Annual Recurrence Rate Research Articles

Outcome of CO2 laser vaporization for oral potentially malignant disorders treatment.

BackgroundOral cancer is a public health issue worldwide. Oral potentially malignant disorders (OMPDs) are lesions of the oral mucosa that are predisposed to malignant transformation. The mainstay of OMPDs treatment around the world is now the carbon dioxide (CO2) laser but the reported recurrence and malignant transformation rates vary widely in the literature. We aimed to estimate the recurrence and the malignant transformation rates of OPMDs treated with CO2 laser at the University Hospital of Bordeaux, in France, from 2010 to 2014, and to identify associated factors with recurrence or malignant transformation.Material and MethodsWe conducted a retrospective study in patients with a minimum follow-up of 12 months. Collected variables included characteristics of the patients (gender, age, alcohol and tobacco consumption, previous diagnosis of graft-versus-host disease, previous treatments for OPMD or for upper aerodigestive tract cancers and human immunodeficiency virus infection), characteristics of the lesions (form, colour, size, location, degree of dysplasia), laser treatment outcome (complications, recurrence, malignant transformation).ResultsTwenty-five patients were included. Mean follow-up was 28.9 months. Recurrence was observed in 11 patients (44%). Annual recurrence rate was 18.3% and annual malignant transformation rate was 1.7%. Hyperplasia without dysplasia was the only factor found to be statistically associated with recurrence.ConclusionsOur results suggest that OMPDs treated by CO2 laser vaporization have high recurrence rates, particularly those presenting hyperplasia. A standardized definition of recurrence would be necessary for inter-study comparisons. Long-term follow-up is recommended in order to detect and treat squamous cell carcinoma in its early stages. Key words:CO2 lasers, precancerous conditions, malignant transformation, oral cancer, recurrence.

Abstract P5-16-08: Risk factors of locoregional relapse in locally advanced breast cancer treated with neoadjuvant chemotherapy following mastectomy and radiotherapy

Abstract Purpose: We seek to investigate the prognostic factors that could possibly affect the local-regional recurrence (LRR) of breast cancer patients who do not achieve pathological complete response (pCR) after neoadjuvant chemotherapy (NCT), and to build a prognostic nomogram to predict patients' outcome. Methods: The retrospective analysis included 510 patients who had received NCT followed by surgery and radiotherapy. The NCT regimens included anthracycline-containing, vinorelbinecontaining, and taxane-containing regimens for a median of 3 cycles. The clinical responses to neoadjuvant chemotherapy were evaluated based on MRI and ultrasound examinations and in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The Miller-Payne (MP) grading system was employed to evaluate the decrease in cancer cellularity. Multivariate analyses were used to identify independent predictors of LRR. Results: The median follow-up for the entire study population was 61 months (range 5-128 months). There were 40 isolated local recurrences, 17 regional-only recurrences and 5 patients with local and regional recurrences. Sixteen patients (25.8%) occurred synchronously with distant metastasis, and no LRR was detected after distant failure. Fifteen patients had recurrences in the supraclavicular field. The 5-year cumulative LRR-free survival rate was 88.0% (95% CI: 85.2%-90.1%). The 5-year overall survival and disease-free survival rates were 79.0% (75.5%-82.6%) and 63.1% (58.9%-67.3%), respectively. Multivariate analysis revealed that positivity for ≥ 4 lymph nodes and Ki-67 index ≥ 14% were independent factors for LRR-free recurrence. The prognostic model was established based on the sum of both independent prognostic factors, with positivity for ≥ 4 lymph nodes and Ki-67 index ≥ 14% individually contributing 1 point to the risk score. The patients in the validation set were assigned to a low-risk group (0 point), median-risk group (1 point) and high-risk group (2 points). The 5-year LRR-free survival rates in the low, intermediate, and high-risk groups were 95.5%, 89.1%, and 67.1%, respectively (p < 0.001). We also show the annual LRR rate among these 3 groups using our single-institution data, as well as to review relevant literature-based data to compare with our observations. Four publications that reported ARR (annual recurrence rate) after surgery for primary breast cancer were identified as eligible. In the relevant literature, the annual risk of local-regional recurrence peaked between two and three years after the initial diagnosis. In contrast, the ARR curve of the high risk subgroup for neoadjuvant patients exhibited one peak near 1 year (17% per annum). The median and low-risk subgroups did not have an obvious recurrence peak. Conclusion: This prognostic model has considerable clinical value in predicting local-regional recurrence, which could help clinicians to design appropriate local-regional treatment specifically and to perform surveillance individually. Citation Format: Chen S, Huang L, Shao Z-M. Risk factors of locoregional relapse in locally advanced breast cancer treated with neoadjuvant chemotherapy following mastectomy and radiotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-08.

Effect of Background Liver Cirrhosis on Outcomes of Hepatectomy for Hepatocellular Carcinoma

ImportanceBackground hepatocarcinogenesis is considered a major cause of postoperative recurrence of de novo hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). The degree of underlying liver injury has reportedly correlated with surgical outcomes of HCC. However, the pattern and annual rate of recurrence of postoperative de novo HCC are still unclear.ObjectiveTo clarify the pattern and rate of recurrence of de novo HCC in patients with LC.Design, Setting, and ParticipantsData from 799 patients who underwent curative hepatectomy for HCC at Toranomon Hospital and The Johns Hopkins Hospital between January 1, 1995, and December 31, 2014, were retrospectively collected and analyzed. Of the patients who underwent curative hepatectomy for HCC, 424 met inclusion criteria: 73 with normal liver (NL) and 351 with LC. Sixty-four patients who had histologically proven NL parenchyma were matched with an equal number of patients who had established LC, and postoperative outcomes were compared.InterventionsHepatectomy in patients with HCC.Main Outcomes and MeasuresPatterns of recurrence of HCC and chronological changes in recurrence rates.ResultsAmong 128 matched patients in the study (mean [SD] age, 64.0 [12.7] years; 93 men and 35 women) 1-, 3-, and 5-year cumulative recurrence was 17.2%, 23.0%, and 37.5%, respectively, in the NL group vs 25.0%, 55.5%, and 72.1%, respectively, in the LC group (P = .001). The 3- and 5-year disease-specific survival was 85.7% and 75.4%, respectively, in the NL group vs 74.9% and 59.1%, respectively, in the LC group (P = .04). The median annual incidence of postoperative recurrence of HCC within 5 years after surgery was lower in the NL group (5.9%) compared with the LC group (12.7%) (P = .003). Assessment of recurrence patterns revealed that multiple recurrences near the resection margin or at extrahepatic sites were more frequent in the NL group (9 [50.0%] vs 6 [15.4%]; P = .01), whereas solitary recurrence at a distant site was more common in the LC group (21 [53.8%] vs 1 [5.6%]; P < .001).Conclusions and RelevanceComparison of the patterns and annual incidence of recurrence of HCC demonstrated that the poorer prognosis in the LC group was likely owing to a higher hepatocarcinogenic potential among patients with cirrhosis. Annual recurrence rates in the 2 groups indicate that de novo recurrence may continuously occur from the early postoperative period until the late period after resection of HCC.

Impact of Viral Etiology on Postoperative De Novo Recurrence After Hepatectomy for Hepatocellular Carcinoma in Cirrhotic Patients

Background and AimLiver cirrhosis (LC) and hepatocellular carcinoma (HCC) are associated with viral hepatitis, especially hepatitis B virus (HBV) and hepatitis C virus (HCV). Whether differences exist in postoperative de novo carcinogenesis from established cirrhosis according to viral etiology remains unclear. MethodsData from 313 LC patients with viral hepatitis (HBV-LC, n = 108 and HCV-LC, n = 205) who underwent curative-intent hepatectomy for HCC were retrospectively collected. Clinicopathological characteristics, cumulative recurrence, chronological change of recurrence rate, and predictors of recurrence were analyzed. ResultsBaseline patient characteristics were different among patients with HBV versus HCV as HCC-LC patients had a lower albumin, higher alanine transaminase, and higher incidence of tumor multicentricity (all P < 0.050). The 1-, 3-, and 5-year cumulative recurrence was 16.7, 38.6, and 53.7% in HBV-LC versus 20.8, 52.2, and 71.6% in HCV-LC (P = 0.002) patients, respectively. The postoperative annual recurrence rates of HCV-LC were consistently higher than that of HBV-LC patients. After matching on clinicopathologic characteristics, while recurrence was comparable in the early time period, HCV-LC patients had a 2–5% higher incidence of recurrence compared with HBV-LC patients after 20 months post-resection. On multivariable analysis, HCV infection was an independent predictor of recurrence (HR 1.55; 95% CI 1.13–2.13). ConclusionHCV-related LC was associated with a higher postoperative de novo carcinogenesis than HBV-related LC. Establishment of different treatment algorithms as well as follow-up surveillance protocols stratified by viral etiology may be warranted.

Eradication of Helicobacter pylori in patients without gastric symptoms suffering from recurrent aphthous stomatitis: A pilot study

Background/Aim. Helicobacter (H.) pylori is a widespread bacterium and its involvement in pathogenesis of gastric diseases is well-known. However, H. pylori role in etiology of other histologically similar conditions, especially recurrent aphthous stomatitis (RAS) is still controversial. Research regarding H. pylori and its association with RAS, as well as the treatment options were always conducted on patients with diagnosed gastric problems. The aim of this study was to determine whether H. pylori is present in the oral cavity of patients suffering from RAS but without any symptoms or medical history of gastric disease. Methods. A total of 15 patients with RAS participated in the study. None of the participants suffered from any gastrointestinal disorders. Two dental plaque samples from each participant were collected. The first was analyzed using rapid urease test and the second one was put in transport medium and sent for cultivation. The sensitivity of H. pylori to antibiotics was established using disk diffusion method of sensitivity testing for every patient individually and adequate therapy was prescribed. Results. Before the treatment the mean annual recurrence rate of RAS was 8.1 ? 2.1, with the average number of lesions being 3.9 ? 1.9. During the 12-month observation period after the eradication therapy, none of the patients reported recurrence of aphthous lesions. The treatment was successful in all cases. Conclusion. This study shows that RAS can be effectively treated by successful eradication of oral H. pylori, and that RAS could be possibly considered as an early warning sign of potential gastric infection by H. pilory.

Recurrence of Helicobacter pylori infection and the affecting factors: A follow-up study.

Recurrence of Helicobacter pylori (H. pylori) infection weakens the protective effect and long-term prognosis of eradication. With the widespread therapies, decreasing prevalence of H. pylori infection and improvement in living conditions, the recurrence of H. pylori infection may present with new features. We conducted this prospective, large-scale, multicenter follow-up study to determine the recurrence rate of H. pylori infection and its affecting factors. A total of 827 patients receiving successful H. pylori eradication in our previous randomized controlled trial were enrolled. 13 C-urea breath test (UBT) was repeated one year after the eradication therapy to determine its recurrence. Moreover, a questionnaire survey was performed to explore the potential factors affecting the recurrence. A total of 743 patients completed 13 C-UBT (follow-up rate 89.8%), and the result was positive in 13 patients one year after eradication therapy, with an annual recurrence rate of 1.75% (95% confidence interval [CI] 0.81-2.69%). Six hundred and ninety-two patients (13 with recurrence and 679 without recurrence) returned their questionnaires, with a response rate of >80%. Multivariate analysis revealed that peptic ulcer (odds ratio [OR] 3.385, 95% CI 1.016-11.274), close contact with individuals having H. pylori infection (OR 4.231, 95% CI 1.201-14.911), and hospitalization (OR 9.302, 95% CI 2.441-35.440) were independent risk factors of H. pylori infection recurrence. The recurrence of H. pylori infection one year after eradication therapy is low in urban population of China. Peptic ulcer, contact history with individuals having H. pylori infection and hospitalization are risk factors.

Incidence of Recurrent Intracerebral Hemorrhages in a Multiethnic South Asian Population

Spontaneous primary intracerebral hemorrhage (ICH) accounts for approximately 25% of all strokes in Singapore. Incidence of recurrent ICH is not well studied, and previous studies have reported inconsistent findings in the rate and risk factors associated with ICH recurrences. We aimed to study the incidence of recurrent ICHs in Singapore and to identify the associated risk factors as well as pattern of ICH recurrence. A retrospective review of all consecutive admissions for intracerebral hemorrhage at the National Neuroscience Institute between January 2006 and November 2013 was performed. Imaging and computerized clinical records were reviewed. The demographic, clinical, and radiological characteristics of index and recurrent ICH were compared. Univariate analysis was performed using chi-square and Student's t-test, and logistic regression was used to analyze the predictors of ICH recurrence. In total, 1708 patients who survived the index ICH beyond 14 days were followed up for 6398 person-years. Sixty patients developed 68 recurrences of ICH, giving rise to an annual incidence rate of ICH recurrence of 1.1%. A history of previous ischemic stroke (P = .001) and index lobar location of ICH (P = .004) were significantly associated with the occurrence of ICH recurrences on multivariate analysis. The most common pattern on ICH recurrence was ganglionic-ganglionic (44.1%), followed by lobar-lobar (17.6%). Overall mortality of recurrent ICH was 17.6%. The average annual incidence rate of primary ICH recurrence in Singapore is 1.1%, and is associated with previous ischemic stroke and lobar location of index ICH.

Impact of high-risk thrombophilia status on recurrence among children with a first non-central-venous-catheter-associated VTE: an observational multicentre cohort study.

Deficiency of antithrombin (AT), protein C (PC) or protein S (PS) constitutes a major risk factor for venous thromboembolism (VTE). Individuals at high risk for recurrence who benefit from screening need to be identified. The primary study objective was to determine the individual recurrence risk among children with a first non-central-venous-catheter-associated VTE with respect to their thrombophilia status and to evaluate if the clinical presentation at first VTE onset differs between children with AT, PC or PS deficiency versus no thrombophilia. We calculated the absolute risk of VTE recurrence and event-free-survival adjusted for thrombophilia, age, sex and positive family VTE history in 161 consecutively enrolled paediatric VTE patients. The presence of a deficiency relative to no thrombophilia was evaluated as a potential predictor of recurrence. Predictors for recurrence were AT deficiency (hazard ratio/95% CI: 6·5/2·46-17·2) and female gender (2·6/1·1-6·35). The annual recurrence rates (95% CIs) were 5·4% (2·6-10) in AT-deficient children, 1·3% (0·3-3·8) in patients with PC deficiency, 0·7% (0·08-2·4) in the PS-deficient cohort and 0·9% (0·4-1·8) in patients with no thrombophilia. Positive family VTE history or combined thrombophilias did not predict recurrence. Given the overall annual incidence rate of recurrence of 1·5% we suggest screening for AT deficiency in children with VTE.

Techniques and long-term outcomes of cotton-clipping and cotton-augmentation strategies for management of cerebral aneurysms.

OBJECTIVE To address the challenges of microsurgically treating broad-based, frail, and otherwise complex aneurysms that are not amenable to direct clipping, alternative techniques have been developed. One such technique is to use cotton to augment clipping ("cotton-clipping" technique), which is also used to manage intraoperative aneurysm neck rupture, and another is to reinforce unclippable segments or remnants of aneurysm necks with cotton ("cotton-augmentation" technique). This study reviews the natural history of patients with aneurysms treated with cotton-clipping and cotton-augmentation techniques. METHODS The authors queried a database consisting of all patients with aneurysms treated at Barrow Neurological Institute in Phoenix, Arizona, between January 1, 2004, and December 31, 2014, to identify cases in which cotton-clipping or cotton-augmentation strategies had been used. Management was categorized as the cotton-clipping technique if cotton was used within the blades of the aneurysm clip and as the cotton-clipping technique if cotton was used to reinforce aneurysms or portions of the aneurysm that were unclippable due to the presence of perforators, atherosclerosis, or residual aneurysms. Data were reviewed to assess patient outcomes and annual rates of aneurysm recurrence or hemorrhage after the initial procedures were performed. RESULTS The authors identified 60 aneurysms treated with these techniques in 57 patients (18 patients with ruptured aneurysms and 39 patients with unruptured aneurysms) whose mean age was 53.1 years (median 55 years; range 24-72 years). Twenty-three aneurysms (11 cases of subarachnoid hemorrhage) were treated using cotton-clipping and 37 with cotton-augmentation techniques (7 cases of subarachnoid hemorrhage). In total, 18 patients presented with subarachnoid hemorrhage. The mean Glasgow Outcome Scale (GOS) score at the time of discharge was 4.4. At a mean follow-up of 60.9 ± 35.6 months (median 70 months; range 10-126 months), the mean GOS score at last follow-up was 4.8. The total number of patient follow-up years was 289.4. During the follow-up period, none of the cotton-clipped aneurysms increased in size, changed in configuration, or rebled. None of the patients experienced early rebleeding. The annual hemorrhage rate for aneurysms treated with cotton-augmentation was 0.52% and the recurrence rate was 1.03% per year. For all patients in the study, the overall risk of hemorrhage was 0.35% per year and the annual recurrence rate was 0.69%. CONCLUSIONS Cotton-clipping is an effective and durable treatment strategy for intraoperative aneurysm rupture and for management of broad-based aneurysms. Cotton-augmentation can be safely used to manage unclippable or partially clipped intracranial aneurysms and affords protection from early aneurysm re-rupture and a relatively low rate of late rehemorrhage.

Cost-Utility Analysis of Ingenol Mebutate Versus Imiquimod 5% for Actinic Keratosis Treatment In Spain

To estimate the incremental cost utility ratio (ICUR) for ingenol mebutate vs imiquimod 5% for actinic keratosis (AK) patient’s treatment on the face and scalp, in Spain. A Markov model was used to simulate AK patient treatment evolution for a 5-year horizon from the Spanish National Health System (NHS). Duration of ingenol mebutate treatments was 3 days and 12 days for imiquimod 5%. Effectiveness measure was total clearance rate obtained from indirect mixed comparisons (42.24% for ingenol mebutate and 44.54% for imiquimod) and adjusted according compliance (90% for ingenol mebutate and 60% for imiquimod). Annual recurrence rate (20%) derived from literature. Annual discount rate of 3% was applied for costs and outcomes. Total cost estimation (€,2015) included: drug (retail price VAT included with mandatory deduction), and dermatology visits cost (for adverse events and disease management).Utilities values (0.986 for AK and 1 for clearance) were used to derive quality-adjusted-life years (QALY). Probabilistic and deterministic sensitivity analyses were performed to confirm the robustness of the obtained results. Ingenol mebutate showed higher effectiveness than imiquimod 5%, 0.535 vs 0.503 total gained clearances and 4.451 vs 4.449 total QALYs and accounted higher total costs, €551.50 (46% drug cost) versus €527.89 (36% drug cost) compared to imiquimod 5%. Estimated ICUR was €10.906/QALY gained with ingenol mebutate vs imiquimod 5%. In probabilistic sensitivity analysis performed, 78% of simulations yielded an ICUR below €30,000/QALY for ingenol mebutate versus imiquimod. Ingenol mebutato vs imiquimod 5% was an efficient alternative for NHS for patients with AK, on face and scalp, considering an acceptable threshold of €30,000/QALY.

Fistula and Infratentorial Location, Characteristics That Contribute to Cerebral Arteriovenous Malformations, Lead to the Formation of Associated Aneurysms in Patients

Because the formation of associated aneurysms (AAs) related to the characteristics of cerebral artriovenous malformations (cAVMs) is poorly recognized, the purpose of this study was to identify the responsible characteristics of cAVMs related to the formation of AAs and to identify patients with responsible characteristics related to the formation of AAs through the analysis of the outcomes of these patients after treatment. This study was performed to analyze the baseline characteristics of patients with cAVMs and AAs. The recurrent AA and residual size of cAVMs were used to evaluate the outcomes of patients after treatment. At the same time, the ROC curve was measured to gauge the relationship between the residual size of cAVMs and recurrent AAs in eligible patients. Fifty (15.0%) patients with cAVMs and AA were confirmed; these patients had twice the hazard of hemorrhage as patients with only isolated cAVMs. An infratentorial location (P < 0.001) and fistula (P= 0.002) were independent predictors of the formation of AAs. After a mean 22.7 months follow-up, 2 patients developed recurrent AAs, and the annual recurrence rate for patients with responsible characteristics was 17.6%, but for all patients was 7.2%. The ROC curve showed that patients, specifically patients with responsible characteristics, the residual size of the cAVM was closely related to recurrent AA (area= 0.89, 95% confidence interval 0.81-0.97, P=0.023, cut-off value= 82.5%). Patients with cAVMs and AA who harbor a fistula or an infratentorial location tend to form AAs. To prevent recurrent AAs and decrease the subsequent risk of hemorrhage, complete obliteration of cAVMs or retrograding over 80% size of cAVMs is recommended.

Transient Global Amnesia as a Presenting Manifestation of Cerebral Venous Thrombosis

Transient Global Amnesia as a Presenting Manifestation of Cerebral Venous Thrombosis

Estrogen Receptor Expression in 21-Gene Recurrence Score Predicts Increased Late Recurrence for Estrogen-Positive/HER2-Negative Breast Cancer.

To identify the individual genes or gene modules that lead to the OncoptypeDx 21-gene recurrence score's reduced performance after 5 years and thereby identify indices of residual risk that may guide selection of patients for extended adjuvant therapy. We conducted a retrospective assessment of the relationship between (i) the individual genes and gene modules of the Recurrence Score and (ii) early (0-5 years) and late (5-10 years) recurrence rates in 1,125 postmenopausal patients with primary estrogen receptor-positive breast cancer treated with anastrozole or tamoxifen in the Arimidex, Tamoxifen, Alone or Combined (ATAC) randomized clinical trial. In the HER2-negative population (n = 1,009), estimates of recurrence risk were similar between years 0-5 and 5-10 for proliferation and invasion modules but markedly different for the estrogen module and genes within it (all split at the median): for low estrogen module, annual recurrence rates were similar across the two time windows (2.06% vs. 2.46%, respectively); for high estrogen module, annual rates were 1.14% versus 2.72%, respectively (P interaction = 0.004). Estrogen receptor transcript levels showed inverse prediction across the time windows: HR, 0.88 (0.73-1.07) and 1.19 (0.99-1.43), respectively (P interaction = 0.03). Similar time-, module-, and estrogen-dependent relationships were seen for distant recurrence. Patients with tumors with high estrogen receptor transcript levels benefit most from 5 years' endocrine therapy but show increased recurrence rates after 5 years and may benefit from extended therapy. Improved prognostic profiles may be created by considering period of treatment and follow-up time.

Abstract OT1-4-01: HIOB trial - Hypofractionated whole-breast irradiation preceded by intraoperative radiotherapy with electrons as anticipated boost

Abstract ClinicalTrials.gov Identifier: NCT01343459 Brief background discussion: The commonly accepted standard fractionation schedule for whole breast irradiation (WBI) consists of 25fractionations with single fractional doses of 2 Gy, resulting in cumulative doses of 50 Gy to the whole breast. Hypofractionation trials from UK and Canada demonstrated a similar outcome in local control and cosmesis compared to conventional fractionation. The combination of IOERT boost and hypofractionation was not yet evaluated. Trial design: Prospective one-armed multi-center trial - ISIORT 01 Eligible patients are treated with hypofractionated whole breast irradiation (WBI) of 40.5 Gy in 2.7 Gy per fraction for 15 days, preceded by an intraoperative electron boost (IOERT) to the tumor bed of 10 Gy (90% isodose) during breast conserving surgery. Eligibility criteria: Inclusion criteria: Invasive breast cancer Age 35 years and older T1/T2, N1/N2, G1 - G3 Hormone receptor and Her 2 status: no limitations Exclusion criteria: Non-invasive breast cancer Age less than 35 years T3/T4, N2/N3 Neoadjuvant chemotherapy Aim of the study: To assess the effectiveness of IOERT in combination with hypofractionated WBI in terms of in-breast tumor control and cosmetic outcome, by matching or exceeding the best published results for annual LR rates in 3 different age groups in reference to an upper limit (exceeding = inferiority) and a lower limit (undershooting = superiority) which were estimated on the basis of the existing literature as follows: Age 35 – 40 years: Upper limit (best published evidence): 1.2 % (EORTC 22881- Boost trial) Lower limit (commonly expected dimension): 0.72 % (CONSORT trial) Age 41 – 50 years: Upper limit (best published evidence): 1.2 % (EORTC 22881- Boost trial) Lower limit (commonly expected dimension): 0.72 % (CONSORT trial) Age over 50 years: Upper limit (best published evidence): 0.7 % (EORTC 22881- Boost trial) Lower limit (commonly expected dimension): 0.4 % (START B trial) Primary endpoint: Proof of superiority or iso-effectiveness. Secondary endpoints: Acute toxicity (CTC- toxicity scoring system) and late toxicity (LENT SOMA scoring system), cosmetic results (Van Limbergen - Score), DFS, OS. Statistical methods: Sequential Probability Ratio Test (SPRT): As a consequence of best published analyses for this patient selection, stopping rules for annual local recurrence rates are defined as follows: Age group 35-40: H0: p1 &amp;lt;= 0.72% vs H1: p1 &amp;gt; 0.72% with p2 = 4.0% Age group 41-50: H0: p1 &amp;lt;= 0.72% vs H1: p1 &amp;gt; 0.72% with p2 = 2.4% Age group 51+: H0: p1 &amp;lt;= 0.4% vs H1: p1 &amp;gt; 0.4% with p2 = 1.4% H0-Hypothesis means no superiority to standard regimen. H1-Hypothesis means superiority of HIOB against best published evidence. Present accrual and target accrual: Start date: January 2011 Estimated enrollment: 1500 patients 542 patients recruited by March 2014 10 international institutions recruiting. Citation Format: Roland Reitsamer, Gerd Fastner, Michael Kopp, Felix Sedlmayer. HIOB trial - Hypofractionated whole-breast irradiation preceded by intraoperative radiotherapy with electrons as anticipated boost [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-4-01.

Abstract P3-06-01: Nuclear β-catenin negativity predicts for late relapse in ER+, tamoxifen-treated breast cancer

Abstract Background: The annual recurrence rates of post-menopausal ER-positive breast cancers persist beyond the first 5 years of diagnosis and treatment and the mortality rates in this period are higher versus ER-negative cancers. Extended endocrine therapy past 5 years has been shown to be of benefit but is associated with increased toxicity and cost thus the ability to predict patients who are at highest risk of late relapse would be of significant benefit in clinical decision making in this context. β-catenin is an intracellular protein that undergoes Wnt-mediated nuclear translocation where it transactivates genes implicated in tumour development and progression. We have also previously reported that β-catenin can play a role in aggressive resistance that accompanies prolonged endocrine treatment in vitro. In this study, we thus investigated whether β-catenin expression in ER+ breast cancer was predictive of recurrence beyond 5 years in an analysis of three separate endocrine-treated cohorts. Methods: Associations between β-catenin gene expression and relapse free survival (RFS) were performed using the online KMplotter tool. Immunostaining for total β-catenin was performed on tissue samples from 3 ER+ primary breast cancer series with long-term follow-up data: Nottingham 2000 (n=384, tamoxifen-only); ABC (n=570; tamoxifen only); transATAC (n=743; tamoxifen or ansatrozole). The association between subcellular (nuclear or cytoplasmic) β-catenin expression and RFS was determined in (i) the entire cohort, (ii) the first 5 years of tamoxifen treatment versus post-5 years. Results: KMplotter analysis of β-catenin in ER+, tamoxifen-treated patient samples (n=665) revealed a significant relationship with improved RFS in the post-five year cohort [HR: 0.48 (0.34-0.68); p=0.000019) versus the first 5 years [HR: 0.91 (0.61-1.36; p=0.64)]. No significant association was observed in untreated ER+ patients. In the Nottingham series, nuclear β-catenin positivity was significantly associated with improved survival in the 20-year follow-up for tamoxifen-treated patients (p=0.047) but not in the first five years (p=0.239). Cytoplasmic β-catenin did not associate with survival. Further analysis in the ABC series revealed an association between nuclear β-catenin positivity and improved survival for tamoxifen-treated patients in the entire cohort (HR: 0.52 (0.18, 0.55); p=0.00005). However, nuclear β-catenin was more strongly associated with improved outcome in the post 5-year treatment group (HR: 0.30 (0.14, 0.66); p=0.01) versus the first five years of treatment (HR: 0.33 (0.15,0.73); p=0.06). No significant associations were seen with cytoplasmic β-catenin. The transATAC trial material again revealed an association between presence of nuclear β-catenin and reduced distant recurrence in the post 5-years endocrine-treated cohort (HR: 0.54 (0.33, 0.91): x2=5.52, p=0.018) versus years 1-5 (HR: 1.16 (0.67, 2.01); x2=0.29, p=0.59). Conclusions: This is the first study to demonstrate that nuclear β-catenin may represent a predictive biomarker for late relapse following tamoxifen treatment in ER+ breast cancer where, contrary to traditional hypotheses and pre-clinical data, its nuclear expression is strongly associated with good outcome post-five years of treatment. Citation Format: Stephen Hiscox, Chris Smith, Robert I Nicholson, Julia Gee, Adrian Harris, Judith Bliss, Eleftheria Kalaizak, Ivana Sestak, Mitch Dowsett, Jack Cuzick, Ian Ellis, Peter Barrett-Lee. Nuclear β-catenin negativity predicts for late relapse in ER+, tamoxifen-treated breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-01.

High Incidence of Dementia Conversion than Stroke Recurrence in Poststroke Patients of Late Elder Society

This study investigated the incidence of current poststroke dementia (PSD), the annual conversion ratio into PSD, and the risk factors for conversion. In a 4.8-year follow-up period, 112 poststroke patients (ischemic stroke and intracerebral hemorrhage) were retrospectively investigated in cognitive examinations. They were categorized into 3 subgroups: converters into PSD, nonconverters who maintained their normal cognitive functions, and reverters who recovered to the normal mentality range. The clinical and demographic characteristics of these 3 subgroups were analyzed. Among all 112 poststroke patients (61.6% male, 73.6 ± 10.4 years old), 16.1% had PSD. During the follow-up period, a part of the normal baseline mentality group (83.9% of 112 original patients) newly developed PSD (subdivided into converters) with an annual conversion rate of 7.6%. The reversion rate from the baseline PSD group was 11.3%. There were significant differences in age (P < .05), baseline mini-mental state examination scores (P < .05), body mass index (P < .05), and periventricular and deep white matter hyperintensity grades (P < .05 and P = .01, respectively) between converters and nonconverters. The annual rate of stroke recurrence was only 2.2% in all stroke subtypes. In comparison with stroke recurrence (2.2%), 7.6% of the annual PSD conversion rate was very high. Therefore, prevention of direct conversion into PSD without stroke recurrence may be another important aspect of poststroke clinics, especially in late elder society.

Su1138 Concomitant Therapy Appeared Superior to Sequential, Tailored, or PAC, PAM Based Triple Therapy for the Eradicatino of Helicobacter in Prospective, Multi-Center, Radomized Controlled Trial

Objective of the study: Since 2013, H. pylori eradication therapy for atrophic gastritis associated with H. pylori became available for coverage by insurance in Japan. For first-line therapy, triple eradication therapy (proton pump inhibitor (PPI) + amoxicillin (AMPC) + clarithromycin (CAM) is available for H. pylori eradication, in Japan. The resistance of H. pylori strains to CAM accounts for the majority of eradication failures, the incidence of which is currently increasing and it affects H. pylori eradication rate in Japan. Another matter is recurrence of H. pylori infection after eradication. H. pylori infection sometimes recurs after successful eradication. The rate of recurrence after successful eradication is reported to be 0.5% to 2.0% in the western countries. In this study, we investigated about the long term transition of primary drug susceptibility ofH. pylori strains to CAM, and the rate of recurrence after successful eradication in Japan.Methods: Three hundred sixty six patients after successful eradication of H. pylori were followed up by culture, histological examination and urea breath tests. In 22 patients in whom H. pylori recurred during follow-up, the susceptibility of the H. pylori strains to clarithromycin was investigated. And in 17 recurrent patients, H. pylori strains isolated initially and after recurrence were compared using PCR-based restriction fragment length polymorphism (RFLP) analysis. Results: The primary resistance of H. pylori to CAM is increasing, especially in these 6 years, its rate is very high at 35%. Ten of 22 (45.5%) recurrences appeared at 6 months after successful eradication of H. pylori, and after 1 year, the annual recurrence rate of H. pylori infection was 0.29% per patient year. In recurrent cases, 50.0% (5/10) of the strains detected 6 months after successful eradication were found to be susceptible to clarithromycin. And 58.3% (7/12) of the strains detected at 12 months or later were found to be susceptible to clarithromycin. In the 10 patients who showed a recurrence of H. pylori after 12 months, all the patients showed different DNA profiles, and 5 of 7 (71.4%) patients showed different DNA profiles at 6 months after eradication Conclusions: The rate of CAM-resistant H. pylori strains is very high in Japan. Because of that, for the recurrence cases, it occurs with low frequency (0.29% per patient year), drug sensitivity examination may be necessary in Japan.

Su1137 The Recurrence and Clarithromycin Resistant Rate of Helicobacter pylori After Successful Eradication Therapy in Japan

Objective of the study: Since 2013, H. pylori eradication therapy for atrophic gastritis associated with H. pylori became available for coverage by insurance in Japan. For first-line therapy, triple eradication therapy (proton pump inhibitor (PPI) + amoxicillin (AMPC) + clarithromycin (CAM) is available for H. pylori eradication, in Japan. The resistance of H. pylori strains to CAM accounts for the majority of eradication failures, the incidence of which is currently increasing and it affects H. pylori eradication rate in Japan. Another matter is recurrence of H. pylori infection after eradication. H. pylori infection sometimes recurs after successful eradication. The rate of recurrence after successful eradication is reported to be 0.5% to 2.0% in the western countries. In this study, we investigated about the long term transition of primary drug susceptibility ofH. pylori strains to CAM, and the rate of recurrence after successful eradication in Japan.Methods: Three hundred sixty six patients after successful eradication of H. pylori were followed up by culture, histological examination and urea breath tests. In 22 patients in whom H. pylori recurred during follow-up, the susceptibility of the H. pylori strains to clarithromycin was investigated. And in 17 recurrent patients, H. pylori strains isolated initially and after recurrence were compared using PCR-based restriction fragment length polymorphism (RFLP) analysis. Results: The primary resistance of H. pylori to CAM is increasing, especially in these 6 years, its rate is very high at 35%. Ten of 22 (45.5%) recurrences appeared at 6 months after successful eradication of H. pylori, and after 1 year, the annual recurrence rate of H. pylori infection was 0.29% per patient year. In recurrent cases, 50.0% (5/10) of the strains detected 6 months after successful eradication were found to be susceptible to clarithromycin. And 58.3% (7/12) of the strains detected at 12 months or later were found to be susceptible to clarithromycin. In the 10 patients who showed a recurrence of H. pylori after 12 months, all the patients showed different DNA profiles, and 5 of 7 (71.4%) patients showed different DNA profiles at 6 months after eradication Conclusions: The rate of CAM-resistant H. pylori strains is very high in Japan. Because of that, for the recurrence cases, it occurs with low frequency (0.29% per patient year), drug sensitivity examination may be necessary in Japan.

Relapse profile of early breast cancer according to immunohistochemical subtypes: guidance for patient's follow up?

To analyze the profile of annual recurrence rate (ARR) of patients with early breast cancer (BC) in Tunisia. We classified 293 patients with histologically confirmed early BC relapsing after 1 year of follow up into three subgroups: hormone receptor (HR)+ 'HR' [estrogen receptor (ER)+ or progesterone receptor (PR)+ and human epidermal growth factor receptor 2 (HER2)-], triple negative 'TN' (ER-, PR- and HER2 score 0/1 or fluorescence in situ hybridization (FISH)/chromogenic in situ hybridization negative) and HER2 overexpression 'HER2' (HER2+). ARR was restricted to follow-up contribution of each specified time interval. The HR group was the reference group for comparison. A higher proportion of patients who were up to 35 years old (18% versus 10%, p = 0.04), and patients with obesity (46% versus 26%, p = 0.045) was seen in the TN group. Median time to relapse (MTR) was shorter in TN and HER2 groups than in HR patients (20 and 29 months compared with 56 months, respectively, p < 0.001). In the HR group, the ARR was 22%, 16% and 10% at 3, 4 and 5 years respectively, becoming less than 3% at 7 years. In the TN group, 71% of patients relapsed during the first 2 years and the ARR declined rapidly to less than 1.5% after 4 years. In the HER2 group, the ARR peaked at 2 years (29%) and decreased significantly to 7% and 3% at 5 and 7 years respectively. Adjuvant trastuzumab delayed the MTR from 24 to 34 months (p = 0.022). The relapse risk in Tunisian patients is higher in young women and patients with HER2+ and TN tumors. A long and close follow up is recommended for patients with HR and HER2. Conversely, we suggest that follow up in patients with TN could be spaced after 4 years (ARR being <1.5% after this period).

Microsurgical treatment of arteriovenous malformations in pediatric patients: the Boston Children's Hospital experience.

Outcomes of microsurgical treatment of arteriovenous malformations (AVMs) in children are infrequently reported across large cohorts. The authors undertook a retrospective review of departmental and hospital databases to obtain the medical data of all patients up to 18 years of age who were diagnosed with cerebral AVMs. Demographic and AVM angioarchitectural characteristics were analyzed, and for the patients who underwent surgery, the authors also analyzed the estimated intraoperative blood loss, postoperative angiographically confirmed obliteration rates, and neurological complications and outcomes classified according to the modified Rankin Scale (mRS). Of 117 children with cerebral AVMs, 94 underwent microsurgical resection (80%). Twenty (21%) of these 94 patients underwent adjunctive preoperative embolization. The overall postoperative angiographically confirmed obliteration rate was 94%. As part of a new protocol, the last 50 patients in this series underwent immediate perioperative angiography, improving the subsequent obliteration rate from 86% to 100% (p = 0.01). No other factors, such as a hemorrhagic AVM, size of the AVM, location, drainage, or Spetzler-Martin grade, had a statistically significant impact on the obliteration rate. Perioperative neurological deficits occurred in 17% of the patients, but the vast majority of these (77%) were predictable visual field cuts. Arteriovenous malformations that were hemorrhagic or located in noneloquent regions were each associated with lower rates of postoperative neurological complications (p = 0.05 and 0.002, respectively). In total, 94% of the children had good functional outcomes (mRS Scores 0-2), and these outcomes were significantly influenced by the mRS score on presentation before surgery (p = 0.01). A review of 1- and 5-year follow-up data indicated an overall annual hemorrhage rate of 0.3% and a recurrence rate of 0.9%. Microsurgical resection of AVMs in children is associated with high rates of angiographically confirmed obliteration and low rates of significant neurological complications. Implementation of a protocol using perioperative angiography in this series led to complete radiographically confirmed obliteration of all AVMs, with low annual repeat hemorrhage and recurrence rates.