Currently, antiangiogenic strategies in metastatic breast cancer have demonstrated modest improvements in progression-free survival (PFS) but not improved quality or duration of survival, warranting ...evaluation of new agents in a placebo-controlled setting. Ramucirumab is a human immunoglobulin G1 antibody that binds vascular endothelial growth factor receptor-2 and blocks ligand-stimulated activation. The ROSE/TRIO-012 trial evaluated ramucirumab with docetaxel in unresectable, locally recurrent, or metastatic breast cancer.
In this double-blind, placebo-controlled, randomized, multinational phase III trial, 1,144 patients with human epidermal growth factor receptor 2 (HER2) -negative breast cancer who had not received cytotoxic chemotherapy in the advanced setting were randomly assigned at a two-to-one ratio to receive docetaxel 75 mg/m(2) plus ramucirumab 10 mg/kg or docetaxel 75 mg/m(2) plus placebo once every 3 weeks. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria. Patients were stratified by previous taxane therapy, visceral metastasis, hormone receptor status, and geographic region. An independent data monitoring committee oversaw the trial. The primary end point was investigator-assessed PFS.
Median PFS in patients treated with ramucirumab plus docetaxel was 9.5 months, compared with 8.2 months in patients who received placebo plus docetaxel (hazard ratio HR, 0.88; P = .077). Median overall survival was 27.3 months in patients who received ramucirumab plus docetaxel, compared with 27.2 months in patients who received placebo plus docetaxel (HR, 1.01; P = .915). Toxicities seen at significantly higher rates in patients receiving ramucirumab included fatigue, hypertension, febrile neutropenia, palmar-plantar erythrodysesthesia syndrome, and stomatitis.
Addition of ramucirumab to docetaxel in HER2-negative advanced breast cancer did not meaningfully improve important clinical outcomes.
•Deregulation of the PI3K pathway is common in many cancers since it is responsible for the control of cell survival, growth, and cycle progression.•PIK3CA gene mutations are found in many cancers. ...Studies have started reporting on the prevalence of such mutations in different populations and communities.•Detection of PIK3CA gene mutations prevalence has implications on treatment modalities and general epidemiological and healthcare strategies.•This study is the first report from Lebanon and the largest from the Arab World.
The PIK3CA pathway is one of the most frequently altered pathways in human cancers, especially in breast cancer with approximately 40% of HR+/HER2– advanced breast cancer cases exhibiting mutations in the PIK3CA gene. While the mutations can occur across the entire gene, the most common are observed in exon 9 corresponding to the helical domain, and in exon 20 encompassing the kinase domain. This study constitutes the first attempt at determining the frequency and mutational spectrum in Lebanese breast cancer patients. For this purpose, DNA samples from 280 breast cancer patients from across Lebanon were screened for PIK3CA mutations using the Therascreen® PIK3CA RGQ Real-time PCR assay. In line with previous reports, 38.57% of cases were positive for at least one PIK3CA mutation, among which approximately 59% were in exon 9 and 37% in exon 20. However, PIK3CA mutations are breast cancer are heterogeneous whereby 20% of known PIK3CA mutants might not be detected by compact PCR based assays. Thus, the adoption of comprehensive Next Generation Sequencing based panels to decipher the complete clinical, molecular and immunohistochemical profile of breast cancer tumor requires further investigation.
Docetaxel (D) plus gemcitabine (G) is an active combination in anthracycline pre-treated breast cancer. Impact of sequential administration of these drugs is unclear. This trial aimed to compare ...concomitant DG with sequential D → G. Patients were randomised to eight cycles of gemcitabine 1,000 mg/m
2
on days 1 + 8 plus docetaxel 75 mg/m
2
on day 8, or 4 cycles of docetaxel 100 mg/m
2
on day 1, followed by four cycles of gemcitabine 1,250 mg/m
2
on days 1 + 8, in a 21-day schedule. Time to progression (TTP) was defined as primary endpoint; secondary endpoints were overall response rate (ORR), response duration (RD), overall survival (OS) and toxicity. Due to poor recruitment, the trial was terminated after 100 of a pre-planned 430 patients. Patient characteristics were well balanced. No significant difference was observed in terms of TTP, ORR, RD and OS. Grade 3/4 adverse events encompassed leucopoenia (29 vs. 68%,
P
< 0.001), neutropoenia (49 vs. 83%,
P
< 0.001) and febrile neutropoenia (4 vs. 9%, n.s.), all favouring D → G. No difference in efficacy was observed between concomitant and sequential treatment. D → G produced significantly more episodes of haematological toxicity due to the administration of docetaxel at 100 mg/m² without GCSF-support.
Incidence of various Hodgkin (HL) and non-Hodgkin lymphoma (NHL) subtypes and association with viruses in Lebanon are not known. We undertook a nationwide study of 272 patients diagnosed with ...lymphoma in 2007. HL comprised 32.7 % (
n
= 89) of cases while NHL represented 67.3 % (
n
= 183). Consistent with the literature, nodular sclerosis was the most predominant HL subtype (
n
= 57/89). Among NHL, B-cell NHL represented 88 % (
n
= 161/183), T-cell NHL 9 % (
n
= 17/183), whereas in 2.7 % it was not classifiable. The B-cell NHL comprised predominantly diffuse large B-cell lymphoma (46 %) and follicular lymphoma (23 %). 81 cases were reviewed by a panel of pathologists with 87.6 % concordance rate. Serology was negative for hepatitis C in 122 tested cases. HIV was positive in 2 cases. Two adult T-cell leukemia/lymphoma were HTLV-I positive. EBV IgG were positive in 88.5 % of cases. 38 EBV seropositive cases 27 NHL (24 B-cell, 3 T-cell) and 11 HL were studied for EBV genome expression using EBV-encoded RNA (EBER)-in situ hybridization. EBER expression was positive in 8 (21 %) cases (6 HL, 2 T-cell NHL). The distribution of lymphoma subtypes in Lebanon appears similar to that of Western countries. The high rate of EBV positivity in HL and T-cell lymphoma by EBER deserves further investigation.
Discordant lymphoma is the condition in which two subtypes of lymphoma occur synchronously in different anatomical sites. The objective is to highlight this exceptionally rare combination in order to ...prevent inaccurate diagnosis.
A 20-year-old female presented with typical signs of diffuse supraclavicular and mediastinal lymph node enlargement. Based on the characteristic histological appearance of lymph nodes, she was diagnosed with classical mixed cellularity Hodgkin Lymphoma. Treatment was initiated with ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy. Following four cycles of therapy, the patient underwent a PET scan that revealed partial remission with persistence of mediastinal lymph nodes. Two additional cycles of ABVD were initiated, followed by a repeat PET scan that revealed new anterior and mediastinal lymph nodes with a necrotic center. Radiotherapy was done with a dose of 36 Gy in 20 fractions. Three months later following therapy, the patient underwent a PET scan that showed new onset sub-diaphragmatic lymph nodes with necrotic centers, although it showed a major decrease in the mediastinal lymph nodes previously described. A biopsy was performed on the new appearing nodes and was in favour of diffuse large B cell lymphoma, most likely of non-germinal center cell of origin, and was expressing CD30. Following this discovery, additional cycles of R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) were administered, resulting in a significant decrease in sub-diaphragmatic lymph nodes.
Even if strict guidelines are followed, we must remain aware that several types of lymphoma can coexist simultaneously, and discordant lymphoma should be considered, especially when new lymph nodes appear despite adequate therapy, and a biopsy is always recommended. Identifying this rare entity can offer a survival benefit.
Abstract 5220
lymphoid neoplasms represent a diverse group of neoplasms that are broadly classified into non-Hodgkin lymphomas (NHL) and Hodgkin lymphoma (HL). Incidence of particular subtypes and ...pathogenic associations with certain viral infections are derived from data from the Western world. Little is known about such associations in developing countries; accordingly, this prospective study evaluates newly diagnosed cases of lymphomas in Lebanon and evaluates the incidence of particular subtypes and possible association with various viral infections.
this was a collaborative nationwide study that included all patients diagnosed with lymphoma in Lebanon in 2007. Epidemiological, clinical and histological data were collected. Available lymphoma tissue (stained slides and paraffin-embedded tissue) was reviewed by a panel of pathologists. Blood was collected for serologic testing for the following viruses: hepatitis C (HCV), HIV, EBV, and HTLV-I.
275 cases, 140 (50.7%) males and 136 (49.3%), with lymphoma were diagnosed. Eighty one cases (76 from academic centers and 5 from community hospitals) were reviewed by the pathology panel. The overall concordance rate was 87.6% (71/81); there was discordance in 6 (7.4%) cases: 3 originally diagnosed as diffuse large B cell lymphoma (DLBCL) were revised to high-grade follicular lymphomas, 1 small lymphocytic lymphoma (SLL) previously DLBCL, 1 DLBCL previously low grade lymphoma, 1 DLBCL previously lymphoblastic lymphoma; 4 cases were considered equivocal on revision. The enrolled cases were classified as follows: 183(66.5%) NHL (150 cases B cell lymphoma - 81 DLBCL, 35 follicular, 12 marginal zone/MALT, 11 mantle cell, 7 SLL/CLL, 2 transformed follicular/DLBCL, 2 lymphoblastic; 16 cases T cell lymphoma - 7 peripheral T cell NOS, 4 anaplastic, 2 lymphoblastic, 1 angioimmunoblastic, 1 NK cell, 1 adult T cell leukemia/lymphoma (ATLL); 17 unclassified); and 92(33.5%) HL (60 nodular sclerosis, 5 mixed cellularity, 5 lymphocyte predominant, 1 lymphocyte-rich, 21 unclassified). Blood was obtained from 120 patients. Serology was negative for HCV in all tested cases. HIV was positive in 2 cases (1 NHL, 1 HL). EBV IgG were positive in 106 (88.3%) cases (68/77 NHL, 38/43 HL). Also, 38 EBV seropositive cases (27 NHL (24 B-cell type & 3 T-cell type), 11 HL) were studied for latent membrane protein-1 (LMP-1); LMP-1 staining was positive in 8(21%) cases, of which 6 were HL and 2 were T-cell NHL. Only one case with peripheral T cell lymphoma (ATLL) tested positive for HTLV-1.
our epidemiological study showed that two-thirds of lymphoma cases diagnosed over a year were NHL. Reviewing almost one-third of cases showed an 87.6% concordance rate in diagnosis. Serologic testing of viruses did not reveal any specific pattern that suggests an association between the tested viruses (HCV, HIV, EBV, and HTLV-I) and lymphoma. However, LMP-1 testing was positive in 54.5% of IgG positive HL cases and in 66.7% of IgG positive T-cell NHL. These finding confirm a strong association of EBV with HL and T-cell lymphoma.
Bazarbachi:Hoffman La Roche: Research Funding.
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