Early-Onset Colorectal Cancer in Egypt: Pathological Characters, Patterns of Care, and Survival Compared to Average-Age Onset Colorectal Cancer: A Retrospective Multicenter Study.

PURPOSE: Early-onset colorectal cancer (EOCRC) is a rising health problem. The incidence of EOCRC has increased over the past 2 decades all over the world. Reports from Egypt since the 1990s have reported a higher incidence among young populations with no identifiable risk factors. The aim of this study was to assess EOCRC in Egypt regarding incidence, characteristics, treatment pattern, and survival compared with average age onset and elderly patients. MATERIALS AND METHODS: This was a retrospective, record-based, cohort study combining data from four different cancer centers in Egypt. We grouped patients according to age into three categories: the EOCRC group for patients age ≤45 years and the average age onset and elderly cancer group (for patients age ≥65 years). RESULTS: The study included 1,310 patients with histopathologically proven colorectal cancer, representing four different geographical areas in Egypt. Patients with EOCRC represented 42.4% of the study population. Female patients were 50.6% among the EOCRC group and 52.5% among the average age group. Rectal tumors were significantly higher in EOCRC (54.7% v 40.6%; P < .001). There was no significant difference between both groups regarding the tumor stage at presentation, obstruction, or presence of metastases at presentation. Patients with EOCRC had a significantly higher rate of peritoneum/adnexa metastases than the average age ones (12.3% in EOCRC v 6.9% in the average age group; P < .001). No statistically significant differences between EOCRC and average age groups in both disease-free survival and overall survival were reported. CONCLUSION: A comprehensive framework for the study of EOCRC is required in Egypt as well as a genomic analysis to identify possible underlying genetic alterations responsible for the high incidence of EOCRC.

Resource Oriented Decision Making for Treatment of Metastatic Colorectal Cancer (mCRC) in a Lower-Middle Income Country: Egyptian Foundation of Medical Sciences (EFMS) Consensus Recommendations 2020.

PURPOSE: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second cause of cancer related mortality. Treatment options for patients with metastatic CRC (mCRC) expanded during the last two decades, with introduction of new chemotherapeutic and targeted agents. Egypt is a lower middle-income country; Egyptian health care system is fragmented with wide diversity in drug availability and reimbursement policies across different health care providing facilities. We report the results of consensus recommendations for treatment of patients with metastatic colorectal cancer developed by Egyptian Foundation of Medical Sciences (EFMS), aiming to harmonize clinical practice through structured expert consensus-based recommendations consistent with the national status. EFMS recommendations could be utilized in other countries with similar economic status. METHODS: EFMS recommendations were developed using a modified Delphi process, with three rounds of voting till the final recommendations were approved. A non-systematic review of literature was conducted before generating the provisional statements. Content experts were asked to vote on some recommendations in two different resource groups (restricted resources and non-restricted resources). External review board of experts from a low income and lower-middle countries voted on the applicability of EFMS recommendations in their countries. RESULTS: The current recommendations highlighted the discrepancy in health care between restricted and non-restricted resources with expected survival loss and quality of life deterioration. Access to targeted agents in first line is very limited in governmental institutions, and no access to agents approved for third line in patients who failed oxaliplatin and irinotecan containing regimens for patients treated in restricted resource settings. CONCLUSION: Management of mCRC in developing countries is a challenge. The currently available resource-stratified guidelines developed by international cancer societies represent a valuable decision-making tool, adaptation to national status in each country based on healthcare system status is required.

Primary Osteosarcoma of the Urinary Bladder Metastatic to Lung.

Extra-skeletal osteosarcoma (ESOS) is a rare neoplasm that represents less than 2% of all soft tissue sarcomas. Common reported sites of involvement include limbs, retroperitoneum, chest wall and buttocks. ESOS arising primarily in parenchymatous organs are extremely uncommon, with the involvement of the urinary bladder is even rarer. We herein report a case of primary ESOS of the urinary bladder in a 48 year-old male patient.

Cost-effectiveness of six months versus 1-year adjuvant trastuzumab in HER2 positive early breast cancer in Egypt.

Introduction: Breast cancer is the most prevalent cancer among women in Egypt. Trastuzumab is administered with chemotherapy for patients with HER2-positive advanced breast cancer (HER2 + ve ABC) in the metastatic and adjuvant settings resulting in improved treatment outcomes, and long-term follow-up. Some studies have evaluated whether equivalent outcomes can be achieved with reduced treatment duration. This study evaluates the cost-effectiveness of 6-month versus 1-year trastuzumab treatments from payer perspective over a 10 year time horizon.Methods: A half-cycle corrected Markov model was developed with five mutually exclusive health states; patient with HER2 +ve ABC, disease-free survival (DFS), local or regional relapse, metastatic relapse, and death. A cycle length of 6 months was applied, direct medical costs including cost of treatments, day-care, surgery, health states and follow-up visits were collected, and indirect costs such as lost productivity were not estimated. The transition probabilities and utilities were extracted from published literature, and deterministic sensitivity analyses were conducted.Results: Among the HER2 +ve ABC patient population in Egypt, the total QALYs of the 6-month trastuzumab were estimated to be 2.99 compared with 2.93 for the 1-year trastuzumab which resulted in a difference of 0.06 QALYs. The total costs were EGP 271,647 ($106,947) and EGP 381,248 ($150,097), respectively. These costs yielded an ICER of -109,600 EGP/QALY (-43,149 $/QALY) for the 6-month trastuzumab. The 6-month trastuzumab is a dominant strategy when compared to 1-year trastuzumab, resulting in improved effectiveness at a reduced cost. All analyses results confirmed the dominance of 6-month trastuzumab and our model robustness.Conclusions: This study concluded that 6-month trastuzumab is a cost-effective option when compared to 1-year trastuzumab in patients with HER2 +ve ABC in Egypt. Our findings provide health care decision makers with additional insights to best allocate available resources concurrently with the improvement of the Egyptian patient's outcomes.

Capecitabine-Based Chemoendocrine Combination as First-Line Treatment for Metastatic Hormone-Positive Metastatic Breast Cancer: Phase 2 Study.

BACKGROUND: Preclinical studies have suggested a synergistic effect of tamoxifen and capecitabine in estrogen receptor-positive cell lines. We evaluated the safety and efficacy of first-line chemoendocrine treatment in patients with metastatic breast cancer. Biochemical assessment was performed of serum levels of thymidine phosphorylase enzyme (TP), serum tamoxifen, hydroxytamoxifen, and 5-fluorouracil in relationship to efficacy. PATIENTS AND METHODS: This prospective phase 2 interventional study studied patients with estrogen receptor-positive, HER2- metastatic breast cancer who received either tamoxifen/capecitabine or letrozole/capecitabine as first-line treatment. The dose of capecitabine provided at 2000 mg per day continuously as a fixed dose. RESULTS: Forty women with a median age of 49.3 years were enrolled. For the whole study group, median progression-free survival (PFS) was 10 months and median overall survival (OS) was 23.3 months. The overall response rate was 60% and the clinical benefit rate 82.5%. Progesterone receptor positivity was associated with significantly longer PFS (12 vs. 7 months, P = .021). The most frequent adverse events were palmar-plantar erythrodysesthesia (62.5%), fatigue (62.5%), diarrhea (30%), abdominal pain (12.5%), and constipation (10%). Changes in serum level of TP were not correlated to response to treatment, PFS, or OS. Higher serum levels of tamoxifen and hydroxytamoxifen were correlated with higher response rates and longer PFS but not OS. CONCLUSION: Chemoendocrine treatment is well tolerated, with no evidence of contradictory effects between the combination components. However, the efficacy data need more validation.

Cost-effectiveness of sorafenib versus best supportive care in advanced hepatocellular carcinoma in Egypt.

BACKGROUND: In light of constrained budgets and the need to fund efficient treatment options, this study set out to assess the cost-effectiveness of sorafenib as a first-line treatment of hepatocellular carcinoma (HCC) compared to best supportive care (BSC) from the military hospital perspective in Egypt. METHODS: A decision analytic Markov model simulated disease progression with clinical parameters and utility values derived from published data. Data on direct medical costs were collected from the local healthcare system or payer. Costs and effects were discounted at 3.5% annually and reported in USD using purchasing power parity adjustments. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Mortality occurred less frequently in the sorafenib group (sorafenib group: 99.96%, BSC group: 99.99%). The total quality-adjusted life years (QALYs) of the sorafenib cohort were estimated to be 46.24 compared with 42.27 for the BSC cohort, which resulted in an incremental gain of 3.96 QALYs. The total costs for the sorafenib and BSC cohorts were USD 4,229,940 and USD 3,092,886, respectively (incremental cost = $1,137,054), resulting in an incremental cost-effectiveness ratio (ICER) of USD 286,776 per QALY gained for the sorafenib cohort. One-way sensitivity analyses that addressed the uncertainty of the BSC estimates indicated that the progression-free survival for BSC and utility value of progression had the greatest effects on the results. CONCLUSION: This study concluded that sorafenib does offer increased survival and quality-of-life at an increased cost but at an ICER that exceeds the nationally accepted cost-effectiveness threshold. The findings support healthcare decision-making of the efficient allocation of healthcare system resources to improve the health of the Egyptian population. Whether sorafenib is cost-effective in specific sub-groups with additional risk factors needs to be addressed in future studies.

Outcomes of treatment with sorafenib in Egyptian patients with hepatocellular carcinoma: a retrospective cohort study.

BACKGROUND: Sorafenib is the standard of care, first line treatment for advanced HCC. This study aims to evaluate real-life efficacy and safety of sorafenib in Egyptian patients with Hepatocellular carcinoma (HCC). METHODS: This retrospective cohort study was conducted in the medical oncology department at Maadi Armed Forces Medical Compound. Patients with advanced HCC who received sorafenib between January and December 2015 were included (130 patients). RESULTS: The median overall survival of patients with HCC treated with sorafenib was 5 months (CI: 4.166-5.834), and progression free survival was 4 months (CI: 3.479-4.521). Disease control rate was 45.44% with 2 patients experiencing complete remission (1.2%). The adverse events rate was 76.1% for toxicities of all grades; with hand and foot syndrome being the most common (32.3% of any grade) and liver dysfunction the most common grade III toxicity (13.8%). Treatment was stopped for radiological progression based on modified RECIST criteria in 47 patients (36.3%), 18 patients stopped the treatment for intolerable toxicity. At the end of treatment upon radiological progression, 51 patients (39.2%) were still classified as Child A class of cirrhosis. CONCLUSION: Sorafenib use should be limited to patients with Child A, PS 0-1, and low disease burden.

Differential clinical pharmacology of rolapitant in delayed chemotherapy-induced nausea and vomiting (CINV).

Rolapitant is a highly selective neurokinin-1 receptor antagonist, orally administered for a single dose of 180 mg before chemotherapy with granisetron D1, dexamethasone 8 mg BID on day 2-4. It has a unique pharmacological characteristic of a long plasma half-life (between 163 and 183 hours); this long half-life makes a single use sufficient to cover the delayed emesis risk period. No major drug-drug interactions between rolapitant and dexamethasone or other cytochrome P450 inducers or inhibitors were observed. The clinical efficacy of rolapitant was studied in two phase III trials in highly emetogenic chemotherapy and in one clinical trial in moderately emetogenic chemotherapy. The primary endpoint was the proportion of patients achieving a complete response (defined as no emesis or use of rescue medication) in the delayed phase (>24-120 hours after chemotherapy). In comparison to granisetron (10 µg/kg intravenously) and dexamethasone (20 mg orally) on day 1, and dexamethasone (8 mg orally) twice daily on days 2-4 and placebo, rolapitant showed superior efficacy in the control of delayed and overall emesis. This review aims at revising the pharmacological characteristics of rolapitant, offering an updated review of the available clinical efficacy and safety data of rolapitant in different clinical settings, highlighting the place of rolapitant in the management of chemotherapy-induced nausea and vomiting (CINV) among currently available guidelines, and exploring the future directions of CINV management.

Intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with curative treatment of colorectal liver metastases: an updated systematic review.

INTRODUCTION: We aimed to assess the efficacy and safety of delivering intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with curative treatment of colorectal liver metastases. Areas covered: A comprehensive literature search using PubMed was conducted to screen for eligible records. Studies evaluating colorectal surgery and intraperitoneal chemotherapy combined with curative treatment of liver metastases were included. We excluded duplicate publications. Sixty-seven full-text papers were assessed and six papers were finally included. The overall survival in the included studies ranged from 6-49 months. Five-year survival ranged from 18%-28%, three-year survival ranged from 22%-42% and two-year survival ranged from 34%-78%. Survival was lower in patients with liver metastases and peritoneal carcinomatosis (PC) than those with PC alone in the majority of studies. Expert commentary: This review poses questions rather than presenting answers. The heterogeneity of survival data suggests the possible benefit of this aggressive treatment approach in selected patients. Standardization of the technique used for intraperitoneal chemotherapy instillation, agent used as well as the systemic chemotherapy and targeted therapy type and duration through prospective controlled trials is required to provide an evidence of a higher strength to support or prohibit this treatment strategy.

A review on thyroid cancer during pregnancy: Multitasking is required.

Thyroid cancer is the second most common cancer diagnosed during pregnancy after breast cancer. The goal of management is to control malignancy and prevent maternal and fetal complications as a result of maternal hypothyroidism. The role of female sex hormones as an etiologic factor was investigated, with no clear association. Pregnancy can cause an increase in size of a previously existed thyroid nodule through the structural similarity between TSH and BHCG, and the normally expressed estrogen receptors on thyroid gland cells. Effect of pregnancy on development and prognosis of differentiated thyroid malignancies (papillary and follicular) has also been studied. The prognosis of thyroid cancer is not worse in patients diagnosed during pregnancy or those who got pregnant after curative treatment. Termination of pregnancy is not indicated at all, surgery can be delayed till after delivery except in rapidly growing aggressive tumors. While radioactive iodine ablation is absolutely contra-indicated, the new systemic therapies are not well studied during pregnancy. However, almost all these new agents are classified as FDA category C or D and are better to be avoided. The effect of pregnancy on other types of thyroid cancer (medullary and anaplastic thyroid tumors) is not well studied because of very low incidence with pregnancy. The endocrinological management of thyroid cancer during pregnancy is of utmost importance. The hypothyroidism after total thyroidectomy can cause fetal hypothyroidism. Therefore, the management of thyroid cancer related to pregnancy needs a multidisciplinary team.

Review on renal cell carcinoma and pregnancy: A challenging situation.

Renal cell carcinoma is rarely diagnosed during pregnancy. Its management is a real challenge due to the sparse literature and lack of standard guidelines. In this situation, the diagnosis is often delayed as the clinical presentation might resemble other pregnancy-related disorders but it should be one of the diagnostic possibilities in women with recurrent or refractory urinary tract symptoms, renal pain, or mass that could be palpated. Diagnostic approach may include ultrasound examination and sometimes magnetic resonance imaging. If localized, surgery would be the preferred line of treatment. Other treatment modalities, end results of treatment, and review of literature of this rare association will be presented.