Tailoring neo/adjuvant systemic therapy in breast cancer: "The advent of a personalized approach"-The Breast-Gynecological and Immuno-Oncology International Cancer Conference (BGICC) consensus and recommendations.

BACKGROUND: The management of early breast cancer (BC) has witnessed an uprise in the use of neoadjuvant therapy and a remarkable reshaping of the systemic therapy postneoadjuvant treatment in the last few years, with the evolution of many controversial clinical situations that require consensus. METHODS: During the 14th Breast-Gynecological and Immuno-Oncology International Cancer Conference held in Egypt in 2022, a panel of 44 BC experts from 13 countries voted on statements concerning debatable challenges in the neo/adjuvant treatment setting. The recommendations were subsequently updated based on the most recent data emerging. A modified Delphi approach was used to develop this consensus. A consensus was achieved when ≥75% of voters selected an answer. RESULTS AND CONCLUSIONS: The consensus recommendations addressed different escalation and de-escalation strategies in the setting of neoadjuvant therapy for early BC. The recommendations recapitulate the available clinical evidence and expert opinion to individualize patient management and optimize therapy outcomes. Consensus was reached in 63% of the statements (52/83), and the rationale behind each statement was clarified.

The Role of Direct Oral Anticoagulants in the Treatment of Cancer-Associated Venous Thromboembolism: Review by Middle East and North African Experts.

Venous thromboembolism is a leading cause of morbidity and mortality in patients with active cancer who require anticoagulation treatment. Choice of anticoagulant is based on careful balancing of the risks and benefits of available classes of treatment: vitamin K antagonists, low-molecular-weight heparin (LMWH), and direct oral anticoagulants (DOACs). Results from randomized controlled trials have shown the consistent efficacy of DOACs versus LMWH in the treatment of cancer-associated venous thromboembolism (VTE). However, increased major gastrointestinal bleeding was observed for edoxaban and rivaroxaban, but not apixaban, compared with LMWH dalteparin. Most guidelines recommend DOACs for the treatment of cancer-associated VTE in patients without gastrointestinal or genitourinary cancer, and with considerations for renal impairment and drug-drug interactions. These updates represent a major paradigm shift for clinicians in the Middle East and North Africa. The decision to prescribe a DOAC for a patient with cancer is not always straightforward, particularly in challenging subgroups of patients with an increased risk of bleeding. In patients with gastrointestinal malignancies who are at high risk of major gastrointestinal bleeds, apixaban may be the preferred DOAC; however, caution should be exercised if patients have upper or unresected lower gastrointestinal tumors. In patients with gastrointestinal malignancies and upper or unresected lower gastrointestinal tumors, LMWH may be preferred. Vitamin K antagonists should be used only when DOACs and LMWH are unavailable or unsuitable. In this review, we discuss the overall evidence for DOACs in the treatment of cancer-associated VTE and provide treatment suggestions for challenging subgroups of patients with cancer associated VTE.

Patients with cancer are at risk of blood clots forming in their veins, which can cause illness and death. To prevent such blood clots, most patients with cancer need anticoagulant therapy. There are three types of anticoagulants available for the treatment of cancer-associated blood clots in a vein, namely, vitamin K antagonists, low-molecular-weight heparin (LMWH), and direct oral anticoagulants (DOACs). Drug trials have shown that DOACs are more effective than LMWH; however, DOACs can have a greater risk of causing major gastrointestinal bleeding. Among DOACs, edoxaban and rivaroxaban are drugs associated with higher rates of gastrointestinal bleeding. Recently updated guidelines for doctors recommend that DOACs be used as the first treatment for patients with cancer at risk of blood clot formation in a vein. For doctors in the Middle East and North Africa, this new approach differs from existing practices. Notably, choosing a treatment also depends on the type of cancer, because gastrointestinal cancers and cancers of the genitals and urinary system have an especially high risk of gastrointestinal bleeding. The choice also depends on the presence of kidney problems, drug­drug interactions, and access to the drugs. Apixaban may be the preferred DOAC in patients with gastrointestinal cancer, but this drug should be used with care in patients with upper or unresected lower gastrointestinal tumors. For patients with upper or unresected lower gastrointestinal tumors, treatment with LMWH may be preferred. Vitamin K antagonists should be used only when DOACs and LMWH are unavailable or unsuitable.

Prognostic Value of Tumor Infiltrating Lymphocytes in Locally Advanced HER2 Enriched Breast Cancer.

PURPOSE: We aim to study the association between stromal tumor infiltrating lymphocytes (TILs) level and disease free survival (DFS) in a group of ER and PR negative, HER2+ locally advanced breast cancer patients who underwent curative intent surgery. METHODS: This is a retrospective cohort study including 66 locally advanced hormone receptor-negative; HER2+ breast cancer patients presented between 2013 and 2015 at NCI-Cairo, Egypt. Enrolled patients had at least clinically T3 and/or node positive disease either clinically or radiologically. Metastatic workup included CT and bone scans or PET-CT. Patients with hormone receptor positive, HER2 negative, inadequate paraffin block and who lost follow up before or immediately after curative surgery were excluded. Patients were followed from breast surgery till relapse date for a minimum of 36 months. TILs and CD8 antigen were assessed on paraffin-embedded blocks using immunohistochemistry. RESULTS: Patients with a median age of 52 years presented with clinical T3 stage (53%) and N1 stage (61%). Modified radical mastectomy was performed in 79%. Only 41% received neoadjuvant chemotherapy and 56% received trastuzumab. TILs were 50, 17 and 33% for absent, intermediate and extensive groups and CD8+ lymphocytes were present in 80% of cases. At the end of follow-up period, 23 patients (35%) were found to have disease recurrence either loco-regional (22%) or distant (78%). TILs were 14, 4 and 5% for absent, intermediate and extensive respectively; while CD8+ lymphocytes were absent in 6% and present (≥1%) in 17%. Higher DFS was recorded for patients with extensive TILs level only who received trastuzumab. CONCLUSION: High TILs is good prognosis in HER2 enriched breast cancer provided that patients received HER2 directed therapy. Moreover, CD8+ lymphocytes are highly representative and maybe used as an alternative for TILs. We recommend considering TILs and specifically CD8+ as one of the risk factors that predict prognosis of HER2+ breast cancer.

Breast-Gynaecological & Immuno-Oncology International Cancer Conference (BGICC) Consensus and Recommendations for the Management of Triple-Negative Breast Cancer.

Background: The management of patients with triple-negative breast cancer (TNBC) is challenging with several controversies and unmet needs. During the 12th Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020, a panel of 35 breast cancer experts from 13 countries voted on consensus guidelines for the clinical management of TNBC. The consensus was subsequently updated based on the most recent data evolved lately. Methods: A consensus conference approach adapted from the American Society of Clinical Oncology (ASCO) was utilized. The panellists voted anonymously on each question, and a consensus was achieved when ≥75% of voters selected an answer. The final consensus was later circulated to the panellists for critical revision of important intellectual content. Results and conclusion: These recommendations represent the available clinical evidence and expert opinion when evidence is scarce. The percentage of the consensus votes, levels of evidence and grades of recommendation are presented for each statement. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials.

The first BGICC consensus and recommendations for breast cancer awareness, early detection and risk reduction in low- and middle-income countries and the MENA region.

In low-middle income countries (LMICs) and the Middle East and North Africa (MENA) region, there is an unmet need to establish and improve breast cancer (BC) awareness, early diagnosis and risk reduction programs. During the 12th Breast, Gynecological & Immuno-oncology International Cancer Conference - Egypt 2020, 26 experts from 7 countries worldwide voted to establish the first consensus for BC awareness, early detection and risk reduction in LMICs/MENA region. The panel advised that there is an extreme necessity for a well-developed BC data registries and prospective clinical studies that address alternative modalities/modified BC screening programs in areas of limited resources. The most important recommendations of the panel were: (a) BC awareness campaigns should be promoted to public and all adult age groups; (b) early detection programs should combine geographically distributed mammographic facilities with clinical breast examination (CBE); (c) breast awareness should be encouraged; and (d) intensive surveillance and chemoprevention strategies should be fostered for high-risk women. The panel defined some areas for future clinical research, which included the role of CBE and breast self-examination as an alternative to radiological screening in areas of limited resources, the interval and methodology of BC surveillance in women with increased risk of BC and the use of low dose tamoxifen in BC risk reduction. In LMICs/MENA region, BC awareness and early detection campaigns should take into consideration the specific disease criteria and the socioeconomic status of the target population. The statements with no consensus reached should serve as potential catalyst for future clinical research.

Novel therapeutic strategies in the treatment of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that is defined by negative estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Treating patients with TNBC remains clinically challenging, as patients are not candidates for endocrine or HER2-directed therapy. As a result, chemotherapy with traditional agents such as anthracyclines and taxanes remains the only available option with moderate success. Recent discoveries have revealed that TNBC is a heterogeneous disease at the clinical, histological and molecular levels. The use of biomarkers to identify distinct subsets of TNBC that derive the greatest benefit from presently approved as well as novel therapeutics has become the main focus of current research. The aim of this review is to explore the clinical and biological complexity of TNBC as well as identify novel therapeutic options that target the various molecular subsets of TNBC.

Vascular endothelial growth factor before and after locoregional treatment and its relation to treatment response in hepatocelluar carcinoma patients

Objective: To evaluate vascular endothelial growth factor (VEGF) levels in hepatocel-lular carcinoma patients before and after transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) and its relation to treatment response. Methods: A total of 40 patients with unrespectable hepatocelluar carcinoma were assessed clinically. Twenty patients were suitable to be treated by TACE, while other 20 patients were treated with PEI. Serum VEGF levels were measured before and 1 month after each procedure by ELISA. Response was assessed after 1 month according to Union Internationale Contre le Cancer evaluation criteria based on change in tumor size as measured by ultrasound. Results: There was no significant difference between TACE and PEI groups with regard to age, sex, tumor size, response to local therapy, or VEGF and alpha-fetoprotein before and after therapy. VEGF levels after TACE were significantly higher than before TACE [(298.1 ± 123.6) pg/mL vs. (205.8 ± 307.3) pg/mL;P=0.001]. Also, VEGF levels were significantly higher after PEI than before PEI [(333.8 ± 365.6) pg/mL vs. (245.3 ± 301.8) pg/mL;P=0.000]. Non-responders of both groups had significantly high VEGF levels than responder's, both before [(985.0 ± 113.2) pg/mL vs. (117.1 ± 75.3) pg/mL;P Conclusions: Both TACE and PEI were associated with an increase in serum VEGF in hepatocelluar carcinoma patients. Higher levels of VEGF before and after therapy were found in non-responders, suggesting that VEGF is a useful marker in predicting treatment response.

Cost and outcome of treatment of adults with acute myeloid leukemia at the National Cancer Institute-Egypt.

BACKGROUND: Despite important advances in the therapy of acute myeloid leukemia (AML), the majority of patients die of their disease, unless bone marrow transplantation (BMT) is done. Infection and hemorrhage are still the major causes of mortality in AML patients. Progress in therapy and supportive care has led to gradual improvement in the overall results, but further improvements are still needed. PATIENTS AND METHODS: The aim of this study is to identify the outcome and costs of adult AML patients treated with conventional chemotherapy (CCT) at the National Cancer Institute (NCI), Cairo University during the time period from April 1999 to January 2002. Clinical, laboratory characteristics were all recorded. Data regarding different types of therapies given for these patients including response, outcome and costs were also collected. RESULTS: The median age of 82 identified AML patients was 34 years. The complete remission (CR) rate after induction with CCT was 52% (42/82 patients) with a median CR duration of 9 months. Twenty-eight percent of patients who achieved CR subsequently relapsed. By January 2003, fifty-eight patients were dead (70.7%). Infections were the major mortality cause, followed by disease progression then bleeding (65% , 28% and 7% respectively). The median treatment cost per patient was 33158 Egyptian Pounds (LE). It was higher for patients who achieved CR compared to those who relapsed and/or died. Drugs contributed by 78 % to the total treatment cost, while hospitalization, investigations and blood-component therapy contributed by 6%, 7% and 8% respectively. CONCLUSIONS: Outcome of patients with AML treated at NCI- Cairo University can be enhanced by improvement of supportive therapy; mainly infection control and expanding BMT programs to accommodate all eligible patients.

Gemcitabine plus doxorubicin as first-line treatment in advanced or metastatic breast cancer (MBC), a phase II study.

INTRODUCTION: Doxorubicin and Gemcitabine have promising antineoplastic activity and manageable toxicity as a single agent in the treatment of patients (pts) with advanced breast cancer. AIM OF THE STUDY: This study evaluated the efficacy and toxicity of the combination of gemcitabine plus doxorubicin as first-line treatment of advanced or MBC patients. PATIENTS AND METHODS: Patients with advanced or MBC received gemcitabine 1250mg/m2 IV on days 1 and 8 plus doxorubicin 60mg/m2 IV on day 1 every 21 days for a maximum of 6 cycles. RESULTS: Thirty-five patients were included, and all are evaluable for safety and efficacy. Median age was 47 years (range, 33 to 60 years). Fourteen patients (40%) were post-and 21 (60%) were premenopausal. Prior treatment included mastectomy (23pts); adjuvant nonanthracycline containing combination chemotherapy (18pts); adjuvant hormonal therapy (3pts) and 2 pts did not receive any adjuvant therapy. Twelve patients had metastatic disease at presentation. Seventeen pts were chemonaive. Hormonal receptors were positive in 6, negative in 21, and unknown in 8 pts. Site of metastasis included one site in 15 pts, two sites in 14, and three sites in 6 pts. Complete remission was observed in 6/35 (17.1%) and partial remission in 14/35 (40%) pts, for an overall response rate of 57.1%. Stable disease was observed in 8 (22.9%) and progressive disease in 7 (20%) pts. The median time to tumor progression was 7 months (range, 5-23 months; 95% CI, 6-8 months) and the median survival time was 16 months (range, 6-43 months; 95% CI, 13-19 months). The overall survival at 1 and 2 years was 74.2% and 34.2%; respectively; with 4/35 (11.4%) patients alive at 40 months. A total of 186 cycles of treatment were administered (range2-6 cycles, median 6 cycles). The doses of both doxorubicin and gemcitabine were modified after interim analysis of toxicity following the first 22 cycles administered to the first 10 patients [Mucositis grade 3-4 occurred in 6/10 (60%), grade 3-4 neutropenia in 3/10 (30%), and febrile neutropenia grade 3 in 2/10 (20%) patients] to doxorubicin 50mg/m2 on day 1 and gemcitabine to 1000 mg/m2 on days 1 and 8 in the remaining cycles. After doses reduction, the toxicity was generally tolerable. CONCLUSION: The combination of gemcitabine plus doxorubicin after doses modification can be safely administered every 21 days with promising response as first-line therapy for MBC. The response rate, time to disease progression and overall survival rates of this regimen are comparable to other standard therapies for MBC, as well as other gemcitabine combinations.

Prognostic factors of Hodgkin's lymphoma and their impact on response to chemotherapy and survival.

OBJECTIVE: The aim of this study was to compare the standard prognostic factors of Hodgkin's lymphoma (HL) in relation to response to first line chemotherapy, disease free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: The study was performed on a group of 100 adult patients diagnosed as HL and who were treated and followed-up in the years 1999 to 2001, in the Medical Oncology Department at National Cancer Institute (NCI), Cairo. The first line chemotherapy was COPP in 40%, ABVD in 35% and COPP/ABV hybrid in 25%. Patients were classified into early stage disease: Stages I, IIA and IIB without poor risk factors, n=43 and advanced stage disease: Stages III, IV and IIB with poor risk factors, n=57 analysis of the prognostic factors for early versus advanced-stage disease was done by univariate and multivariate regression analysis. RESULTS: Complete remission (CR) was attained in 69% of the patients after first line chemotherapy; being 87.8 % and 54.7% for early and advanced disease, respectively, (p=0.0001). The CR rates after different chemotherapy regimens were 81.8%, 90% and 90% for the ABVD, COPP and COPP/ABV hybrid regimens in the early-disease group; respectively; in contrast to the corresponding figures of 54.5%, 50% and 61.5% in the advanced- stage group. The DFS at 4 years, was 94 %, 55% and 54.5% for the patients treated with ABVD, COPP and COPP/ABV hybrid, respectively (p=0.2). The DFS and OS in this series of patients were 61.3% and 53.7%, being 69.8% and 70.7% for the early and 45.1% and 38.9% for the advanced-disease, respectively The OS of the whole group was significantly related to age (p=0.04), sex (p=0.005), early versus advanced disease (p=0.0001) and B symptoms (p=0.0006). CONCLUSIONS: The adequate response and DFS of the early compared to the advanced-stage disease supported the evolving role of risk adapted chemotherapy for HL. The prognostic factors proved to be of significant impact in our series. The results of this study pointed to the need for an improved treatment strategy in this potentially curable disease,especially for the advanced disease.