Benefit Of RT Research Articles

Superior Attentional Efficiency of Auditory Cue via the Ventral Auditory-thalamic Pathway.

Auditory commands are often executed more efficiently than visual commands. However, empirical evidence on the underlying behavioral and neural mechanisms remains scarce. In two experiments, we manipulated the delivery modality of informative cues and the prediction violation effect and found consistently enhanced RT benefits for the matched auditory cues compared with the matched visual cues. At the neural level, when the bottom-up perceptual input matched the prior prediction induced by the auditory cue, the auditory-thalamic pathway was significantly activated. Moreover, the stronger the auditory-thalamic connectivity, the higher the behavioral benefits of the matched auditory cue. When the bottom-up input violated the prior prediction induced by the auditory cue, the ventral auditory pathway was specifically involved. Moreover, the stronger the ventral auditory-prefrontal connectivity, the larger the behavioral costs caused by the violation of the auditory cue. In addition, the dorsal frontoparietal network showed a supramodal function in reacting to the violation of informative cues irrespective of the delivery modality of the cue. Taken together, the results reveal novel behavioral and neural evidence that the superior efficiency of the auditory cue is twofold: The auditory-thalamic pathway is associated with improvements in task performance when the bottom-up input matches the auditory cue, whereas the ventral auditory-prefrontal pathway is involved when the auditory cue is violated.

The Effectiveness of Reminiscence Therapy in Improving Cognitive Functions And Psychological Wellbeing in Older Adults With Early Dementia ‐ The Randomized Control Trial

AbstractBackgroundReminiscence therapy (RT) is a trending type of non‐pharmacological intervention in dementia care. RT is using life histories recalling and re‐experiencing the life events in older people in order to improve their psychological well‐being through the volitional or non‐volitional process of recollecting memories from their past.MethodParticipants' selection inclusion criteria are: (a) aged 65 or above, (b) early stage of dementia that was screened by the Montreal Cognitive Assessment (MoCA) with scoring of 17‐19, and (c) can read written instruction and consent. Participants were randomly assigned by block randomization with randomized block procedure. The participants attended eight group sessions, with each session lasting for 60 minutes. Sessions were administered two times a week over a 4‐week period. Participants' depressive symptoms were evaluated by Geriatric Depression Scale (GDS), Subjective well‐being (the cognitive components) was measured by Satisfaction With Life Scale (SWLS), mood change as measured by Visual Analogue Mood Scale (VAMS). All these evaluation were conducted baseline, mid‐way evaluation and post‐evaluation by a registered Occupational Therapist.ResultForty older people (29 male and 11 female) were eligible for the study. There was significant difference on depressive symptoms (p = .02, t = ‐2.38), mood change (p = .03, t = ‐3.38), but marginally significant in subjective well‐being (p = .05, t = ‐1.03) between intervention and control group. Further analyses were conducted whether depressive symptoms and mood change effect individuals' subjective well‐being. A two‐way ANOVA revealed that there was not a statistically significant interaction between the effects of depressive symptoms and mood change (F(3, 16) = 1.242, p = .311). Simple main effects analysis showed that depressive symptoms did not have a statistically significant effect on subjective well‐being (p = .975). Simple main effects analysis showed that mood change did have a statistically significant effect on subjective well‐being (p < .000).ConclusionThe findings of this study affirmed the benefit of RT to older people with early stage of dementia through improving depressive symptoms, mood and marginally on their subjective well‐being. The research data available support the inclusion of a structured RT as a part of the routine care given to older people. There are some limitations of our study.

Radiation-based Therapy for Muscle-invasive Bladder Cancer: Contemporary Outcomes Across Tertiary Centers

BackgroundRadiation therapy (RT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). ObjectiveTo analyze predictors of complete response (CR) and survival after RT for MIBC. Design, setting, and participantsThis was a multicenter retrospective study of 864 patients with nonmetastatic MIBC who underwent curative-intent RT from 2002 to 2018. Outcome measurements and statistical analysisRegression models were used to explore prognostic factors associated with CR, cancer-specific survival (CSS), and overall survival (OS). Results and limitationsThe median patient age was 77 yr and median follow-up was 34 mo. Disease stage was cT2 in 675 patients (78%) and cN0 in 766 (89%). Neoadjuvant chemotherapy (NAC) was given to 147 patients (17%) and concurrent chemotherapy to 542 (63%). A CR was experienced by 592 patients (78%). cT3–4 stage (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.29–0.63; p < 0.001) and hydronephrosis (OR 0.50, 95% CI 034–0.74; p = 0.001) were significantly associated with lower CR. The 5-yr survival rates were 63% for CSS and 49% for OS. Higher cT stage (HR 1.93, 95% CI 1.46–2.56; p < 0.001), carcinoma in situ (HR 2.10, 95% CI 1.25–3.53; p = 0.005), hydronephrosis (HR 2.36, 95% CI 1.79–3.10; p < 0.001), NAC use (HR 0.66, 95% CI 0.46–0.95; p = 0.025), and whole-pelvis RT (HR 0.66, 95% CI 0.51–0.86; p = 0.002) were independently associated with CSS; advanced age (HR 1.03, 95% CI 1.01–1.05; p = 0.001), worse performance status (HR 1.73, 95% CI 1.34–2.22; p < 0.001), hydronephrosis (HR 1.50, 95% CI 1.17–1.91; p = 0.001), NAC use (HR 0.69, 95% CI 0.49–0.97; p = 0.033), whole-pelvis RT (HR 0.64, 95% CI 0.51–0.80; p < 0.001), and being surgically unfit (HR 1.42, 95% CI 1.12–1.80; p = 0.004) were associated with OS. The study is limited by the heterogeneity of different treatment protocols. ConclusionsRT for MIBC yields a CR in most patients who elect for curative-intent bladder preservation. The benefit of NAC and whole-pelvis RT require prospective trial validation. Patient summaryWe investigated outcomes for patients with muscle-invasive bladder cancer treated with curative-intent radiation therapy as an alternative to surgical removal of the bladder. The benefit of chemotherapy before radiotherapy and whole-pelvis radiation (bladder plus the pelvis lymph nodes) needs further study.

Re-Thinking Clinicopathologic Risk Assessment in DCIS: Pooled Data from Validation Studies Comparing a 7-gene DCIS Assay to Clinicopathologic Features Alone

<h3>Purpose/Objective(s)</h3> There is a need for a tool to predict recurrence risk and RT benefit to enable personalized management of DCIS after breast conserving surgery (BCS). Clinicopathologic (CP) factors alone have failed to identify a low-risk group with little benefit from RT, or a high-risk group with high recurrence risk after RT. The purpose of this study was to prospectively validate a novel biosignature, Residual Risk Subtype (RRt), integrated with the 7-gene DCIS assay to assess 10yr ipsilateral breast recurrence (IBR) rates and RT benefit compared to CP criteria alone. <h3>Materials/Methods</h3> Women (n=926) from four international cohorts treated with BCS with negative margins had FFPE tissue samples analyzed at a CLIA lab. The 7-gene DCIS assay combines biomarkers with CP factors (age, size, palpability, and margin status) using an algorithm and reports a decision score (DS). Women were classified into 3 risk groups, using DS (0-10) with integrated RRt (yes/no): 1) Low Risk DS ≤2.8 without RRt), 2) Elevated Risk (DS >2.8 without RRt), 3) Residual Risk (DS >2.8 with RRt). Within these 3 biosignature risk groups, IBR Kaplan-Meier rates by RT treatment and Cox proportional hazard ratios for RT-effect were assessed and reported by CP criteria, including RTOG 9804 study ‘good-risk' groupings. <h3>Results</h3> The biosignature classified 37% of the women as Low Risk who had low 10yr IBR rates with or without RT (4.8% vs 5.6%) and 43% as Elevated Risk who had an 20.6% IBR rate without RT and 4.9% after RT, which was an 80% IBR benefit from RT (p<0.001). The significant benefit persisted even in 'good risk' CP patients (∼17% IBR without RT and ∼6% with RT, p<0.03). 20% of women were classified as Residual Risk and had a 42.1% IBR rate without RT and a significantly elevated IBR rate of 14.7% after RT (p<0.001). The distribution of patients in the 3 biosignature risk groups differed by CP criteria (RTOG 9804 'good-risk', or young age or high grade). However, once classified into these 3 biosignature risk groups, the IBR rates and RT benefit were independent of CP criteria. About 30% of women with a high-risk CP profile were re-classified as Low Risk by the biosignature with almost no benefit of RT while ∼30% were re-classified as Residual Risk with ∼14% IBR risk after RT. In women with favorable CP criteria, the biosignature reclassified > 50% of patients as Elevated Risk or Residual Risk, where Residual Risk patients had high IBR (27.1%) risk remaining after BCS. <h3>Conclusion</h3> The 7-gene predictive DCIS assay integrated with the novel Residual Risk Subtype (RRt) biosignature classified women into 3 risk groups with distinct 10yr IBR rates and RT-benefit profiles. Within biosignature risk groups, CP criteria were not prognostic or predictive for 10yr IBR rates or RT benefit while a clear delineation was seen for the 3 risk groups. The incorporation of genomic information yields superior risk and RT benefit prediction as compared to CP features alone.

The Prognostic Value of Liquid Biopsies for Benefit of Salvage Radiotherapy in Relapsed Oligometastatic Prostate Cancer.

Simple SummaryAround 30% of patients with oligometastatic prostate cancer relapse will benefit from local PET/CT-guided ablative radiotherapy (RT) with improved progression-free and ADT (Androgene Deprivation Therapy)-free survivals. Therefore, there is an urgent need for predictive testing for therapeutic benefits prior to initiation. Various tests have already been established on tumor specimens for the prediction of prostate cancer’s behavior or therapy outcome. However, in imaging-proven relapse tumor tissue from the local recurrence or metastases is often not available. Hence, there is a need for a liquid biopsy-based testing. We aimed to assess the prognostic value of CTCs- associated mRNA and blood-derived RNA for the benefit of PSMA PET-guided salvage RT in oligometastatic prostate cancer relapses. Significant correlations were found between the relative transcript levels of several investigated genes and clinicopathological parameters. Furthermore, distinct “transcriptional signatures” were found in patients with temporary and long-term benefits from RT.To assess the prognostic value of “liquid biopsies” for the benefit of salvage RT in oligometastatic prostate cancer relapse, we enrolled 44 patients in the study between the years 2016 and 2020. All the patients were diagnosed as having an oligometastatic prostate cancer relapse on prostate-specific membrane antigen (PSMA)-targeted PET-CT and underwent irradiation at the Department of Radiotherapy at the Hannover Medical School. Tumor cells and total RNA, enriched from the liquid biopsies of patients, were processed for the subsequent quantification analysis of relative transcript levels in real-time PCR. In total, 54 gene transcripts known or suggested to be associated with prostate cancer or treatment outcome were prioritized for analysis. We found significant correlations between the relative transcript levels of several investigated genes and the Gleason score, PSA (prostate-specific antigen) value, or UICC stage (tumor node metastasis -TNM classification of malignant tumors from Union for International Cancer Control). Furthermore, a significant association of MTCO2, FOXM1, SREBF1, HOXB7, FDXR, and MTRNR transcript profiles was found with a temporary and/or long-term benefit from RT. Further studies on larger patients cohorts are necessary to prove our preliminary findings for establishing liquid biopsy tests as a predictive examination method prior to salvage RT.

Adjuvant Treatment of Gastric Cancer in the D2 Dissection Era: A Real-life Experience from a Multicenter Retrospective Cohort Study.

BackgroundThe role of radiotherapy in the adjuvant treatment of gastric cancer (GC) remains to be elucidated. This study aimed to assess the additional benefit of radiotherapy in the adjuvant treatment of GC.Materials and methodsIn this retrospective cohort study, we included 230 gastric adenocarcinoma patients who underwent D2 dissection between January 2004 and December 2019. Patients without R0 resection, who underwent metastasectomy at surgery, and treated with the neoadjuvant treatment were excluded. The co-primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were the locoregional and distant metastasis risk and adverse events (AEs) leading to treatment discontinuation.ResultsOne hundred and sixty-six and 64 patients were included in the chemoradiotherapy (CRT) and chemotherapy (ChT) arms, respectively. The median OS was 135.8 months [interquartile range (IQR): 99.4–172.2] and 97 months (IQR: 59.7–134.3) in the CRT and the ChT arms, respectively. No statistical significance was observed between the arms in OS (p = 0.3). Locoregional or distant recurrence rates were similar in each group. AEs leading to treatment discontinuation were higher in the CRT arm than in the ChT arm (13.2 vs 9.3%), and the difference between the arms was not statistically significant (p = 0.4).ConclusionIn this real-life study, we established that there was no additional benefit of RT in GC patients who underwent D2 dissection.How to cite this articleYekedüz E, Doğan İ, Birgi SD, et al. Adjuvant Treatment of Gastric Cancer in the D2 Dissection Era: A Real-life Experience from a Multicenter Retrospective Cohort Study. Euroasian J Hepato-Gastroenterol 2021;11(2):51–58.

Renal Transplantation Improves Erectile Function in Patients with End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

Erectile dysfunction has a lower prevalence in renal transplant recipients compared to dialysis patients. Despite this observation, the effect of renal transplantation on erectile function remains unknown. We aimed to assess the role of renal transplantation on erectile function and to determine potential factors improving or deteriorating erectile dysfunction. We conducted a systematic review and random effects meta-analysis of observational studies comparing erectile function preoperatively and postoperatively in renal transplant recipients (PROSPERO ID: CRD42020189580). Records reporting relevant outcomes were identified through search of PubMed®, Embase®, Cochrane Library and Scopus® databases from inception to September 2020. Judgment of the strength of evidence was performed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We included 20 studies with 1,695 renal transplant recipients. At postoperative evaluation the number of patients with erectile dysfunction was reduced (RR 1.21, 95% CI 1.02-1.45, I2=88%). Renal transplant recipients reported an improvement in erectile function (RR 2.53, 95% CI 1.44-4.44, I2=90%) and the mean International Index of Erectile Function score increased by 3.04 points (95% CI 0.63-5.45, I2=96%) after renal transplantation. These effects were not demonstrated in the sensitivity analysis. In individuals reporting severe erectile dysfunction, no favorable effect of renal transplantation was observed (RR 1.51, 95% CI 0.85-2.68, I2=33%). For all outcomes the strength of evidence was considered low or very low due to methodological concerns and high heterogeneity among the included studies. Renal transplantation improves erectile function and the risk of erectile dysfunction reduces postoperatively compared to preoperatively. However, evidence on the matter is mostly based on low quality data. More studies with standardized outcomes are needed to validate and strengthen our findings.

Incorporating sarcopenia and inflammation with radiation therapy in patients with hepatocellular carcinoma treated with nivolumab.

We investigated the combined effects of sarcopenia and inflammation on outcomes in patients with HCC treated with nivolumab. We reviewed 102 patients treated with nivolumab between 2017 and 2018. Sarcopenia was diagnosed when the L3 skeletal muscle indices were < 42cm2/m2 and < 38cm2/m2 in men and women, respectively. Baseline neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count were used as surrogate markers of inflammation and immune cell reservoir. High NLR (hNLR) was defined as NLR ≥ 3, and severe lymphopenia (sLP) was defined as lymphocyte < 800/μL. The overall survival (OS) and progression-free survival (PFS) were analyzed. With a median follow-up of 21.9 (interquartile range, 8.3-58.3) months, patients with sarcopenia showed shorter OS than those without sarcopenia (median, 2.9 vs. 7.5months, respectively). Patients with either hNLR or sLP exhibited inferior survival than those without risk factor (median OS, 2.8 vs. 14.5months; median PFS, 1.3 vs. 3.7months, respectively). Among 70 patients treated with RT, benefit of RT was observed in patients with sarcopenia or those without hNLR/sLP (all p < 0.05). After multivariable analysis, RT, hNLR/sLP, albumin-bilirubin (ALBI) grade, and alpha-fetoprotein were significantly associated with OS (all p < 0.05), and hNLR/sLP was also associated with decreased PFS together with ALBI grade, alpha-fetoprotein, and RT (all p < 0.05). The current study hypothetically demonstrated that the risk group stratified by hNLR/sLP outweighs the significance of sarcopenia in predicting outcomes after nivolumab. Furthermore, patients with sarcopenia might benefit from RT, especially those without risk factors of hNLR/sLP.

Abstract IA15: Suppression of intratumoral regulatory T cells restores radiosensitivity in head and neck cancer: Role for Stat3 inhibition

Abstract Radiation is commonly used in the definitive management of for head and neck cancer. Yet, many patients still fail treatment and develop resistance, especially non-virally driven tumors. Head and neck tumors are highly enriched in regulatory T cells that dampen the response to radiotherapy by creating an immune-inhibitory microenvironment. A key way by which CD4 T cells convert to FOXP3 positive regulatory T cells (Tregs) is through activation of STAT3. We explored mechanisms of Treg signaling and infiltration and assessed their modulation by RT in murine models of head and neck squamous cell carcinoma (HNSCC). Mechanisms of Treg infiltration were investigated in orthotopic murine HNSCC tumors using flow cytometry, multiplex cytokine arrays and targeted therapeutics. Mice were treated with STAT3 ASO, anti-CTLA-4, anti-CD25, and/or anti-PD-L1 alone and in combination with RT. Tumor growth and survival were assessed. Flow cytometry was used to assess phenotypic and functional changes in intratumoral T-cell populations. Multiplex ELISA was performed for assessment of cytokines. Treatment with anti-CD25 concurrently with RT led to tumor eradication, enhanced T-cell cytotoxicity, induced an antitumor antigen-specific memory response, decreased Tregs, and improved survival in orthotopic HNSCC tumor-bearing mice. Treg depletion induced an influx of CD8 and CD4 T cells when combined with RT. In addition, Treg depletion in combination with RT transformed myeloid populations, decreasing M2 macrophages and myeloid-derived suppressor cells (MDSCs) and increasing M1 macrophages. In contrast, RT alone or when combined with anti-CTLA4 and/or anti-PD-L1 did not lead to durable tumor control. To assess whether STAT3 inhibition can target Tregs we employed the STAT3 anti-sense oligonucleotide, AZD5149. STAT3 inhibition in combination with RT, but not as single agent, led to significant tumor growth delay and resulted in significant downregulation of immunosuppressive cytokines including TGF-β1 and IL10 and upregulation of IL2. Analysis of immune populations showed that STAT3 inhibition when combined with RT significantly decreases intratumoral Tregs and enhanced effector T-cell function. Experiments in nude mice demonstrated complete abolishment of the benefit of STAT3 ASO and RT, demonstrating the dependency on T cells for achieving tumor control. These data reveal a critical role for Tregs in mediating resistance to RT. Targeted depletion of Tregs represents an important mechanism of sensitizing tumors to RT. We propose that STAT3 inhibition is a viable and potent therapeutic target against Tregs. Our data support the design of clinical trials integrating STAT3 ASO in the standard of care for cancer patients receiving RT. Citation Format: Sana Karam. Suppression of intratumoral regulatory T cells restores radiosensitivity in head and neck cancer: Role for Stat3 inhibition [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr IA15.

“Radiotherapy for older women (ROW)”: A risk calculator for women with early-stage breast cancer

ObjectiveAmong older adult women with early-stage breast cancer who undergo lumpectomy, the benefits of radiotherapy vary according to tumor characteristics and life expectancy. We aimed to develop a risk calculator to predict individualized probability of long-term survival and local recurrence, accounting for these factors. MethodsWe developed a simulation model to estimate an individual patient's risk of local recurrence and all-cause mortality according to age, comorbidities, functional status, tumor characteristics, and radiotherapy status. We integrated two existing prediction models, the Early Breast Cancer Trialist's Collaborative Group prediction model for breast cancer specific outcomes and ePrognosis for life expectancy. An online risk calculator “Radiotherapy for Older Women (ROW)” was developed through an iterative multi-stage process, that included individual consultation and group meetings with an advisory committee (AC) comprised of patients, advocates, clinicians, and researchers. ResultsWe developed the tool over 40 months and had 15 group meetings. The risk calculator developed as a simulation model with 16 factors (5 tumor-related, 3 demographic, 4 comorbidities, and 4 functional statuses). Across 56,700 simulated scenarios, the benefit of RT in terms of absolute 10-year local recurrence reduction, ranged from 0% to 34%, depending on individual characteristics. Based on feedback from the AC, overall survival and local recurrence were chosen as the output for ROW, with these outcomes displayed numerically (percentages and natural frequencies) and graphically (pictographs). ConclusionsThis tool “ROW” could facilitate shared decision making regarding receipt of radiotherapy for older women with early breast cancer. Additional studies to examine usability testing are underway.

Probing early attention following negative and positive templates.

In visual search tasks, cues indicating the upcoming distractor color can benefit search performance compared with uninformative cues. However, benefits from these negative cues are consistently smaller than benefits from positive cues (cuing target color), even when both cues are equally informative. This suggests that using a negative template is less effective than using a positive template. Here, we contrast the early attentional effects of negative and positive templates using the letter probe technique. On most trials, participants searched for a shape-defined target after receiving a positive, negative, or neutral color cue. On occasional probe trials, letters briefly appeared on the search items, and participants reported as many letters as possible. Examining the proportion of letters reported on potential targets versus distractors provided a snapshot of attentional allocation at the time of the probe. Across probes at 100, 250, and 400 ms, participants recalled more letters on target-colored objects than letters on distractor-colored objects following both negative and positive cues. These cuing benefits on probe report trials were larger at later probe times than early probe times, indicating both types of cues became more effective across time. Importantly, negative cue probe benefits were consistently smaller than positive cue benefits. Finally, following an extremely short probe (25 ms), we found no RT benefit following negative cues as well as no evidence that negatively cued items capture attention. These results help explain the previously reported differences in RT benefit following positive and negative cues, and support the idea of early active attentional suppression.

Surface microrelief changes affect the soil and water conservation benefits of rainwater harvesting tillage operation during rainfall events

AbstractReservoir tillage (RT) improves the soil rainwater harvesting capacity and reduces soil erosion on cropland, but there is some debate regarding its effectiveness. The objective of this study was to further verify the effect of RT on soil erosion and explore the reasons for this effect by analysing microrelief changes during rainfall. Rainfall intensities of 60, 90, and 120 mm/hr and three slope degrees (5, 15, and 25°, representing gentle, medium, and steep slopes) were considered. A smooth surface (SS) served as the control. The microrelief changes were determined based on digital elevation models, which were measured using a laser scanner with a 2‐cm grid before and after rainfall events. The results showed that compared with the values for the SS, RT reduced both the runoff and sediment by approximately 10‐20% on the gentle slope; on the medium slope, although RT also reduced the runoff in the 90‐ and 120‐mm/hr intensity rainfall events, the sediment increased by 158.90% and 246.08%; on the steep slope, the sediment increased by 92.33 to 296.47%. Overall, when the runoff control benefit of RT was lower than 5%, there was no sediment control benefit. RT was effective at controlling soil loss on the gentle slopes but was not effective on the medium and steep slopes. This is because the surface depressions created by RT were filled in with sediment that eroded from the upslopes, and the surface microrelief became smoother, which then caused greater soil and water loss than that on an SS at the later rainfall stage.

T1-2N0M0 Triple-Negative Breast Cancer Treated With Breast-Conserving Therapy Has Better Survival Compared to Mastectomy: A SEER Population-Based Retrospective Analysis

BackgroundFor early-stage breast cancer, the two current mainstay treatments are breast-conserving therapy (BCT; lumpectomy followed by radiotherapy [RT] and BCT) and mastectomy. Generally, triple-negative breast cancer (TNBC) is more aggressive compared to hormone receptor–positive breast cancer. We sought to investigate the effect of BCT compared to mastectomy on overall survival (OS) and breast cancer–specific survival (BCSS) in T1-2N0M0 TNBC. Patients and MethodsA population-based retrospective analysis was performed using the Surveillance, Epidemiology, and End Results (SEER) database. Patients included in the analysis were divided into 3 groups according to surgical modality and RT: BCT, mastectomy alone, and mastectomy with RT. The survival end points were OS and BCSS, and survival analysis was performed by the Kaplan-Meier method and the log-rank test among treatment types. ResultsA total of 14,910 female subjects with T1-2N0M0 TNBC diagnosed between 2010 and 2014 were included. A total of 7381 patients had BCT; 6967 had mastectomy alone, and 562 had mastectomy with RT. Patients treated with BCT had better OS (log-rank P < .05) and BCSS (log-rank P < .05) than those receiving mastectomy with or without RT. The 5-year OS was 88.6% for BCT, 83.0% for mastectomy alone, and 79.6% for mastectomy with RT. The 5-year BCSS was 94.3% for BCT, 93.3% for mastectomy alone, and 83.7% for mastectomy with RT. ConclusionIn patients with T1-2N0M0 TNBC, BCT was associated with superior OS and BCSS compared to mastectomy with or without RT. After mastectomy, there was no evidence of survival benefit of RT.

Carbon-ion radiotherapy for lymph node oligo-recurrence: a multi-institutional study by the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS)

BackgroundThe efficacy of carbon-ion radiotherapy (C-ion RT) for lymph node (LN) oligo-recurrence has only been evaluated in limited single-center studies. We aimed to investigate the benefit of C-ion RT for LN oligo-recurrence in a large multi-center study.MethodsPatients who received C-ion RT between December 1996 and December 2015 at 4 participating facilities and who met the following eligibility criteria were included: (i) histological or clinical diagnosis of LN recurrence; (ii) controlled primary lesion; (iii) no recurrence other than LN; (iv) LN recurrence involved in a single lymphatic site; and (v) age ≥ 20 years.ResultsA total of 323 patients were enrolled. Median follow-up period was 34 months for surviving patients. The most common dose fractionation of C-ion RT was 48.0 Gy (relative biological effectiveness) in 12 fractions. Forty-seven patients had a history of RT at the recurrent site. The 2-year local control (LC) and overall survival (OS) rates after C-ion RT were 85% and 63%, respectively. Only 1 patient developed grade-3 toxicity. Factors such as LN diameter, histology, and history of previous RT did not correlate with LC. Smaller diameters (< 30 mm) and numbers (≤ 3) of LN metastases as well as longer disease-free intervals post-primary therapy (≥ 16 months) were associated with significantly better OS.ConclusionsC-ion RT for LN oligo-recurrence appeared to be effective and safe. C-ion RT may provide a survival benefit to patients with LN oligo-recurrence, particularly to those with few LN metastases, smaller LN diameters, and longer disease-free intervals.

RT Slowing to Valid Cues on a Reflexive Attention Task in Children and Young Adults.

Peripheral cueing tasks can be used to measure reflexive (automatic) attention. In these tasks, increases in response time or RT (costs) typically follow contralateral (invalid) cues as attention must move from the location of the cue to the target. Reductions in RT (benefits) to a target typically follow ipsilateral (valid) cues because the cue draws attention to where the target will appear. Two exceptions to RT benefits are inhibition of return (IOR) and masking. IOR is the tendency to respond slower to targets that appear in locations attended within the last 200–2000 ms. Masking occurs when the visibility of a target is blocked by another stimulus (e.g., the cue). Herein, we describe two experiments, both using a modified Posner task with “earth rockets” as cues and “alien spaceships” as targets. Cues were equally likely to appear on the left or right side of a display following targets. Participants were instructed to press a left or right key corresponding to a left or right target. In Experiment 1, we obtained data from 203 children (10.58–16.55 years old). We discovered unexpected costs following cues that typically provide RT benefits. In Experiment 2, we explored IOR, masking, and age differences in the occurrence of these costs. We manipulated the cue-target temporal distance (“stimulus onset asynchrony” or SOA) to explore IOR and the cue-target spatial distance to explore masking. We also considered a wider age range. Sixty-three children and 41 young adults participated. Experiment 2 revealed a three-way interaction between SOA, spatial distance, and age. At the shorter SOA (100 ms) and moderate spatial distance, unexpected costs followed valid cues for younger children (7.07–10.15 years old). These costs also occurred in young adults (18.00–23.02 years old) following far distance cues at this SOA. At the longer SOA (200 ms), these costs followed moderate and far cues for younger children and near cues for young adults. Older children (10.31–14.92 years) did not have unexpected costs. We explain the findings in terms of masking, IOR, and possible developmental mechanisms.

TEDDI: radiotherapy delivery in deep inspiration for pediatric patients \u2212 a NOPHO feasibility study

BackgroundRadiotherapy (RT) delivered in deep inspiration breath-hold (DIBH) is a simple technique, in which changes in patient anatomy can significantly reduce the irradiation of the organs at risk (OARs) surrounding the treatment target. DIBH is routinely used in the treatment of some adult patients to diminish the risk of late effects; however, no formalized studies have addressed the potential benefit of DIBH in children.Methods/DesignTEDDI is a multicenter, non-randomized, feasibility study. The study investigates the dosimetric benefit of RT delivered in DIBH compared to free breathing (FB) in pediatric patients. Also, the study aims to establish the compliance to DIBH and to determine the accuracy and reproducibility in a pediatric setting. Pediatric patients (aged 5–17 years) with a tumor in the mediastinum or upper abdomen with the possible need of RT will be included in the study. Written informed consent is obligatory. Prior to any treatment, patients will undergo a DIBH training session followed by a diagnostic PET/CT- or CT-staging scan in both DIBH and FB. If the patient proceeds to RT, a RT planning CT scan will be performed in both DIBH and FB and two separate treatment plans will be calculated. The superior treatment plan, i.e. equal target coverage and lowest overall dose to the OARs, will be chosen for treatment. Patient comfort will be assessed daily by questionnaires and by adherence to the respiratory management procedure.DiscussionRT in DIBH is expected to diminish irradiation of the OARs surrounding the treatment target and thereby reduce the risk of late effects in childhood cancer survivors.Trial registrationThe Danish Ethical Committee (H-16035870, approved November 24th 2016, prospectively registered). The Danish Data Protection Agency (2012–58-0004, approved January 1st 2017, prospectively registered). Registered at clinicaltrials.gov (NCT03315546, October 20th 2017, retrospectively registered).

The population benefit of evidence-based radiotherapy: 5-Year local control and overall survival benefits

BackgroundTo describe the population benefit of radiotherapy in a high-income setting if evidence-based guidelines were routinely followed. MethodsAustralian decision tree models were utilized. Radiotherapy alone (RT) benefit was defined as the absolute proportional benefit of radiotherapy compared with no treatment for radical indications, and of radiotherapy over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemoradiotherapy over RT. Five-year local control (LC) and overall survival (OS) benefits were measured. Citation databases were systematically queried for benefit data. Meta-analysis and sensitivity analysis were performed. Findings48% of all cancer patients have indications for radiotherapy, 34% curative and 14% palliative. RT provides 5-year LC benefit in 10.4% of all cancer patients (95% Confidence Interval 9.3, 11.8) and 5-year OS benefit in 2.4% (2.1, 2.7). CRT provides 5-year LC benefit in an additional 0.6% of all cancer patients (0.5, 0.6), and 5-year OS benefit for an additional 0.3% (0.2, 0.4). RT benefit was greatest for head and neck (LC 32%, OS 16%), and cervix (LC 33%, OS 18%). CRT LC benefit was greatest for rectum (6%) and OS for cervix (3%) and brain (3%). Sensitivity analysis confirmed a robust model. InterpretationRadiotherapy provides significant 5-year LC and OS benefits as part of evidence-based cancer care. CRT provides modest additional benefits.

Fragile temporal prediction in patients with schizophrenia is related to minimal self disorders

Patients with schizophrenia have difficulty in making sensory predictions, in the time domain, which have been proposed to be related to self-disorders. However experimental evidence is lacking. We examined both voluntary and automatic forms of temporal prediction in 28 patients and 24 matched controls. A visual cue predicted (temporal cue) or not (neutral cue) the time (400 ms/1000 ms) at which a subsequent target was presented. In both patients and controls, RTs were faster for targets presented after long versus short intervals due to the temporal predictability inherent in the elapse of time (“hazard function”). This RT benefit was correlated with scores on the EASE scale, which measures disorders of the self: patients with a high ‘self-awareness and presence’ score did not show any significant benefit of the hazard function, whereas this ability was preserved in patients with a low score. Moreover, all patients were abnormally sensitive to the presence of “catch” trials (unexpected absence of a target) within a testing block, with RTs actually becoming slower at long versus short intervals. These results indicate fragility in patients’ ability to continuously extract temporally predictive information from the elapsing interval. This deficit might contribute to perturbations of the minimal self in patients.

Feasibility of Postoperative Radiotherapy Using Conventional Fractionation for Lymph Node Metastasis from Cutaneous Melanoma

In the present study we assessed if postoperative radiotherapy (PORT) using conventional fractionation confers a benefit in cutaneous melanoma patients with lymph node (LN) metastasis. Sixty-two patients with axillary or inguinal LN metastasis were retrospectively reviewed. Twenty-eight patients received PORT. The median RT dose was 50 Gy in 25 fractions. The high-risk group was defined by the presence of any of the following: ≥3 LNs, size ≥3 cm, extranodal extension. The median follow-up time was 34 months. PORT showed a significant benefit on 5-year axilla-inguinal recurrence-free survival (RFS) in high-risk patients (RT 100% vs. No-RT 37%, p=0.001). There was also a benefit of RT on 5-year out-field RFS in the high-risk population (RT 93% vs. No-RT 29%, p=0.002). There were no ≥grade 2 lymphedemas after RT. PORT using conventional fractionation for high-risk LN metastasis from cutaneous melanoma is feasible with comparable regional control and minimal toxicity.

Risk factors associated with metastatic site failure in patients with high-risk neuroblastoma.

10557 Background: This retrospective study sought to identify predictors of metastatic site failure (MSF) in patients with high-risk (HR) neuroblastoma (NB). Methods: Seventy-six patients with HR NB treated on prospective trials at from 1997 to 2014 were eligible for inclusion. All patients were treated with induction chemotherapy (chemo) with surgery followed by myeloablative chemo &amp; stem cell rescue. Primary &amp; metastatic site (MS) RT were applied according to institutional protocol. CT &amp; I-123 MIBG scans were used to assess Curie scores at diagnosis, post-induction, post-transplant &amp; failure. Overall (OS), &amp; progression-free survival (PFS) were described using the Kaplan-Meier estimator. Cox proportional hazards frailty (cphfR) &amp; CPH regression (CPHr) were used to identify covariates predictive of MSF &amp; new site MSF. Results: Forty-two (55%) patients had documented MSFs. Consolidative MS RT was applied to 30 MSs in 10 patients. Original site MSF occurred in 146 of 383 (38%) &amp; 18 of 30 (60%) non-irradiated &amp; radiated MSs respectively. Original site MSF occurred in post-induction MIBG avid lesions in 68 of 81 (84%) &amp; 12 of 14 (85%) non-irradiated &amp; radiated MSs respectively. The median OS &amp; PFS were 61 mo (95% CI 42.6-NR) &amp; 24.1 mo (95% CI 16.5-38.7). Univariate cphfR identified an increased hazard for original MSF when MIBG avid following induction chemo (HR 4.9, 95%CI 1.1-20.9, p = 0.03) &amp; transplant (HR 7.3 95%CI 1.8-30.2, p = 0.006) relative to lesions that cleared after induction. Notably, MS RT nor site location did not modify the hazard for MSF. Multivariate CPHr identified inability to undergo transplant (HR 32.4 95%CI 9.3-96.8, p &lt; 0.001) &amp;/or maintenance chemo (HR 5.2, 95%CI 1.7-16.2, p = 0.005) &amp; the presence of lung metastases (HR 4.4 95%CI 1.7-11.1, p = 0.002) at diagnosis as predictors of new site MSF. The new MSF free survival at 3 years was 25% vs. 87% in patients with high-risk factors relative to those without the risk factors suggesting limited benefit of consolidative MS RT in this population. Conclusions: Metastatic lesions that remained MIBG avid following induction chemo &amp; post-transplant had an increased hazard for MSF. Consolidative site RT likely has limited benefit in patients with HR features.