e23501 Background: Ewing sarcoma family of tumors (ESFT) is a rare malignancy among adults. Most studies from western countries have reported improvement in outcomes following multi-agent chemotherapy. We report our experience in the management of this disease among Arab ethnicity. The aim of this study is to assess the outcome of VAIA combination as a first-line treatment in Adult-patients with metastatic Ewing sarcoma. Methods: Patients who were newly diagnosed as metastatic Ewing sarcoma between 03/1997 and 11/2016 at King Faisal Specialist Hospital and Research Center, who received VAIA as first-line therapy were eligible. The patient's characteristics were summarized using Medians with interquartile ranges (IQR) and frequencies for continuous and categorical variables, respectively. Variables including age, sex, primary tumor size, site (skeletal vs extraskeletal) and extent of metastasis in correlation with progression and overall survival were analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results: Thirty-nine patients were identified. Male (26, 66.7%), Female (13, 33.3%). Skeletal (27, 69.2%), Extraskeletal (12, 30.8%). The median longest diameter of the primary tumor 9.75 (IQR 8-15). The most common metastatic sites were Lungs (22, 56.4%) & Bone (10, 25.6%), however, the least common sites were Bone Marrow (3, 7.7%) and liver (2, 5.1%). The median number of VAIA cycles was 10 cycles (IQR 5-14). Objective response rate (ORR) was noticed in 20 patients (51.2%) (Complete Remission (7, 17.9%), Partial Remission (13, 33.3%). One patient had stable disease and 12 (30.8%) patients had progressive disease. The assessment was not feasible in 3 (7.7%) patients. With a median follow up duration of 18 months (1-44).20 patients died (62.5%). The median PFS and OS was 10,18 months respectively with 3,5 years overall survival rate of;35.7%,26.9% respectively. Univariate analysis correlation among different variables were insignificant. Conclusions: VAIA chemotherapy combination showed poor outcomes among our patients in comparison to literature further improvement is needed in this aggressive malignancy in our region.
e15021 Background: Regorafenib is a multi-kinase inhibitor that was FDA approved for the treatment of refractory advanced colorectal cancer. It has been found in the clinical trials to have modest benefit and relatively high toxicity, but the outcome of its routine use in the clinic practice is lacking. Our aim is to assess the outcome in our local clinic practice. Methods: Records of all colorectal cases who were treated with regorafenib were reviewed. Structured CRF was developed. Clinical, pathological and molecular data were collected. Efficacy and toxicity details were analyzed. Results: Thirty-two cases of metastatic colorectal cancer were treated with regorafenib from February 2014 to February 2016. All patients received prior oxaliplatin, irinotecan and bevacizumab based regimens, and cetuximab if wild type. Median age: 53.5 years. Male: 15 (46.9%). Primary tumor was right sided in 10 patients (31.3%), and left sided (including rectum) in 22 (68.7%). Pan RAS mutant: 21 (65.6%). Fifteen patients (46.9 %) had ECOG Performance Status of one, whereas 16 patients (50%) have ECOG 2. Starting dose was reduced to 120mg in 11 (34.4%). Only 5 (15.6%) continued beyond 3 cycles. 18 patients (56.3%) required dose reduction. Overall response: PR/CR: zero; Stable disease: 4 (12.5%); Progressive disease: 25 (78.1%); Clinical progression in 1 (3.1%), and 2 cases were not evaluated. After median follow up of 7 months, 22 patients (68.8%) have died, 5 (15.6%) are still alive and 5 (15.6%) are lost to follow up. Median survival: 9.3 months, and median PFS: 2.5 months. Conclusions: Regorafenib has poor tumor response in the routine clinic practice when given to patients with ECOG PS > 1. The median survival in this series is probably overestimated because of the relatively high rate of loss to follow up. Selection of patients is required in the routine clinic practice. Predictive markers are more important for such treatment with modest benefit, and significant toxicity and cost.
e13001 Background: Trastuzumab emtansine (T-DM1) significantly prolongs progression-free survival (PFS) with a safe drug profile in advanced HER-2-positive (HER+) breast cancer (BC) patients. However, there are currently no reports regarding its efficacy and safety in the Middle East. Methods: We retrospectively reviewed the data of 55 metastatic HER+ BC patients who received T-DM1 at our center. Results: The median age at diagnosis was 44 years (25-69). 65.45% patients presented as a de novo metastatic presentation and 56.46% were hormone receptor-positive (Table). 80%, 65.45%, 43.63% suffered visceral, CNS, and skeletal metastasis, respectively. The median duration of follow up was 31.5 months (3-61). 54.45% of patients were alive with disease at the date of last follow up, and 35.45% passed away. The median number of cycles given was 12 cycles (1-60). The best response, according to RECIST criteria v1.1, was complete remission in 5.45%, partial response in 40%, and stable disease in 23.64%. The mean overall survival (OS) was 117.3 months (95% CI: 97.35-137.24), and the median OS was not reached. The median PFS was 10.91 months (95% CI: 5.61-16.21) and the 3-year PFS was 17.6%. Four patients are still receiving T-DM1 treatment at the time of analysis. 85.45% stopped their treatment due to disease progression, and two (3.63%) patients stopped due to severe drug toxicity. Drop in ejection fraction and allergic reactions were the most common side effects, which were both seen in 18.18% of patients. Conclusions: The efficacy and safety profile of T-DM1 in our patient is comparable to that of other international populations. Larger, multicenter studies are needed to confirm our findings. ECOG performance status at presentation 0 6 (10.7%) 1 45 (80.4%) 2 4 (7.1%) Metastectomy Brain 10 (18.18%) Bone 1 (1.81%) Lungs 1 (1.81%) Total number of drug lines 2-4 31 (56.36%) 5-7 23 (41.81%) 8 1 (1.81%)
e16277 Background: Small bowel adenocarcinoma (SBA) is a rare disease. We aim to describe patient's characteristics and clinical outcomes among Saudi patients. Methods: All patients with SBA diagnosed between 2007 - 2020 were reviewed. Logistic regression was used to assess variables associated with metastasis at diagnosis, and a log-rank test was used to compare factors associated with survival. Results: Forty-three patients were eligible for analysis, and (76.7%) were males. The median age at diagnosis was 53 years. History was significant for colon cancer in two patients, celiac disease in three patients, Lynch syndrome, Familial adenomatous polyposis (FAP), Non-APC in one patient, and cholecystectomy in seven patients. The common initial presenting symptoms were abdominal pain (58.8%), bowel obstruction (30.2%), Overt gastrointestinal bleeding (9.3%). Tumor markers were elevated in 21 patients. EGD was used for diagnosis in 60.5%, while CT scan in 23.3%. The most common primary site was duodenum 60.5%, jejunum 27.9%, ilium 7%. Stage IV was (41.9%). The most common site for metastases was the liver in 10 patients. Patients' ECOG performance status was 0/1 in 51% at diagnosis. Univariate analysis did not reveal that patients with high Neutrophil-lymphocyte Ratio (NLR) (≥0.85) are more likely to be metastatic; P = 009. There was no association of sex, presenting complaints, tumor markers with the stage at diagnosis. Surgery was performed for 53.4% of patients (RO, 73%), and the median DFS was 49 vs. 8 months in R0 vs. R1 group, respectively (p = 0.01). FOLFOX Chemotherapy regimen was given for 10 patients as adjuvant treatment and for 8 patients for metastatic sitting. The median duration of follow-up was 12 months. The median overall survival (OS) for localized stages was not reached, and for the metastatic stage was 10 months. The 3 years OS based on stages were 100% (I), 85% (II), 53% (III) and 35% for (IV), p = 0.001. Other factors associated with survival were ECOG Performance status (p < 0.001), NLR ( < 0.001), CA19-9 (p = 0.04), and receiving chemotherapy in a metastatic setting (p = 0.02). Conclusions: SBA is diagnosed at a younger age in Saudi patients and more in males. The advanced stage, lower performance status score, high CA19-9, and high NLR at diagnosis are associated with poor OS. NLR could be a prognostic factor for a metastatic stage at diagnosis.
e12534 Background: Metaplastic breast cancer (MPBC) accounts for less than 1% of all breast cancer subtypes. Methods: Patients diagnosed with MPBC between 2001 are 2018 were reviewed. Disease characteristics, progression-free survival (PFS), and overall survival (OS) were estimated by the Kaplan-Meier method and compared by log-rank test. Results: Fifty-five MPBC patients were analyzed. The median was 46 years (IQR 40–55). 14.5% had a positive family history of cancer. The majority (98.2%) presented with a lump, and two patients presented with bilateral disease. The median BMI was 31 (IQR 24.5–37.5). The majority had stage III (56.4%), and stage IV was (7.3%). Most patients (90.9%) had triple-negative disease. The tumor grade (G) was available for 63.6% of patients (G2 11.4% and G3 88.6%). Nineteen patients (34.5%) received neoadjuvant chemotherapy (NAC) [anthracycline-based (15,78.9%), and platinum-taxane (11, 57.8%)]. The majority (92.7%) underwent surgery, 56.4% MRM, 12.7% BCT, 12.7% simple mastectomy, 7.3% palliative mastectomy. 54.5% underwent ALND and 20% SLNB. One patient had pCR. Adjuvant radiation was given for (33, 60%) and (37, 67.3%) received adjuvant radiation therapy. The median follow-up duration is 44 months (IQR 21–69). For nonmetastatic disease, 3-years DFS was 67.5%. There was no difference in DFS with using NAC (p-0.96) or being obese (p = 0.50). The 3-years OS was 72.9%, and the Log-rank test revealed prolonged survival with radiation therapy 87.1% vs. 56.6% ( p = 0.02) and earlier stage at diagnosis. 3-years OS for stage II was 92.9%, stage III was 71%, and no survival in stage IV (p < 0.001). There was a clinical difference in 3 years OS between obese vs. nonobese 61.3% vs. 85.9%, with no statistical significance (p = 0.15). Conclusions: The majority of patients diagnosed with MPBC had large tumor size, nodal disease, and more triple-negative disease, locally advanced and nonmetastatic. The DFS and OS were comparable to reported survival. There is a significant correlation between survival and stage and adjuvant radiation therapy.
e23581 Background: Sarcomas are aggressive malignancy,30-40% of them originate from retroperitoneal space. which makes adequate free surgical margin after surgical debulking mostly not achievable. The addition of Hyperthermic intraperitoneal chemotherapy (HIPEC)+/- Intraoperative radiation therapy (IORT) may overcome local failure with an overall survival benefit. we studied the outcome of cytoreductive surgery (CRS)+ HIPEC +/- IORT on patients with peritoneal sarcomatosis,at our institute. Methods: Patients with peritoneal sarcomatosis treated with CRS+ HIPEC +/- IORT, in the period between 2011-2016 were included. Results: 24 patients identified;15(62.5%) were males. Median age was 58(31-77). Liposarcoma was the most frequent diagnosis in 50% of them. Neoadjuvant chemotherapy was received in 5 patients, while neoadjuvant radiation therapy was received in 3 patients. Cytoreduction completeness score (CC-0/1) was achieved in 19(79.17%), with median peritoneal cancer index (PCI) of 11 (3–28). Melphalan was the most commonly used agent for HIPEC chemotherapy, it was used in 16(66.67%) patients. IORT was given in 16(66.67%) patients. 8 patients developed grade III-IV Clavien-Dindo (CD) complications, with one died 5 days post operatively due to pulmonary embolism. Adjuvant chemotherapy was received in 9 patients. After a median follow up of 21 months, the mean, 2 years and estimated 4 years progression free survival was 19.6 months, 30.6% and 15.3% respectively, 13(54.2%) patients developed systemic progression, lung was the most affected site at time of progression in 8/13(61.5%) patients. Local progression occurred in two patients, while both systemic and local progression occurred in one patient. The 3 cases progressed locally underwent redo CRS and HIPEC with average 18 months between the first and redo surgery. The mean, 2 years and estimated 4 years overall survival was 21.2 months, 75.7% and 75.7% respective. In univariate analysis only CC score correlate with PFS, the mean PFS for those patients with CC (0-1) vs (2-3) was 13.7 vs 11.5 months ( p = 0.036). Conclusions: Addition of HIPEC+IORT to surgical debulking in the management of peritoneal sarcomatosis; seems to be safe and may improve local control rate with a questionable survival benefit, a larger cohort with a multicentric study is needed for further evaluation.
665 Background: Tyrosine kinase inhibitors remain a corner stone in the management of metastatic clear cell renal cell carcinoma (RCC). The intermittent schedule of sunitinib with 4 weeks on/2 weeks off could result in a rebound angiogenesis and tumor progression in the 2 weeks rest period. We propose the use of bevacizumab to alternate with sunitinib to attain continuous anti-angiogenesis during sunitinib therapy. Methods: This was a phase I/II design. Patients advanced clear cell RCC were recruited. Sunitinib was given as 50 mg daily on 4 weeks on/2 weeks off schedule. Bevacizumab was given on day 29 of each sunitinib cycle. Bevacizumab starting dose was 5 mg/kg and the dose was escalated to 10 mg if no dose limiting toxicity. Primary endpoints were response rate and progression-free survival. Results: Twenty-five patients were recruited. The study was closed prematurely because of poor accrual. No dose limiting toxicity was found on the 5 mg dose level of bevacizumab. One patient achieved complete response and 12 achieved partial response for a response rate of 52%. At a median follow up was 42.2 months (95%, confidence interval (CI) 32.9 to 51.4), the median progression-free survival was 16.5 months (95% CI 4.1-28.8), and the median overall survival was 33.3 months (95% CI 19.4-47.3). Twenty-two patients (88%) had at least one grade 3 or 4 toxicity. The commonest grade 3 or 4 toxicity was thrombocytopenia and lymphopenia each occurring at a rate of 32%, followed by hypertension at a rate of 28% followed by fatigue at a rate of 24%. Conclusions: Continuous angiogenesis blockade by adding bevacizumab to sunitinib 4 weeks on and 2 weeks break regimen in advanced RCC produce significant anti-tumor activity with manageable increased toxicity. Clinical trial information: NCT02919371 .
e16348 Background: Pancreatic Cancer is one of the leading causes of cancer death in Saudi Arabia. Surgery is the mainstay of treatment in resectable non-metastatic cases. Working on improving the resectability rate to achieve R0 resection is the standard of care. Methods: Unresectable cases of pancreatic adenocarcinoma seen from 2004 till 2018 in three hospitals in Saudi Arabia were reviewed to know the conversion rate from unresectable or borderline resectable to resectable after neoadjuvant chemotherapy and to explore the possible prognostic factors. The characteristics and outcomes of these patients were reviewed, with more attention on the known prognostic factors and their impact on the outcome. Notably, performance status, CA19-9, Neutrophil Lymphocyte Ration (NLR), and Platelet Lymphocyte Ratio (PLR). Overall response to neoadjuvant therapy, R0 resection, relapse free survival and overall survival were all reported. Results: Two hundred seventy-three captured cases of all types of pancreatic tumors from the tumor registry in the years between 2004 and 2018. 39 cases were unresectable or borderline resectable cases. The median age was 60 years (range:29-79), and 25 patients were males. 30 patients had an ECOG PS of 0-1and 6 had an ECOG PS of 2. The head of the pancreas was the primary tumor site in 31 patients and the body or tail was in 8 patients. 21 patients (54%) presented with weight loss ( > 5kg), and 21 patients (54%) presented with obstructive jaundice. Neoadjuvant chemotherapy protocols were FOLFORINOX (13 patients, 33%), Gemcitabine/Capecitabine (10 patients), single agent Gemcitabine (10 patients), and other regimens in 6 patients. The median number of chemotherapy cycles was 6 (range: 1-14). 17 patients had dose reduction. 6 patients had preoperative radiation. Response to chemotherapy: ORR: 36%, SD: 26% and PD: 38% .Surgery was done after neoadjuvant therapy in 12 patients (31%). Only 4 out 12 had confirmed R0. Median Overall Survival (MS) and Progression-Free survival (PFS) in all patients were 30 mo (95% CI: 17.75 - 42.56) and 8 mo (95% CI: 5.65 - 11.89) respectively. MS in the surgery and the non-surgery groups was 30 and 25 mo (p- value = 0.26) respectively. The median PFS in the surgery and the non-surgery groups was 19.6 and 5.8 mo (p- value = 0.008) respectively. Multivariate regression analysis done for the following variables: ECOG PS of 2, elevated CA 199, high NLR > 3, high PLR > 225, weight loss and results showed numerical difference of both MS and PFS with no statistical significance (Type 2 error). Conclusions: The conversion rate from unresectable or borderline resectable to resectable after neoadjuvant therapy is 31% which is consistent with the international data. There is PFS improvement in those who underwent surgery (19.6 mo vs. 5.8 mo) with statistical significance (p:0.008), and there is numerical improvement of MS (30 mo vs. 25 mo) that did not reach statistical significance.
e23085 Background: Little data are available surrounding the outcomes and risk factors of COVID-19 in Saudi oncological patients. This study aims to elucidate the outcomes of COVID-19 infection among Saudi oncology patients and associated risk factors. Methods: We retrospectively reviewed the medical files of oncology patients who were diagnosed with COVID-19 at the King Faisal Specialist Hospital and Research Centre. The time from a positive PCR until death or last follow-up was calculated as COVID-specific survival. A p-value less than 0.05 was selected as the threshold for statistical significance. Results: 161 oncological patients were included in our analysis. The mean age was 53.83±15.81. 85 (52.8%) patients were female, 17 (10.6%) had a positive history of smoking, and 57 (35.4%) were obese. 70 (43.5%) patients had diabetes mellitus, 64 (39.8%) had hypertension, and 25 (15.5%) had dyslipidemia. The most common cancer in the group was breast cancer, which was present in 24 (14.9%), followed by non-Hodgkin lymphoma, colon cancer, and acute leukemia, respectively. 57 (35.4%) patients had no evidence of disease (NED) at presentation. Furthermore, 65 (40.4%) patients had received antineoplastic therapy within 30 days before infection. 25 (15.5%) patients had stage A COVID-19, 59 (36.6%) had stage B, 48 (29.8%) had stage C, and 29 (18%) had stage D. There was no difference between active and no NED patients in remission in regard to the stages of COVID-19 infection at presentation (p = 0.05). However, the stages of COVID were less severe in patients who received antineoplastic therapy (p = 0.02). 32 (19.9%) patients received tocilizumab during the acute phase of infection. Only 5 (3.1%) patients suffered COVID-specific death. Therefore, the median COVID-specific survival was not reached. Tocilizumab (p = 0.34), corticosteroids (p = 0.77), ACE inhibitors (p = 0.45) had no impact on COVID-specific death in our patient population. In patients who received steroid treatment, the duration of corticosteroid had no impact on survival (HR: 0.76, p = 0.39). Ventilation also had no impact on survival (p = 0.55). There was no difference between patients who received antineoplastic therapy within 30 days from infection and those who did not (p = 0.99). Finally, we noted no difference in survival between patients with active disease and NED patients (p = 0.17). Conclusions: COVID-related mortality is lower in Saudi oncology patients compared to other countries. Early management and admission of oncological patients may result in overall improved outcome. In line with some studies, antineoplastic therapy can reduce COVID-19 severity, possibly due to reduced ACE receptor expression.
28 Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) in addition to Cytoreductive surgery (CRS) has survival benefit observed in management of Peritoneal Carcinomatosis (PC) from Colo-rectal cancer (CRC)origin. We report the outcomes and prognostic factors of patients with CRC, who presented with PC and underwent CRS and HIPEC at King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia. Methods: Patients presented with PC from CRC origin and underwent CRS and HIPEC; from February 2009 to September 2015 were recruited. Results: 52 patients identified. A total of 55 CRS procedures were performed, where 3 patients underwent repeated CRS and HIPEC for tumor recurrence. All except 3 used mitomycin-C for HIPEC, the remaining received either melphalan (2 patients) or cisplatin plus mitomycin-C regimen (1 patient). Melphalan used for patients who underwent repeated HIPEC as 2nd line chemotherapeutic agent. Intraoperative Radiation therapy performed in 5 patients with tumor invading the surrounding structures, where performing a safe or complete resection was either technically difficult or carried high risk. Complication assessment by Clavien-Dindo score, 62 % grade (I-II), while 31% had grade (3–4). Two patients (3.6%) died postoperatively; both from sepsis. Respiratory complications were the most commonly encountered morbidities. The 5-year overall survival(OS) was 50% with disease free survival (DFS) 29.5%. Univariate analysis showed poor OS and DFS encountered in; Signet-ring tumors (p < 0.0001) for both, peritoneal cancer index (PCI) ≥ 6 (p < 0.0009) for both, completeness of cytoreduction(CC) score >1 (p < 0.0001) for both, and high 3-month postoperative carcinoembryonic antigen value (p <0.0001) for both. In multivariate analysis; DFS was significant for (PCI) ≥ 6 (p < 0.0131) and (CC) score >1 (p < 0.0031) while PCI > 6 was the only significant factor (p < 0.0030) for OS. Conclusions: Addition of HIPEC to CRS was safe, and improved survival in patient with peritoneal Carcinomatosis of colo-rectal origin. PCI and CC score are prognostic factors of survival, signet-ring subtype may not benefit of this procedure.
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