Effect of young age (below 40 years) on oncologic outcomes in Lebanese patients with breast cancer: a matched cohort study.

BACKGROUND: Developing countries have a significantly higher incidence of breast cancer in patients younger than 40 years as compared to developed countries. This study aimed to examine if young age at diagnosis is an independent prognostic factor for worse survival outcomes in breast cancer as well as the effect of age on Disease-free survival (DFS) and local recurrence free survival (LRFS) after adjusting for various tumor characteristics, local and systemic treatments. METHODS: This is a secondary analysis of prospective cohort of patients from two existing databases. We identified patients with breast cancer aged 40 years or less and we matched them to those older than 40 years. We also matched based on stage and molecular subtypes. In cohort 1, we matched at a ratio of 1:1, while in cohort 2 we matched at a ratio of 1:3. RESULTS: In cohort 1, Disease-free survival (DFS) at 5 years was significantly shorter for those younger than 40 years (75.6% and 92.7% respectively; p < 0.03). On multivariate analysis, only chemotherapy was found to be significant, while age was not found to be an independent predictor of prognosis. Local recurrence free survival at 5 years was similar between both age categories. Only hormonal therapy is a significant predictor for LRFS at 5 years. In the second cohort, DFS and LRFS at 3 years were similar between those younger and those older than 40 years. On multivariate analysis, no factor including age was found to be an independent predictor of prognosis. CONCLUSION: Data in the literature is controversial on the effect of young age on breast cancer prognosis. Our findings could not demonstrate that age is an independent prognostic factor in our population. There is a need for outcomes from larger, prospective series that have longer follow-ups and more data from our region.

Prostate cancer across four countries in the Middle East: a multi-centre, observational, retrospective and prognostic study.

Prostate cancer (PC) is the second most prevalent cancer in males, with a steadily increasing incidence in the Middle East (ME). The aim of this study was to capture real-world data on the characteristics, disease progression, and treatment patterns among PC patients in the ME. This was a retrospective, observational, multi-centre study conducted across ten hospitals/research centers in Lebanon, Kingdom of Saudi Arabia, Iraq and Kuwait. Data were abstracted from medical records of 615 male patients who were diagnosed with PC between January 2012 and the site initiation date (December 2018-May 2019) and received at least one PC treatment/intervention. The observation period ranged between 84 and 88 months. Data were collected on demographics, clinical characteristics, time to progression to the subsequent clinical state or therapy (progression from localised/locally advanced PC to castration and to metastatic PC (metastatic castration-sensitive PC (mCSPC) or metastatic castration-resistant PC (mCRPC)), progression from mCSPC to mCRPC, and mCRPC patients' progression to first subsequent line of therapy), treatment patterns, and mortality. Most patients had localised/locally advanced PC (57.7%), followed by mCSPC (37.4%), and mCRPC (4.1%) at the time of inclusion in the study. Most patients were at tumours, nodes and metastases (TNM) stage IIIa (40.1%) or TNM stage IVb (27.8%) at study entry. Median time to metastatic disease, castration-resistance and next line therapy was 84 months (95% CI: 68-84), 41 months (95% CI: 30-56) and 7 months (95% CI: 0-41), respectively. The mortality rate was 3.6%. Disease progression was most common among patients with mCSPC (35.1%) or mCRPC (14.8%), and treatment discontinuation was most common among patients with mCRPC (36.6% treatments discontinued). The results show that most patients were at an advanced TNM stage at study entry, suggestive of a lack of awareness regarding PC. Disease progression was most common among patients with metastatic disease, reflecting the challenge of treating metastatic disease and highlighting the need for novel treatments.

Personalized treatment with PARP inhibitors in advanced urothelial carcinoma: a case report and literature review.

Bladder cancer (BC) poses a significant health challenge, particularly in metastatic cases, where the prognosis is unfavorable and therapeutic options are limited. Poly ADP-ribose polymerase (PARP) inhibitors have gained approval for use in various cancer types, but their application in BC remains controversial, despite the notable prevalence of DNA damage response alterations in advanced or metastatic urothelial carcinomas. In this report, we describe a 66-year-old heavy-smoking female diagnosed with muscle-invasive BC. She underwent multiple rounds of chemotherapy and radiation, yet her disease remained poorly controlled, leading to metastasis in the left obturator internus muscle. Comprehensive genomic profiling through FoundationOne® Liquid CDx, examining a 324-gene panel using circulating tumor DNA from blood samples, revealed a pathogenic ATM gene alteration (p.Q654fs*10, c.1960delC), suggesting potential eligibility for PARP inhibitor therapy. Remarkably, the patient achieved a complete response to talazoparib, prompting an optimal investigation into BC candidates for this promising therapy.

A new hope for advanced bladder cancer treatment: a case study on the success of PARP inhibitors Bladder cancer is a significant health problem, particularly when it spreads to other parts of the body. The outcome for these advanced cases is often poor and treatment options are limited. One type of treatment, called PARP inhibitors, has shown success in treating other types of cancer, but its use in bladder cancer is still under investigation. This article presents the case of a 66-year-old heavy-smoker woman who was diagnosed with an aggressive form of bladder cancer. Despite several rounds of chemotherapy and radiation, her cancer was not well-controlled and spread to a hip muscle. A detailed genetic analysis revealed specific alterations that suggested she might benefit from treatment with a PARP inhibitor. This type of treatment works by blocking a protein that cancer cells need to repair their DNA, causing the cancer cells to die. The patient was treated with a PARP inhibitor called talazoparib and her cancer completely disappeared with this treatment. This positive response highlights the potential of PARP inhibitors as a promising treatment for bladder cancer, especially in patients who don't respond to conventional treatments and whose cancer has specific genetic changes. Our study also provides an overview of clinical trials evaluating PARP inhibitors in bladder cancer and summaries reported bladder cancer cases in the literature showing a good response to PARP inhibitors, along with their respective genetic alterations. In conclusion, this case study contributes to the growing understanding of personalized medicine, where treatment is tailored to the specific genetic mutations of each patient's cancer. It emphasizes the importance of identifying bladder cancer patients who could benefit most from PARP inhibitor therapy, offering a potential lifeline for those who haven't responded to initial treatment.

Esophageal cancer: a twenty-four-year experience at a tertiary care center with an evaluation of the prognostic significance of the neutrophil-lymphocyte ratio.

BACKGROUND: A high neutrophil-lymphocyte ratio (NLR) may be associated with worse survival in esophageal cancer (EC). Our aims were to describe the demographic and clinical data of EC in a tertiary referral center in Lebanon and to determine the prognostic value of NLR. METHODS: A retrospective cohort study based on chart review of patients diagnosed with EC was conducted at the American University of Beirut Medical Center (AUBMC). The demographic characteristics, clinical presentation and outcomes were described and compared between squamous cell carcinomas (ESCC) and adenocarcinomas (EAC). Data about esophageal cancer incidence were obtained from the National Cancer Registry, the Ministry of Public Health and GLOBOCAN 2020. Cox regression analysis was performed to determine whether the NLR is an independent predictor of survival, using variables based on clinical knowledge and previously established data. RESULTS: 110 patients were diagnosed with EC, which was the least common among other gastrointestinal malignancies. Our follow up rates reached 86.4%. The median survival was 9 months (IQR 3-25.5.) and was comparable between ESCC (median of 7 months, IQR 2-25) and EAC (median of 9 months, IQR 3-26.3), p = 0.803. Advanced stage was associated with a worse prognosis (p = 0.037). The mean NLR(±SD) was 5.20 ± 6.8, with no significant difference between EAC and ESCC (4.5 ± 3.4 vs. 5.9 ± 9.2, p = 0.420) or between early or advanced stages (5.4 ± 8.1 vs. 4.7 ± 6.8, p = 0.732). The area under the curve for the NLR was 0.560 (95% CI: 0.374-0.746, p = 0.488). After adjusting for age, gender, TNM staging and grading, cox regression analysis showed that an increased NLR was a significant predictor of mortality, with an adjusted hazard ratio of 1.095 (p = 0.011). CONCLUSION: EC is quite uncommon in Lebanon despite a high prevalence of smoking and obesity. Advanced stage and high NLR were associated with a negative prognostic value.

Metastatic well differentiated serotonin-producing pancreatic neuroendocrine tumor with carcinoid heart disease: a case report.

Background: Less than two percent of pancreatic neuroendocrine tumors (NETs) produce serotonin. Serotonin can cause carcinoid syndrome and less commonly carcinoid heart disease (CHD). CHD is associated with increased mortality and requires a more aggressive approach. Here we present a rare case of a serotonin-producing pancreatic NET complicated by CHD at presentation and discuss timing of systemic therapy, liver-directed therapy, and heart failure management. Case Description: A 36-year-old white man presented with diarrhea, lower extremity edema, and exertional dyspnea. He was found to have a well-differentiated serotonin-producing pancreatic NETs grade three with bilobar liver metastasis complicated by carcinoid syndrome and CHD. His symptoms and disease burden improved with somatostatin analog and liver-directed therapy with bland embolization to control carcinoid symptoms and obtain rapid hormonal control to prevent progression of CHD. He concurrently received diuretics to manage his heart failure and was considered for valvular replacement surgery, which was deferred for optimal hormonal control. Conclusions: Our case highlights the importance of multidisciplinary care for patients with pancreatic NETs and early identification and management of CHD. Although uncommon, serotonin-producing pancreatic NETs can present with CHD and require combination of somatostatin analogs, liver-directed therapy, and heart failure management.

The first Middle East and North Africa expert consensus recommendations for management of advanced gastric cancer.

Gastric cancer (GC) ranks as the fifth most prevalent cancer and the fourth deadliest cancer worldwide. In the Middle East and North Africa (MENA) region, GC represents about 4.8% of cancer cases with more than 35,000 new cases in 2020. To strengthen and improve the management of this cancer in the region, a group of MENA experts in the field of GC developed the first MENA consensus recommendations for the management of advanced GC. A total of 28 statements were drafted, discussed and voted on, using a modified Delphi process, during a virtual consensus meeting. The statements addressed the areas of epidemiology, biomarkers and treatment.

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.

Renal cell carcinoma management: real-world practice and challenges at a national level.

Renal cell carcinoma (RCC) management has seen a revolution over the last decades. Six Lebanese oncologists discussed recent updates in RCC management and outlined the challenges and future directions in Lebanon. Sunitinib continues to be a first-line choice for metastatic RCC in Lebanon, except for intermediate- and poor-risk patients. Immunotherapy is not always accessible to patients or selected routinely as first-line therapy. More data are needed on the sequencing of immunotherapy and tyrosine kinase inhibitor treatments and on the use of immunotherapy beyond progression and/or after failure of immunotherapy in the first-line setting. For second-line management, the clinical experience with axitinib for low tumor growth rate and nivolumab after progression on tyrosine kinase inhibitors make those two agents the most widely used. Several challenges affect the Lebanese practice, limiting the accessibility and availability of the medications. Reimbursement remains the most critical challenge, especially with the socioeconomic crisis of October 2019.

Consensus on the management of platinum-sensitive high-grade serous epithelial ovarian cancer in Lebanon.

Ovarian cancer is the most lethal gynecologic cancer. The high grade serous epithelial (HGSE) subtype is the most aggressive and it often presents at advanced stages, while screening programs have not proven beneficial. Management of the advanced stages (FIGO III and IV), which constitute the majority of diagnoses, usually consists of platinum-based chemotherapy and cytoreductive surgery (primary or interval) followed by maintenance therapy. Currently, the standard-of-care for advanced newly diagnosed HGSE ovarian cancer, as per international medical societies, starts with upfront cytoreductive surgery, followed by platinum-based chemotherapy (mostly carboplatin and paclitaxel) and/or anti-angiogenic agent bevacizumab, then maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor with/without/or bevacizumab (continued). PARP inhibitor use depends on the patient's genetic signature, mainly the breast cancer gene (BRCA) mutation and the homologous recombination deficiency (HRD) status. Therefore, genetic testing is recommended at diagnosis to inform treatment and prognosis. In line with the evolving standard-of-care for ovarian cancer, a panel of experts in treating advanced ovarian cancer convened to lay down practical recommendations on the management of advanced ovarian cancer in Lebanon; since the currently applicable guidelines by the Lebanese Ministry of Public Health for cancer treatment have not been updated yet to reflect the treatment paradigm shift brought upon by the development and approval of PARP inhibitors. The current work reviews the leading clinical trials on PARP inhibitors (as maintenance for newly diagnosed advanced and platinum-sensitive relapsed ovarian cancer), presents international recommendations, and proposes treatment algorithms for optimal local practice.

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.

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.

Overcoming EGFR Resistance in Metastatic Colorectal Cancer Using Vitamin C: A Review.

Targeted monoclonal antibody therapy against Epidermal Growth Factor Receptor (EGFR) is a leading treatment modality against metastatic colorectal cancer (mCRC). However, with the emergence of KRAS and BRAF mutations, resistance was inevitable. Cells harboring these mutations overexpress Glucose Transporter 1 (GLUT1) and sodium-dependent vitamin C transporter 2 (SVCT2), which enables intracellular vitamin C transport, leading to reactive oxygen species generation and finally cell death. Therefore, high dose vitamin C is proposed to overcome this resistance. A comprehensive search strategy was adopted using Pubmed and MEDLINE databases (up to 11 August 2022). There are not enough randomized clinical trials to support its use in the clinical management of mCRC, except for a subgroup analysis from a phase III study. High dose vitamin C shows a promising role in overcoming EGFR resistance in mCRC with wild KRAS mutation with resistance to anti-epidermal growth factor inhibitors and in patients with KRAS and BRAF mutations.

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.

Thrombotic Microangiopathy in the Setting of Colorectal Cancer: A Therapeutic Challenge with a Bad Prognosis.

While most cases of thrombotic microangiopathic hemolytic anemias are idiopathic, some can occur in the setting of a malignancy. Differentiating both conditions is crucial to initiate the appropriate treatment. In this case report and literature review, we discuss the occurrence of a thrombotic microangiopathy in a 61-year-old male patient with a treatment-refractory metastatic colorectal cancer invading his bone marrow. Plasmapheresis does not constitute the mainstay of treatment in this setting, as targeting the primary disease is the ultimate management. Treating the condition of our patient has been challenging as multiple lines of treatments of his primary disease had been exhausted. The discrepancy in KRAs status obtained between PCR and later NGS offered a new treatment line with Cetuximab. In this article, we will discuss the different factors that differentiate between idiopathic and cancer-induced microangiopathy. We will emphasize on the fact that the treatment of the primary disease constitutes the most important step in the treatment of cancer-induced thrombotic microangiopathy. We will also raise several explanations to target the disagreement in KRAS status obtained by the different technical modalities.

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.

Adjusting the duration of androgen deprivation therapy (ADT) based on nadir PSA for high risk localized prostate cancer patients treated with definitive external beam radiation therapy and ADT.

BACKGROUND: A nadir Prostate-Specific Antigen (nPSA) of 0.06 ng/mL has been shown to be a strong independent predictor of biochemical recurrence-free survival (bRFS) in patients with intermediate or high-risk (HR) prostate cancer treated with definitive external beam radiation therapy (RT) and androgen deprivation therapy (ADT). We aimed to examine the association between the duration of ADT and bRFS in HR localized prostate cancer, based on nPSA. METHODS: Between 1998 and 2015, 204 patients with HR localized prostate cancer were identified. Of them, 157 patients (77.0%) reached the desired nPSA of < 0.06 ng/mL (favorable group), while 47 (23.0%) did not (unfavorable group). Duration of ADT varied among patients depending on physician preference, patient tolerance, and/or compliance. Survival outcomes were calculated using Kaplan-Meier methods and predictors of outcomes using multi-variable cox regression model. RESULTS: In the favorable group, ADT for at least 12 months lead to superior bRFS compared to ≤ 9 months of ADT (P = 0.036). However, no significant difference was seen when examining the value of receiving ADT beyond 12, 18, or 24 months, respectively. On univariate analysis for bRFS, the use of ADT for at least 12 months was significant (P = 0.012) as well as time to nadir PSA (tnPSA), (≤ 6 vs > 6 months); (P = 0.043). The presenting T stage was borderline significant (HR 3.074; 95% CI 0.972-9.719; P = 0.056), while PSA at presentation, Gleason Score and age were not. On multivariate analysis, the use of ADT for 12 months (P = 0.012) and tnPSA (P = 0.037) remained significant. In the unfavorable group, receiving ADT beyond 9 and 12 months was associated with improved bRFS (P = 0.044 and 0.019, respectively). However, beyond 18 months, there was no significant difference. CONCLUSION: In HR localized prostate cancer patients treated with definitive RT and ADT, the total duration of ADT may be adjusted according to treatment response using nPSA. In patients reaching a nPSA below 0.06 ng/mL, a total of 12 months of ADT may be sufficient, while in those not reaching a nPSA below 0.06 ng/mL, a total duration of 18 months is required.

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.

Cancer registration in the Middle East, North Africa, and Turkey (MENAT) region: A tale of conflict, challenges, and opportunities.

Cancer registration is a core component of national and regional cancer control strategies. In the Middle East, North-Africa and Turkey (MENAT) region, capacity and resources for cancer registration is variable and shaped by multiple contextual challenges. This viewpoint maps out practical recommendations around cancer registration, in an attempt to inform cancer control planning, policy, and implementation. The recommendations laid out in this viewpoint are informed by the discussions held at the Initiative for Cancer Registration in the MENAT (ICRIM) virtual workshop, which convened registry managers, policy makers, and international agencies from 19 countries in the MENAT region. The discussions were distilled in four categories of recommendations, revolving around cancer registration procedures, collaborative governance, putting cancer registration on the map, and capacity building. This viewpoint provides a much-needed mapping of practical recommendations around cancer registration, informed by direct key stakeholders in the region. These practical recommendations offer a road map for policy making, cancer control planning, and future regional capacity strengthening initiatives.

68Ga-PSMA PET/CT in early relapsed prostate cancer patients after radical therapy.

Biochemical recurrence (BCR) of prostate cancer (PCa) occurs in about 25% of patients treated with radical prostatectomy (RP) and up to 45% in patients who receive external beam radiotherapy (RT). Early diagnosis of PCa recurrence is of high importance for successful salvage therapy. The aim of the present study is to analyze the efficacy of 68 Ga-PSMA PET/CT in detecting the presence of local and/or systemic disease in patients with a history of PCa who have BCR. A total of 52 PCa patients with BCR referred for 68 Ga-PSMA PET/CT were recruited from the American University of Beirut Medical Center between November 2017 and December 2019. We compared the performance of PSMA PET/CT to the results and clinical factors based on follow up: PSA, PSA kinetics, primary treatment, and Gleason score. The relationship between the PET/CT findings and clinical indicators of disease were assessed by univariate and multivariate logistic regression. From a total of 52 patients, 34 (65.4%) had positive PSMA-PET/CT scans. Among those, 8/34 (23.5%) received primary RT. For all patients with a positive PSMA-PET: the detection rate was 2/4 (50%) for PSA < 0.2, 5/10 (50%) for PSA 0.2-0.49, 3/6 (50%) for PSA 0.5-0.99, 6/12 (50%) for PSA 1-1.99, 8/9 (88.9%) for PSA 2-3.99, and 10/11 (90.9%) for PSA 4-10.PSMA-PET/CT positivity was significantly associated with PSA level at time of PET scan, PSA doubling time, Gleason score and TNM staging. However, it did not show a significant correlation with radiotherapy as primary treatment, ongoing androgen deprivation therapy (ADT), time to relapse, and initial PSA before therapy. In our single center prospective trial, 68 Ga-PSMA PET/CT successfully detected the recurrence of PCa in patients with BCR. Scan positivity was significantly associated with PSA level at time of PET scan, PSA doubling time, Gleason score, and TNM staging. PSMA- PET/CT is a highly promising modality in the work up of patients with PCa in the setting of BCR for earlier detection of disease recurrence.

Immunotherapy for metastatic liver disease from colorectal carcinoma: case series from the Middle East.

Immunotherapy poses new considerations and alterations to the management of metastatic colorectal carcinoma (mCRC), where chemotherapy achieves complete radiological response but yields complete pathological response in few patients only. Immunotherapy may be superior in the conversion of unresectable disease to resectable liver lesions from mCRC and downsizing borderline lesions for more feasible resectability and achieving complete pathologic response, with the potential for cure and to alter current, established guidelines for surgical resection with a shift from chemotherapy. We present two patients with hepatic lesions from mCRC characterized by deficient mismatch repair (dMMR) which were unresectable after traditional chemotherapy but were converted to resectable lesions with a complete histopathological response following immunotherapy. Complete histopathologic response and radiologic regression or disappearance of liver lesions was observed in patients with dMMR mCRC after pembrolizumab. Immunotherapy exhibits notable potential for cure, achieving complete, successful surgical resection and improving prognosis.