Local Treatment Failure Research Articles

In-vivo treatment accuracy analysis of active motion-compensated liver SBRT through registration of plan dose to post-therapeutic MRI-morphologic alterations

Background/purposeIn-vivo-accuracy analysis (IVA) of dose-delivery with active motion-management (gating/tracking) was performed based on registration of post-radiotherapeutic MRI-morphologic-alterations (MMA) to the corresponding dose-distributions of gantry-based/robotic SBRT-plans. MethodsForty targets in two patient cohorts were evaluated: (1) gantry-based SBRT (deep-inspiratory breath-hold-gating; GS) and (2) robotic SBRT (online fiducial-tracking; RS). The planning-CT was deformably registered to the first post-treatment contrast-enhanced T1-weighted MRI. An isodose-structure cropped to the liver (ISL) and corresponding to the contoured MMA was created. Structure and statistical analysis regarding volumes, surface-distance, conformity metrics and center-of-mass-differences (CoMD) was performed. ResultsLiver volume-reduction was −43.1 ± 148.2 cc post-RS and −55.8 ± 174.3 cc post-GS. The mean surface-distance between MMA and ISL was 2.3 ± 0.8 mm (RS) and 2.8 ± 1.1 mm (GS). ISL and MMA volumes diverged by 5.1 ± 23.3 cc (RS) and 16.5 ± 34.1 cc (GS); the median conformity index of both structures was 0.83 (RS) and 0.80 (GS). The average relative directional errors were ≤0.7 mm (RS) and ≤0.3 mm (GS); the median absolute 3D-CoMD was 3.8 mm (RS) and 4.2 mm (GS) without statistically significant differences between the two techniques. Factors influencing the IVA included GTV and PTV (p = 0.041 and p = 0.020). Four local relapses occurred without correlation to IVA. ConclusionsFor the first time a method for IVA was presented, which can serve as a benchmarking-tool for other treatment techniques. Both techniques have shown median deviations <5 mm of planned dose and MMA. However, IVA also revealed treatments with errors ≥5 mm, suggesting a necessity for patient-specific safety-margins. Nevertheless, the treatment accuracy of well-performed active motion-compensated liver SBRT seems not to be a driving factor for local treatment failure.

Outcomes After Reduced-Dose Intensity Modulated Radiation Therapy for Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

In patients with gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, the standard radiation therapy (RT) dose is ≥30Gy. We report the outcome of patients treated with reduced dose 24Gy compared with those treated with ≥30Gy. We reviewed results from 32 patients who received a diagnosis of gastric MALT lymphoma between 2007 and 2017 who were treated with involved site RT using intensity modulated radiation therapy (IMRT). Response to therapy was based on post-RT endoscopic biopsy. Freedom from local treatment failure (FFLTF), freedom from treatment failure (FFTF), and overall survival (OS) outcomes were determined. The median age of patients at diagnosis was 58years. Therapy for MALT was given prior to RT in 14 patients with residual biopsy proven disease documented in all cases (anti-microbial, n=11; rituximab, n=2; rituximab, cyclophosphamide, doxorubicin, vincristine, n=1). One patient received RT (36Gy) and concurrent rituximab. The median RT dose was 30Gy; it was 30 to 36Gy in 66% of patients (n=21) and 24Gy in 34% of patients (n=11). Post-RT biopsy documented a complete response in all patients. Failures occurred in the stomach and duodenum, respectively, at 3.6 and 4.5years, after 30Gy. At a median follow-up of 55.2months (73.8 for ≥30Gy compared with 28.7 for 24Gy; P<.001), the 2-year FFLTF, FFTF, and OS were 100%, 100%, and 97%, respectively. No association was found between the lower (24-Gy) dose and FFLTF (P=.819), FFTF (P=.819), or OS (P=.469). Contemporary RT with involved site targeting using IMRT is associated with high complete response rates for patients with gastric MALT lymphoma, even using reduced doses of 24Gy. Additional follow-up and increased patient numbers are required to confirm equivalent disease control.

Iodine-125 Episcleral Plaque Brachytherapy for AJCC T4 Posterior Uveal Melanoma: Clinical Outcomes in 158 Patients

Background/Aims: The aim of this study is to report the burden of ocular morbidity following iodine-125 episcleral plaque brachytherapy (EPBT) in the treatment of American Joint Committee on Cancer (AJCC) T4-staged posterior uveal melanoma (PUM). Methods: Clinical records of patients with T4-staged PUM treated with ¹²⁵I EPBT were analyzed for incidence of treatment failure and radiation-induced complications. Results: Cumulative incidence of local treatment failure was 9% (95% CI 5–15%) at 5 years and was associated with decreased tumor height (HR = 0.78; p = 0.01). Cumulative incidence of enucleation at 5 years was 21% and was correlated with worsening baseline visual acuity (HR = 1.42; p = 0.05). Increasing patient age was associated with higher rates of vitreous hemorrhage (HR = 1.03; p = 0.02) and cataract surgery (HR = 1.05; p < 0.001). Increased tumor height was associated with higher rates of neovascular glaucoma (HR = 1.16; p = 0.03) and vitreous hemorrhage (HR = 1.23; p < 0.001). Conclusion: ¹²⁵I EPBT is an effective treatment for T4-staged PUM and achieves high rates of local control. Treatment failure appears to be more common among minimally elevated tumors. Other causes of ocular morbidity were associated with increasing tumor height, patient age, and baseline visual acuity.

High HLA-F Expression Is a Poor Prognosis Factor in Patients with Nasopharyngeal Carcinoma.

Background and Aims In patients with nasopharyngeal carcinoma (NPC), local treatment failure and distant metastasis contribute largely to poor outcomes. The nasopharynx is an important lymphoid tissue, and NPC tumourigenesis and development are partly attributed to immune system disorders. Human leukocyte antigen F (HLA-F) has shown a close correlation with NPC in many genome-wide association studies (GWASs). However, clinical studies rarely explore the relationship of HLA-F expression with the clinical parameters and outcomes in patients with NPC. Methods In this study, we used immunohistochemistry to evaluate HLA-F expression in 74 paraffin-embedded NPC tissue sections and then analysed the association between HLA-F expression and clinical parameters and outcomes. The plasma concentration of soluble HLA-F (sHLA-F) in NPC patients and normal controls was also detected, via enzyme-linked immunosorbent assay (ELISA). Results Low, moderate, and high HLA-F expression levels were observed in 47.3% (35/74), 35.1% (26/74), and 17.6% (13/74), respectively, of the tissue samples. HLA-F expression showed a significant correlation with local recurrence (p = 0.037) and distant metastasis (p = 0.024) and was also an independent factor for local recurrence-free survival (LRFS; p = 0.016) and distant metastasis-free survival (DMFS; p = 0.004). Although the mean concentration of plasma sHLA-F in the NPC patients was higher than that in the normal controls (13.63 pg/ml vs. 10.06 pg/ml), no statistical significance was observed (p = 0.118). Conclusions Our study provides the first evidence that high HLA-F expression is associated with NPC local recurrence and distant metastasis and may be regarded as a poor prognostic factor for NPC patients. Additional studies using larger sample sizes may be necessary to determine whether sHLA-F is a feasible NPC diagnostic indicator.

The total number of lymph nodes harvested from pathological T3N0 rectal cancer patients

Lymph node status is important in staging colorectal cancer. The use of combination treatment for pathological T3N0 (pT3N0) rectal cancer patients has been controversial. We aimed to explore the prognostic significance of the total number of lymph nodes harvested from pT3N0 rectal cancer patients. Between June 2004 and November 2011, 289 pT3N0 rectal cancer patients who received total mesorectal excision (TME) with or without postoperative chemotherapy were retrospectively reviewed. The main independent variable was the total number of harvested lymph nodes, and the endpoints included local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). The patients had a median of 13 lymph nodes harvested. When compared with patients who had < 12 lymph nodes harvested, patients who had ≥12 lymph nodes harvested had higher 5-year LRFS (84.7% vs. 98.0%, P < 0.001), DFS (71.4% vs. 86.8%, P < 0.001), and OS (77.6% vs. 94.9%, P < 0.001) rates. Multivariate analysis demonstrated that the patients who had ≥12 lymph nodes harvested had a significantly lower risks of local relapse (hazard ratio [HR], 0.099; P < 0.001), treatment failure (HR: 0.291; P < 0.001), and death (HR: 0.231; P < 0.001) when compared with patients who had <12 lymph nodes harvested. The number of lymph nodes harvested was independently associated with local relapse, treatment failure, and OS rates in pT3N0 rectal cancer patients who received initial TME with or without postoperative chemotherapy. Postoperative radiotherapy should not be omitted for pT3N0 rectal cancer patients who had <12 lymph nodes harvested.

A prospective pilot study on early toxicity from a simultaneously integrated boost technique for canine sinonasal tumours using image-guided intensity-modulated radiation therapy.

In order to overcome the common local treatment failure of canine sinonasal tumours, integrated boost techniques were tried in the cobalt/orthovoltage era, but dismissed because of unacceptable early (acute) toxicity. Intriguingly, a recent calculation study of a simultaneously integrated boost (SIB) technique for sinonasal irradiation using intensity-modulated radiation therapy (IMRT) predicted theoretical feasibility. In this prospective pilot study we applied a commonly used protocol of 10 × 4.2 Gy to the planning target volume (PTV) with a 20%-SIB dose to the gross tumour volume (GTV). Our hypothesis expected this dose escalation to be clinically tolerable if applied with image-guided IMRT. We included 9 dogs diagnosed with sinonasal tumours without local/distant metastases. For treatment planning, organs at risk were contoured according to strict anatomical guidelines. Planning volume extensions (GTV/CTV/PTV) were standardized to minimize interplanner variability. Treatments were applied with rigid patient positioning and verified daily with image guidance. After radiation therapy, we set focus on early ophthalmologic complications as well as mucosal and cutaneous toxicity. Early toxicity was evaluated at week 1, 2, 3, 8 and 12 after radiotherapy. Only mild ophthalmologic complications were found. Three patients (33%) had self-limiting moderate to severe early toxicity (grade 3 mucositis) which was managed medically. No patient developed ulcerations/haemorrhage/necrosis of skin/mucosa. The SIB protocol applied with image-guided IMRT to treat canine sinonasal tumours led to clinically acceptable side effects. The suspected increased tumour control probability and the risk of late toxicity with the used dose escalation of 20% has to be further investigated.

Salvage Surgery for Locoregional Failure in Anal Squamous Cell Carcinoma.

Anal squamous cell carcinoma is a rare cancer with a high cure rate, making research into the treatment of locoregional failure difficult. The purpose of this study was to examine factors related to local treatment failure and determine the outcomes of patients undergoing local salvage resection. This was a retrospective cohort study. This study was conducted at a quaternary referral center. Patients with anal squamous cell carcinoma treated with chemoradiotherapy between January 1983 and December 2015 were included. The influence of patient-, tumor-, and treatment-related factors on the primary outcome measures of locoregional failure, overall survival, and disease-free survival were investigated. Of 467 patients with anal squamous cell carcinoma, 63 experienced locoregional failure with 41 undergoing salvage resection. Twenty-seven patients (38%) had persistent disease and 36 (62%) developed locoregional recurrence. Multivariate analysis identified tumor stage (HR, 3.16; p < 0.002) as an independent predictor of locoregional failure. Thirty abdominoperineal resections and 11 pelvic exenterations were undertaken with no surgical mortality. At a median follow-up of 20 months (range, 4-150 months), 5-year overall and disease-free survival for the salvage cohort was 51% and 47%. Margin positivity was an independent predictor for relapse post-salvage surgery on multivariate analysis (HR, 20.1; p = 0.027). Nineteen patients (48%) developed further relapse, which included all 10 patients with a positive resection margin, 3 of whom underwent re-resection. Of the 19 patients with relapse, 3 remain alive and 2 have persistent disease. Limitations include the retrospective nature of the database, the prolonged time period of the study, and episodes of incomplete data. Advanced T stage is an independent predictor of local failure in anal squamous cell carcinoma. Most patients can be salvaged, with a positive resection margin being a strong predictor of further relapse and poor outcome. See Video Abstract at http://links.lww.com/DCR/A515.

Risk-Adapted, Combined-Modality Therapy for Unfavorable Pediatric Hodgkin Lymphom

Background and Objectives: Risk-adapted therapy for children with HL is directed toward high survival, minimal toxicity and optimal quality of life, with long term follow up. We assess the impact of prognostic factors associated with local treatment failure of pediatric HL patients with unfavorable criteria treated with combined modality: Alternating ABVD (Doxorubicin, Bleomycin, Vinblastine and Decarbazine) and COEP (Cyclophosphamide, Oncovin, Etoposide and Prednisone) chemotherapy and response-based, involved-field radiation for newly diagnosed unfavorable pediatric HL patients, also will detect toxicities and long-term complications observed in the patients. Methods: This prospective study was carried out from January 2010 to January 2018, with a median follow up of 74 months (range 8 - 103 months). 54 patients were eligible for this study stratified into two groups: intermediate risk (IR) and high-risk group (HR). Patients were treated with (4 - 6 cycles) and (6 - 8 cycles) respectively of alternating ABVD/COEP chemotherapy followed by involved-field radiation therapy (IFRT): 15 Gy for patients achieved complete response, and 25.5 Gy for those achieved a partial response. Results: 27 patients were IR and 27 patients were HR. There were 16 treatment failures; 5 patients had progressive disease; and 11 patients had a relapse. 9 patients died from their disease progression. The 5-year overall survival (OS) and event-free survival (EFS) rates (±SE) were 81.8% ± 5.7% and 71.8% ± 6.2% respectively. Multivariate analysis revealed that the only independent factor for inferior OS was radiotherapy. Conclusion: Treatment results of unfavourable HL patients in our study are satisfactory for with IR group but not for HR group who needs intensification of therapy. Radiotherapy is considered as a cornerstone in the treatment of the patients with unfavourable criteria with better assessment of early responders needed by PET-CT to identify patients at risk for relapse.

Incidence of Local and Marginal Treatment Failure Following Postoperative Single Fraction Spine Stereotactic Radiosurgery

Incidence of Local and Marginal Treatment Failure Following Postoperative Single Fraction Spine Stereotactic Radiosurgery

P135 A review of local test of cure (TOC) practice following treatment for rectal chlamydia and lymphogranuloma venereum

IntroductionPrevious reports of up to 22% treatment failure in rectal Chlamydia informed our local clinic policy of routine test of cure (TOC) following rectal chlamydia or lymphogranuloma venereum (LGV) treatment. We set out to review our local TOC practice and treatment failure rates for both chlamydia and LGV.MethodsCase notes of patients diagnosed with rectal chlamydia and LGV between 01/07/15 and 01/07/16 were reviewed. Data was collected on symptoms, antibiotic choice, compliance and TOC.ResultsThere were 89 patients identified with rectal chlamydia; 7 (8%) were confirmed LGV. Median age was 30 years; 69 (78%) men who have sex with men (MSM) and 20 (22%) female. Treatment was primarily with 1 week of doxycycline (81/89; 91%).Of 89 patients, 53 (60%) attended for a TOC with the remainder (36; 40%) lost to follow-up. There were 3/48 (6%) positive TOC results in those with non-LGV rectal chlamydia with one reporting sexual contact during treatment giving a failure rate of 4% (2/48). Of those with LGV 5/7 (71%) attended for a TOC and all were negative. Of those with a negative TOC 3/45 (6%) patients reported sexual contact during treatment.DiscussionOver a 12-month period our local treatment failure rate was low at 4% for rectal chlamydia and 0% for LGV. A significant proportion of patients failed to return for TOC. These results suggest that removal of routine TOC would be locally acceptable, reduce health advisor workload and be in line with current BASHH guidance.

Integrative Analysis Identifies a Novel AXL-PI3 Kinase-PD-L1 Signaling Axis Associated with Radiation Resistance in Head and Neck Cancer.

Purpose: The primary cause of death due to head and neck squamous cell carcinoma (HNSCC) is local treatment failure. The goal of this study was to examine this phenomenon using an unbiased approach.Experimental Design: We utilized human papilloma virus (HPV)-negative cell lines rendered radiation-resistant (RR) via repeated exposure to radiation, a panel of HPV-negative HNSCC cell lines and three cohorts of HPV-negative HNSCC tumors (n = 68, 97, and 114) from patients treated with radiotherapy and subjected to genomic, transcriptomic, and proteomic analysis.Results: RR cell lines exhibited upregulation of several proteins compared with controls, including increased activation of Axl and PI3 kinase signaling as well as increased expression of PD-L1. Additionally, inhibition of either Axl or PI3 kinase led to decreased PD-L1 expression. When clinical samples were subjected to RPPA and mRNA expression analysis, PD-L1 was correlated with both Axl and PI3K signaling as well as dramatically associated with local failure following radiotherapy. This finding was confirmed examining a third cohort using immunohistochemistry. Indeed, tumors with high expression of PD-L1 had failure rates following radiotherapy of 60%, 70%, and 50% compared with 20%, 25%, and 20% in the PD-L1-low expression group (P = 0.01, 1.9 × 10-3, and 9 × 10-4, respectively). This finding remained significant on multivariate analysis in all groups. Additionally, patients with PD-L1 low/CD8+ tumor-infiltrating lymphocytes high had no local failure or death due to disease (P = 5 × 10-4 and P = 4 × 10-4, respectively).Conclusions: Taken together, our data point to a targetable Axl-PI3 kinase-PD-L1 axis that is highly associated with radiation resistance. Clin Cancer Res; 23(11); 2713-22. ©2017 AACR.

Pattern of Local Recurrence After I-125 Episcleral Brachytherapy for Uveal Melanoma in a Spanish Referral Ocular Oncology Unit

To describe the time, frequency, and clinical characteristics of treatment failure after I-125 brachytherapy in patients with uveal melanoma treated and followed in a Spanish referral ocular oncology unit. Prospective, consecutive, interventional case series. Patients diagnosed with uveal melanoma from 1995 to 2016 and treated with episcleral brachytherapy were included. Demographic data collection, ophthalmic evaluation, ultrasound scan, and systemic studies were performed at baseline, every 6months thereafter for 5 years, and subsequently at annual intervals. Recurrence was defined as presence of tumor growth after treatment. Baseline analysis was performed by descriptive methods and survival by Kaplan-Meier curves. From 732 patients diagnosed with uveal melanoma, 311 were treated with brachytherapy. In the follow-up (mean 79months, standard deviation= 55), 16 local tumor recurrences (5.1%) were detected. All relapsing patients had choroidal tumors and 15 presented with visual symptoms. All patients were treated with I-125 brachytherapy, and 2 received associated transpupillary thermotherapy. All the eyes were enucleated after recurrence. Kaplan-Meier analysis showed a mean time of recurrence of 3.7 years (standard deviation= 2.94 years, ranging from 1 to 12 years). Three patients had metastasis in the follow-up. Kaplan-Meier analysis showed worse survival for patients with recurrence. Local treatment failure was a relatively infrequent event after I-125 brachytherapy in our series. Recurrences appear not only early but also late in the follow-up. They do not have a distinctive clinical pattern and are associated with poorer survival.

MP70-13 CRYOSURGICAL ABLATION OF THE PROSTATE: LOCAL DISEASE CONTROL FOR INTERMEDIATE /HIGH-GRADE GLEASON PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy I1 Apr 2017MP70-13 CRYOSURGICAL ABLATION OF THE PROSTATE: LOCAL DISEASE CONTROL FOR INTERMEDIATE /HIGH-GRADE GLEASON PROSTATE CANCER Ahmed El Shafei, Mohamed Eltemamy, Yaw Nyame, Hans Arora, and J Stephen Jones Ahmed El ShafeiAhmed El Shafei More articles by this author , Mohamed EltemamyMohamed Eltemamy More articles by this author , Yaw NyameYaw Nyame More articles by this author , Hans AroraHans Arora More articles by this author , and J Stephen JonesJ Stephen Jones More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2289AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Our objective is to report local disease control after primary whole gland cryoablation when used to treat Gleason ≥ 7 localized prostate cancers at our institution. METHODS We analyzed 134 prostate cryoablation patients who had a Gleason score of ≥ 7 who underwent primary whole gland cryoablation. Progression free survival (PFS) was defined according to Phoenix definition of PSA nadir +2 ng/ml. Among the biochemical failure (BF) patients, we assessed local disease control by postoperative prostate biopsy, pelvic MRI or CT. BS was used to assess metastatic disease. We defined local treatment failure by a positive post cryoablation prostate biopsy and/or MRI/CT scan findings suggesting local recurrence within the prostate. RESULTS PFS was noted in 101 patients (75%) with median follow up time of 31.5 months. Among the 33 patients who showed BF, 3 patients did not have a metastatic workup. Of the remaining 30 patients, 15 (11.2% of treated patients) showed only local treatment failure as indicated by positive post cryoablation prostate biopsy and/or MRI/CT scan findings suggesting local recurrence within the prostatic gland. The other 15 patients (11.2%) showed metastatic disease with no evidence of local treatment failure. (Table 1) CONCLUSIONS Cryoablation is a successful primary treatment option for patients with intermediate/high grade prostate cancer. Up to half of patients who showed biochemical failure had good local disease control but had distant failure as evident by post cryoablation prostate biopsy and/or MRI/CT scans; this suggests patient selection failing to identify micro metastasis present at the time of treatment rather than local treatment failure. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e940 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ahmed El Shafei More articles by this author Mohamed Eltemamy More articles by this author Yaw Nyame More articles by this author Hans Arora More articles by this author J Stephen Jones More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Local Failure After Episcleral Brachytherapy for Posterior Uveal Melanoma: Patterns, Risk Factors, and Management

To evaluate the patterns, the risk factors, and the management of recurrence following brachytherapy in patients with posterior uveal melanoma, given that an understanding of the recurrence patterns can improve early recognition and management of local treatment failure in such patients. Retrospective cohort study. Setting: Multispecialty tertiary care center. A total of 375 eyes treated with episcleral brachytherapy for posterior uveal melanoma from January 2004 to December 2014. Exclusion criteria included inadequate follow-up (<1 year) and previous radiation therapy. Main Outcomes and Measures: Local control rate and time to recurrence were the primary endpoints. Kaplan-Meier estimation and Cox proportional hazards models were conducted to identify risk factors for recurrence. Twenty-one patients (5.6%) experienced recurrence (follow-up range 12-156months; median 47months). The median time to recurrence was 18months (range 4-156months). Five-year estimated local recurrence rate was 6.6%. The majority (90.5%) of the recurrences occurred within the first 5 years. The predominant site of recurrence was at the tumor margin (12 patients, 57.1%). Univariate analysis identified 3 statistically significant recurrence risk factors: advanced age, largest basal diameter, and the use of adjuvant transpupillary thermotherapy (TTT). Recurrent tumors were managed by repeat brachytherapy, TTT, or enucleation. Local recurrences following brachytherapy are uncommon 5 years after episcleral brachytherapy. Follow-up intervals can be adjusted to reflect time to recurrence. Most of the eyes with recurrent tumor can be salvaged by conservative methods.

Spine radiosurgery: lessons learned from the first 100 treatment sessions.

OBJECTIVE Local therapy to spine tumors has been shown to be effective in selected cases. Spinal radiosurgery (SRS) is an evolving radiotherapy regimen allowing for noninvasive, highly efficacious local treatment. The learning curve can compromise the results of any newly employed technology and should be studied to minimize its effects. In this paper the first 100 SRSs performed at several medical centers are presented and analyzed for the effects of the learning curve on outcome. METHODS A retrospective analysis was undertaken to evaluate data from patients treated with SRS at Sheba Medical Center and Assuta Medical Centers in the period from September 2011 to February 2016. Medical history, clinical and neurological findings, pathological diagnoses, SRS variables, complications, and follow-up data were collected and analyzed. Local control rates were calculated, and local treatment failure cases were qualitatively studied. RESULTS One hundred treatment sessions were performed for 118 lesions at 179 spinal levels in 80 patients. The complication rate was low and did not correlate with a learning curve. Mean follow-up time was 302 days, and the overall local control rate was 95%. The local control rate was dose dependent and increased from 87% (among 35 patients receiving a dose of 16 Gy) to 97% (among 65 patients receiving a dose of 18 Gy). The 6 treatment failure cases are discussed in detail. CONCLUSIONS Spinal radiosurgery is a safe and effective treatment. Comprehensive education of the treating team and continuous communication are essential to limit the effects of the learning curve on outcome.

Transarterial chemoembolization for early stage hepatocellular carcinoma decrease local tumor control and overall survival compared to radiofrequency ablation.

Background & AimsTo compare treatment failure and survival associated with ultrasound-guided radiofrequency ablation (RFA) and trans-arterial chemoembolization (TACE) for early-stage HCC in Child-Pugh A cirrhosis patients.Methods122 cirrhotic patients (RFA: 61; TACE: 61) were well matched according to cirrhosis severity; tumor size and serum alpha-fetoprotein. TACE was performed in case of inconspicuous nodule on US or nodule with “at risk location”. Treatment failure was defined as local tumor progression (LTP) and primary treatment failure (failing to obtain complete response after two treatment session). Treatment failure and overall survival (OS) were compared after coarsened exact matching. Cox proportional model to assess independent predictive factors was performed.ResultsNo significant difference was seen for baseline characteristics between the two groups. Mean tumor size was 3cm in both group with 41% HCC>3cm. Treatment failure rates after TACE was 42.6% (14 primary treatment failures and 12 LTP) and 9.8% after RFA (no primary treatment failure and 6 LTP) P < 0.001. TACE was the only predictive factor of treatment failure (Hazard ratio: 5.573). The 4-years OS after RFA and TACE were 54.1% and 31.5% (P = 0.042), respectively.ConclusionFor Child-Pugh A patients with early-stage HCC, alternative treatment as supra-selective TACE to RFA regarded as too challenging using common US guidance decrease significantly the local tumor control and overall survival. Efforts to improve feasibility of RFA especially for inconspicuous target have to be made.

777. Image guided treatment of lymph nodal recurrence after radical prostatectomy

Background: Advances in imaging techniques are allowing early diagnosis and localization of tumor recurrence after local treatment failure. In this context, patients with lymph nodal recurrence (LNR) after radical prostatectomy (RP) can benefit from a rescue lymphadenectomy (LDNR) or radiotherapy (RT). We analyze our series of treated patients diagnosed with LNR after RP.

Profiling and bioinformatics analyses reveal differential circular RNA expression in radioresistant esophageal cancer cells.

BackgroundAcquired radioresistance during radiotherapy is considered as the most important reason for local tumor recurrence or treatment failure. Circular RNAs (circRNAs) have recently been identified as microRNA sponges and involve in various biological processes. The purpose of this study is to investigate the role of circRNAs in the radioresistance of esophageal cancer.MethodsTotal RNA was isolated from human parental cell line KYSE-150 and self-established radioresistant esophageal cancer cell line KYSE-150R, and hybridized to Arraystar Human circRNA Array. Quantitative real-time PCR was used to confirm the circRNA expression profiles obtained from the microarray data. Bioinformatic tools including gene ontology (GO) analysis, KEGG pathway analysis and network analysis were done for further assessment.ResultsAmong the detected candidate 3752 circRNA genes, significant upregulation of 57 circRNAs and downregulation of 17 circRNAs in human radioresistant esophageal cancer cell line KYSE-150R were observed compared with the parental cell line KYSE-150 (fold change ≥2.0 and P < 0.05). There were 9 out of these candidate circRNAs were validated by real-time PCR. GO analysis revealed that numerous target genes, including most microRNAs were involved in the biological processes. There were more than 400 target genes enrichment on Wnt signaling pathway. CircRNA_001059 and circRNA_000167 were the two largest nodes in circRNA/microRNA co-expression network.ConclusionsOur study revealed a comprehensive expression and functional profile of differentially expressed circRNAs in radioresistant esophageal cancer cells, indicating possible involvement of these dysregulated circRNAs in the development of radiation resistance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0977-7) contains supplementary material, which is available to authorized users.

Grape seed proanthocyanidins induce apoptosis through the mitochondrial pathway in nasopharyngeal carcinoma CNE-2 cells

Although modern radiotherapy offers excellent local control in the treatment of nasopharyngeal carcinoma (NPC), current therapeutic decisions remain burdensome due to the frequency of local recurrence and treatment failure at distant sites. One potential and promising strategy for the prevention or treatment of cancers is the use of bioactive components of plant origin, including dietary plant products. Herein, we studied one class of these bioactive compounds, grape seed proanthocyanidins (GSPs), and explored their effect on NPC CNE-2 cells, as well as the primary mechanism underlying this effect. Our results revealed that treatment of human NPC CNE-2 cells with GSPs reduced cell viability in a dose-and time-dependent manner, and moreover, markedly induced cell cycle arrest at the G2/Mphase, leading to induction of apoptosis. In addition, we found that the underlying mechanism was associated with increased expression of the pro-apoptotic protein Bax, decreased expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, upregulation of cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PRAP) protein, and the loss of mitochondrial membrane potential (MMP) (Δψm). Furthermore, GSPs upregulated the Bcl-2 homology3 (BH3)-only proteins, Bim and Bad, in a concentration-dependent manner. Taken together, these data supported our hypothesis that, in human NPCCNE-2 cells, GSPs could induce apoptosis through the mitochondrial pathway and ultimately reduce cell viability. Collectively, the results discussed above provide substantive evidence for the potential of GSPs as an effective bioactive phytochemical for the treatment of NPC.

Pelvis Plus Prostate Radiation Therapy and the Risk of Death in Men With Newly Diagnosed Node-Positive Prostate Cancer.

Both single-institutional retrospective series and a multiinstitutional observational study1,2 find a significant association between a reduced risk of death and treatment of nodepositiveprostatecancerusing both external-beam radiation treatment (EBRT) of the prostate and pelvic lymph nodes (LNs) and androgen deprivation therapy (ADT) compared with ADT alone. However, whether this association is causal remains unanswered and requires testing in aprospective randomized trial. In this issue of JAMA Oncology, James and colleagues3 use data from the control arm in the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) Trial to investigate this issue. Specifically, they perform a Cox regressionmultivariable analysis4 evaluating the riskof failure-free survivalwhere failure is defined as prostate-specific antigen (PSA) level; local, regional, or distant treatment failure; or death from prostate cancer, adjusting forhighest initialGleason score category (≤7, ≥8, unknown), log-transformed pre-ADT PSA level (continuous), age (<60, 60-64, 65-69, ≥70years), andWorldHealthOrganization performance status (0 vs 1 or 2) at randomization. Among 177 men with node-positive prostate cancer, 97 were planned for EBRT and 68 of these, plus 10men not originally slated for EBRT,were recordedashaving receivedEBRT to the prostate with or without pelvic LNs. After a median follow-up of 17months in the overall study cohort, 20menwith node-positiveprostate cancer experienceda failure event.The authors report that both planned and delivered prostatewith orwithoutpelvicEBRTwasassociatedwith reducedriskof failure, with adjusted hazard ratios of 0.48 (95% CI, 0.29-0.79) and 0.35 (95% CI, 0.19-0.65), respectively. There are several reasons to interpret these results with caution. First, as the authors note, EBRT use was prescribed by physician choice and therefore nonrandomized. In addition, the short median follow-up of 17 months in a study in which at least 2 years of ADTwas required and a primary end point (ie, failure-free survival) that is likely driven by PSArelated failureeventsat this shortmedian follow-up timemake it difficult topredictwhat effect a reduction inmostlyPSA failure–free survivalwill haveonoverall survival.Moreover, given the lowevent rate (20of 177 [11.3%]), theauthorswerenot able to analyze overall survival as an end point or adjust for all knownprostate cancer prognostic factors in theirmodel, such as tumor category, tertiary grade 5 inmenwith Gleason score 7prostate cancer, andpercent positive biopsies. Also,with40 deaths in the overall study cohort of which 9 could not be attributed to prostate cancer, a competing risk5 and not Cox regression analysis4 would have beenmore appropriate to analyze the end point of time to first failure or prostate cancer death. Finally, treatment use varied, in that somemen could have received irreversible and life-long testosterone suppression via bilateral orchiectomy as comparedwith 2 years of reversible ADT using a luteinizing hormone–releasing hormoneagonist.Moreover, inmen inwhomEBRTwasdelivered, the prostate was always treated whereas the pelvic LNs were only treated in a subset and thedose fractionation scheme for EBRTdeliveryvaried.Both thevariations inEBRTandADTcan affect time to first failure. Ideally, to account for these variations in treatment an adjustment in the model using a treatment propensity score would have been used, but the short median follow-up and consequently a low event rate would likelynotpermit the inclusionof thetreatmentpropensityscore and other known prostate cancer prognostic factors without running the risk of overfitting the model. Given these limitations, the conclusion that the addition of prostate and pelvic EBRT to ADT in the treatment of nodepositiveprostate cancer reduces the riskof failure,whileprobably true, cannot be rigorously concluded from the present analysisbecauseof theshortmedian follow-up, lowevent rate, nonrandomized data, and lack of adjustment for treatment variation and some known prostate cancer prognostic factors. Moreover, to affect clinical practice, at a minimum one should provide evidence in amodel powered for survival and adjusted for age, comorbidity, known prostate cancer prognostic factors, and type and duration of ADT that treatment using both pelvic and prostate RT andADT as comparedwith Related article page 348 Failure-Free Survival and Nonmetastatic Prostate Cancer Radiotherapy Original Investigation Research