Deep learning with biopsy whole slide images for pretreatment prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer：A multicenter study

IntroductionPredicting pathological complete response (pCR) for patients receiving neoadjuvant chemotherapy (NAC) is crucial in establishing individualized treatment. Whole-slide images (WSIs) of tumor tissues reflect the histopathologic information of the tumor, which is important for therapeutic response effectiveness. In this study, we aimed to investigate whether predictive information for pCR could be detected from WSIs.Materials and methodsWe retrospectively collected data from four cohorts of 874 patients diagnosed with biopsy-proven breast cancer. A deep learning pathological model (DLPM) was constructed to predict pCR using biopsy WSIs in the primary cohort, and it was then validated in three external cohorts. The DLPM could generate a deep learning pathological score (DLPs) for each patient; stromal tumor-infiltrating lymphocytes (TILs) were selected for comparison with DLPs.ResultsThe WSI feature-based DLPM showed good predictive performance with the highest area under the curve (AUC) of 0.72 among the cohorts. Alternatively, the combination of the DLPM and clinical characteristics offered a better prediction performance (AUC >0.70) in all cohorts. We also evaluated the performance of DLPM in three different breast subtypes with the best prediction for the triple-negative breast cancer (TNBC) subtype (AUC: 0.73). Moreover, DLPM combined with clinical characteristics and stromal TILs achieved the highest AUC in the primary cohort (AUC: 0.82) and validation cohort 1 (AUC: 0.80).ConclusionOur study suggested that WSIs integrated with deep learning could potentially predict pCR to NAC in breast cancer. The predictive performance will be improved by combining clinical characteristics. DLPs from DLPM can provide more information compared to stromal TILs for pCR prediction.     

Dry eye signs and symptoms in aromatase inhibitor treatment and the relationship with pain

PurposeAromatase inhibitors (AIs) limit the synthesis of oestrogen in peripheral tissues thus lowering levels of oestrogen. The primary aim was to evaluate whether women treated with AIs have altered dry eye symptoms and signs. A sub-aim was to investigate whether symptoms of dry eye in postmenopausal women were associated with symptoms of non-eye pain, ocular pain and self-rated pain perception.MethodsThis cross-sectional, observational, single visit study recruited 56 postmenopausal women (mean age 64.1 + 7.9 years) and 52 undergoing AI treatment (mean age 66.6 + 9.0). Ocular symptoms (OSDI, MGD14) and pain questionnaires (PSQ, OPAS) were administered and signs of dry eye and meibomian gland dysfunction were evaluated.ResultsAlmost half of each group reported dry eye symptoms, defined as OSDI>12 (48% control, 46% AI). The PSQ score was significantly higher in the AI group (p = 0.04). Neither frequency or severity of dry eye (or MGD) symptoms scores were significantly different between groups. In the AI group, meibomian gland expressibility score was worse (p = 0.003); there were no differences in any other signs. Higher OSDI scores were associated with higher OPAS eye-pain scores (r = 0.49, p < 0.001), but not OPAS non-eye pain (r = 0.09, p = 0.35). Pain perception (PSQ) showed a moderate positive association with OPAS eye-pain (r = 0.30, p = 0.003).ConclusionsIn this study elevated ocular symptoms were observed in both the AI treated and the untreated groups, with no difference between the groups. Women undergoing AI treatment for early stage breast cancer had worse meibum expressibility score and increased pain perception compared to an untreated group of women.     

Patient preferences and predicted relative uptake for targeted therapies in metastatic colorectal cancer: a discrete choice experiment

Abstract

Objective

Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients’ preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies.     

El papel de la resonancia magnética multiparamétrica en el diagnóstico de la recidiva local tras la prostatectomía radical y antes de la radioterapia de rescate

PurposeAssess multiparametric-MRI (mp-MRI) diagnostic accuracy in the detection of local recurrence of prostate cancer (PCa) after radical prostatectomy (PR) and before radiation therapy (RT).Materials and methodsA total of 188 patients underwent 1.5-T mp-MRI after RP before RT. Patients were divided into 2 groups: with biochemical recurrence (group A) and without but with high risk of local recurrence (group B). Continuous variables were compared between 2 groups using Student-t test; categoric variables were analyzed using Pearson chi-square. ROC analysis was performed considering PSA before RT, ISUP, pT and pN as grouping variables.ResultsPCa recurrence (reduction of PSA levels after RT) was 89.8% in group A and 80.3% in group B. Comparing patients with and without PCa recurrence, there was a significant difference in PSA values before RT for group A and for PSA values before RT and after RT for group B. In group A, there was a significant correlation between PSA before RT and diameter of recurrence and between PSA before RT and time spent before recurrence. The mp-MRI diagnostic accuracy in detecting PCa local recurrence after RP is of 62.2% in group A and 38% in group B. Diffusion weighted imaging is the most specific MRI-sequence and dynamic contrast enhanced the most sensitive. For PSA = 0.5 ng/ml, the AUC decreases while sensitivity and accuracy increase for each MRI-sequence. For PSA = 0.9 ng/ml, dynamic contrast enhanced-AUC increases significantly.Conclusionmp-MRI should always be performed before RT when a recurrence is suspected. New scenarios can be opened considering the role of diffusion weighted imaging for PSA ≤ 0.5 ng/ml.     

Caffeic Acid–coated Nanolayer on Mineral Trioxide Aggregate Potentiates the Host Immune Responses,Angiogenesis, and Odontogenesis

IntroductionThe aim of this study was to investigate whether mineral trioxide aggregate (MTA) can be modified with caffeic acid (CA) to form caffeic acid/mineral trioxide aggregate (CAMTA) cement and to evaluate its physicochemical and biological properties as well as its capability in immune suppression and angiogenesis.MethodsMTA was immersed in trishydroxymethyl aminomethane buffer with CA to allow coating onto MTA powders. X-ray diffractometry and tensile stress-strain tests were conducted to assess for physical characteristics of CAMTA and to evaluate for successful modification of MTA. Then, the CAMTA cement was immersed in simulated body fluid to evaluate its hydroxyapatite formation capabilities and Si release profiles. In addition, RAW 264.7 cells and human dental pulp stem cells were used to evaluate CAMTA’s immunosuppressive capabilities and cell responses, respectively. hDPSCs were also used to assess CAMTA’s angiogenic capabilities.ResultsThe X-ray diffractometry results showed that CA can be successfully coated onto MTA without disrupting or losing MTA’s original structural properties, thus allowing us to retain the initial advantages of MTA. CAMTA was shown to have higher mechanical properties compared with MTA and had rougher pitted surfaces, which were hypothesized to lead to enhanced adhesion, proliferation, and secretion of angiogenic- and odontogenic-related proteins. In addition, it was found that CAMTA was able to enhance hydroxyapatite formation and immunosuppressive capabilities compared with MTA.ConclusionsCAMTA cements were found to have improved physicochemical and biological characteristics compared with their counterpart. In addition, CAMTA cements had enhanced odontogenic, angiogenic, and immunosuppressive properties compared with MTA. All of the results of this study proved that CAMTA cements could be a biomaterial for future clinical applications and tissue engineering use.     

电视辅助胸腔镜下解剖性肺切除治疗I期肺癌的临床效果

目的 探讨电视辅助胸腔镜下解剖性肺切除治疗Ⅰ期肺癌的临床效果。方法 采用回顾性研究方法,选取2015年5月至2017年1月广西医科大学附属肿瘤医院收治的I期肺癌患者84例,按照手术方法不同将患者分为两组:观察组和对照组,每组各42例。观察组患者实施电视辅助胸腔镜下解剖性肺切除术治疗,对照组患者给予传统开胸肺叶切除术治疗。比较两组患者的住院时间、切口长度、术中出血量、手术时间、1年和3年生存情况及生活质量评分(SF-36生活量表)变化。结果 观察组患者的住院时间短于对照组(6. 13±1. 46 vs. 10. 39±2. 41 d),切口长度小于对照组(4. 38±1. 09 vs. 11. 84±3. 25 cm),术中出血量少于对照组(284. 62±54. 21 vs. 397. 57±61. 49 ml),差异均具有统计学意义(P <0. 05);而两组手术时间比较(165. 28±33. 24 vs. 156. 39±30. 92 min),差异无统计学意义(P> 0. 05)。观察组患者的1、3年生存率[97. 62%(41/42)、90. 48%(38/42)]均高于对照组[88. 10%(37/42)、76. 19%(32/42)],但差异无统计学意义(P> 0. 05)。观察组患者的各项生活质量评分[精神健康(75. 42±6. 87 vs 61. 30±4. 15分)、情感职能(81. 38±7. 15 vs. 73. 49±5. 76分)、社会功能(82. 67±5. 78 vs. 75. 42±4. 35分)、一般健康状况(79. 49±6. 17 vs.70. 31±5. 04分)、精力(84. 37±5. 45 vs. 74. 13±6. 07分)、生理职能(86. 52±6. 88 vs. 76. 93±6. 42分)、躯体疼痛(83. 46±7. 49 vs. 74. 33±5. 79分)、生理功能(70. 39±4. 31 vs. 61. 38±3. 56分)]均高于对照组,且差异具有统计学意义(P <0. 05)。结论 与传统开胸肺叶切除术相比,电视辅助胸腔镜下解剖性肺切除治疗I期肺癌手术损伤更小、短期生存率更高,且有助于提高患者术后生活质量水平,这对改善患者预后有重要意义,值得临床推广应用。     

Stereotactic body radiotherapy for Stage I lung cancer with chronic obstructive pulmonary disease: special reference to survival and radiation-induced pneumonitis

This retrospective study aimed to evaluate radiation-induced pneumonitis (RIP) and a related condition that we define in this report—prolonged minimal RIP (pmRIP)—after stereotactic body radiotherapy (SBRT) for Stage I primary lung cancer in patients with chronic obstructive pulmonary disease (COPD). We assessed 136 Stage I lung cancer patients with COPD who underwent SBRT. Airflow limitation on spirometry was classified into four Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, with minor modifications: GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe) and GOLD 4 (very severe). On this basis, we defined two subgroups: COPD-free (COPD −) and COPD-positive (COPD +). There was no significant difference in overall survival or cause-specific–survival between these groups. Of the 136 patients, 44 (32%) had pmRIP. Multivariate analysis showed that COPD and the Brinkman index were statistically significant risk factors for the development of pmRIP. COPD and the Brinkman index were predictive factors for pmRIP, although our findings also indicate that SBRT can be tolerated in early lung cancer patients with COPD.     

Use of a dual lumen port for automated red cell exchange in adults with sickle cell disease

Red cell exchange (RCE) is a common procedure in adults with sickle cell disease (SCD). Implantable dual lumen Vortex (DLV) ports can be used for RCE in patients with poor peripheral venous access. We performed a retrospective cohort study of RCE procedures performed in adults with SCD. The main objective of the study was to compare the inlet speed, duration of procedures and rate of complications performed through DLV ports to those performed through temporary central venous and peripheral catheters. Twenty‐nine adults with SCD underwent a total of 318 RCE procedures. Twenty adults had DLV ports placed and 218 procedures were performed using DLV ports. Mean length of follow‐up after DLV port placement was 397 ± 263 days. Six DLV ports were removed due to infection and 1 for malfunction after a mean of 171 ± 120 days. Compared to temporary central venous and peripheral catheters, DLV port procedures had a greater rate of procedural complications, a longer duration, and a lower inlet speed (all P < 0.01). When accounting for the maximum allowable inlet speed to avoid citrate toxicity, 40% of DLV port procedures were greater than 10% below maximum speed, compared to 7 and 14% of procedures performed through temporary central venous and peripheral catheters (P < 0.0001). In conclusion, DLV ports can be used for RCE in adults with SCD, albeit with more procedural complications and longer duration. The smaller internal diameter and longer catheter of DLV ports compared to temporary central venous catheters likely accounts for the differences noted. J. Clin. Apheresis 30:353–358, 2015. © 2015 Wiley Periodicals, Inc.