405 Background: Perioperative chemotherapy is a standard of care (SOC) for patients with resectable gastroesophageal junction adenocarcinoma (GEA), with FLOT as the reference regimen therapy. Preoperative chemoradiotherapy (CRT), another SOC also showed survival improvement compared to surgery alone. The recent ESOPEC trial showed the superiority of FLOT compared to CRT in both esophageal and gastroesophageal junction adenocarcinomas. Nonetheless, few studies have directly compared these two therapeutic approaches. The CHUM (Centre Hospitalier de l’Universite de Montreal) is a tertiary referral center for the management of these patients. Methods: From Jan 2011 to Dec 2024, 660 pts were operated at the CHUM for esophageal and GEJ adenocarcinoma. We retrospectively reviewed the clinical and pathological characteristics of patients who have received perioperative FLOT or CRT (per CROSS protocol). We report preliminary real-life data of 161 patients using Kaplan-Meier survival curves to compare the overall survival (OS) and disease-free survival (DFS), and pathological complete response (pCR) rates between these two populations using OR. Results: As of September 2025, the data of 161 patients (79 FLOT, 82 CROSS) have been analyzed. More than 80% were male patients. Median age was 65 years and comparable between 2 groups. In the CROSS group 97.5% had Siewert I/II and 2.5% Siewert III. In the FLOT group Siewert III represented 24.4%. Most patients in both groups had a T3 clinical stage (94,9% in FLOT vs 92,6% in CROSS) and a positive nodal status (71.8 vs 71.6%). Median DFS was 36.0 months in the FLOT arm (95% confidence interval [CI], 24.0 months to not-reached), as compared to 19.5 months in the CROSS group (95% CI, 13.0 to 38.0 months). Median OS was 81.7 months in the FLOT arm (95% CI, 36.1 months to not-reached) and 36.0 months in the CROSS group (95% CI, 22.0 to 60.0 months). pCR was noted in 12.8% of FLOT patients and 19.8% of CROSS patients. Conclusions: Our results showed that perioperative treatment with FLOT confers better DFS and OS as compared to CROSS. More patient data as well as additional subgroup analyses are currently underway.

Background and study aims: Pancreatic cancer is a devastating disease with limited locoregional treatment options. Diffusing alpha-emitter radiation therapy (Alpha DaRT), a novel cancer treatment using alpha-particle interstitial radiotherapy, may help address this challenge. The aim of this study was to evaluate the feasibility and safety of endoscopic ultrasound (EUS)-guided Alpha DaRT for advanced pancreatic cancer. Patients and methods: Patients with inoperable locally advanced or metastatic pancreatic adenocarcinoma were treated with EUS-guided Alpha DaRT insertion. The Alpha DaRT sources were delivered into pancreatic tumors using a standard EUS needle with a novel proprietary applicator. Adverse events (AEs) were assessed based on the Common Terminology Criteria for Adverse Events version 5.0. Tumor response was evaluated by imaging 4 to 6 weeks post treatment. Results: The first five patients were treated between March and September 2023. The procedure was technically successful in all cases, with Alpha DaRT sources inserted into the target tumor. Estimated gross tumor volume coverage ranged from 8% to 44%. Fourteen AEs were reported among three patients. Four were serious AEs, none of which was associated with the treatment, but rather, with disease progression or medical assistance in dying. Only two AEs (mild) were deemed possibly related to the study device. At the 35-day visit, two patients had progressive disease and three had stable disease, with one of the latter showing partial response 2 months post procedure. Conclusions: Preliminary results from this first-in-human trial indicate that EUS-guided Alpha DaRT treatment for unresectable pancreatic cancer is feasible and safe, with no device-associated serious AEs. Further investigation of this promising novel modality is underway.

Purpose This study aimed to evaluate if the F18-fluorodeoxyglucose positron emission tomography (F18-FDG PET) response after two weeks of chemoradiation for locoregionally advanced esophageal cancer (staged Tumor (T) 3 and/or Nodes (N)+ Metastases (M) 0) was linked to the pathologic response for patients undergoing surgery, to disease-free survival (DFS) or overall survival (OS). Materials and Methods Between March 2006 and September 2017, 40 patients were prospectively enrolled in our study, gave written consent, and had PET scans performed before treatment and after two weeks of chemoradiation. One patient did not undergo his two-week PET without informing study coordinators and was excluded from analyses. Results The median age at diagnosis was 62 years. Seventy-two percent of patients had N+ disease. Median OS for the entire group was 24 months. Five-year overall survival was 17%. Survival curves for patients with no PET response, minor PET response, or good PET response overlapped and were not statistically different. For the 25 patients who underwent surgery, the positive predictive value (PPV) of the PET response relative to the pathologic response was 75% and the negative predictive value (NPV) was 62%. In study patients, the crude recurrence rate was 68% and there was no correlation between PET response and DFS. Conclusion In our study, interim PET response after two weeks of chemoradiation for locoregionally advanced esophageal cancer was not predictive of outcome or pathologic response. Based on our data and current literature, interim PET should not be used to alter treatment (whether to escalate neo-adjuvant treatment or omit surgery).

The oligometastatic state refers to a clinical scenario where a cancer is no longer localized, but not yet widely metastatic. Although many trials define the oligometastatic state as 1 to 3 or 1 to 5 metastatic lesions, there is no universally accepted definition. 1 Palma DA Olson R Harrow S et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): A randomized, phase 2, open-label trial. Lancet. 2019; 393: 2051-2058 Abstract Full Text Full Text PDF PubMed Scopus (920) Google Scholar , 2 Gomez DR Blumenschein Jr., GR Lee JJ et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: A multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016; 17: 1672-1682 Abstract Full Text Full Text PDF PubMed Scopus (665) Google Scholar , 3 Iyengar P Wardak Z Gerber DE et al. Consolidative radiotherapy for limited metastatic non-small-cell lung cancer: A phase 2 randomized clinical trial. JAMA Oncol. 2018; 4:e173501 Crossref Scopus (528) Google Scholar , 4 Ruers T Punt C Van Coevorden F et al. Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: A randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol. 2012; 23: 2619-2626 Abstract Full Text Full Text PDF PubMed Scopus (289) Google Scholar A recently published ESTRO-ASTRO consensus article, in defining oligometastasis, states that "the possibility to safely deliver curative intent metastasis-directed radiation therapy determines the maximum number." 5 Lievens Y Guckenberger M Gomez D et al. Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document. Radiother Oncol. 2020; 148: 157-166 Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar However, the maximum number of metastases that can be safely treated is unknown.

The aim of this study was to evaluate if the FDG-PET response after 2 weeks of chemoradiation for locoregionally advanced esophageal cancer (T3 and/or N+ M0) was linked to the pathologic response for patients undergoing surgery, to disease-free survival (DFS) or overall survival (OS). Between March 2006 and October 2017, 40 patients were prospectively enrolled in our study, gave IRB-approved written consent and were planned to have PET scans performed prior to treatment and after 2 weeks of chemoradiation. One patient did not undergo his 2-week PET and was excluded from analyses. Median age at diagnosis was 62 years old. 72 % of patients had N+ disease. Median OS for the entire group was 24 months. Five-year overall survival was 17%. Survival curves for patients with no PET response, moderate PET response or important PET response overlapped and were not statistically different. For the 25 patients who underwent surgery, the PPV (positive predictive value) of the PET response relative to the pathologic response was 75% and the NPV (negative predictive value) was 62%. In study patients, the crude recurrence rate was 69% and there was no correlation between PET response and DFS. In our study, interim PET response after 2 weeks of chemoradiation for locoregionally advanced esophageal was not predictive of outcome or pathologic response. Based on our data and current literature, interim PET should not be used to alter treatment (whether to escalate neo-adjuvant treatment or omit surgery).

e15747 Background: Surgical resection of PAC followed by adjuvant therapy is the standard of care for non-metastatic resectable tumors. Surgical resection with clear margins of borderline (BR) or locally advanced (LA) tumors is either challenging or impossible. Furthermore, there are no clear recommendations concerning NAT for non-upfront resectable PAC. Thus we reviewed our own experience with different NAT modalities for BR and LA PAC. Methods: Medical records of patients identified by Tumor Board as BR or LA PAC and treated with NAT at Centre Hospitalier de l’Université de Montréal (CHUM) were retrospectively reviewed. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test. For both univariate and subgroup analyses, hazard ratio and 95% confidence interval were estimated by Cox proportional hazard regression. Results: Between 2009 and 2017, 90 patients (50 BR, 40 LA) were identified. Chemotherapy, mostly FOLFIRINOX, was the only NAT in 51 patients (56.6%), 23 patients (25.3%) received chemoradiotherapy alone and 16 patients (17.7%) received sequential treatment of both modalities. Tumor resection was achieved in 44 patients, with 32 BR patients (R0: 68.7%) and 12 LA patients (R0: 75%). Median Disease free survival (DFS) of patients that underwent resection was 12.3 months. mPFS was 29 vs 10 months (HR:0.2; p < 0.001) and mOS was 41.7 vs 15.7 months (HR:0.3; p < 0.001) in resected and non-resected patients, respectively. In subgroup analysis, resection statistically improved PFS and OS regardless of age, sex, T stage and type of vessel involvement. Treatment with more than one modality showed better clinical outcomes (PFS and OS) and a non-statistically higher R0 resection rate that was 100% in BR tumors. OS in patients with resected cancers was not reached for the multimodality group, 41.7 months for chemotherapy alone group and 22.4 months in patients treated with chemoradiotherapy group (p = 0.017). Conclusions: In this retrospective single center analysis, NAT with chemotherapy and/or chemoradiotherapy appears to improve patients’ clinical resection results and outcomes. These results validate previous retrospective studies but warrant large prospective trials to define the best NAT.

The benefits of SBRT in pain control await confirmation in two large North American trials (RTOG0631 and CCTG SC24) but SBRT is already commonly used to improve local control. We hypothesized that systemic therapy may influence the efficacy of spine SBRT in controlling pain and increase the risk of vertebral compression fracture (VCF). We retrospectively reviewed the clinical data of 155 patients treated with SBRT between June 2009 and June 2016. In the current analysis, we included the 127 patients for which SBRT was administered in a context of oligometastatic or oligoprogressive disease (either alone or postoperatively). Outcomes were calculated actuarially and comparisons were performed using log-rank tests (significance set at <0.05). The mean age was 64 (range: 22.67-81.82). Forty-nine patients (39%) had cancers considered radioresistant (kidney 16%, thyroid 9%, melanoma 3 %) and 63 patients had breast (26%), prostate (14%), or lung (13%) cancers. Prior to SBRT, 33%, 63% and 3% had stable (SINS 0-6), potentially unstable (SINS 7-12) and unstable vertebrae (SINS 13-14). Postoperative SBRT was administered in 41%. Pain was present in 78% of patients prior to SBRT. Forty-two percent of the patients received systemic therapy during or within 7 days of SBRT, including chemotherapy and immunotherapy. The median BED10 was 48. Median local recurrence free survival, distant progression free survival and overall survival were 20.5 months, 9 months and 25 months, respectively. There were 14 VCFs. No case of radiation myelopathy was reported. On univariate analysis, patients who were receiving systemic treatment were significantly at a higher risk of developing VCF (p=0.014) or pain recurrence (p=0.001). SINS score, Bilsky scale and pre-SBRT stabilization surgery were not significantly associated with VCF, local recurrence or pain. In our single center retrospective review, we observed that patients on systemic treatments prior to spine SBRT were are high risk of developing VCF and pain recurrence/progression. These results suggest that pain response analyses in ongoing trials need to take into account concurrent systemic treatments as a potential confounding factor. Patient and clinician expectations in the pain response to spine SBRT need to be adapted according to the patient's systemic disease status as to the risk of VCF may also need to be modulated.

ResultsOverall 447 patients were included; 300 in the discovery cohort (median follow-up: 4.2 years) and 147 in the validation cohort (median follow-up: 3 years).Between the two cohorts, there were no significant difference in the 3-year DC (88% [95% CI: 84%-91%] vs. 84% [95% CI: 77%-89%], p=0.16) or OS (72% [95% CI: 67%-77%] vs. 69% [95% CI: 61%-77%], p=0.26).The Multivariable analysis identified pN2-3 and histological grade 2-3 (G2-3) as DM predictors.The high-risk group included patients who had both poor predictors (pN2-3 and G2-3), while low-risk group consisted of patients who had one or no poor predictors.In the discovery cohort, the 3-year DC rate was 78% (95% CI: 70%-84%) and 97% (95% CI: 92%-99%) in high-and low-risk groups respectively (p<0.001), with the concordance index (c-index) of 0.72.In the validation cohort, the risk group classification performed similarly (3-year DC: 69% [95% CI: 54%-79%] vs. 95% [95% CI: 87%-98%], p<0.001) with the c-index value of 0.73.The 3-year OS for the high-vs.low-risk group was 85% (95% CI: 79-91%) vs. 95% (95% CI: 91%-98%) in the discovery cohort (p<0.001), and 74% (95% CI: 63-86%) and 93% (95% CI: 87%-99%) in the validation cohort (p<0.001). ConclusionThe proposed classification allowed for the definition of a high risk group of DM with poor survival.This validated model (G2-3/pN2-3) could be used to identify OSCC patients who may benefit from: 1) more aggressive screening for DM (before initiating the treatment) in order to avoid unnecessary or inappropriate management, 2) experimental systemic treatment intensification to impact development of DM, and 3) a more aggressive post-treatment surveillance schedule for early detection of DM and consideration of experimental ablative treatments for oligometastatic or early systemic treatment for non-oligometastatic disease.

Purpose To compare the impact of the fusion of intraoperative transrectal ultrasound (TRUS) images with day 30 computed tomography (CT) and magnetic resonance imaging (MRI) on prostate volume and dosimetry. Methods and materials Seventy-five consecutive patients with CT and MRI obtained on day 30 with a Fast Spin Echo T2-weighted magnetic resonance (MR) sequence were analyzed. A rigid manual registration was performed between the intraoperative TRUS and day-30 CT based on the prostate volume. A second manual rigid registration was performed between the intraoperative TRUS and the day-30 MRI. The prostate contours were manually modified on CT and MRI. The difference in prostate volume and dosimetry between CT and MRI were compared. Results Prostate volume was on average 8% (standard deviation (SD) ± 16%) larger on intraoperative TRUS than on CT and 6% (18%) larger than on MRI. In 48% of the cases, the difference in volume on CT was > 10% compared to MRI. The difference in prostate volume between CT and MRI was inversely correlated to the difference in D90 (minimum dose that covers 90% of the prostate volume) between CT and MRI (r = -0.58, P < .001). A D90 < 90% was found in 5% (n = 4) on MRI and in 10% (n = 7) on CT (Fisher exact test one-sided P = .59), but in no patient was the D90 < 90% on both MRI and CT. Conclusions When fusing TRUS images with CT and MRI, the differences in prostate volume between those modalities remain clinically important in nearly half of the patients, and this has a direct influence on how implant quality is evaluated.

Purpose : To analyze intraoperative (IO) dosimetry using transrectal ultrasound (TRUS), performed before and after prostate low-dose-rate brachytherapy (LDR-BT), and compare it to dosimetry performed 30 days following the LDR-BT implant (Day 30). Material and methods : A total of 236 patients underwent prostate LDR-BT using 125 I that was performed with a three-dimensional TRUS-guided interactive inverse preplanning system (preimplant dosimetry). After the implant procedure, the TRUS was repeated in the operating room, and the dosimetry was recalculated (postimplant dosimetry) and compared to dosimetry on Day 30 computed tomography (CT) scans. Area under curve (AUC) statistics was used for models predictive of dosimetric parameters at Day 30. Results : The median follow-up for patients without BF was 96 months, the 5-year and 8-year biochemical recurrence (BR)-free rate was 96% and 90%, respectively. The postimplant median D 90 was 3.8 Gy lower (interquartile range [IQR], 12.4-0.9), and the V 100 only 1% less (IQR, 2.9-0.2%) than the preimplant dosimetry. When comparing the postimplant and the Day 30 dosimetries, the postimplant median D 90 was 9.6 Gy higher (IQR [–] 9.5-30.3 Gy), and the V 100 was 3.2% greater (0.2-8.9%) than Day 30 postimplant dosimetry. The variables that best predicted the D 90 of Day 30 was the postimplant D 90 (AUC = 0.62, p = 0.038). None of the analyzed values for IO or Day 30 dosimetry showed any predictive value for BR. Conclusions : Although improving the IO preimplant and postimplant dosimetry improved dosimetry on Day 30, the BR-free rate was not dependent on any dosimetric parameter. Unpredictable factors such as intraprostatic seed migration and IO factors, prevented the accurate prediction of Day 30 dosimetry.

INTRODUCTION:Despite advances in treatment, notably in systemic therapy, the prognosis of pancreatic adenocarcinoma (PADC) remains dismal. Stereotactic body radiotherapy (SBRT) is an emerging tool in the complex management of PADC. We review outcomes of SBRT for PADC at our institution. METHODS:We reviewed patients treated with SBRT for either unresectable PADC or locally recurrent PADC after surgery. Treatment was delivered using a robotic radiosurgery system with respiratory tracking. The median prescribed dose was 30 Gy (30-35 Gy), delivered in 5-6 fractions. Toxicities were reported as per CTCAE v4.0. Survival was estimated using the Kaplan-Meier method. RESULTS:Between October 2010 and March 2016, 21 patients were treated at our institution. The median follow-up was 7 months (range: 1-28). The 1-year local control rate was 57%. The 1-year overall survival was 25% for locally advanced patients and 67% for those with local recurrences (p = 0.27). Eighty percent of cancer related deaths were due to metastatic progression. Five patients (24%) had Grade I-II gastrointestinal acute toxicity; one patient had fatal gastrointestinal bleeding 6 months after SBRT. CONCLUSION:In PADC, fractionated SBRT dose schedules near 30 Gy may strike the best balance of local control and bowel toxicity. More work is required to integrate pancreatic SBRT with modern systemic therapy.

Purpose: To determine the incidence of pseudoprogression (P P) post-spine SBRT based on a detailed and quantitative assessment of MRI morphol ogic tumor alterations, and to identify predictive factors distinguishing PP from local rec urrence (LR). Materials/Methods: A retrospective analysis of 35 patients with 49 sp inal segments treated with spine SBRT, from 2009 to 2014, was conducted. Media n number of follow-up MR studies was 4 (range: 2-7). The gross tumor volumes (GTV) within each of the 49 spinal segments were contoured on the pre-treatment and each subsequent follow-up T1 and T2 weighted MRI sagittal sequence. T2 signal intensity was reported as the m ean intensity of voxels constituting each volume. LR was defined as persistent GTV enlargeme nt on at least 2 serial MRI for at least 6 months, and/or upon pathological confirmation. PP w as defined as a GTV enlargement, followed by stability or regression on subsequent imaging wi thin 6 months. Kaplan Meier analysis was used for estimation of actuarial LC, disease-free s urvival (DFS) and overall survival (OS). Results: Median follow-up was 23 months (1-39 months). PP w as identified in 18% (9/49) of treated segments, and LR in 29% (14/49). Earlier vo lume enlargement (5 months for PP vs. 15 months for LR, p=0.005), greater GTV to reference n on-irradiated vertebral body (VB ref) T2 intensity ratio (+30% vs. -10% for LR, p=0.005) and growth confined to the 80% prescription isodose line (IDL) (8/9 vs. 1/14, p = 0.002) were a ssociated with PP on univariate analysis. Multivariate analysis confirmed an earlier time to v lume enlargement and growth within 80% IDL as significant predictors of PP. LR involved t he epidural space in all but 1 lesion, whereas PP was confined to the VB in 7/9 cases. Conclusions: PP was observed in 18% of treated spinal segments. Tumor growth confined to the 80% IDL and earlier time to tumor enlargement predi cted for PP. M AN US CR IP T AC CE PT ED ACCEPTED MANUSCRIPT INTRODUCTION Spine stereotactic body radiation therapy (SBRT) is an emerging therapy for patients with spinal metastases. The high in-field biologically effectiv e dose (BED) and steep dose gradients allow for delivery of a highly focused ablative dose. Unc o trolled data suggest greater rates of complete response to pain, local control and possib ly neurological function as compared to conventional external beam palliative radiation [17]. This technique is still considered emerging and several questions remain as to the optimal dose and fractionation, tolerance to the critical organs-at-risk (OAR) and, moreover, how to judge tr eatment response. The latter is of significant importance as it is only recently that we have rout inely incorporated MRI into the treatment planning and follow-up of spinal metastases treated with radiation. As suggested by the recently reported SPIne response assessment in Neuro-Oncolog y (SPINO) group [8], MRI is the recommended imaging modality for diagnostic evaluat ion and assessment of tumor response following spine SBRT [9]. This is due to the abilit y o visualize the tumor within the bony segment as opposed to a more crude delineation limi ted to the bony anatomy possible with CT. The impact of post radiation MRI signal change has only begun to be investigated, and as a direct result of SBRT practice that demands rigorous follo w-up given the potential for serious complications like radiation myelopathy [10] and ve rtebral compression fracture (VCF) [11]. Moreover, when applying such a high dose technique, documentation and understanding of treatment response is imperative to reassure the pa ti nt and also for the field to evolve. At present, the morphologic changes associated with ra diation in the spine remains poorly understood [8]. PP is defined as a treatment-related transient tumo r growth that mimics true progression [12,13]. It was first described in gliomas undergoing high d ose radiation and chemotherapy [12,14-16], and has been well documented following brain radios urgery [17-22], lung SBRT [16,23-26] and M AN US CR IP T AC CE PT ED ACCEPTED MANUSCRIPT liver SBRT [27]. However, literature on osseous PP post spine SBRT is limited and although its occurrence was suggested in some early spine SBRT l iterature [28,29], it was only recently that Taylor et al. [30] reported a detailed summary of 2 patients that experienced imaging-based PP. Most recently, the MD Anderson Cancer Center group reported the occurrence of PP in 5 of 37 lesions treated with spine SBRT [31]. They suggeste d that PP should be considered before assuming local relapse (LR) and that serial imaging should be considered; however, their analysis did not focus on quantitative MR based signal chara cte istics. In the spine, the consequence of misdiagnosing LR can be significant, as often the n ext step in the management of SBRT failures is a spine surgery which has risks of morbidity. Fu rthermore, if a second course of radiation is delivered assuming LR, the patient may be at seriou s risk of irreversible devastating toxicities that include radiation myelopathy. A clear underst anding of response is needed in order to make appropriate treatment decisions, in particular give n the potential for PP. The aim of this study was to determine the incidence of PP post-spine SBRT, b ased on a detailed and quantitative assessment of MRI morphologic tumor alterations, as well as to identify predictive factors distinguishing PP from LR. MATERIAL AND METHODS Patient selection From July 2009 to March 2014, 127 patients were tre ated with spine SBRT at our center. Patients were included in this analysis if they had a pre-tr eatment MRI demonstrating spinal metastatic disease and at least 2 post-treatment follow-up MRI studies. Patients undergoing systemic therapy such as cytotoxic chemotherapy, hormone the rapy or bisphosphonates could be included in the study if they were stable on treatment based on the baseline assessment. This left 35 M AN US CR IP T AC CE PT ED ACCEPTED MANUSCRIPT patients with 49 spinal segments as the study cohor t. Institutional ethics review board approval was obtained for this study. In general, our institutional indications for spine SBRT include treatment of oligometastatic disease, re-treatment after conventional radiothera py nd treatment of residual disease after surgical debulking. Patients with spinal cord compr ession or a mechanically unstable spine were only treated with SBRT after surgical decompression or stabilisation. Radiosensitive histologies including lymphoma, seminoma and multiple myeloma w ere excluded. A radioresistant histology was defined as those metastases arising from thyroi d, enal, melanoma or sarcomas. All other histologies were classified as neutral. Epidural di sease grading was based on Bilsky criteria [32], and extra-compartmental vs. intra-compartmental dis ease classification was categorized as per the Tomita guideline [33]. SBRT treatment Patients were treated with either Cyberknife (XSigh t Spine, Cyberknife (G4 2009-2013, VSI 2013-2014), Accuray, Sunnyvale, CA), linac-based vo lumetric intensity-modulated radiotherapy (RapidArc®, Varian Medical Systems, Palo Alto, CA) (VMAT) or helical tomotherapy (HT) (Tomotherapy Hi-Art, Accuray, Sunnyvale, CA). Immob ilization devices included a custom foam cushion for Cyberknife Xsight Spine® based SBR T. A BodyFix (Elekta AB, Stockholm, Sweden) was used for HT and VMAT based SBRT for spi nal segments involving the thoracic 4 th vertebrae (T4) and lower; otherwise, a thermoplasti c head and neck mask was used for spinal segments involving the 3 rd thoracic vertebrae to the 1 st cervical vertebrae. Pre-treatment contours for all treatment modalities were performed on Ecli pse treatment planning system (Varian Medical Systems, Palo Alto, CA). All patients underwent a 1.5 mm slice thickness non -c trast planning CT-scan in the supine M AN US CR IP T AC CE PT ED ACCEPTED MANUSCRIPT position. Sagittal non-enhanced 3D T1 SPACE (TR 420 ms, TE 14 ms, FOV adjusted to volume of interest, slice thickness 1 mm, voxel size 1.0x1 x1.0 mm) and 3D T2 SPACE (TR 1200 TE 154 FOV adjusted to volume of interest, voxel size 1.0x1.0 x1.0 mm). MRI sequences acquired on a 1.5 Tesla system (Aera, Siemens, Forchheim, G ermany) extending cranio-caudally by at least one vertebral body below and above the treate d lesion were co-registered with the planning CT scan. The fused images were used to delineate tu mor and spinal cord. The CTV was based on the discretion of the treating radiation oncologist and typically involved at least a 5 mm margin beyond the GTV until 2012. Thereafter, the Internat ional Spine Radiosurgery Consortium (ISRC) consensus guidelines for target volume definition w ere implemented as standard of practice. A planning target volume (PTV) margin of 2 mm was app lied excluding the spinal cord and/or thecal sac, and a 2mm planning risk volume (PRV) wa s applied to the spinal cord as a safety margin. Dose restrictions to spinal cord were per ublished constrains [10,34]; limitations for other OAR as per RTOG 0631 [35]. Follow-up, image analysis and statistics Standard follow-up for all patients included a medi cal visit and a non-contrast enhanced MRI every 2 to 6 months. MRIs were performed on a 1.5T system (Avanto, Siemens, Forchheim, Germany), different from the treatment planning MRI system. Follow-up studies were on varied 1.5T devices, and routinely included non-enhanced T 1 turbo Spin Echo (TR 685 ms, TE 13 ms, FOV 330 mm, slice thickness 3.5 mm, interslice gap 0.3 mm) and T2 Turbo Spin Echo (TR 4330 ms, TE 83 ms, FOV 330 mm, slice thickness 3.5 mm, i nterslice gap 0.3 mm) MRI sequences. Pre-treatment and follow-up sagittal T1and T2-wei ghted sequences were imported into a single treatment planning system (Eclipse, Varian Medical Systems, Palo Alto, CA). Bony registration M AN US CR IP T AC CE PT ED ACCEPTED MANUSCRIPT between pre-treatment and follow-up MRI was perform ed on

Purpose: To determine the incidence of pseudoprogression (PP) after spine stereotactic body radiation therapy based on a detailed and quantitative assessment of magnetic resonance imaging (MRI) morphologic tumor alterations, and to identify predictive factors distinguishing PP from local recurrence (LR).Methods and Materials: A retrospective analysis of 35 patients with 49 spinal segments treated with spine stereotactic body radiation therapy, from 2009 to 2014, was conducted. The median number of follow-up MRI studies was 4 (range, 2-7). The gross tumor volumes (GTVs) within each of the 49 spinal segments were contoured on the pretreatment and each subsequent follow-up T1- and T2-weighted MRI sagittal sequence. T2 signal intensity was reported as the mean intensity of voxels constituting each volume. LR was defined as persistent GTV enlargement on >= 2 serial MRI studies for >= 6 months or on pathologic confirmation. PP was defined as a GTV enlargement followed by stability or regression on subsequent imaging within 6 months. Kaplan-Meier analysis was used for estimation of actuarial local control, disease-free survival, and overall survival.Results: The median follow-up was 23 months (range, 1-39 months). PP was identified in 18% of treated segments (9 of 49) and LR in 29% (14 of 49). Earlier volume enlargement (5 months for PP vs 15 months for LR, P = .005), greater GTV to reference nonirradiated vertebral body T2 intensity ratio (+30% for PP vs -10% for LR, P = .005), and growth confined to 80% of the prescription isodose line (80% IDL) (8 of 9 PP cases vs 1 of 14 LR cases, P = .002) were associated with PP on univariate analysis. Multivariate analysis confirmed an earlier time to volume enlargement and growth within the 80% IDL as significant predictors of PP. LR involved the epidural space in all but 1 lesion, whereas PP was confined to the vertebral body in 7 of 9 cases.Conclusions: PP was observed in 18% of treated spinal segments. Tumor growth confined to the 80% IDL and earlier time to tumor enlargement were predictive for PP. (C) 2016 Elsevier Inc. All rights reserved.

ObjectivesStereotactic body radiation therapy (SBRT) is an emerging treatment option for liver tumors unsuitable for ablation or surgery. We report our experience with SBRT in the treatment of liver tumors.Materials and methodsPatients with primary or secondary liver cancer were identified in our local SBRT database. Patients were included irrespective of prior liver-directed therapies. The primary endpoint of our review was in-field local control (LC). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity.ResultsFrom 2009 to 2015, a total of 71 liver lesions in 68 patients were treated with SBRT (three patients had two liver lesions treated). The median age was 71 years (27-89 years). Hepatocellular carcinoma (HCC) was the diagnosis in 23 patients (34%), with the grade of Child-Pugh A (52%), B (39%), or C (nine percent) cirrhosis. Six patients (nine percent) had intrahepatic cholangiocarcinoma (IHC). The remaining 39 patients (57%) had metastatic liver lesions. Colorectal adenocarcinoma was the most common primary tumor type (81%). The median size for HCC, IHC, and metastatic lesions was 5 cm (2-9 cm), 3.6 cm (2-4.9 cm), and 4 cm (1-8 cm), respectively. The median prescribed dose was 45 Gy (16-50 Gy).Median follow-up was 11.5 months (1-45 months). Actuarial one-year in-field LC for HCC and metastatic lesions was 85% and 64% respectively (p=0.66). At one year, the actuarial rate of new liver lesions was 40% and 26%, respectively, (p=0.58) for HCC and metastases. Only six patients with IHC were treated with SBRT in this study - in these patients, one-year LC was 78% with new liver lesions in 53%.The SBRT treatments were well tolerated. The side effects included common criteria for adverse events (CTCAE) v4 grade 1 acute gastrointestinal toxicity in three patients, grade 3 nausea in one patient, and grade 3 acute dermatitis in another patient. Two patients had grade 5 toxicity. Radiation pneumonitis was observed in one patient two months post-SBRT treatment, and another patient was suspected to have had radio-induced liver disease (RILD) two months after SBRT. No late toxicity was seen.ConclusionSBRT is a well-tolerated and effective alternative treatment option for selected patients with primary and metastatic liver tumors.

PURPOSE:To analyze the difference in prostate coverage and dose to the rectum in men with prostate carcinoma treated with permanent seed brachytherapy with different seed activities. METHODS:Forty-nine patients treated with iodine-125 permanent seed prostate brachytherapy with low-activity seeds of 0.30-0.37 mCi were identified. For each of these patients, 2 patients with similar prostate volume (±2 cc) were paired: one treated with intermediate seed activity (0.44-0.46 mCi) and one with high seed activity (0.60-0.66 mCi). The doses to prostate and rectum were compared using CT on Day 30. RESULTS:A total of 147 patients divided into the three seed activity groups were analyzed. Mean prostate volume was 35.7 cc (standard deviation [SD], 11.70). Compared with low-activity seeds, implants with high-activity seeds consisted of an average of 22 seeds and 4.7 needles less. The dose to the prostate (prostate volume receiving 100% of the prescribed dose [V100], prostate volume receiving 150% of the prescribed dose, and minimal dose covering 90% of the prostate volume expressed in Gy) was not higher on Day 30 (p = 0.58-0.97). The mean volume (in cubic centimeters) of rectal wall receiving 100% of the prescribed dose (V100) increased with activity: low activity, 0.34 cc (SD, 0.49), intermediate activity, 0.47 cc (SD, 0.48), and high activity, 0.72 cc (SD, 0.79) (p = 0.009). There was a trend (p = 0.073) toward a higher frequency of clinically unfavorable rectal dosimetry (V100 > 1.3 cc) in patients with high-activity seeds (16.7%) compared with low-activity (6.3%) or intermediate-activity (4.2%) seeds. CONCLUSION:High-activity seeds do not result in a higher dose to the prostate but in a higher dose to the rectum.

Introduction: To identify risk factors for PSA bounce (PSAb) and compare characteristics of prostate cancer patients treated with brachytherapy and external beam radiotherapy (EBRT).Materials and methods: We identified 362 patients treated for low risk prostate adenocarcinoma (D'Amico criteria) with a follow up time of at least 36 months. Patients received either: 1) EBRT 76 Gy in 38 fractions (n = 58); 2) hypofractionated EBRT, 45 Gy in 9 once-weekly fractions (n = 74); 3) seed brachytherapy (n = 230). PSAb was defined as a rise 0.2 ng/mL with subsequent return to baseline within the first 3 years after treatment. Univariate and multivariate logistic regression models were estimated to assess the association between clinical factors and occurrence of PSAb.Results: There was no significant difference between treatment groups (p = 0.349), with an overall PSAb rate of 28.5%. Upon univariate analysis, the following were predictive of a lower PSAb rate: older age (OR = 0.96), higher P SA at diagnosis (OR = 0.87), more positive biopsy cores (OR = 0.98), and a higher Cancer of the Prostate Risk Assessment (CAPRA) score (CAPRA of 3 versus 1: OR = 0.33). Multivariate analysis confirmed the significance of fewer positive biopsy cores (OR = 0.99) and a lower CAPRA score (CAPRA 3 versus 1: OR = 0.34). These factors also predicted a shorter time to first PSAb.Conclusions: We found comparable rates of PSAb after different regimens of radiotherapy. We hypothesize that it results from late damage to healthy prostatic tissue. This idea is supported by the fact that we found that clinical factors indicative of a lower tumor burden were predictive of a PSAb.

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