Differential diagnosis between progression and radionecrosis in brain metastases after stereotactic radiosurgery using hybrid FDG-PET and MRI coregistered images

IntroductionDual phase 18 FDG brain PET is helpful to assess brain metastases (BM) as tracer will build up in metastases or tumor recurrences while its retention remains stable within normal tissue or inflammatory processes. This is useful when MRI can’t discriminate brain tumor recurrence (TR) rom radionecrosis (RN) after stereotaxic radiosurgery (SRS) for BM. Many studies have sought to improve diagnostic performance by associating FDG-PET and MRI with interesting results but many biases, mostly within image post-processing. Coregistered MRI and dual phase FDG-PET images could alleviate these biases and be used to extract prognostic biomarkers.Materials and methodsWe retrospectively evaluated patients treated with SRS for BM which developed a contrast-enhanced MRI lesion with non-conclusive diagnosis for TR or RN. All patients underwent MRI and FDG-PET at least 3 months after their last SRS session. Dual FDG-PET consisted in an “early” and “delayed” acquisition, respectively 30 minutes and 4 h after injection. MRI included permeability and perfusion sequences. PET and MRI data were all coregistered on the contrast enhanced T1 MRI images. Semi-automated Volumes of Interest (VOI) of the tumor were drawn on the BM and a reference contralateral white-matter ROI (WM) was drawn for standardization; every metric was calculated inside these ROIs, in particular the tumor SUVmax and its variation in time. A 20% increase in the tumor SUVmax was in favor of TR while a modification of less than 100% was in favor of RN. Imaging metrics were then evaluated for their association with TR or RN based on histological, radiological and clinical criteria after at least 6 months follow-up.ResultsNine patients were ruled out as TR and 6 as RN. After standardization, there was a significant difference between groups for VP (P = 0.042), Washin (P = 0.035), Peak Enhancement (P = 0.037), standardized delayed SUVmax (P = 0.008) and RI (P = 0.016). Semi-quantitative analysis found respectively for PET and MRI a Sensitivity of 100% and 87.5% and a Specificity of 100% and 85.71%.ConclusionCoregistered PET-MRI images accurately discriminate between TR and RN. With FDG being the most commonly used PET radiotracer, this protocol remains easily transposable and should be encouraged to obtain non-invasive prognostic and clinically relevant biomarkers.     

Clinicopathological Characteristics and Prognosis of Poorly Differentiated Thyroid Carcinoma Diagnosed According to the Turin Criteria

ObjectivePoorly differentiated thyroid carcinoma (PDTC) is the primary cause of death in patients with nonanaplastic follicular cell-derived thyroid carcinoma. We purposed to identify the clinical and pathological characteristics of PDTC and their relationship with prognosis.MethodsA retrospective analysis was conducted on patients diagnosed with PDTC at our institution from 2010 to 2018. All of their histopathology slides were reviewed by 2 experienced pathologists based on the Turin criteria. Furthermore, information regarding clinical characteristics, pathological characteristics, treatment strategy, and follow-up events were collected. The Kaplan-Meier method was used for survival analysis, while the log-rank test was used to compare survival curves. Then, the Cox proportional hazards model was used to perform univariate and multivariate analyses.ResultsTwenty-six patients with PDTC who met the Turin criteria were enrolled in this study. The median follow-up period of the included 26 patients was 76 months, while the 3- and 5-year survival rates were 40% and 18%, respectively. Notably, univariate analysis revealed that tumor size >4 cm (P = .038), extrathyroidal extension (ETE) (P = .020), distant metastases (P = .047), poorly differentiated areas >60% (P = .049), and Ki-67 labeling index >30% (P = .040) were associated with poor prognosis. On the other hand, multivariate analysis identified ETE (P = .007) and distant metastases (P = .031) as independent risk factors for poor prognosis.ConclusionPDTC is a rare carcinoma with high invasiveness and poor prognosis. Patients with ETE or distant metastases may have adverse outcomes.     

Radiosurgery dose reduction for brain metastases on immunotherapy (RADREMI): A prospective phase I study protocol

IntroductionUp to 20% of patients with brain metastases treated with immune checkpoint inhibitor (ICI) therapy and concomitant stereotactic radiosurgery (SRS) suffer from symptomatic radiation necrosis. The goal of this study is to evaluate Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) on six-month symptomatic radiation necrosis rates.MethodsThis study is a prospective single arm Phase I pilot study which will recruit patients with brain metastases receiving ICI delivered within 30 days before SRS. All patients will be treated with RADREMI dosing, which involves SRS doses of 18 Gy for 0−2 cm lesions, 14 Gy for 2.1−3 cm lesions, and 12 Gy for 3.1−4 cm lesions. All patients will be monitored for six-month symptomatic radiation necrosis (defined as a six-month rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with imaging findings consistent with radiation necrosis) and six-month local control. We expect that RADREMI dosing will significantly reduce the symptomatic radiation necrosis rate of concomitant SRS + ICI without significantly sacrificing the local control obtained by the present RTOG 90−05 SRS dosing schema. Local control will be defined according to the Response Assessment in Neuro-Oncology (RANO) criteria.DiscussionThis study is the first prospective trial to investigate the safety of dose-reduced SRS in treatment of brain metastases with concomitant ICI. The findings should provide fertile soil for future multi-institutional collaborative efficacy trials of RADREMI dosing for this patient population.Trial RegistrationClinicaltrials.gov identifier: NCT04047602 (registration date: July 25, 2019).     

Survival and prognostic factors for patients with melanoma brain metastases in the era of modern systemic therapy

Historically, the prognosis of patients with melanoma brain metastases is poor, with median overall survival (OS) of 4‐6 months. Little is known of OS in the era of modern systemic therapies and local therapy with stereotactic radiosurgery (SRS) or surgery. Patients diagnosed with melanoma brain metastases at Melanoma Institute Australia from January 2011 to December 2014 were included. OS and prognostic factors were analysed using Cox regression and Kaplan‐Meier survival analyses.355 patients were included. The median OS was 7.1 months (95% confidence interval [CI] 6.0‐8.1). Median OS differed by treatment modality: systemic therapy and SRS and/or surgery 14.9 months (95% CI 10.7‐19.0), SRS and/or surgery with or without whole brain radiotherapy (WBRT) 6.4 months (95% CI 5.4‐7.5), systemic therapy 5.4 months (95% CI 3.1‐7.7), systemic therapy and WBRT 5.2 months (95% CI 4.1‐6.4), WBRT 4.4 months (95% CI 2.4‐6.3), and best supportive care 1.8 months (95% CI 1.2‐2.3). OS for patients with melanoma brain metastases appears improved in the modern era, particularly for patients who are candidates for systemic therapy with SRS and/or surgery.     

Ultrasound-guided axillary vein puncture for cardiac devices implantation in patients under antithrombotic therapy

BackgroundUltrasound-guided axillary venous puncture (UGAVP) for cardiac devices implantation has been developed because of its rapidity, safety and potential long-term lead protection. Early work excluded defibrillators (ICD), cardiac resynchronization therapy (CRT) and upgrade procedures. Compared to the cephalic approach, in previous studies, there was a greater use of pressure dressings with this technique, suggesting a higher risk of bleeding.AimsTo assess UGAVP in patients under antithrombotic therapy (ATT) undergoing cardiac devices implantation including CRT/ICD.MethodsProspectively, consecutive patients eligible for a pacemaker or ICD implantation were included. All procedures were performed by a single operator, experienced with UGAVP for femoral access, and fluoroscopy-guided axillary vein access. Guidewires insertion time (from lidocaïne administration), and complications were systematically studied.ResultsFrom 457 cardiac device implantations, 200 patients (77.8 ± 10 y, male 58%) 360 leads were implanted by UGAVP including 36 ICD, 54 CRT and 14 upgrade procedures. A majority (90%) was under ATT: Vitamin K Antagonist or Heparin (n = 58, 29%), direct oral anticoagulant (n = 46, 23%), dual antithrombotic therapy (n = 18, 9%) and single antiplatelet drug (n = 82, 41%). UGAVP was successful in 95.78%. Mean insertion time for 1.8 guidewires per patient was 4.68 ± 3.6 min. No complication (no hematoma) was observed during the follow-up (mean of 45 ± 10 months). Guidewires insertion time reached its plateau after 15 patients.ConclusionUGAVP is fast, feasible and safe for patients under ATT undergoing device implantation including CRT/ICD and upgrade procedures, with a short learning curve.     

Incidence and prognosis of patients with small intestinal neuroendocrine tumors in a population based nationwide study

Background & aimsSmall intestinal neuroendocrine tumours (SI-NETs) are the most frequent malignant tumours of the small intestine. Population based studies on SI-NETs are scarce. We aimed to examine the incidence, presentation of disease and prognosis of SI-NET and to determine patient prognosis in those undergoing emergency or elective surgery.MethodsThis was a retrospective population-based study. Information on all patients diagnosed with neuroendocrine tumours of the small intestine (excluding duodenum) from the beginning of the Icelandic Cancer Registry and the pathology departments in the country (1966–2017). Detailed phenotypic information was obtained from medical records on symptoms at diagnosis, treatment, recurrence and survival.ResultsA total of 113 patients with SI-NETs were identified, 3 patients were excluded due to lack of data and/or diagnostic error, leaving 110 patients for final analysis. The incidence of SI-NET was 0.78/100,000 and did not increase during the study period. A total of 42 % (n = 46) of patients were diagnosed incidentally. Long-term prognosis, after a landmark of 12 months, was better in patients who were diagnosed incidentally (HR 0.52; p = 0.03). Overall 89 % (n = 98) of cases underwent surgical resection of the primary tumor, 31 % (n = 30) patients acute or semi-acute surgery and 69 % (n = 68) elective surgery. Emergency surgery was associated with a 6-fold risk of death in the first 12 months after surgery (HR: 5.99; p = 0.01) and associated with more severe surgical complications. However, there was no difference in the long-term risk of death after the first 12 months (HR: 1.39; p = 0.27).ConclusionsThe incidence of SI-NETs has not changed significantly in the last decades. Incidentally diagnosed SI-NET was associated with a favorable long-term prognosis. Emergency surgery in patients with SI-NET was associated with a significantly worse short-term risk of mortality compared to those who underwent elective surgery.     

Patient Understanding of Discharge Instructions for Home Diabetes Self-Management and Risk for Hospital Readmission and Emergency Department Visits

ObjectiveThe primary objective of this study was to examine the patient comprehension of diabetes self-management instructions provided at hospital discharge as an associated risk of readmission.MethodsNoncritically ill patients with diabetes completed patient comprehension questionnaires (PCQ) within 48 hours of discharge. PCQ scores were compared among patients with and without readmission or emergency department (ED) visits at 30 and 90 days. Glycemic measures 48 hours preceding discharge were investigated. Diabetes Early Readmission Risk Indicators (DERRIs) were calculated for each patient.ResultsOf 128 patients who completed the PCQ, scores were similar among those with 30-day (n = 31) and 90-day (n = 54) readmission compared with no readmission (n = 72) (79.9 ± 14.4 vs 80.4 ± 15.6 vs 82.3 ± 16.4, respectively) or ED visits. Clarification of discharge information was provided for 47 patients. PCQ scores of 100% were achieved in 14% of those with and 86% without readmission at 30 days (P = .108). Of predischarge glycemic measures, glycemic variability was negatively associated with PCQ scores (P = .035). DERRIs were significantly higher among patients readmitted at 90 days but not 30 days.ConclusionThese results demonstrate similar PCQ scores between patients with and those without readmission or ED visits despite the need for corrective information in many patients. Measures of glycemic variability were associated with PCQ scores but not readmission risk. This study validates DERRI as a predictor for readmission at 90 days.     

Évaluation par la TEMP–TDM des lésions classées indéterminées en scintigraphie osseuse chez les patients de cancérologie

The aim of the present study was to investigate the contribution of the single photon emission computed tomography/computed tomography (SPECT/CT) in cancer patients and to evaluate its ability to correctly classify indeterminate lesions on planar bone scintigraphy (PBS).MethodsFrom November 2006 to August 2007, all patients with confirmed malignancy, whose PBS showed indeterminate lesions, underwent without delay a SPECT/CT. The study included 120 patients (67 men, 53 women), with a mean age of 69 ± 12 years (range 42–96 years). The patients with obvious metastases, important pains or who did not accept the examination were excluded from the study. The location of the lesions was described either as precise, probable or indeterminate. The lesions were classified either as definitely malignant, definitely benign or indeterminate.ResultsBreast, prostate, lung and kidney neoplasms represented approximately 80% of all cancers. The PBS highlighted 267 lesions of location either as precise (n = 29), probable (n = 129) or indeterminate (n = 109), classified either as definitely malignant (n = 28), definitely benign (n = 27) or indeterminate (n = 212). The SPECT/CT revealed 440 lesions, of location either as precise (n = 353), likely (n = 39) or indeterminate (n = 48), classified either as definitely malignant (n = 84), definitely benign (n = 305) or indeterminate (n = 51). Thoracic and lumbar spine and pelvis were the locations of 79% of the scintigraphic lesions and of 88% of the osseous metastases. SPECT/CT modified the final report of 80 patients, by excluding from metastases (n = 2), by showing metastases (n = 23) and by showing the benign character of indeterminate lesions (n = 55). Moreover, 69 patients out of 120 (> 57%) had an evolution confirmed with 35 true positives, 31 true negatives, one false negative and two patients with indeterminate lesions on SPECT/CT, without osseous metastasis.ConclusionThe assessment of the indeterminate scintigraphic lesions of oncologic patients benefits from the SPECT/CT. The lesion-based analysis showed that the SPECT/CT detected more lesions (+64%) and correctly classified 88% of the detected lesions. The patient-based analysis highlighted that SPECT/CT modified the final report for more than 66% of the patients. The follow-up showed that SPECT/CT correctly classified for more than 95% of the patients.     

Quality of life and radiotherapy in brain metastasis patients

AimThe primary objective of this study was to assess whether there was an improvement in QoL for patients with brain metastases after radiotherapy treatments.BackgroundAssessment of quality of life (QoL) in brain metastasis patients has become increasingly recognized as an important outcome.Materials and methodsPatients treated for brain metastasis in our department during 2010 were included in our prospective study. QoL assessments were conducted at baseline, 1 month, and 3 months after completion of whole-brain radiotherapy (WBRT). Wilcoxon test for multiple comparisons was calculated to detect significant differences in global QoL scores.ResultsThirty-nine patients with brain metastases completed the EORTC QLQ-C30/BN-20 questionnaire independently. Median age was 59.9 years (from 37 to 81 years). Our results report differences between the baseline and 3 months in worsening of a global health status (p = 0.034) and cognitive function (p = 0.004), as well as drowsiness (p = 0.001), appetite loss (p = 0.031) and hair loss (p = 0.005). There is a tendency for deterioration of physical function (p = 0.004), communication deficit (p = 0.012), and weakness of legs (p = 0.024), between the baseline and 1 month evaluation. There was no difference in a global cognitive status between different evaluations. Median survival time was 3 months (CI 95% 1.85; 4.15).ConclusionsOur findings indicate a small deterioration for a global QoL status, and large deterioration for cognitive function after radiation treatments, as well as worsening of brain metastasis related symptom items. Further research is necessary to refine treatment selection for patients with brain metastases, since it may at least contribute to the stabilization of their QoL status.     

Unique features of epicardial ventricular arrhythmias/premature ventricular complexes ablated from coronary venous system in veteran population

IntroductionVentricular arrhythmias/premature ventricular complexes (VA/PVCs) that can be ablated from within the coronary venous system (CVS) have not been described in the United States Veterans Health Administration (VHA) population. We retrospectively studied the VA/PVCs ablations that were performed in the VHA population.MethodsData from 42 consecutive patients who underwent VA/PVCs ablation at Veterans Affairs Hospital, Indianapolis, IN, with 44 VA/PVCs was included in the study. Patients were divided into two groups (CVS group [n = 10], and non-CVS group [n = 32]) based on where the earliest pre-systolic activation was seen with >95% pacematch.ResultsThe mean age in CVS group was 65 ± 8 years versus 64 ± 12 years (p = 0.69) in non-CVS group. Overall there was a statistically significant reduction in PVC burden post ablation (27.7% (pre-ablation) versus 4.7% (post-ablation). In the 10 patients in the CVS group, either ablation or catheter-related mechanical trauma resulted in complete (n = 6 [60%]) or partial (n = 4 [40%]) long-term suppression of VA/PVCs. Right bundle branch block-type VA/PVC (9/11: 82%) was the most common morphology in the CVS group, whereas in the non-CVS group, this type was seen in only 3/33 (9%). The CVS group (25% of total VA/PVCs) had shorter activation time compared to non CVS group.ConclusionIn our experience VA/PVCs with electrocardiograms suggestive of epicardial origin can often be safely and successfully ablated within the coronary venous system. These arrhythmias have unique features in Veterans patient population.     

Valeur pronostique de la TEP/TDM dans le bilan initial du cancer du col utérin : SUVmax de la tumeur primitive et stadification ganglionnaire

PurposeWe investigated the prognostic significance of F-18 fluorodeoxyglucose (FDG) uptake measured as maximum Standardized Uptake Value (SUV_max) in primary tumor by positron emission tomography/computed tomography (PET/CT) in cervical cancer. The secondary objective was to determine the accuracy of the PET/CT for detecting pelvic lymph node (PLN) and para-aortic lymph node (PALN) metastases.MethodsThis retrospective study included 49 consecutive patients with stage IB1 to IVB cervical cancer. Univariate analysis was performed to determine the relationships between SUV_max value and pathological prognostics factors. Survival was estimated by Kaplan-Meier method. The gold standard of LN metastases was histologic.ResultsA significant difference in SUV_max was observed between stage I and stage II, stage I and stage IV and tumor size ≤ 4 cm and > 4 cm (P = 0.0001). There was a significant correlation between the SUV_max and tumor maximal size (r = 0.597) (P < 0.0001). PLN metastasis was found to be predictive of progression-free survival (P = 0.0007). The negative predictive value (NPV) of the PET/CT for PALN was 100% for locally advanced cervical carcinoma in 24 patients. The specificity and NPV of the PET/CT for PLN in eight early-stage cervical cancer were 100% and 87.5% (7/8) respectively. The PET/CT false-negative PLN measured less than 2 mm.ConclusionOur results demonstrate a correlation between SUV_max and tumor maximal size, which represents an indicator of tumor aggressiveness. PET/CT is effective to predict the absence of PALN in locally advanced cervical carcinoma. PET/CT is not sufficient to predict PLN in early-stage cancer without lymphadenectomy.     

Local impedance-guided ablation and ultra-high density mapping versus conventional or contact force-guided ablation with mapping for treatment of cavotricuspid isthmus dependent atrial flutter

Introduction– Local impedance (LI) guided ablation as a method of judging lesion effectiveness for cavotricuspid isthmus dependent atrial flutter (CTI-AFL), and ultra-high density (UHD) mapping when breakthrough occurred across an ablation line has not previously been assessed.MethodsThis retrospective observational study evaluated patients undergoing CTI-AFL ablation using conventional, contact force (CF) and LI guided strategies. Ablation metrics were collected, and in the LI cohort, the use of UHD mapping for breakthrough evaluated.Results30 patients were included, 10 per group. Mean total ablation time was significantly shorter with LI (3.2 ± 1.3min) vs conventional (5.6 ± 2.7min) and CF (5.7 ± 2.0min, p = 0.0042). Time from start of ablation to CTI block was numerically shorter with LI (14.2 ± 8.0min) vs conventional and CF (19.7 ± 14.1 and 22.5 ± 19.1min, p = 0.4408). Mean lesion duration was significantly shorter with LI, but there were no differences in the number of lesions required to achieve block, procedural success, complication rates or recurrence. 15/30 patients did not achieve block following first-pass ablation. UHD mapping rapidly identified breakthrough in the five LI patients, including epicardial-endocardial breakthrough (EEB).Conclusion– The use of LI during ablation for real-time lesion assessment was as efficacious as the conventional and CF methods. UHD mapping rapidly identified breakthrough, including EEB.     

Stereotactic radiosurgery for patients with breast cancer brain oligometastases — molecular subtypes and clinical outcomes

BackgroundWe sought to determine the clinical outcomes of patients with breast cancer (BC) who had undergone stereotactic radiosurgery (SRS) for a limited number of brain metastases (BM) and to identify factors influencing overall survival (OS) and local control.Materials and methodsThe records of 45 patients who underwent SRS for 72 brain lesions were retrospectively evaluated. Statistics included the chi-squared test, Kaplan-Meier method, and the multivariate Cox model.ResultsThe median number of treated BM was 2 (range 1–10). Median OS from BM diagnosis and post-SRS were 27.6 [95% confidence interval (CI): 14.8–40.5) and 18.5 months (95% CI: 11.1–25.8), respectively. One-year and two-year survival rates after BM diagnosis were 55% and 41%, respectively. In a univariate analysis, the Luminal-B-human-epidermal-growth-receptor-positive (HER2+) subtype had the longest median OS at 39.1 months (95% CI: 34.1–44.1, p = 0.004). In an adjusted analysis, grade 2 [hazard ratio (HR): 0.1; 95% CI: 0.1–0.6, p = 0.005), craniotomy (HR: 0.3; 95% CI: 0.1–0.7; p = 0.006), and ≥ 2 systemic therapies received (HR: 0.3; 95% CI: 0.1–0.9, p = 0.028) were associated with improved OS. One-year and two-year intracranial progression-free survival rates were 85% and 63%, respectively. Four factors for a higher risk of any intracranial recurrence remained significant in the adjusted analysis, as follows: age < 50 years (HR: 4.2; 95% CI: 1.3–36.3; p = 0.014), grade 3 (HR: 3.7; 95% CI: 1.1–13.2; p = 0.038), HER2+ (HR: 6.9; 95% CI: 1.3–36.3; p = 0.023), and whether the brain was the first metastatic site (HR: 4.7; 95% CI: 1.6–14.5; p = 0.006).ConclusionIntrinsic BC characteristics are important determinants for both survival and intracranial control for patients undergoing SRS for oligometastatic brain disease.     

Low baseline vitamin D levels increase the risk of bone metastases among females with breast cancer − Hospital based cohort study

BackgroundSerum vitamin D (Vit-D) has been linked to the development of breast cancer (BC); however, their effect on pathological features and outcomes is undetermined. The purpose of this study was to examine the prognostic significance of baseline Vit-D levels and their effect on clinical outcomes.MethodsWe evaluated baseline serum Vit-D levels and baseline clinic-pathological features of female patients with non-metastatic BC between October 2018 and December 2019. A low Vit-D level was described as less than 30 nanogram per liter (ng/l). Patients were observed for a median of 24 months. To evaluate relationships between qualitative variables, the chi-square test was used. The Kaplan-Meier technique was used for survival analysis, and the log-rank test was used to compare the two survival curves. Correlation analysis was also used to examine the link between Vit-D levels and clinical outcomes.ResultsThe eligibility criteria were fulfilled by 221 patients. The median age of onset was (50.7). The median Vit-D level was (23.1 ng/l) with a range of (4–46 ng/l). Approximately half of the patients (56.5%) had Vit-D levels < 30 ng/l, with HER2 positive and triple negative (TNBC) patients having a greater proportion of low Vit-D levels (p = <0.001). Patients with low baseline Vit-D levels had a larger tumor size, more positive lymph nodes, and were diagnosed at a later stage. Following follow-up, Vit-D deficiency was associated with a significantly increased risk of bone metastases (HR 3.37, 95% CI 1.32–8.59, p = 0.006), and Vit-D levels were significantly correlated with disease-free survival (DFS) and overall survival (OS) (r = 0.850, r = 0.573, p < 0.00, p < 0.001, respectively).ConclusionsLow serum Vit-D is associated with advanced stage and adverse characteristics. It is more prevalent in HER-2 positive and TNBC patients; it increases the chance of bone metastases, and has a significant correlation with DFS and OS.     

非小细胞肺癌脑转移瘤综合治疗的预后影响因素分析

目的:研究综合治疗的非小细胞肺癌(non-small cell lung cancer,NSCLC)脑转移瘤患者生存预后影响因素,为NSCLC脑转移瘤的治疗提供更多的参考依据。方法:收集83例诊断为NSCLC脑转移瘤的患者进行回顾性研究,随访后建立临床资料数据库,采用单因素分析及Cox回归模型分析不同因素对非小细胞肺癌脑转移瘤患者生存期的影响。结果:患者中位生存期为11个月,6月、12月、18月的生存率分别为79.0%、32.7%、19.4%。经单因素和多因素分析结果显示脑转移瘤的病理类型、原发灶控制情况、治疗方式、靶向治疗是NSCLC脑转移生存的独立影响预后因素。单发转移瘤中,手术联合全脑放疗(Whole brain radiotherapy,WBRT)与手术相比风险率(hazard rate,HR)为0.645(P>0.05),说明联合方式并没有在生存中获益。多发转移瘤中,手术与WBRT相结合与单纯手术对比HR=0.297(P<0.05),有统计学意义。结论:病理类型为非腺癌,原发灶未得到控制,治疗方式不当以及未应用靶向治疗是NSCLC脑转移瘤的独立危险因素。对于单发脑转移瘤患者的局部治疗,单独手术治疗可能具有更高的优势;对于多发脑转移瘤患者的局部治疗,手术与WBRT联合可能具有更多的生存获益。     

Overcoming minimal residual disease using intensified conditioning with medium-dose etoposide,cyclophosphamide and total body irradiation in allogeneic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults

Background aimsAn intensified conditioning regimen incorporating medium-dose etoposide (VP16) is an option for patients with acute lymphoblastic leukemia (ALL). However, the prognostic impacts of the addition of VP16 to cyclophosphamide (CY) and total body irradiation (TBI) in patients with Philadelphia chromosome-positive (Ph+) ALL with regard to minimal residual disease (MRD) status have not been elucidated.MethodsThe authors retrospectively compared the outcomes of patients with Ph+ ALL who underwent allogeneic transplantation following VP16/CY/TBI (n = 101) and CY/TBI (n = 563).ResultsAt 4 years, the VP16/CY/TBI group exhibited significantly better disease-free survival (DFS) (72.6% versus 61.7%, P = 0.027) and relapse rate (11.5% versus 21.1%, P = 0.020) and similar non-relapse mortality (16.0% versus 17.2%, P = 0.70). In subgroup analyses, the beneficial effects of the addition of VP16 on DFS were more evident in patients with positive MRD status (71.2% versus 48.4% at 4 years, P = 0.022) than those with negative MRD status (72.8% versus 66.7% at 4 years, P = 0.24). Although MRD positivity was significantly associated with worse DFS in patients who received CY/TBI (48.4% versus 66.7%, P < 0.001), this was not the case in those who received VP16/CY/TBI (71.2% versus 72.8%, P = 0.86).ConclusionsThis study demonstrated the benefits of the addition of VP16 in Ph+ ALL patients, especially those with positive MRD status. VP16/CY/TBI could be a potential strategy to overcome the survival risk of MRD positivity.     

Nasopharyngeal carcinoma in Slovenia, 1990–2003 (results of treatment with conventional two-dimensional radiotherapy)

AimTo review the treatment results and identify prognostic factors for disease control and survival in a cohort of nasopharyngeal carcinoma (NPC) patients from a non-endemic population in Slovenia, diagnosed between 1990 and 2003.BackgroundIn Caucasians, nasopharyngeal carcinoma is a rare malignant tumor. Its diagnosis and treatment are complex and have been dramatically impacted by recent technological advances.Materials and methodsIn the Cancer Registry of Slovenia database, a total of 126 patients with NPC were identified, 93 of whom were available for analysis. All patients were treated with conventional two-dimensional radiotherapy (RT) and 29.3% underwent chemotherapy (ChT).ResultsThe median follow-up time for those alive at the last follow-up examination was 74.5 months. Disease recurred locally in 17 patients, regionally in 4 patients and at distant sites in 18 patients, resulting in 5-year locoregional control (LRC), distant failure-free survival (DFFS) and disease-free survival (DFS) of 73.7%, 78.6% and 59.3%, respectively. Disease-specific survival at 5 years was 59% and overall survival (OS) was 49.7%. In a multivariate analysis, LRC was favorably affected (P < 0.05) by an undifferentiated histology (hazard ratio [HR] = 2.86), DFFS through the absence of neck metastases (HR = 0.28), DFS by younger age (HR = 0.46), and more intensive RT (expressed as the isoeffective dose, EQD_2,T; HR = 2.08). The independent prognosticator for OS was age (≤55 years vs. >55 years, HR = 0.39); in the ≤55 years subgroup, an improved OS was connected to a more intensive RT regimen of EQD_2,T ≥ 66 Gy (HR = 4.17).ConclusionsOur results confirm an independent and favorable effect from an undifferentiated histology, the absence of neck metastases, a younger patient age at diagnosis, and more intensive RT regimens for disease control and survival.     

Preoperative neutrophil-to-lymphocyte ratio (preNLR) for the assessment of tumor characteristics in lung adenocarcinoma patients with brain metastasis

ObjectivesBrain metastases from lung adenocarcinoma cause significant patient mortality. This study aims to evaluate the role of preoperative Neutrophil-to-Lymphocyte ratio (preNLR) in predicting the survival and prognosis of Lung adenocarcinoma (LUAD) patients with brain metastasis (BM) and provide more references for predicting peritumoral edema.MethodsWe retrospectively reviewed 125 LUAD-BM patients who had undergone surgical resection from December 2015 to December 2020. The clinical characteristic, demographic, MRI data, and preNLR within 24–48 h before craniotomy were collected. Patients were divided into two groups based on preNLR (high NLR and low NLR), with cutoff values determined by receiver operating characteristic (ROC) analysis. Association between preoperative NLR and clinical features was determined by using Pearson chi-squared tests. Uni- and multivariate analyzes were performed to compare the overall survival (OS) of clinical features.ResultsThe patients were divided into NLR-low (64 patients) and NLR-high (61 patients) groups based on receiver operating characteristic analysis of NLR area. According to correlation analysis, a high preNLR (NLR≥2.8) is associated with the both supra- and infratentorial location involved (P = 0.017) and a greater incidence of severe peritumoral edema (P = 0.038). By multivariable analysis, age ≥ 65 years (P = 0.011), KPS < 70 (P = 0.043), elevated preNLR (P = 0.013), extracerebral metastases (P = 0.003), EGFR/ALK+ (P = 0.037), postoperative radiotherapy (P = 0.017) and targeted therapy (P = 0.007) were independent prognostic factors. OS nomogram was constructed based on cox model and model performance was examined (AUC = 0.935).ConclusionsPreNLR may serve as a prognosis indicator in LUAD patients with brain metastasis, and high preNLR tends to be positively associate with multiple locations and severe peritumoral edema.     

Outcomes following stereotactic radiosurgery or whole brain radiation therapy by molecular subtype of metastatic breast cancer

BackgroundThis study quantified clinical outcomes by molecular subtype of metastatic breast cancer (BC) following whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Doing so is important for patient counseling and to assess the potential benefit of combining targeted therapy and brain radiotherapy for certain molecular subtypes in ongoing trials.Materials and methodsThe National Cancer Database was queried for BC (invasive ductal carcinoma) cases receiving brain radiotherapy (divided into WBRT and SRS ). Statistics included multivariable logistic regression to determine factors associated with SRS delivery, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling.ResultsOf 1,112 patients, 186 (16.7%) received SRS and 926 (83.3%) underwent WBRT. Altogether, 410 (36.9%), 195 (17.5%), 162 (14.6%), and 345 (31.0%) were ER+/HER2−, ER+/HER2+, ER−/HER2+, and ER−/HER2−, respectively. In the respective molecular subtypes, the proportion of subjects who underwent SRS was 13.4%, 19.4%, 24.1%, and 15.7%. Respective OS for WBRT patients were 12.9, 22.8, 10.6, and 5.8 months; corresponding figures for the SRS cohort were 28.3, 40.7, 15.0, and 12.9 months (p < 0.05 for both). When comparing OS between treatment different histologic subtypes, patients with ER−/HER2+ and ER−/HER2− disease had worse OS than patients with ER+/HER2− disease, for both patients treated with SRS and for patients treated with WBRT.ConclusionsMolecular subtype may be a useful prognostic marker to quantify survival following SRS/WBRT for metastatic BC. Patients with HER 2-enriched and triple-negative disease had the poorest survival following brain irradiation, lending credence to ongoing studies testing the addition of targeted therapies for these subtypes.     

Improved durable pulmonary vein isolation with shorter procedure times and lower energy levels using RF ablation with ablation index and a stringent lesion contiguity

BackgroundThe single procedure success rates of durable pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) varies between 80 and 90%. Ablation index, incorporating contact force, stability, time and power is a more profound parameter of significant lesion size and has been established. Equally important is a stringent contiguity of the lesion set.Methods and resultsA total number of 100 consecutive patients undergoing de-novo catheter ablation for paroxysmal atrial fibrillation (PAF) were analyzed between 2016 and 2019. In the first 50 patients (group A) PVI was performed using a surround flow, contact force catheter (Biosense Webster Thermocool STSF, Biosense Webster, USA) with a drag-and-ablate technique to encircle the PVs. In the following 50 patients (group B), PVI was performed using ablation index and a stringent lesion contiguity with an interlesion distance (ILD) of <5 mm. The baseline characteristics showed no significant differences between both groups. During a mean follow-up of 18 ± 3 months after a single procedure, 36 (72%) patients of group A were free of arrhythmia recurrence versus 43 (86%) patients in group B (p = 0.047). A total of 14 patients (group A: 10 (20%), group B: 4 (8%); underwent a redo-procedure. 7 patients of group A (14%) and 2 patients of group B (4%) showed recovered veins. In 3 patients of group A and 2 patients of group B the PVs were durably isolated. In these patients persistent AF recurrence was caused by extra-PV AF sources. Four patients of group A and three patients of group B had continued paroxysmal or persistent AF but did not undergo redo-procedure. With regard to the procedural data, the procedure time, the total energy and the fluoroscopy time were significantly lower in group B (AI and ILD <5 mm) (128.86 ± 18.19 versus 115.35 ± 15.38; p < 0.05; 1619.16 ± 988.56 versus 1186.26 ± 756.34; p < 0.05; 11.49 ± 3.20 versus 9.66 ± 3.86; p = 0.04). Both procedures were performed with a low number of complications, no pericardial effusion was seen in either group.ConclusionsPVI using ablation index in combination with a stringent lesion contiguity improves clinical outcome after first-time PVI with lower PVI recovery, shorter procedure times, lower total energy and shorter fluoroscopy times and therefore, is more efficient.