RT Target Research Articles

Voxel based morphometry-detected white matter volume loss after multi-modality treatment in high grade glioma patients.

Radiotherapy (RT) and chemotherapy are components of standard multi-modality treatment of high grade gliomas (HGG) aimed at achieving local tumor control. Treatment is neurotoxic and RT plays an important role in this, inducing damage even distant to the RT target volume. This retrospective longitudinal study evaluated the effect of treatment on white matter and gray matter volume in the tumor-free hemisphere of HGG patients using voxel based morphometry (VBM). 3D T1-weighted MR images of 12 HGG patients at multiple timepoints during standard treatment were analyzed using VBM. Segmentation of white matter and gray matter of the tumor-free hemisphere was performed. Multiple general linear models were used to asses white matter and gray matter volumetric differences between time points. A mean RT dose map was created and compared to the VBM results. Diffuse loss of white matter volume, mainly throughout the frontal and parietal lobe, was found, grossly overlapping regions that received the highest RT dose. Significant loss of white matter was first noticed after three cycles of chemotherapy and persisted after the completion of standard treatment. No significant loss of white matter volume was observed between pre-RT and the first post-RT follow-up timepoint, indicating a delayed effect. This study demonstrated diffuse and early-delayed decreases in white matter volume of the tumor-free hemisphere in HGG patients after standard treatment. White matter volume changes occurred mainly throughout the frontal and parietal lobe and grossly overlapped with areas that received the highest RT dose.

Hotspot on 18F-FET PET/CT to Predict Aggressive Tumor Areas for Radiotherapy Dose Escalation Guiding in High-Grade Glioma.

The standard therapy strategy for high-grade glioma (HGG) is based on the maximal surgery followed by radio-chemotherapy (RT-CT) with insufficient control of the disease. Recurrences are mainly localized in the radiation field, suggesting an interest in radiotherapy dose escalation to better control the disease locally. We aimed to identify a similarity between the areas of high uptake on O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography/computed tomography (PET) before RT-CT, the residual tumor on post-therapy NADIR magnetic resonance imaging (MRI) and the area of recurrence on MRI. This is an ancillary study from the IMAGG prospective trial assessing the interest of FET PET imaging in RT target volume definition of HGG. We included patients with diagnoses of HGG obtained by biopsy or tumor resection. These patients underwent FET PET and brain MRIs, both after diagnosis and before RT-CT. The follow-up consisted of sequential brain MRIs performed every 3 months until recurrence. Tumor delineation on the initial MRI 1 (GTV 1), post-RT-CT NADIR MRI 2 (GTV 2), and progression MRI 3 (GTV 3) were performed semi-automatically and manually adjusted by a neuroradiologist specialist in neuro-oncology. GTV 2 and GTV 3 were then co-registered on FET PET data. Tumor volumes on FET PET (MTV) were delineated using a tumor to background ratio (TBR) ≥ 1.6 and different % SUVmax PET thresholds. Spatial similarity between different volumes was performed using the dice (DICE), Jaccard (JSC), and overlap fraction (OV) indices and compared together in the biopsy or partial surgery group (G1) and the total or subtotal surgery group (G2). Another overlap index (OV') was calculated to determine the threshold with the highest probability of being included in the residual volume after RT-CT on MRI 2 and in MRI 3 (called "hotspot"). A total of 23 patients were included, of whom 22% (n = 5) did not have a NADIR MRI 2 due to a disease progression diagnosed on the first post-RT-CT MRI evaluation. Among the 18 patients who underwent a NADIR MRI 2, the average residual tumor was approximately 71.6% of the GTV 1. A total of 22% of patients (5/23) showed an increase in GTV 2 without diagnosis of true progression by the multidisciplinary team (MDT). Spatial similarity between MTV and GTV 2 and between MTV and GTV 3 were higher using a TBR ≥ 1.6 threshold. These indices were significantly better in the G1 group than the G2 group. In the FET hotspot analysis, the best similarity (good agreement) with GTV 2 was found in the G1 group using a 90% SUVmax delineation method and showed a trend of statistical difference with those (poor agreement) in the G2 group (OV' = 0.67 vs. 0.38, respectively, p = 0.068); whereas the best similarity (good agreement) with GTV 3 was found in the G1 group using a 80% SUVmax delineation method and was significantly higher than those (poor agreement) in the G2 group (OV'= 0.72 vs. 0.35, respectively, p = 0.014). These results showed modest spatial similarity indices between MTV, GTV 2, and GTV 3 of HGG. Nevertheless, the results were significantly improved in patients who underwent only biopsy or partial surgery. TBR ≥ 1.6 and 80-90% SUVmax FET delineation methods showing a good agreement in the hotspot concept for targeting standard dose and radiation boost. These findings need to be tested in a larger randomized prospective study.

RADT-25. UNDERSTANDING PATTERNS OF TUMOUR INFILTRATION IN PATIENTS WITH MULTIFOCAL GLIOBLASTOMA AND IMPACT ON SURVIVAL OUTCOMES

Abstract BACKGROUND Multifocal glioblastoma(MF-G) are often clustered with presumed uniform worse prognosis. This study explores varying patterns of infiltration of MF-G in relation to radiological features, including presence of contiguous MRI T2-weighted abnormalities and adjacent neural tract pathway involvement. METHODS Consecutive patients with glioblastoma from 2016-2020 managed under EORTC-NCI(Stupp60Gy) Protocol had manual tumour segmentation on T1gd and T2w sequences. Multifocal disease was defined as T1gd or solid T2w-abnormality a minimum of 10mm from the dominant lesion. Number of foci, maximum dimension, cortical/white matter site and distance from dominant lesion were recorded. Presence of contiguous T2w-abnormality was recorded, and correlated to ten major neural tract pathways. Progression-free(PFS) and overall survival(OS) were analysed. RESULTS Forty of 177 patients(23%) were identified with MF-G. These had less near-total resection(p = 0.001), but no difference in ECOG(p = 0.16), or MGMT-methylation(p=0.23). Foci had median size of 14.5mm (q1-3: 10-20); 73% enhancing and 58% solitary. Median distance from dominant lesion was 23mm (q1-3:15-25). Contiguous T2w abnormality and involvement of identified neural tract was evident in 78% and 83% respectively. The multifocal lesion was based in cortex in 33%, and white matter in 67%. Survival outcomes were worse with MF-G: OS (p < 0.01) was 16.0 months (95%CI: 13.6-18.4) versus 19.9 months (95%CI: 17.6-22.2); and PFS (p = 0.01) was 10.8 months (95%CI: 9.9-11.7) versus 13.6 months (95%CI: 11.1-16.1). Improved PFS was associated with larger lesion size(p = 0.04), and cortical lesions(0.04). Those MF-G with contiguous T2w-abnormality(p = 0.06); identified neural tract(p = 0.07) or enhancement(p = 0.08) had trend to worse PFS. MGMT(p = 0.10), ECOG(p = 0.62) and extent of resection(p = 0.07) were not associated with PFS, nor radiological factors of foci number(p = 0.19) and lesion distance(p = 0.16). CONCLUSIONS Radiological pattern of infiltration in MF-G is associated with different natural history. Improved PFS was associated with cortical foci without contiguous T2 abnormality or tract involvement. Recognising infiltration patterns may impact on RT target volume delineation and understanding prognosis.

Patient-reported Outcomes in Oropharyngeal Cancer Treated With Definitive Chemoradiation vs. Surgery With Postoperative Radiation With or Without Chemotherapy

Patient-reported Outcomes in Oropharyngeal Cancer Treated With Definitive Chemoradiation vs. Surgery With Postoperative Radiation With or Without Chemotherapy

Outcomes and Patterns of Recurrence for Anaplastic Thyroid Cancer Treated With Comprehensive Chemoradiotherapy

PurposeRadiation therapy (RT) plays an important role in locoregional tumor control for anaplastic thyroid cancer (ATC). Due to its rarity, RT guidelines for ATC are lacking. We describe ATC patterns of nodal disease at presentation and progression and propose corresponding RT target volumes. Methods and MaterialsWe identified all patients with ATC treated at our institution with definitive or adjuvant intensity modulated radiation therapy and concomitant chemotherapy from 2006 to 2020. We identified in-field, marginal, and out-of-field sites of locoregional recurrence and progression (LRR). ResultsForty-seven patients met inclusion. Median follow-up was 6.6 months (interquartile range, 1.9-19.6). Nodal levels involved at presentation included: IB (2.1%), II (23.4%), III (21.3%), IV (21.3%), V (12.8%), VI (34%), and mediastinal (6.4%). All patients received elective nodal RT to levels II-IV and VI. RT volumes also included: IA (23.4%), IB (44.7%), V (87.2%), retropharyngeal/retrostyloid (RP/RS) (27.7%), and mediastinal 1 to 6 (53.2%). Cumulative incidence of LRR at 3- and 12-months was 26.1% (95% confidence interval, 15.9-42.8) and 35.7% (23.9-53.4). Isolated LRR risk at 3- and 12-months was 6.5% (2.2-19.8) and 8.9% (3.4-22.9). Fourteen (29.8%) patients experienced in-field LRR in the thyroid gland or postoperative tumor bed, II-IV, VI, and mediastinal 1 and 3A. Four (8.5%) patients had marginal LRRs, 3 of whom progressed in the mediastinum at 2, 3P, 4, and 6. Two (4.3%) patients experienced out-of-field LRRs. Throughout the pretreatment and follow-up period, no patients had disease at IA, and 1 (2.1%) patient each had disease at IB and RP/RS. No baseline or treatment characteristics, including RT dose (stratified by < or ≥66 Gy), were significant predictors of LRR on univariate analysis. ConclusionsIsolated LRR risk in patients with ATC treated with comprehensive RT and chemotherapy is low. Aggressive multimodality therapy should be reserved for willing, fit patients with no or limited distant disease burden. When treating comprehensively, complete inclusion of mediastinal levels 1 to 6 may be warranted to avoid marginal disease progression. Omission of levels I and RP/RS can be considered.

MS08.01 Adjuvant Radiotherapy for Resected Thymic Carcinoma

Thymic carcinoma is a rare malignancy with peak incidence in the 4th-6th decade. In contrast to thymoma, it is commonly associated with higher rates of both lymph node and distant metastatic spread and also with shorter disease free survival. For localized or locally advanced disease, surgical resection, with the intention of complete disease extirpation, remains the standard of care. Due to its rarity however, definitive clinical trial data regarding optimal and appropriate addition of adjuvant therapy is lacking. Thus, decision making for post-operative patients is guided by data from large institutional, national or international retrospective series or databases (evidence level IV or V). Recommendations for adjuvant therapy for thymic carcinoma are influenced principally by stage and adequacy of resection (R0 vs R1 vs R2). Thymic carcinoma is classically staged us the Masaoka-Koga (MK) system but, based on recommendation to the AJCC by the IASLC Staging Prognostic Factors Committee and the International Thymic Malignancy Interest Group (ITMIG), using a database of more than 10 000 patients (Detterbeck et al 2014), a TNM-based system has now been incorporated into the 8th Edition of the AJCC/UICC TNM Classification of Malignant Tumours. However, since much of the published data regarding thymic malignancies is based on the Masaoka-Koga system, at present this remains commonly used for clinical decision-making but, as data continues to accumulate, will likely be superseded by the TNM system over time. Post-operative radiotherapy is routinely recommended for patients with MK stage III (TNM Stage I – T1bN0, Stage II, IIIA/B) thymic carcinoma following R0 resection. Similarly, adjuvant radiation is recommended following R1 resection, regardless of stage, with adjuvant chemoradiation recommended following R2 resection. Adjuvant radiotherapy is not recommended for MK I or IIA (TNM Stage 1 T1aN0 with no extension to mediastinal fat) disease. Controversy exists regarding the utility of adjuvant radiotherapy in the management of MK IIB (TNM Stage I – T1aN0 with extension to mediastinal fat) disease but can be considered for this group of patients. The optimal adjuvant radiotherapy dose remains undefined for thymic carcinoma patients but typical doses reported in the literature for patients in the above recommended groups range from 45-50 Gy in 1.8-2 Gy per fraction daily. Following R1 resection, 50-54 Gy in 1.8-2 Gy per fraction is typically recommended. Following R2 resection, 60-70 Gy (with or without concurrent chemotherapy) is considered standard. Nodal involvement is much more frequent in patients with thymic carcinoma compared with thymoma. Resected, unexpectedly N+ patients are typically recommended to receive adjuvant RT to 45-60 Gy if complete resection was obtained or 60-70 Gy (with or without concurrent chemotherapy) if residual nodal disease is suspected/documented. Under the TNM staging system, N1 nodes are defined as those in the anterior mediastinal compartment (IASLC levels 1, 3a, 6 and/or supradiaphragmatic/inferior phrenics/pericardial) and N2 nodes are defined as deep intrathoracic or cervical nodes (IASLC levels 2, 4, 5, 7, 10 and/or internal mammary nodes). Whether inclusion of N1 or N2 nodal compartments in adjuvant RT target volumes is of benefit for N0 or completely resected N1 or N2 patients remains unknown but may be prudent to consider during radiotherapy planning based on clinical factors. Radiotherapy should conform to modern standards with CT-based simulation with photon-based 3D conformal or beam-modulated treatment delivery, motion management and image guidance to reduce margins and dose to organs at risk. The utility of adjuvant proton-based RT for patients with resected thymic malignancy remains the focus of ongoing study but may offer some dosimetric advantages with respect to OAR dose (e.g. lung or heart). Selected

In silico study of pseudoprogression in glioblastoma: collaboration of radiologists and radiation oncologists in the estimation of extent of high dose RT region.

Oncologists play a vital role in the interpretation of radiographic results in glioblastoma patients. Molecular pathology and information on radiation treatment protocols among others are all important for accurate interpretation of radiology images. One important issue that may arise in interpreting such images is the phenomenon of tumor "pseudoprogression"; oncologists need to be able to distinguish this effect from true disease progression.Exact knowledge about the location of high-dose radiotherapy region is needed for valid determination of pseudoprogression according to RANO (Response Assessment in Neuro-Oncology) criteria in neurooncology. The aim of the present study was to evaluate the radiologists' understanding of a radiotherapy high-dose region in routine clinical practice since radiation oncologists do not always report 3-dimensional isodoses when ordering follow up imaging. Eight glioblastoma patients who underwent postresection radiotherapy were included in this study. Four radiologists worked with their pre-radiotherapy planning MR, however, they were blinded to RT target volumes which were defined by radiation oncologists according to current guidelines. The aim was to draw target volume for high dose RT fields (that is the region, where they would consider that there may be a pseudoprogression in future MRI scans). Many different indices describing structure differences were analyzed in comparison with original per-protocol RT target volumes. The median volume for RT high dose field was 277 ccm (range 218 to 401 ccm) as defined per protocol by radiation oncologist and 87 ccm (range 32-338) as defined by radiologists (median difference of paired difference 31%, range 15-112%). The Median Dice index of similarity was 0.46 (range 0.14 - 0.78), the median Hausdorff distance 25 mm. Continuing effort to improve education on specific procedures in RT and in radiology as well as automatic tools for exporting RT targets is needed in order to increase specificity and sensitivity in response evaluation.

Integration of 68Ga-PSMA-PET/CT in Radiotherapy Planning for Prostate Cancer Patients.

The clinical data of 191 prostate cancer patients treated with definitive intensity-modulated RT were retrospectively analyzed. All patients were initially staged with thoracoabdominal CT and bone scintigraphy, and the second staging was performed using Ga-PSMA-PET/CT. Both stages were evaluated for the decision making of RT and any change in RT target volumes. After staging with Ga-PSMA-PET/CT, 26 patients (13.6%) had risk group changes, 16 patients (8.4%) had an increase in risk group, and 10 patients (5.2%) had a decrease in risk group. Down-staging occurred in 22 patients (11.5%), and upstaging was observed in 30 patients (15.7%). A total of 26 patients (13.6%) had nodal stage changes. After the Ga-PSMA-PET/CT scans, the number of metastatic patient increased to 17 (8.9%), with 4 of them moving from oligo- to polymetastatic disease. An additional irradiation of pelvic lymphatics and metastatic site was performed in 13 patients (6.8%) and 6 patients (3.2%), respectively. The RT was aborted in 4 patients (2.1%) because of parenchymal or distant site metastasis observed in the Ga-PSMA-PET/CT. We found that Ga-PSMA-PET/CT causes considerable migration in stage, risk group, and RT field arrangements, especially in high-risk patients regardless of the GS and baseline prostate-specific antigen values alone. Ga-PSMA-PET/CT seems to have a great influence on RT decision making in prostate cancer patients.

Randomized phase II study with or without induction chemotherapy combined with accelerated high dose radiotherapy and cetuximab in locally advanced unresectable HPV positive squamous cell carcinoma of the head and neck.

6077 Background: Concomitant chemoradiotherapy (CT/RT) is the standard treatment for locally advanced non- resectable squamous cell carcinoma of the head and neck. Acute side effects can be serious and late effects important. Patients with HPV+ tumors carry a better prognosis than other patients. De-escalation studies are explored with respect to RT, dose, fractionation, target volumes, adjuvant pharmacotherapy, with encouraging results. However, several patients still recur locoregionally, also in high dose RT volumes. Some patients have distant metastases, often with massive tumor burden and late during follow up (FU). Purpose of the study: 1.To evaluate the effect of induction chemotherapy (IC) on (a) progression free survival (b) distant metastases as first site of failure (c) locoregional failure (d) pattern of tumor response, spatial and timely, exploring the possibility to reduce RT dose and/or target volume(s) in future protocols. 2. to address the impact of high dose RT for bulky disease, T3/T4 given concurrent with cetuximab (E). Methods: Patients had previously untreated stage III/IV (&gt;80 % st IV; TNM 7th), M0 disease, WHO 0-1, unresectable squamous cell carcinoma of the head and neck, HPV positive as evaluated with p16 and/or PCR. Pts were randomised between 2 arms. Pts in arm A were scheduled for 2 cycles of TPF : T (docetaxel) 75 mg/m2 day 1, P (cisplatin) 75 mg/m2 day 1 and F (fluorouracil) 1000 mg/m2 over 24 hours day 1-4. RT was delivered with IMRT to all pts : 68 Gy in 6 weeks for T1/T2 tumors, 76 Gy in 6.5 weeks for T3/T4 tumors with E given one week before and weekly during RT. Tumor response was evaluated according to RECIST with CT, MRI or PET/CT after IC, at 6-8 weeks, 1 and 2 years FU. Results: From january 2011 to february 2016, 152 consecutive pts were enrolled, 77 in arm A. All pts had oropharyngeal cancer. In arm A, 7 pts had CR after TPF, 19 had PR out of 36 evaluable pts. At 2 years FU 70/77 pts (91%) were alive in arm A, 69/75 (92%) in arm B. Distant metastases as first site of failure was 3 (3.9%) in arm A and 7 (9.3%) in arm B. Adverse events grade 3-4, ever registered, were seen in 71 pts in arm A and 63 in arm B, were transient, most often related to RT. Conclusions: Survival and locoregional control at 2 years was high and similar in both arms. Distant metastases as first site of failure was more than doubled in arm B, not having induction chemotherapy (IC). Clinical trial information: EudraCT number: 2009-013438-26.

To Evaluate the Feasibility of Minimizing Ovarian Dose in Irradiation of Abdominal and Pelvic Malignancies by applying Optimal Margin in Helical Tomotherapy

This study aimed to evaluate the dosimetric impact on target volume and organs at risk (OARs) in irradiation of abdominal and pelvic malignancies with and without the addition of block and margin (B&M). Based on the results, optimal margins for ovaries will be recommended. The ovaries of 16 patients were contoured by tracing the ovarian veins in CTs. Reference plans (Plan(ref)) were generated following the original physician dose prescriptions. Another 16 plans (Plan(B&M)) with Peters N., suggested margins of 2.2cm and 2.9cm for left (Lt) and right (Rt) ovaries respectively were generated by adding directional or complete block to the ovarian margin. Dose constraints of maximal dose(Dmax) <2Gy and <3Gy were applied to ovaries and ovarian margins respectively in order to achieve the ovarian dose of 2Gy while maintaining the original plan quality. The differences between Plan(ref) and Plan(B&M) in ovary Dmax, ovarian margin Dmax, target Dmax, Dmin,homogeneity index (HI), conformation index(CI) and OARs doses were compared by 2 tailed paired t-tests. A one tailed one sample t-test was used to test if the mean ovary Dmax could be lowered than 2Gy with p<0.05. If not, the lowest achievable ovarian dose after B&M would be found out by subsequent one-tailed one sample t-tests. Pearson correlation test were performed to investigate the correlation between a)ovarian dose and target-ovary distance; b) ovarian dose and target dose; and c) ovarian dose and target volume after B&M was added. Optimal ovarian margins for ovaries <3Gy based on the ovarian margin doses calculation in Plan(B&M) would be estimated. After B&M was added, 75% of patients showed at least one ovary had the Dmax <2Gy while 50% of them had both the Lt and Rt ovaries Dmax less than 2Gy; Also, there were 74.6% and 48.5% average Lt and Rt ovarian doses reduction after the application of B&M respectively. Statistical analysis showed that there were significant difference between the 2 sets of plans in Lt ovary Dmax(p=0.000), Rt ovary Dmax(p=0.037), Lt ovarian margin Dmax(p=0.034), Rt ovarian margin Dmax(p=0.014), target Dmin(p=0.039) and CN(p=0.046), but not for the target Dmax(p=0.077) and HI(p=0.685) as well as all OARs. One-tailed one sample t-test failed to show significant difference between 2Gy and Lt/Rt ovarian Dmax with B&M. Subsequent t-tests showed that the lowest achievable dose of at least one ovary was 5Gy in Plan(B&M). Pearson correlation tests showed significant correlation between target volume and Lt ovary dose (p=0.011) as well as Rt ovary dose (p=0.042). The suggestion of optimal ovarian margins in Plan(B&M) was 1.91cm and 2.57cm for Lt and Rt ovaries respectively. After B&M added, the ovaries doses could be significantly reduced without much affecting target quality. The ovarian dose ≤3Gy could be achieved with the suggested ovarian margin. B&M application offered advantage of lowering the ovarian dose in unilateral small volume target.

Efficacy of Postoperative Radiotherapy Using Modern Techniques in Patients with Retroperitoneal Soft Tissue Sarcoma.

PurposeLocal recurrence is the most common cause of failure in retroperitoneal soft tissue sarcoma patients after surgical resection. Postoperative radiotherapy (PORT) is infrequently used due to its high complication risk. We investigated the efficacy of PORT using modern techniques in patients with retroperitoneal soft tissue sarcoma.Materials and MethodsEighty patients, who underwent surgical resection for non-metastatic primary retroperitoneal soft tissue sarcoma at the Yonsei Cancer Center between 1994 and 2015, were retrospectively reviewed. Thirty-eight (47.5%) patients received PORT: three-dimensional conformal radiotherapy in 29 and intensity-modulated radiotherapy in nine patients. Local failure-free survival (LFFS), overall survival (OS), and RT-related toxicities were investigated.ResultsMedian follow-up was 37.1 months (range, 5.8–207.9). Treatment failure occurred in 47 (58.8%) patients including local recurrence in 33 (41.3%), distant metastasis in eight (10%), and both occurred in six (7.5%) patients. The 2-year and 5-year LFFS rates were 63.9% and 47.9%, respectively. The 2-year and 5-year OS rates were 87.5% and 71.1%. The 5-year LFFS rate was significantly higher in PORT group than in no-PORT group (74.2% vs. 24.3%, p<0.001). In multivariate analysis, PORT was the only independent prognostic factor for LFFS. However, there was no significant correlation between RT dose and LFFS. OS showed no significant difference between the two groups. Grade ≤2 acute toxicities were observed in 63% of patients, but no acute toxicity ≥grade 3 was observed.ConclusionPORT using modern technique markedly reduced local recurrence in retroperitoneal sarcoma patients, with low toxicity. The optimal RT technique, in terms of RT dose and target volume, should be further investigated.

Preoperative Intensity-Modulated Radiation Therapy Compared to Three-Dimensional Conformal Radiation Therapy for High Grade Extremity Sarcomas in Children: An Analysis of Children's Oncology Group (COG) Study ARST 0332

One of the potential disadvantages of neoadjuvant chemoradiation therapy for high grade extremity soft tissue sarcomas (STS) is an increased risk of peri-operative wound complications. In adults, studies have demonstrated reduced radiation dose to the skin and subcutaneous soft tissues may decrease the acute wound complication rate and lead to better limb function. Intensity modulated radiotherapy (IMRT) allows delivery of dose to the target volume with the potential advantage of highly conformal therapy to reduce dose to subcutaneous tissues thus limiting dose to the skin. The purpose of this study was to assess tumor coverage and skin dose in pediatric patients treated with IMRT vs. 3D conformal radiation therapy (3D-CRT) on ARST 0332. Of the 551 eligible patients, 200 were enrolled in Arm D of ARST 0332 in which patients <30 years of age were treated with neoadjuvant ifosfamide/doxorubicin chemotherapy and 45 Gy RT, then surgery, and an RT boost based on margins. A total of 121 RT plans of patients were available for review through remote access of the Imaging and Radiation Oncology Core (IROC) Rhode Island database. Of these, 56 RT plans for patients with extremity STS were reviewed to evaluate the dose delivered to the clinical target volume (CTV) and skin (contoured from the surface to a depth of 5 mm). Of the 56 pediatric patients with extremity STS with RT plans available for review, 38 (65%) were treated with 3D-CRT and 18 (32%) with IMRT. There was no difference in distribution of site treated with IMRT vs. 3D-CRT (upper leg: 53% vs. 50%; knee: 16% vs. 17%; lower leg: 11% vs. 17%; lower arm: 11% vs. 17%, IMRT vs. 3D-CRT, respectively) with the exception of 0% vs. 11% of patients treated with IMRT vs. 3D-CRT to the upper arm. There was no difference in CTV volume between groups of patients treated with IMRT (median 1027 cc, range 66-2867 cc) or 3D-CRT (median 647 cc, range 30-4854 cc) (P = 0.920); however, patients treated with IMRT had significantly improved CTV coverage with 100% of the prescription dose compared to those receiving 3D-CRT (median CTV coverage, 95% vs. 87% respectively, P = 0.011). In patients without skin bolus, the percentage of skin receiving 45 Gy or more was significantly lower in patients treated with IMRT compared to 3D-CRT (mean percentage, 3% vs. 8% respectively, P = 0.039). Pre-operative IMRT compared to 3D-CRT may result in improved RT target coverage with reduced dose to the skin. Future studies are important to assess if this lower skin dose translates to reduced wound complications and/or improved limb function.

ESTABLISHMENT OF THE ONE HOUSE ONE Jumantik PROGRAM IN ORDER TO CONTROL DENGUE FEVER (DBD)

Control of DHF with the establishent of the program Jumantik One Home is the vector control of dengue is the Aedes aegypti mosquito by increasing the participation and empowerment of community-based family for the prevention of the spread of dengue. The purpose community service is to increase the participation and empowerment of the family-based society for the prevention Dengue Fever. The benefits of community service is expected to help local authorities in the success of dengue Disease Control Program and can help people in Kramas in an effort to minimize cases of DHF. Community service is implemented in Kramas District Tembalang Semarang with representatives from each RT target in the Kramas which amounted to 30 people and was conducted in July-August 2016. This dedication method consists of three steps, preparation step, the implementation step is filled the training materials with a lecture/discussion and simulation and practice, and the evaluation step or. The Results show court of this society Formation Program One Jumantik one house has been carried out and in the process of publishing Decision Letter by Kramas Chief. Figures Free Flick (ABJ) Kramas village has not reached the minimum target of 90%.

P2.02-020 Pattern of Care of Inoperable Locally Advanced (LA) NSCLC in Elderly Patients: Analysis of the Experience of Two Academic Italian Hospitals

Optimal treatment in LA NSCLC patients is still debated. In fit patients concomitant radio-chemotherapy (RCT) seems to be the best treatment in terms of local control (LC), progression free survival (PFS) and overall survival (OS) while sequential RCT is a good alternative in unfit patients. Moderately hypofractionated radiotherapy improve OS in recent studies. Elderly patients often cannot be offered multimodality treatments. We report our experience with over 70 years old LA NSCLC patients deemed unfit for surgery. Tabled 1Patients' CharacteristicsAgeMedian75Range70-83GenderMale50 (70%)Female21 (30%)Performance Status (ECOG)0129 (41%)36 (51)26 (8%)HistologyAdenocarcinoma31 (44%)Squamous Cell Carcinoma39 (55%)Large Cell Carcinoma1 (1%)StageIIa/IIb12 (17%)IIIa39 (55%)IIIb20 (28%)ChemotherapyConcomitant9 (13%)Sequential62 (87%)Cycles: median4Cycles: range1-8RadiotherapyMedian Dose62,3 GyModerate hypofractionation26 (37%)Conventional fractionation45 (63%) Open table in a new tab Characteristics of patients and treatments are summarized in table 1. All patients were treated with a platinum based doublet of chemotherapy (CT). RT target volumes included the primary lung tumor and involved mediastinal lymphnodes as defined on pre-treatment contrast enhanced CT scan. Elective nodal irradiation was not performed. Acute/late toxicities were reported in accordance to 4.0 CTCAE scale. Clinical response was evaluated according to RECIST criteria. At a median follow up of 10 months clinical response was evaluable in 69/71 patients obtaining a partial response in 35 of them, stable disease in 17, progressive disease in 17 patients. Twenty six patients experienced a local relapse within RT primary tumor volume, while 13 on nodal volume (5 patients both tumor and nodal relapse). 22 patients developed metastatic disease. One and 3-year OS was 62.3% (SE±6.2%) and 24,5% (SE±7.8%) respectively, while 1- and 3 year PFS was 45.1% (SE±6.9%) and 9,7% (SE±5.7%) respectively. At univariate analysis, tumor dimension (p<0,002) was the only prognostic factor statistically significant for OS. G1-G2 acute toxicity was observed in 45 patients: 36/62 in sequential CRT (3/36 developed also chronic toxicities) and 9/9 in concomitant CRT; most events were G1 oesophagitis (27 patients) and G1 cough (17 patients). No G3-4 event was reported. CRT is feasible in elderly patients; multidisciplinary evaluation is needed in order to reserve CRT to very fit patients.

P2.05-022 Is Post-Chemotherapy Tumor Volume Sufficient RT Target Volume in Patients with LD-SCLC?: Topic: Clinical Outcome

P2.05-022 Is Post-Chemotherapy Tumor Volume Sufficient RT Target Volume in Patients with LD-SCLC?: Topic: Clinical Outcome

Hardware-in-the-loop testing of bypass valve actuation system: Design and validation of a simplified real time model

During the start-up and shut-down phases of steam power plants many components are subjected to pressure and temperature transients that have to be carefully regulated both for safety and reliability reasons. For this reason, there is a growing interest in the optimization of turbine bypass controllers and actuators which are mainly used to regulate the plant during this kind of operations. In this work, a numerically efficient model for real-time simulation of a steam plant is presented. In particular, a modular Simulink™ library of components such as valves, turbines, and heaters has been developed. In this way, it is possible to easily assemble and customize models able to simulate different plants and operating scenarios. The code, which is implemented for a fixed, discrete step solver, can be easily compiled for a RT target (such as a Texas Instrument DSP) in order to be executed in real time on a low-cost industrial hardware. The proposed model has been used for quite innovative applications such as the development of a hardware-in-the-loop test rig of turbine bypass controllers and valve positioners. Preliminary experimental activities and results of the proposed test rig developed for Velan ABV are introduced and discussed.

Abstract P3-12-23: Breast and chest wall edema during and following radiotherapy in breast cancer patients: Prevalence, risk factors and quality of life

Abstract PURPOSE/OBJECTIVE Innovations in loco-regional breast cancer treatment, such as oncoplastic surgery and neoadjuvant chemotherapy, have been suggested to increase the risk of breast and chest wall edema, which may impair quality of life (QoL) during and after treatment. The objective of this study is to evaluate prevalence and risk factors of breast and chest wall edema and its effect on quality of life. METHODS We conducted this study within a prospective observational cohort of breast cancer patients indicated to undergo radiation treatment after being treated with surgery (Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation, UMBRELLA). At the time of inclusion all participants consented to the collection of clinical data and 'patient reported outcomes' (PROMs) at regular intervals during and after treatment. Presence of breast and chest wall edema was registered by radiation oncologists according to CTCAE V4.0 scoring system, at weekly follow-up visits during radiation treatment, and at standard follow-up intervals after radiation treatment. When present, edema was defined as 'acute' (i.e. breast and chest wall edema within 0-90 days after the start of radiation treatment), 'late' (i.e. &amp;gt;90 days) or both. Information on potential risk factors, such as patient and tumor characteristics, and treatment (e.g. surgical procedure, RT target volumes, (neo)adjuvant chemotherapy) was collected from electronic patient files and questionnaires. We performed univariate and multivariable logistic regression analysis to identify determinants that were (independently) associated with breast and chest wall edema. PROMs on quality of life and pain (i.e. EORTC QLQ-C30/BR23) were collected regularly (i.e. baseline, 3, 6 and 12 months) and compared between patients with and without edema. RESULTS We included 427 patients with at least 3 months follow-up (median follow-up 48 weeks). Sixteen percent (70/427) had acute edema, 23% (73/314) had late edema and 8% (25/314) had both acute and late edema. The proportion of women with acute edema was significantly higher in patients treated with oncoplastic surgery (31% vs. 15%, p=0.03) or mastectomy (31% vs. 14% p&amp;lt;0.01). Risk factors for late edema were oncoplastic surgery (p=0.04), mastectomy (p=&amp;lt;0.001), axillary lymph node dissection (ALND) (p=0.01), loco-regional radiotherapy (p=0.02) and acute edema (p=&amp;lt;0.001). Mean QoL scores were lower, and mean pain scores were higher, in patients with edema compared to those without edema at all intervals in time (i.e baseline, 3, 6 and 12 months; figures will be presented at the symposium including stratified analyses). CONCLUSION Breast and chest wall edema is associated with reduced quality of life during the first year of treatment. Oncoplastic surgery and mastectomy increase the risk for acute edema, while oncoplastic surgery, mastectomy, axillary treatment (i.e. ALND, radiation therapy) and the presence of acute edema are associated with late edema. Early treatment of acute edema may reduce the risk for late edema, prolonged pain and impaired quality of life. Citation Format: Young-Afat DA, Verkooijen HM, Gregorowitsch ML, van Gils CH, van der Pol CC, Witkamp AJ, Burgmans I, Jonasse Y, van Vulpen M, van den Bongard DJ. Breast and chest wall edema during and following radiotherapy in breast cancer patients: Prevalence, risk factors and quality of life. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-23.

Implantable marker to facilitate use of hypofractionated radiation in early breast cancer.

38 Background: Shorter courses of radiation therapy have advantages for patients and could result in significant cost savings for the healthcare system. The British and Canadian experience with hypo-fractionated regimens have shown that survival rates in appropriately selected patients is equivalent to other methods. However, adoption of these techniques has been hindered by fear of potential complications such as poor cosmetic outcomes. By improving targeting of the surgical tumor bed, an increased use of "field in field" planning helps to decrease "hot spots" commonly related to toxicities. This could potentially assist with increased use of hypo-fractionated regimens in a reliable, safe and cost-effective manner. To determine the ability of a new surgical implant marker to facilitate use of hypofractionated radiation delivery, we prospectively studied the radiation regimens delivered to 100 patients implanted with the device in our community-based practice. Methods: Over a 36 month period, 110 volumetric tissue markers were surgically implanted at the tumor bed excision site in 109 patients during partial mastectomy (PM). Routine CT imaging of the breast was performed for treatment planning and the marker was rated for visibility and its utility in delineating the target region. Radiation treatment regimens were recorded and reported. A cost analysis was also performed. Results: In all patients, the marker was easily visible and in 95.7% of cases, it was found to be useful during radiation treatment planning for RT target delineation. 36.8% of patients received conventional full-course whole breast irradiation plus boost, 56.6% received hypo-fractionation plus boost, and 4.3% received accelerated partial breast irradiation. With routine use of the implant, there was a marked increase in the use of hypo-fractionated regimens, resulting in a 25% cost savings per patient. Conclusions: This 3-dimensional implant was easily visible and particularly useful in targeting the tumor bed when implanted during PM. With routine use of the device we observed an unanticipated increased use of accelerated radiation protocols, a net cost savings in patients' treatment and a significant improvement in cosmetic outcomes.

An impact of pelvic MRI (PMRI) to radiotherapy (RT) target volumes definition in prostate cancer patients (pts).

78 Background: PMRI is a standard pre-RT evaluation procedure in pts with intermediate and high-risk prostate cancer. We conducted a retrospective study to evaluate an influence of PMRI to delineation of RT clinical target volume (CTV). Methods: Medical records of prostate cancer pts treated with intensity-modulated RT (IMRT) in single institution retrieved and examined retrospectively. Initial risk group affiliation was defined using D'Amico method. PMRI reports of pts with intermediate and high-risk prostate cancer were reviewed and risk group affiliation was re-defined in regards of T- and N-stage. IMRT treatment plans were re-assessed. In regards to PMRI T-stage, extra-capsular extension (ECE) and seminal vesicles invasion (SVI) were included to high-dose CTV. Pelvic lymph nodes (PLN) were planned to treat in all high-risk pts. PLN considered pathological by PMRI were included to separate CTV to receive RT dose higher than unaffected PLN stations. Results: Between 2008 and 2014, 169 pts with intermediate and high-risk prostate cancer underwent PMRI at around 1 month before commencing IMRT. Initially, 89 pts were affiliated to intermediate-risk and 80 to high-risk group. In general, PTV-changes based on PMRI data required in 77 pts (45.5%). Thirty seven of 89 intermediate-risk pts (41.6%) have been switched to high-risk group, necessitating irradiation of PLN. ECE and SVI were included to high-dose CTV in 64 (37.8%) and 29 pts (17.2%) respectively. PLN were thought pathological in 10 pts (5.9%), which demanded contouring of a separate CTV. Conclusions: In our series PMRI-scans had a significant impact on RT target coverage decision in pts with intermediate and high-risk prostate cancer.

Local Failure in Parameningeal Rhabdomyosarcoma: Does Response to Induction Chemotherapy Matter?

year EFS for localized and metastatic patients are 81% and 29% (p 8 cm), 95% vs 77%. General toxicities are shown in the table. In 31 patients with head and neck disease sites the CI of cataract is 35% at 5 years and is highly correlated with orbital disease site (100% vs 21%, p < 0.01) and dose to the lens (p < 0.01). Tumor size at diagnosis correlates with reduced mandibular ROM (p Z 0.04), while site does not (fav/unfav, p Z 0.15). In 14 patients with extremity disease sites, the CI of fracture is 17%, with an average max dose to bone of 46.8 Gy for all 14 patients. In a proportional hazard model, increasing age correlates with physis closure (p Z 0.01), while mean physis dose approaches, but is not significant (p Z 0.13). Growth rate of the bone is reduced by increasing age at RT (p < 0.01), while the impact of mean physis dose approaches significance (p Z 0.10). In 14 patients with pelvic disease 5/14 experienced at least one episode of 3+ hematuria within the first year of RT. Nine of 14 had a measurable degree of hematuria during that year. Ten of 14 had some degree of bladder wall thickening post RT on imaging. No patient required permanent urinary diversion. Conclusions: Modern 3DCRT/IMRT with specific targeting guidelines yields excellent local control for most children with RMS. Despite the use of modern RT and limited target volumes, measurable toxicities are evident and can be correlated with age and RT dose. Techniques and targeting paradigms that further reduce normal tissue exposures are needed. Author Disclosure: M. Krasin: E. Research Grant; Lance Armstrong Foundation Survivorship Grant 2005-2007. C. Hua: None. L.E. Kun: None. A. Pappo: None. A. Pai Panandiker: None. M. Brown: None. A. Davidoff: None. B. Shulkin: None. B. McCarville: None. T.E. Merchant: None.