Concurrent Arm Research Articles

Safety and immunogenicity of Anti PD-L1 (Atezolizumab) given as an immune primer or concurrently with extended field chemoradiotherapy for node positive locally advanced cervical cancer: an NRG Oncology trial (024)

Safety and immunogenicity of Anti PD-L1 (Atezolizumab) given as an immune primer or concurrently with extended field chemoradiotherapy for node positive locally advanced cervical cancer: an NRG Oncology trial (024)

Extrapolating evidence for molecularly targeted therapies from common to rare cancers: a scoping review of methodological guidance

ObjectivesCancer is increasingly classified according to biomarkers that drive tumour growth and therapies developed to target them. In rare biomarker-defined cancers, randomised controlled trials to adequately assess targeted therapies may...

CONCURRENT CHEMORADIOTHERAPY VERSUS ACCELERATED RADIOTHERAPY AFTER INDUCTION CHEMOTHERAPY IN INOPERABLE STAGE III NON-SMALL CELL LUNG CARCINOMA: A PROSPECTIVE COMPARATIVE STUD

INTRODUCTION: There is considerable debate over ideal treatment approach for inoperable stage III non-small cell lung carcinoma. Accelerated radiotherapy is an emerging modality based on it's radio-biological advantage of inhibiting accelerated repopulation and negate the development of radioresistance. .Our study was aimed at comparing the response rate and toxicity pattern between concurrent chemoradiotherapy and accelerated radiotherapy in non-resectable stage III NSCLC patient who have already received induction chemotherapy. MATERIALAND METHODS: Patients with histologically proven non-metastatic, inoperable stage III Non-small cell carcinoma of lung were 2 2 randomized into two groups and was given three cycles of induction chemotherapy with paclitxel (175mg/m ) and cisplatin (80mg/m ). After that 2 patients of control arm received EBRT at a dose of 66Gy (2Gy/fraction/day, 5 days in a week) with concurrent cisplatin (40mg/m ) weekly and patients of study arm received EBRT alone at a dose of 66 Gy (2 Gy /fraction/day, 6 days in a week).Patients were evaluated weekly for acute toxicity during radiation therapy, then six weeks after completion of treatment for response assessment and thereafter every three months for at least twelve months . RESULTS: Overall response rate (Complete response+ Partial response) was higher in study arm (62.5% VS 69.5%,p-value 0.963). Signicantly less higher grade of acute pharyngeal and esophageal toxicity was seen in accelerated radiotherapy arm(45.8% vs 13%,p-value 0.033) than concurrent chemoradiotherapy arm. DFS,PFS were comparable between two arms. CONCLUSION: In the treatment of inoperable stage III NSCLC, after induction chemotherapy both the Accelerated radiotherapy and concurrent chemoradiotherapy were comparable in terms of loco-regional control, toxicity prole, disease free survival and progression free survival.

Matching design for augmenting the control arm of a randomized controlled trial using real-world data

ABSTRACT Randomized clinical trials (RCTs) have often been considered as the gold standard in drug development, but they may not be fully powered due to limited patient population and can even lead to ethical concerns in rare disease studies. In situations like this, real-world data (RWD)/historical data can be utilized to augment or possibly serve as the control arm for the current trial. If a subset of subjects from the RWD/historical trial could be matched to the concurrent control arm subjects and they are deemed comparable following certain criteria, then pooling the matched subjects from the historical control arm and the concurrent control arm can boost the power. In this paper, we propose two matching methods of borrowing historical control data that not only balance key observed baseline covariates but also ensure the comparability of responses between the historical and concurrent controls. Close similarity in response variables among controls reduces Type I error inflation and provides further protection against unmeasured confounding bias, which is a major challenge in using RWD. Simulation studies are conducted to evaluate the empirical performance of the two matching methods in terms of Type I error rate and power, and an illustrative description of a planned study is presented.

Exploring the Potential of External Control Arms created from Patient Level Data: A case study in non-small cell lung cancer

ABSTRACT Randomized controlled trials (RCTs) are the gold standard for evaluation of new medical products. However, RCTs may not always be ethical or feasible. In cases where the investigational product is available outside the trial (e.g., through accelerated approval), patients may fail to enroll in clinical trials or drop out early to take the investigational product. These challenges to enrolling or maintaining a concurrent control arm may compromise timely recruitment, retention, or compliance. This can threaten the study’s integrity, including the validity of results. External control arms (ECAs) may be a promising augmentation to RCTs when encountered with challenges that threaten the feasibility and reliability of a randomized controlled clinical trial. Here, we propose the use of ECAs created from patient-level data from previously conducted clinical trials or real-world data in the same indication. Propensity score methods are used to balance observed disease characteristics and demographics in the previous clinical trial or real-world data with those of present-day trial participants assigned to receive the investigational product. These methods are explored in a case study in non-small cell lung cancer (NSCLC) derived from multiple previously conducted open label or blinded phase 2 and 3 multinational clinical trials initiated between 2004 and 2013. The case study indicated that when balanced for baseline characteristics, the overall survival estimates from the ECA were very similar to those of the target randomized control, based on Kaplan–Meier curves and hazard ratio and confidence interval estimates. This suggests that in the future, a randomized control may be able to be augmented by an ECA without compromising the understanding of the treatment effect, assuming sufficient knowledge, measurement, and availability of all or most of the important prognostic variables.

The role of exercise training on cardiovascular peptides in patients with heart failure: A systematic review and meta-analysis.

BackgroundThe purpose of this systematic review & meta-analysis was to determine the roles of aerobic, resistance or concurrent exercises vs. control (CON) group on B-type natriuretic peptide (BNP) and N-terminal-pro hormone BNP (NT-proBNP) in patients with heart failure.MethodsThe electronic databases of PubMed, Scopus, Web of Science, and Google Scholar were searched up to May 2022 for aerobic vs. CON, resistance vs. CON, and concurrent vs. CON studies on circulating (serum or plasma) levels of BNP and NT-proBNP in patients with heart failure. Non-randomized or randomized controlled trial studies were included. Standardized mean difference (SMD) and 95% confidence intervals (95% CIs) were calculated. This systematic review & meta-analysis was registered in PROSPERO at the University of York with the registration number [CRD42021271632].ResultsA total of 28 articles (37 intervention arms), 26 aerobic intervention arms, 3 resistance intervention arms, and 8 concurrent intervention arms were included. A total of 2563 participants (exercise groups = 1350 and CON groups = 1213) were included. Exercise training significantly decreased NT-proBNP marker [-0.229 (SMD and 95% CI: 0.386 to −0.071), p = 0.005], irrespective of overweight/obesity status. Analysis of subgroup by type of exercise training revealed that there was a significant reduction in the NT-proBNP marker for aerobic exercise group compared to the CON group [-0.336 (SMD and 95% CI: 0.555 to −0.105), p = 0.004], whereas concurrent exercise did not show significant changes in the NT-proBNP marker [-0.134 (SMD and 95% CI: 0.350 to 0.083), p = 0.227]. In addition, exercise training did not significantly change the BNP marker [-0.122 (SMD and 95% CI: 0.322 to 0.079), p = 0.235].ConclusionsThe results suggested that exercise training, especially aerobic exercise can be improved the NT-proBNP concentrations in patients with HF (irrespective of overweight/obesity status), which may be a sign of positive physiological adaptations to aerobic exercise.

Whole body adaptation to novel dynamics does not transfer between effectors.

How does the brain coordinate concurrent adaptation of arm movements and standing posture? From previous studies, the postural control system can use information about previously adapted arm movement dynamics to plan appropriate postural control; however, it is unclear whether postural control can be adapted and controlled independently of arm control. The present study addresses that question. Subjects practiced planar reaching movements while standing and grasping the handle of a robotic arm, which generated a force field to create novel perturbations. Subjects were divided into two groups, for which perturbations were introduced in either an abrupt or a gradual manner. All subjects adapted to the perturbations while reaching with their dominant (right) arm and then switched to reaching with their nondominant (left) arm. Previous studies of seated reaching movements showed that abrupt perturbation introduction led to transfer of learning between arms, but gradual introduction did not. Interestingly, in this study neither group showed evidence of transferring adapted control of arm or posture between arms. These results suggest primarily that adapted postural control cannot be transferred independently of arm control in this task paradigm. In other words, whole body postural movement planning related to a concurrent arm task is dependent on information about arm dynamics. Finally, we found that subjects were able to adapt to the gradual perturbation while experiencing very small errors, suggesting that both error size and consistency play a role in driving motor adaptation.NEW & NOTEWORTHY This study examined adaptation of arm and postural control to novel dynamics while standing and reaching and subsequent transfer between reaching arms. Neither arm nor postural control was transferred between arms, suggesting that postural planning is highly dependent on the concurrent arm movement.

Safety of radiosurgery concurrent with systemic therapy (chemotherapy, targeted therapy, and/or immunotherapy) in brain metastases: a systematic review.

Stereotactic radiosurgery (SRS) is a standard option for brain metastases (BM). There is lack of consensus when patients have a systemic treatment, if a washout is necessary. The aim of this review is to analyze the toxicity of SRS when it is concurrent with chemotherapies, immunotherapy, and/or targeted therapies. From Medline and Embase databases, we searched for English literature published up to April 2020 according to the PRISMA guidelines, using for key words the list of the main systemic therapies currently in use And "radiosurgery," "SRS," "GKRS," "Gamma Knife," "toxicity," "ARE," "radiation necrosis," "safety," "brain metastases." Studies reporting safety or toxicity with SRS concurrent with systemic treatment for BM were included. Of 852 abstracts recorded, 77 were included. The main cancers were melanoma, lung, breast, and renal carcinoma. These studies cumulate 6384 patients. The median SRS dose prescription was 20Gy [12-30] .For some, they compared a concurrent arm with a non-concurrent or a SRS-alone arm. There were no skin toxicities, no clearly increased rate of bleeding, or radiation necrosis with significant clinical impact. SRS combined with systemic therapy appears to be safe, allowing the continuation of treatment when brain SRS is considered.

Prostate Radiotherapy With Adjuvant Androgen Deprivation Therapy (ADT) Improves Metastasis-Free Survival Compared to Neoadjuvant ADT: An Individual Patient Meta-Analysis

There remains a lack of clarity regarding the influence of sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) on outcomes in prostate cancer (PCa). Herein, we evaluate the optimal sequencing of ADT with prostate-directed RT in localized PCa. MEDLINE (1966-2018), Embase (1982-2018), ClinicalTrials.gov, and conference proceedings (1990-2018) were searched to identify randomized trials evaluating the sequencing, but not duration, of ADT with RT. Two randomized phase III trials were identified, and individual patient data were obtained: Ottawa 0101 and NRG Oncology's Radiation Therapy Oncology Group 9413. Ottawa 0101 randomly assigned patients to neoadjuvant or concurrent versus concurrent or adjuvant short-term ADT. Radiation Therapy Oncology Group 9413, a 2 × 2 factorial trial, included a random assignment of neoadjuvant or concurrent versus adjuvant short-term ADT. The neoadjuvant or concurrent ADT arms of both trials were combined into the neoadjuvant group, and the arms receiving adjuvant ADT were combined into the adjuvant group. The primary end point of this meta-analysis was progression-free survival (PFS). The median follow-up was 14.9 years. Overall, 1,065 patients were included (531 neoadjuvant and 534 adjuvant). PFS was significantly improved in the adjuvant group (15-year PFS, 29% v 36%, hazard ratio [HR], 1.25 [95% CI, 1.07 to 1.47], P = .01). Biochemical failure (subdistribution HR [sHR], 1.37 [95% CI, 1.12 to 1.68], P = .002), distant metastasis (sHR, 1.40 [95% CI, 1.00 to 1.95], P = .04), and metastasis-free survival (HR, 1.17 [95% CI, 1.00 to 1.37], P = .050) were all significantly improved in the adjuvant group. There were no differences in late grade ≥ 3 gastrointestinal (2% v 3%, P = .33) or genitourinary toxicity (5% v 5%, P = .76) between groups. The sequencing of ADT with prostate-directed RT has significant association with long-term PFS and MFS in localized PCa. Our findings favor use of an adjuvant over a neoadjuvant approach, without any increase in long-term toxicity.

Robust Adaptive Incorporation of Historical Control Data in a Randomized Trial of External Cooling to Treat Septic Shock.

This paper proposes randomized controlled clinical trial design to evaluate external cooling as a means to control fever and thereby reduce mortality in patients with septic shock. The trial will include concurrent external cooling and control arms while adaptively incorporating historical control arm data. Bayesian group sequential monitoring will be done using a posterior comparative test based on the 60-day survival distribution in each concurrent arm. Posterior inference will follow from a Bayesian discrete time survival model that facilitates adaptive incorporation of the historical control data through an innovative regression framework with a multivariate spike-and-slab prior distribution on the historical bias parameters. For each interim test, the amount of information borrowed from the historical control data will be determined adaptively in a manner that reflects the degree of agreement between historical and concurrent control arm data. Guidance is provided for selecting Bayesian posterior probability group-sequential monitoring boundaries. Simulation results elucidating how the proposed method borrows strength from the historical control data are reported. In the absence of historical control arm bias, the proposed design controls the type I error rate and provides substantially larger power than reasonable comparators, whereas in the presence bias of varying magnitude, type I error rate inflation is curbed.

Concurrent Palliative Chemoradiotherapy versus Definitive Chemoradiotherapy in Poor Prognosis Stage III non-small-cell lung cancer

Abstract Background The palliative role of chemoradiation in treatment of patients with locally advanced non-small-cell lung cancer remains unresolved; Controversy remains about whether long term and high doses radiotherapy provide better results than short course schedules in treatment of inoperable stage III NSCLC and negative prognostic factors poor performance status (PS), large tumor, poor pulmonary functions and comorbidities.Hypofractionated radiotherapy can expose tumors to a high dose of radiation in a short period of time. Methods One hundred and ten patients with locally advanced stage III NSCLC with poor prognosyic factors were randomized to receive either definitive chemoradiation or palliative chemoradiation in cancer department of faculty of medicine of AIN SHAMS UNIVERSITY .Arm (A) patients will receive induction chemotherapy with two cycles of carboplatin(AUC6) and paclitaxel 175mg/m²) cycles every 21 day, the third cycle administrated with radiotherapy with low dose of carboplatin(AUC 2) and paclitaxel 60 mg/m² on day 1& 8 administrated concomitant with the radiotherapy 42 Gy over 15 fraction over 3 weeks. Arm (B) patients will receive standard-dose fractionation of radiation 60Gy/6 weeks 2Gy once per day with concurrent weekly low dose of carboplatin (AUC 2) and paclitaxel 60 mg/m² followed by two cycles of full doses of carboplatin (AUC 6) /paclitaxel 175mg/ m² every 21 days.the primary end points were overall survival and progression free survival;secondary end points were health related quality of life(HRQOL) and toxicity. Results The median follow-up duration was 24 months in surviving patients’ .Median survival and 2-year OS were in concurrent palliative chemoradiation arm 4.7 and 12.3-months respectively and was 7.3 and 17.6 in concurrent definitive chemoradiatiobn arm respectively (p < 0.01). HRQOL was better in the palliative arm during the treatment but remained unchanged in both arms during the follow up visits. There were more hospital admissions related to side effects in the definitive chemoradiation arm (p < 0.05). Conclusions This study confirmed that the definitive chemoradiation was superior to palliative chemoradiation arm with respect to survival.the treatment related toxicity and HRQOL were better in the palliative chemoradiation arm than the definitive arm.

A prospective study comparing induction chemotherapy followed by chemoradiation versus chemoradiation alone in stage III non-small cell lung cancer

Background: Although concurrent chemoradiation (CCRT) is the standard of care for stage III non-small cell lung cancer(NSCLC), the five years overall (OS) survival is very poor. Most of the patients developed distant metastasis later which can be improved by induction chemotherapy. Aims: This study was designed to observe the difference in epidemiology, acute toxicities, overall responses [complete response (CR)+partial response (PR)] after treatment completion, disease-free survival (DFS) and progression-free survival (PFS) at the end of the study. Settings and Design: This was a prospective, interventional, randomized hospital-based study. Methods and Material: Eligible patients were randomized into arm A (CCRT with weekly paclitaxel(P) + Carboplatin(C) with 66 Gray radiation) and arm B (two cycles of induction chemotherapy consisted of P+C followed by CCRT as of arm A. During treatment weekly, after completion of treatment at 6th week and thereafter 3 monthly evaluation was done till the end of study. S tatistical analysis used: Chi-Square and Fisher Exact test did statistical analysis, t-test with 95%CI, Kaplan Meier survival analysis, Log Rank test using SPSS version 18. Results: Among 44 patients, male (88.6%), Smokers (85.1%) were predominant with the most common histology was squamous cell carcinoma (52.4%). Overall response (Complete Response +Partial Response) was higher in Arm B 66.66% but statistically non-significant. Acute toxicities in both the arms were comparable and similar. DFS and PFS in the induction chemotherapy arm (Arm B) were numerically superior to concurrent chemoradiation arm (Arm A) but statistically nonsignificant Conclusion: To conclude there were no significant differences in results between two arms in the present study population. Further studies with the larger sample size and longer duration of follow up are necessary.

A comparative study of two schedules of concomitant Chemo-radiation with Cisplatin in locally advanced Head and Neck Cancer in Southern Rajasthan of India

Introduction: Head and neck cancer is the most common cancer in south-central Asia. It constitutes about 17.7% of all cancers occurring in India. Majority of them present with locoregionally advanced stage. Concurrent chemo-radiotherapy (CCRT) is recognized worldwide as a standard treatment option for locally advanced disease not amenable to surgical resection. Aims: To compare the differences in acute toxicities and response rate between two schedules (weekly and 3-weekly divided dose cisplatin-based) of concomitant chemo-radiation (CCRT) regimens in locally advanced head and neck squamous cell carcinoma (LHNSCC). Methods and Material: Total of 62 eligible patients of LHNSCC who satisfying the eligibility criteria were included in this study. After pre-treatment evaluation, patients were sequentially randomized into two arms: 31 patients were taken in each arm, Arm-A (weekly concurrent cisplatin group) and Arm- B (three weekly divided dose concurrent cisplatin groups). One patient in each arm dropped out due to poor compliance. In both the arms, radiotherapy was delivered to a dose of 66-70 Gy with a telecobalt machine as a conventional fractionation schedule. The primary endpoints of the study were to know the disease response and assessment of acute toxicity profile in both arms. Results: Among the in-field toxicity, we found mucositis as the commonest toxicity in both arms. Incidence of Grade-III (33.33% vs 40%) & Grade-IV mucositis (6.66% vs 10%), acute gastrointestinal toxicity (Nausea- 33.33% vs 46.33% & vomiting- 13.33% vs 20%), and acute renal toxicity (16.66% vs 10%) were found to be slightly higher in 3-weekly arm compared to weekly arm. Our study showed that higher the incidence of neutropenia grade-I (23.33% VS 16.66%) and acute skin reaction (40% vs 33.33%) occurred in the weekly CCRT arm compared to the 3-weekly CCRT arm. In view of treatment compliance and response rate, our study showed 3-weekly arm have a higher compliance rate of scheduled chemotherapy cycles and a higher response rate (CR=80% vs 70%) compared to the weekly arm. Conclusions: The present study concluded that the three weekly divided dose concurrent cisplatin arms having a slightly better response rate with a slight increase in mucosal toxicity while the weekly concurrent cisplatin arm having a reduced requirement of feeding tube placement, colony-stimulating factor and hospitalization for supportive care.

Benchmarking single-arm studies against historical controls from non-small cell lung cancer trials – an empirical analysis of bias

Background: Recent trials of novel agents in ‘rare’ molecular subtypes of non-small cell lung cancer (NSCLC) have used single-arm trial designs and benchmarked outcomes against historical controls. We assessed the consistency of historical control outcomes using docetaxel data from published NSCLC randomized controlled trials (RCTs).Material and methods: Advanced NSCLC RCTs including a docetaxel monotherapy arm were included. Heterogeneity in tumor objective response rates (ORRs), progression-free survival (PFS) and overall survival (OS), and correlations between outcomes and year of trial commencement were assessed.Results: Among 63 trials (N = 10,633) conducted between 2000 and 2017, ORR ranged from 0% to 26% (I2 = 76.1%, pheterogeneity < .0001). Mean of the median PFS was 3.0 months (range: 1.4–6.4), 3-month PFS ranged from 25% to 85% (I2 = 86.0%, pheterogeneity < .0001). Mean of the median OS was 9.1 months (range: 4.7–22.9), 9-month OS ranged from 23% to 79% (I2 = 83.0%, pheterogeneity < .0001). Each later year of trial commencement was associated with 0.3% (p = .046), 0.5% (p = .11) and 0.9% (p = .001) improvement in ORR, 3-month PFS and 9-month OS rates, respectively.Conclusions: There was significant heterogeneity and an improving trend in docetaxel outcomes across trials conducted over 20 years. Benchmarking biomarker-targeted agents against historical controls may not be a valid approach to replace RCTs. Innovative study designs involving a concurrent control arm should be considered.

EP1.01-46 Acute Esophageal Damage in Patients with Inoperable Non-Small Cell Lung Cancer Treated with Concurrent and Sequential Chemoradiotherapy

Acute esophageal damage may be dose-limitation factor for application of the full planning radiotherapy dose in patients with inoperable Non Small Lung Cancer-NSCLC. Combination of chemotherapy and radiotherapy may increase esophageal toxicity, however three-dimensional conformal radiotherapy offers better spearing. To evaluate the treatment results, study of 75 patients was randomly assigned to one of the two treatment arms. In the sequential arm, 26 (34.7%) patients had previously received sequential chemotherapy with 4 cycles of carboplatin and etoposide followed by conformal radiotherapy (RT). In the second concurrent arm, 49 (65.3%) patients received concurrent chemotherapy of cisplatine and etoposide and conformal RT. We described all phases of the conformal RT. Treatment-related toxicities were assessed according RTOG/EORTC criteria. From 2010 to 2013, 73 patients were enrolled in this study. From all included patients, 43 (57.3%) did not present any grade of esophagitis during the treatment. In sequential group 73.1% presented no esophagitis and in concurrent group 49%, respectively. Although there were differences between the two groups, none was statistically significant. The median survival was 13 months for the patients in the sequential arm and 17 months for those in the concurrent treatment arm. The differences were statistically significant (log-rank test p=0.0039). Table 1 and 2 present grade of ezophagitis and the needs of analgesia in the patients of sequential and concurrent treatment arm. The risk of esophagitis was 22%, in patients whose esophageal volume (V50) recieved less than 30% of prescribed dose in comparation, the risk of esophagitis was 71%, in patients whose V50 recieved dose higher than 30% (p=0.0009).View Large Image Figure ViewerDownload Hi-res image Download (PPT) The reason for good tolerability of the combination of chemotherapy and radiotherapy for patients in this study is using three-dimensional conformal radiotherapy. Further improvements may be obtained with more sophisticated radiotherapy techniques or by using radio protective drags.

Utilizing shared internal control arms and historical information in small-sized platform clinical trials

ABSTRACTRecruitment of patients in concurrent control arms can be very challenging for clinical trials for pediatric and rare diseases. Innovative approaches, such as platform trial designs, including shared internal control arm(s), can potentially reduce the needed sample size, improving the efficiency and speed of the drug development program. Furthermore, historical borrowing, which involves leveraging information from control arms in previous relevant clinical trials, may further enhance a clinical trial’s efficiency. In this paper, we discuss platform trials highlighting their advantages and limitations. We then compare various strategies that borrow historical data or information, such as pooling data from different studies, analyzing data from studies separately, test-then-pool, dynamic pooling, and Bayesian hierarchical modeling, which focuses on the meta-analytic-predictive (MAP) prior. We further propose a procedure to illustrate the feasibility of utilizing historical controls under a platform setting and describe the statistical performance of our method via simulations.

A COMPARATIVE STUDY TO EVALUATE THE CONCURRENT CHEMORADIOTHERAPY VERSUS RADIOTHERAPY ALONE IN THE MANAGEMENT OF BREAST CANCER

Background: We designed a study to compare radiotherapy alone in sandwich set up with concurrent chemo radiotherapy in the management of breast cancer.&#x0D; Methods: This study was conducted on 30 patients suffering from advanced breast carcinoma who visited Department of Radiotherapy and Clinical Oncology, S. N. Medical College, Agra. All these patients were referred from Department of Surgery, S.N. Medical College or from other nearby centers. Out of 30 patients 25 patients completed the treatment and were enrolled for analysis.&#x0D; Results: 84.61% of patients had no evidence of disease and were alive without disease in arm A vs 100% in arm B. The overall survival at 1 year was 100% in both the arms. The disease free survival at 1 year was 84.61% in arm-A and 100% in arm-B.&#x0D; Conclusion: The overall adverse effects were higher in ARM-B (concurrent arm) as compared to ARM-A but it was acceptable without any drop out during the treatment.&#x0D; Keywords: Breast cancer, concurrent chemoradiotherapy, neoadjuvant therapy, locally advanced disease.

Sequential versus concurrent use of chemotherapy and endocrine therapy in the adjuvant treatment of ER-positive breast cancer: A systematic review and Bayesian network meta-analysis.

e12040 Background: Chemotherapy followed by endocrine therapy is the standard adjuvant treatment strategy for estrogen receptor-positive breast cancer patients. However, no direct evidence so far demonstrated better efficacy of sequential use of chemotherapy and endocrine therapy over concurrent. Objective: To evaluate the efficacy between sequential and concurrent use of chemotherapy and endocrine therapy in the adjuvant treatment of ER positive breast cancer. Methods: Randomized clinical trials comparing chemotherapy and/or endocrine therapy in the adjuvant treatment of ER positive breast cancer were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted and analyzed in Bayesian analysis. Patients were stratified by menopause status for subgroup analysis. Results: 37 trials were identified with 37225 patients enrolled in total, 37 trials with DFS results and 24 with OS. 3 comparisons were done between sequential and concurrent arms. In DFS analysis, no statistical significance was found in all 3 comparisons [CHE seq/con TAM (HR 1.01, 95%CI 0.8497 - 1.199); CHE seq/con OFS+TAM (HR 0.9119, 95%CI 0.5666 - 1.49); CHE seq/con OFS+AI (HR 1.032, 95%CI 0.6291 - 1.776)]. The same were seen in OS analysis [CHE seq/con TAM (HR 0.9512, 95%CI 0.8053 - 1.125); CHE seq/con OFS+TAM (HR 1.065, 95%CI 0.6344 - 1.789); CHE seq/con OFS+AI (HR 1.069, 95%CI 0.665 - 1.717)]. Rankings were done for preferable treatment recommendations. In DFS analyses, sequential arms ranked higher than concurrent arms [CHE seq/con OFS+AI (1 vs. 3); CHE seq/con OFS+TAM (6 vs. 7); CHE seq/con TAM (8 vs. 8)]. The same tendency was seen in OS analyses [CHE seq/con OFS+AI (1 vs. 2); CHE seq/con TAM (4 vs. 5)] except for CHE seq/con OFS+TAM (11 vs. 6-9). In subgroup ranking results, CHE seq/con OFS+AI and CHE seq/con OFS+TAM showed consistency among comparisons with concurrent arms ranked higher than sequential arms. However, CHE seq TAM ranked higher than CHE con TAM in all comparisons. Conclusions: The combination of chemotherapy and endocrine therapy in the adjuvant treatment of ER positive breast cancer demonstrated equal efficacy either used sequentially or concurrently. However, concurrent arms were recommended over sequential arms in premenopausal patients for better DFS and OS, except for the combination of chemotherapy and tamoxifen which was recommended to be used sequentially. Others: This study has been registered in PROSPERO (CRD42018104889).

Effect of Whitening Toothpastes on Extrinsic Dental Stains

Aim and objectives:To compare the effectiveness of the stain removing property of the whitening toothpastes (silica [Colgate Visible White], silica, papain and bromelain [Whitospark], and silica and calcium carbonate [Snowdent] containing toothpastes) on extrinsic dental stains and to assess the lasting of tooth whitening effect produced by the whitening toothpastes.Materials and methods:It is a randomized, concurrent parallel arm, non-invasive, controlled trial designed to compare the effectiveness of the whitening toothpastes on reducing extrinsic dental stains. Parametric t-test was used.Results:A statistically significant difference can be seen between Groups A and B, Groups B and C, and Groups B and D. Maximum mean and percentage reduction was found in Group B at the end of the second month in stain extent and intensity. A statistically significant difference was seen between subgroups B1 and B2. Maximum mean and percentage reduction was found in subgroup B1 at the end of the fourth month in stain extent and intensity.Conclusion:Silica, papain, and bromelain containing toothpastes (Whitospark) show effectiveness on reducing extrinsic dental stains.

A Mixed-Mode and Incentive Experiment Using Administrative Data

Abstract This research note compares sequential and concurrent web-mail mixed-mode approaches and incentives for a survey on US consumers’ use of financial products, especially when their finances are tight. The sample (n = 2,000) was drawn from credit bureau data. We examine the effects on response rates, survey costs, and possible nonresponse bias in an experiment varying two factors in a 2x2 design: (1) using concurrent or sequential web and then mail survey modes, and (2) different incentive amounts given to initial survey nonrespondents ($5 versus $10). The sequential (web-first) design had a significantly lower response rate (3.9 percent) at week five—before the paper questionnaire was mailed—than the concurrent group (11.0 percent). This difference was nearly fully eliminated by the end of the field period. The higher incentive brought in slightly more respondents in the concurrent arm and slightly fewer respondents in the sequential arm, but neither difference is statistically significant. Compared with the sample frame, respondents in both groups were generally older and had many of the characteristics that come from being older: higher credit scores, more open credit cards, lower credit card utilization, greater likelihood of having a mortgage, and lower likelihood of being delinquent on credit card payments. Given the lower initial response rate and the need for more follow-up mailing, the sequential mixed-mode approach resulted in a higher cost per complete survey.