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1.
Objective
To investigate the impact of 5?alpha-reductase inhibitor (5-ARI) use on radiotherapy outcomes for localized prostate cancer.Patients and methods
We included 203 patients on a 5-ARI from our institutional database comprising over 2500 patients who had been treated with either external beam radiotherapy (EBRT) or brachytherapy for localized prostate cancer. Patients received a 5-ARI for urinary symptoms or active surveillance. Cancer progressions at the time of definitive treatment were analyzed according to the following criteria: (a) progression of Gleason score or increase in cancer volume on biopsy, (b) first biopsy positive for cancer after being treated for urinary symptoms with a 5-ARI, and (c) prostate-specific antigen (PSA) progression with or without a previous cancer diagnosis. Biochemical failure (BF) was defined by the Phoenix definition. Log-rank test was used for survival analysis.Results
At a median follow-up of 38.2 months (standard deviation 22.2 months), 10 (4.9%) patients experienced BF. Concerning prostate cancer progression criteria, 52% of men demonstrated none, 37% showed only one criterion, and 11% showed two. Using univariate analysis, PSA progression (p = 0.004) and appearance of a positive biopsy (p < 0.001) were significant predictive factors for BF, while Gleason progression (p = 0.3) was not. In multivariate analysis adjusted for cancer aggressiveness, rising PSA (hazard ratio, HR, 5.7; 95% confidence interval, CI, 1.1–28.8; p = 0.04) and the number of cancer progression factors (HR 2.9, 95% CI 1.2–7.0, p = 0.02) remained adverse risk factors.Conclusion
PSA progression experienced during 5?ARI treatment before radiotherapy is predictive of worse biochemical outcome. Such details should be considered when counseling men prior to radiation therapy.2.
Purpose
To evaluate the patterns of relapse and impact on the intended treatment when using 68Ga-prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) imaging for restaging of disease in patients with biochemical relapse after radical prostatectomy (RP) before salvage radiotherapy (sRT).Methods
In all, 39 patients with biochemical recurrence after RP who had no primary indication for adjuvant RT due to the absence of biologically unfavorable disease (e.g., extracapsular extension, seminal vesicle invasion, positive margins, or lymph node involvement) underwent a 68Ga-PSMA ligand PET/CT for planning of sRT.Results
PET/CT was positive in 84.6% (33/39) of patients. A total of 61 lesions were observed in these patients (on average 1.8 lesions per patient); 30.3% (10/33) of patients had locally recurrent disease in the prostatic bed. The clinical TNM stage (TNM: tumour-lymph nodes-metastasis-classification) was altered in 69.7% (23/33) of patients following PET, resulting in individualized treatment concepts. A prostate-specific antigen (PSA) >1.0?ng/mL was significantly associated with an increased risk of extrapelvic metastatic disease (p = 0.048). The PSA level at the time of PSMA ligand PET/CT correlated with the peak standardized uptake value (SUVpeak; p = 0.002). According to current clinical guidelines, the remaining 15.4% (6/39) of patients without evidence of disease on PET received sRT with a dose of 66.0?Gy.Conclusion
Our results suggest that in patients with biochemical recurrence who did not receive early sRT, a 68Ga-PSMA ligand PET/CT for restaging of disease allows for tailoring and individualizing treatment. Particularly in patients with PSA levels above 1.0?ng/mL, a 68Ga-PSMA ligand PET/CT should be performed for therapy planning, since patients often have metastases not confined to the pelvis.3.
Defining biochemical recurrence after radical prostatectomy and timing of early salvage radiotherapy
Background
The optimal prostate-specific antigen (PSA) level after radical prostatectomy (RP) for defining biochemical recurrence and initiating salvage radiation therapy (SRT) is still debatable. Whereas adjuvant or extremely early SRT irrespective of PSA progression might be overtreatment for some patients, SRT at PSA >0.2?ng/ml might be undertreatment for others. The current study addresses the optimal timing of radiation therapy after RP.Patients and methods
Cohort 1 comprised 293 men with PSA 0.1–0.19?ng/ml after RP. Cohort 2 comprised 198 men with SRT. PSA progression and metastases were assessed in cohort 1. In cohort 2, we compared freedom from progression according to pre-SRT PSA (0.03–0.19 vs. 0.2–0.499?ng/ml). Multivariable Cox regression analyses predicted progression after SRT.Results
In cohort 1, 281 (95.9%) men had further PSA progression ≥0.2?ng/ml and 27 (9.2%) men developed metastases within a median follow-up of 74.3 months. In cohort 2, we recorded improved freedom from progression according to lower pre-SRT PSA (0.03–0.19 vs. 0.2–0.499?ng/ml: 69 vs. 53%; log-rank p = 0.051). Patients with higher pre-SRT PSA ≥0.2?ng/ml were at a higher risk of progression after SRT (hazard ratio: 1.8; p < 0.05).Conclusion
The vast majority of patients with PSA ≥0.1?ng/ml after RP will progress to PSA ≥0.2?ng/ml. Additionally, early administration of SRT at post-RP PSA level <0.2?ng/ml might improve freedom from progression. Consequently, we suggest a PSA threshold of 0.1?ng/ml to define biochemical recurrence after RP.4.
Purpose
The antiapoptotic B?cell lymphoma 2 (BCL2) gene is a key player in cancer development and progression. A functional single-nucleotide polymorphism (c.-938C>A, rs2279115) in the inhibitory P2 BCL2 gene promoter has been associated with clinical outcomes in various types of cancer. Aim of the present study was to analyze the role of BCL2-938C>A genotypes in prostate cancer mortality.Methods
The association between BCL2-938C>A (rs2279115) genotypes and prostate cancer outcome was studied within the prospective PROCAGENE study comprising 702 prostate cancer patients.Results
During a median follow-up time of 92 months, 120 (17.1%) patients died. A univariate Cox regression model showed a significant association of the CC genotype with reduced cancer-specific survival (CSS; hazard ratio, HR, 2.13, 95% confidence interval, CI, 1.10–4.12; p = 0.024) and overall survival (OS; HR 2.34, 95% CI 1.58–3.47; p < 0.001). In a multivariate Cox regression model including age at diagnosis, risk group, and androgen deprivation therapy, the CC genotype remained a significant predictor of poor CSS (HR 2.05, 95% CI 1.05–3.99; p = 0.034) and OS (HR 2.25, 95% CI 1.51–3.36; p < 0.001).Conclusion
This study provides evidence that the homozygous BCL2-938 CC genotype is associated with OS and C in prostate cancer patients.5.
Background
PET-CT is widely used for both the staging and planning of primary or neoadjuvant chemoradiotherapy for esophageal cancer. Inclusion of PET-CT information into radiotherapy planning often leads to substantial modifications of the target volume. In the case of detection of distant metastases, it may also result in a switch to a palliative treatment approach. This spares patients from therapy-related toxicities that provide no clinical benefit. However, due to a lack of studies, it is currently unclear whether the advantages of PET-CT also translate into a measurable improvement in patient survival.Patients and methods
A retrospective analysis assessed the survival data of 145 patients with esophageal carcinoma stages I (eight patients; 5%), II (45; 31%), III (79; 55%), IV (8; 5%) and unknown (5; 4%). Patients were treated between 1999 and 2014 either with primary chemoradiation (n = 101) or neoadjuvant chemoradiation at the Department of Radiation Oncology, University Medical Center Mainz, followed by transabdominal or transthoracic tumor resection (n = 44). Of the 145 patients, 64 (44%) had undergone PET-CT.Results
Univariate analysis showed the use of PET-CT to be associated with significantly longer local recurrence-free survival (p = 0.006) and tended to translate into a measurable improvement of overall survival (p = 0.071). Since more patients underwent surgery in the group planned using PET-CT (20% vs. 44%; p = 0.002), we carried out a multivariate Cox regression analysis to adjust for this possible confounding factor. Surgery (p = 0.042; HR 0.55; 95% confidence interval: 0.31–0.98) as well as the use of PET-CT (p = 0.048; HR 0.60; 95% confidence interval: 0.36–0.99) nearly halved the risk of local recurrence. It was only in the group of patients with PET-CT that a trend towards a shorter overall survival was evident in lymph node-positive patients (p = 0.16), whereas nodal stage did not impact on survival in patients staged without PET-CT (p = 0.97).Conclusion
To the best of our knowledge these data suggest for the first time that the use of PET-CT in the framework of staging and planning of primary or neoadjuvant chemoradiotherapy for esophageal cancer has a favorable impact on patient survival.6.
Purpose
Using prospectively collected patient-related, dose-related, and pulmonary function test (PFT) data before radiotherapy (RT) and at several follow-up visits after RT, the time course of PFT changes after high-dose radio(chemo)therapy and influencing factors were analyzed.Materials and methods
From April 2012 to October 2015, 81 patients with non-small-cell lung carcinoma (NSCLC), small cell lung carcinoma (SCLC), or esophageal carcinoma where treated with high-dose radio(chemo)therapy. PFT data were collected before treatment and 6 weeks, 12 weeks, and 6 months after RT. The influence of patient- and treatment-related factors on PFT was analyzed.Results
Mean forced expiratory volume in 1 s (FEV1) constantly declined during follow-up (p = 0.001). In total, 68% of patients had a reduced FEV1 at 6 months. Mean vital capacity (VC) didn’t change during follow-up (p > 0.05). Mean total lung capacity (TLC) showed a constant decline after RT (p = 0.026). At 6 months, 60% of patients showed a decline in VC and 73% in TLC. The mean diffusion capacity for carbon monoxide (DLCO) declined at 6 and 12 weeks, but recovered slightly at 6 months (p < 0.0005). At 6 months, 86% of patients had a reduced DLCO. After treatment, the partial pressure of CO2 in the blood (pCO2) was increased and pO2 was decreased (p > 0.05). Only the pretreatment PFT classification had a significant influence on the post-RT FEV1.Conclusion
DLCO seems to be the most reliable indicator for lung tissue damage after thoracic RT. Ventilation parameters appear to be less reliable. Concerning patient- or treatment-related factors, no reliable conclusion can be drawn regarding which factors may be relevant.7.
Objective
The aim of this publication is to present long-term data on functional outcomes and tumor control in a cohort of 107 patients treated with stereotactic radiotherapy (RT) for vestibular schwannoma.Patients and methods
Included were 107 patients with vestibular schwannoma (primary or recurrent following resection) treated with stereotactic RT (either fractioned or single-dose radiosurgery) between October 2002 and December 2013. Local control and functional outcomes were determined. Analysis of hearing preservation was limited to a subgroup of patients with complete audiometric data collected before treatment and during follow-up. Vestibular function test (FVT) results could be analyzed in a subset of patients and were compared to patient-reported dizziness.Results
After a mean follow-up of 46.3 months, actuarial local control for the whole cohort was 100% after 2, 97.6% after 5, and 94.1% after 10 years. In patients with primary RT, serviceable hearing was preserved in 72%. Predictors for preservation of serviceable hearing in multivariate analysis were time of follow-up (odds ratio, OR = 0.93 per month; p = 0.021) and pre-RT tumor size (Koos stage I–IIa vs. IIb–IV; OR = 0.15; p = 0.031). Worsening of FVT results was recorded in 17.6% (N = 3). Profound discrepancy of patient-reported dizziness and FVT results was observed after RT. In patients with primary RT, worsening of facial nerve function occurred in 1.7% (N = 1).Conclusion
Stereotactic RT of vestibular schwannoma provides good functional outcomes and high control rates. Dependence of hearing preservation on time of follow-up and initial tumor stage has to be considered.8.
Frederik A. Verburg David Pfister Axel Heidenreich Andreas Vogg Natascha I. Drude Stefan Vöö Felix M. Mottaghy Florian F. Behrendt 《European journal of nuclear medicine and molecular imaging》2016,43(3):397-403
Purpose
To examine the relationship between the extent of disease determined by [68Ga]PSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time (PSAdt) and Gleason score.Methods
We retrospectively studied the first 155 patients with recurrent prostate cancer (PCA) referred to our university hospital for [68Ga]PSMA-HBED-CC PET/CT.Results
PET/CT was positive in 44 %, 79 % and 89 % of patients with PSA levels of ≤1, 1 – 2 and ≥2 ng/ml, respectively. Patients with high PSA levels showed higher rates of local prostate tumours (p?<?0.001), and extrapelvic lymph node (p?=?0.037) and bone metastases (p?=?0.013). A shorter PSAdt was significantly associated with pelvic lymph node (p?=?0.026), extrapelvic lymph node (p?=?0.001), bone (p?<?0.001) and visceral (p?=?0.041) metastases. A high Gleason score was associated with more frequent pelvic lymph node metastases (p?=?0.039). In multivariate analysis, both PSA and PSAdt were independent determinants of scan positivity and of extrapelvic lymph node metastases. PSAdt was the only independent marker of bone metastases (p?=?0.001). Of 20 patients with a PSAdt <6 months and a PSA ≥2 ng/ml, 19 (95 %) had a positive scan and 12 (60 %) had M1a disease. Of 14 patients with PSA <1 ng/ml and PSAdt >6 months, only 5 (36 %) had a positive scan and 1 (7 %) had M1a disease.Conclusion
[68Ga]PSMA-HBED-CC PET/CT will identify PCA lesions even in patients with very low PSA levels. Higher PSA levels and shorter PSAdt are independently associated with scan positivity and extrapelvic metastases, and can be used for patient selection for [68Ga]PSMA-HBED-CC PET/CT.9.
Background and purpose
A prospective instrumental assessment of late dysphagia using swallowing organs at risk (SWOARs)-sparing IMRT for nasopharyngeal and oropharyngeal cancers.Materials and methods
Objective instrumental assessment included fiberoptic endoscopic evaluation of swallowing (FEES) and videofluoroscopy (VFS) at baseline, and at 6 and 12 months after treatment. FEES assessed the pharyngeal residue according to the Farneti pooling score (P-score) as follows: 4–5 no dysphagia; 6–7 mild dysphagia; 8–9 moderate dysphagia; 10–11 severe dysphagia. Three different consistencies were tested for the P?score: liquid (L), semisolid (SS), and solid (S). VFS assessed penetration-aspiration according to the Penetration-Aspiration Scale (PAS) and two different consistencies of the bolus were tested: thin liquid barium (L) and paste barium (S).Results
38 patients were evaluable. There was a significant worsening of the P?score at 6 months both for SS (p?=?0.015) and S (p?<?0.001), which persisted only for S at 12 months (p?<?0.0001). Similarly, there was a significant worsening of the PAS score at 6 and 12 months (p?=?0.065 and 0.039, respectively) for the S bolus. Overall, 3–7 and 10–14% aspiration after L and S was observed, respectively.Conclusions
Promising results using a SWOARs-sparing IMRT technique are reported. Therefore, treatment plans should be optimized for reducing doses to these structures.10.
S.?Janssen D.?Rades A.?Meyer F.?B.?Fahlbusch I.?Wildfang A.?Meier S.?Schild H.?Christiansen C.?Henkenberens
Purpose
To assess the outcome of breast cancer patients with local recurrence who underwent partial external beam re-irradiation (re-RT) either as part of a second breast-conserving therapy or following mastectomy.Methods
Between 03/2004 and 10/2016, 83 breast cancer patients with local recurrence were treated with surgery followed by re-RT. The re-RT schedules were 45?Gy (1.8?Gy per fraction) administered either to the partial breast (n?=?42) or mastectomy scar (n?=?41). The patients and tumor characteristics predictive of local control, distant control, and survival (overall and breast-cancer specific) were evaluated by univariate and multivariate analyses.Results
The median follow-up was 35 months (range 3–143 months). The median time interval between the first irradiation and re-RT was 117 months (range 16–357 months). The prognostic factors for favorable overall survival rates were younger age (p?=?0.045), lower T?category (p?=?0.019), and N0 category (p?=?0.005). N0 was also superior to N+ with respect to outfield recurrences (p?=?<0.001) and breast cancer-specific survival (p?=?0.025). Acute and late skin toxicity was generally low (<grade 3).Conclusion
Re-RT with 45?Gy (1.8?Gy per fraction) for partial breast or mastectomy scar after the second surgery resulted in high local control rates and tolerable skin toxicity.11.
N.?Andres?Parra Amber?Orman Kyle?Padgett Victor?Casillas Sanoj?Punnen Matthew?Abramowitz Alan?Pollack Radka?Stoyanova
Purpose
This study aimed to develop an automated procedure for identifying suspicious foci of residual/recurrent disease in the prostate bed using dynamic contrast-enhanced-MRI (DCE-MRI) in prostate cancer patients after prostatectomy.Materials and methods
Data of 22 patients presenting for salvage radiotherapy (RT) with an identified gross tumor volume (GTV) in the prostate bed were analyzed retrospectively. An unsupervised pattern recognition method was used to analyze DCE-MRI curves from the prostate bed. Data were represented as a product of a number of signal-vs.-time patterns and their weights. The temporal pattern, characterized by fast wash-in and gradual wash-out, was considered the “tumor” pattern. The corresponding weights were thresholded based on the number (1, 1.5, 2, 2.5) of standard deviations away from the mean, denoted as DCE1.0, …, DCE2.5, and displayed on the T2-weighted MRI. The resultant four volumes were compared with the GTV and maximum pre-RT prostate-specific antigen (PSA) level. Pharmacokinetic modeling was also carried out.Results
Principal component analysis determined 2–4 significant patterns in patients’ DCE-MRI. Analysis and display of the identified suspicious foci was performed in commercial software (MIM Corporation, Cleveland, OH, USA). In general, DCE1.0/DCE1.5 highlighted larger areas than GTV. DCE2.0 and GTV were significantly correlated (r = 0.60, p < 0.05). DCE2.0/DCA2.5 were also significantly correlated with PSA (r = 0.52, 0.67, p < 0.05). Ktrans for DCE2.5 was statistically higher than the GTV’s Ktrans (p < 0.05), indicating that the automatic volume better captures areas of malignancy.Conclusion
A software tool was developed for identification and visualization of the suspicious foci in DCE-MRI from post-prostatectomy patients and was integrated into the treatment planning system.12.
Background
Temozolomide-(TMZ)-based chemoradiotherapy defines the current gold standard for the treatment of newly diagnosed glioblastoma. Data regarding the influence of TMZ dose density during chemoradiotherapy are currently not available. We retrospectively compared outcomes in patients receiving no TMZ, TMZ during radiotherapy on radiotherapy days only, and TMZ constantly 7 days a week.Patients and methods
From 2002–2012, a total of 432 patients with newly diagnosed glioblastoma received radiotherapy in our department: 118 patients had radiotherapy alone, 210 had chemoradiotherapy with TMZ (75?mg/m2) daily (7/7), and 104 with TMZ only on radiotherapy days (5/7). Radiotherapy was applied to a total dose of 60?Gy.Results
Median survival after radiotherapy alone was 9.1 months, compared to 12.6 months with 5/7-TMZ and to 15.7 months with 7/7-TMZ. The 1?year survival rates were 33, 52, and 64%, respectively. Kaplan–Meier analysis showed a significant improvement of TMZ-7/7 vs. 5/7 (p = 0.01 by the log-rank test), while 5/7-TMZ was still superior to no TMZ at all (p = 0.02). Multivariate Cox regression showed a significant influence of TMZ regimen (p = 0.009) on hazard rate (+58% between groups) even in the presence of confounding factors age, sex, resection status, and radiotherapy dose concept.Conclusion
Our results confirm the findings of the EORTC/NCIC trial. It seems that also a reduced TMZ scheme can at first prolong the survival of glioblastoma patients, but not as much as the daily administration.13.
Purpose
The incidence of prostate cancer is 60% higher and the mortality rate is two- to three-times greater in black versus white men. We report on differences in 68Ga-PSMA-11 PET/CT imaging findings in 77 black South-African (BSAs) and 18 white South-African (WSAs) treatment-naïve primary prostate carcinoma (PPC) patients.Methods
68Ga-PSMA-11 PET/CT imaging findings were compared to histological, biochemical and morphological imaging data. Patients were grouped into three Gleason grade groups (GG), GG 1 (scores 3 + 3 and 3 + 4), GG2 (scores 4 + 3 and 4 + 4) and GG3 (scores 9 and 10), and the PSA difference among the groups was determined. Inter-racial difference in SUVmax of the primary tumor as well as its correlation with serum PSA were also determined.Results
Ninety-three out of 95 PPC where readily identified on 68Ga-PSMA-11 PET/CT imaging. Median PPC SUVmax and serum PSA values proved significantly higher (p = 0.033 and p = 0.003) in GG3 patients (median 16.4 and 180 ng/ml) when compared to GG1 patients (median 9.6 and 25.1 ng/ml) or GG2 patients (median 8.8 and 46.2 ng/ml). SUVmax significantly correlated with serum PSA-values (r = 0.377 (p = 0.0001)). Age, frequency of lymph node involvement and distant metastases, and GGs (p ≥ 0.153) were similar in BSAs and WSAs, both median serum PSA-values as well as SUVmax values proved significantly higher in BSAs when compared to WSAs, respectively, 81.6 ng/ml versus 14.5 ng/ml (p = 0.0001) and 11.9 versus 4.38 (p = 0.004). Moreover, Gleason-score normalized median SUVmax values proved 2.5 times higher in BSAs when compared to WSAs (p = 0.005).Conclusion
SUVmax values proved significantly related to GG and to be significantly higher in BSAs when compared to WSAs. Also, SUVmax significantly correlated with serum PSA values, which was significantly higher in BSAs when compared with WSAs.14.
Marsha?Schlenter Vanessa?Berneking Barabara?Krenkel Felix?M.?Mottaghy Thomas-Alexander?V?geli Michael?J.?Eble Michael?Pinkawa
Purpose
To analyze clinical results and quality of life of patients with localized prostate cancer after irradiation of the prostate with an 18F-choline-PET/CT-based simultaneous integrated boost (SIB) in comparison to a control group without SIB.Methods
A total of 134 patients underwent intensity-modulated radiotherapy from 2007–2010. All patients received a total dose of 76?Gy with 2?Gy fractions to the prostate; 67 patients received an additional SIB of 80?Gy. The median follow-up was 65 months. Quality of life was evaluated with the EPIC (Expanded Prostate Cancer Index Composite) questionnaire.Results
Baseline characteristics were similar in both groups (prostate-specific antigen 11?ng/ml vs. 8?ng/ml, p?=?0.20, Gleason score <6 in 36% vs. 46%, p?=?0.22, with vs. without SIB). No prostate cancer-related death was observed. No significant difference of quality of life scores was found. The largest difference after 5–6 years in comparison to baseline was reported for sexual bother (mean 15 vs. 17 points with vs. without SIB). Mean urinary scores did not decrease. Bowel bother scores changes were larger in the SIB group (mean 5 vs. 2 points, dependent on SIB volume), with increased bowel problems (15 vs. 2% big/moderate problem with bowel movements, p?=?0.03). However, a trend towards higher efficacy with SIB resulted (biochemical recurrence-free survival of 92% vs. 85%, p?=?0.17).Conclusions
The first long-term analysis of patients treated with SIB based on molecular imaging with 18-F-choline-PET/CT showed an excellent biochemical recurrence-free survival, but a larger percentage of bowel problems in comparison to the control group.15.
Aim
Retrospective Investigation of the prognostic relevance of clinicopathologic parameters in patients with salivary duct carcinoma (SDC).Methods
An experienced pathologist reviewed 67 patients with de novo SDC or SDC ex pleomorphic adenoma. Paraffin-embedded tumor samples were examined by immunohistochemistry for expression of HER2/neu, androgen (AR), progesterone (PR), estrogen (ER), epidermal growth factor (EGFR) and programmed death ligand 1 (PD-L1-R) receptor. In 45 patients who had cM0 and follow-up data available, survival rates were calculated (Kaplan–Meier method) and prognostic variables were analyzed (univariate analysis: log-rank test; multivariate analysis: Cox-regression analysis).Results
Overexpression of HER2/neu, AR, ER, PR, EGFR, PD-L1-R was found in 25.4%, 84%, 0%, 0%, 17.9%, 16.4% of patients. Overall (OS), disease-free (DFS), distant-metastases-free survival (DMFS) and locoregional control (LRC) were 92.3/72.4/56.9%, 78.2/58.1/58.1%, 85.4/65.2/65.2% and 89.7/81.9/81.9% after 1/3/5 years (medial follow-up 26 months). In univariate analysis a positive resection margin (p = 0.008) and no postoperative radiotherapy (p = 0.001) predict an increased locoregional recurrence rate. In multivariate analysis only postoperative radiotherapy is statistically significant (p = 0.004). Presence of lymph node metastases, a lymph node density >4 and HER2/neu overexpression predict decreased DFS and DMFS. In multivariate HER2/neu overexpression was the only significant predictor for reduced DFS (p = 0.04) and DMFS (p = 0.02).Conclusion
Postoperative radiotherapy is the only significant predictor for LRC. HER2/neu receptor expression is an independent prognostic factor for decreased DFS and DMFS in patients with SDC. In addition to radio(chemo)therapy, intensified first-line treatment regimens should also be evaluated in the future.16.
Marcelo Magalhães Sales Caio Victor de Sousa Hugo Alexandre de Paula Santana Daisy Motta-Santos Lucas Pinheiro Barbosa Patrick Anderson Santos Taia Maria Berto Rezende Rodrigo Alberto Vieira Browne Rosângela Vieira de Andrade Herbert Gustavo Simões 《Sport Sciences for Health》2018,14(3):597-606
Background
Type-2 diabetes (T2D) is associated with endothelial dysfunction, increase in sympathetic tone and several cardiovascular disorders, such as systemic arterial hypertension and coronary artery disease.Aims
To determine the effects of resistance training (RT) on the responses of nitric oxide (NO) and blood pressure (BP) in individuals with T2D and their controls peers.Methods
Randomized controlled trial in which T2D patients and non-diabetic individuals (ND) performed 8 weeks of RT. Participants were 22 women and 12 men (age 62.3?±?2.5 years) that were randomly allocated into four groups: T2D training (n?=?9), ND training (n?=?10), T2D control (n?=?8), and ND control (n?=?7). NO and BP were measured before and after the whole intervention.Results
There were no significant differences in nitrite concentrations between and within groups, with values varying between 1.22?±?0.15 and 1.45?±?0.13 Log µM. The T2D and ND experimental groups decreased systolic blood pressure (SBP) by 8.1 and 1.4 mmHg, respectively. However, the control groups showed elevation of SBP (3.6 mmHg for T2D and 4.1 mmHg for ND). Although none of these changes were significant (p?>?0.05). In addition, T2D subjects who did not undergo the training increased diastolic blood pressure (p?=?0.030) and mean arterial pressure (p?=?0.054).Conclusions
Eight weeks of RT does not increase NO bioavailability, and in turn, does not reduce BP in T2D patients—though it prevented its increase.Trial registration
ensaiosclinicos.gov.br (ID: RBR-4d39z9).17.
Purpose
Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1–4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT.Methods
A total of 52 patients were identified in the authors’ cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS.Results
The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06–4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11–0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14–4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35–0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15–0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09–4.45; p = 0.028).Conclusions
Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response to initial chemotherapy appeared to be major prognostic factors. Multivariate analysis revealed metachronous disease as a significantly negative prognostic factor on OS. The value of WBRT, stereotactic radiosurgery (SRS), or surgery alone or in combination for patients with a limited number of BM in SCLC should be evaluated in further prospective clinical trials.18.
Introduction
The use of targeted intraoperative radiotherapy (TARGIT-IORT) as a tumour bed boost during breast-conserving surgery (BCS) for breast cancer has been reported since 1998. We present its use in patients undergoing breast conservation following neoadjuvant therapy (NACT).Method
In this retrospective study involving 116 patients after NACT we compared outcomes of 61 patients who received a tumour bed boost with IORT during lumpectomy versus 55 patients treated in the previous 13 months with external (EBRT) boost. All patients received whole breast radiotherapy. Local recurrence-free survival (LRFS), disease-free survival (DFS), distant disease-free survival (DDFS), breast cancer mortality (BCM), non-breast cancer mortality (NBCM) and overall mortality (OS) were compared.Results
Median follow up was 49 months. The differences in LRFS, DFS and BCM were not statistically significant. The 5?year Kaplan–Meier estimate of OS was significantly better by 15% with IORT: IORT 2 events (96.7%, 95%CI 87.5–99.2), EBRT 9 events (81.7%, 95%CI 67.6–90.1), hazard ratio (HR) 0.19 (0.04–0.87), log rank p = 0.016, mainly due to a reduction of 10.1% in NBCM: IORT 100%, EBRT 89.9% (77.3–95.7), HR (not calculable), log rank p = 0.015. The DDFS was as follows: IORT 3 events (95.1%, 85.5–98.4), EBRT 12 events (69.0%, 49.1–82.4), HR 0.23 (0.06–0.80), log rank p = 0.012.Conclusion
IORT during lumpectomy after neoadjuvant chemotherapy as a tumour bed boost appears to give results that are not worse than external beam radiotherapy boost. These data give further support to the inclusion of such patients in the TARGIT-B (boost) randomised trial that is testing whether IORT boost is superior to EBRT boost.19.
Purpose
To retrospectively evaluate long-term treatment results following neoadjuvant chemoradiation (CRT) and radical surgery in patients with advanced adenocarcinoma (AC) of the oesophagus.Patients and methods
Between 2005 and 2015, a total of 102 consecutive patients with a median age of 64 years (range, 44–86 years) and AC of the oesophagus were evaluated of whom 84 received a full CRT. A group of 51 patients was treated with neoadjuvant intent followed by radical surgery. A total dose of 50.4?Gy with mostly weekly paclitaxel/fluorouracil chemotherapy was administered. Six to eight weeks following CRT, a transthoracic subtotal oesophageal and proximal gastric resection was performed. Survival curves for overall survival and no evidence of disease (NED) survival (primary endpoints) were calculated according to Kaplan–Meier, and possible prognostic factors were evaluated by the log-rank test as well as by a Cox regression analysis.Results
Median follow-up time of the surviving patients was 48 months (range, 14–134 months). Overall and NED survival rates for patients of the study group (n?=?51) were 40 and 32%, respectively, at 5 years. Age (p?=?0.04), ypT category (p?=?0.1) and the development of distant metastases (p?=?0.05) were identified as (marginally) independent prognostic variables with impact on survival. Median survival time for patients of the study group (n?=?51) was 45?±?18 months (95%CI 9–81 months). Clear resection margins were achieved in 46/51 patients (92%). Regression rates with complete regression rare residual cancer and increased number of residual cells, but predominantly fibrosis were 33, 41, and 10%, respectively. Patterns of failure revealed local with distant recurrence in 2/51 (4%), regional recurrence alone in 2/51 (4%), and distant metastases in 27/51 (53%) patients.Conclusion
Neoadjuvant CRT in patients with AC of the oesophagus followed by thoracoabdominal surgery is a locally very effective concept. A significant tumour regression in almost 75% of the patients may stimulate prospective trials on the omission of radical surgery for some elderly patients. Due to a high rate of distant metastases further investigations in terms of effective systemic therapy may be warranted.20.
Lorraine?Krebs Sandy?Amorin Pauline?Brice Sophie?Guillerm Jean?Menard Christophe?Hennequin Laurent?Quéro