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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Enhanced Pancreatitis Detection: FAPI PET/CT Emerging Utility in Patient with Pancreatic Mass.

Fibroblast Activation Protein Inhibitor (FAPI) positron emission tomography (PET) imaging has emerged as a useful method for identifying pancreatic disorders, notably pancreatitis. Unlike Fluorine-18 fluorodeoxyglucose (FDG), FAPI uptake is directly proportional to the degree of fibrosis, making it very useful in separating pancreatic tumors from inflammation. Recent investigations have shown that FAPI positron emission tomography/computer tomography (PET/CT) can identify pancreatic inflammation with great sensitivity, providing vital diagnostic information. In this case study, a 52-year-old male with a history of Ewing sarcoma presented with epigastric pain. Pancreatitis was confirmed on a computer tomography (CT) scan showing mild fat stranding in the pancreatic body and tail, in addition to a significant increase in pancreatic head mass, necessitating further evaluation with FDG PET/CT and FAPI PET/CT, as the patient was known to have metastatic sarcoma. While FDG PET/CT revealed an avid infiltrative lesion in the duodenal/pancreatic head area, FAPI PET/CT showed diffuse uptake in the pancreatic body and tail, indicating fibroblast-mediated inflammation consistent with pancreatitis. This case demonstrates the usefulness of FAPI imaging in discriminating between pancreatic metastasis and pancreatitis, with FAPI PET/CT providing crucial diagnostic information when FDG uptake is ambiguous.

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.

Performance and oncologic safety of sentinel lymph node biopsy after neoadjuvant chemotherapy: Results from a tertiary care center in Lebanon.

BACKGROUND: The feasibility of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NACT) in initially node-positive patients is still controversial. We aim to evaluate the oncologic outcomes of SLNB after NACT and further compare the results between those who were initially node-negative and node-positive. METHODS: This is a retrospective cohort that included patients diagnosed with invasive breast cancer and had surgical management between January 2010 and December 2016. Survival and recurrence data after 3-5 years were collected from patients' records. We divided patients into Group A who were initially node-negative and had SLNB ± axillary lymph node dissection (ALND) and Group B who were node-positive and had SLNB ± ALND. RESULTS: Among initially node-negative patients, 43 out of 63 patients did SLNB (Group A). However, among initially node-positive patients only 28 out of 123 patients did SLNB (Group B). Out of the 71 patients who did SLNB after NACT, 26 patients had positive SLNs with only 14 patients who further underwent ALND. The identification rate of SLNB was 100% in Group A and 96.4% in Group B. The survival curves by nodal status showed no significant difference between overall survival and recurrence-free survival at 5 years between patients in Group A versus Group. CONCLUSION: The results suggest that in properly selected patients, SLNB can be feasible after NACT. Our results resemble the reported literature on accuracy of SLNB after NACT and adds to the growing pool of data on this topic.

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.

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.

Frequency and mutational spectrum of PIK3CA gene mutations in breast cancer patients: Largest and first report from Lebanon.

The PIK3CA pathway is one of the most frequently altered pathways in human cancers, especially in breast cancer with approximately 40% of HR+/HER2- advanced breast cancer cases exhibiting mutations in the PIK3CA gene. While the mutations can occur across the entire gene, the most common are observed in exon 9 corresponding to the helical domain, and in exon 20 encompassing the kinase domain. This study constitutes the first attempt at determining the frequency and mutational spectrum in Lebanese breast cancer patients. For this purpose, DNA samples from 280 breast cancer patients from across Lebanon were screened for PIK3CA mutations using the Therascreen® PIK3CA RGQ Real-time PCR assay. In line with previous reports, 38.57% of cases were positive for at least one PIK3CA mutation, among which approximately 59% were in exon 9 and 37% in exon 20. However, PIK3CA mutations are breast cancer are heterogeneous whereby 20% of known PIK3CA mutants might not be detected by compact PCR based assays. Thus, the adoption of comprehensive Next Generation Sequencing based panels to decipher the complete clinical, molecular and immunohistochemical profile of breast cancer tumor requires further investigation.

Extra-gastrointestinal stromal tumors (EGISTs): A case report for a mischief entity.

BACKGROUND: Extra-gastrointestinal stromal tumor is a rare subtype of soft tissue sarcomas with significantly variable presentation, management, and prognosis. This makes it crucial to report the different institutional experiences of encountering extra-gastrointestinal stromal tumors (EGIST). CASE PRESENTATION: We report 3 cases of EGIST diagnosis at American University of Beirut Medical Center for 2 males and 1 female in the 5th, 6th, and 7th decades of life, respectively. For the first case, the tumor was initially suspected to be ovarian cancer, but biopsy revealed a diagnosis of EGIST, and the patient was started on neoadjuvant therapy. In the second case, the tumor was retro-gastric and prelim diagnosis was gastric cancer but again biopsy revealed an EGIST histopathology, and the patient underwent surgery and adjuvant treatment. For the third case, a previous history of testicular cancer prompted an initial suspicion of recurrence with metastasis but biopsy and immunohistochemistry staining revealed EGIST with related markers. The patient underwent treatment at a different institution in his home country. CONCLUSION: This report sheds light on the importance of keeping EGIST amongst any differential list for abdominal and pelvic tumors. It also shows that EGIST-focused studies are needed to assess the effectiveness of the different treatment modalities available when utilized specifically for EGIST. This would allow for better oncological outcomes and improved quality of life.

Diagnosis and management of patients with stage III non­small cell lung cancer: A joint statement by the Lebanese Society of Medical Oncology and the Lebanese Pulmonary Society (Review).

Proper management of stage III non-small cell lung cancer (NSCLC) might result in a cure or patient long-term survival. Management should therefore be preceded by adequate and accurate diagnosis and staging, which will inform therapeutic decisions. A panel of oncologists, surgeons and pulmonologists in Lebanon convened to establish a set of recommendations to guide and unify clinical practice, in alignment with international standards of care. Whilst chest computerized tomography (CT) scanning remains a cornerstone in the discovery of a lung lesion, a positron-emission tomography (PET)/CT scan and a tumor biopsy allows for staging of the cancer and defining the resectability of the tumor(s). A multidisciplinary discussion meeting is currently widely advised for evaluating patients on a case-by-case basis, and should include at least the treating oncologist, a thoracic surgeon, a radiation oncologist and a pulmonologist, in addition to physicians from other specialties as needed. The standard of care for unresectable stage III NSCLC is concurrent chemotherapy and radiation therapy, followed by consolidation therapy with durvalumab, which should be initiated within 42 days of the last radiation dose; for resectable tumors, neoadjuvant therapy followed by surgical resection is recommended. This joint statement is based on the expertise of the physician panel, available literature and evidence governing the treatment, management and follow-up of patients with stage III NSCLC.

Prone versus Supine FDG PET/CT in the Staging of Breast Cancer.

Supine [18F]Fluorodeoxyglucose (FDG) positron emission technology/computed tomography (PET/CT) is a commonly used modality for the initial staging of breast cancer, and several previous studies have shown superior sensitivity and specificity of prone FDG PET/CT in comparison to its supine counterpart. This retrospective study included 25 females with breast cancer referred for staging. They underwent supine FDG PET/CT followed by prone FDG PET/CT. The outcomes were: number of primary breast lesions, anatomical site of FDG-avid lymph nodes (LNs), and number and type of bone lesions, with SUVmax of all corresponding parameters. Performance was superior in prone acquisition compared to supine acquisition, with the respective results: 29 vs. 22 breast tumor lesions detected, 62 vs. 27 FDG-avid axillary LNs detected, sensitivity of 68% vs. 57%, specificity of 64% vs. 53%. The detection rate of axillary LNs in the prone position was significantly higher (p = 0.001). SUVmax for breast tumor lesions (p = 0.000) and number of detected axillary LNs (p = 0.002) were significantly higher in prone acquisition. Five patients were upstaged after experts read the prone acquisition. Prone FDG PET/CT acquisition is a promising technique in detecting primary breast lesions and metastatic LNs possibly missed in supine acquisition, which may lead to change in patient staging and management.

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.

Spinal intradural extramedullary granular cell tumor.

Background: Granular cell tumors (GCTs) are uncommon peripheral nerve sheath tumors of Schwann cell origin that may occur throughout the body. However, they rarely occur in the spinal canal. Case Description: A 49-year-old male presented with burning sensation in the left knee. The MRI of the lumbar spine showed an L3-L4 intradural extramedullary tumor. Complete surgical resection was successfully performed and the L3 root burning improved. Histopathologically, the lesion proved to be a benign GCT. Conclusion: Spinal GCTs are rare benign tumors that may be found in an intradural extramedullary location in the spine. The preferred treatment is complete surgical resection as subtotal/partial resection may result in recurrence warranting radiation therapy.

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.