Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa.

BACKGROUND: Our review discuss (i) the findings from analyzed data that have examined KRAS, NRAS and BRAF mutations in patients with colorectal cancer (CRC) in North Africa and to compare its prevalence with that shown in other populations and (ii) the possible role of dietary and lifestyle factors with CRC risk.  METHODS: Using electronic databases, a systematic literature search was performed for the KRAS, NRAS, and BRAF mutations in CRC patients from Morocco, Tunisia, Algeria and Lybia.  RESULTS: Seventeen studies were identified through electronic searches with six studies conducted in Morocco, eight in Tunisia, two in Algeria, and one in Libya. A total of 1843 CRC patients were included 576 (31.3%) in Morocco, 641 (34.8%) in Tunisia, 592 (32.1%) in Algeria, and 34 (1.8%) in Libya. Overall, the average age of patients was 52.7 years old. Patients were predominantly male (56.6%). The mutation rates of KRAS, NRAS and BRAF were 46.4%, 3.2% and 3.5% of all patients, respectively. A broad range of reported KRAS mutation frequencies have been reported in North Africa countries. The KRAS mutation frequency was 23.9% to 51% in Morocco, 23.1% to 68.2% in Tunisia, 31.4% to 50% in Algeria, and 38.2% in Libya. The G12D was the most frequently identified KRAS exon 2 mutations (31.6%), followed by G12V (25.4%), G13D (15.5%), G12C (10.2%), G12A (6.9%), and G12S (6.4%). G12R, G13V, G13C and G13R are less than 5%. There are important differences among North Africa countries. In Morocco and Tunisia, there is a higher prevalence of G12D mutation in KRAS exon 2 (≈50%). The most frequently mutation type in KRAS exon 3 was Q61L (40%). A59T and Q61E mutations were also found. In KRAS exon 4, the most common mutation was A146T (50%), followed by K117N (33.3%), A146P (8.3%) and A146V (8.3%). CONCLUSION: KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.

Prevalence of specific and recurrent/founder pathogenic variants in BRCA genes in breast and ovarian cancer in North Africa.

BACKGROUND: Elucidation of specific and recurrent/founder pathogenic variants (PVs) in BRCA (BRCA1 and BRCA2) genes can make the genetic testing, for breast cancer (BC) and/or ovarian cancer (OC), affordable for developing nations. METHODS: To establish the knowledge about BRCA PVs and to determine the prevalence of the specific and recurrent/founder variants in BRCA genes in BC and/or OC women in North Africa, a systematic review was conducted in Morocco, Algeria, and Tunisia. RESULTS: Search of the databases yielded 25 relevant references, including eleven studies in Morocco, five in Algeria, and nine in Tunisia. Overall, 15 studies investigated both BRCA1 and BRCA2 genes, four studies examined the entire coding region of the BRCA1 gene, and six studies in which the analysis was limited to a few BRCA1 and/or BRCA2 exons. Overall, 76 PVs (44 in BRCA1 and32 in BRCA2) were identified in 196 BC and/or OC patients (129 BRCA1 and 67 BRCA2 carriers). Eighteen of the 76 (23.7%) PVs [10/44 (22.7%) in BRCA1 and 8/32 (25%) in BRCA2] were reported for the first time and considered to be novel PVs. Among those identified as unlikely to be of North African origin, the BRCA1 c.68_69del and BRCA1 c.5266dupC Jewish founder alleles and PVs that have been reported as recurrent/founder variants in European populations (ex: BRCA1 c.181T>G, BRCA1 c1016dupA). The most well characterized PVs are four in BRCA1 gene [c.211dupA (14.7%), c.798_799detTT (14%), c.5266dup (8.5%), c.5309G>T (7.8%), c.3279delC (4.7%)] and one in BRCA2 [c.1310_1313detAAGA (38.9%)]. The c.211dupA and c.5309G>T PVs were identified as specific founder variants in Tunisia and Morocco, accounting for 35.2% (19/54) and 20.4% (10/49) of total established BRCA1 PVs, respectively. c.798_799delTT variant was identified in 14% (18/129) of all BRCA1 North African carriers, suggesting a founder allele. A broad spectrum of recurrent variants including BRCA1 3279delC, BRCA1 c.5266dup and BRCA2 c.1310_1313detAAGA was detected in 42 patients. BRCA1 founder variants explain around 36.4% (47/129) of BC and outnumber BRCA2 founder variants by a ratio of ≈3:1. CONCLUSIONS: Testing BC and/or OC patients for the panel of specific and recurrent/founder PVs might be the most cost-effective molecular diagnosis strategy.

Lambert-Eaton myasthenic syndrome revealed after surgery of lung adenocarcinoma.

We report a very rare case of cT1N0M0 lung adenocarcinoma reveling Lambert-Eaton myasthenic syndrome (LEMS). A 69-year-old nonsmoking woman, with several comorbidities consulted for cough and dyspnea. Chest radiograph and CT scanning detected a left lower lobe mass; Needle biopsy confirmed differentiated adenocarcinoma; 18FDG-PET scan and Brain MRI eliminated metastatic disease dissemination. Our patient underwent a left lower lobectomy with mediastinal lymphadenectomy (pT1N0M0), no adjuvant chemotherapy was administrated. One month later patient present a muscle weakness in both lower limbs and fatigability followed by an inability to walk. The diagnosis of LEMS was made from the distinctive electromyogram (EMG) findings and a treatment with Amifampridine (3, 4-diaminopyridine phosphate [3, 4-DAP]) was prescribed with evident efficacy for symptoms.

When tyrosine kinase inhibitor sunitinib can be discontinued in metastatic renal cell carcinoma to pancreas: a case report.

BACKGROUND: Long-term survival with durable response remains possible in the area of targeted therapies. Discontinuation of sunitinib could improve quality of life and reduce treatment costs in metastatic renal cell carcinoma with long-term disease stabilization. We discuss a case of successful interruption of antiangiogenic therapy in a patient with persisting evidence of metastases. The discontinuation of antiangiogenic therapy seems to be an option, even in indolent oligo-metastatic renal cell carcinoma with long disease stabilization before sunitinib. This observation contributes important data to the ongoing discussion on the discontinuation of treatment with kinase inhibitors in selected patients with metastatic renal cell carcinoma. CASE PRESENTATION: We report a case of an 80-year-old Moroccan man treated for renal clear cell carcinoma with multiple pancreatic metastases. He was not on any other medications. He underwent active surveillance with deferred sunitinib at disease progression. He showed significant disease control on sunitinib therapy demonstrating partial response with stable disease after a total of 28 months of therapy. He experienced toxicities which were manageable with supportive care and dose adjustments. Our patient asked for a break of the sunitinib administration, and the treatment was stopped. The disease remained stable after 13 months' discontinuation of sunitinib therapy. The patient was in excellent overall health. CONCLUSIONS: All available agents for metastatic renal cell carcinoma have side effects, which may become serious in a minority of patients. Clinicians and patients must therefore carefully balance the goals of maximal efficacy with minimal toxicity. Sunitinib can be discontinued without negatively impacting outcomes in indolent disease. Further research is needed to characterize the molecular determinants of response and resistance to targeted therapy.

Visceral Crisis Means Short Survival Among Patients With Luminal A Metastatic Breast Cancer: A Retrospective Cohort Study.

BACKGROUND: Patients with visceral crisis from luminal metastatic breast cancer (mBC) are often treated with palliative chemotherapy. No studies have analyzed the aggressiveness of the care in visceral crisis from luminal mBC patients. The objective of this study was to assess practices in this setting in a university medical oncology department. METHODS: This retrospective study included all patients who were managed for luminal mBC between January 2013 and April 2016. The analysis focused on the characteristics of the patients, the modalities of cancer treatment and delays between visceral crisis and death. RESULTS: Thirty-five patients pre-treated with two hormonal therapy lines were enrolled retrospectively. Worse performance status and a higher proportion of severe organ dysfunction for luminal mBC were observed among patients with visceral crisis. Sixty-five percent of patients received cytotoxic treatment. One cycle of chemotherapy was administrated in the majority of patients. Palliative care was performed in 35% of patients. Chemotherapy did not have any significant effect on patient outcome in the present study. The mean time between visceral crisis and death was 4.7 weeks (standard deviation = 1.9). CONCLUSION: Our study showed that visceral crisis in patients with luminal mBC is a complex problem. We need more comprehension of molecular pathogenesis to visceral crisis disease to propose efficacious treatments for these patients and to identify subgroup of patients who need chemotherapy followed by maintenance endocrine therapy.

Renal damage induced by pemetrexed causing drug discontinuation: a case report and review of the literature.

BACKGROUND: Pemetrexed maintenance therapy holds tremendous potential in improving the survival of patients with advanced pulmonary adenocarcinoma. Major side effects include myelosuppression and cutaneous reactions. However, little data are available on pemetrexed nephrotoxicity. Our case describes clinically relevant renal events leading to treatment discontinuation in routine practice. CASE PRESENTATION: We report a case of a 69-year-old Moroccan man treated for metastatic non-small cell lung cancer. He was not on any other medications and he did not receive any nephrotoxic agents. He was exposed to intravenously administered contrast from thoracoabdominal computed tomography in the week of his last pemetrexed treatment. He developed kidney disease related to pemetrexed. He was submitted to renal biopsy, which showed acute tubular damage and interstitial fibrosis. His kidney function remained impaired, but stable, after discontinuation of pemetrexed therapy. He died 5 months later. CONCLUSIONS: Medical oncologists should be aware of renal adverse events for patients with advanced non-small cell lung cancer eligible for pemetrexed maintenance therapy. Suggestions for mitigating the risk for renal toxicities (dehydration, non-steroidal anti-inflammatory drugs and zoledronic acid, radiocontrast agents) during pemetrexed maintenance should be followed to enable early detection and management of this adverse event.

Metachronous pancreatic metastases from renal cell carcinoma: is there a place of Active-Surveillance before deferred deliberately Molecular Target Agent?

BACKGROUND: Metastatic renal cell cancer is a heterogeneous disease due to its diverse morphological features, the prognostic categories based on clinical criteria. Sometimes indolent course without any significant symptoms can be differentiated before the introduction of novel targeted agents. This observation led to interest in a strategy of deferring systemic therapy in the era of effective systemic therapies. CASE PRESENTATION: We report of a 78-year-old Moroccan man with pancreatic metastasis from renal cell carcinoma which occurred 14 years from right nephrectomy. Indolent disease based on body computed tomography imaging with 4 years follow-up was recognized. Active surveillance with deferred antiangiogenic multikinase inhibitor at disease progression was proposed. Nowadays, the patient is under oncological follow-up, he is in a good state of health, and he is disease-free for 48 months from the diagnosis of the tumor and for 20 months from the start of the treatment with Sunitinib CONCLUSIONS: Active surveillance before target therapy may be a suitable approach to ensure long progression-free survival with minimal side-effects and better quality of life in asymptomatic, low-volume, metastatic disease. Further prospective studies with biomarker validation are required to define the patients most likely to benefit from this approach.

Long-standing insulinoma: two case reports and review of the literature.

BACKGROUND: Insulinomas are rare pancreatic endocrine tumors. Most are benign and solitary. However, the nonspecific symptoms and small size of these tumors led to difficulties of diagnosis and localization. CASE PRESENTATION: We present two Arab patients with pancreatic long-standing insulinoma. Both patients presented episodic hypoglycemic symptoms respectively during 10 and 2 years. Biochemical and morphological workup detected localized pancreatic insulinoma. Open procedure surgery was done for the two patients and insulinomas were successfully removed by enucleation. CONCLUSION: Insulinoma remains a diagnostic challenge to practitioners. Diagnosis of suspected cases is easily confirmed by standard endocrine tests, especially the supervised fasting test. Accurate preoperative localization is essential for more effective and safest surgery.

The single nucleotide polymorphism +936 C/T VEGF is associated with human epidermal growth factor receptor 2 expression in Moroccan breast cancer women.

The vascular endothelial growth factor (VEGF), a potent regulator of angiogenesis, is involved in the development and progression of breast cancer (BC). The functional +936 C/T polymorphism of the VEGF-A gene has been implicated in BC susceptibility; however, published data are conflicting. In the current case-control study, we analyzed the association of the +936 C/T polymorphism with BC risk and tumor markers expression, human epidermal growth factor receptor 2 (HER2/neu) and caner antigen 15.3 (CA 15.3) in Moroccan women. We genotyped the DNA of 70 BC patients and 70 healthy women by TaqMan SNP assays. The χ(2) test and Fisher's exact test were used for statistical analyses. The overall results revealed that there is no association between the +936 C/T polymorphism and BC risk [p = 0.8; OR 0.87, 95 % CI (0.32-2.42)]. However, when we stratified the group of patients according to the status of tumor markers, a statistical significant association of +936 C/T SNP and HER2/neu expression was observed (p = 0.009). In contrast, no association with the other tumor marker, CA 15.3, was found (p = 0.090). Thus, the +936 C/T polymorphism seems to have a correlation with HER/neu expression in BC disease.

Conjonctival melanoma metastatic to the breast: a case report.

BACKGROUND: Breast metastasis is fairly uncommon and prognosis is dismal. Breast metastasis might be the first symptom or may occur during the course of other malignancies dominantly arising from the contralateral breast. Leukemia, lung cancer and conjunctival melanoma may spread to the breast. CASE PRESENTATION: A 43-year-old female patient was operated on for conjunctival melanoma. After two years the disease progressed quickly and cutaneous nodes appeared on the back and paraumbilical region. Physical and radiological examination showed a breast mass. No palpable lymph's nodes were noted. She underwent an open biopsy. Histopathologic examination and immunohistochemistry confirmed breast metastases from melanoma. During post-operative staging multiple nasopharyngeal and oropharyngeal lesions were also objective. The patient was given palliative dacarbazine (250 mg/m2 per day for 4 days) for 4 cycles. She died 4 months after the diagnosis of breast metastases. CONCLUSION: Histopathological evaluation should be mandatory in patients with medical history of malignancies in order to differentiate new primary tumors, metastases, and benign tumors.

Investigating the association of vascular endothelial growth factor polymorphisms with breast cancer: a Moroccan case-control study.

The main mediator of breast cancer (BC) angiogenesis is the vascular endothelial growth factor (VEGF). Variation of VEGF-A gene may influence the BC susceptibility. The present case-control study investigated the association of the four commonly studied single nucleotide polymorphisms (SNP) of VEGF-A, namely: -1154A/G (rs1570360), -2578C/A (rs699947), -634G/C (rs2010963) and -460T/C (rs833061) with BC susceptibility and aggressiveness in Moroccan women. After genomic DNA extraction, genotyping was performed by TaqMan SNP assays on 70 BC patients and 70 healthy women. The χ2 test was used to detect differences in the genotype frequencies of VEGF between the groups and to stratify genotypes by the clinico-pathological characteristics in patient's group. Women carriers of -1154AG + AA and -2578AC + AA VEGF genotypes had a reduced risk to develop BC [p = 0.018, OR 2.25 95 % CI (1.14-4.42) and p = 0.022, OR 2.26 95 % CI (1.12-4.58), respectively]. Carriers of -460CT and CT + CC genotypes had also a reduced risk to develop BC [p = 0.045, OR 2.63 95 % CI (1.19-5.84) and p = 0.043, OR 2.12 95 % CI (1.01-4.43), respectively]. Moreover, the A-1154A-2578G-634C-460 haplotype seems to have a protective effect against BC risk [p = 0.007, OR 2.41 95 % CI (1.27-4.55)]. Stratification for BC patients according to clinico-pathological characteristics reveals no association with any of VEGF-A SNPs. In conclusion, the data indicated significant associations of VEGF -1154A/G, -2578C/A and -460T/C polymorphisms with BC susceptibility in Moroccan individuals. These VEGF-A polymorphisms can be useful as predisposing genetic markers for BC. Further larger-scale studies are necessary to confirm our finding.

Mutation screening of the BRCA1 gene in early onset and familial breast/ovarian cancer in Moroccan population.

Worldwide variation in the distribution of BRCA mutations is well recognised, and for the Moroccan population no comprehensive studies about BRCA mutation spectra or frequencies have been published. We therefore performed mutation analysis of the BRCA1 gene in 121 Moroccan women diagnosed with breast cancer. All cases completed epidemiology and family history questionnaires and provided a DNA sample for BRCA testing. Mutation analysis was performed by direct DNA sequencing of all coding exons and flanking intron sequences of the BRCA1 gene. 31.6 % (6/19) of familial cases and 1 % (1/102) of early-onset sporadic (< 45 years)were found to be associated with BRCA1 mutations. The pathogenic mutations included two frame-shift mutations (c.798_799delTT, c.1016dupA), one missense mutation (c.5095C>T),and one nonsense mutation (c.4942A>T). The c.798_799delTT mutation was also observed in Algerian and Tunisian BC families, suggesting the first non-Jewish founder mutation to be described in Northern Africa. In addition, ten different unclassified variants were detected in BRCA1, none of which were predicted to affect splicing. Most unclassified variants were placed in Align-GVGD classes suggesting neutrality. c.5117G>C involves a highly conserved amino acid suggestive of interfering with function (Align-GVGD class C55), but has been observed in conjunction with a deleterious mutation in a Tunisian family. These findings reflect the genetic heterogeneity of the Moroccan population and are relevant to genetic counselling and clinical management. The role of BRCA2 in BC is also under study.

Successful management of primary non Hodgkins lymphoma of the cranial vault.

Primary bone lymphoma (PBL) is a relatively uncommon entity. However, involvement of the cranial vault is an unusual manifestation of aggressive non-Hodgkin's lymphoma. We report the case of a 42-year old immunocompetent woman who presented with an enlarging mass involving the right parietal bone. Magnetic resonance imaging (MRI) of the brain revealed an expansive tumor that affects the right parietal bone. Computed tomographic (CT) scans of the abdomen, chest and pelvis were negative for lymphadenopathy or organomegaly. Biopsy of the mass showed diffuse large B-cell non-Hodgkin's lymphoma confirmed by immunohistochemical study. The patient had a complete response after 4 cycles of chemotherapy followed by external beam radiotherapy. After a follow-up of more than 9 months the patient is still in good local control without distant metastasis. The aim of our work is to report a case of Primary bone lymphoma of the cranial vault with good response to treatment combining sequential chemotherapy and radiotherapy.

Is there any advantage to combined trastuzumab and chemotherapy in perioperative setting her 2neu positive localized gastric adenocarcinoma?

We report here a 44-year-old Moroccan man with resectable gastric adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2) by immunohistochemistry who was treated with trastuzumab in combination with chemotherapy in perioperative setting. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, and capecitabine. Afterwards, he received total gastrectomy with extended D2 lymphadenectomy without spleno-pancreatectomy. A pathologic complete response was obtained with a combination of trastuzumab and oxaliplatin and capecitabine. He received 3 more cycles of trastuzumab containing regimen postoperatively.We conclude that resectable gastric carcinoma with overexpression of the c-erbB-2 protein should ideally be managed with perioperative combination of trastuzumab with chemotherapy. Further research to evaluate trastuzumab in combination with chemotherapy regimens in the perioperative and adjuvant setting is urgently needed.

Diagnostic challenge for ovarian malignant melanoma in premenopausal women: primary or metastatic?

BACKGROUND: In the ovary, metastatic malignant melanoma may be confused with primary malignant melanoma and presents a diagnosis challenge. Most cases are associated with disseminated diseases and poor prognosis. We present this case report of a metastatic ovarian malignant melanoma simulating primary ovarian cancer. CASE REPORT: A 45-year-old premenopausal woman was incidentally found to have an abdominal mass, 3 years after removal of a cutaneous melanoma lesion. Ultrasound and CT scan revealed left two solid masses, which were found to be an ovarian tumor at laparotomy. Left oophorectomy was performed. Histopathology and immunohistochemistry showed melanoma metastasis to the ovary. Nine months later, the patient developed epilepsy and confusion. Magnetic Resonance Imaging showed unique Wright frontal lobe lesion. She underwent stereotactic radio surgery and dacarbazine monotherapy. For months later, the patient is died from disseminate disease progression. CONCLUSION: Ovarian metastasis is an unusual presentation of cutaneous melanoma and the prognosis was dismal. As illustrated by this case report, a differential diagnosis of a metastatic malignant melanoma must be considered.

Breast cancer treatment and sexual dysfunction: Moroccan women's perception.

BACKGROUND: This exploratory prospective study evaluated women's responses to questions that asked them to describe how their body image and sexual functioning had changed since their breast cancer diagnosis to treatment. METHODS: A questionnaire concerning body image scale and various sexual problems experienced after diagnosis and treatment was anonymously completed by 120 women in the outpatient clinic of our hospital's Division of medical Oncology. To be eligible, subjects had to be sexually active and had histology proven breast cancer. They also had to have received treatment for breast cancer. RESULTS: 100% of participants have never spoken with their doctor about this subject. 84% of the participants continued sexual activity after treatment, but there was an increase in the incidence of sexual functioning problems which resulted in a slight reduction in the quality of their sex lives. 65% of the women experienced dyspareunia followed by lubrication difficulties (54%) and the absence or reduction of sexual desire (48% and 64%, respectively) while, 37% had lack of satisfaction (37%). Female orgasmic disorder and brief intercourse and arousal were reported respectively by 40% and 38% of the subjects. The sexual dysfunctions were absent before diagnosis and management of breast cancer in 91.5% subjects and of these 100% subjects complained of a deterioration of the symptomatology after the various treatments. 90% of the dysfunctions were observed after chemotherapy, 9% after surgery and 3% after radiotherapy; none of the subjects indicated the onset of dysfunctions to have been associated with hormonotherapy. 100% expressed not having received sufficient information about how the disease and treatment (including surgery) might affect their sexual life. CONCLUSION: Breast cancer and its treatment may result in significant difficulties with sexual functioning and sexual life. Addressing these problems is essential to improve the quality of life of Moroccan women with breast cancer.

Treatment of Liver Metastases From Colorectal Cancer: Medico-Surgical Strategies.

BACKGROUND: The management of hepatic metastases from colorectal cancer can be understood only as part of a multidisciplinary strategy. Progress experienced by medical treatment, surgical techniques and ways of imaging, has improved the prognosis of patients with liver metastases of colorectal cancers. This work displays the experience of Medical Oncology unit at the Military training hospital in Rabat. METHODS: From January 2007 to December 2009, 60 patients with liver metastases from colorectal cancer, synchronous or metachronous were supported in the Medical Oncology unit at the Military training hospital in Rabat. RESULTS: Liver metastases were synchronous in 41 (68%) patients and metachronous in 19 (32%). Patients were classified into 3 categories according to their resectability: 14 (22%) were resectable at the outset, 28 (47%) were unresectable and 18 (31%) were considered uncertain resectability. Thirty-five patients (58%) received neoadjuvant chemotherapy before surgical gesture, 25 (42%) received chemotherapy after resection of primary tumor. This chemotherapy enabled the resection of liver metastases in 5 patients initially deemed uncertain resectability. The average objective responses to chemotherapy were in the range of 59% with 4 complete responses and one confirmed histologically. Twenty-three patients (38%) underwent surgery including 15 liver resections with R0 (25%). The median progression-free survival in this series was 15.5 months. Some minor side effects were noted, which have not entered the prognosis of patients. CONCLUSIONS: Hepatic resection remains the only potentially curative treatment of liver metastases of colorectal cancers. Perioperative chemotherapy is a promising standard, which has improved the prognosis of patients historically associated with a poor prognosis.

Symptomatic hypopituitarism revealing primary suprasellar lymphoma.

BACKGROUND: The most common cause of hypopituitarism is pituitary adenoma. However, in the case of suprasellar masses different etiologies are possible. We report an unusual case of primary suprasellar lymphoma presented with hypopituitarism. CASE PRESENTATION: A 26 year old woman presented with amenorrhea, galactorrhea and neurological disorders. Also, the laboratory work-up revealed partial hypopituitarism. The magnetic resonance imaging of the head showed a suprasellar mass. A presumptive diagnosis of granulomatous processes was made and the patient was given steroid therapy. Repeated brain MRI detected new lesions in the brain with regression of the suprasellar mass. Stereotactic biopsy of the paraventricular lesion revealed the diagnosis of B-cell lymphoma. CONCLUSION: This case presentation reports a rare cause of hypopituitarism. Primary suprasellar lymphoma is extremely rare and represented a real diagnostic challenge. Besides, suprasellar masses are varied in aetiology and can present diagnostic problems for a radiologist. Also, because of the increased incidence of PCNSL, lymphoma must be kept in mind in the differential diagnosis of lesions in the suprasellar region.

Anthracycline and concurrent radiotherapy as adjuvant treatment of operable breast cancer: a retrospective cohort study in a single institution.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) after breast surgery was investigated by few authors and remains controversial, because of concerns of toxicity with taxanes/anthracyclines and radiation. This treatment is not standard and is more commonly used for locally advanced breast cancer. The aim of our study was to evaluate the efficacy and safety of the concomitant use of anthracycline with radiotherapy (RT). FINDINGS: Four hundred women having operable breast cancer, treated by adjuvant chemotherapy (CT) and RT in concomitant way between January 2001 and December 2003, were included in this retrospective cohort study. The study compares 2 adjuvant treatments using CCRT, the first with anthracycline (group A) and the second with CMF (group B). The CT treatment was repeated every 21 days for 6 courses and the total delivered dose of RT was 50 Gy, divided as 2 Gy daily fractions. Locoregional recurrence free (LRFS), event free (EFS), and overall survivals (OS) were estimated by the Kaplan-Meier method. The log-rank test was used to compare survival events. Multivariate Cox-regression was used to evaluate the relationship between patient characteristics, treatment and survival.In the 2 groups (A+B) (n = 400; 249 in group A and 151 in group B), the median follow-up period was 74.5 months. At 5 years, the isolated LRFS was significantly higher in group A compared to group B (98.7% vs 95.3%; hazard ratio [HR] = 0.258; 95% CI, 0.067 to 0.997; log-rank P = .034). In addition, the use of anthracycline regimens was associated with a higher rate of 5 years EFS (80.4% vs 75.1%; HR = 0.665; 95% CI, 0.455 to 1.016; log-rank P = .057). The 5 years OS was 83.2% and 79.2% in the anthracycline and CMF groups, respectively (HR = 0.708; 95% CI, 0.455 to 1.128; log-rank P = .143). Multivariate analysis confirmed the positive effect of anthracycline regimens on LRFS (HR = 0.347; 95% CI, 0.114 to 1.053; log-rank P = .062), EFS (HR = 0.539; 95% CI, 0.344 to 0.846; P = 0.012), and OS (HR = 0.63; 95% CI, 0.401 to 0.991; P = .046). LRFS, EFS and OS were significantly higher in the anthracycline group where the patients (n = 288) received more than 1 cycle of concurrent CT (P = .038, P = .026 and P = .038, respectively). LRFS and EFS were significantly higher in the anthracycline group within the BCT subgroup (P = .049 and P = .04, respectively). There were more hematologic, and more grade 2/3/4 skin toxicity in the anthracycline group. CONCLUSIONS: After mastectomy or BCT, the adjuvant treatment based on anthracycline and concurrent RT reduced breast cancer relapse rate, and significantly improved LRFS, EFS and OS in the patients receiving more than 1 cycle of concurrent CT. There were more hematologic and non hematologic toxicities in the anthracycline group.