Implementation of Universal Pan-Cancer Germline Genetic Testing in an Arab Population: The Jordanian Exploratory Cancer Genetics Study.

PURPOSE: Germline genetic testing (GGT) significantly affects cancer care. While universal testing has been studied in Western societies, less is known about adoption elsewhere. MATERIALS AND METHODS: In this study, 3,319 unselected, pan-cancer Jordanian patients diagnosed between April 2021 and September 2022 received GGT. Pathogenic germline variant (PGV) frequency among patients who were in-criteria (IC) or out-of-criteria (OOC; 2020 National Comprehensive Cancer Network criteria) and changes in clinical management in response to GGT results were evaluated. Statistical analysis was performed using two-tailed Fisher's exact test with significance level P < .05. RESULTS: The cohort was predominantly female (69.9%), with a mean age of 53.7 years at testing, and 53.1% were IC. While patients who were IC were more likely than patients who were OOC to have a PGV (15.8% v 9.6%; P < .0001), 149 (34.8%) patients with PGVs were OOC. Clinical management recommendations in response to GGT, including changes to treatment and/or follow-up, were made for 57.3% (161 of 281) of patients with high- or moderate-risk PGVs, including 26.1% (42 of 161) of patients who were OOC. CONCLUSION: Universal GGT of patients with newly diagnosed cancer was successfully implemented in Jordan and led to identification of actionable PGVs that would have been missed with guidelines-based testing.

Germline Genetic Mutations in Adult Patients with Sarcoma: Insight into the Middle East Genetic Landscape.

Data on germline mutations in soft tissue and bone sarcomas are scarce. We sought to identify the prevalence of germline mutations in adult sarcoma patients treated at a tertiary cancer center. Newly diagnosed patients were offered germline genetic testing via an 84-gene panel. The prevalence of pathogenic germline variants (PGVs) and their association with disease-, and patient- related factors are reported. A total of 87 patients were enrolled, the median age was 48 (19-78) years, and 47 (54%) were females. Gastrointestinal stromal tumors (n = 12, 13.8%), liposarcoma (n = 10, 11.5%), and Ewing sarcoma (n = 10, 11.5%) were the main subtypes. A total of 20 PGVs were detected in 18 (20.7%) patients. Variants of uncertain significance, in the absence of PGVs, were detected in 40 (45.9%) patients. Young age (p = 0.031), presence of a second primary cancer (p = 0.019), and female gender (p = 0.042) were correlated with the presence of PGVs. All identified PGVs have potential clinical actionability and cascade testing, and eight (44.44%) suggested eligibility for a targeted therapy. Almost one in five adult patients with soft tissue and bone sarcomas harbor pathogenic or likely pathogenic variants. Many of these variants are potentially actionable, and almost all have implications on cancer screening and family counselling. In this cohort from the Middle East, younger age, presence of a second primary tumor, and female gender were significantly associated with higher PGVs rates. Larger studies able to correlate treatment outcomes with genetic variants are highly needed.

Prostate cancer presentation and management in the Middle East.

BACKGROUND: Although prostate cancer is a prevalent malignancy worldwide, its clinical presentation and management in the Middle East are not well-documented. This study aims to provide insights into the initial clinical presentation and management of prostate cancer in this region. METHODS: A retrospective review was conducted on seven institutional databases from six Middle Eastern countries, including Türkiye, Lebanon, Iraq, Syria, Bahrain, and Jordan, to identify patients diagnosed with prostate cancer in 2021. Descriptive analysis was performed on the collected data to provide an overview of the demographic, clinical, and treatment variables. RESULTS: A total of 1,136 patients were identified with a median age of 70 (range, 50-84). Most patients (78%) received their prostate cancer diagnosis after presenting with symptoms, as opposed to routine PSA screening. At the time of diagnosis, 35% of men had clinical T3 or T4 disease, 54% with Stage IV disease and 50% with Gleason score ≥ 8. Regarding treatment, 20% of non-metastatic and 22% of metastatic patients received no treatment. CONCLUSION: Most men in this study sought prostate cancer evaluation due to symptoms and were subsequently diagnosed with advanced-stage disease, providing a foundation for future research aimed at understanding the underlying factors behind the observed trends and enabling informed interventions.

Doxorubicin Dose Deintensification in Pediatric Osteosarcoma, Is Less Better?

Hadeel HalalshehIntroduction 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/m 2 . Aiming to reduce cardiac toxicity at our center, we opted to reduce the cumulative dose of doxorubicin to 375 mg/m 2 . Materials and Methods This is a retrospective cohort of osteosarcoma patients aged <18 years, treated at our center between 2009 and 2018. Patients were treated with unified CPG and were prospectively followed. Disease and treatment characteristics were depicted, and survival rates were calculated. When needed, comparison of survival of different groups were conducted using log-rank test. 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.

Molecular Imaging in Recurrent Prostate Cancer Presented as a Mixed Small Neuroendocrine Tumor/Acinar Adenocarcinoma.

Molecular imaging is an important tool for evaluating patients with prostate cancer, including those with hybrid histopathology. Although rare, mixed small neuroendocrine tumor/acinar adenocarcinoma exhibit aggressive behavior that necessitates optimal therapy. Molecular imaging has been implemented previously to assess radioligand therapy eligibility in such cases. Interestingly, the uptake of radiotracers targeting prostate-specific membrane antigen (PSMA) and somatostatin receptor may be reduced and can potentially lead to false negative readings in certain tumor types with hybrid features. Therefore, physicians should be aware of different kinds of disparities when assessing these tumor types with the aforementioned modalities.

Fluorodeoxyglucose positron emission tomography (18F-FDG PET)-computed tomography (CT) in the initial staging of bladder cancer: a single institution experience.

BACKGROUND: The purpose of this study was to assess the usefulness of fluorodeoxyglucose positron emission tomography (18F-FDG PET)-computed tomography (CT) scan for staging urinary bladder cancer. The study also sought to determine the effect of 18F-FDG PET/CT on management decisions and its implications for patient care. METHODS: A total of 133 patients with bladder cancer who had both conventional imaging and 18F-FDG PET/CT for initial staging were identified. All 18F-FDG-PET/CT findings were classified as true positive, true negative, false positive, or false negative based on their potential to impact the intent of treatment. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated using the standard definition. Furthermore, the rate of change in therapy intent was determined for the entire sample and for subgroups with non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) patients. RESULTS: The overall concordance rate between PET/CT and conventional imaging was around 54%. On conventional images, 18% of patients had localized disease, which was upstaged in 6.8% of cases using 18F-FDG PET/CT. Pelvic lymph node involvement was detected in 18.8% of cases using conventional imaging, which was downstaged to localized disease in 4.5% of cases using 18F-FDG PET/CT. While 63.2% of patients had systemic disease on a CT scan, 24.7% of cases were downstaged using PET/CT. Overall, the rate of change in therapy intent was 26.3% for the entire sample, 24.5% for NMIBC subgroup, and 27.3% for MIBC patients. CONCLUSIONS: The study found that 18F-FDG PET/CT is an effective and accurate tool for staging bladder cancer in newly diagnosed patients. Approximately one quarter of patients had a change in management intent based on 18F-FDG PET/CT results. The study suggests that PET/CT should be used as a standard for newly diagnosed patients, but more research is needed to confirm this.

Bladder cancer in young adults: Disease and treatment characteristics of patients treated at a tertiary cancer center.

Objectives: The incidence of bladder cancer in the Middle East is increasing. Nevertheless, data on the young population with urothelial carcinoma (UC) of the urinary bladder in this region is scarce. Therefore, we evaluated clinical and tumor characteristics, in addition to treatment details in patients younger than 45 years old. Methodology: We reviewed all patients presenting with UC of the urinary bladder from July 2006 to December 2019. Clinical characteristics including demographics, stage at presentation, and treatment outcomes were extracted. Results: Out of 1272 new cases of bladder cancer, a total of 112 (8.8%) patients were ≤45 years old. Seven patients (6%) had nonurothelial histology and were excluded from the study. The remaining 105 eligible patients with UC had a median age at presentation of 41 years (35-43). Ninety-three patients (88.6%) were males. Tumor stage at presentation: nonmuscle invasive disease (Ta-T1), locally advanced muscle-invasive bladder cancer (MIBC) (T2-3), and metastatic disease were 84.7%, 2.8%, and 12.5%, respectively. All patients with MIBC received neoadjuvant cisplatin-based chemotherapy. Radical cystectomy was performed in 8 (7.6%) cases; three patients with MIBC and five with high-volume non-MIBC. Neobladder reconstruction was done in six patients. A total of 13 patients with metastatic disease (93%) received palliative chemotherapy (gemcitabine/cisplatin), and one (7%) was a candidate for best supportive care only. Conclusion: Bladder cancer is relatively rare in the young population, although the incidence at our region is higher than other reports in the literature. Most patients present with early disease. Early diagnosis and multidisciplinary approach are paramount for the management of these patients.

Re-Irradiation for Recurrent Head and Neck Cancer: Freedom from Cancer Recurrence Rate.

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.

A Rare Case of Nasal Sarcoma with BCOR Internal Tandem Duplication Showing Complete Pathologic Response to the VDC-IE Chemotherapy Protocol.

Sarcoma with BCOR genetic alteration is an exceptionally rare and emerging subtype of sarcoma. It is categorized into two types: BCOR-related gene fusions such as BCOR::CCNB3 sarcomas and other BCOR-rearranged sarcoma and sarcomas with internal tandem duplication of BCOR genes such as infantile undifferentiated round cell sarcomas and primitive myxoid mesenchymal tumors of infancy. BCOR::CCNB3 sarcomas predominantly arise in bone rather than soft tissue and exhibit a higher occurrence in children and adolescent males, whereas sarcomas with BCOR internal tandem duplication show a wider age range but usually arise in the first year of life. Due to their rarity, there is ongoing debate and uncertainty regarding the best treatment approach, with a lack of specific clinical trials addressing these tumors. In this report, we present a unique case of sarcoma with internal tandem duplication of BCOR gene originating in the nasal region. The tumor was successfully and completely resected using the standard VDC-IE chemotherapy protocol, resulting in an unprecedented 100 percent tumor necrosis. The patient has completed the protocol and remains recurrence-free 13 months after diagnosis. This case suggests potential efficacy of the standard VDC-IE protocol in achieving remarkable responses in BCOR rearrangement sarcomas, including the internal tandem duplication subtype. However, further studies are needed to determine the optimal treatment strategies for this disease.

Bone marrow involvement in patients with metastatic castration sensitive prostate cancer.

INTRODUCTION: The clinical significance of bone marrow (BM) metastasis in prostate cancer as well as impact on oncological prognosis is unclear. We aim to assess the prevalence and clinical outcomes of BM metastasis at initial presentation of metastatic castrate sensitive prostate cancer (CSPC). PATIENTS AND METHODS: Retrospective chart review of newly diagnosed metastatic CSPC patients was performed with collection of clinicopathologic and radiologic characteristics. Descriptive univariate and multivariate analysis was performed as well as survival measures (OS and PFS), which was done using the Kaplan-Meier survival and the Log-rank test. RESULTS: 189 patients were eligible, of which, eleven patients (6%) had biopsy proven BM involvement at diagnosis. There was a trend to poorer PFS and OS in patients with BM involvement but not statistically significant; however, factors that correlated with inferior PFS and OS in the multivariate analysis included ECOG PS, ALP, and Hb. CONCLUSION: BM metastasis in prostate cancer may lead to poorer survival. Clinical features including poor performance status, anemia, and elevated ALP, could guide bone marrow biopsies in the future to diagnose bone marrow metastasis at an earlier stage.

Impact of head-and-neck radiation oncology clinical fellowship on multidisciplinary assessment, radiation workflow, and survival of adult patients with nasopharyngeal carcinoma.

Purpose: 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). Materials and Methods: 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. Results: 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. Conclusions: Clinical fellowship training results in increase multidisciplinary referrals to supportive services, improves radiotherapy workflow, but had no significant impact on survival outcomes.

Creation and validation of the harmonized Arabic version of the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP).

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.

Moving Experience from North America to Developing Country to Approach a Desired Level of Quality Assurance in Head and Neck Radiation Therapy.

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.

Comparison of Two Standard Treatment Approaches in Locoregionally Advanced Nasopharyngeal Carcinoma.

Issa MohamadObjectives 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 < 0.01), late G II brain toxicity (4 vs. 1, p < 0.01), and late G II dysphagia (32 vs. 11, p = 0.01). 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.

Pretreatment neutrophil-to-lymphocyte ratio as a potential prognostic biomarker for newly diagnosed patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: Although the prognostic role of neutrophil-to-lymphocyte ratio (NLR) has been assessed in patients with metastatic castration-resistant prostate cancer, data on its impact on oncological outcomes of patients with metastatic castration-sensitive prostate cancer (mCSPC) are scarce. AIM: This study aims to examine the influence of elevated pretreatment NLR on time to prostatic-specific antigen (PSA) progression and overall survival (OS) of patients with mCSPC. METHODS: We retrospectively reviewed patients presenting between June 2007 and June 2019 with mCSPC. Survival was estimated by the Kaplan-Meier method and compared by the log-rank test. Multivariate analyses were used to assess the factors influencing time to PSA progression and OS. RESULTS: A total of 189 patients were included; median age = 69 years, median PSA = 155 ng/mL, 41(22%) had visceral metastasis. Median time to PSA progression was shorter for patients with NLR ≥4 (n = 37) compared to patients with NLR < 4 (n = 146); 11.3 and 18.3 months, respectively, P = .015. Patients with NLR ≥4 also had inferior median OS (23.9 vs 49.5 months, P = .001). On multivariate analysis, NLR ≥4 was not an independent factor for time to PSA progression. However, NLR ≥4 was an independent factor of inferior OS (HR: 2.75, 95% CI: 1.01-7.87, P = .047). Other independent factors predicting inferior OS included Eastern Cooperative Oncology Group Performance Status ≥1, high-volume status, and Hb < 12. CONCLUSION: Elevated pretreatment NLR independently predicts inferior OS in newly diagnosed patients with mCSPC. However, NLR was not a predictor of time to PSA progression.

The influence of 68Ga-prostate-specific membrane antigen PET/computed tomography on prostate cancer staging and planning of definitive radiation therapy.

OBJECTIVES: Prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) is a novel imaging tool with an evolving role in the management of prostate cancer. This study aims to retrospectively evaluate the impact of 68Ga-PSMA PET/CT on prostate cancer staging and definitive radiation therapy planning. METHODS: Between April 2015 and June 2020, 366 men with prostate cancer were evaluated with 68Ga-PSMA PET/CT. Of these, 108 patients had PSMA PET/CT before radiation therapy. Radiation was given as primary treatment in 58 (54%) and as salvage radiation therapy for biochemical recurrence after primary surgery in 50 (46%) patients, respectively. Patient and disease characteristics were analyzed, and impact of PSMA PET/CT on disease staging and radiotherapy planning was evaluated in comparison to conventional imaging. RESULTS: Median age at presentation was 69 years, and median prostate-specific antigen was 18 ng/mL (3.6-400) for primary and 0.4 ng/mL (0.1-4.6) for salvage radiation, respectively. The combined change of disease stage rate was 36% (39/108) with 45% (26/58) in the subgroup of primary radiation and 26% (13/50) in the patients intended for salvage radiation. Upstaging was found in 24 (22%) and downstaging in 15 (14%) patients. Radiation planning was changed based on PSMA PET/CT in 34 (31%) patients, including 7 (6.4%) patients in which stereotactic body radiotherapy (SBRT) was added to oligometastatic sites. The radiation field was extended to include pelvic lymph node involvement in 21 patients. CONCLUSIONS: 68Ga-PSMA PET/CT changed the prostate cancer stage in around one-third of men. PSMA PET/CT significantly impacted radiation planning. Further prospective studies are still required.

Factors influencing the use of adaptive radiation therapy in vulvar carcinoma.

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.

The impact of local control timing in Ewing sarcoma.

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 <90% as opposed to ≥90% (5-year OS 55% vs. 90%, respectively, p = 0.01). CONCLUSION: Delay in definitive therapy, local control with radiation as opposed to surgery and poor post-chemotherapy tumor necrosis predict inferior OS in ES. Adopting strategies to minimize delay in local control could improve survival outcomes.