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

Colorectal cancer (CRC) is ranked as the third most prevalent and the second deadliest cancer worldwide. In the Middle East and North Africa (MENA) region, the number of CRC cases increased over the past decades and will nearly double by 2030. The lack of clear MENA guidelines for the management of patients with CRC represents a step backwards in the fight against this burden. Therefore a panel of 24 MENA experts in the field of gastrointestinal oncology developed, using a Delphi process, the first consensus recommendations for the management of patients with advanced CRC. Forty-seven different statements were formulated in the areas of epidemiology, screening, biomarkers and treatment. These recommendations will guide, standardize and unify the management of this cancer in the MENA region.

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.

Hepatocellular Carcinoma: The Evolving Role of Systemic Therapies as a Bridging Treatment to Liver Transplantation.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths. Classically, liver transplantation (LT) can be curative for HCC tumors within the Milan criteria. Bridging strategies to reduce the dropouts from LT waiting lists and/or to downstage patients who are beyond the Milan criteria are widely utilized. We conducted a literature-based review to evaluate the role of systemic therapies as a bridging treatment to liver transplantation (LT) in HCC patients. Tyrosine kinase inhibitors (TKIs) can be used as a systemic bridging therapy to LT in patients with contraindications for locoregional liver-directed therapies. Immune checkpoint inhibitor (ICI) treatment can be utilized either as a monotherapy or as a combination therapy with bevacizumab or TKIs prior to LT. Acute rejection after liver transplantation is a concern in the context of ICI treatment. Thus, a safe ICI washout period before LT and cautious post-LT immunosuppression strategies are required to reduce post-LT rejections and to optimize clinical outcomes. Nevertheless, prospective clinical trials are needed to establish definitive conclusions about the utility of systemic therapy as a bridging modality prior to LT in HCC patients.

Metastatic esophageal carcinoma to the eye masquerading as inflammatory vitreo-retinitis: A case report and literature review.

We report an unusual case of metastatic esophageal carcinoma to the vitreous associated with focal retinitis in a 44-year-old male. A 44-year-old male patient, known case of locally advanced esophageal carcinoma, presented with a 3-day history of left eye floaters. The initial diagnosis was inflammatory vitreo-retinitis that responded to systemic steroids. Four months later, the patient presented with relapsed intraocular inflammation, vitreous biopsy using a 25G needle was performed, and cytology confirmed the presence of metastatic carcinoma consistent with his primary esophageal cancer. The patient received external beam radiotherapy to his ocular and brain metastasis, and his eye examination was stable. Five months later, the patient passed away due to progressive brain metastasis.

Comparing real-world outcomes of total neoadjuvant treatment and CRT at a tertiary medical center.

Introduction: For years, standard treatment for locally advanced rectal cancer (LARC) has included neoadjuvant chemoradiotherapy (CRT), followed by surgery and adjuvant chemotherapy. Although CRT has helped reduce local recurrence rates, it hasn't consistently improved overall survival. Recent trials have unveiled a different approach called total neoadjuvant treatment (TNT), involving pre-surgery radiotherapy followed by chemotherapy (CAPOX/FOLFOX). TNT shows promise with improved treatment response and lower distant metastasis rates without compromising local control. Consequently, many healthcare institutions have adopted TNT as their preferred neoadjuvant treatment. This study, conducted at a tertiary center, compares the real-world outcomes of both CRT and TNT protocols. Methods: In this retrospective study of 390 patients treated between 2015 and 2021, aged 18 or older with LARC and tumors within 12 cm of the anal verge, we compared treatment outcomes. We assessed factors like pathological complete remission (pCR), three-year event-free survival (EFS), and overall survival (OS) between the two treatment groups using the Chi-squared test. Results: Out of the 390 eligible patients, 256 underwent CRT, while 84 received TNT. Surgery was performed on 215 (84%) patients in the CRT group, compared to 55 (65.5%) in the TNT group. Notably, 33 (12.8%) achieved pCR in the CRT group, whereas 23 (27.7%) achieved pCR in the TNT group (P <.001). Regardless of whether surgery was performed or not, the TNT group exhibited lower recurrence rates (12.7% vs. 18.6% with surgery, 28.6% vs. 45% without surgery). The 3-year EFS rate was 80% in the CRT group and 90% in the TNT group (P = .05). Additionally, the 3-year OS rates favored the TNT group, standing at 96.4% compared to 84.4% in the CRT group (P = .005). Conclusion: Our findings indicate that patients who underwent TNT demonstrated a higher likelihood of achieving pCR and experienced lower recurrence rates compared to those in the CRT group. Additionally, the TNT group exhibited superior 3-year EFS and OS. It is important to note, however, that a longer follow-up period is required to further validate these results.

Efficacy and safety-in analysis of short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma.

BACKGROUND: Neoadjuvant chemotherapy and short-course radiotherapy followed by resection has been gaining recognition in the treatment of rectal cancer. Avelumab is a fully human immunoglobulin that binds Programmed Death-Ligand 1 (PD-L1) and prevents the suppression of the cytotoxic T cell immune response. This phase II trial evaluates the safety and pathologic response rate of short-course radiation followed by 6 cycles of mFOLFOX6 with avelumab in patients with locally advanced rectal cancer (LARC). METHODS: This study is prospective single-arm, multicenter phase II trial adopting Simon's two-stage. Short-course radiation is given over 5 fractions to a total dose of 25 Gy. mFOLFOX6 plus avelumab (10 mg/kg) are given every 2 weeks for 6 cycles. Total mesorectal excision is performed 3-4 weeks after the last cycle of avelumab. Follow up after surgery is done every 3 months to a total of 36 months. Adverse event data collection is recorded at every visit. RESULTS: 13 out of 44 patients with LARC were enrolled in the first stage of the study (30% from total sample size). All patients met the inclusion criteria and received the full short-course radiation course followed by 6 cycles of mFOLFOX6 plus avelumab. 12 out of the 13 patients completed TME while one patient had progression of disease and was dropped out of the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33-73) years. The first interim analysis revealed that 3 (25%) patients achieved pathologic complete response (pCR) (tumor regression grade, TRG 0) out of 12. While 3 (25%) patients had near pCR with TRG 1. In total, 6 out of 12 patients (50%) had a major pathologic response. All patients were found to be MMR proficient. The protocol regimen was well tolerated with no serious adverse events of grade 4 reported. CONCLUSION: In patients with LARC, neoadjuvant radiation followed by mFOLFOX6 with avelumab is safe with a promising pathologic response rate. Trial Registration Number and Date of Registration ClinicalTrials.gov NCT03503630, April 20, 2018. https://clinicaltrials.gov/ct2/show/NCT03503630?term=NCT03503630&draw=2&rank=1 .

Validation of the Survival Benefits of Metformin in Middle Eastern Patients With Type II Diabetes Mellitus and Colorectal Cancer.

Purpose Epidemiologic data from several populations suggest that metformin may decrease cancer risk and mortality in patients with colorectal cancer (CRC) and type II diabetes mellitus (DM). Although type II DM and CRC are major health problems in the Middle East, no investigations have been performed to test the effect metformin has on the outcome of patients with type II DM and CRC who are also treated with metformin. Materials and Methods We retrospectively reviewed the medical records of 1,902 patients diagnosed with CRC at King Hussein Cancer Center between January 2004 and December 2012, and identified 349 patients (18%) with type II DM; we censored the data of 28 patients because their antidiabetic medications were unknown. We then categorized these 321 patients into two groups: 192 patients treated with metformin (group A) and 129 patients treated with other antidiabetic medications (group B). Results Group A patients had significantly longer overall survival (89 months; 95% CI, 66 to 112 months) and progression-free survival (47 months; 95% CI, 15 to 79 months) than group B patients (overall survival: 36 months; 95% CI, 24 to 48 months; P ≤ .001; progression-free survival: 21 months; 95% CI, 13 to 29 months; P = .016). After adjustment for age, sex, body mass index, aspirin use, anticholesterol treatment, and CRC stage, group A patients had a 40% reduction in mortality (hazard ratio, 0.58; 95% CI, 0.4% to 0.85%; P = .005). Conclusion Our results support findings from other populations that patients with diabetes and CRC who are also treated with metformin have better outcomes than those treated with other antidiabetic medications.

The application of clinical variables and models to predict pulmonary embolism in cancer patients: a comprehensive single cancer center experience.

INTRODUCTION: Prompt diagnosis and treatment of pulmonary embolism (PE) can help reduce its associated morbidity and mortality. Computed tomography chest angiography (CTA) scanning is the most widely used diagnostic modality. In noncancer patients, only 10% of such studies are positive for PE. Clinical variables, individual or in combination, that can predict test positivity are highly needed. MATERIALS AND METHODS: All CTAs requested to confirm or exclude a diagnosis of PE in a single comprehensive cancer center were reviewed. In addition to the Wells score, other clinical variables known to increase the risk of PE were analyzed. RESULTS: A total of 778 adult cancer patients were treated at King Hussein Cancer Center (Amman, Jordan) and were included in this study; the majority of patients (64.2%) had stage 4 disease. Overall, 129 (16.6%) patients had positive scans for PE, while alternative diagnoses were made in 308 (39.6%) patients. Cancer stage and anticancer treatment had no impact on positive PE rates. However, Wells criteria classified patients into three risk groups with PE rates of 10.2%, 16.1%, and 62.5% among the patients with low, moderate, and high risk, respectively (P < 0.0001). Duration of cancer diagnosis (<12 months versus >12 months) had a significant impact on positive PE studies (22.0% versus 12.4%, respectively, P = 0.007). CONCLUSION: The rate of positive PE studies in cancer patients is higher than previously reported in noncancer patients. Positivity for PE was higher during the first 12 months of cancer diagnosis and in those with high probability score according to the Wells criteria. Factors like primary tumor stage and anticancer therapy had no significant impact on PE-positive studies.

Multiple primary malignancies: analysis of 23 patients with at least three tumors.

BACKGROUND: There is scarcity of reports addressing patients with three or more malignancies. The aim of this study is to present a detailed analysis of patients presenting with at least three primary malignant tumors. PATIENTS AND METHODS: Records of cancer patients presenting to King Hussein Cancer Center (Amman, Jordan) between June 2006 and March 2011 were retrospectively reviewed. Patients harboring multiple primary tumors were included for detailed analysis. Data relating to epidemiological features, pathological characteristics, and disease outcomes were extracted. RESULTS: Out of 14,040 cases, 319 patients (2.3%) harbored two or more while 23 patients (0.16%) harbored three or more primary malignant tumors. This study included 17 males and six females between 4 and 78 years of age (median, 52 years) at the time of diagnosis of the first malignancy. The most prevalent tumor was colorectal adenocarcinoma found in nine, followed by lymphoma in seven, and prostate adenocarcinoma in six patients. The most common tumor combinations were colorectum-non-melanoma skin, colorectum-kidney, and non-melanoma skin-kidney all found in four patients, respectively. At a median follow-up of 96 months from the time of diagnosis of the first primary (range, 2-337 months) and 8 months from the time of diagnosis of the last primary (range, 1-48 months), 13 were alive with no evidence of disease, six were alive with residual disease, three were dead due to disease, and one patient was alive with unknown disease status. CONCLUSIONS: The possibility of multiple primary malignancies should always be considered during the treatment and follow-up of cancer patients. This case series could prove helpful to clinicians faced with similar, however, exceedingly rare scenarios. Due to the realistic potential for long-term survival, we recommend aggressive treatment of these patients.