Factors influencing the accuracy and safety of preoperative computed tomography (CT)-guided soft hook-wire localization for pulmonary nodules: a comprehensive analysis.

Background: The necessity of localization of pulmonary nodules lies in ensuring the ability to locate the nodule quickly and accurately during surgery, thereby improving the success rate of the operation. The accuracy and risk of preoperative localization of pulmonary nodules need further exploration. Therefore, the purpose of this study was to investigate the factors of accuracy and safety of computed tomography (CT)-guided localization of pulmonary nodules using a flexible wire hook positioner. Methods: In this retrospective cross-sectional analysis, 281 patients with a single pulmonary nodule underwent video-assisted thoracoscopic surgery (VATS) following localization with a soft hook-wire guided by CT scan from January 2021 to July 2022 at Nanjing Drum Tower Hospital. The patients underwent VATS to remove pulmonary nodules within 24 hours after localization. The demographic, pulmonary nodule, and technical factors were analyzed retrospectively. Univariate and multivariate analysis were used to analyze the identified factors that influence pulmonary nodule localization accuracy and complications. Results: Localization was successfully performed in 280 patients, with only 1 patient being excluded due to a displaced positioner and the hook wire failing to enter the lung parenchyma as a result of pneumothorax. Out of the total cases, 191 (68.2%) were accurately positioned in group G0, whereas 89 cases (31.7%) were inaccurately positioned in group G1. Hemorrhage and self-limited hemoptysis were observed in 64 patients (22.8%), whereas pneumothorax was observed in 84 patients (29.9%). There were no serious complications such as air embolism or death. The accuracy of localization was found to be influenced by both the depth of pulmonary nodules [odds ratio (OR) =22.610, 95% confidence interval (CI): 10.351-49.391, P=0.001] and the depth of the needle used (OR =0.322, 95% CI: 0.136-0.765, P=0.010). Additionally, postoperative hemorrhage was found to be affected by several important factors, including the diameter (P=0.036) and depth of the nodule (P=0.011), as well as the thickness of the chest wall (P=0.043) and the depth of the needle used (P=0.005). Conclusions: The CT-guided flexible wire hook positioner has been found to be a safe and effective device for locating pulmonary nodules. The depth of pulmonary nodules and needle penetration are key factors affecting the accuracy of lung nodule localization under CT guidance and are important factors affecting postoperative bleeding.

The management of stage I Non-Small cell lung cancer (NSCLC) in Ontario: A Population-Based study of patterns of care and Stereotactic Ablative Body radiotherapy (SABR) utilization from 2010 to 2019.

BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is the standard of care for medically inoperable patients with Stage I NSCLC. The adoption of SABR and its association with cancer outcomes requires characterization. AIM: We described the management of biopsy-proven Stage I NSCLC with SABR, surgery, non-SABR curative radiotherapy (RT) and observation in Ontario, Canada, between 2010 and 2019. Temporal and geographic trends in practice and survival outcomes were analyzed. METHODS: This was a retrospective population-based cohort study conducted by linking electronic radiotherapy (RT) records to a population-based cancer registry. RESULTS: A total of 12,065 patients were identified, 61.7 % underwent surgery, 17.9 % received SABR, 8.6 % received non-SABR curative RT and 11.7 % were observed. Between 2010 and 2019, the utilization of surgery decreased (63.8 % to 49.9 %, p < 0.0001), while SABR use increased (7.5 % to 24.4 %, p < 0.0001), non-SABR curative RT use increased (6.7 % to 9.6 %, p < 0.0014) and patients observed decreased (14.4 % to 12.0 %, p < 0.0001). Substantial variation in practice exists across Ontario. Two- yr CSS improved for the entire cohort (81.9 % to 85.0 %, p < 0.0001). While there was improvement in 2 yr CSS for surgical patients (92.1 %% to 95.7 %, p < 0.001), survival for patients who received SABR, Non-SABR curative RT and observation remained stable. CONCLUSION: There has been an increase in SABR utilization and a reduction in surgical utilization with a corresponding increased survival of stage I patients in Ontario between 2010 and 2019. Substantial differences in practice patterns exist across health regions, suggesting the need for strategies to improve access to SABR in many jurisdictions.

Real-world outcomes associated with bevacizumab combined with chemotherapy in platinum-resistant ovarian Cancer.

OBJECTIVES: The addition of bevacizumab to chemotherapy for platinum-resistant (PL-R) ovarian cancer (OC) improved progression-free (PFS) but not overall survival (OS) in clinical trials. We explored real-world outcomes in Ontario, Canada, and compared survival in the pre- and post-bevacizumab era. METHODS: Administrative databases were utilized to identify all patients treated with bevacizumab for PL-R OC. Time on treatment (ToT) was used as surrogate for PFS. Median OS was determined using the Kaplan-Meier method. Factors associated with ToT/OS were identified using a Cox proportional hazard model. A before and after comparative effectiveness analysis was performed to determine mOS for patients treated pre- and post-bevacizumab approval. RESULTS: From 2017 to 2019, 176 patients received bevacizumab. Median ToT was 3 months and OS was 11 months. Sixty-four percent received liposomal doxorubicin and 34% received paclitaxel. ToT (6 vs 3 months; HR 0.44; p < 0.0001) and OS (14 vs 9 months; HR 0.45; p = 0.0089) were longer with bevacizumab/paclitaxel. OS was not significantly different pre- and post-bevacizumab funding (8 vs 9 months; HR 1.01; 0.937). Median OS increased for those receiving paclitaxel (6 vs 11 months), but those in the post group were younger, more likely to have undergone primary surgery and had less co-morbidities. CONCLUSION: Real-world outcomes with bevacizumab in PL-R OC are inferior to those in the pivotal clinical trial. Survival has not significantly improved since funding became publicly available, indicating a substantial efficacy-effectiveness gap between trial and real-world outcomes. Median OS and ToT were significantly better when bevacizumab was given with paclitaxel.

Characterizing Variability in Lung Cancer Outcomes and Influence of a Lung Diagnostic Assessment Program in Southeastern Ontario, Canada.

INTRODUCTION: Regional variability in lung cancer (LC) outcomes exists across Canada, including in the province of Ontario. The Lung Diagnostic Assessment Program (LDAP) in southeastern (SE) Ontario is a rapid-assessment clinic that expedites the management of patients with suspected LC. We evaluated the association of LDAP management with LC outcomes, including survival, and characterized the variability in LC outcomes across SE Ontario. METHODS: We conducted a population-based retrospective cohort study by identifying patients with newly diagnosed LC through the Ontario Cancer Registry (January 2017-December 2019) and linked to the LDAP database to identify LDAP-managed patients. Descriptive data were collected. Using a Cox model approach, we compared 2-year survival for patients managed through LDAP vs. non-LDAP. RESULTS: We identified 1832 patients, 1742 of whom met the inclusion criteria (47% LDAP-managed and 53% non-LDAP). LDAP management was associated with a lower probability of dying at 2 years (HR 0.76 vs. non-LDAP, p < 0.0001). Increasing distance from the LDAP was associated with a lower likelihood of LDAP management (OR 0.78 for every 20 km increase, p < 0.0001). LDAP-managed patients were more likely to receive specialist assessment and undergo treatments. CONCLUSIONS: In SE Ontario, initial diagnostic care provided via LDAP was independently associated with improved survival in patients with LC.

Real-world outcomes associated with use of front-line bevacizumab in ovarian cancer.

BACKGROUND: In the pivotal ICON7 study, addition of bevacizumab to front-line treatment of ovarian cancer (OC) significantly improved overall survival (OS) (p = 0.03) in a high-risk subgroup of patients with suboptimally debulked/unresectable stage III or IV disease, leading to approval in Ontario, Canada in March 2016. Here we describe utilization of bevacizumab for front-line, high-risk OC and determine outcomes in routine clinical practice. METHODS: Provincial administrative databases were utilized to identify all patients treated with front-line bevacizumab following its approval. Median OS (mOS) was determined using the Kaplan-Meier method. Factors associated with OS were identified using a Cox proportional hazard model. A comparative effectiveness analysis was performed to determine mOS pre- (2006-2016) and post- (2016-2019) approval. RESULTS: From March 2016 to October 2019, 282 patients received bevacizumab. Mean age was 64 years old, and 58% had stage IV disease. Median survival was 29 months and was longer in stage III (37 months) compared to stage IV disease (28 months). In a comparative effectiveness analysis of patients with stage IV serous OC, post-approval uptake of bevacizumab was low (23%). Median OS was similar pre (26 months) and post (27 months) approval (HR 0.92, 0.75-1.12, p = 0.383). CONCLUSIONS: Survival in real-world patients treated with front-line bevacizumab is shorter than in pivotal clinical trials. Survival in stage IV serous patients has not significantly improved post public reimbursement of bevacizumab. This analysis was limited by poor uptake, however mOS was similar in patients who did and did not receive bevacizumab.

Palliative Radiotherapy for Esophageal and Gastric Cancer: Population-Based Patterns of Utilization and Outcomes in Ontario, Canada.

OBJECTIVE: Patients with incurable esophageal and gastric cancer may develop local symptoms for which palliative radiotherapy (PRT) may be considered. We sought to evaluate patterns in utilization and outcomes of patients receiving PRT for incurable esophageal and gastric cancer in Ontario, Canada using health administrative data. METHODS: Linked health administrative databases were used to identify patients receiving PRT for incurable esophageal and gastric cancer. Primary outcomes were utilization and delivery of PRT, utilization of endoscopic dilation with or without stent insertion after completion of PRT and survival from 1) date of diagnosis and 2) start of PRT. RESULTS: We identified 2500 patients who received PRT. Mean age was 70 ± 13 years and the majority (75%, n = 1873/2500) were male. Over half of the patients had a diagnosis of gastric cancer (58%, n = 1453/2500) and began PRT within 6 months of cancer diagnosis (85%, n = 2125/2500). Of the 2500 patients in the cohort, 2174 patients received EBRT with few receiving brachytherapy (n = 326) or EBRT and brachytherapy combined (n = 88). Over the study period, there was an increase in the number of patients receiving PRT (136 in 2007 to 290 in 2016), as well as in the use of advanced conformal radiotherapy techniques. Only 5% (115/2500) required dilation with or without stent insertion after completion of PRT. Median overall and cancer-specific survival of the cohort was 205 days and 209 days from date of diagnosis and 108 days and 110 days from start of PRT. CONCLUSIONS: PRT is an important treatment for patients with incurable esophageal and gastric cancer who present with local symptoms. Utilization of PRT and advanced EBRT techniques increased over the study period. Few patients require endoscopic dilation with or without stent insertion after completion of PRT suggesting that PRT provides favorable symptom control.

Explaining regional variations in colon cancer survival in Ontario, Canada: a population-based retrospective cohort study.

OBJECTIVES: Regional variation in cancer survival is an important health system performance measurement. We evaluated if regional variation in colon cancer survival may be driven by differences in the patient population, their health and healthcare utilisation, and/or cancer care delivery. DESIGN: Population-based retrospective cohort study using routinely collected linked health administrative data. SETTING: Ontario, Canada. PARTICIPANTS: Patients with colon cancer diagnosed between 1 January 2009 and 31 December 2012. OUTCOME: Cancer-specific survival was compared across the province's 14 health regions. Using accelerated failure time models, we assessed whether regional survival variations were mediated through differences in case mix, including age, sex, comorbidities, stage at diagnosis and colon subsite, potential marginalisation and/or prediagnosis healthcare. RESULTS: The study population included 16 895 patients with colon cancer. There was statistically significant regional variation in cancer-specific survival. Three regions had cancer-specific survival that was between 30% (95% CI 1.03 to 1.65) and 39% (95% CI 1.13 to 1.71) longer and one region had cancer-specific survival that was 26% shorter (95% CI 0.58 to 0.93) than the reference region. For three of these regions, case mix explained between 26% and 56% of the survival variation. Further adjustment for rurality explained 22% of the remaining survival variation in one region. Adjustment for continuity of primary care and the diagnostic interval length explained 10% and 11% of the remaining survival variation in two other regions. Socioeconomic marginalisation, recent immigration and colonoscopy history did not explain colon cancer survival variation. CONCLUSIONS: Case mix accounted for much of the regional variation in colon cancer survival, indicating that efforts to monitor the quality of cancer care through survival metrics should consider case mix when reporting regional survival differences. Future work should repeat this approach in other settings and other cancer sites considering a broad range of potential mediators.

Incidence, Timing, and Outcomes of Venous Thromboembolism in Patients Undergoing Surgery for Esophagogastric Cancer: A Population-Based Cohort Study.

BACKGROUND: Abdominal surgery and chemotherapy are well-established risk factors for venous thromboembolism (VTE) in patients with cancer, but their specific contribution in patients with esophageal and gastric cancer is unclear. We aim to quantify the risk of VTE, identify risk factors associated with VTE, and determine the association between VTE and survival in patients undergoing surgery for esophageal or gastric cancer. METHODS: A retrospective, population-based cohort study was conducted using linked administrative healthcare databases. We used the Ontario Cancer Registry to identify patients with esophageal or gastric cancer between January 1, 2007 and December 31, 2016 who underwent surgical resection. Incidence of first VTE event was identified using International Classification of Diseases 9 and 10 codes. VTE incidence was calculated at clinically relevant time points 180 days before and after surgery. Logistic regression was used to identify factors associated with VTE with odds ratios (OR) and 95% confidence intervals (CI) reported. Cox proportional hazards regression models were used to estimate associations between covariates and survival. Kaplan-Meier method was used to compare overall (OS) and cancer-specific survival (CSS) by VTE status. RESULTS: A total of 4894 patients had esophagectomy or gastrectomy, of which 8% (n = 383/4894) had VTE. VTE risk was 2.5% (n = 123/4894) 180 days before surgery, 2.8% (n = 138/4894) within 30 days of surgery, and 2.5% (n = 122/4894) from 31 to ≤ 180 days after surgery. Of the patients with VTE within 30 days of surgery, 34% (n = 47/138) were diagnosed after discharge from hospital. Receipt of preoperative chemotherapy was associated with VTE 180 days before surgery (odds ratio [OR] 3.84, 95% confidence interval [CI] 2.41, 6.11). Increased hospital length of stay (LOS) was associated with VTE 30 days after surgery (OR 1.08, 95% CI 1.02, 1.14, per week). Patients with VTE had inferior median OS and CSS (2.2 vs. 3.7 years; 2.3 vs. 4.4 years, respectively). In adjusted models VTE was associated with inferior OS (HR 1.36, 95% CI 1.13, 1.63) and CSS (HR 1.42, 95% CI 1.16, 1.75). CONCLUSIONS: The highest risk of VTE is within 30 days of surgery with one third of patients diagnosed after discharge from hospital. Longer hospital LOS and receipt of preoperative chemotherapy are associated with increased risk of VTE. VTE is an independent risk factor for inferior survival in patients with esophageal or gastric cancer.

Apoptosis-promoting properties of miR-3074-5p in MC3T3-E1 cells under iron overload conditions.

BACKGROUND: Iron overload can promote the development of osteoporosis by inducing apoptosis in osteoblasts. However, the mechanism by which miRNAs regulate apoptosis in osteoblasts under iron overload has not been elucidated. METHOD: The miRNA expression profile in MC3T3-E1 cells under iron overload was detected by next generation sequencing. qRT-PCR was used to determine the expression of miR-3074-5p in MC3T3-E1 cells under iron overload. The proliferation of MC3T3-E1 cells was tested using CCK-8 assays, and apoptosis was measured using flow cytometry. The miRanda and TargetScan databases were used to predict the target genes of miR-3074-5p. Interaction between miR-3074-5p and the potential target gene was validated by qRT-PCR, luciferase reporter assay and western blotting. RESULTS: We found that iron overload decreased the cell viability and induced apoptosis of MC3T3-E1 cells. The results of next generation sequencing analysis showed that miR-3074-5p expression was significantly increased in MC3T3-E1 cells under iron overload conditions, which was confirmed by further experiments. The inhibition of miR-3074-5p attenuated the apoptosis of iron-overloaded MC3T3-E1 cells. Furthermore, the expression of Smad4 was decreased and was inversely correlated with miR-3074-5p expression, and overexpression of Smad4 partially reversed the viability inhibition of iron-overloaded MC3T3-E1 cells by relieving the suppression of ERK, AKT, and Stat3 phosphorylation, suggesting its regulatory role in the viability inhibition of iron-overloaded MC3T3-E1 cells. The luciferase reporter assay results showed that Smad4 was the target gene of miR-3074-5p. CONCLUSION: miR-3074-5p functions as an apoptosis promoter in iron-overloaded MC3T3-E1 cells by directly targeting Smad4.

Practice Patterns and Outcomes of Novel Targeted Agents for the Treatment of ERBB2-Positive Metastatic Breast Cancer.

Importance: Clinical trials have shown that the addition of pertuzumab to trastuzumab-based chemotherapy for first-line treatment of ERBB2-positive metastatic breast cancer is associated with considerable improvement in overall survival (OS). In the second-line setting, trastuzumab emtansine (T-DM1) improves OS compared with capecitabine/lapatinib in patients previously treated with trastuzumab-based chemotherapy. However, there are few data describing long-term real-world outcomes with these agents. Objective: To describe practice patterns and outcomes associated with pertuzumab and T-DM1 in routine clinical practice. Design, Setting, and Participants: This population-based retrospective cohort study used the Ontario Cancer Registry linked to electronic treatment databases to identify all patients treated with pertuzumab and T-DM1 following reimbursement approval in Ontario, Canada, which has a single-payer public health system. Participants included women with stage IV ERBB2-positive metastatic breast cancer receiving treatment with pertuzumab for first-line metastatic indication from December 2013 through December 2017, and those treated with T-DM1 from May 2014 through December 2017. Pertuzumab and T-DM1 cohorts were analyzed separately. Data were analyzed December 2019 to December 2020. Exposures: Treatment with pertuzumab or T-DM1. Main Outcomes and Measures: The primary outcome was OS, determined using the Kaplan-Meier method. Factors associated with OS were identified using a Cox proportional hazard model. Results: The median (interquartile range [IQR]) age of the 795 women who received pertuzumab and 506 women who received T-DM1 was 57 (49-67) and 56 (48-66) years, respectively. Among the cohort of patients who received pertuzumab, the median (IQR) OS and time on treatment was 43 (16.2-unavailable) and 14 (6.0-26.2) months, respectively. In the T-DM1 cohort, the proportion of pertuzumab-naive patients decreased over time from 68 of 91 [74.7%] in 2014 to 16 of 89 [18.0%] in 2017 (P < .001). The median (IQR) OS and time on treatment was 15 (6.7-27.7) and 4 (1.4-9.0) months, respectively. Median OS was shorter for patients with prior pertuzumab treatment than in the pertuzumab-naive subgroup (12 vs 19 months; adjusted hazard ratio, 0.70; 95% CI, 0.55-0.89; P = .004). Conclusions and Relevance: In this population-based cohort study, the survival of patients treated with pertuzumab and T-DM1 in routine practice appeared inferior to results from pivotal clinical trials. Differences in outcome likely reflect differences in patient population and previous lines of therapy in routine practice. Further work is needed to understand the effectiveness of T-DM1 after pertuzumab exposure.

First-Line Palliative Chemotherapy for Esophageal and Gastric Cancer: Practice Patterns and Outcomes in the General Population.

PURPOSE: Clinical trials have shown that palliative chemotherapy (PC) improves survival in patients with incurable esophageal and gastric cancer; however, outcomes achieved in routine practice are unknown. We describe treatment patterns and outcomes among patients treated in the general population of Ontario, Canada. METHODS: The Ontario Cancer Registry was used to identify patients with esophageal or gastric cancer from 2007 to 2016, and data were linked to other health administrative databases. Patients who received curative-intent surgery or radiotherapy were excluded. Factors associated with the receipt of PC were determined using logistic regression. First-line PC regimens were categorized, and trends over time were reported. Survival was determined using the Kaplan-Meier method. RESULTS: The cohort included 9,848 patients; 22% (2,207 of 9,848) received PC. Patients receiving PC were younger (mean age, 63 v 74 years; P < .0001) and more likely male (71% v 65%; P < .0001). Thirty-seven percent of non-PC patients saw a medical oncologist in consultation. Over the study period, utilization of PC increased (from 11% in 2007 to 19% in 2016; P < .0001), whereas the proportion of patients receiving triplet regimens decreased (65% in 2007 to 56% in 2016; P = .04). In the PC group, the median overall and cancer-specific survival from treatment initiation was 7.2 months. CONCLUSION: One fifth of patients with incurable esophageal and gastric cancer in the general population receive PC. Median survival of patients treated in routine practice is inferior to that in clinical trials. Only one third of patients not treated with PC had consultation with a medical oncologist. Further work is necessary to understand low utilization of PC and medical oncology consultation in this patient population.

Symptom Evolution in Patients with Esophageal and Gastric Cancer Receiving Palliative Chemotherapy: A Population-Based Study.

INTRODUCTION: Palliative chemotherapy (PC) is associated with a modest survival benefit in patients with incurable esophageal and gastric cancer; however, changes in symptom profile during treatment are not well described. Understanding the trajectory of symptoms during treatment may lead to improved care and facilitate shared decision making. In this study, we address this knowledge gap among all patients receiving PC in the Canadian province of Ontario. METHODS: Patients diagnosed with incurable esophageal and gastric cancer who received PC from 2012 to 2017 were identified from the Ontario Cancer Registry. Patients with one or more recorded Edmonton Symptom Assessment System (ESAS) scores in the 12 months following cancer diagnosis were included. The ESAS includes scores from 0 to 10 in nine domains (anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and lack of well-being). Symptom severity is categorized as none-mild (≤ 3), moderate (4-6), or severe (7-10). We focused on potentially modifiable symptoms, i.e. nausea, pain, and anxiety/depression. Logistic regression was used to identify factors associated with moderate-severe ESAS scores in these domains. Among those patients with serial ESAS scores (at 8 ± 2 and 12 ± 2 weeks) receiving chemotherapy, we describe changes during treatment (decrease by ≥ 1 = improved; - 1 > 0 > 1 = unchanged; increase by ≥ 1 = deteriorated). RESULTS: The cohort included 1900 patients who received PC, of whom 79% (1497/1900) had one or more recorded ESAS scores. In multivariate analysis, younger patients were more likely to have moderate-severe scores in nausea (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.23-2.90 [p < 0.01] in patients aged 41-50 years compared with patients aged ≥ 71 years) and pain (OR 1.88, 95% CI 1.36-2.60 [p < 0.01] in patients aged 51-60 years compared with patients aged ≥ 71 years). Compared with males, females were more likely to report moderate-severe scores in anxiety/depression (OR 1.58, 95% CI 1.21-2.08 [p < 0.01]). At 8 ± 2 weeks from PC initiation, symptom scores were unchanged in 19-42% of patients, improved in 30-51% of patients, and deteriorated in 17-35% of patients. The greatest change in symptom burden was observed for appetite (51% improvement) and anxiety/depression (35% deterioration). Similar trends were observed at 12 ± 2 weeks. CONCLUSIONS: In this large, population-based study, we observed that younger patients were more likely to report moderate-severe symptoms in pain and nausea, and females were more likely to report moderate-severe symptoms in anxiety/depression. Anxiety/depression symptoms become increasingly problematic for a substantial proportion of patients receiving PC. Supportive care efforts to mitigate these symptoms in routine practice are needed.

Combined T2 SPAIR, Dynamic Enhancement and DW Imaging Reliably Detect T Staging and Grading of Bladder Cancer With 3.0T MRI.

OBJECTIVES: To evaluate bladder cancer by integrating multiple imaging features acquired using multimodal 3.0T magnetic resonance imaging (MRI). METHODS: We prospectively enrolled 163 consecutive patients including 142 men (mean age, 65.2 years) and 21 women (mean age, 65.8 years). We evaluated the efficiency and reliability of the multiple imaging modalities including T2-weighted spectral attenuated inversion recovery (SPAIR) imaging, dynamic contrast-enhanced (DCE) imaging and diffusion-weighted (DW) imaging, and the imaging feature, apparent diffusion coefficient (ADC) in the identification of the T staging and grading. We compared our imaging findings with the results of histological examination using McNemar's test. We reported the results under the significance of p < 0.05. Approval for the study was obtained from the local institutional review board. RESULTS: The sensitivity and specificity using T2 SPAIR plus DW imaging (sensitivity: 85.2%; specificity: 93.2%), DCE plus DW imaging (sensitivity: 92.4%; specificity: 96.8%), and all the three imaging modalities combined, i.e., T2 SPAIR plus DCE plus DW imaging (sensitivity: 92.5%; specificity: 97.4%), were significantly greater than using T2 SPAIR imaging alone (sensitivity: 74.1%; specificity: 72.2%). One hundred six (93.0%) lesions showed a thin, pedicle arch-like shape and thus primarily demonstrated to be in Ta stage; by contrast, a large number of lesions (137 [85.6%]) were sessile and were found to be in T1 stage. The differences in the ADC were significant between low-grade (877.57 ± 24.15) and high-grade (699.54 ± 23.82) lesions (P < .01). CONCLUSIONS: T2 SPAIR and DCE plus DW imaging provided useful information for evaluating T staging and grading in bladder cancer. Those imaging features to distinguish Ta stage from T1 stage were presented.

The efficacy and safety of Chinese herbal compound or combined with western medicine for pediatric adenoidal hypertrophy: A protocol for systematic review and meta-analysis.

BACKGROUND: Traditional Chinese medicine (TCM) or combined with western medicine in the treatment of pediatric adenoidal hypertrophy has been widely used in clinical practice, but the overall efficacy and safety is still unclear. This paper aims to evaluate the efficacy and safety analysis of TCM or combined with western medicine for pediatric adenoidal hypertrophy. METHODS: PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database (CBM) were searched for randomized controlled trials of TCM or combined with western medicine for pediatric adenoidal hypertrophy from the date of establishment to July 2020, and Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform (ICTRP), and Chinese Clinical Trials Registry (ChiCTR) were searched for unpublished grey literature. Two researchers independently applied RevMan 5.3 software for data extraction and risk assessment of bias. RESULTS: The effectiveness and safety of TCM or combined with western medicine for pediatric adenoidal hypertrophy is evaluated by means of the Adenoid (A) /(Nasopharyngeal (N) ratio, clinical efficacy, integral score of TCM syndromes, clinical single symptom score, disease specific quality of life for children with obstructive sleep apnea 18 items survey (OSA-18), Interleukin 4 (IL-4) and adverse reaction incidence. CONCLUSION: This study will provide theoretical support for the clinical application of TCM or combined with western medicine for pediatric adenoidal hypertrophy. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/J76AG.

The radiation dose tolerance of the brachial plexus: A systematic review and meta-analysis.

PURPOSE: We performed a systematic review and meta-analysis of studies reporting the incidence of radiation induced brachial plexopathy (RIBP) and the associated radiotherapy doses to this structure. METHODS: Databases were queried without language restriction for cohort studies reporting RIBP incidence and associated brachial plexus dose maximum dose (bpDmax). Studies specifying RIBP relative risk (RR) effect size were selected for meta-analysis. RRs for RIBP from each study were converted to a regression coefficient (ß) and standard error corresponding to a continuous representation of bpDmax. The adjusted ß from individual studies were combined using a random effects model and weighted by inverse variance (1/SE2). The trim and fill approach was used to assess publication bias. RESULTS: We identified 25 studies that included 37 unique patient cohorts eligible for analysis. Seventeen cohorts experienced an RIBP incidence ≤5%, of which 6 cohorts exceeded conventional plexus constraints of 60 Gy for bpDmax. Five of the 6 cohorts were simulated with 3D-CT techniques. Meta-analysis of eligible studies demonstrated a significant increase in RIBP risk for each Gy increase in bpDmax (RR, 1.11; 95% CI 1.07-1.15). Results remained significant after adjustment for publication bias and when sensitivity analysis was performed. CONCLUSIONS: Our results suggest that current brachial plexus constraints of 60-66 Gy are safe. Meta-analysis provides a log-linear model to quantify the association of brachial plexus dose and RIBP risk, and thus inform the therapeutic ratio for dose escalation. Further prospective studies reporting dosimetric data can better refine this model and inform brachial plexus constraint guidelines.

Estimating the need for palliative radiotherapy for non-small cell lung cancer: A criterion-based benchmarking approach.

BACKGROUND AND PURPOSE: Estimates of appropriate treatment rates are required for monitoring and improving access to cancer care. Optimal utilization rates for palliative radiotherapy (PRT) for patients with non-small cell lung cancer (NSCLC) remain undefined. We aim to estimate the appropriate PRT rate for the general NSCLC population. MATERIALS AND METHODS: Ontario's population-based cancer registry identified patients with NSCLC who died of their disease between 2006 and 2010. Multivariate analysis identified factors affecting PRT use, enabling us to define a benchmark population with unimpeded access to PRT. Proportion of cases treated in the last 2 years of life (PRT2y) was standardized to overall population characteristics. Benchmarks were compared to province-wide PRT2y rates. RESULTS: Availability of RT at the diagnosing hospital was the dominant determinant of increased PRT utilization. Patients diagnosed at hospitals with on site RT were therefore designated the benchmark population. The standardized benchmark for PRT2y was 56%, compared to the province-wide rate of 49%. The gap between actual and optimal rates varied across patient ages, treatment indications, and geographic regions. CONCLUSIONS: Approximately 56% of patients who die of NSCLC in Ontario need PRT, but many are never treated.

Do radiation oncology outreach clinics affect the use of radiotherapy?

BACKGROUND AND PURPOSE: The scope and effect of radiation oncology (RO) outreach activities within centralized radiotherapy (RT) systems is poorly defined. The purpose of this study was to describe the outreach activities of Ontario's regional cancer centres, and to explore the relationship between radiation oncology (RO) outreach clinics and rates of radiotherapy (RT) utilization at hospitals without RT on site (HWOS-RT). MATERIALS AND METHODS: Ontario RO centres' outreach activities were identified by semi-structured interview. A multivariate analysis determined the association between on-site RT facilities, or presence of RO clinic at HWOS-RT, and RT utilization within one year of diagnosis (RT1Y), for all patients diagnosed with cancer in Ontario in 2011-2012. RESULTS: RO outreach varied widely by region. Of the largest 58 diagnosing hospitals, 14 had RT on-site, 19 had no RT but RO outreach clinic(s) and 25 had no RT or RO clinic. RT was used more frequently for patients diagnosed at hospitals with on-site RT compared to those at HWOS-RT (RT1Y = 35% vs. 29%, RR = 1.32 [95% CI 1.27-1.38]). For HWOS-RT, RT was used more frequently if there was an RO clinic (RT1Y = 31% vs. 29%, RR = 1.06 [95% CI 1.02-1.10]). CONCLUSIONS: RO outreach clinics were associated with a small but significant increase in RT utilization. There is opportunity to improve access to RT by optimizing the effectiveness of RO outreach.

Iron overload induces G1 phase arrest and autophagy in murine preosteoblast cells.

This study aimed to investigate the cell cycle arrest and autophagy induced by iron overload in MC3T3-E1 cells. MC3T3-E1 cells were cultured in different concentrations of ferric ammonium citrate (FAC), and Perls' Prussian blue reaction was used to detect the iron levels of the cells. CCK-8 assays were used to detect the growth of MC3T3-E1. The level of reactive oxygen species (ROS) within cells was investigated with DCFH-DA. PI staining was used to analyze the cell cycle distribution of MC3T3-E1 cells. Finally, the expression levels of cell cycle related proteins, autophagy related proteins, AKT, p38 MAPK, Stat3, and their downstream proteins were detected with Western blot assays. The results showed that the iron levels of MC3T3-E1 cells increased with increasing concentrations of FAC. High levels of ferric ion inhibited proliferation of MC3T3-E1 cells and increased their ROS levels. Additionally, iron overload induced G1arrest in MC3T3-E1 cells and down-regulated the expression of Cyclin D1 , Cyclin D3 , CDK2, CDK4 and CDK6, but up-regulated p27 Kip1. In addition, the expression levels of Beclin-1 and LC3 II increased, but that of p62 decreased. Further experiments showed that the phosphorylation of AKT and its downstream proteins p-GSK-3ß(Ser9) and p-mTOR (Ser2448) were decreased. The levels of p-p38 and p53 were up-regulated while those of cdc25A and p-ERK 1/2 were down-regulated. Phosphorylation of Stat3 and its downstream proteins was all decreased. These results show that iron overload generates ROS, blocks the PI3K/AKT and Jak/Stat3 signal pathways, and activates p38 MAPK, subsequently inducing G1 arrest and autophagy in MC3T3-E1 cells.

A monomer purified from Paris polyphylla (PP-22) triggers S and G2/M phase arrest and apoptosis in human tongue squamous cell carcinoma SCC-15 by activating the p38/cdc25/cdc2 and caspase 8/caspase 3 pathways.

Recent studies have shown that the aqueous, ethanolic extracts and a monomer compound of Paris polyphylla exhibit anticancer activity toward several types of cancer cell lines, but the anticancer activity of (3ß,17α,25R)-spirost-5-ene-3,17-diol 3-O-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-glucopyranoside, a monomer isolated from P. polyphylla (PP), named PP-22, has not been reported previously. In this study, we investigated the effect of PP-22 on human tongue squamous cell carcinoma SCC-15 cells in vitro. MTT assays showed that PP-22 inhibited the growth of SCC-15 cells and had no obvious inhibitory effects on human liver L02 cells. Flow cytometry assays showed that the percentages of apoptotic cells were increased. In addition, cleaved caspase-8, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) could be detected by Western blotting. Flow cytometry also showed that PP-22 triggered S and G2/M phases arrest in SCC-15 cells, and on the other hand, the expression of cyclin A, cyclin E2, cyclin B1, phospho-cell division cycle2 (p-cdc2)(Tyr15), p-Wee1, Myt1, and p53 was upregulated. Moreover, p-p38 levels increased, p-extracellular signal-regulated kinase (ERK) levels decreased, and cdc25B expression was inhibited. Furthermore, the p38/mitogen-activated protein kinase (MAPK) inhibitor SB203580 reversed the increase of the expression level of p38, p-cdc2 (Tyr15), cleaved caspase 3, cleaved PARP, p-p53, and p53 and reversed the decrease in cdc25B expression. In conclusion, these results demonstrated that PP-22 activated p38, inhibited cdc25B, increased p-cdc2 (Tyr15), and triggered S and G2/M phase arrest, as well as activated p53 through the p38-p53 pathway, inhibited the MAPK/ERK pathway, activated the caspase 8/caspase 3 pathway, and triggered the extrinsic apoptotic pathway in SCC-15 cells.

The relationship between time to initiation of adjuvant chemotherapy and survival in breast cancer: a systematic review and meta-analysis.

BACKGROUND: It is known that adjuvant chemotherapy improves survival in women with breast cancer. It is not known whether the interval between surgery and the initiation of chemotherapy influences its effectiveness. PURPOSE: To determine the relationship between time to initiation of adjuvant chemotherapy and survival in women with breast cancer, through a systematic review of the literature and meta-analysis. METHODS: Systematic review of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Database of Controlled Trials, Google Scholar, and abstracts presented at major international oncology conferences. The primary meta-analysis included only high-validity studies which directly measured the time from surgery to initiation of adjuvant chemotherapy and which controlled for major prognostic factors. Outcomes reported in the original studies were converted to a regression coefficient (ß) and standard error corresponding to a 4-week delay in the initiation of chemotherapy. These relative risks were combined in both fixed- and random-effects models. Homogeneity was assessed by the Cochran χ 2 statistic and the I 2 statistic. Potential publication bias was investigated using standard error-based funnel plots. RESULTS: Meta-analysis of 8 high-validity studies demonstrated that a 4-week increase in TTAC was associated with a significant increase in the risk of death in both the fixed-effects model (RR 1.04; 95 % CI, 1.01-1.08) and random-effects model (RR 1.08; 95 % CI, 1.01-1.15). The association remained significant when the most highly weighted studies were sequentially removed from this analysis, and also when additional, lower validity studies were included in this analysis. Funnel plots showed no significant asymmetry to suggest publication bias. CONCLUSIONS: Increased waiting time from surgery to initiation of adjuvant chemotherapy is associated with a significant decrease in survival. Avoidance of unnecessary delays in the initiation of adjuvant chemotherapy has the potential to save the lives of many women with breast cancer.