The impact of young age (< 40 years) on the outcome of a cohort of patients with primary non-metastatic breast cancer: analysis of 10-year survival of a prospective study.

BACKGROUND: The role of young age (< 40 years) at diagnosis as an independent risk factor for adverse outcomes in female patients with breast cancer has been highlighted in several studies. In this prospective study, we assessed the difference in 10-year survival between two groups of patients diagnosed with non-metastatic breast cancer based on an age cutoff of 40 years. We also assessed the impact of factors including tumor characteristics, molecular markers and immunohistochemical markers on survival outcomes, highlighting the interaction of those variables with age. METHODS: A total of 119 female patients with newly diagnosed non-metastatic breast cancer were recruited at the American University of Beirut Medical Center (AUBMC) between July 2011 and May 2014. Patients were recruited and divided into 2 age groups (< 40 and ≥ 40 years). In addition to clinical characteristics, we assessed immunohistochemistry including estrogen, progesterone and HER2 receptors, p53, cyclin B1, vascular endothelial growth factor receptor (VEGFR), and ki-67. Germline BRCA mutations were also performed on peripheral blood samples. Patient and tumor characteristics were compared between the age groups. 10-year overall survival (OS) and disease-free survival (DFS) were estimated accordingly. Cox regression analysis was performed in order to assess the effect of the different variables on clinical outcomes. RESULTS: After a median Follow-up of 96 (13-122) months, the estimated 10-year OS was 98.6% for patients ≥40 as compared to 77.6% in patients < 40 (p = 0.001). A similar trend was found for 10-year DFS reaching 90% for patients ≥40 and 70.4% for those < 40 (p = 0.004). On multivariate analysis for DFS and OS, only younger age (< 40 years), higher stage and triple negative phenotype among other parameters assessed significantly affected the outcome in this cohort. CONCLUSION: This prospective study confirms the association between younger age and adverse survival outcomes in patients with non-metastatic breast cancer. Future studies of the whole genome sequences may reveal the genomic basis underlying the clinical differences we have observed.

A phase II single arm study of Nivolumab with stereotactic Ablative radiation Therapy after induction chemotherapy in CHOlangiocarcinoma (NATCHO).

BACKGROUND: Intrahepatic cholangiocarcinoma (CCA) is amongst the most common primary liver tumors worldwide. CCA carries a bad prognosis prompting research to establish new treatment modalities other than surgery and the current chemotherapeutic regimens adopted. Hence, this trial explores a new therapeutic approach, to combine stereotactic body radiation therapy (SBRT) and immunotherapy (Nivolumab), and asses its clinical benefit and safety profile after induction chemotherapy in CCA. METHODOLOGY: This is a Phase II open-label, single-arm, multicenter study that investigates Nivolumab (PD-1 inhibitor) treatment at Day 1 followed by SBRT (30 Gy in 3 to 5 fractions) at Day 8, then monthly Nivolumab in 40 patients with non-resectable locally advanced, metastatic or recurrent intrahepatic or extrahepatic CCA. Eligible patients were those above 18 years of age with a pathologically and radiologically confirmed diagnosis of non-resectable locally advanced or metastatic or recurrent intrahepatic or extrahepatic CCA, following 4 cycles of cisplatin-based chemotherapy with an estimated life expectancy of more than 3 months, among other criteria. The primary endpoint is the progression free survival (PFS) rate at 8 months and disease control rate (DCR). The secondary endpoints are overall survival (OS), tumor response rate (TRR), duration of response, evaluation of biomarkers: CD3 + , CD4 + and CD8 + T cell infiltration, as well as any change in the PD-L1 expression through percutaneous core biopsy when compared with the baseline biopsy following 1 cycle of Nivolumab and SBRT. DISCUSSION: SRBT alone showed promising results in the literature by both inducing the immune system locally and having abscopal effects on distant metastases. Moreover, given the prevalence of PD-L1 in solid tumors, targeting it or its receptor has become the mainstay of novel immunotherapeutic drugs use. A combination of both has never been explored in the scope of CCA and that is the aim of this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT04648319 , April 20, 2018.

Proportion of cancers attributable to major lifestyle and environmental risk factors in the Eastern Mediterranean region.

Cancer is a major contributing cause of morbidity and mortality in the Eastern Mediterranean region. The aim of the current study was to estimate the cancer burden attributable to major lifestyle and environmental risk factors. We used age-, sex- and site-specific incidence estimates for 2012 from IARC's GLOBOCAN, and assessed the following risk factors: smoking, alcohol, high body mass index, insufficient physical activity, diet, suboptimal breastfeeding, infections and air pollution. The prevalence of exposure to these risk factors came from different sources including peer-reviewed international literature, the World Health Organization, noncommunicable disease Risk Factor Collaboration, and the Food and Agriculture Organization. Sex-specific population-attributable fraction was estimated in the 22 countries of the Eastern Mediterranean region based on the prevalence of the selected risk factors and the relative risks obtained from meta-analyses. We estimated that approximately 33% (or 165,000 cases) of all new cancer cases in adults aged 30 years and older in 2012 were attributable to all selected risk factors combined. Infections and smoking accounted for more than half of the total attributable cases among men, while insufficient physical activity and exposure to infections accounted for more than two-thirds of the total attributable cases among women. A reduction in exposure to major lifestyle and environmental risk factors could prevent a substantial number of cancer cases in the Eastern Mediterranean. Population-based programs preventing infections and smoking (particularly among men) and promoting physical activity (particularly among women) in the population are needed to effectively decrease the regional cancer burden.

Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma.

BACKGROUND: Current standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy. This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer. METHODS: The study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6 cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression. DISCUSSION: Recent studies show an increase in PD-L1 expression and density of CD8+ TILs after CRT in rectal cancer patients, implying a potential role for combinatory strategies using PD-L1- and programmed-death- 1 inhibiting drugs. We aim through this study to evaluate pCR following SCRT, followed by mFOLFOX-6 with avelumab, and then TME procedure in patients with LARC. TRIAL REGISTRATION: Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT03503630, April 20, 2018.

The unveiling of a new risk factor associated with bladder cancer in Lebanon.

BACKGROUND: No accurate evaluation of smoking and water pollution on bladder cancer has been conducted in the Lebanese population. Our aim is to examine the significance of smoking and one of the main water pollutants Trihalomethanes (THM) on bladder cancer risk. METHODS: Population Attributable Fraction (PAF) was used to quantify the contribution of the risk factors smoking and THMs on bladder cancer in Lebanon. To calculate PAF for each risk factor, we used the proportion of the population exposed and the relative risk for each risk factor. Relative risks for each risk factor were obtained from published meta-analyses. The population at risk values were obtained from a report on chronic disease risk factor surveillance in Lebanon which was conducted by the World Health Organization between 2008 and 2009 and a national study by Semerjian et al. that conducted a multipathway exposure assessment of selected public drinking waters of Lebanon for the risk factors smoking and THMs, respectively. RESULTS: Bladder cancer cases that were the result of smoking in Lebanon among males and females are 33.4 and 18.6%, respectively. Cases attributed to mid-term exposure to THM contamination of drinking water is estimated at 8.6%. CONCLUSION: This paper further highlights the negative impact of smoking on bladder cancer risk and adds an overlooked and often underestimated risk that THMs have on this type of cancer. Thus, it is imperative that a national based study which assesses THM exposure by gender and smoking status be implemented to determine the real risk behind this byproduct.

Gut Microbiome: A Promising Biomarker for Immunotherapy in Colorectal Cancer.

Research has been driven towards finding therapy predictive biomarkers for colorectal cancer (CRC) with a special interest in studying the gut microbiome. Gut microbiome acts not only as a barrier to prevent bacterial invasion and infection, but it also affects the efficacy of hematopoietic-cell transplantation, chemotherapy, and immunotherapy. Recently, immunotherapy, which potentiates the host immune system, has revolutionized cancer therapy in general and CRC treatment specifically by increasing the quality of life and the survival of a subset of patients with this disease. In immunotherapy, the gut microbiome plays an important role in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade, programmed cell death protein 1 (PD-L1) mediation, and T cell stimulation. As such, this review will cover the role of gut microbiome in CRC, summarize approved immunotherapy treatments for CRC, and focus on the potential use of gut microbiome as a biomarker for immunotherapy.

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.

Proportion of cancer in a Middle eastern country attributable to established risk factors.

BACKGROUND: Providing an estimate of the percentage of cancer in Lebanon by 2018 that is due to the exposure to risk factors in 2008. Factors include: smoking, body mass index (BMI), physical inactivity, dietary factors, alcohol consumption, infections, and air pollution in adults. METHOD: Population Attributable Fraction (PAF) was calculated using the proportion of the population exposed and relative risks for each risk factor from meta-analyses. The PAF estimates the proportion of cases in which exposure may have played a causal role. RESULTS: Smoking caused most cancer cases, and it will further add a total of 1800 new cases by 2018. Among many other cancers, lung cancer had the largest proportion attributable of around 75%. BMI is expected to increase colorectal, liver and gastric cardia carcinoma specifically in males. High physical activity has a an average of 15% protection rate on cancer on colorectal cancer. Minimal adherence to Mediterranean diet will affect gastric cancer incidence by 7%. Cases of oropharyngeal and esophageal cancer will be the result of alcohol consumption mainly in males. H.Pylori infection is expected to result in half of the gastric cases by 2018. The high exposure to air pollution is expected to contribute by 13% to lung cancer cases in 2018. CONCLUSION: The highest benefits can be achieved by controlling tobacco smoking. Interrelated and small changes in weight, physical activity and healthy diet with limited alcohol consumption can protect against several GI cancers in the long run. These results can be used to determine public health interventions that target important risk factors in the general population.

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

BACKGROUND: The 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. METHODS: Using 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. RESULTS: Between 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. CONCLUSION: The 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.

Preoperative lymphocyte-to-monocyte ratio predicts clinical outcome in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder: a retrospective analysis.

BACKGROUND: Inflammation is a critical component of tumorigenesis, and many cancers arise from sites of infection, chronic irritation, and inflammation. Inflammatory cytokines triggered by tumors alter hematologic components, including neutrophil, lymphocyte, and monocyte counts. The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios have been shown to be valuable prognostic markers in various types of cancers, including bladder cancer. Risk stratification based on clinicopathologic data is insufficient to support treatment-related choices in patients with bladder cancer. Novel prognostic markers are therefore needed. An elevated pretreatment lymphocyte-to-monocyte ratio (LMR) is reportedly associated with improved overall survival (OS) and a longer time to treatment recurrence (TTR) in some types of cancers. However, these data are lacking in patients with bladder cancer. The aim of the present study was to investigate the effect of the preoperative LMR on OS and TTR in a cohort of patients with bladder cancer. METHODS: Sixty-eight patients with transitional cell carcinoma of the bladder were included in this retrospective analysis. The associations between a high and low LMR with OS and TTR were analyzed using Kaplan-Meier curves and compared by the log-rank test. RESULTS: In our study cohort, an elevated preoperative LMR was significantly associated with an increased TTR (P = 0.001) and OS (P = 0.020). Patients with an LMR of ≤2.87 showed a median TTR of 2.0 years (95% CI, 0.27-3.73), whereas patients with an LMR of >2.87 had a median TTR of 11.1 years (95% CI, 2.31-19.88) (P = 0.001). Patients with an LMR of ≤2.81 showed a median OS of 2.7 years (95% CI, 0.63-4.70), whereas patients with an LMR of >2.81 had a median OS of 6.0 years (95% CI, 3.60-8.40) (P = 0.020). The clinical stage at diagnosis was the only clinicopathologic feature associated with the LMR, while tumor invasion depth showed borderline significance. CONCLUSIONS: The LMR is an easily measured and inexpensive prognostic marker that was significantly correlated with OS and TTR in the present retrospective analysis. However, because of the small sample size in this study, larger multicenter, prospective studies are needed.

Colorectal Cancer Screening in the Middle East: What, Why, Who, When, and How?

The incidence of colorectal cancer (CRC) in the Middle East is increasing, especially among those younger than 50 years. Risk factors including obesity, sedentary lifestyle, and dietary changes are associated with the epidemiologic shift and are a result of socioeconomic changes happening in the region. Worldwide, CRC screening is associated with decreased incidence and mortality of CRC, but screening uptake is still low in the Middle East because of cultural barriers and lack of awareness; in addition, most countries do not have national screening programs. Knowledge of CRC screening and participation rates vary among different countries, but overall they are low. Both primary and secondary prevention approaches are needed in the Middle East, and cost-effectiveness is important in choosing screening modalities. Although colonoscopy is considered the most robust screening method, stool-based testing may be an acceptable screening strategy in resource-limited settings, and focusing on high-risk individuals such as those with hereditary CRC might be the most cost-effective strategy. In addition to financial limitations in many countries in the Middle East, human displacement places an extra toll on cancer control strategies in the region.

Maintenance chemotherapy in advanced and metastatic pancreatic cancer, a narrative review and case series.

Limited data exist on the management of patients with locally advanced (aPC) or metastatic pancreatic (mPC) cancer who achieve stable disease/response after first-line chemotherapy. In this setting, maintenance therapy is important to minimize toxicity while preserving survival benefits. The aim of this study is to conduct a narrative review of the evidence available on the topic and present the results of a retrospective case series of patients with aPC or mPC who received maintenance therapy following a good response to induction chemotherapy. Olaparib is the only drug approved for maintenance therapy in patients with metastatic pancreatic cancer and germline Breast Cancer gene mutation. Data from several trials, including the phase II PANOPTIMOX-PRODIGE35 trial, showed clinical benefit from the use of 5-fluorouracil (5-FU) as maintenance. We also conducted a case series including 12 patients who received FOLFIRINOX as induction chemotherapy for aPC or mPC followed by fluorouracil (5-FU) or FOLFIRI maintenance therapy. Median progression-free survival is 22.13 months which is higher than that reported in the literature, which ranges between 5 and 10.6 months. Although further conclusions cannot be drawn because of the small sample size, the results are promising and encourage further exploration of this topic in larger prospective trials.

Well-differentiated gastro-entero-pancreatic neuroendocrine tumors with positive FDG-PET/CT: a retrospective chart review.

PURPOSE: Rarely, well-differentiated gastro-entero-pancreatic neuroendocrine tumors (GEP NETs) can have positive uptake on 18F-fluorodeoxyglucose-PET/computerized tomography ( 18 F-FDG-PET/CT), with or without a positive 68 Ga-PET/CT. We aim to evaluate the diagnostic role of 18 F-FDG-PET/CT in patients with well-differentiated GEP NETs. METHODS: We retrospectively reviewed a chart of patients diagnosed with GEP NETs between 2014 and 2021, at the American University of Beirut Medical Center, who have low (G1; Ki-67 ≤2) or intermediate (G2; and Ki-67 >2-≤20) well-differentiated tumors with positive findings on FDG-PET/CT. The primary endpoint is progression-free survival (PFS) compared to historical control, and the secondary outcome is to describe their clinical outcome. RESULTS: In total 8 out of 36 patients with G1 or G2 GEP NET met the inclusion criteria for this study. The median age was 60 years (range 51-75 years) and 75% were male. One patient (12.5%) had a G1 tumor whereas 7 (87.5%) had G2, and seven patients were stage IV. The primary tumor was intestinal in 62.5% of the patients and pancreatic in 37.5%. Seven patients had both 18 F-FDG-PET/CT and 68 Ga-PET/CT positive and one patient had a positive 18 F-FDG-PET/CT and negative 68 Ga-PET/CT. Median and mean PFS in patients positive for both 68 Ga-PET/CT and 18 F-FDG-PET/CT were 49.71 months and 37.5 months (95% CI, 20.7-54.3), respectively. PFS in these patients is lower than that reported in the literature for G1/G2 NETs with positive 68 Ga-PET/CT and negative FDG-PET/CT (37.5 vs. 71 months; P = 0.0217). CONCLUSION: A new prognostic score that includes 18 F-FDG-PET/CT in G1/G2 GEP NETs could identify more aggressive tumors.

Preferences for the sequencing of first-line systemic treatments in metastatic hormone receptor-positive, HER2-negative breast cancer.

Introduction: Metastatic breast cancer (MBC) is a diverse disease. Therapeutic options include hormonal therapy, chemotherapy, and targeted therapies. The optimal treatment sequence for patients with hormone receptor-positive (HR-positive), HER2-negative metastatic breast cancer remains unknown. Methods: This was a retrospective and prospective study. The data was collected from the medical records of patients in a tertiary healthcare center in Lebanon between the years 2016 and 2019, and patients were followed up for a 3-year duration. The main aim was to identify oncologists' preferences in the choice and sequence of treatment for newly diagnosed and/or recurrent cases of HR-positive, HER2-negative MBC. Results: A total of 51 patients were included. 24 patients received chemotherapy, while 27 received endocrine therapy as first-line treatment after a diagnosis of MBC, with a median overall survival (OS) of 13 months and a median progression-free survival (PFS) of 12 months after first-line treatment with chemotherapy, compared to 27 months and 18 months with endocrine therapy. A higher percentage of patients have received chemotherapy in the first-line setting compared to the data reported in the literature, with the choice being multifactorial. Conclusion: Factors to consider in MBC management include the choice of first-line treatment, the optimal sequence of treatment, and the combination of available treatment options.

Can plasma vitamin C predict survival in stage IV colorectal cancer patients? Results of a prospective cohort study.

Background and Aims: In light of the inconclusive evidence on the association between vitamin C status and colorectal cancer (CRC) outcome, this study assessed the prognostic value of vitamin C in participants with metastatic CRC (mCRC). Methods: Adults with mCRC and cancer-free controls were recruited in this prospective cohort study to allow for comparison of vitamin C levels with healthy individuals from the same population. Sociodemographic, lifestyle, medical variables, BRAF and KRAS mutations, as well as Vitamin C plasma level and food intake were evaluated. Predictors of diminished vitamin C level were assessed via multivariate logistic regression. Mortality and progression free survival (PFS) among mCRC participants were analyzed based on plasma vitamin C level. Results: The cancer group (n = 46) was older (mean age: 60 ± 14 vs. 42 ± 9.6, p = 0.047) and included more males (29% vs. 19%, p < 0.001) than the cancer-free group (n = 45). There was a non-significant difference in the vitamin C intake between the two groups; however, the mean plasma vitamin C level was lower in the cancer group (3.5 ± 3.7 vs. 9.2 ± 5.6 mg/l, p < 0.001). After adjusting for age and gender, the cancer group was more likely to be deficient compared to the cancer-free group [Adjusted Odds Ratio (95%CI): 5.4 (2.1-14)]. There was a non-significant trend for higher mortality in the vitamin C deficient cancer group (31% vs. 12%, p = 0.139). PFS did not differ based on vitamin C deficiency and patients with BRAF and KRAS mutations did not have significant differences in vitamin C levels. Conclusion: mCRC patients have lower plasma vitamin C levels than healthy controls. The trend toward higher mortality in the vitamin C deficient cancer group was not statistically significant. Whether this phenomenon affects survival and response to treatment warrants further exploration in phase III clinical trials.

Breast cancer knowledge in Lebanese females with positive family history.

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer-related death worldwide. Positive family history increases the likelihood of developing this disease. As late-stage presentation and poor survival rates are associated with a lack of knowledge about breast cancer and its screening methods, this study aimed to evaluate the knowledge of Lebanese women with first-degree relatives who were diagnosed with breast cancer. In this cross-sectional study, 200 women with a positive family history accompanying their relatives to oncology clinics or the infusion center at the American University of Beirut Medical Center, completed an online survey after institutional review board approval was granted. Demographic information and answers to questions related to breast cancer risk factors, warning signs, and screening techniques were collected and analyzed using descriptive statistics and chi-square tests. Eighty-one percent of the study participants agreed that a history of breast cancer is associated with a higher disease risk. The smaller portions were aware of other potential risk factors, such as hormone replacement therapy, alcohol consumption, late menopause, early menarche, and overweight and sedentary lifestyles. Also, 93% to 96.5% of the participants recognized breast self-examination and mammography as useful tools for early detection. Furthermore, younger participants who reached university level and were employed had more insights into breast cancer. Breast cancer knowledge and early diagnosis are key elements in preventing late presentations and reducing the associated morbidity and mortality. Further educational and awareness campaigns should be conducted in Lebanon to improve women knowledge of breast cancer.

Improved Survival of Young Patients With Breast Cancer 40 Years and Younger at Diagnosis.

PURPOSE: Around 50% of patients with breast cancer in low- or middle-income countries are younger than 50 years, a poor prognostic variable. We report the outcome of patients with breast cancer 40 years and younger. METHODS: We reviewed 386 patients with breast cancer 40 years and younger and retrieved demographic, clinicopathologic, treatment-related, disease progression, and survival data from electronic medical records. RESULTS: The median age at diagnosis was 36 years, and infiltrating ductal carcinoma was present in 94.3% of patients, infiltrating lobular carcinoma in 1.3%, and ductal carcinoma in situ in 4.4%. Grade 1 disease was present in 8.5% of patients, grade 2 in 35.5%, and grade 3 in 53.4%; 25.1% had human epidermal growth factor receptor 2 (HER2)-positive, 74.6% had hormone receptor (HR)+, and 16.6% had triple-negative breast cancer. Early breast cancer (EBC) constituted 63.6% (stage I, 22.4%; stage II, 41.2%) of patients, whereas 23.2% had stage III, and 13.2% had metastatic disease at diagnosis. Of patients with EBC, 51% had partial mastectomy and 49.0% had total mastectomy. And 77.1% had chemotherapy with or without anti-HER2 therapy. All HR+ patients received adjuvant hormonal therapy. The disease-free survival at 5 years was 72.5% and 55.9% at 10 years. The overall survival (OS) was 89.4% at 5 years and 76% at 10 years. Patients with stages I/II had an OS of 96.0% at 5 years and 87.1% at 10 years. Patients with stage III had an OS of 88.3% at 5 years and 68.7% at 10 years. The OS of patients with stage IV was 64.5% at 5 years and 48.4% at 10 years. CONCLUSION: We report survival rates of 89% at 5 years and 76% at 10 years with modern multidisciplinary management. Best results were seen in EBC: OS rates of 96% and 87% at 5 years and 10 years.

Comparison Between Liver Stiffness Measurement by Fibroscan and Splenic Volume Index as NonInvasive Tools for the Early Detection of Oxaliplatin-induced Hepatotoxicity.

Background: Oxaliplatin remains an essential component of many chemotherapy protocols for gastrointestinal cancers; however, neurotoxicity and hepatotoxicity may be dose-limiting. The gold standard for the diagnosis of oxaliplatin-induced hepatotoxicity is liver biopsy, which is invasive and costly. Splenomegaly has also been used as a surrogate for liver biopsy in detecting oxaliplatin-induced sinusoidal obstruction syndrome (SOS), but splenic measurement is not routine and can be inaccurate and complex. We investigated the correlation between increased liver elasticity assessed by Fibroscan and the increase in spleen volume on cross-sectional imaging after oxaliplatin as a noninvasive technique to assess liver stiffness associated with oxaliplatin-induced SOS. Methods: Forty-six patients diagnosed with gastrointestinal cancers and planned to take oxaliplatin containing regimens were included in this prospective study at the American University of Beirut Medical Center (AUBMC). Measurement of spleen volume using cross-sectional imaging and of liver elasticity using Fibroscan was performed at baseline, 3 and 6 months after starting oxaliplatin. Mean liver elasticity measurements were compared between patients stratified by the development of splenomegaly using the Student t-test. Splenomegaly was defined as 50% increase in spleen size compared with baseline. Results: Patients who developed splenomegaly after oxaliplatin use had significantly higher mean elasticity measurements as reported by Fibroscan at 3 (16.2 vs. 7.8 kPa, P = 0.036) and 6 (9.3 vs. 6.7 kPa, P = 0.03) months. Conclusion: Measurement of elasticity using Fibroscan could be potentially used in the future as a noninvasive test for predicting oxaliplatin-induced hepatotoxicity.

Neo-adjuvant FOLFIRINOX in borderline resectable and locally advanced pancreatic adenocarcinoma.

BACKGROUND: Surgery and systemic therapy provide the best option for long-term cancer control in localized resectable pancreas cancer. The present study assessed the efficacy and safety of neoadjuvant treatment with FOLFIRINOX in patients with borderline resectable (BR) and locally advanced (LA) pancreas cancer (PDAC). METHODS: This was a prospective noninterventional observational trial of neoadjuvant FOLFIRINOX in BR and LA PDAC. The primary objective was the R0/R1 surgical resection rate. Secondary objectives included progression free survival (PFS) and overall survival (OS), tolerability, and toxicity. RESULTS: Forty-nine patients were enrolled between 2013 and 2019; the majority had LA disease (59.2%). Median age was 61 years, and median Ca 19-9 level pretreatment was 523.4 µmol/L. Following neoadjuvant FOLFIRINOX, 11 patients (22.5%) underwent surgical resection, the majority of which were BR at diagnosis (72.7%). Median OS and PFS for the entire group were 25 (95% CI: 17.2-32.8) and 12 months (95% CI: 9.7-13.3), respectively. Median PFS in BR patients was 14 (95% CI: 10.5-17.5) compared to 12 months (95% CI: 5.2-18.8) in patients with LA patients. Median OS and PFS were not reached in patients who underwent surgical resection as compared to 22 (95% CI: 18.6-25.4) and 9 months (95% CI: 4.2-13.9) in those who did not, respectively. Grade 3/4 neutropenia, leukopenia, neuropathy, nausea/vomiting, and diarrhea occurred in 6.3%, 2.1%, 10.4%, 4.2%, and 8.3%, respectively. CONCLUSION: Neoadjuvant FOLFIRINOX is an active regimen for patients with LA/BR PDAC with a resection rate of 22.5%. These results are in line with prior data.

Total neoadjuvant therapy in patients with locally advanced rectal cancer: A tertiary medical center experience.

The current standard of care for locally advanced rectal cancer (LARC) includes preoperative chemoradiation, followed by total mesorectal excision and adjuvant chemotherapy. This multimodality treatment improves local control but is associated with low compliance rates without clear beneficial effects on overall survival (OS) and distant metastasis. In this retrospective study, the charts of patients diagnosed with cT3/4 or cT2-node-positive rectal cancer between January 2011 and June 2019 were reviewed. The chemoradiation therapy (CRT) group received a long course of CRT with capecitabine followed by surgery and adjuvant chemotherapy. The total neoadjuvant therapy (TNT) group received 6 cycles mFOLFOX and a short course of radiation therapy followed by surgery. A total of 81 patients were included, among which 55 (67.9%) received CRT and 26 (32.1%) received TNT. In the CRT group, 15 (27.3%) patients achieved pathologic complete response (pCR) compared with 10 (38.5%) in the TNT group (P=0.22). A total of 19 (35.8%) cases in the CRT group downstaged to pT0N0 or pT1N0 compared with 11 (42.3%) in the TNT group (P=0.33). The 2-year disease-free survival (DFS) rate was 81.0% in the TNT group and 84.0% in the CRT group (P=0.15). Out of 55 patients in the CRT group, 30 patients received adjuvant chemotherapy, 22 (40.0% of CRT cases) of which completed a full course. All 26 patients in the TNT group received neoadjuvant chemotherapy, where 22 (84.6%) patients took a full course (P<0.001). In conclusion, the present study revealed that patients treated with TNT were more compliant to chemotherapy than those treated with CRT. A numerically higher pCR rate, and nodal and tumor downstaging were noted in the TNT group without significance. No difference was noted in the 2-year DFS. Longer follow-up is required.