is not validated. Understanding the molecular mechanisms of carcinogenesis of GBC has opened the way for the use of targeted therapies. This new treatment would improve survival and quality of life of our patients.

Breast cancer in moroccan young women: a retrospective study.

BACKGROUND: Breast cancer is uncommon in young women and induces more aggressive biologic characteristics. Survival in young women has been widely studied in developed countries. Less favorable prognosis and low survival were found.In Morocco, this study is the first investigation of clinical features, treatment and prognosis associated with breast cancer in young women. FINDINGS: Four hundred and nine women aged 35 years or less were included in this study. All these women were diagnosed as having breast cancer at the National Institute of Oncology in Rabat, Morocco between 2003 and 2007. The relation between clinical and therapeutic characteristics and event-free survival (EFS) and overall survival (OS) were assessed by Cox regression analysis.The median age of the patients was 32 years. Fifty three patients (13%) have metastatic disease at diagnosis and 356 patients (87%) had localised disease. In 57.9% of the cases, the estrogen receptors status was positive. The median follow-up was 32.2 months. After 3 years the survival rate was 80.6%. In the case of localised disease, OS and EFS at 3 years were 83.2% and 62.5%, respectively. OS and EFS at 3 years was higher in patients with stage I than patients with stage II and stage III (p = 0.001). Positive estrogen receptors was significantly associated to OS and EFS at 3 years compared to negative estrogen receptors (p = 0.001). Adjuvant chemotherapy, adjuvant radiotherapy and adjuvant hormone therapy were associated with net benefit in OS and EFS at 3 years. Cox regression analysis showed that negative ER was significantly associated with poorer OS (HR = 2.42, 95% CI = 1.25 - 4.66, p < 0.009) and poorer EFS (HR = 1.73, 95%CI = 1.05 - 2.86, p = 0.03). Stage III disease were associated to poorer EFS (HR = 5.35, 95%CI = 1.60 -17.84, p = 0.006). CONCLUSIONS: In Morocco, young women with breast cancer had less favorable prognosis. Multivariate analysis showed that negative hormone receptor status was associated with lower EFS and OS. Clinical trials should be launched to improve the survival of these young women with breast cancer.