Efficacy of Chemotherapy Rechallenge Versus Regorafenib or Trifluridine/Tipiracil in Third-Line Setting of Metastatic Colorectal Cancer: A Multicenter Retrospective Comparative Study.

PURPOSE: Metastatic colorectal cancer (mCRC) is a significant global health burden. This retrospective study compared the effectiveness of trifluridine/tipiracil (FTD/TPI), regorafenib, and chemotherapy rechallenge for third-line mCRC treatment. MATERIALS AND METHODS: We reviewed the medical records of 132 patients with mCRC treated with regorafenib, FTD/TPI, or a rechallenge with the initial chemotherapy regimen in a third-line setting from four different institutions. The primary end point was progression-free survival (PFS). Secondary end points were objective response rate and overall survival (OS) across the three treatment approaches. RESULTS: Twenty-nine patients received chemotherapy rechallenge, and 103 received FTD/TPI or regorafenib. Patients' characteristics were comparable, except for a lower number of left-sided primaries and KRAS wild-type tumors in the FTD/TPI-regorafenib group. The median PFS for the entire group was 3.0 months, and the median OS was 13.7 months. Chemotherapy rechallenge has resulted in a median PFS of 3.1 months and a median OS of 21.2 months, compared with 2.9 months (PFS) and 12.6 months (OS) for the FTD/TPI-regorafenib group. Multivariate analyses identified male sex and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 as independent prognostic factors for better PFS, whereas chemotherapy rechallenge, localized stage at diagnosis, and an ECOG PS of 0-1 were significant prognostic factors for better OS. CONCLUSION: This study suggests that chemotherapy rechallenge may provide a survival benefit in the third-line treatment of mCRC. However, patient characteristics, such as sex and ECOG PS, should also be considered in treatment decisions. Further prospective studies are required to confirm our findings.

Phase II Trial of FOLFIRINOX in Advanced Biliary Tract Cancer.

INTRODUCTION: Biliary tract cancers (BTCs), characterized by poor prognosis and limited treatment options, are increasingly prevalent malignancies with a five-year survival rate of less than 20% for advanced-stage disease. The standard first-line chemotherapy combining gemcitabine and cisplatin offers modest survival benefits, necessitating the exploration of more effective therapies. This study reports the results of a single-arm, open-label, phase 2 trial assessing the efficacy and safety of fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) as a first-line treatment for metastatic or locally advanced unresectable BTC. METHODS: Patients aged ≥18 with measurable disease and adequate organ function were enrolled, receiving biweekly FOLFIRINOX for up to 12 cycles with follow-up imaging every four cycles. The primary endpoint was the overall response rate (ORR), with progression-free survival (PFS), overall survival (OS), and safety as secondary endpoints. RESULTS: Thirteen patients were enrolled from December 2016 to September 2021 before early termination due to slow accrual and the emergence of immunotherapy. The ORR was 54%, with a disease control rate of 77%. Median PFS and OS were 6.8 and 19.25 months, respectively. Grade 3/4 toxicities were predominantly hematologic, with neutropenia being the most common severe adverse event. CONCLUSION: The trial suggests that FOLFIRINOX is a potentially effective first-line therapy for unresectable or metastatic BTC with a manageable safety profile. However, the early termination of the study and the introduction of immunotherapy warrant further research to confirm these findings.

Characteristics and treatment results of patients with gastroenteropancreatic neuroendocrine tumors in a tertiary care centre.

BACKGROUND: Gastroenteropancreatic Neuroendocrine tumors (GEP-NET) are rare neoplasms with limited reported data from the Middle East. Our study aims to report the clinicopathological feature, treatment patterns, and survival outcomes of patients with GEP-NET from our part of the world. METHODS: Medical records of patients diagnosed with GEP-NET between January 2011 and December 2016 at a single center in Saudi Arabia were reviewed retrospectively, and complete clinicopathological and treatment data were collected. Patients' survival was estimated by the Kaplan-Meier method. RESULTS: A total of 72 patients were identified with a median age of 51 years (range 27-82) and male-to-female ratio of (1.1). The most common tumor location was the pancreas (29.1%), followed by small bowel (25%), stomach (12.5%), rectum (8.3%), colon (8.3%), and appendix (6.9%). Forty-one patients (57%) had well-differentiated grade (G)1, 21 (29%) had G2, and 4 (6%) had G3. In five patients, the pathology was neuroendocrine carcinoma and in one it could not be classified. 54.2% of the patients were metastatic at diagnosis. Forty-two patients underwent surgical resection as primary management while 26 underwent systemic therapy, three patients were put on active surveillance, and one was treated endoscopically with polypectomy. The 5-year overall survival and progression-free survivals were 77.2% and 49%, respectively, for the whole group. Patients with G1 and 2 disease, lower Ki-67 index, and surgically treated as primary management had significantly better survival outcomes. CONCLUSION: Our study suggests that the most common tumor locations are similar to western reported data. However, there seems to be a higher incidence of metastatic disease at presentation than in the rest of the world.

Characteristics and outcomes of small bowel adenocarcinoma: 14 years of experience at a single tertiary hospital in Saudi Arabia.

Small bowel adenocarcinoma (SBA) is an extremely rare cancer type. In the present study, the patient characteristics and clinical outcomes of patients diagnosed and treated for SBA at a single tertiary hospital were reported. All patients diagnosed and managed between 2007 and 2020 were reviewed. Regression analysis was used to assess variables associated with the metastatic stage at diagnosis. The Kaplan-Meier method was used to estimate survival and the log-rank test was used to determine factors associated with survival outcomes. Out of 137 cases of small bowel primary tumor, 43 consecutive patients with SBA were diagnosed with a median age of 53 years and the majority (76.7%) were males. The common initial presenting symptoms were abdominal pain (58.8%) and bowel obstruction (30.2%). The most common primary site was the duodenum (60.5%) and the majority (65.1%) were diagnosed with stage III/IV disease. Patients with a high neutrophil-lymphocyte ratio (NLR) (≥0.85) were more likely to be in the metastatic stage at diagnosis (P=0.01). The 3-year overall survival (OS) rates based on stage were 100% (I), 85% (II), 53% (III) and 33.9% (IV) (P=0.001). In addition to the stage, the Eastern Cooperative Oncology Group Performance Status (P<0.001), NLR (P<0.001), hypoalbuminemia (P=0.02) and chemotherapy in a metastatic setting (P=0.02) were prognostic factors for OS. In conclusion, NLR is a potential prognostic biomarker for a metastatic stage at diagnosis. Advanced stage, lower performance status score, low albumin level and high NLR are associated with short OS.

Thyroid Abscess in a Young Postpartum Female.

Due to the characteristics of the thyroid gland that prevent infiltration of pathogens, suppurative thyroid gland infections causing thyroid gland abscess are rarely encountered. Herein, we report a young female who presented to our hospital with pulmonary tuberculosis and Klebsiella pneumonia complicated with empyema. During her admission, she developed a rapidly enlarging and tender thyroid gland that produced respiratory obstructive symptoms. Upon clinical examination and radiological imaging, the diagnosis of thyroid abscess was confirmed. Surgical incision and drainage of the abscess was performed along with proper coverage of antibiotics. Thereafter, the patient's clinical status improved dramatically. Although thyroid gland abscesses are rare in clinical practice, a rapidly enlarging thyroid gland in a patient with overt bacterial infection should raise the suspicion of thyroid abscess. Timely diagnosis and proper management can be life-saving in such cases.

Outcomes of Patients with Metastatic Colorectal Cancer Treated with Trifluridine/Tipiracil beyond the Second Line: A Multicenter Retrospective Study from Saudi Arabia.

Background: The outcome of patients with refractory metastatic colorectal cancer (mCRC) treated with trifluridine/tipiracil (FTD/TPI) beyond the second-line has not been studied in Saudi Arabia. Therefore, this multicenter retrospective analysis was conducted to evaluate the efficacy of FTD/TPI. Methods: This multicenter retrospective analysis included five centers in Saudi Arabia. FTD/TPI was administered to all the patients beyond the oxaliplatin- and irinotecan-based chemotherapy regimens. The electronic medical records were reviewed, and progression-free survival (PFS) and overall survival (OS) were determined. Results: The study included 100 patients with a mean age of 55.4 ± 11.8 years. The overall response to FTD/TPI was 4%. The median PFS was 4 months (95% confidence interval (CI) 3.487-4.513), and the median OS was 11 months (95% CI, 9.226-12.771). In a Cox regression analysis of the independent predictors for PFS, advanced stage of the disease (P = 0.037; HR, 2.614; and CI, 1.102-7.524), presence of lymph node metastasis (P = 0.018; HR, 3.664; and 95% CI, 1.187-8.650), and >2 metastatic sites (P = 0.020; HR, 1.723; and 95% CI, 1.089-2.727) were independent factors predicting disease progression. The Cox regression analysis confirmed that age ≥ 55 years (P = 0.046; HR, 1.667; and 95%, 1.097-3.100), advanced disease stage (P = 0.044; HR, 1.283; and 95% CI, 1.035-2.940), prior use of adjuvant chemotherapy (P = 0.037; HR, 0.892; and 95% CI, 0.481-0.994), liver metastasis (P = 0.025; HR, 2.015; and 95% CI, 1.091-3.720), >2 metastatic sites (P = 0.038; HR, 1.248; and 95% CI, 1.036-1.846), development of neutropenia after receiving first cycle of FTD/TPI (P = 0.042; HR, 1.505; and 95% CI, 1.064-2.167), and increased number of FTD/TPI cycles (P = 0.002; HR, 0.769; and 95% CI, 0.664-0.891) were independent variables for OS. Conclusion: Treatment with FTD/TPI is feasible and effective in daily clinical practice in Saudi Arabian patients. The risk of progression increased with advanced disease stage, lymph node metastasis, bone metastasis, and metastasis to >2 sites. Age ≥ 55 years, advanced disease stage, liver metastasis, metastasis to >2 sites, neutropenia after the first cycle of FTD/TPI, and increased number of FTD/TPI cycles were independent factors predicting mortality.

Outcomes and Prognostic Factors of Metastatic Gastric Cancer: A Single-Center Experience.

Background Gastric cancer (GC) carries a poor survival outcome despite the availability of many therapeutic agents active in treatment. In this study, we aimed to evaluate the survival outcomes of metastatic GC treatment from a single center in Saudi Arabia and identify possible prognostic factors. Methodology Data on patients diagnosed with metastatic GC between December 2009 and November 2013 were collected and analyzed. Results During this period, 41 patients were diagnosed with a median age at diagnosis of 52 years, and 56.1% of patients were males. Only four (9.2%) patients had human epidermal growth factor receptor 2 overexpression. Overall, 83% were treated with oxaliplatin-based chemotherapy. The median progression-free survival (PFS) and overall survival (OS) were 4.1 and 15.4 months, respectively. Female sex was an independent prognostic factor for better PFS and OS. Normal lymphocyte count was associated with improved PFS. Conclusions Our study highlights poor outcomes in patients with metastatic GC and the need for further research in this field.

Pazopanib as Treatment Option for Pseudomyogenic Hemangioendothelioma: A Case Report.

Pseudomyogenic hemangioendothelioma (PHE) also known as epithelioid sarcoma-like hemangioendothelioma (ES-H) is a vascular lesion of intermediate grade biologically behaving between benign hemangioma and malignant angiosarcoma. We present a 35-year-old male with an unremarkable medical history, who was referred to a sarcoma clinic complaining of right heel pain with equinus deformity and a mass in his right lower limb for 6 months. Biopsy was performed and reported as Pseudomyogenic Hemangioendothelioma. The patient was started on pazopanib with a favorable clinical and radiological response. Long-term follow-up is still needed, however further studies are vital to clarify the role of Tyrosine Kinase Inhibitor therapy.

Prognostic significance of peritoneal metastasis from colorectal cancer treated with first-line triplet chemotherapy.

BACKGROUND: Peritoneal metastasis from colorectal cancer (CRC) carries a poor prognosis in most studies. The majority of those studies used either a single-agent or doublet chemotherapy regimen in the first-line setting. AIM: To investigate the prognostic significance of peritoneal metastasis in a cohort of patients treated with triplet chemotherapy in the first-line setting. METHODS: We retrospectively evaluated progression-free survival (PFS) and overall survival (OS) in 51 patients with metastatic CRC treated in a prospective clinical trial with capecitabine, oxaliplatin, irinotecan, and bevacizumab in the first-line setting according to the presence and absence of peritoneal metastasis. Furthermore, univariate and multivariate analyses for PFS and OS were performed to assess the prognostic significance of peritoneal metastasis at the multivariate level. RESULTS: Fifty-one patients were treated with the above triplet therapy. Fifteen had peritoneal metastasis. The patient characteristics of both groups showed a significant difference in the sidedness of the primary tumor (left-sided primary tumor in 60% of the peritoneal group vs 86% in the nonperitoneal group, P = 0.03) and the presence of liver metastasis (40% for the peritoneal group vs 75% for the nonperitoneal group, P = 0.01). Univariate analysis for PFS showed a statistically significant difference for age less than 65 years (P = 0.034), presence of liver metastasis (P = 0.046), lung metastasis (P = 0.011), and those who underwent metastasectomy (P = 0.001). Only liver metastasis and metastasectomy were statistically significant for OS, with P values of 0.001 and 0.002, respectively. Multivariate analysis showed that age (less than 65 years) and metastasectomy were statistically significant for PFS, with P values of 0.002 and 0.001, respectively. On the other hand, the absence of liver metastasis and metastasectomy were statistically significant for OS, with P values of 0.003 and 0.005, respectively. CONCLUSION: Peritoneal metastasis in patients with metastatic CRC treated with first-line triple chemotherapy does not carry prognostic significance at univariate and multivariate levels. Confirmatory larger studies are warranted.

Thromboembolic Events Burden in Patients With Solid Tumors and Their Predisposing Factors.

INTRODUCTION: The relationship between cancers and thromboembolic events is well established. In our study, we aim to determine the burden of thromboembolic events in patients with solid tumors and identify the risk factors related to their development. MATERIALS & METHODS: Data on patients with solid tumors and thromboembolism between January 2013 and September 2014 were collected and analyzed. RESULTS: During the study period 174 patients were identified. Of which, 172 (98.9%) had venous thrombus embolism, 137 (79%) were diagnosed with deep vein thromboses, 67 (38.5%) with pulmonary embolism, 84 (48.3%) were symptomatic and 90 (51.7) were incidental at diagnosis. The most common patients and disease characteristics were female sex, high body mass index (BMI), metastatic stage, colorectal and breast primaries, and anti-neoplastic therapy. CONCLUSION:  Our study confirmed the high burden of thromboembolic events in cancer patients and the relevant factors associated with its development.

Population-based survival for cancer patients in Saudi Arabia for the years 2005-2009.

The Saudi Cancer Registry reported in 2007 the 5-year observed survival for the most common cancer sites for the years 1994-2004. In this report we looked at the cancer survival in the period 2005-2009 and evaluated the trend over the 15 years period from 1994 to 2009. Cases of the top 14 cancer sites reported by the population based Saudi Cancer Registry from 1 January 2005 to December 31, 2009, were submitted for survival analysis. The vital status of those patients was collected. Analysis of survival for the above period was compared with the prior reported 2 periods (1994-1999, 2000-2004). In addition, analysis was done according to age, sex, disease stage and the province. Data of 25,969 patients of the commonest cancer sites were submitted. Of those 14,146 patients (54%) had complete demographic data available and vital status was reported. Thyroid cancer had the highest 5- year observed survival of 94% (95% confidence interval (CI) 93-95%)), followed by Breast (72%, 95% CI 71-74%). In hematological malignancies, Hodgkin's Lymphoma had the highest 5-year survival of 86% (95% CI 84-88%). Survival rates has improved in most of the cancers sites for the studied periods except for lung, uterine and Hodgkin's lymphoma which plateaued. Our study confirms a steady improvement in the 5-year observed survival over time for the majority of cancers. Our survival data were comparable to western countries. This data should be used by policy makers to improve on cancer care in the kingdom.