Maya Charafeddine

Effects of young age at presentation on survival in breast cancer

BackgroundYoung age remains a controversial issue as a prognostic factor in breast cancer. Debate includes patients from different parts of the world. Almost 50% of patients with breast cancer seen at the American University of Beirut Medical Center (AUBMC) are below age 50.MethodsWe reviewed 1320 patients seen at AUBMC between 1990 and 2001. We divided them in three age groups: Below 35, 35–50, and above 50. Data and survival were analyzed using Chi-square, Cox regression analysis, and Kaplan Meier.ResultsMean age at presentation was 50.8 years. 107 patients were below age 35, 526 between 35–50 and 687 patients above age 50. Disease stages were as follows: stage I: 14.4%, stage II: 59.9%, stage III: 20% and stage IV: 5.7%. Hormone receptors were positive in 71.8% of patients below 35, in 67.6% of patients 35–50 and in 78.3% of patients above 50. Grade of tumor was higher as age at presentation was lower. More young patients received anthracycline-based adjuvant chemotherapy. Of hormone receptor-positive patients, 83.8% of those below age 35 years, 87.76% of those aged 35–50 years, and 91.2% of those aged above 50 years received adjuvant tamoxifen. The mean follow up time was 3.7 +/- 2.9 years. Time to death was the only variable analyzed for survival analysis. Excluding stage IV patients, tumor size, lymph node, tumor grade and negative hormone receptors were inversely proportional to survival. Higher percentage of young patients at presentation developed metastasis (32.4% of patients below 35, as compared to 22.9% of patients 35–50 and 22.8% of patients above 50) and had a worse survival. Young age had a negative impact on survival of patients with positive axillary lymph nodes, and survival of patients with positive hormonal receptors, but not on survival of patients with negative lymph nodes, or patients with negative hormonal receptors.ConclusionYoung age at presentation conferred a worse prognosis in spite of a higher than expected positive hormone receptor status, more anthracycline-based adjuvant chemotherapy and equivalent adjuvant tamoxifen hormonal therapy in younger patients. This negative impact on survival was seen in patients with positive lymph nodes and those with positive hormonal receptors.

Cancer trends in Lebanon: a review of incidence rates for the period of 2003–2008 and projections until 2018

BackgroundThe analysis of cancer incidence trends is essential to health care planning. The aim of this study is to examine variations in cancer incidence rates in Lebanon between 2003 and 2008 and use the observed trends to project cancer incidence until 2018.MethodsUsing secondary data with a cumulative caseload of 45,753 patients from the National Cancer Registry database of the Ministry of Public Health in Lebanon, we estimated sex- and site- specific incidence of cancer for each year of the six-year period between 2003 and 2008. Logarithmic regressions were fitted to estimate the cancer incidence for the forecast years until 2018.ResultsBetween 2003 and 2008, males and females presented with an overall 4.5% and 5.4% annual increase, respectively. Significant increases were observed for cancers of the liver and prostate among males, and for cancers of the liver, thyroid, and corpus uteri among females. By 2018, incidence rates were projected to approach 296.0 and 339.5 cases per 100,000 for males and females, respectively. The most common five types of cancer are expected to be prostate, bladder, lung, non-Hodgkin, and colon among males; and breast, ovarian, non-Hodgkin, lung, and colon among females.ConclusionThe increased availability of screening programs and a growing smoking epidemic, most notably in women, are the most likely explanations behind the increased cancer incidence in the past decade. An aging population and higher proportion of older people suggest further increases in the cancer caseload in the future. The health care system in Lebanon will be required to adapt to the growing burden of cancer in our population.

Programmed Death-Ligand 1 Expression in Muscle-Invasive Bladder Cancer Cystectomy Specimens and Lymph Node Metastasis: A Reliable Treatment Selection Biomarker?

BACKGROUND The programmed death-1 (PD-1) pathway negatively regulates T-cell activation and has an important role in regulating antitumor host immunity. Monoclonal antibodies directed against PD-1 or the PD-1 ligand (PD-L1) have shown activity in several tumor types with preliminary data suggesting a relationship between PD-L1 expression and response. The aim of this study was to establish the frequency of PD-L1 expression in muscle-invasive bladder cancer and associated lymph node metastasis using immunohistochemistry and to investigate the feasibility of using PD-L1 expression as a biomarker to select patients for PD-1-directed therapy. PATIENTS AND METHODS Cases of radical cystectomy for muscle-invasive bladder cancer with no exposure to previous chemotherapy were identified and representative slides from archived paraffin-embedded blocks stained with anti-PD-L1 antibody (5H1 clone) were identified. PD-L1 positivity was defined by a 5% expression threshold. RESULTS Fifty-two radical cystectomy specimens were reviewed. PD-L1 was overexpressed in the tumor cells of 5/52 (9.6%) of cystectomy specimens in this cohort with 17/52 (32.7%) of cases showing PD-L1 overexpression in tumor-infiltrating immune cells. Discordance was observed between PD-L1 expression in lymph node metastasis and the primary tumor. CONCLUSION Standard assays for PD-L1 expression have yet to be established. The observation of discordance between PD-L1 expression in metastatic sites and primary tumors suggests that prospective biomarker studies should aim to acquire material immediately before treatment initiation rather than archived tissue from resected specimens that might not reflect the current immune-active microenvironment.

A phase II randomized trial comparing radiotherapy with concurrent weekly cisplatin or weekly paclitaxel in patients with advanced cervical cancer

Purpose/ObjectiveThis is a prospective comparison of weekly cisplatin to weekly paclitaxel as concurrent chemotherapy with standard radiotherapy for locally advanced cervical carcinoma.Materials/MethodsBetween May 2000 and May 2004, 31 women with FIGO stage IB2-IVA cervical cancer or with postsurgical pelvic recurrence were enrolled into this phase II study and randomized to receive on a weekly basis either 40 mg/m2 Cisplatin (group I; 16 patients) or 50 mg/m2 paclitaxel (group II; 15 patients) concurrently with radiotherapy. Median total dose to point A was 74 Gy (range: 66-92 Gy) for group I and 66 Gy (range: 40-98 Gy) for group II. Median follow-up time was 46 months.ResultsPatient and tumor characteristics were similar in both groups. The mean number of chemotherapy cycles was also comparable with 87% and 80% of patients receiving at least 4 doses in groups I and II, respectively. Seven patients (44%) of group I and 8 patients (53%) of group II developed tumor recurrence. The Median Survival time was not reached for Group I and 53 months for group II. The proportion of patients surviving at 2 and 5 years was 78% and 54% for group I and 73% and 43% for group II respectively.ConclusionsThis small prospective study shows that weekly paclitaxel does not provide any clinical advantage over weekly cisplatin for concurrent chemoradiation for advanced carcinoma of the cervix.

Prostate Cancer in the Arab World: A View From the Inside.

The rates of prostate cancer vary by more than 50-fold across different international populations. The aim of this review was to explore the differences in epidemiology and risk factors between the Middle Eastern Arab countries and some of the developed countries in Europe and North America. The age-standardized incidence rate of prostate cancer in the Arab countries is still lower than that in the Western countries, but is steadily increasing with time. Several factors come into play to explain this difference. There are health care systems-related factors such as the lack of good population-based registries, and population-related factors. The latter include the relatively young age structure in the Arab countries, lower reported androgen and prostate-specific antigen levels in Arab men, the effect of genetic differences on prostate cancer risk, the metabolic syndrome paradox, and the protective effect of the Mediterranean diet on a subset of the Arab population. In conclusion, the study of prostate cancer in the Arab world represents a challenge with the currently available cancer care systems and the increase in the burden of the disease. A multinational prospective study to investigate the epidemiology of prostate cancer in the Middle East, with specific attention to country/geographic variability along with a comparative analysis to that of the Western hemisphere is needed.

Hyper-CVAD Compared With BFM-like Chemotherapy for the Treatment of Adult Acute Lymphoblastic Leukemia. A Retrospective Single-Center Analysis

Background Several induction regimens have been developed for treatment of adult patients with acute lymphoblastic leukemia (ALL). However, only a few prospective randomized trials have directly compared these regimens. Patients and Methods In this report, we retrospectively evaluated the outcome of 62 adult ALL patients treated with either hyper‐CVAD (hyper fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone; n = 38) or a BFM (Berlin–Frankfurt–Munster)‐like regimen (n = 24) between November 2000 and January 2016 at the American university of Beirut Medical Center in Lebanon. The feasibility of allogeneic stem cell transplantation (allo‐SCT) for those patients was also evaluated. Results The median follow‐up time was 29 (range, 1‐129) months. Fifteen (39%) and 10 (42%) patients underwent allo‐SCT in the hyper‐CVAD and BFM‐like group, respectively. At the time of the last follow‐up, 28 patients (74%) were in complete remission in the hyper‐CVAD group versus 18 patients (75%) in the BFM‐like group. Of those, 20 patients (53%) versus 11 patients (46%) were minimal residual disease‐negative at the last follow‐up, respectively. The 3‐year overall survival rate (71.9% vs. 76.9%; P = .808) and 3‐year disease‐free survival (54.7% vs. 76.4%; P = .435) were similar in hyper‐CVAD group compared with the BFM‐like group, respectively. Both chemotherapies were relatively well tolerated. Conclusion Overall, despite the older age and a greater number of patients with high‐risk category (including Philadelphia chromosome‐positive) in the hyper‐CVAD group, this did not translate into a difference in survival outcome between the 2 groups. The hyper‐CVAD regimen appears to be feasible for adult patients with ALL in terms of tolerability and efficacy. Micro‐Abstract Several induction regimens have been developed for adult patients with acute lymphoblastic leukemia (ALL). We show that the hyper‐CVAD (hyper fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen appears to be feasible for adult patients with ALL in terms of tolerability and efficacy. The combination of tyrosine kinase inhibitors for Philadelphia chromosome‐positive (+) patients and rituximab for CD20+ patients were significantly more frequent in the hyper‐CVAD arm and might have affected outcomes favorably. There is still a need for large, prospective, randomized studies to establish the best induction regimen for adult ALL patients.

A clinical phase II study of a non-anthracycline sequential combination of cisplatin-vinorelbine followed by docetaxel as first-line treatment in metastatic breast cancer.

Background: We tested a sequential combination regimen using cisplatin and vinorelbine (PVn) followed by docetaxel as first-line chemotherapy in a phase II clinical trial in metastatic breast cancer (MBC). Patients and Methods: Thirty-five patients were enrolled. Cisplatin 80 mg/m2 was given on day 1 and vinorelbine 30 mg/m2 on days 1 and 8 every 3 weeks for 4 cycles. Responding patients received docetaxel 75 mg/m2 every 21 days for a maximum of 4 cycles. Three patients were excluded from analysis because of death unrelated to treatment. Results: After a median follow-up of 14 months, 32 patients completed the study. The overall response rate was 53.1%. Complete remission was seen in 5 patients (15.6%), partial response in 12 (37.5%), stable disease in 6 (18.75%), and progressive disease in 9 patients (28.1%). Median time to disease progression was 8 months (range 1–24). At 24 months, 12 (37.5%) patients were alive. A total of 183 cycles were administered. Febrile neutropenia was observed in 4 patients (2.2%). Grade II nephrotoxicity occurred in 12 cycles (6.5%) and grade III vomiting in 31/183 cycles (16.9%). Discussion: PVn is a feasible non-anthracycline option as first-line chemotherapy in patients with metastatic breast cancer and has acceptable toxicity. The sequential addition of 4 cycles of docetaxel following 4 cycles of PVn did not improve the overall response rate and results.

Trends in lung cancer incidence in Lebanon by gender and histological type over the period 2005–2008

Introduction: Lung cancer incidence rates, overall and by histologic subtypes, vary substantially by gender and smoking. This study’s aim was to review data regarding trends in the number of cases of different lung-cancer histologies and relate these to smoking habits by gender in Lebanon. Materials and methods: Lung cancer data using ICD-O, 3rd edition, from the Lebanese National Cancer Registry from 2005 to 2008 were stratified by gender for histology type for patients aged over 18 years. Results: Lung cancer cases among males were 2.5 times higher than those in females. The most common lung cancer histology type for males and females was adenocarcinoma for all observed years. The proportion of squamous cell carcinoma in incident cases was significantly higher in males than in females for the total period from 2005 to 2008, P = 0.032, but not in individual years. The ratio of adenocarcinoma to squamous cell carcinoma in incident cases between 2005 and 2008 was 2:45 for males and 3:15 for females. Conclusion: Lung cancer histology in Lebanon is following a pattern similar to that found in most countries of North America and in Europe, where adenocarcinoma is the most prevalent subtype among both males and females.

Perceptions of Cancer Status Disclosure in Lebanon

In Lebanon, cancer used to be regarded as a taboo and referred to as “the disease” and was rarely disclosed to patients. However, patients are now increasingly interested in knowing their cancer status but with varying degrees of information requested. The aim of this qualitative descriptive study was to explore the perceptions of cancer patients, their families, oncologists, and healthy individuals concerning the disclosure of cancer prognosis. In-depth interviews were conducted with 21 family members, 20 middle-aged cancer patients, 11 elderly cancer patients, 22 healthy individuals, and 6 oncologists at the American University of Beirut Medical Center. The interviews focused on the following: general perception of cancer in Lebanese society, type, and extent of information that should be disclosed, factors affecting patient autonomy, and elements contributing to the decisions taken by oncologists and patients. The oncologist’s compassion and communication with patients affected their emotional status greatly, and some gaps in communication skills of oncologists were in need of standardized training courses to improve the process of cancer status disclosure. Also, patients had an increased preference towards the disclosure of cancer prognosis, and a desire to know the truth and this need increased as the patient progressed to a terminal state. Future work should be directed at addressing the needs of cancer patients through every disease stage. More research and further deliberation are needed to confirm the findings of this study since the Lebanese Code of Medical Practice does not protect the right of full disclosure.

Cytomegalovirus reactivation in lymphoma and myeloma patients undergoing autologous peripheral blood stem cell transplantation

BACKGROUND Cytomegalovirus reactivation is often diagnosed in allogeneic hematopoietic cell transplant recipients and therefore could lead to CMV-related disease, involving many organs in these immunocompromised patients. In contrast, few studies investigated CMV reactivation and end-organ disease in patients undergoing Autologous Peripheral Blood Stem Cell Transplant (ASCT) since they are considered at low risk for both reactivation and disease. OBJECTIVES The primary outcome of the analysis was to understand the difference in incidence of CMV reactivation between MM and Lymphoma patients. Secondary outcomes included the difference between MM and Lymphoma patients when considering the effect of CMV reactivation on transplant related mortality (TRM) overall survival (OS) progression free survival (PFS), risk factors for reactivation, and median time to reactivation. STUDY DESIGN In this report, we retrospectively compared the incidence, risk factors, and outcome of CMV reactivation in adult patients with Myeloma (MM) and Lymphoma undergoing ASCT at the American university of Beirut Medical Center in Lebanon (AUBMC). A total of 324 consecutive ASCT were performed between January 2005 and March 2016. Serial weekly monitoring for CMV quantification was done using a quantitative PCR, starting from transplantation until the hospital discharge and afterwards based on the clinical symptoms in cases of clinical suspicion of reactivation after discharge from the hospital. RESULTS The cumulative incidence of CMV reactivation was 16% (n=53) with a median time of 16 (range, 4-242) days after ASCT. The incidence of reactivation was significantly higher in the MM (22%) and NHL (20%) groups, when compared to the HL (4%) (P=0.001). There was a higher incidence of CMV reactivation according to age (≥50 vs ≤50 years) with higher incidence in the older population 24% vs 10% respectively (p=0.0043). The mean time to CMV reactivation was significantly higher in the NHL group with a mean of 53.7days when compared to the HL and MM groups with mean 19.75days and 12.66 (range, 4-34) days respectively (P=0.003). Twenty-two patients (76%) and three patients (75%) patients required specific antiviral therapy in the MM group and HL groups respectively; which was significantly higher (P<0.001) then the NHL group with 13 (65%) patients requiring specific antiviral therapy. Five patients (1.5%) developed CMV disease at a median of 60days (range, 7-107) post ASCT: there was significant difference in the mean-time to reactivation based on disease type MM versus lymphoma 10 versus 33days (P=0.007). In multivariate analysis, a higher age was associated with an increased risk of CMV reactivation; MM and NHL had higher risk of CMV reactivation when compared to HL, and progressive disease at transplant was associated with increased risk of CMV reactivation. After a median follow-up of 21.5 months (range: 1-125), there was no significant impact on PFS, however there was significant decrease in OS of lymphoma patients who had CMV reactivation when compared to those without CMV reactivation (204 and 112days respectively P=0.045). TRM increased from 1.1% in patients with no CMV reactivation to 13% in patients with CMV reactivation (P=0.003). CONCLUSION Our data suggests that CMV reactivation is not uncommon in ASCT recipients and may contribute to increase TRM. MM patients may have a higher incidence, of CMV reactivation with more anti-viral treatment requirements when compared to lymphoma patients, especially in older population.