Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication.

BACKGROUND: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. PATIENTS AND METHODS: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. RESULTS: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade ≥3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). CONCLUSIONS: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.

Evolution of quality of life in patients with breast cancer during the first year of follow-up in Morocco.

BACKGROUND: Quality of life has an important place in the future of patients with breast cancer. The objective of this study is to assess the evolution of the patient's quality of life with breast cancer in Morocco after a year of follow-up. METHODS: This study involved the patients with breast cancer with all types of treatment as determined by their physicians. Patient's quality of life was assessed with the Moroccan Arabic version of QLQ- EORTC QLQ C30 and EORTC-BR23 questionnaires. Data were analyzed using SPSS Version 20 software. RESULTS: Regarding EOTRC questionnaires QLQ C-30, there was a significant improvement in global health status and all scales of the functional dimension except the social functional where there was a trend towards improvement and the financial impact of the disease where the situation has deteriorated. Quality of life was improved for most symptom-sized scales dimension of EORTC QLQ- C30 with the exception of diarrhea where it was observed degradation. Most of the EORTC QLQ-scales BR23 questionnaires showed a favorable trend in the quality of life except those of sexual functioning, sexual enjoyment, hair loss and the side effects of systemic therapy. CONCLUSION: The quality of life of the patient is significantly improved after 1 year of follow up. Quality of life instruments can be useful in the early identification of patients whose score low on functional scales and symptoms.

[Meningeal carcinomatosis in breast cancer: from diagnosis to treatment]. / Carcinomatosis meningea en el cancer de mama: del diagnostico al tratamiento.

The appearance of meningeal carcinomatosis in breast cancer is an event that is being reported increasingly more frequently in the literature. It seems to be related with the lengthening of the patients' lives, improved sensitivity to diagnostic imaging and impermeability of the blood-brain barrier to the chemotherapeutic agents. It is an evolutionary form that affirms the metastatic invasion of the subarachnoidal space and is correlated with limited survival. Its diagnosis is difficult, due to the lack of specificity of the clinical signs dominated by headaches, cognitive disorders and possible signs and symptoms of progressive focal lesions. Magnetic resonance imaging of the brain and the spinal cord interpreted by a specialist in neuro-oncology is the preferred examination in this indication, in the search for an increase in meningeal enhancement. Biological analysis of the cerebrospinal fluid is an essential element in the diagnosis. In addition to the biochemical study, the presence of neoplastic cells is in itself enough to confirm the diagnosis. False negatives are very common and represent an important diagnostic problem that entails the need to repeat the lumbar punctures. The therapeutic methods are standard, often invasive, dominated by intrathecal chemotherapy and are based on low-level scientific evidence. This study analyses the epidemiology, the prognostic factors, the diagnostic tools, currently available treatments and the possible future therapies of meningeal carcinomatosis in breast cancer.

TITLE: Carcinomatosis meningea en el cancer de mama: del diagnostico al tratamiento.La aparicion de carcinomatosis meningea en el cancer de mama es un suceso cada vez mas comunicado en la bibliografia. Parece relacionarse con el alargamiento de la vida de las pacientes, la mejor sensibilidad al diagnostico por imagen y la impermeabilidad de la barrera hematoencefalica a los agentes quimioterapicos. Es una forma evolutiva que afirma la invasion metastasica del espacio subaracnoideo y se correlaciona con una supervivencia limitada. El diagnostico es dificil, debido a la inespecificidad de los signos clinicos dominados por cefaleas, trastornos cognitivos, y posibles sintomas y signos de lesiones focales progresivas. La resonancia magnetica del cerebro y de la medula espinal interpretada por un especialista en neurooncologia es el examen de eleccion en esta indicacion, en busqueda de un incremento en la captacion meningea. El analisis biologico del liquido cefalorraquideo es un elemento esencial en el diagnostico. Ademas del estudio bioquimico, la presencia de celulas neoplasicas es por si sola suficiente para confirmar el diagnostico. El numero de falsos negativos es muy comun y representa un gran problema diagnostico que requiere una repeticion de las punciones lumbares. Los metodos terapeuticos son estandares, a menudo invasivos, dominados por la quimioterapia intratecal y se basan sobre una evidencia cientifica de bajo nivel. Se analiza la epidemiologia, los factores pronosticos, las herramientas diagnosticas, los tratamientos disponibles en la actualidad y las posibles terapias futuras de la carcinomatosis meningea en el cancer de mama.

[Male breast cancer in Morocco: Epidemiology and prognostic factors. A report of 140 cases]. / Cancer du sein chez l'homme au Maroc : épidémiologie et facteurs pronostiques. À propos de 140 cas.

OBJECTIVES: Male breast cancer is rare; it constitutes 0.2-1.5 % of all malignant tumors in men and 1 % of all breast cancers. METHODS: The goal of this retrospective study is to analyze the epidemiologic, clinic, therapeutic and evolutive profiles of this disease in 140 cases collected at the National Institute of Oncology and military hospital in Rabat, Morocco, between the years 1998 and 2007. RESULTS: The mean age was 61 years. A high incidence of overweight was found. The most frequent clinical presentation was a firm subareolar lump in 83 % of cases. The most common pathological type was an infiltrating ductal carcinoma (93 %). Hormone receptors were positive in 86 % of cases. Eighty-five percent of patients underwent simple mastectomy and axillary dissection, 68 % chest wall irradiation after surgery, 54 % received chemotherapy and 82 % hormonal therapy. Median follow-up was 91.1 months. The estimated 5-year and 10-year overall survival was respectively 68 % and 74 %. CONCLUSION: The management of male and female breast carcinoma is the same, as well as their prognosis at equal stages. Future research for better understanding of this disease are needed to improve the management and prognosis of male patients.

FOLFOX as Perioperative Chemotherapy of localized Gastric Cancer: Efficacy and Tolerance.

BACKGROUND: Use of perioperative chemotherapy had significantly improved prognosis of localized gastric cancer. Two studies have validated this approach using cisplatin based chemotherapy despite important toxicities. We conducted this study with the aim to evaluate efficacy and toxicity of FOLFOX regimen in this setting. MATERIAL AND METHODS: This is a retrospective study including patients followed for gastric cancer in the Oncology Department of the military hospital Mohamed V in Rabat, Morocco over a period of 7 years from 2007 to 2013. Patients received 4 cycles of mFOLFOX as perioperative regimen. Assessment of tumor response after completion of preoperative chemotherapy was granted by comparative CT scan, tumor markers measurements and R0 surgery rate.Adverse events were graded according to classification of the National Cancer Institute Common Toxicity Criteria version 4.0. RESULTS: Thirty-one patients were included in this study. Use of preoperative chemotherapy showed partial response in fourteen patients (45.1%), stabilization in fifteen patients (48.4%). Tumor markers CEA and CA 19- 9 were significantly decreased. R0 resection rate was 83.87%. Only 2 (6.45%) cases of grade 3/4 hematologic toxicity were reported in our study. Achieving programmed postoperative chemotherapy was possible in 72.41% of patients. CONCLUSIONS: Our study is limited by the retrospective design and small sample size but FOLFOX chemotherapy seems effective and well tolerated in this setting and its place deserves to be studied in a larger study.

Novel agents in second-line therapy for EGFR wild-type Advanced Non-Small-Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related mortality worldwide owing to its advanced-stage at the time of diagnosis. The majority of patients will require a second-line therapy after progression during first-line treatment. While treatment for NSCLC with EGFR mutation or EML4/ALK fusion, target therapy is the favored second-line therapy if not already used in first-line therapy, NSCLC with EGFR wild-type remains an unmet need and many oncologists favor cytotoxic therapy. Recently, a better understanding of lung cancer biology, with a better selection of patients based on histology, molecular biology and the identification of potential target antigens in the immune system have significantly improved patient outcome. This article will provide an update on different treatment options available for patients with EGFR wild-type advanced NSCLC who relapse after first-line therapy, which includes essentially ramucirumab, vandetanib, nivolumab, and pembrolizumab and considerations that may allow clinicians to a better choice of agent for second-line therapy.

[Nasopharyngeal adenoid cystic carcinoma, a rare but highly challenging disease with unmet therapeutic needs: A case-report and review of the literature]. / Carcinome adénoïde kystique du nasopharynx, une entité clinique rare en quête d'innovations thérapeutiques : cas clinique et revue de la littérature.

Nasopharyngeal adenoid cystic carcinoma is a rare tumour. Compared with others nasopharyngeal tumours, it is characterised by slow evolution but it is locally aggressive and has a high tendency to recurrences. Due to the rarity of cases, no consensus exists about treatment approaches. We report the case of 45-year-old-man with a locally advanced adenoid cystic carcinoma. The patient received concurrent chemoradiation and had a good objective response. After one year, he developed a paucisymptomatic lung metastasis. The follow-up showed local recurrence after 3 years. One cycle of chemotherapy was given but poorly supported. Carbon ion radiotherapy was proposed. The aim of this work is to review the literature concerning this rare malignancy and discusses treatment approaches in initial situations and during recurrences.

Bevacizumab in clinical practice.

The development of targeted therapies and especially angiogenesis inhibitor drugs is undoubtedly a major advancement in the treatment of cancer in the 21st century. Bevacizumab is a recombinant humanized monoclonal antibody directed against vascular endothelial growth factor that was approved for the treatment of multiple solid tumors, we have reviewed the side effects cited in clinical trials of bevacizumab and the guidelines for their management and we can conclude that bevacizumab, is generally well tolerated but is associated with increase in some adverse side effects for which monitoring is required particularly vascular and renal side effects including hypertension, proteinuria, thromboembolic events and hemorrhage. The better understanding of bevacizumab toxicity profile and the guidelines for their optimal management as well as the education of patients may allow prolonged therapy and thus improved clinical outcomes.

Isolated thyroid metastasis revealed an unknown lung adenocarcinoma: a case report.

INTRODUCTION: Cancer metastasis to the thyroid is extremely rare. The most common sites that have been reported to metastasize to the thyroid gland are breast and kidney. As to primary lung cancer metastasizing to the thyroid gland, only a few cases have been described in the literature. CASE PRESENTATION: We report a case of a 37-year-old white Arabian woman who had never smoked tobacco products for whom a malignant thyroid mass revealed a primary lung tumor. She had a surgical excision for both the thyroid and the pulmonary tumors, and received adjuvant chemotherapy. At 1 year, she is still in remission. CONCLUSIONS: Our case is rare as it describes a case where the thyroid lesion was the revealing sign of an unknown lung carcinoma. Management of thyroid metastases should depend on the individual situation and surgical excision should be proposed whenever a patient's condition is favorable.

Pain and Cancer: A systematic review.

Pain is the most common symptoms in patients with cancer, a significant number of cases it is undiagnosed and under treated. It is important to understand the nature of the pain experienced by patients, to distinguish between nociceptive and neuropathic pain. Successful management of cancer pain requires a good knowledge of the causes of pain and various treatment available and information to manage their side effects. Pain has a significant negative impact on the patient and his family, therefore it needs to be managed urgently and appropriately.

[Targeted therapy in thyroid cancer: Towards a treatment card]. / Les thérapies ciblées dans le cancer de la thyroïde: vers un traitement personnalisé?

Thyroid cancer is an uncommon cancer. Molecular biology plays a vital role in its development. Chemotherapy showed unsatisfactory results in advanced stages where surgery and iodine therapy are not appropriate. These last ten years have been marked by a major advance in understanding the molecular features of this cancer and therapeutic correlations, moreover, clinical trials have focused on the treatment of this disease on metastatic stages and led to a significant therapeutic panel targeting angiogenesis, mutations frequently found in cervical cancer: RET, BRAF, RAS... these are the motesanib, axitinib, sunitinib, pazopanib, vandetanib, cabozotinib and sorafenib. The last three molecules have already the autorisation of FDA and EMA. In this review, we will put the item on oncogenetic characteristics of thyroid carcinoma as well as new targeted therapies in patients refractory to conventional treatment.

Efficacy and safety of bevacizumab in the treatment of human epidermal growth factor receptor type 2 negative metastatic breast cancer: About a large series in moroccan population.

Context: Randomized studies have shown different magnitude of bevacizumab (BV) benefit in the treatment of advanced breast cancer. Aims: The aim of the study is to evaluate the efficacy and safety of BV for the treatment of human epidermal growth factor receptor type 2 (HER2) negative metastatic disease. Settings and Design: A large observational institutional study in Moroccan population. Materials and Methods: From January 2009 to December 2011, 42 patients with HER2 negative metastatic breast cancer were analyzed. Results: The median age was 51 years. Approximately two-third of patients analyzed were treated at the first line with BV in association with (paclitaxel, docetaxel or capecitabine) in (40.7%; 40.7% and 18.5%) and the other third at second-line therapy with a combination of the same drugs in (46.6%, 26.6% and 266% respectively); the median number of cycles was 15. In terms of the clinical benefit rate there was a trend in favor of the combination with taxanes and among responders, median duration of objective response was longer with paclitaxel. In addition, analyses of progression-free survival (PFS) across subgroups in both first and second line therapy showed consistent improvements in PFS with the combination of BV and paclitaxel the difference was statistically significant. Concerning safety, the BV was generally well-tolerated. Conclusions: BV in HER2 negative metastatic diseases potentially improved objective response rate and PFS especially in combination with Paclitaxel, which confirm and expand on the results from published literature, with tolerable toxicity.

Clinical prognostic factors in locally advanced nasopharyngeal carcinoma in Moroccan population.

BACKGROUND: Nasopharyngeal carcinoma is a distinct cancer of head and neck by its pathology, etiology, epidemiology and clinical behavior. Morocco is considered an endemic region with intermediate incidence. The aim of our report is to underline some clinical determinants of survival in locally advanced disease. PATIENTS AND METHODS: We conducted a retrospective study from January 2003 to December 2005. All patients with undifferentiated nasopharyngeal carcinoma treated in the National Institute of Oncology of Rabat, Morocco were recorded. Classified stage II to IVB disease according to TNM classification adopted by the AJCC (American Joint Committee of Cancer) 6th edition. RESULTS: The study included 339 patients, 122 women and 217 men (sex-ratio: 1.7). Mean age was 43 years old (range: 6-91years). Median duration to diagnosis was 6 months (range: 1-72) presenting symptoms at diagnosis were predominantly cervical lymph node in 79%. Forty- two patients have T1 tumors, 159 = T2 tumors, 64 = T3 tumors and 69 = T4 tumors. Sixty-five patients do not have lymph-node involvement, 49 have N1, 128 have N2 and 95 have N3. Three patients were at stage IIA, 57 patients were at stage IIB, 40 patients were at stage III, and 57 patients were at stage IVA and the remaining 96 patients were at stage IVB. Eighty-seven percent of patients underwent sequential chemoradiation and 17% underwent concurrent chemo-radiation (CTR). Response to induction chemotherapy was assessed in 235 patients. There were 31 patients with complete response and 59 patients have partial response. Complete response to radiotherapy was reached in 235 patients. Mean overall survival (OS) was 66.2%. Gender was a prognostic factor of OS (p=0.045) and DFS favoring women. Age wasn't a prognostic factors determining the outcome with no difference between patients aged more than 40 years old and patients younger. Tumor size was not a determinant of survival with a non-significant p in OS and DFS (0.27 and 0.46 respectively) but T4 stage patients appear to have a worse prognosis. Lymph node involvement was significantly determining the outcome either in OS and DFS (p=0.001 and 0.009 respectively). TNM stage was also a significant prognostic factor in OS but not in DFS favoring those with early stage (p= 0, 004 and p= 0, 13 respectively). The treatment strategy was not a significant prognostic factor with no difference between patients who underwent sequential or concurrent chemoradiation (OS p= 0, 48 and DFS p= 0, 9). In multivariate analysis, lymph-node involvement is the most significant factor. CONCLUSION: Our findings were mostly concordant with the literature data in endemic areas for TNM staging; however we are limited by the bias of retrospective studies. Prospective studies would be more accurate to define those prognostic factors in our population. KEYWORDS: UCNT, prognostic factors, endemic areas, lymph node involvement.

Bilateral ewing sarcoma/primitive neuroectodermal tumor of the breast: a very rare entity and review of the literature.

Peripheral primitive neuroectodermal tumors (PNET) are rare malignant tumors, affecting mostly children and adolescents and have been described in breast in eight case reports only. In this paper, we present a case of bilateral mammary ES/PNET where distinction between primary and metastatic diseases was discussed through a literature review. The aim of this work is to demonstrate that although rare, the possibility of PNET should be kept in mind while evaluating a palpable breast abnormality in a young female.

[Dietary risk factors of undifferenced nasopharyngeal carcinoma : a case-control study]. / Les facteurs de risque alimentaires du carcinome indifférencié du nasopharynx : Une étude cas témoin.

BACKGROUND: The incidence of nasopharyngeal carcinoma (NPC) is relatively high in Maghreb countries. This cancer is a model of multifactorial oncogenesis, but the role of food as risk factor in ethiopathogenesis of this tumor is not negligible. AIM: To identify the association between risk of NPC and some dietary factors in Morocco. METHODS: It is a case-control study including all new cases of NPC in our department between December 2009 and May 2010. Frequency consummation of foods was compared between cases and controls matched for age, sex and socio economic level. A high frequency consummation of a food was defined as consumption once or more by a week. Some traditional foods in Moroccan cooking like Harissa (hot red pepper), Qadid (mutton dried and salted), Khlii (dried meat, salted, spiced cooked and preserved in a mixture of oil and rendered beef fat) and Smen (rancid butter) were analyzed in this study. A conditional logistic regression was used to identify the association between dietary factors and the risk of NPC. RESULTS: Cases were more likely to have high frequency consumption of Harissa, Smen and Black Pepper, and less frequency consumption of fruts and vegetables. There was significant association between the risk of NPC and the frequency consumption of Qadid, khlii and cooking with olive oil. CONCLUSIONS: Some of these risk factors (Harissa, Black pepper) were found in 3 North Africain studies. This study indicates the involvement of dietary factors, and thus the lifestyle in the development of NPC and the need of biochemical analysis of food specimens to search for the carcinogenic agents.

Prognostic impact of the combination of erythropoiesis-stimulating agents to cancer treatment: literature review.

Cancer patients commonly develop anaemia. Erythropoiesis-stimulating agents (ESAs) are frequently used in cancer treatment. Numerous controlled studies indicate that ESAs can raise haemoglobin levels, reduce transfusion requirements and improve quality of life in anaemic cancer patients receiving chemotherapy. They were previously used to enhance response to radiation therapy, via increasing tumour cell oxygenation. Since the 2002 guideline, there has been increasing attention to the safety of ESA treatment in patients with cancer. Two placebo-controlled phase III randomised clinical trials published in 2003 showed evidence of harmful effects of ESAs on survival and/or tumour outcomes. Subsequently, recent trials and several large meta-analyses have confirmed negative impact on survival and/or disease progression. To comprehensively examine whether ESA use affects safety outcomes in cancer patients in different settings (chemotherapy, radiotherapy and targeted therapies), we conducted a literature review of all clinical trials, small and large meta-analyses from 1990 to 2012.

[Fever and cancer: components of diagnosis for optimal management]. / Fièvre et cancer : éléments de diagnostic pour une prise en charge adaptée.

Fever is defined as a body temperature above 37.8°C in the absence of antipyretic drug. It is a frequent and potentially severe event and its interpretation can be difficult in patients with solid tumors. It is usually alleged that more than half of cancer patients will be affected by the occurrence of this event during the course of their disease. Underlying causes are multiple but most frequent and severe causes include infections, the most life-threatening causes being, firstly, febrile neutropenia and secondly, healthcare-associated infections and more particularly infections related to catheter. Opportunistic infections are much less frequent than in hematology oncology but clinicians should be aware of two severe opportunistic infections: systemic candidiasis and Pneumocystis jiroveci pneumonia. Fever related to paraneoplastic or tumor necrosis complicates the diagnosis process. Other common causes of fever include venous thromboembolic disease or more rarely treatment related fever. We aim at examining the optimal diagnostic and therapeutic strategies when facing a cancer patient with fever.