The challenges and clinical landscape of glioblastoma immunotherapy.

Glioblastoma is associated with a dismal prognosis with the standard of care involving surgery, radiation therapy and temozolomide chemotherapy. This review investigates the features that make glioblastoma difficult to treat and the results of glioblastoma immunotherapy clinical trials so far. There have been over a hundred clinical trials involving immunotherapy in glioblastoma. We report the survival-related outcomes of every Phase III glioblastoma immunotherapy trial with online published results we could find at the time of writing. To date, the DCVax-L vaccine is the only immunotherapy shown to have statistically significant increased median survival compared with standard-of-care in a Phase III trial: 19.3 months versus 16.5 months. However, this trial used an external control group to compare with the intervention which limits its quality of evidence. In conclusion, glioblastoma immunotherapy requires further investigation to determine its significance in improving disease survival.

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Prevalence of depression and anxiety among newly diagnosed cancer patients: a single centre experience in the Middle East.

Failure to identify and treat depression and anxiety affecting 10% of patients with cancer, increases the disease burden. This study aimed to assess the psychological well-being of newly diagnosed patients in a tertiary healthcare centre in Lebanon. In this cross-sectional study, data were collected for 187 adult patients, from medical records and interviews using standardised questionnaires (Personal health questionnaire-9 (PHQ-9) and generalised anxiety disorder-7). Karnofsky performance status was also assessed, and incidence was calculated using descriptive statistics, chi-square, and T-tests. The rates of moderate or severe anxiety, minimal anxiety, mild depression, moderate or severe depression, and suicidality are 14.9%, 35.6%, 40.7% 22.7% and 6.2%, respectively. Participants with a past history of seeking help from mental health services (OR: 3.978, CI: (1.680-9.415), p = 0.002), those developing cancer-related complications (OR: 3.039, CI: (1.187-7.777), p = 0.020), and those who had an Eastern Cooperative Oncology Group of ≥2 (OR: 5.306, CI: (1.582-17.797), p = 0.007) were independently associated with depression (diagnosed with PHQ-9) in multivariate logistic regression analysis. Patients with cancer exhibit higher evidence of depression and anxiety and should have a thorough psychiatric history and additional psychiatric care.

Primary alveolar rhabdomyosarcoma of the brain: a case report.

BACKGROUND: Primary brain rhabdomyosarcoma is a rare primary brain malignancy with few case reports. The vast majority of cases of primary brain rhabdomyosarcoma occur in pediatric patients, and immunohistochemistry can distinguish it from embryonal subtypes; however, few cases of primary brain rhabdomyosarcoma in adults have been reported in the literature. CASE PRESENTATION: We report the case of a 26-year-old White male patient who was found to have primary brain alveolar rhabdomyosarcoma after developing headaches for several months. A brain MRI revealed a mixed cystic and solid tumor along the vermis of the cerebellum. The patient underwent a gross total surgical resection, which confirmed the diagnosis of alveolar rhabdomyosarcoma. Further staging workup for another primary focus or disseminated disease yielded negative results, confirming the diagnosis of primary alveolar rhabdomyosarcoma of the brain. CONCLUSION: The standard of care for managing this rare type of brain tumor involves surgery with adjuvant chemoradiotherapy. Further studies should be conducted for a better diagnostic and therapeutic understanding.

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.

Immunotherapy and immunoevasion of colorectal cancer.

The tremendous success of immunotherapy in clinical trials has led to its establishment as a new pillar of cancer therapy. However, little clinical efficacy has been achieved in microsatellite stable colorectal cancer (MSS-CRC), which constitutes most CRC tumors. Here, we discuss the molecular and genetic heterogeneity of CRC. We review the immune escape mechanisms, and focus on the latest advances in immunotherapy as a treatment modality for CRC. By providing a better understanding of the tumor microenvironment (TME) and the molecular mechanisms underlying immunoevasion, this review offers an insight into developing therapeutic strategies that are effective for patients with various subsets of CRC.

Value of chemotherapy post immunotherapy in stage IV non-small cell lung cancer (NSCLC).

BACKGROUND: Lung cancer is the number one cause of mortality among all types of cancer worldwide. Its treatment landscape has shifted from the classic chemotherapy alone to newer regimens based on the discovery of new immunotherapy and targeted therapy drugs. However, chemotherapy is still an option for treatment of advanced non-small cell lung cancer (NSCLC) after progression on immunotherapy alone or in combination with first-line chemotherapy. METHODS: This is a retrospective study based on chart review of patients diagnosed with advanced NSCLC cases who received Docetaxel as second or third line after being treated by immunotherapy and/or chemotherapy in previous lines. The data was collected from the medical records of physicians' clinics in three different hospital centers in Lebanon over the period of 5 years from July 2015 until December 2020. February 2021 was data analysis cut off time. The main aim was to assess the role of Docetaxel post-chemoimmunotherapy for patients with diagnosed NSCLC. RESULTS: A total of 21 patients were included in this study. The majority of our patients were males (81%). As for histologic type, most patients had non-squamous lung cancer (67%) as compared to 33% who had squamous lung cancer. Overall, our study reported a 24% response rate to Docetaxel including stable disease and partial response and a median progression free survival (PFS) of 3 months. The mean time interval elapsed from diagnosis to the initiation of Docetaxel was 11.5 months. CONCLUSION: New therapeutic options should be validated for the treatment of NSCLC in the second and subsequent lines of therapy considering the poor prognosis of this disease. The chemotherapy in second and third line may keep an important role in the treatment after progression on newer agents, but it needs more evidence in prospective studies including a larger number of patients.

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.

Latest updates on cellular and molecular biomarkers of gliomas.

Gliomas are the most common central nervous system malignancies, compromising almost 80% of all brain tumors and is associated with significant mortality. The classification of gliomas has shifted from basic histological perspective to one that is based on molecular biomarkers. Treatment of this type of tumors consists currently of surgery, chemotherapy and radiation therapy. During the past years, there was a limited development of effective glioma diagnostics and therapeutics due to multiple factors including the presence of blood-brain barrier and the heterogeneity of this type of tumors. Currently, it is necessary to highlight the advantage of molecular diagnosis of gliomas to develop patient targeted therapies based on multiple oncogenic pathway. In this review, we will evaluate the development of cellular and molecular biomarkers for the diagnosis of gliomas and the impact of these diagnostic tools for better tailored and targeted therapies.

Emerging genetic biomarkers in lung adenocarcinoma.

Comprehensive genomic profiling is a next-generation sequencing approach used to detect several known and emerging genomic alterations. Many genomic variants detected by comprehensive genomic profiling have become recognized as significant cancer biomarkers, leading to the development of major clinical trials. Lung adenocarcinoma has become one of the most targeted cancers for genomic profiling with a series of actionable mutations such as EGFR, KRAS, HER2, BRAF, FGFR, MET, ALK, and many others. The importance of these mutations lies in establishing targeted therapies that significantly change the outcome in lung adenocarcinoma besides the prognostic value of some mutations. This review sheds light on the development of the comprehensive genomic profiling field, mainly lung adenocarcinoma, and discusses the role of a group of mutations in this disease.

COVID-19 and lung cancer: update on the latest screening, diagnosis, management and challenges.

Lung cancer, considered one of the most common causes of cancer deaths worldwide, is a complex disease with its own challenges. The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), compounded these challenges and forced the medical healthcare system to alter its approach to lung cancer. This narrative review aims to identify the effect of the COVID-19 pandemic on lung cancer screening, diagnosis and management. During this public health crisis, various medical societies have worked on developing guidelines to protect patients with lung cancer from the deleterious effects of SARS-CoV-2 infection, as well as from the complications imposed by treatment delays. The different therapeutic approaches, such as surgery, radiation oncology and immune checkpoint inhibitor therapy, along with the latest international recommendations, will be discussed. Protecting patients with lung cancer from COVID-19 complications, while avoiding barriers in treatment delays, has brought unique challenges to healthcare facilities. Prompt modifications to guidelines, and constant evaluation of their efficacy, are thus needed.

Treatment Strategies for Residual Disease following Neoadjuvant Chemotherapy in Patients with Early-Stage Breast Cancer.

Breast cancer continues to be the most diagnosed cancer among women worldwide. Neoadjuvant chemotherapy is the standard of care for breast cancer patients with locally advanced disease and patients with poor pathological features, such as triple-negative (TN) or human epidermal growth factor receptor-2 (HER2)-positive subtypes. Neoadjuvant therapy offers several advantages, including better surgical outcomes, early systemic treatment for micro-metastases, and accurate tumor biology and chemosensitivity assessment. Multiple studies have shown that achieving pathological complete response (pCR) following neoadjuvant chemotherapy is associated with better prognosis and better treatment outcomes; almost half of such patients may fail to achieve pCR. Tumor proliferative index, hormone receptor (HR) status, and HER2 expression are the major predictors of pCR. Strategies to improve pCR have been dependent on augmenting neoadjuvant chemotherapy with the addition of taxanes and dual anti-HER2 targeted therapy in patients with HER2-positive tumor, and more recently, immunotherapy for patients with TN disease. The clinical management of patients with residual disease following neoadjuvant chemotherapy varies and depends mostly on the level of HR expression and HER2 status. Recent data have suggested that switching trastuzumab to trastuzumab-emtansine (T-DM1) in patients with HER2-positive disease and the addition of capecitabine for patients with HER2-negative and HR-negative subtype is associated with a better outcome; both strategies are incorporated into current clinical practice guidelines. This paper reviews available and ongoing studies addressing strategies to better manage patients who continue to have residual disease following neoadjuvant chemotherapy.

A Survey on the Knowledge, Attitudes, and Practices of Lebanese Physicians Regarding Air Pollution.

INTRODUCTION: Air pollution imposes a significant burden on public health. It is emerging as a modifiable risk factor for cancer, diabetes, and respiratory and cardiovascular diseases. This study aims to assess the knowledge, attitudes, and practices of Lebanese physicians regarding air pollution. METHODS: This observational study uses a descriptive cross-sectional correlational design. The data were collected using a self-administered online survey that was sent to 874 potential respondents who are members of the Lebanese Order of Physicians. Data analysis was done using descriptive statistics and a chi-square test. RESULTS: The results show a deficiency in the knowledge of physicians regarding many sources of air pollution, including dust, the smell of perfume, candles, vacuum cleaners, air fresheners, electronic cigarettes, etc. The majority of physicians agree that air pollution increases the risk of several health problems. Only 38% of physicians routinely ask their patients about exposure to air pollution, and 75% of them believe that they have a role as physicians in reducing air pollution levels. Over half of the sample are confident in counseling their patients on sources of air pollution, and two thirds of them are in support of including assessment of air pollution exposure during regular medical visits. CONCLUSION: Air pollution levels are progressively increasing over time. Given the health impact of exposure to air pollution, healthcare professionals need to stay up to date on this topic. The results of this study suggest the need for continuing education about air pollution for physicians and developing guidelines for what exactly to ask patients in assessing their exposure.

Primary Squamous Cell Carcinoma of the Liver: Case Report and Review of Literature.

Primary squamous cell carcinoma (SCC) of the liver is a rare cancer type. The overall survival of this cancer is short despite treatment and prognosis are poor. To our knowledge, there are around 30 cases of primary SCC of the liver described in the literature. Primary SCC of the liver is thought to be associated with a wide variety of hepatic conditions such as hepatic cyst, hepatolithiasis, or hepatic teratoma. We present the case of a 33-year-old male patient diagnosed with primary keratinizing SCC of liver associated with a hepatic cyst.

MDACT: A New Principle of Adjunctive Cancer Treatment Using Combinations of Multiple Repurposed Drugs, with an Example Regimen.

In part one of this two-part paper, we present eight principles that we believe must be considered for more effective treatment of the currently incurable cancers. These are addressed by multidrug adjunctive cancer treatment (MDACT), which uses multiple repurposed non-oncology drugs, not primarily to kill malignant cells, but rather to reduce the malignant cells' growth drives. Previous multidrug regimens have used MDACT principles, e.g., the CUSP9v3 glioblastoma treatment. MDACT is an amalgam of (1) the principle that to be effective in stopping a chain of events leading to an undesired outcome, one must break more than one link; (2) the principle of Palmer et al. of achieving fractional cancer cell killing via multiple drugs with independent mechanisms of action; (3) the principle of shaping versus decisive operations, both being required for successful cancer treatment; (4) an idea adapted from Chow et al., of using multiple cytotoxic medicines at low doses; (5) the idea behind CUSP9v3, using many non-oncology CNS-penetrant drugs from general medical practice, repurposed to block tumor survival paths; (6) the concept from chess that every move creates weaknesses and strengths; (7) the principle of mass-by adding force to a given effort, the chances of achieving the goal increase; and (8) the principle of blocking parallel signaling pathways. Part two gives an example MDACT regimen, gMDACT, which uses six repurposed drugs-celecoxib, dapsone, disulfiram, itraconazole, pyrimethamine, and telmisartan-to interfere with growth-driving elements common to cholangiocarcinoma, colon adenocarcinoma, glioblastoma, and non-small-cell lung cancer. gMDACT is another example of-not a replacement for-previous multidrug regimens already in clinical use, such as CUSP9v3. MDACT regimens are designed as adjuvants to be used with cytotoxic drugs.

Descriptive epidemiology of soft tissue and bone sarcomas in Lebanon.

OBJECTIVES: Most epidemiologic studies on soft tissue sarcomas (STS) and bone sarcomas (BS) are performed in western countries, with few in the Middle East and North Africa region. We describe the epidemiology of sarcomas in Lebanon using the medical records database at the American University of Beirut Medical Center (AUBMC). METHODS: This single-center retrospective cohort study included patients with sarcomas registered in the database between 2015 and 2019. Their charts were reviewed for baseline characteristics, tumor biology and location, treatment modalities, recurrence, metastasis, and death. RESULTS: The cohort included 234 patients with STS and 99 patients with BS. Most tumors were <10 cm in size. The most common subtypes were liposarcoma for STS and osteosarcoma for BS. The most common location of STS was the thigh. The most frequent sites of STS metastasis were the lungs. Histological subtype, smoking status, and tumor size and grade were significant for progression-free survival (PFS) in patients with STS. By multivariable analysis, smoking was significantly associated with poorer PFS in STS. For BS, only tumor grade was significant for PFS. CONCLUSION: The epidemiology of sarcomas at AUBMC is similar to that previously reported. Smoking history was associated with poorer survival in patients with STS.

Role of circulating tumor DNA and circulating tumor cells in breast cancer: History and updates.

Circulating tumor DNA, cell-free DNA, and circulating tumor cells have been at the epitome of recent research in breast cancer. These forms of liquid biopsies have been used in monitoring disease progression, estimating the risk of relapse, and response to treatment. Much has been done in relation to serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. Some studies have also explored their use in monitoring treatment response. As the field of liquid biopsies expands, more prospective studies are needed to tailor management in an individualistic approach. In this literature review, the authors explore the multiple uses of circulating tumor DNA and circulating tumor cells in breast cancer.

Clinical Significance of Breast Cancer Molecular Subtypes and Ki67 Expression as a Predictive Value for Pathological Complete Response following Neoadjuvant Chemotherapy: Experience from a Tertiary Care Center in Lebanon.

INTRODUCTION: Breast cancer is considered nowadays the most prevalent cancer worldwide. The molecular era has successfully divided breast cancer into subtypes based on the various hormonal receptors. These molecular subtypes play a major role in determining the neoadjuvant chemotherapy to be administered. It was noted that the use of neoadjuvant chemotherapy was associated with higher achievement of pathological complete response. The aim of the study was to determine the predictive role of breast cancer subtypes in the efficacy and prognosis of neoadjuvant chemotherapy regimens. METHODS: Combining dose dense anthracycline-based, regular dose anthracycline-based, and nonanthracycline-based chemotherapy, we observed data from 87 patients with breast cancer who received surgery after administration of neoadjuvant chemotherapy at our institution between January 2015 and July 2018. The patients were classified into luminal A, luminal B, HER2 overexpression, and triple negative breast cancer as well as low Ki67 (≤14%) and high Ki67 (>14%) expression groups using immunohistochemistry. Pathologic complete response was the only neoadjuvant chemotherapy outcome parameter. To evaluate variables associated with pathologic complete response, we used univariate analyses followed by multivariate logistic regression. RESULTS: 87 patients with breast cancer were classified into different subtypes according to the 12th St. Gallen International Breast Cancer Conference. The response rate to neoadjuvant chemotherapy was significantly different (p = 0.046) between the subgroups. There were significant correlations between pathological complete response (pCR) and ER status (p < 0.0001), HER2 (p = 0.013), molecular subtypes (p = 0.018), T stage (p = 0.024), N stage before chemotherapy (p = 0.04), and type of chemotherapy (p = 0.029). Luminal B type patients had the lowest pCR, followed by luminal A type patients. CONCLUSION: Evaluating molecular subtype's significance in breast cancer prognosis warrants additional studies in our region with extensive data about patient-specific neoadjuvant chemotherapy regimens. Our study was able to reproduce results complementary to those present in the literature in other outcomes.

Glioblastoma multiforme metastasizing to the skin, a case report and literature review.

Glioblastoma Multiforme (GBM) is the most common primary central nervous system (CNS) malignancy in adults. It is very aggressive and is notorious for its fast and local invasion of nearby brain parenchyma. Consequently, the overall survival (OS) of patients with GBM is short despite resection, radiotherapy and chemotherapy regimens. The most common sites of metastasis of GBM are the lungs and pleura, cervical lymph nodes, and bone. Metastasis to the skin is a rare event and to our knowledge, there are less than 30 cases of GBM metastasizing to cutaneous or subcutaneous tissue described in the literature. None of these cases were diagnosed and/or treated in the Middle East region; and the majority of the metastases found were adjacent to the site of surgery undergone to remove the primary malignancy. We present the case of a 53-year-old male diagnosed with GBM and later showing signs of metastases at the anterio-auricular side of his face near-distant from the site of previous surgery done to remove the primary tumor.

Drug-Induced Peripheral Neuropathy: Diagnosis and Management.

Peripheral neuropathy comes in all shapes and forms and is a disorder which is found in the peripheral nervous system. It can have an acute or chronic onset depending on the multitude of pathophysiologic mechanisms involving different parts of nerve fibers. A systematic approach is highly beneficial when it comes to cost-effective diagnosis. More than 30 causes of peripheral neuropathy exist ranging from systemic and auto-immune diseases, vitamin deficiencies, viral infections, diabetes, etc. One of the major causes of peripheral neuropathy is drug-induced disease, which can be split into peripheral neuropathy caused by chemotherapy or by other medications. This review deals with the latest causes of drug-induced peripheral neuropathy, the population involved, the findings on physical examination and various workups needed and how to manage each case.

Oligodendroglioma: A Review of Management and Pathways.

Anaplastic oligodendrogliomas are a type of glioma that occurs primarily in adults but are also found in children. These tumors are genetically defined according to the mutations they harbor. Grade II and grade III tumors can be differentiated most of the times by the presence of anaplastic features. The earliest regimen used for the treatment of these tumors was procarbazine, lomustine, and vincristine. The treatment modalities have shifted over time, and recent studies are considering immunotherapy as an option as well. This review assesses the latest management modalities along with the pathways involved in the pathogenesis of this malignancies.