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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.

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 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.

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.

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.

e15586 Background: In Saudi Arabia, the incidence of colorectal cancer has been increased over the past few years. The optimal treatment beyond the second line is not fully understood. To the best of our knowledge, the efficacy and disease outcomes of triflurodine/tipiracil in Saudi patients with refractory metastatic colorectal cancer(mCRC) has not been studied yet. Our study is a real-life practice evaluation of the efficacy of triflurodine/tipiracil in patients with refractory mCRC. Moreover, the prognosis and the prognostic significance of the different clinical variables have been analyzed. Methods: A retrospective, multi-centers ( 5 centers representative of Saudi Arabia )observational study in patients with mCRC who have received triflurodine/tipiracil beyond oxaliplatin & Irinotecan-based chemotherapy between December 2018-December 2020.We aimed to assess the response to triflurodine/tipiracil, to evaluate the progression-free survival (PFS ), the overall survival (OS), and the associated factors of prognostic significance. Results:The data of 100 patients with refractory mCRC who has received triflurodine/tipiracil have been analyzed. The mean age was 55.2 +11.8 years. Forty-two patients were (42%) females and 58 (58%) were male patients. Sigmoid was the most common primary site of cancer in 35 (35%) patients, followed by rectum 29 (29%). Peritoneal metastasis was present in 17 (23.3%) patients ,liver in 51(56.6%) and lung in 39 (50.7%). Metastatic sites were ≥ 2 in 45 (45%) patients. Metastatic lesions were ≥ 5 in 65 (65%) patients. Xelox chemotherapy regimen was the most commonly used first-line chemotherapy which represents 43%, while Folfiri or Xeliri combination was the most used second line in 57 (60%). For the third line, Folfox or Xelox was used in 81 (83.5%) patients. The fourth line was given to 49 (67.1%). For first-line biological agents, Cetuximab was used most frequently 31 (46.3%).Evaluation of the response to treatment with triflurodine/tipiracil revealed one patient (1%) with a complete response,3 patients (3%) with partial response, 28 (28%) patients with stable disease, and 66 (66%) showed progressive disease. The estimated median progression-free survival was 5 months ( 3.839 - 6.161) and the median overall survival was 12 months (9.732-14.268). The log-rank analysis showed that the baseline neutrophils ≤ 75 % ( P-value= 0.0092) and low hemoglobin level (P-value= 0.0245) were strongly associated with a higher survival. By multivariate Cox regression analysis, the neutrophil count ≤ 75 % was the only independent predictor for survival. Conclusions: Trifluridine/tipiracil is effective in patients with refractory mCRC. The low neutrophil count might predict a better overall survival.

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.

Background BC screening by mammography is associated with a significant reduction in mortality (19 % overall reduction of the relative risk), however with significant limitations and debatable cost-effectiveness. Screening individuals for cancer using liquid biopsies (LB) represents an unmet need. We report the first prospective “proof of concept” study using the QO technology combined with an AI approach using the concept of “MPnV” applied to BC detection. Methods QO (femto/atto-second infrared laser spectroscopy) on LB is a simple, non-invasive and reproducible method allowing to identify individualized molecular spectra (MS). These highly detailed MS can be correlated to physiological or pathological changes allowing detection and translation of differences. Integrated into a super-computational approach using a non-hierarchical deep data mining strategy (MPnV concept), MS could discriminate individuals with and without BC. The plasma of 68 controls and 27 BC patients, accrued at the King Saud University BC screening program, Riyadh, Saudi Arabia (KSA), were studied by QO (Max Planck Institute of Quantum Optics /Ludwig Maximillian University Munich, Garching, Germany). The MS were analysed on the Shaheen II supercomputer at King Abdallah University for Science and Technology (KAUST), KSA, in order to generate comparative algorithms. Results The use of special feature selection, followed by class analysis allowed to differentiate profiles between the two groups with a sensitivity of 97% and a specificity of 72% (variables n = 1,100). A more in-depth analysis led to 99% sensitivity, but with a lower specificity of 64%. Further analysis of the series, using an age-matched approach led to 97% sensitivity with 98% specificity in differentiating women with or without BC. Conclusions These results warrant a large scale prospective validation BC screening trial (ongoing) and “proof of concept trials” in other frequent cancers, in particular those without existing screening programs. Editorial acknowledgement Prof. Ferenc Krausz, Director, and Dr. Mihaela Zigman, Leader of the Broadband Infrared Diagnostics, Max Planck Institute of Quantum Optics (MPQ), Faculty of Physics at Ludwig-Maximilians Universitat Munchen (LMU), Garching, Germany. Legal entity responsible for the study Jean Marc Nabholtz, Oncology Centre, King Saud University, Riyadh, Saudi Arabia. Funding 1. Oncology Centre, King Saud University Medical City, King Saud University, Saudi Arabia. 2. Max-Planck-Institut fur Quantenoptik and Faculty of Physics at Ludwig-Maximilians Universitat Munchen, Garching, Germany. 3. Computational Bioscience Research Centre, King Abdallah University for Science and Technology (KAUST), Thuwal, Saudi Arabia. Disclosure M.R.K. Bahadoor: Travel / Accommodation / Expenses, ASCO Participation Funded: Pfizer; Advisory / Consultancy, Pancreas Expert Opinion Advisory: Baxter. All other authors have declared no conflicts of interest.

Background NA chemotherapy (CT) +/- anti-Her2 treatment of operable breast cancer (BC) is considered a standard option in the management of BC. However, pathologic complete response (pCR) rates with CT in HR+/Her2- BC are usually low: 7% (Luminal A) to 16% (Luminal B). Alternatively, NA endocrine therapy (ET) has not been established as a standard treatment because of low pCRs. Methods This is a multicenter phase III, 3rd generation NA trial performed in 34 centers and 7 countries of Middle-East and North Africa (MENA Region). The objective is to investigate the potential role of adding Palbociclib to ET (Fulvestrant +/- Goserelin) compared to ET alone as NA therapy of HR+/Her2- operable BC sensitive to ET. The primary endpoint is pCR with the hypothesis that the addition of Palbociclib would increase the pCR rate from 5% to 15%. Clinical/radiological response, conservative surgery rate, safety, disease-free and OS are secondary endpoints. Exploratory endpoints encompass biomarker serial analysis of liquid biopsies with Quantum Optic and DNA methylation technologies. Results A total of 400 pre and post-menopausal pts with stage II and IIIA are planned to be recruited. Oncotype DX is performed upfront in order to eliminate CT candidates. All pts with a recurrence score (RS) Conclusions SAFIA trial aims to evaluate whether or not the addition of a CDK 4/6 inhibitor to pts sensitive to ET would validate a neo-adjuvant strategy without CT in luminal operable BC. Clinical trial identification NCT03447132. Legal entity responsible for the study International Cancer Research Group (ICRG). Funding Pfizer, AstraZeneca and Genomic Health. Disclosure All authors have declared no conflicts of interest.