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Salvage re-irradiation (rRT) for patients with locoregionally recurrent head and neck cancer (rHNC) remains challenging. A retrospective analysis was performed on 49 patients who received rRT between 2011 and 2018. The co-primary endpoint of the study was 2-year freedom from cancer recurrence rate (FCRR) and overall survival (OS), and secondary endpoints were 2-year disease-free survival (DFS), local failure (LF), regional failure (RF), distant metastases (DM), and RTOG grade 3 ≥ late toxicities. Adjuvant and definitive rRT were delivered to 22 and 27 patients, respectively. A total of 91% of patients were managed with conventional re-RT and 71% of patients received concurrent chemotherapy. The median follow-up after rRT was 30 months. The 2-year FCRR, OS, DFS, LF, RF, and DM were 64%, 51%, 28%, 32%, 9%, and 39% respectively. MVA showed that poor performance status (PS: 1–2 vs. 0) and age > 52 years were predictive of worse OS. In comparison, poor PS (1–2 vs. 0) and total dose of rRT < 60 Gy were predictive of worse DFS. Late RTOG toxicity of grade 3 ≥ was reported in nine (18.3%) patients. FCRR at 2 years after salvage rRT for rHNC was higher than other traditional endpoints and could be an important endpoint to be included in future rRT studies. rRT for rHNC at our cohort was relatively successful, with a manageable level of late severe toxicity. Replacing this approach in other developing countries is a viable option.

Introduction We implemented new clinical practice guidelines (CPG) for patients with osteosarcoma starting in January 2009. These guidelines were based on standard European and American Osteosarcoma Study regimen, which includes six cycles of doxorubicin with a cumulative dose of 450 mg/m2. Aiming to reduce cardiac toxicity at our center, we opted to reduce the cumulative dose of doxorubicin to 375 mg/m2. Methods This is a retrospective cohort of osteosarcoma patients aged Results After a median follow-up of 43.3 months (range, 2–153 months), 79 patients were diagnosed with osteosarcoma and treated with dose-reduced doxorubicin. Median age at diagnosis was 12.8 years. At diagnosis, 58 patients (73%) had localized disease. The 5-year event-free survival (EFS) for the whole group was 50 ± 5.9%, and overall survival (OS) was 64 ± 5.7%. For patients with extremity nonmetastatic tumors (N = 56), 5-year EFS and OS were 60 ± 6.9% and 70 ± 6.8%, respectively, and for this group of patients, response to chemotherapy was associated with better EFS (p = 0.0048) and OS (p = 0.013). Only two patients suffered transient cardiac dysfunction, which was resolved after treatment. Conclusion Our findings suggest that deintensification of doxorubicin may provide adequate control for pediatric osteosarcoma. In the absence of large randomized clinical trials addressing this issue, developing countries with less resources to treat patients with heart failure may consider using the lower dose.

Objectives To compare outcomes and toxicity of two standard treatment approaches of advanced nasopharyngeal carcinoma (NPC). Methods Between 2010 and 2016, patients with NPC, stage II–IVa, treated with induction chemotherapy (IC) (TPF), followed by concurrent chemoradiotherapy (CCRT) (induction group), or CCRT, followed by adjuvant chemotherapy (AC) (PF) (no-induction group), were retrospectively reviewed. CCRT included platinum-based chemotherapy with intensity-modulated radiotherapy. Survival outcomes, the pattern of failures, toxicity, and predictors for survival outcomes were evaluated. Results A total of 110 patients were included, 65 in the induction group and 45 in the no-induction group. There were no significant differences in the DFS and overall survival (OS) at 3 years between the two groups. On multivariate analysis, performance status (1 vs. 0) predicted worse OS. The 3-year cumulative incidence rates for local, regional, and distant failures were 58.5% (95% confidence interval [CI]: 8.4–89%), 58.00% (95% CI: 8–88.8%), and 63.90% (95% CI: 14.1–90.2%), respectively. IC had more frequent acute grade (G) II anemia (13 vs. 1, p Conclusions Survival outcomes were comparable between the two groups. IC had more frequent acute G II anemia and late G II brain and esophageal toxicities.

The purpose of the study wast to evaluate the influence of head-and-neck clinical fellowship training on multidisciplinary assessment, radiation workflow, and clinical outcomes of patients with nasopharyngeal carcinoma (NPC).This was a retrospective review of patients with NPC treated between 2010 and 2017. The study cohort was allocated into prefellowship cohort (pre-FSC) (January 2010-September 2014) and postfellowship cohort (post-FSC) (October 2014-December 2017). Patient demographics, tumor characteristics, multidisciplinary assessment, radiation workflow, and treatment were reviewed. Univariable, multivariable, and relapse-free survival (RFS) and overall survival (OS) were performed.One hundred and forty-three patients were included, 68 in the pre-FSC and 75 in the post-FSC. For the post-FSC versus pre-FSC, there were increased multidisciplinary referrals to dental (100% vs. 79.4%, P = 0.001), nutritional (94.7% vs. 70.6%, P = 0.0001), peg-tube insertion (84% vs. 64.7%, P = 0.0001), speech and swallow (94.7% vs. 13.2%, P = 0.0001), psychosocial (100% vs. 26.5%, P = 0.0001), and smoking cessation clinic (33.3% vs. 5.9%, P = 0.0001). For the post-FSC versus pre-FSC, there were statistically significant differences in the elements of radiation workflow; mean time required for contouring was 3.2 vs. 8.8 days (P = 0.0001), radiotherapy plan implementation: 1.9 vs. 4.8 days (P = 0.0001), and plan approval: 0.4 vs. 0.9 day (P = 0.00012). On multivariable analysis, smoking was associated with poor RFS (P = 0.04). There were no statistically significant differences in OS (94.7% vs. 87.2% at 3 years; P = 0.126) and RFS (88.4% vs. 84.4% at 3 years; P = 0.281) between post and pre-FSCs, respectively.Clinical fellowship training results in increase multidisciplinary referrals to supportive services, improves radiotherapy workflow, but had no significant impact on survival outcomes.

Aim We aim to evaluate the variables affecting the frequency of adaptive radiotherapy (ART) in vulvar cancer. Background ART may be needed throughout a definitive RT course for vulvar carcinoma due to changes in patient’s anatomy and tumor response. Materials and methods Charts of patients charts who had been treated with definitive concurrent chemo-radiotherapy for vulvar carcinoma, between January 2015 and December 2019 were inquired. Radiation therapy was delivered using intensity modulated radiotherapy (IMRT) with daily image-guided radiotherapy (IGRT). ART was defined as re-simulation and re-planning based on deformation in the irradiated volume by more than 1 cm. Univariate analysis was conducted to study the impact of patient’s demographics as well as tumor characteristics on the frequency of ART. Results 22 patients were eligible for analysis. Median age at diagnosis was 55 years (range 43–82). Radiotherapy dose was 60−66 Gy over 30–35 fractions (fx). Median primary tumor volume was 30cc (9–140). Median Body Mass Index (BMI) was 32 (range 21–40). Thirteen out of 22 patients (59%) required ART, with median timing at 25 fx (19–31). On univariate analysis, larger primary tumor volume (> = 30cc) was associated significantly with increased frequency of ART (p value = 0.0005). There was no significant impact of ART on the frequency with respect to patient’s age, BMI, tumor stage, grade and location. Conclusion Changes in radiation target volume are common among vulvar carcinoma patients who are treated with definitive radiotherapy, especially large primary tumors. This review highlights the importance of ART for patients with vulvar carcinoma treated with definitive radiotherapy.

Irinotecan and temozolomide (IT) is a widely used regimen for relapsed Ewing sarcoma (ES), although studies are largely limited to paediatric populations. We retrospectively reviewed paediatric (

Aim The aim of this study is to evaluate tumor volume changes during preoperative radiotherapy and to assess the role of adaptive radiation. Background Contemporary neoadjuvant radiotherapy utilizes image guidance for precise treatment delivery. Moreover, it may depict changes in tumor size and shape. Materials and methods Between 2016 and 2018, 23 patients aged ≥18 years with soft tissue sarcoma were treated with neoadjuvant radiation followed by surgical resection. The tumor volumes (cc) were measured using the Pinnacle planning system prior to starting radiotherapy and during treatment, the changes in volume and absolute differences were estimated. Moreover, patient's position on the machine was evaluated to assess setup offsets. The triggers for plan adaptation were >1 cm expansion or unacceptable setup offsets. Results The mean tumors volume at presentation was 810 cc (range, 55–4000). At last cone beam CT the tumor volume had changed in 14 patients (61%); it was stable in nine patients (39%). Disease regression was documented in eight patients (35%), with median shrinkage of −20.5% (range, −2 to −29%), while tumor progression was observed in six cases (26%), the median change was 12.5% (range, +10 to +25%). Adaptive radiation was required in four patients (17%). For the remaining 19 cases (83%), the dose distribution was adequate to cover target volumes. Conclusions Change in soft tissue sarcoma volume during radiation is not uncommon. Image guidance should be used to reduce setup errors and to detect differences in tumor volume. Image guidance and adaptive radiation are paramount to ensure optimal radiation delivery.

Purpose The quality assurance (QA) chart rounds are multidisciplinary meetings to review radiation therapy (RT) treatment plans. This study focus on describing the changes in RT management based on QA round reviews in a single institution. Materials and methods After 9 full years of implementation, a retrospective review of all patients whose charts passed through departmental QA chart rounds from 2007 to 2015. The reviewed cases were presented for RT plan review; subcategorized based on decision in QA rounds into: approved, minor modifications or major modifications. Major modification defined as any substantial change which required patient re-simulation or re-planning prior to commencement of RT. Minor modification included treatment plan changes which didn't necessarily require RT re-planning. Results Overall 7,149 RT treatment plans for different anatomical sites were reviewed at QA rounds. From these treatment plans, 6,654 (93%) were approved, 144 (2%) required minor modifications, while 351 (5%) required major modifications. Major modification included changes in: selected RT dose (96/351, 27%), target volume definition (127/351, 36%), organs-at-risk contouring (10/351, 3%), dose volume objectives/constraints criteria (90/351, 26%), and intent of treatment (28/351, 8%). The RT plans which required major modification according to the tumor subtype were as follows: head and neck (104/904, 12%), thoracic (12/199, 6%), gastrointestinal (33/687,5%), skin (5/106, 5%), genitourinary (16/359, 4%), breast (104/2387, 4%), central nervous system (36/846, 4%), sarcoma (11/277, 4%), pediatric (7/251, 3%), lymphoma (10/423, 2%), gynecological tumors (2/359, 1%), and others (11/351, 3%). Conclusion Multi-disciplinary standardized QA chart rounds provide a comprehensive and an influential method on RT plans and/ or treatment decisions.

Background Respiratory gated CT simulation (4D-simulation) has been evolved to estimate the internal body motion. This study aimed to evaluate the impact of tumor volume and location on the planning target volume (PTV) for primary lung tumor when 4D simulation is used. Methods Patients who underwent CT simulation for primary lung cancer radiotherapy between 2012 and 2016 using a 3D- (free breathing) and 4D- (respiratory gated) technique were reviewed. For each patient, gross tumor volume (GTV) was contoured in a free breathing scan (3D-GTV), and 4D-simulation scans (4D-GTV). Margins were added to account for the clinical target volume (CTV) and internal target motion (ITV) in 3D and 4D simulation scans. Additional margins were added to account for planned target volume (PTV). Univariate and multivariate analyses were performed to test the impact of the volume of the GTV and location of the tumor (relative to the bronchial tree and lung lobes) on PTV changes by more than 10% between the 3D and 4D scans. Results A total of 10 patients were identified. 3D-PTV was significantly larger than the 4D-PTV; median volumes were 182.79 vs. 158.21 cc, p = 0.0068). On multivariate analysis, neither the volume of the GTV (p = 0.5027) nor the location of the tumor (peripheral, p = 0.5027 or lower location, p = 0.5802) had an impact on PTV differences between 3D-simulation and 4D-simluation. Conclusion The use of 4D-simulation reduces the PTV for the primary tumor in lung cancer cases. Further studies with larger samples are required to confirm the benefit of 4D-simulation in decreasing PTV in lung cancer.

Radiation therapy (RT) is considered one of the cornerstone modalities of treatment for different cancer types. The preparation and delivery of RT requires a number of staff members from different disciplines within the radiation oncology department. Since the emergence of the corona virus disease 2019 (COVID-19) pandemic, RT, similar to other cancer care modalities, has been adapted to minimize patient and staff exposure without compromising the oncological outcomes. This was reflected in the dramatic practice changes that occurred in the past year to address the lockdown restrictions and fulfill the infection control requirements. RT practices differ across regions based on financial and training levels, and developing countries with limited resources have struggled to maintain radiation treatment services at a level equivalent to that in developed countries while following pandemic control guidelines. The response during the COVID-19 pandemic varied between developing countries according to the infection rate and RT technological capabilities. In this editorial, we review recently published articles addressing radiotherapy practice reports during the COVID-19 pandemic in developing countries.

Objectives Tocreate and validate a translated Arabic version of the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP), a validated patient-reported outcome (PRO) widely used for assessing the quality of life in patients with prostate cancer (PCa). Patients and Methods Using the established protocol as defined by the Professional Society for the Health Economics and Outcomes Research (ISPOR) for translating patient care questionnaires, a harmonised translated Arabic version of EPIC-CP was created. The questionnaire was tested in native Arabic speakers from four different Arabic countries (Saudi Arabia, United Arab Emirates, Jordan, and Kuwait). Cronbach’s alpha and interclass coefficient correlation (ICC) analyses were used to test the internal consistency and test–retest reliability, respectively. In addition, PCa characteristics were collected for participants. Results In total, 168 patients with PCa participated in the study (39 from Saudi Arabia, 23 from United Arab Emirates, 65 from Jordan, and 41 from Kuwait). In all, 52 (31%) participants repeated the questionnaire for test–retest reliability analysis. The median (interquartile range [IQR]) age of patients included in the study was 66 (61–71) years. The median (IQR) PSA level was 9.8 (6–19) ng/mL. Most patients had Grade Group 2 PCa at diagnosis (31%), clinical stage cT1 (42%), managed primarily by urology (79%), and the primary treatment was radical prostatectomy (71%). The total Cronbach’s alpha coefficient was 0.84 demonstrating an acceptable internal consistency. The total ICC was also acceptable at 0.64. Conclusion The Arabic version of the EPIC-CP is a reliable and valid tool for assessing health-related quality of life for Arabic patients with PCa.

Evidence is lacking correlation between head and neck (HN) radiation oncology fellowship training and quality assurance (QA) round decision for plan modifications. This study was conducted to identify the association between training and changes in QA decisions. From 2007 to 2018, data on HN cancer cases presented at departmental QA rounds were prospectively collected. Then, we retrospectively analyzed the collected data to determine the impact of fellowship training on QA decisions. Cases were divided into pre-fellowship group (January 2007–September 2014) and post-fellowship group (October 2014–December 2018). Multivariable analysis (MVA) evaluated variables that could be associated with decreased frequencies of QA modification rates. From 2007 to 2018, 1266 HN cancer patients were identified; 728 patients were in the pre-fellowship group and 538 patients in the post-fellowship group. On MVA, fellowship training transformed QA decisions from more to less modifications (modified vs. approved; OR, 0.135; 95% CI, 0.076–0.240; p = 0.0001), increased approval rate for advanced T and N categories (T3–4 vs. T0–T2; OR, 0.798; 95% CI, 1.892–4.929; p = 0.0001 and N2–3 vs. N0–1; OR, 0.865; 95% CI, 1.454–3.423; p = 0.0002). By type of modification, fellowship training demonstrated a statistically significant reduction in rates of several types of modification that include target volume definition, target volume delineation, and dose (all p < 0.05). Our study determines the impact of the HN radiation oncology fellowship on decreased QA modification rates.

Management of craniopharyngioma in children is challenging, and their quality of life can be significantly affected. Series describing this from low-middle income countries (LMIC) are few.The study provides a retrospective chart review of pediatric patients18 years old, diagnosed with craniopharyngioma between 2003 and 2014, and treated at King Hussein Cancer Center, Jordan.Twenty-four patients (12 males) were identified. Median age at diagnosis was 7.4 years (0.9-16.4 years). Commonest symptoms were visual impairment and headache (71%). Review of seventeen preoperative MRIs showed hypothalamic involvement in 88% and hydrocephalus in 76%. Thirteen patients (54%) had multiple surgical interventions. Five patients (21%) had initial gross total resection. Eleven patients (46%) received radiotherapy and six (25%) intra-cystic interferon. Five years' survival was 87 ± 7% with a median follow-up of 4.5 years (0.3-12.3 years). Four patients (17%) died; one after post-operative cerebral infarction and three secondary to hypothalamic damage. At their last evaluation, all but one patient required multiple hormonal supplements. Ten patients (42%) had best eye visual acuity (VA)20/40, and four (16%) were legally blind. Eleven patients (46%) were overweight/obese; one had gastric bypass surgery. Seven patients had hyperlipidemia, and eight developed fatty liver infiltration. Eleven patients (65%) were attending schools and one at college. Nine of the living patients (53%) expressed difficulty to engage in the community.Management of pediatric craniopharyngioma is particularly complex and demanding in LMIC. Multidisciplinary care is integral to optimize the care and minimize the morbidities. A management outline for LMIC is proposed.

AIM: To assess the impact of delay in local control on survival outcomes of Ewing sarcoma (ES) patients. BACKGROUND: The cornerstone of therapy of localized ES includes chemotherapy and local control with surgery or radiotherapy. We sought to assess the impact of delay (>15 weeks) in timing of local control on survival outcomes of ES patients. METHODS: Data of consecutive patients with primary non-metastatic ES of the extremities, treated at a single institution were collected. The impact of delay of timing for local control, demographics, and disease characteristics on overall survival (OS) was analyzed. RESULTS: A total of 43 patients with ES of the extremity were included. All patients received neoadjuvant chemotherapy. Local control was by surgery in 36 patients and definitive radiation in 7. A total of 16 patients had delay in local control. At a median follow of up of 48 months, patients with delay in local control had significantly inferior OS compared to those with optimal local control timing (5-year OS 56% vs. 80%, respectively, p = 0.044). Other factors that predicted inferior OS included definitive radiation as opposed to definitive surgery (5-year OS 25% vs. 79%, respectively, p = 0.041) and tumor necrosis

Purpose To compare the outcomes of extraskeletal and skeletal Ewing sarcomas treated with standard chemotherapy protocol. Methods We retrospectively collected data on primary localized skeletal and extraskeletal ES patients. Demographics and disease characteristics were compared between the two groups. The influence of presentation (skeletal vs. extraskeletal) on overall survival (OS) and local recurrence-free survival (LRFS) was assessed and compared by the log-rank test. Results A total of 120 patients were included; 29 (24%) had extraskeletal and 91 (76%) had skeletal ES. All patients received vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE) chemotherapy, with a plan for local control at week 12. At a median follow-up of 38 months, there was no difference in OS between skeletal and extraskeletal ES; 5-year OS 70% and 67% respectively, p = 0.96. Patients with extraskeletal ES had inferior 5-year LRFS compared to skeletal ES; 74% vs. 83%; p = 0.042. Local recurrence occurred at a higher frequency in the extraskeletal group; 28% vs. 11%, p = 0.034, although more extraskeletal patients received adjuvant radiotherapy; 73% vs. 36%, p = 0.01. Among patients who underwent surgery (n = 76), there was no difference in R0 resection rate (skeletal: 89%, extraskeletal: 86%, p = 0.52, or good ( ≥ 90%) tumor necrosis; skeletal: 54%, extraskeletal: 38%, p = 0.31. Conclusion Patients with localized extraskeletal ES have comparable OS outcomes to patients with skeletal ES utilizing the standard VDC-IE chemotherapy. However, extraskeletal patients are at significantly higher risk for local recurrence.

e23507 Background: There remains an unmet need to identify prognostic and predictive molecular biomarkers in advance Ewing sarcoma (ES). We sought to assess the influence of MGMT promoter methylation status on response rate, time to progression (TTP), and overall survival (OS) following salvage irinotecan and temozolomide (IT) chemotherapy. Methods: Data of advanced ES patients, treated with IT chemotherapy from Jan, 2014 to Jan, 2020 were retrospectively collected. Patients were required to have previously received and progressed after vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE). MGMT promoter methylation status was assessed by Methylation Sensitive Restriction Enzyme quantitative-PCR (MSRE-qPCR) on non-decalcified Formalin-fixed paraffin embedded (FFPE) tissue using internally developed primers and the OneStep qMethyl Kit (ZYMO RESEARCH CORP). Responses were assessed by response evaluation criteria in solid tumors (RECIST v. 1.1). TTP and OS were assessed by the Kaplan-Meier method. Survival comparisons were performed by the Log-rank test. Results: Herein, we present data of the preliminary analysis of the first 18 patients who underwent MGMT promoter methylation testing. Patients had a median age of 18 years (range: 5-34 years), and were predominantly male ( n=11; 61%). The primary tumor was located in the pelvis in 9 patients (50%), femur in 3 (17%), tibia in 2 (11%), kidney in 2 (11%), chest wall in one (6%), and scapula in one patient (6%). IT was given in a second ( n=15) or third-line setting ( n=3). At the time of initiation of IT, 13 patients (72%) had distant metastasis, and 5 (28%) had unresectable local progression in the pelvis ( n=4) or chest wall ( n=1). The mean percentage of MGMT promoter methylation was 29% (range: 3-98%). Five patients (28%) had methylated MGMT promoter, whereas the remaining had partially methylated ( n=6; 33%) or unmethylated ( n=7;39%) promoter. Five patients (28%) had objective response, with no observed difference according to MGMT promoter methylation ( p=0.58 for comparison between methylated and unmethylated/ partially methylated). Median TTP was 4.9 and 2.2 months for patients with methylated and partially methylated/ unmethylated MGMT respectively; p=0.76. The corresponding median OS was 69.4 and 14.3 months in favor of the methylated group; p=0.3. Conclusions: This preliminary data suggests a possible prognostic role for MGMT promoter methylation, with a markedly extended median OS for the methylated group. Nevertheless, the median OS difference did not reach statistical significance in this preliminary analysis. We plan to report data of the final analysis after finalizing MGMT testing for the rest of our study patients.

Objective(s): We aim to investigate the clinical impact of 18F-FDG PET/CT in managing patients with gynecological malignancies and pelvic or extrapelvic lymph nodes that are of equivocal significance on conventional imaging. Methods: We retrospectively evaluated 18F-FDG PET/CT scans of patients with gynecologic tumors who were referred to King Hussein Cancer Center from January 2010 to August 2014. PET/CT results were compared with MRI and CT findings. We evaluated sensitivity and specificity of 18F-FDG PET/CT, its role in changing treatment plan and its positive predictive value (PPV) and negative predictive value (NPV). Results: Ninety seven patients (mean age: 49 years) underwent 18F-FDG/PET in the study period (40 cervical, 37 endometrial and 20 ovarian cancers). PET/CT scan provided additional information in 23 patients; upstaging 4.1% (4 patients; 3 true positive) and down staging in 19.5% (19 patients; 15 true negative). As a result, treatment strategy was changed from curative to palliative in three patients, and modification of radiation field or additional curative therapy was implemented following exclusion of distant metastasis in 11 patients. Mean follow up time for the whole cohort was 35 months (range 6 - 60 months). NPV of 18F-FDG PET/CT in detecting extrapelvic lymphadenopathy was 83.3%. Conclusion: 18F-FDG PET/CT has high clinical impact in management of gynaecological cancers as it alters the treatment plan in a substantial number of patients who had equivocal findings on conventional imaging, as well as it offers excellent validity in lymph nodes staging.

An "ontology" is a technology that is used to represent information or knowledge within a specific domain. It not only defines concepts but it expresses the relationship between these concepts. For radiation oncology, an ontology would elucidate concepts such as "CTV", "Tangent beam" and "radiation dose" [1] .

PURPOSE: The purpose of this study is to compare treatment outcomes of methotrexate, cisplatin, and 5-fluorouracil (MPF) or cisplatin and 5-fluorouracil (PF) in pediatric NPC patients treated with sequential chemoradiotherapy.PATIENTS AND METHODS: A total of 25 patients aged 18 years or below with stage II-IV NPC treated with IC using PF (n=16) or MPF (n=9) followed by radiotherapy between 2003 and 2009 were retrospectively reviewed. Radiotherapy dose was 61.2 to 66.6 Gy to the gross disease. Age, stage, radiation dose, and chemotherapy regimen were tested as prognostic factors for event-free survival (EFS) and overall survival (OS) on univariate and multivariate analyses.RESULTS: The median age at diagnosis was 13.3 years. All patients completed planned chemotherapy. All patients who received MPF achieved PR whereas 15 patients (93.8%) who received PF achieved PR (P=1). There were no differences in EFS (68.75% vs. 66.67%; P=0.84) and OS (81.25% vs. 66.67%; P=0.39) at 5 years between PF and MPF, respectively. On multivariate analysis, only tumor stage (IV vs. II-III) predicted worse OS (hazard ratio, 10.3; 95% confidence interval, 1.197-88.974) but not EFS (hazard ratio, 4.805; 95% confidence interval, 0.95-24.336). Distant metastases was the predominant site of failure, seen in 5 patients (20%).CONCLUSIONS: Omission of methotrexate from the induction chemotherapy regimen did not affect treatment outcome.

11027 Background: Extra-skeletal ewing sarcomas (ES) are rare, and data on outcomes following standard ES chemotherapy protocols are very limited. Methods: We retrospectively collected data on skeletal and extra-skeletal ES patients who presented with localized disease from January, 2006 to June, 2018. Disease and treatment characteristics were compared between the two groups by the chi-square test. Overall survival (OS) and local recurrence free survival (LRFS) were estimated by the Kaplan-Meier method and compared by the Log-rank test. Results: A total of 120 patients were included. Twenty-nine (24%) had extra-skeletal and 91 (76%) had skeletal ES. Location was in the extremity in 51 (43%) and non-extremity in 69 (57%). For extra-skeletal ES, tumors originated from soft tissue in 23 (79%), and viscera in 6 (21%). All patients received standard vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE), with a plan for local control at week 12 of the protocol. Local control was by surgery in 76 (63%) and radiotherapy in 44 (37%). At a median follow up of 38 months, there was no difference in 5-year OS between extra-skeletal and skeletal ES patients (67% and 70% respectively, p = 0.96). Patients with visceral ES had inferior 5-year OS compared to all others (soft-tissue extra-skeletal and skeletal ES); 33% vs. 72%; p = 0.013. Resectability rate was not different between extra-skeletal and skeletal ES patients (54% and 69% respectively, p= 0.11). Furthermore, among patients who underwent surgery, there was no difference between extra-skeletal and skeletal ES patients in R0 resection rate (86% and 89% respectively, p= 0.52) and poor ( < 90%) tumor necrosis rate (62% and 46% respectively, p= 0.31). However, more local recurrences (28% vs. 10%, p= 0.034) and inferior 5-year LRFS (74% vs. 83%; p = 0.042) were observed in the extra-skeletal group, although more extra-skeletal patients received adjuvant radiotherapy; 11 (73%) vs. 21 (36%), p = 0.01. Conclusions: Patients with localized extra-skeletal ES have OS outcomes that are comparable to skeletal ES treated with standard VDC-IE chemotherapy. However, extra-skeletal ES patients are at significantly higher risk of local recurrence.

e22500 Background: Irinotecan and temozolomide (IT) is a widely used regimen for relapsed Ewing Sarcoma (ES), although studies are largely limited to the paediatric population. We aimed to compare the tolerability and efficacy of IT between paediatric and adult patients. Methods: We retrospectively reviewed paediatric (< 18 years) and adult patients treated with salvage IT chemotherapy at two institutions from March, 2010 to June, 2018. Toxicities were graded according to common terminology criteria of adverse events (CTCAE v. 4.03) and compared using the Chi Square test. Responses were interpreted by Response Evaluation Criteria in Solid Tumors (RECIST). The Kaplan-Meyer method was used to estimate progression free survival (PFS); survival comparisons were carried out by the Log-rank test. Results: Fifty-three patients were included ( n= 16 paediatric; n= 37 adult). Median age was 20 (range, 5 – 45 years). A total 236 IT cycles were delivered (median = 4, range:1-7). IT was given as second-line ( n= 34; 64%) or ≥third-line ( n= 19; 36%). There was no difference in ≥grade 3/4 haematologic toxicity between paediatric and adult patients (31% vs. 35% respectively; p= 0.76), whilst febrile neutropenia was observed in two (4%) patients (one adults and one paediatric). The frequency of diarrhoea of any grade was similar (38% in each group). Of 43 patients assessable for response, 12 (28%) had objective response (1 CR, 11 PR), 19 (44%) had disease progression and 12 (28%) had stable disease. Objective response rate did not differ between the two groups (36% in paediatrics vs. 25% in adults; p = 0.47). Median PFS was superior in paediatrics vs. adults (7.4 vs. 2.1 months, p = 0.001). Superior PFS for the paediatric population was observed in both, the second-line (6.2 vs. 2.2 months; p= 0.060) and ≥third-line setting (7.4 vs. 1.2 months, p= 0.014). Conclusions: IT is an effective salvage regimen for ES, with favourable toxicity and equally observed objective responses in paediatric and adult populations. The observed superior PFS for the paediatric cohort requires further confirmation in a larger prospective study.

Retrospective review of children with WT thrombus involving the IVC. We reviewed the charts of 123 patients with WT diagnosed between January 2006 and December 2015. Patients with caval tumor thrombus were identified, demographic data, radiological images, extent of thrombus, chemo- and radiotherapy, surgical approach, pathology reports and outcomes were analyzed. IVC involvement was identified in 11 patients (9%). Left-sided tumors were more common (55%). Sensitivity of CT scan in thrombus identification was 64%. Neoadjuvant chemotherapy was the primary mode of treatment with 19% reduction of primary tumor size, thrombus resolution in four and regression in six patients. No thrombus progression was observed. Delayed surgical treatment was either nephro-ureterectomy (nine patients) or partial nephrectomy in patients with bilateral WT (two patients). During surgery, thrombectomy and intimal stripping achieved local control in patients with persistent caval tumor. Cardiopulmonary bypass was not needed in patients with initial atrial involvement (five patients). Despite adherence and invasion of tumor thrombus to IVC wall, only one patient required segmental vein resection. All patients eventually achieved CR, none had local relapse. One patient had lung relapse treated to complete remission. The 3-year EFS is 85.7 ± 13.2% and the 3-year OS is 100%. IVC tumor thrombus in patients with WT was managed successfully using preoperative chemotherapy followed by surgery with minimal aggressive approach. Luminal thrombus removal and intimal stripping supplanted by local radio boost when indicated seem to be adequate tools for local control with documented good overall outcomes.

There is scarcity of reports addressing patients with three or more malignancies. The aim of this study is to present a detailed analysis of patients presenting with at least three primary malignant tumors. Records of cancer patients presenting to King Hussein Cancer Center (Amman, Jordan) between June 2006 and March 2011 were retrospectively reviewed. Patients harboring multiple primary tumors were included for detailed analysis. Data relating to epidemiological features, pathological characteristics, and disease outcomes were extracted. Out of 14,040 cases, 319 patients (2.3%) harbored two or more while 23 patients (0.16%) harbored three or more primary malignant tumors. This study included 17 males and six females between 4 and 78 years of age (median, 52 years) at the time of diagnosis of the first malignancy. The most prevalent tumor was colorectal adenocarcinoma found in nine, followed by lymphoma in seven, and prostate adenocarcinoma in six patients. The most common tumor combinations were colorectum–non-melanoma skin, colorectum–kidney, and non-melanoma skin–kidney all found in four patients, respectively. At a median follow-up of 96 months from the time of diagnosis of the first primary (range, 2–337 months) and 8 months from the time of diagnosis of the last primary (range, 1–48 months), 13 were alive with no evidence of disease, six were alive with residual disease, three were dead due to disease, and one patient was alive with unknown disease status. The possibility of multiple primary malignancies should always be considered during the treatment and follow-up of cancer patients. This case series could prove helpful to clinicians faced with similar, however, exceedingly rare scenarios. Due to the realistic potential for long-term survival, we recommend aggressive treatment of these patients.

e13500 Background: The primary treatment of medulloblastoma in adults is surgery followed by radiotherapy. Craniospinal irradiation in such patients holds a clinical significant effect on blood count drop, as more than 50% of bone marrow is irradiated during CSI. Precise guidelines on how often a patient's peripheral blood count should be monitored are yet to be established. Methods: A retrospective analysis of blood count data on 42 adult medulloblastoma patients who underwent surgical resection followed by CSI as 36-39.6Gy over 20-22 fractions followed by boost to posterior cranial fossa up to 54Gy and spinal boost up to 45Gy. The manner of blood count cells during radiotherapy and the correlation between WBC drop and outcome were examined. Results: Our study showed a drop in WBCs to 4 and below in 64% of patients during CSI. Eight patients (19%) had Hb drop below 12. There was no grade 3 or 4 anemia. Significant drop in neutrophils below 1500 was observed in 8 patients (20%), with 2.4% had grade 3 neutropenia. In 26 patients (62%) who developed platelets drop, three patients (7%) had platelets of less than 50000 (grade 3 and 4 thrombocytopenia). The Hb, lymphocyte, neutrophils, and platelets nadirs were 8.7 g/dL, 42 cells /microL, 720 cells /microL, and 1000 platelets/microL, respectively. The minimum interval between the nadir and starting radiotherapy for Hb, WBCs, and platelets were 13, 6, and 11 days, respectively. The median interval between the nadir and starting radiotherapy for all cells was 3 weeks. The median WBCs percentage drop was 71%. In 23 patients who had non-metastatic disease, the estimated three year progression free survival was 70%. In those who had WBC drop below 2.7 the PFS was 100% vs. 46%. (P value = 0.042). Conclusions: Some institutions reduced monitoring of CBC during conventional radiotherapy may result in financial saving; however, our study suggests the need for weekly CBC for patients receiving CSI irradiation. Fortunately, no one developed serious infection during radiotherapy, but a precaution should be there. A WBCs change during radiotherapy could reflect the outcome and may suggest more aggressive treatment in patients who had a nadir of 2.7 and above.

e20091 Background: 4D CT simulation has been evolved to estimate the internal body motion and considered as a useful tool for intra-thoracic tumor definition. This study aimed to evaluate the impact of using 4D simulation on the planning target volume (PTV) for primary lung tumor. Methods: Patients who underwent CT simulation for primary lung cancer radiotherapy between 2012-2016 using 3D- (free breathing) and 4D- (respiratory gated) institutional protocol were included in this retrospective review. For each patient, gross tumor volume (GTV) was contoured in free breathing scan (3D-GTV), exhale scan (e-GTV) and inhale scan (i-GTV). The corresponding CTVs (3D-CTV, e-CTV and i-CTV) were created by adding 1 cm in all directions. 3D-internal target volume (3D-ITV) was generated by 0.5 cm cranio-caudal expansion of 3D-CTV, while 4D-ITV was created by combination of e-CTV and i-CTV. Subsequently, a 0.5 cm margin was added to generate the 3D-PTV and 4D-PTV respectively. The volumes of 3D-PTV and 4D-PTV were compared to examine the impact of 4D CT simulation on changes in the volume of PTV. Univariable and multivariable analysis were performed to test the impact of volume and location of GTV on the changes of PTV volume by more than 10 % between free breathing and respiratory gated scans. Results: A total of 10 patients were identified. The median [range] GTV, i-GTV, e-GTV volumes were 13.55 [1.44-628.66], 13.17 [1.77-627.36], 12.85 [1.34-630.25] cc respectively. The 3D-CTV, i-CTV, e-CTV volumes were 86.37 [23.76-1209], 84.97 [25.5- 1220.4], 83.40 [23.36-1224.12] cc respectively. 3D-ITV and 4D-ITV median volume was 106.06 [3.99-1422.8], 88.02 [20.51-1338.18] cc respectively. 3D-PTV was significantly larger than the 4D-PTV; median [range] volumes were 182.79 [58.65- 1861.05] vs. 158.21 [52.76-1771.02] cc, p = 0.0068). On multivariable analysis, neither the volume of GTV (p = 0.4917), nor the location of the tumor (peripheral, p = 0.4914 or lower location, p = 0.9594) had an in impact on PTV differences between free breathing and respiratory gated scans. Conclusions: The use of 4D simulation reduces the PTV for primary lung cancer, and it should be routinely implemented in clinical practice regardless the tumor volume or location.

The incidence of multiple primary malignancies has increased over the past years secondary to the long-term survival of cancer patients due to improvements in the early detection and adequate treatment of cancer. We present a patient with eight primary malignant tumors and review the relevant literature. Our patient was a 59-year-old female with Crohn disease with an otherwise non-contributory medical history. Risk factors for multiple primary tumors were not detected in our patient. At a follow-up of 108 months from the time of diagnosis of the first malignancy, our patient was still alive. Similar long-term survival has been reported in the literature. Due to the realistic potential for long-term survival, we recommend aggressive treatment of these patients.

e16500 Background: Fluoro-Deoxyglucose (FDG-PET) coupled with Magnetic Resonance Imaging (MRI) and Computerized Tomography (CT) provides valuable information in primary staging and evaluation of therapeutic response in gynecological cancer patients. The aim of this study is to investigate the additional value of PET/CT to MRI and CT scan, in patients recently diagnosed with a gynecological tumor or for evaluation of treatment response. Methods: Between January 2010 and June 2012, forty patients with gynecologic tumors (23 cervical, 8 endometrial and 9 ovarian) were evaluated at King Hussein Cancer Center. These patients were divided into two groups: (1) PET scan at presentation for initial staging workup (15 patients) and (2)PET scan at follow up for treatment response evaluation (25 patients). Results: The FDG-PET/CT scan yielded the following additional information: upstaging in 7.5% (3 in 40 patients) and down staging in 32.5% (13 in 40 patients). As a result, treatment strategy was changed from curative to palliative in one patient, and additional curative therapy was implemented following exclusion of distant metastasis in eight patients. Moreover, the discrepancy in nodal status found with FDG-PET/CT compared with anatomical imaging was detected in 8 patients (20%), which led to modifications in radiotherapy field and customizing the radiation dose with minimizing treatment-related toxicity. Conclusions: This study has demonstrated the effectiveness of FDG-PET/CT in the management of gynecological cancer patients. It is a highly valuable utility that raised the accuracy of patients’ stratification to curative or palliative treatments. Furthermore it helped radiotherapy to be more precisely targeted towards the malignant process. However, further prospective studies are still required to identify the group of patients who would benefit the most from this procedure.