Liquid biopsy as a tool for KRAS/NRAS/BRAF baseline testing in metastatic colorectal cancer.

BACKGROUND: The absence of KRAS and NRAS gene mutations (RAS wild type) in metastatic colorectal cancer (mCRC), is associated with a good response to targeted therapy with anti-EGFR receptor antibodies. The current gold standard for RAS mutational status identification is genetic testing on tissue biopsy samples. OBJECTIVE: This study aimed to assess the relevance of liquid biopsy as a less invasive alternative to tissue biopsy for detecting KRAS/NRAS and BRAF mutations in patients with metastatic colorectal cancer (mCRC). The study also aimed to determine the concordance between liquid biopsy and tissue biopsy. METHODS: This is a phase IV, observational, uncontrolled, non-comparative, non-randomized, open label study. RAS/BRAF status will be tested at baseline using tissue and liquid biopsy using the Idylla/Biocartis PCR-based device. The primary endpoint is the comparison of the RAS status based on liquid biopsy with the RAS status based on tissue biopsy. RESULTS: 100 patients with mCRC were included in the study. 75% of patients showed concordant results between liquid biopsy and tissue biopsy, while 25% had discordant results. Liquid biopsy demonstrated a sensitivity of 62% and a specificity of 93%. The accuracy of liquid biopsy was 75%, with a moderate agreement between the two tests. The most frequent mutations in concordant cases were in KRAS (41%), followed by NRAS (4%) and BRAF (3%). Mutations were not detected in 42% of tissue biopsy samples and 60% of liquid biopsy samples. The presence of hepatic metastases did not significantly affect the concordance between the biopsy methods. CONCLUSION: Liquid biopsy using the Idylla™ system showed a relatively low sensitivity but high specificity for detecting KRAS/NRAS and BRAF mutations in mCRC patients. Despite some discordant cases, liquid biopsy remains a promising alternative to tissue biopsy due to its non-invasiveness, ability to provide multiple samples, and better representation of tumor heterogeneity.

Supplement use and its impact on daily life of cancer patients: a cross-sectional study.

PURPOSE: This cross-sectional study aimed to investigate the prevalence and characteristics of supplement usage among cancer patients and explore its potential associations with anxiety, excessive daytime sleepiness, and overall quality of life. METHODS: Cancer patients receiving specific care at Hôtel Dieu de France University Hospital, Beirut, were enrolled between April and June 2023. In face-to-face interviews, participants were asked to complete a questionnaire consisting of sociodemographic information, supplement usage details, and cancer-related variables. Three validated surveys (Epworth Sleepiness Scale, GAD-7, and EORTC-QLQ-C15-PAL) were employed to assess excessive daytime sleepiness, anxiety, and overall quality of life. Statistical analyses, including chi-square tests, t-tests, and multiple regression models, were conducted to examine associations between supplement use and other variables. RESULTS: A total of 202 participants were interviewed. Fifty-two percent reported regular use of supplements following their cancer diagnosis, with vitamin D being the most commonly used supplement. Using multivariate logistic regression, supplement use was associated with being female, having lower educational levels, having a longer duration since cancer diagnosis, and having a poor overall quality of life. The multivariate logistic regression showed no significant correlation between supplement use and excessive daytime sleepiness and anxiety. CONCLUSION: This study highlights a high prevalence of supplement usage among cancer patients in Lebanon, indicating a rising interest in alternative therapies aimed at enhancing quality of life. Larger prospective studies are needed to assess the relation between supplement intake and excessive daytime sleepiness and anxiety and establish clear guidelines pertaining to supplement use in cancer patients.

Management of humoral secondary immunodeficiency in hematological malignancies and following hematopoietic stem cell transplantation: Regional perspectives.

Secondary immunodeficiency (SID) can occur as a result of multiple factors, including hematological malignancies, hematopoietic stem cell transplantation (HSCT), immunosuppressive treatment, biologics, and anti-inflammatory drugs. SID includes disorders resulting from impairment of both cellular and humoral immunity. This review focuses on the current risk factors, implications, and challenges in managing SID patients with impaired humoral immunity, which includes quantitative (hypogammaglobulinemia) and/or functional antibody and B-cell deficiencies specifically related to hematological malignancies and post-HSCT. Increased physician awareness is needed surrounding the disease presentation and early risk factors, as SID may be caused by several etiologies. Careful clinical assessment is then required to optimize management, which encompasses close monitoring of clinical parameters, vaccination, antibiotic prophylaxis, and immunoglobulin replacement therapy (IGRT). Novel methods of IGRT administration are associated with enhanced pharmacokinetics, IgG trough level stability, no need for venous access, as well as fewer systemic adverse events and better administration flexibility compared with traditional methods. Published international guidelines supported by observations from clinical data are broadly followed; however, best practices within each country have nuances that underline the need to tailor treatment plans to the individual patient.

Clinical and genetic factors associated with self-reported cognitive deficits in women with breast cancer: the "CAGE-Cog" study.

BACKGROUND: Breast cancer patients undergoing chemotherapy treatment are at particular risk of experiencing acute cognitive impairment leading to daily challenges in decision-making and reduced quality of life and functional autonomy. The aim was to assess the relationship between clinical and genetic factors and cognitive function in a sample of patients with breast cancer undergoing chemotherapy. METHODS: A cross-sectional study was carried out between November 2017 and June 2019 on women (N = 112) treated for breast cancer by intravenous chemotherapy at the oncology outpatient unit of Hôtel-Dieu de France Hospital, Beirut. Patients were evaluated with the 37-item Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). Other validated scales were also used to assess depression, anxiety, sleep disorders, pain, and fatigue. DNA was obtained by a buccal swab (FTA®technology) for genotyping of different genes (ABCB1, COMT, DRD2, OPRM1, CLOCK, CRY2, and PER2) using the Lightcycler®(Roche). RESULTS: The mean age of participants was 56.04 years. Multivariable analysis, taking the four FACT-Cog subscores as the dependent variables, showed that the mean cognitive score decreased with higher depression, anxiety, and insomnia scores. Patients with university education levels had better perceived cognitive abilities than those with primary education. Moreover, carrying the G allele for the OPRM1 polymorphism (c.118A > G;rs197791) was significantly associated with a better cognitive function compared to AA patients (B = 2.05; p = 0.038). CONCLUSIONS: A comprehensive oncological care plan should include a personalized assessment of all factors related to cognitive functioning in cancer patients, particularly anxiety and depression, to achieve an optimal patient outcome.

Management of Multiple Myeloma in the Middle East: Unmet Needs, Challenges and Perspective.

Multiple myeloma (MM) is a prevalent hematological malignancy. Resource-constrained settings such as the Middle East are particularly burdened by the increasing trends in MM morbidity and mortality in addition to challenges in the management of MM. It thus becomes necessary to identify and address debatable areas of current practice and gaps in the management of MM in the Middle East. With a special focus on the Lebanese situation, the first-line treatment of the very elderly (> 80 years old) is discussed, in addition to the impact of relapse type (biochemical or clinical relapse) on maintenance therapy, the choice of first relapse therapy in relation to maintenance therapy, and the role of MRD in the MM treatment landscape. The need for realistic management guidelines accounting for local resources and expertise, in addition to the reflection of drug accessibility and cost on clinical practice are recognized.

Clinical and genetic factors associated with anxiety and depression in breast cancer patients: a cross-sectional study.

BACKGROUND: Despite the progress in assessment and treatment of breast cancer, being diagnosed with it or receiving chemotherapy treatment is still conceived as a traumatic experience. Women develop negative thoughts about life and death with detrimental effects on their daily physical functioning/activities, emotional state and overall quality of life. The aim of our study was to evaluate the level of anxiety and depression among breast cancer patients receiving chemotherapy and explore the correlation between these psychological disorders, clinical, sociodemographic and genetic factors. METHODS: A cross-sectional study was conducted among breast cancer patients undergoing intravenous chemotherapy at the oncology outpatient unit of Hôtel-Dieu de France hospital (November 2017-June 2019; Ethical approval number: CEHDF1016). All patients gave their written informed consent and completed several validated scales, including the Hospital Anxiety and Depression scale (HADS) for the assessment of anxiety and depression. Sleep quality, insomnia, cognitive function, fatigue and pain were also evaluated. Genotyping for certain gene polymorphisms (CLOCK, PER2, CRY2, OPRM1, ABCB1, COMT, DRD2) was performed using the Lightcycler® (Roche). RESULTS: A total of 112 women was included. The prevalence of depression was 43.4%, and 56.2% of the patients reported anxiety (based on the HADS classification). Multivariable analysis showed that higher cognitive scores and taking fosaprepitant were significantly associated with lower depression and anxiety scores. Moreover, being married compared to single was also associated with lower depression scores, whereas higher PSQI scores (worse sleep quality) and having the PER2 AA variant genotype compared to GG were significantly associated with higher depression scores. Finally, reporting a more severe insomnia and having the COMT Met/Met genotype were significantly associated with a higher anxiety score. CONCLUSIONS: Our study demonstrated a strong relationship between depression scores and cognitive impairment, sleep quality, marital status, fosaprepitant intake, and PER2 polymorphism, while anxiety scores were correlated to cognitive impairment, insomnia severity, fosaprepitant intake, and COMT polymorphism. The association with PER polymorphism was not previously reported. Identification of genetic and clinical risk factors for anxiety and depression would help clinicians implement an individualized management therapy aiming at preventing and alleviating the burden of these symptoms in breast cancer patients, hence improving their overall quality of life.

Clinical and Genetic Factors Associated With the Breast Cancer-Related Sleep Disorders: The "CAGE-Sleep" Study-A Cross-Sectional Study.

CONTEXT: Despite being among the most reported concerns in breast cancer patients, sleep disturbances are still poorly assessed and managed in routine clinical practice. Correctly evaluating these symptoms and understanding the underlying clinical and genetic factors would help medical teams develop an adequate treatment strategy for each patient. OBJECTIVES: 1) To explore the severity of insomnia as well as sleep quality in a sample of Lebanese women with breast cancer undergoing chemotherapy; 2) To examine the correlation between sociodemographic, clinical, psychiatric (anxiety and depression), genetic factors, and alterations in sleep patterns. METHODS: A cross-sectional study was carried out using the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) (December 2017-June 2019; Ethical reference number: CEHDF1016). All patients gave their written consent and were genotyped for several polymorphisms in CLOCK, CRY2, PER2, COMT, DRD2, OPRM1, and ABCB1 genes using Lightcycler® (Roche). RESULTS: Our sample included a total of 112 women. Almost half of the patients reported insomnia problems (with 20.5% moderate insomnia and 7.1% severe insomnia). Multivariable analyses taking the PSQI score as the dependent variable, showed that higher depression score and dyslipidemia (yes versus no) were significantly associated with higher PSQI scores (worse sleep quality), whereas having the DRD2 CT genotype versus CC and a higher chemotherapy cycle number were significantly associated with lower PSQI scores (better sleep quality). Depression was also significantly associated with higher ISI scores. When forcing all the genes in each model, the results remained the same except for depression that has been replaced by anxiety in the multivariable analysis. CONCLUSION: Our study confirms the relationship between anxiety/depression, cycle number, dyslipidemia and DRD2 polymorphism with insomnia and highlights the importance of treating all associated factors to improve the overall QOL of patients.

Lung cancer and immunotherapy: a real-life experience from second line and beyond.

Aim: This study assessed the efficacy of anti-PD-1/PD-L1 agents in real life when used in second line or beyond. Materials & methods: Patients with advanced non-small-cell lung cancer progressing after standard chemotherapy and receiving immunotherapy in the second line or beyond were included. Results: One hundred and ten patients were included with PD-L1 expression above 50%, between 1-49 and <1% in 38.6, 27.3 and 34.1% of patients, respectively. Checkpoint inhibitors were used as second, third and fourth line in 74.7, 21.8 and 3.5%, respectively. Partial response was observed in 25.6% of patients. Median progression-free survival was 4 months and median overall survival was 8.1 months. Conclusion: Immunotherapies are emerging as important tools in the oncologic field with good responses in real-life practice.

Analysis of Survival of Patients with Chronic Myeloid Leukemia Treated with Imatinib in the Last 15 Years in Lebanon.

BACKGROUND: In the 2000s, the introduction of the tyrosine kinase inhibitor (TKI), imatinib, improved the survival outcomes of patients with chronic myeloid leukemia (CML). In Lebanon, we rapidly adopted this treatment strategy. To the best of our knowledge, this is the first study reporting the survival rates of Lebanese CML patients. We examined the rates of major molecular response (MMR) and complete cytogenetic response (CCyR) and analyzed the overall survival, progression-free survival, and event-free survival of CML patients treated with front-line imatinib in 3 university hospitals in Lebanon. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 46 patients diagnosed with CML and treated with front-line imatinib 400 mg/day from 2000 and followed up to 2015. In all patients, initially, 2 diagnostic tests were performed: cytogenetic analysis and qualitative molecular testing of the BCR-ABL transcript. The male-to-female sex ratio was 3:1. The median age at diagnosis was 49 years, and the mean age was 44.52 years. At diagnosis, 46 patients were in the chronic phase. All patients started imatinib 400 mg/day. Of the 46 patients, 35 had a typical karyotype, 8 an atypical karyotype, and 3 hypoploidism. RESULTS: The MMR rate at 18 months was 58.69%. The cumulative CCyR rate at 18 months of therapy with imatinib at the standard dose was 67.39%. The event-free survival rate was 75.86% and 74.14% at 5 and 8 years, respectively. The progression-free survival rate was 77.59% and 75.86% at 5 and 8 years, respectively. The overall survival rate was 98.27% and 98.27% at 5 and 8 years, respectively. Of the 46 patients, 12 developed disease progression and were salvaged by second-generation TKIs. These 12 patients were still alive with a MMR. CONCLUSION: In our study population, the achievement of a MMR and CCyR and overall survival, progression-free survival, and event-free survival were similar to previous published data. Reaching high survival rates with a first-generation TKI in a country with limited resources is a reasonable treatment approach for CML patients.

Survival Pattern of Hodgkin Lymphoma Patients in the Last 25 Years in Lebanon.

CONTEXT: After the emergence of combination chemotherapy in 1960s, survival of patients with Hodgkin lymphoma (HL) has dramatically improved worldwide. We lack studies that document the favorable evolution of survival regarding this disease in Lebanon. OBJECTIVE: To compare the overall survival in HL over 3 different decades in Lebanon. METHODS: We retrospectively reviewed the charts of 196 patients diagnosed with HL, treated and followed from 1990 to 2015 in our center. Patients were divided into 3 groups according to period of analysis: group A (1990-1999), group B (2000-2009), and group C (2010-2015). We studied the characteristics and survival patterns of patients in each group. RESULTS: The male-to-female sex ratio was 1.06. The median age at diagnosis was 33 years in group A, 30.4 in group B, and 33.12 in group C (P = .6). Results showed variations in the subtypes of the disease according to the following: nodular-sclerosis HL 59.5% in group A, 76.2% in group B, and 85.4% in group C. Mixed cellularity HL 21.6% in group A, 2.4% in group B, and 73.7% in group C (P = .0001). Patients presented with localized disease in 58.6%, 73.7%, and 56.4% in groups A, B, and C, respectively (P = .173). Complete remission was achieved in 76.5% in group A, 85.3% in group B, and 69.5% in group C (P = .007). The survival rate at 5 years in group A was 91%, 94% in group B, and 100% in group C. CONCLUSION: The survival of patients with HL has dramatically improved over the past 25 years in Lebanon. These results resemble those achieved in Western countries due to the fast adoption of new molecular imaging technologies at diagnosis and follow-up and the rapid approval of new drugs for relapse in the Lebanese market.

Real-life Experience for Integration of PET-CT in the Treatment of Hodgkin Lymphoma in Lebanon.

BACKGROUND: Hodgkin lymphoma (HL) is a highly curable disease; < 80% of patients will achieve long-term survival. Positron emission tomography-computed tomography (PET-CT) has played a major role in the evaluation of both disease staging and response and has become an essential component in tailoring patients' treatment. We report the effect of integrating PET-CT into the management of HL in Lebanon. PATIENTS AND METHODS: We analyzed the data regarding the usage of PET-CT at diagnosis, during treatment (interim PET), and at the end of treatment. We also analyzed the PET-CT findings from 2009 to 2015. RESULTS: The first PET-CT system was introduced in Lebanon in April 2002 but was not used for the evaluation of HL. Early in 2009, we started to incorporate PET-CT into the treatment of HL. By the end of 2009, 70% of patients were undergoing PET-CT at diagnosis and at the end of treatment. This proportion remained constant until 2013, when an increase occurred, with ≤ 94% of patients undergoing PET-CT at diagnosis. The usage of CT at diagnosis decreased significantly from 70% before 2009 to 52% after 2015. In contrast, CT usage at the end of treatment has fluctuated from 10% in 2009 to 0% in 2012, 2013, and 2014 and 11.76% in 2015. CONCLUSION: Functional imaging techniques are increasing in popularity compared with anatomic imaging. The usage of PET-CT has emerged as a highly valuable staging and follow-up method in the treatment of HL 8 years after the introduction of PET in Lebanon. PET was used first to improve the staging, then to evaluate the treatment response, and, recently, to tailor therapy according to the response.

Bellini duct carcinoma: two case reports.

UNLABELLED: We report two rare cases of Bellini duct carcinoma, a rare variant of renal cell carcinoma. CASE 1: The patient, a 73-year-old female, was admitted to the hospital for macroscopic hematuria and right flank pain. She was diagnosed to have a stage IV Bellini duct carcinoma. There was a progression of the disease despite chemotherapy. She died 21 months later. CASE 2: The patient, an 81-year-old male, was admitted to the hospital for generalized fatigue, weight loss and left flank pain. He was diagnosed to have a stage IV Bellini duct carcinoma. The patient was treated with chemotherapy; he died six months later. We report the clinicopathological features of two cases of Bellini duct carcinoma in order to contribute to the related literature of this rare disease.

A collaborative nationwide lymphoma study in Lebanon: incidence of various subtypes and analysis of associations with viruses.

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.

Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience.

BACKGROUND: Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. METHODS: 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU) and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. RESULTS: This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96%) had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy) was completed by 22 patients (91.7%). Only 7 patients (36.8%) completed the total planned courses of chemotherapy. 2 local relapses (10%), 2 regional relapses (10%) and 2 distant relapses (10%) were recorded. Time to progression has not been reached. 9 patients (37.5%) died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8%) with 9 (36%) patients suffering grade 3 or 4 toxicity and 5 patients (20%) suffering from grade 3 or 4 neutropenia. 4 (17%) patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17%) and 1 patient developed a deep venous thrombosis and a pulmonary embolus. CONCLUSIONS: Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the full planned courses of chemotherapy. This is due to hematological toxicity, mainly febrile neutropenia. This should prompt us to review the subsequent chemotherapy protocol and make it more tolerable.

Weekly docetaxel, zoledronic acid and estramustine in hormone-refractory prostate cancer (HRPC).

Treatment options for patients with hormone refractory prostate cancer (HRPC) showed unsatisfactory outcomes. Docetaxel-based combinations could offer more promising and tolerated results. A phase II trial was conducted with the combination of zoledronic acid, docetaxel and estramustine. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen levels (PSA) despite androgen deprivation therapy. Zoledronic acid was given at a dose of 4 mg on day 1, docetaxel (25 mg/m2) on days 1, 8 and 15, and estramustine orally at 140 mg two times daily on days 1 to 21 of a 28-day cycle. Twenty-seven patients were enrolled between October 2002 and November 2004. Median age was 68 years (53-83 years). A total of 124 cycles were administered with a median of 4.6 cycles per patient (1-8 cycles). The major toxicities were grades 1 to 3 anemia (55%), fatigue (15%), alopecia (11%) and hypocalcemia (11%). Two patients presented with deep venous thrombosis and died from pulmonary embolism. Another third patient died from Stevens-Johnson syndrome and grade 4 hepatic toxicity. Out of the 25 patients assessed for efficacy, 13 (52%) had a biologic response (>50% PSA decline). Three (21%) patients among the 14 with measurable disease had objective response: 1 complete response (CR) and 2 partial responses (PR). Response duration was 2 months for PR and 4 months for CR. A total of 12 patients (48%) experienced clinical benefit with pain reduction. This combination seemed effective; however toxic deaths especially from venous thrombosis counterbalanced the advantage of this regimen.

Gemcitabine plus carboplatin combination therapy as second-line treatment in patients with relapsed breast cancer.

This study was designed to determine the safety and efficacy of the combination therapy of gemcitabine plus carboplatin when used as a second-line treatment in patients with metastatic breast cancer (MBC). From February 2002 to May 2003, 30 previously treated patients with adenocarcinoma of the breast received gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin to an area under the curve (AUC) of 5 on day 1. The carboplatin dose was changed to an AUC of 4.5 because of toxicity, with cycles repeated every 3 weeks. Among 30 patients enrolled, 25 were assessable for response rate (RR). There was no complete response; 9 patients (30%) had partial response, for an overall RR of 30%. The median time to progression for the study group was 20.47 weeks (range, 8-46 weeks). Treatment-related toxicities included grade 3/4 neutropenia in 50% of patients (20% of whom had febrile neutropenia), grade 3/4 anemia in 26.6% of patients, and grade 3/4 thrombocytopenia in 30%. Eleven patients (36.67%) had grade 1 alopecia, and 1 patient (3.33%) had grade 2 alopecia. Moderate nausea was observed in 8 patients (26.67%), and vomiting occurred in 7 patients. Four patients had asthenia and 3 (10%) experienced stomatitis. Three patients discontinued treatment because of hematologic toxicity (thrombocytopenia) and 2 patients are still receiving treatment. Carboplatin plus gemcitabine is an active combination for patients with MBC despite significant but manageable hematologic toxicity.