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.

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.

Psychosocial and clinical predictors of patient satisfaction with cancer care.

Purpose: Patient satisfaction with healthcare was recognized as an indispensable component of healthcare quality assurance programs for decades. Limited research has explored psychosocial variables impacting patient satisfaction with cancer care. The objective of our study was to identify the level of patient satisfaction with cancer care in Riyadh, Saudi Arabia and determine the psychosocial and clinical predictors of patient satisfaction. Methods: A cross-sectional observational study was carried out in 2018-2019 with patients with cancer at the Outpatient Oncology Clinic at King Saud University Medical City in Riyadh, Saudi Arabia. The questionnaire contained a visual analog scale (VAS) of satisfaction with cancer care, a VAS of satisfaction with social support, the Patient Health Questionnaire-9 Depression scale, and the Generalized Anxiety Disorder 7-item scale. Results: Out of the 400 patients approached, 280 agreed to participate in the study. Of the 280 patients participating in the study, 65% were satisfied with cancer care. Higher satisfaction was associated with being non-Saudi, being employed, having fewer household residents (≤4), being satisfied with social support, not receiving radiotherapy, and receiving hormonal or biological therapy. Having anxiety or depression was also associated with lower satisfaction. After adjustment for sociodemographic and clinical characteristics, being satisfied with social support, having ≤ 4 household residents, receiving hormonal therapy, and receiving biological therapy rather than radiotherapy were all independent predictors of higher satisfaction with cancer care. Conclusion: This study found an inadequate level of patient satisfaction with cancer care. Higher levels of satisfaction were associated with being satisfied with social support, using biological and hormonal therapy, while lower satisfaction was associated with a larger number of household residents (>4), depression, anxiety and using radiotherapy.

Incidence of trastuzumab-induced cardiotoxicity and impact of body mass index in patients with breast cancer: Results from a Saudi tertiary cancer center.

The effect of BMI as a risk factor in trastuzumab-induced cardiotoxicity in Saudi patients with HER2-neu positive breast cancer treated with trastuzumab and anthracyclines is not fully understood. The present study retrospectively evaluated the overall incidence of cardiotoxicity and the effect of BMI as a risk factor for cardiotoxicity. A retrospective study performed between 2011 and 2015 of patients with Her2-neu positive early breast cancer who were treated with either a combination of trastuzumab and anthracycline or a combination of trastuzumab with non-anthracycline or hormonal treatment in the adjuvant settings was carried out. The incidence of cardiotoxicity and the effect of BMI, hypertension and diabetes mellitus as risk factors for cardiotoxicity were assessed. Cardiotoxicity was measured using a drop in the ejection fraction of >10 percentage points to a left ventricular ejection fraction of <50%. The present cohort included 105 patients diagnosed with stage I and II breast cancer. The mean age of the present cohort was 47.5±1.0 years (range, 25-76 years), the mean height was 153.9±14.1 cm (range, 126-170 cm), the mean body weight was 75.7±15.6 kg (range, 40-143 kg) and the mean BMI was 31.3±5.8 (range, 18-49). Cardiotoxicity was detected in 21.9% of the cohort. The BMI was calculated for 81 patients who were treated with a combination of trastuzumab and anthracycline. Cardiotoxicity was detected in 3 out of 9 patients with a BMI <25, in 9 out of 23 patients with a BMI between 25 and 29, and in 6 patients with a BMI >30. There was a significant association between cardiotoxicity and BMI (P=0.03). No significant association between age, hypertension and diabetes and cardiotoxicity was identified. In conclusion, compared with global cohorts, the present results revealed a higher incidence of cardiotoxicity among Saudi patients with HER2-neu positive early breast cancer treated with trastuzumab combinations in adjuvant settings. Increased BMI was significantly associated with cardiotoxicity.

Breast-cancer detection using blood-based infrared molecular fingerprints.

BACKGROUND: Breast cancer screening is currently predominantly based on mammography, tainted with the occurrence of both false positivity and false negativity, urging for innovative strategies, as effective detection of early-stage breast cancer bears the potential to reduce mortality. Here we report the results of a prospective pilot study on breast cancer detection using blood plasma analyzed by Fourier-transform infrared (FTIR) spectroscopy - a rapid, cost-effective technique with minimal sample volume requirements and potential to aid biomedical diagnostics. FTIR has the capacity to probe health phenotypes via the investigation of the full repertoire of molecular species within a sample at once, within a single measurement in a high-throughput manner. In this study, we take advantage of cross-molecular fingerprinting to probe for breast cancer detection. METHODS: We compare two groups: 26 patients diagnosed with breast cancer to a same-sized group of age-matched healthy, asymptomatic female participants. Training with support-vector machines (SVM), we derive classification models that we test in a repeated 10-fold cross-validation over 10 times. In addition, we investigate spectral information responsible for BC identification using statistical significance testing. RESULTS: Our models to detect breast cancer achieve an average overall performance of 0.79 in terms of area under the curve (AUC) of the receiver operating characteristic (ROC). In addition, we uncover a relationship between the effect size of the measured infrared fingerprints and the tumor progression. CONCLUSION: This pilot study provides the foundation for further extending and evaluating blood-based infrared probing approach as a possible cross-molecular fingerprinting modality to tackle breast cancer detection and thus possibly contribute to the future of cancer screening.

Response to Induction Neoadjuvant Hormonal Therapy Using Upfront 21-Gene Breast Recurrence Score Assay-Results From the SAFIA Phase III Trial.

PURPOSE: Luminal, human epidermal growth factor receptor 2-negative breast cancer represents the most common subtype of breast malignancies. Neoadjuvant strategies of operable breast cancer are mostly based on chemotherapy, whereas it is not completely understood which patients might benefit from neoadjuvant hormone therapy (NAHT). MATERIALS AND METHODS: The SAFIA trial is a prospective multicenter, international, double-blind, neoadjuvant phase III trial, using upfront 21-gene Oncotype DX Breast Recurrence Score assay (recurrence score [RS] < 31) to select operable luminal human epidermal growth factor receptor 2-negative patients, for induction hormonal therapy HT (fulvestrant 500 mg with or without goserelin) before randomly assigning responding patients to fulvestrant 500 mg (with or without goserelin) plus either palbociclib (cyclin-dependent kinase 4/6 inhibitor) or placebo. The objectives of this interim analysis were to assess the feasibility of upfront RS determination on core biopsies in the Middle-East and North Africa region and evaluate the efficacy of induction NAHT in patients with an RS < 31. RESULTS: At the time of this interim analysis, 258 patients with relative risk were accrued, including 202 patients (RS < 31% to 78.3%) treated with induction NAHT and 182 patients evaluable so far for response. The feasibility of performing the Oncotype DX assays on core biopsy specimens was optimal in 96.4% of cases. Overall, 93.4% of patients showed hormone sensitivity and no difference in NAHT efficacy was noticed between RS 0-10, 11-25, and 26-30. Interestingly, patients with high RS (26-30) showed a trend toward a higher major response rate (P = .05). CONCLUSION: The upfront 21-gene assay performed on biopsies is feasible in our population and has allowed us to select patients with high hormone sensitivity (RS < 31). This approach could be an alternative to upfront surgery without significant risk of progression, particularly during pandemic times.

Prevalence and determinants of distress among oncology patients at a tertiary care medical city in Riyadh, Saudi Arabia.

OBJECTIVES: To estimate the prevalence of distress in patients with cancer in Saudi Arabia and to identify common psychosocial stressors in these patients. We also looked for associations between distress and psychological, sociodemographic, and medical factors. METHODS: This cross-sectional study was performed in the oncology outpatient clinic at King Saud University Medical City, Riyadh, Saudi Arabia, from January 2018 to December 2019. It included 280 patients with breast cancer, colorectal cancer, or lymphoma. Sociodemographic information was collected using questionnaire, along with information on medical history and any psychiatric history. Distress was assessed using the Distress Thermometer and Problem List. Satisfaction with social support was rated using the visual analog scale. All patients were screened for depression using the Patient Health Questionnaire 9-item depression scale and anxiety using the Generalized Anxiety Disorder 7-item scale. RESULTS: The prevalence of distress in our study population was found to be 46%. Distress was associated with several practical, family, emotional, and physical stressors in the problem list. Logistic regression identified predictors of distress to be anxiety (odds ratio [OR] 8.7, confidence interval [CI] 1.98-38.24, p=0.002) and receiving radiotherapy (OR 3.6, CI 1.33-9.99, p=0.009), while Saudi nationality (OR 0.22, CI 0.05-0.95, p=0.037) and stage I cancer (OR 0.18, CI 0.05-1.40, p=0.002) were associated with low distress. CONCLUSION: Approximately half of cancer patients were found to have distress. Anxiety, advanced cancer stage, and radiotherapy were independently associated with distress.

Myeloid Leukemias: A Glance at Middle Eastern Centers.

BACKGROUND AND OBJECTIVES: Myeloid leukemias (MLs) are clonal stem cell disorders affecting myeloid lineage cells. Advances in cytogenetic and molecular studies partially disclosed the mystery about risk factors and pathophysiology of MLs. Regarding incidence, risk factors, response to treatment, and overall survival of patients, research showed differences among different countries. However, the Western registry data are the basis for the documented description of MLs in medical textbooks. This research aimed to study MLs in Middle Eastern health centers. Egypt has the highest population in the Middle East; furthermore, 96.6% of the population is native Egyptians; accordingly the study focused on Egypt. PATIENTS AND METHODS: Data of 468 patients with MLs were collected from hospital records at two big tertiary health centers. They were grouped into group 1 (chronic myeloid leukemia, CML) and group 2 (acute myeloid leukemia, AML); the latter was subgrouped into 2a (primary AML) and 2b (secondary AML). RESULTS AND CONCLUSIONS: The median age of patients was 43 years; males predominate in group 2a and females in groups 1 and 2b. 37.2% of group 1 patients were treated with Gleevec. Hematopoietic stem cell transplantation was planned for only 5% of group 2 and 18% relapsed. Of groups 1 and 2 patients, 25% and 12%, respectively, stopped follow up, and 15% and 35% died. ORR and overall survival were 53%, 27% and 7%, 0.4% for groups 1 and 2, respectively. Conclusively, this study showed a young age of ML patients, with female predominance in CML, and poor outcome. This reflected racial, ethnic and risk factor differences in incidence of MLs.

Validity and feasibility of the Arabic version of distress thermometer for Saudi cancer patients.

BACKGROUND: The distress thermometer (DT) has been studied and validated as an effective screening instrument for identifying distress among cancer patients worldwide. This study aims to evaluate the validity of the Arabic version of the DT in Saudi cancer patients, to define the optimal cutoff point of the Arabic DT for detecting clinically significant distress and to determine whether there is any correlation between clinically significant distress and other demographic and Problem List variables. METHODS: The original form of the DT was translated to Arabic using a forward and backward translation method. Then, a group of 247 cancer patients who were followed up at the Outpatient Oncology Clinic at King Saud Medical City in Riyadh, Saudi Arabia, completed a socio-demographic and clinical status questionnaire, the DT and the Problem List scale, and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Receiver operating characteristic (ROC) curve analyses picked out an area under the curve of 0.76 when compared with a HADS cutoff score of 15. The DT had the best sensitivity (0.70) and specificity (0.63) with cutoff score of 4. A DT score of 4 or more was found to have a statistically significant correlation with female gender, advanced cancer stages and most of the Problem List items, including child care, work or school, treatment decision, dealing with children and partners, depression, fears, nervousness, sadness, loss of interest in usual activity, religious concerns, appearance, bathing/dressing, breathing, diarrhea, fatigue, feeling swollen, fever, getting around, indigestion, memory and concentration, nausea, dry nose, pain, and sexual problems. In contrast, a multivariate regression analysis confirmed only advanced cancer stages, treatment decision, depression, fear, sadness, worry, breathing, feeling swollen, fever, indigestion, memory and concentration, dry nose and congestion, pain and sleep as independent factors associated with distress in cancer patients. CONCLUSIONS: We found the Arabic version of the DT to be a valid instrument for screening distress in Saudi patients with cancer. Our study proposes using a cutoff score of 4 as an indicator of clinically significant distress in this population.

Characteristics of escape mutations from occult hepatitis B virus infected patients with hematological malignancies in South Egypt.

AIM: To investigate the prevalence and virological characteristics of occult hepatitis B virus (HBV) infections in patients with hematological malignancies in South Egypt. METHODS: Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen (HBsAg), and antibodies to HBV core (anti-HBc) and surface antigens. Serum samples negative for HBsAg and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed. RESULTS: HBV DNA was detected in 23 (42.6%) of 54 patients with hematological malignancies who were HBsAg negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120T and S143L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The in vitro analyses revealed that a lower level of extracellular HBsAg was detected by chemiluminescence enzyme immunoassay (CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143L mutation despite the similar levels of extracellular and intracellular HBsAg detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones. CONCLUSION: Occult HBV infection is common in patients with hematological malignancies and associated with P120T and S143L mutations. 120T mutation impairs the detection of HBsAg by CLEIA.

Incidence and characteristics of HBV reactivation in hematological malignant patients in south Egypt.

AIM: To investigate characteristics of hepatitis B virus (HBV) implicated in HBV reactivation in patients with hematological malignancies receiving immunosuppressive therapy. METHODS: Serum samples were collected from 53 patients with hematological malignancies negative for hepatitis B surface antigen (HBsAg) before the start of and throughout the chemotherapy course. HBV reactivation was diagnosed when the HBsAg status changed from negative to positive after the initiation of chemotherapy and/or when HBV DNA was detected by real-time detection polymerase chain reaction (RTD-PCR). For detecting the serological markers of HBV infection, HBsAg as well as antibodies to the core antigen (anti-HBc) and to the surface antigen were measured in the sera by CEIA. Nucleic acids were extracted from sera, and HBV DNA sequences spanning the S gene were amplified by RTD-PCR. The extracted DNA was further subjected to PCR to amplify the complete genome as well as the specific genomic sequences bearing the enhancer II/core promoter/pre-core/core regions (nt 1628-2364). Amplicons were sequenced directly. RESULTS: Thirty-five (66%) of the 53 HBsAg-negative patients were found to be negative serologically for anti-HBc, and the remaining 18 (34%) patients were positive for anti-HBc. Five of the 53 (9.4%) patients with hematologic malignancies experienced HBV reactivation. Genotype D1 was detected in all five patients. Four types of mutant strains were detected in the S gene product of HBV strains and were isolated from 3 patients with HBV reactivation: T/S120, L143, and I126. HBV DNA was detected in the pretreatment HBsAg-negative samples in one of the five patients with HBV reactivation. In this patient, sequences encompassing the HBV full genome obtained from sera before the start of chemotherapy and at the time of de novo HBV hepatitis were detected and it showed 100% homology. Furthermore, in the phylogenetic tree, the sequences were clustered together, thereby indicating that this patient developed reactivation from an occult HBV infection. CONCLUSION: Past infection with HBV is a risk factor for HBV reactivation in Egypt. Mandatory anti-HBc screening prior to chemotherapy in patients with hematological malignancies is recommended.

Transcriptional regulatory regions of the survivin gene activate an exogenous suicide gene in human tumors and enhance the sensitivity to a prodrug.

Selective expression of a therapeutic gene in tumors contributes to the efficacy and the safety of cancer therapy. Regulatory regions of genes that are preferentially expressed in tumors have been examined. The regions of the survivin gene exhibited the greatest activity in human hepatocellular carcinoma cells. Deletion of the survivin regulatory region from the 5'-side demonstrated that the 0.5 kb and the 1.4 kb fragments possessed a strong promoter activity with relative tumor specificity. Human tumors transfected with the herpes simplex virus-thymidine kinase gene, that was powered by the survivin region, became susceptible to a prodrug, ganciclovir. Although survivin gene expression was up-regulated in the G2/M-phase of the cell cycle, taxol or vincristine treatment, which induce cell cycle arrest at the M-phase, did not enhance the transcriptional activity of the survivin promoter. These data collectively suggest that the survivin regulatory region induces the expression of an exogenous gene in tumors, but the transcriptional activity is not directly linked with M-phase induction.