bluuebunny/crossref_metadata_2025 huggingface dataset:
Endolymphatic Hydrops in Patients With Vestibular Migraine and Concurrent Meniere's Disease
Authors: Oh Sun-Young , Dieterich Marianne , Lee Bit Na , Boegle Rainer , Kang Jin-Ju , Lee Na-Ri , Gerb Johannes , Hwang Seung-Bae , Kirsch Valerie
Published: March 2021

Objective: Intravenous contrast agent enhanced, high-resolution magnetic resonance imaging of the inner ear (iMRI) confirmed that patients with Menière's disease (MD) and vestibular migraine (VM) could present with endolymphatic hydrops (EH). The present study aimed to investigate EH characteristics and their interrelation to neurotologic testing in patients with VM, MD, or VM with concurrent MD (VM-MD).

Methods: Sixty–two patients (45 females, aged 23–81 years) with definite or probable VM (n = 25, 19 definite), MD (n = 29, 17 definite), or showing characteristics of both diseases (n = 8) were included in this study. Diagnostic workup included neurotologic assessments including video-oculography (VOG) during caloric stimulation and head-impulse test (HIT), ocular and cervical vestibular evoked myogenic potentials (o/cVEMP), pure tone audiometry (PTA), as well as iMRI. EH's degree was assessed visually and via volumetric quantification using a probabilistic atlas-based segmentation of the bony labyrinth and volumetric local thresholding (VOLT).

Results: Although a relevant number of VM patients reported varying auditory symptoms (13 of 25, 52.0%), EH in VM was only observed twice. In contrast, EH in VM-MD was prevalent (2/8, 25%) and in MD frequent [23/29, 79.3%; χ2(2) = 29.1, p < 0.001, φ = 0.7]. Location and laterality of EH and neurophysiological testing classifications were highly associated (Fisher exact test, p < 0.005). In MD, visual semi-quantitative grading and volumetric quantification correlated highly to each other (rS = 0.8, p < 0.005, two-sided) and to side differences in VOG during caloric irrigation (vestibular EH ipsilateral: rS = 0.6, p < 0.05, two-sided). In VM, correlations were less pronounced. VM-MD assumed an intermediate position between VM and MD.

Conclusion: Cochlear and vestibular hydrops can occur in MD and VM patients with auditory symptoms; this suggests inner ear damage irrespective of the diagnosis of MD or VM. The EH grades often correlated with auditory symptoms such as hearing impairment and tinnitus. Further research is required to uncover whether migraine is one causative factor of EH or whether EH in VM patients with auditory symptoms suggests an additional pathology due to MD.
Compromised Dynamic Cerebral Autoregulation in Patients With Central Disorders of Hypersomnolence
Authors: Deng Fang , Zhang Yanan , Zhang Ran , Tang Qi , Guo Zhenni , Lv Yudan , Wang Zan , Yang Yi
Published: March 2021

Objective: We aimed to investigate the dynamic cerebral autoregulation (dCA) in patients with central disorders of hypersomnolence during wakefulness.

Methods: Thirty-six patients with central disorders of hypersomnolence were divided into three groups according to polysomnography and multiple sleep latency test results: the idiopathic hypersomnia group (IH), narcolepsy type 1 without rapid-eye-movement sleep behavior disorder group (NT1-RBD), and narcolepsy type 1 with rapid-eye-movement sleep behavior disorder group (NT1 + RBD), with 12 patients in each group. Twelve sex- and age-matched healthy controls were recruited. We assessed the Epworth sleepiness scale (ESS) and dCA of all subjects. dCA was assessed by analyzing the phase difference (PD) using transfer function analysis. The ESS and dCA were analyzed before and after standardized treatment in 24 patients with narcolepsy type 1.

Results: The overall PD of the IH, NT1-RBD, and NT1 + RBD groups were lower than that of the control group (P < 0.001). There were no significant differences between the overall PD of the NT1-RBD and NT1 + RBD group (P > 0.05). The ESS scores decreased and the overall PD increased after treatment in 24 patients with narcolepsy type 1 (P < 0.001). Multivariable analysis showed that mean sleep latency in multiple sleep latency test was independently associated with impaired overall PD (P < 0.05).

Conclusions: The dCA is impaired in patients with central disorders of hypersomnolence. The impairment of dCA occurs irrespective of NT1-RBD/+RBD. The ESS score and dCA improved in patients with narcolepsy type 1 after medication treatment. The mean sleep latency in multiple sleep latency test was independently associated with impaired dCA.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02752139.
Prognostic Value of Pretreatment Systemic Immune-Inflammation Index in Gastric Cancer: A Meta-Analysis
Authors: Qiu Ye , Zhang Zongxin , Chen Ying
Published: March 2021

Background

Previous studies have investigated the role of systemic immune-inflammation index (SII) as a prognostic factor for gastric cancer (GC) patients, although with inconsistent results. Thus, the aim of this study was to identify the prognostic value of SII in GC through meta-analysis.

Methods

We systematically searched the PubMed, Embase, and Web of Science databases for relevant studies investigating the prognostic role of SII in GC up to December 2019. The hazard ratios (HRs) and 95% confidence intervals (CIs) related to overall survival (OS) and disease-free survival (DFS) were combined. Odds ratios (ORs) and 95% CIs were pooled to assess the correlation between SII and clinicopathological features of GC.

Results

A total of eight studies, comprising 4,236 patients, were included in this meta-analysis. Pooled analysis indicated that a high pretreatment SII predicted poor OS (HR=1.40, 95% CI=1.08–1.81, p=0.010) but not poor DFS (HR=1.30, 95% CI=0.92–1.83, p=0.140) in GC. In addition, an elevated SII correlated with an advanced tumor–node–metastasis stage (OR=2.34, 95% CI=1.40–3.92, p=0.001), T3–T4 stage (OR=2.25, 95% CI=1.34–3.77, p=0.002), positive lymph node metastasis (OR=1.79, 95% CI=1.12–2.87, p=0.016), and tumor size ≥ 5 cm (OR=2.28, 95% CI=1.62–3.22, p<0.001) in patients with GC.

Conclusions

A high pretreatment SII significantly associated with poorer survival outcomes as well as several clinical characteristics in GC. We suggest that SII could be monitored to guide prognostication and provide reliable information on the risk of disease progression in GC.
Association Between Triglyceride Glucose Index and Non-Small Cell Lung Cancer Risk in Chinese Population
Authors: Yan Xin , Gao Yujuan , Tong Jingzhi , Tian Mi , Dai Jinghong , Zhuang Yi
Published: March 2021

Background

Numerous studies showed that insulin resistance (IR) was associated with cancer risk. However, few studies investigated the relationship between IR and non-small cell lung cancer (NSCLC). The aim of this study is to explore the association of triglyceride glucose (TyG) index, a simple surrogate marker of IR, with NSCLC risk.

Methods

791 histologically confirmed NSCLC cases and 787 controls were enrolled in the present study. Fasting blood glucose and triglyceride were measured. The TyG index was calculated as ln [fasting triglycerides (mg/dl) ×fasting glucose (mg/dl)/2]. Logistic regression analysis was performed to estimate the relationship between NSCLC risk and the TyG index.

Results

The TyG index was significantly higher in patients with NSCLC than that in controls (8.42 ± 0.55 vs 8.00 ± 0.45, P < 0.01). Logistic regression analysis showed that the TyG index (OR = 3.651, 95%CI 2.461–5.417, P < 0.001) was independently associated with NSCLC risk after adjusting for conventional risk factors. In addition, a continuous rise in the incidence of NSCLC was observed along the tertiles of the TyG index (29.4 vs 53.8 vs 67.2%, P < 0.001). However, there were no differences of the TyG index in different pathological or TNM stages. In receiver operating characteristic (ROC) curve analysis, the optimal cut-off level for the TyG index to predict incident NSCLC was 8.18, and the area under the ROC curve (AUROC) was 0.713(95% CI 0.688–0.738).

Conclusions

The TyG index is significantly correlated with NSCLC risk, and it may be suitable as a predictor for NSCLC.
Prognostic Value of Lymph Node Dissection for Intrahepatic Cholangiocarcinoma Patients With Clinically Negative Lymph Node Metastasis: A Multi-Center Study From China
Authors: Ke Qiao , Wang Lei , Lin Ziguo , Lou Jianying , Zheng Shuguo , Bi Xinyu , Wang Jianming , Guo Wei , Li Fuyu , Wang Jian , Zheng Yamin , Li Jingdong , Cheng Shi , Zhou Weiping , Zeng Yongyi
Published: March 2021

Background

The clinical value of lymph-node dissection (LND) for intrahepatic carcinoma (ICC) patients with clinically negative lymph node metastasis (LNM) remains unclear; hence we conducted a multi-center study to explore it.

Methods

Patients who were diagnosed ICC with clinically negative LNM and underwent hepatectomy with or without LND from December 2012 to December 2015 were retrospectively collected from 12 hepatobiliary centers in China. Overall survival (OS) was analyzed using the Kaplan–Meier method, and then subgroup analysis was conducted stratified by variables related to the prognosis.

Results

A total of 380 patients were eligible including 106 (27.9%) in the LND group and 274 (72.1%) in the non-LND group. Median OS in the LND group was slightly longer than that in the non-LND group (24.0 vs. 18.0 months, P = 0.30), but a significant difference was observed between the two groups (24.0 vs. 14.0 months, P = 0.02) after a well-designed 1:1 propensity score matching without increased severe complications. And, LND was identified to be one of the independent risk factors of OS (HR = 0.66, 95%CI = 0.46–0.95, P = 0.025). Subgroup analysis in the matched cohort showed that patients could benefit more from LND if they were male, age <60 years, had no HBV infection, with ECOG score <2, CEA ≤5 ug/L, blood loss ≤400 ml, transfusion, major hepatectomy, resection margin ≥1 cm, tumor size >5 cm, single tumor, mass-forming, no satellite, no MVI, and no perineural invasion (all P < 0.05). Furthermore, only patients with pathologically confirmed positive LNM were found to benefit from postoperative adjuvant therapy (P < 0.001).

Conclusion

With the current data, we concluded that LND would benefit the selected ICC patients with clinically negative LNM and might guide the postoperative management.
Prognosis and Genomic Landscape of Liver Metastasis in Patients With Breast Cancer
Authors: Tian Chonglin , Liu Sujing , Wang Yongsheng , Song Xianrang
Published: March 2021

Objective

The prognosis of breast cancer liver metastasis (BCLM) is poor, and its molecular mechanism is unclear. We aimed to determine the factors that affect the prognosis of patients with BCLM and investigate the genomic landscape of liver metastasis (LM).

Methods

We described the prognosis of patients with BCLM and focused on prognosis prediction for these patients based on clinicopathological factors. Nomogram models were constructed for progression-free survival (PFS) and overall survival (OS) by using a cohort of 231 patients with BCLM who underwent treatment at Shandong Cancer Hospital and Institute (SCHI). We explored the molecular mechanism of LM and constructed driver genes, mutation signatures by using a targeted sequencing dataset of 217 samples of LM and 479 unpaired samples of primary breast cancer (pBC) from Memorial Sloan Kettering Cancer Center (MSKCC).

Results

The median follow-up time for 231 patients with BCLM in the SCHI cohort was 46 months. The cumulative incidence of LM at 1, 2, and 5 years was 17.5%, 45.0%, and 86.8%, respectively. The median PFS and OS were 7 months (95% CI, 6–8) and 22 months (95% CI, 19–25), respectively. The independent factors that increased the progression risk of patients with LM were Karnofsky performance status (KPS) ≤ 80, TNBC subtype, grade III, increasing trend of CA153, and disease-free interval (DFS) ≤ 1 year. Simultaneously, the independent factors that increased the mortality risk of patients with LM were Ki-67 ≥ 30%, grade III, increasing trend of CA153, pain with initial LM, diabetes, and DFI ≤ 1 year. In the MSKCC dataset, the LM driver genes were ESR1, AKT1, ERBB2, and FGFR4, and LM matched three prominent mutation signatures: APOBEC cytidine deaminase, ultraviolet exposure, and defective DNA mismatch repair.

Conclusion

This study systematically describes the survival prognosis and characteristics of LM from the clinicopathological factors to the genetic level. These results not only enable clinicians to assess the risk of disease progression in patients with BCLM to optimize treatment options, but also help us better understand the underlying mechanisms of tumor metastasis and evolution and provide new therapeutic targets with potential benefits for drug-resistant patients.
Adjuvant Therapy for Resectable Biliary Tract Cancer: A Bayesian Network Analysis
Authors: Chen Xiuqiong , Meng Fanqiao , Xiong Hua , Zou Yanmei
Published: March 2021

Background: Selecting proper postoperative adjuvant therapy is of great importance for prolonging overall survival (OS) of patients with biliary tract cancer (BTC). OS is commonly affected by high rate of postoperative recurrence and metastasis.

Purpose: The present study aimed to identify the optimal adjuvant therapy for BTC patients.

Method: A comprehensive search was carried out on Pubmed, Web of science, and Embase databases to acquire articles regarding BTC therapy approaches. Subsequently, the hazard ratio (HR) and its 95% confidence intervals (CIs) were applied to evaluate the efficacy of different adjuvant therapy regimens. The GemTc (GemTc.0.8-2) and R (R.3.6.0) software were employed to perform statistical analyses.

Result: Data from 22 articles, including 14,646 patients, were quantitatively analyzed. The results showed that in terms of 5-year OS, gemcitabine (GEM) was considered as the optimal adjuvant therapy for BTC compared with chemoradiotherapy (CRT; HR = 0.59; 95% CI = 0.34-0.97), observation (OB; HR = 0.49; 95% CI = 0.33-0.73), and radiotherapy (RT; HR = 0.40; 95% CI = 0.22-0.71). Additionally, 5-fluorouracil (5-FU) exhibited improved efficacy compared with RT (HR = 0.52; 95% CI = 0.29-0.91) and OB (HR = 0.63; 95% CI = 0.43-0.92). When the efficacy of 5-FU was compared with that of GEM, the results showed that 5-FU (HR = 1.29) was more effective than GEM. Furthermore, CRT and RT prolonged positive resection margin (R+)-OS (HR = 0.69; 95% CI = 0.49-1.00) and positive lymph node-(N+)-OS (HR = 0.22; 95% CI = 0.074-0.66) in BTC patients. In terms of median recurrence-free survival (RFS) and 1-year OS, the differences were not statistically significant among different therapeutic interventions.

Conclusion: The present study suggested that GEM could be used as a first-line adjuvant therapy for resected BTC patients. Additionally, CRT could be the optimal treatment approach for R+ and N+ patients.
Association Between the Presence of Female-Specific Tumors and Aggressive Clinicopathological Features in Papillary Thyroid Cancer: A Retrospective Analysis of 9,822 Cases
Authors: Zhang Jiao , Zhou Le , Dionigi Gianlorenzo , Zhang Daqi , Zhao Lina , Liang Nan , Xue Gaofeng , Sun Hui
Published: March 2021

Objective

To investigate the association between the presence of female-specific tumors and aggressive clinicopathological features in papillary thyroid cancer (PTC).

Methods

This study retrospectively analyzed 9,822 female cases between June 2008 and December 2017. Odds ratios and corresponding 95% confidence intervals were calculated. Findings were stratified by age and body mass index (BMI) in different models.

Results

1443/9822 (14.7%) patients with PTC had a female-specific tumor. Presence of a benign breast mass was an independent risk factor for a primary PTC lesion > 1 cm in diameter (adjusted OR = 1.446, 95% CI 1.136–1.840, P = 0.003), but a protective factor against extrathyroidal extension of PTC (adjusted OR = 0.650, 95%CI 0.500–0.845, P = 0.001). Presence of a benign uterine mass was an independent risk factor for multifocal PTC (adjusted OR = 1.305, 95%CI 1.113–1.531, P = 0.001). Analyses stratified by age and BMI revealed the presence of a benign breast mass was an independent risk factor for a primary PTC lesion > 1 cm in diameter in patients aged <36 years (adjusted OR = 1.711, 95% CI 1.063–2.754, P = 0.027), and a protective factor against extrathyroidal extension of PTC in patients aged ≥36 - <42 years (OR adjusted = 0.533, 95% CI 0.302–0.941, P = 0.030) or with a BMI ≥ 23.4 kg/m2 (BMI ≥ 23.4 to < 25.7 kg/m2, adjusted OR = 0.441, 95% CI 0.246–0.792, P = 0.006; BMI ≥25.7 kg/m2, adjusted OR = 0.558, 95% CI 0.315–0.998, P2 = 0.045). Presence of a benign uterine mass was an independent risk factor for multifocal PTC in patients aged ≥49 years (adjusted OR = 1.397, 95% CI 1.088–1.793, P = 0.009) or with a BMI <21.5 kg/m2 (OR adjusted = 1.745, 95% CI 1.214–2.509, P = 0.003).

Conclusion

The presence of a benign breast mass was an independent risk factor for a primary PTC lesion > 1 cm in diameter and a protective factor against extrathyroidal extension of PTC, while the presence of a benign uterine mass was an independent risk factor for multifocal PTC. Data from this study may help surgeons propose more personalized treatment plans when encountering patients with PTC and female-specific benign tumors.
Identification of Proteins Deregulated by Platinum-Based Chemotherapy as Novel Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer
Authors: Ryan Sarah-Louise , Dave Keyur A. , Beard Sam , Gyimesi Martina , McTaggart Matthew , Sahin Katherine B. , Molloy Christopher , Gandhi Neha S. , Boittier Eric , O’Leary Connor G. , Shah Esha T. , Bolderson Emma , Baird Anne-Marie , Richard Derek J. , O’Byrne Kenneth J. , Adams Mark N.
Published: March 2021

Platinum-based chemotherapy remains the cornerstone of treatment for most people with non-small cell lung cancer (NSCLC), either as adjuvant therapy in combination with a second cytotoxic agent or in combination with immunotherapy. Resistance to therapy, either in the form of primary refractory disease or evolutionary resistance, remains a significant issue in the treatment of NSCLC. Hence, predictive biomarkers and novel combinational strategies are required to improve the effectiveness and durability of treatment response 6for people with NSCLC. The aim of this study was to identify novel biomarkers and/or druggable proteins from deregulated protein networks within non-oncogene driven disease that are involved in the cellular response to cisplatin. Following exposure of NSCLC cells to cisplatin, in vitro quantitative mass spectrometry was applied to identify altered protein response networks. A total of 65 proteins were significantly deregulated following cisplatin exposure. These proteins were assessed to determine if they are druggable targets using novel machine learning approaches and to identify whether these proteins might serve as prognosticators of platinum therapy. Our data demonstrate novel candidates and drug-like molecules warranting further investigation to improve response to platinum agents in NSCLC.
A Dose-Finding Trial for Hyperthermic Intraperitoneal Cisplatin in Gynecological Cancer Patients Receiving Hyperthermic Intraperitoneal Chemotherapy
Authors: Chan Chui-ying , Li Hui , Wu Miao-fang , Liu Chang-hao , Lu Huai-wu , Lin Zhong-qiu , Li Jing
Published: March 2021

Background: To identify the maximum tolerated dose (MTD) of hyperthermic intraperitoneal cisplatin at 43°C among gynecological cancer patients.

Methods: In this Phase I dose-finding trial, Bayesian optimal interval (BOIN) design was used. We sought to explore the MTD with a target dose-limiting toxicity (DLT) rate of 20%, 4 prespecified doses (70 mg/m2, 75 mg/m2, 80 mg/m2 and 85 mg/m2), and 30 patients.

Results: Between 2019 and 2020, 30 gynecologic cancer patients were enrolled. No patients received bevacizumab in subsequent treatment. The most common adverse events related to cisplatin were nausea and vomiting (100%), followed by tinnitus (26.7%) and kidney injury (23.3%). Of the seven patients with kidney injury, four had persistent renal impairment, and finally progressed into chronic kidney injury. DLTs were noted only in the dose level 4 group (85 mg/m2) and included acute kidney injury, pulmonary embolism, anemia, and neutropenia. When cisplatin was given at dose level four (85 mg/m2), the isotonic estimate of the DLT rate (22%) was closest to the target DLT rate of 20%. Therefore, 85 mg/m2 was selected as the MTD, with a 51% probability that the toxicity probability was greater than the target DLT rate.

Conclusions: For gynecological cancer patients who received HIPEC for peritoneal metastases, the MTD of cisplatin in HIPEC at 43°C was 85 mg/m2. Our findings apply to patients who do not receive bevacizumab (ChiCTR1900021555).
CT-Based Collision Prediction Software for External-Beam Radiation Therapy
Authors: Wang Yu-Jen , Yao Jia-Sheng , Lai Feipei , Cheng Jason Chia-Hsien
Published: March 2021

Purpose

Beam angle optimization is a critical issue for modern radiotherapy (RT) and is a challenging task, especially for large body sizes and noncoplanar designs. Noncoplanar RT techniques may have dosimetric advantages but increase the risk of mechanical collision. We propose a software solution to accurately predict colliding/noncolliding configurations for coplanar and noncoplanar beams.

Materials and Methods

Individualized software models for two different linear accelerators were built to simulate noncolliding gantry orientations for phantom/patient subjects. The sizes and shapes of the accelerators were delineated based on their manuals and on-site measurements. The external surfaces of the subjects were automatically contoured based on computed tomography (CT) simulations. An Alderson Radiation Therapy phantom was used to predict the accuracy of spatial collision prediction by the software. A gantry collision problem encountered by one patient during initial setup was also used to test the validity of the software. Results: In the comparison between the software estimates and on-site measurements, the noncoplanar collision angles were all predicted within a 5-degree difference in gantry position. The confusion matrix was calculated for each of the two empty accelerator models, and the accuracies were 98.7% and 97.3%. The true positive rates were 97.7% and 96.9%, while the true negative rates were 99.8% and 97.9%, respectively. For the phantom study, the collision angles were predicted within a 5-degree difference. The software successfully predicted the collision problem encountered by the breast cancer patient in the initial setup position and generated shifted coordinates that were validated to correspond to a noncolliding geometry.

Conclusion

The developed software effectively and accurately predicted collisions for accelerator-only, phantom, and patient setups. This software may help prevent collisions and expand the range of spatially applicable beam angles.
Progress and Challenges of Predictive Biomarkers for Immune Checkpoint Blockade
Authors: Lei Yanna , Li Xiaoying , Huang Qian , Zheng Xiufeng , Liu Ming
Published: March 2021

Over the past decade, immune checkpoint blockade (ICB) therapy has revolutionized the outlook for oncology with significant and sustained improvement in the overall patient survival. Unlike traditional cancer therapies, which target the cancer cells directly, ICB acts on the immune system to enhance anti-tumoral immunity. However, the response rate is still far from satisfactory and most patients are refractory to such treatment. Unfortunately, the mechanisms underlying such heterogeneous responses between patients to ICB therapy remain unclear. In addition, escalating costs of cancer care and unnecessary immune-related adverse events also are pertinent considerations with applications of ICB. Given these issues, identifying explicit predictive biomarkers for patient selection is an urgent unmet need to increase the efficacy of ICB therapy. The markers can be classified as tumor related and non-tumor-related biomarkers. Although substantial efforts have been put into investigating various biomarkers, none of them has been found to be sufficient for effectively stratifying patients who may benefit from immunotherapy. The present write up is an attempt to review the various emerging clinically relevant biomarkers affecting the efficacy of immune checkpoint inhibitors, as well as the limitations associated with their clinical application.
Outcomes After Accelerated Partial Breast Irradiation in Women With Triple Negative Subtype and Other “High Risk” Variables Categorized as Cautionary in The ASTRO Guidelines
Authors: Goulding Anabel , Asmar Lina , Wang Yunfei , Tole Shannon , Barke Lora , Widner Jodi , Leonard Charles
Published: March 2021

Purpose

To report a primary objective clinical outcome of ipsilateral breast recurrence following accelerated partial breast irradiation (APBI) in women with triple negative and other high risk breast cancer (as described in 2017 ASTRO guidelines) (i.e., age 40–49, size 2.1–3.0 cm, estrogen receptor negative and invasive lobular breast cancer). Secondary objectives of axillary and regional failure as well as overall survival are also reported.

Methods and Material

Patients from two clinical trials (NCT01185145, NCT01185132) were treated with 38.5 Gy IMRT or 3D-CRT APBI w/3.85 Gy fraction/BID fractionation for 10 fractions. Triple negative and other high risk patients (n=269) were compared to a total of 478 low risk patients which ASTRO defined as “suitable” for APBI. High risk patients, for the purpose of this study, were defined as those who possess one or more high risk criteria: triple negative (n=30), tumor size >2 cm <3 cm (n=50), HER 2+ (n=54), age range 40–50 years (n=120), ER- (n=43), and ILC histology (n=52).

Results

Median follow up was 4.0 years for all patients. No significant difference was found for this high-risk cohort at 5 years for ipsilateral breast, or regional recurrences. Axillary recurrence was significantly adversely impacted by triple negative and ER- statuses (p=0.01, p=0.04). There were significant correlations between triple negative type and axillary recurrence on multivariate analysis (p=0.03). Overall survival for all patients was unaffected by any of the high-risk categories.

Conclusion

The data from this study suggests that women possessing high risk features are at no more meaningful risk for recurrence than other patients considered to be acceptable for APBI treatment. However, the finding of axillary recurrence in patients with triple negative breast cancer does warrant a degree of caution in proceeding with accelerated partial breast irradiation technique in this patient group.
Analysis of Radiation Dose to the Shoulder by Treatment Technique and Correlation With Patient Reported Outcomes in Patients Receiving Regional Nodal Irradiation
Authors: Bazan Jose G. , DiCostanzo Dominic , Hock Karen , Jhawar Sachin , Kuhn Karla , Lindsey Kylee , Tedrick Kayla , Healy Erin , Beyer Sasha , White Julia R.
Published: March 2021

Background/Purpose

Shoulder/arm morbidity is a late complication of breast cancer treatment with surgery and regional nodal irradiation (RNI). We set to analyze the impact of radiation technique [intensity modulated radiation therapy (IMRT) or 3D conformal radiation therapy (3DCRT)] on radiation dose to the shoulder with a hypothesis that IMRT use results in smaller volume of shoulder receiving radiation. We explored the relationship of treatment technique on long-term patient-reported outcomes using the quick disabilities of the arm, shoulder, and hand (q-DASH) questionnaire.

Materials/Methods

We identified patients treated with adjuvant RNI (50 Gy/25 fractions) from 2013 to 2018. We retrospectively contoured the shoulder organ-at-risk (OAR) from 2 cm above the ipsilateral supraclavicular (SCL) planning target volume (PTV) to the inferior SCL PTV slice and calculated the absolute volume of shoulder OAR receiving 5–50 Gy (V5–V50). We identified patients that completed a q-DASH questionnaire ≥6 months from the end of RNI.

Results

We included 410 RNI patients: 54% stage III, 72% mastectomy, 35% treated with IMRT. IMRT resulted in significant reductions in the shoulder OAR volume receiving 20–50 Gy vs. 3DCRT. In total, 82 patients completed the q-DASH. The mean (SD) q-DASH=25.4 (19.1) and tended to be lower with IMRT vs. 3DCRT: 19.6 (16.4) vs. 27.8 (19.8), p=0.078.

Conclusion

We found that IMRT reduces radiation dose to the shoulder and is associated with a trend toward reduced q-DASH scores ≥6 months post-RNI in a subset of our cohort. These results support prospective evaluation of IMRT as a technique to reduce shoulder morbidity in breast cancer patients receiving RNI.
Modeling Sarcopenia to Predict Survival for Patients With Nasopharyngeal Carcinoma Receiving Concurrent Chemoradiotherapy
Authors: Hua Xin , Li Wang-Zhong , Huang Xin , Wen Wen , Huang Han-Ying , Long Zhi-Qing , Lin Huan-Xin , Yuan Zhong-Yu , Guo Ling
Published: March 2021

Background

The present study aimed to construct a prognostic nomogram including Epstein-Barr virus DNA (EBV-DNA) and sarcopenia in patients with nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT).

Methods

In this retrospective analysis, we studied 1,045 patients with NPC who had been treated with CCRT between 2010 and 2014. Sarcopenia was determined using routine pre-radiotherapy computed tomography scans of the third cervical vertebrae. A new S-E grade was constructed using a receiver-operating characteristic (ROC) curve analyses determined cutoff values of sarcopenia and plasma EBV-DNA. The nomogram was developed base on the sarcopenia-EBV (S-E) grade and traditional prognostic factors. A calibration curve, time-dependent ROC, decision curve analysis, and the concordance index (C-index) determined the accuracy of prediction and discrimination of the nomogram, and were compared with TNM staging system and a traditional nomogram.

Results

Patient survival was significantly different when sarcopenia (P < 0.001) or EBV-DNA (P = 0.001) were used and they continued to be independent prognostic factors for survival upon univariate (P < 0.001, P = 0.002, respectively) and multivariate (P < 0.001, P = 0.015, respectively) analyses. Predicting overall survival (OS) was more accurate using the S-E grade than using TNM staging and sarcopenia or EBV-DNA alone. Nomogram B (model with sarcopenia) or nomogram A (model without sarcopenia) were then developed based on the identified independent prognostic factors. Comparing nomogram prediction with actual observation showed good agreement among the calibration curves for probability of 1-, 3-, and 5-year OS. Predicted survival (C-index = 0.77) of nomogram B was statistically higher than that of nomogram A (0.676, P = 0.020) and TNM staging (0.604, P < 0.001). Risk group stratification could distinguish between survival curves within respective TNM stages (all stages, P < 0.001; stage III, P < 0.001; stage IV, P = 0.002).

Conclusions

The sarcopenia-EBV DNA nomogram allowed more accurate prediction of prognosis for patients with NPC receiving CCRT.
ESR1 Gene Mutation in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Patients: Concordance Between Tumor Tissue and Circulating Tumor DNA Analysis
Authors: Urso Loredana , Vernaci Grazia , Carlet Jessica , Lo Mele Marcello , Fassan Matteo , Zulato Elisabetta , Faggioni Giovanni , Menichetti Alice , Di Liso Elisabetta , Griguolo Gaia , Falci Cristina , Conte Pierfranco , Indraccolo Stefano , Guarneri Valentina , Dieci Maria Vittoria
Published: March 2021

Endocrine therapy represents the cornerstone of treatment in hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (mBC). The natural course of this disease is marked by endocrine resistance, mainly due to Estrogen Receptor 1 (ESR1) acquired mutations. The aim of this study is to evaluate the concordance between ESR1 status in metastatic tumor specimens and matched circulating tumor DNA (ctDNA). Forty-three patients with HR+, HER2-negative mBC underwent both a metastatic tumor biopsy and a liquid biopsy at the time of disease progression. DNA extracted from formalin fixed paraffin embedded (FFPE) tumor specimens and ctDNA from matched plasma were analyzed by droplet digital (dd)PCR for the main ESR1 mutations (Y537S, Y537C, Y537N, D538G, E380Q). We observed a total mutation rate of 21%. We found six mutations on tissue biopsy: Y537S (1), D538G (2), Y537N (1), E380Q (2). Three patients with no mutations in tumor tissue had mutations detected in ctDNA. The total concordance rate between ESR1 status on tumor tissue and plasma was 91%. Our results confirm the potential role of liquid biopsy as a non-invasive alternative to tissue biopsy for ESR1 mutation assessment in mBC patients.
Lymphopenia in Esophageal Cancer: What Have We Learned?
Authors: Wang Jia-Lin , Ma Rong , Kong Wei , Zhao Ren , Wang Yan-Yang
Published: March 2021

Lymphopenia caused by disease or treatment is frequent in patients with cancer, which seriously affects the prognosis of these patients. Immune checkpoint inhibitors (ICIs) have garnered attention as one of the most promising strategies for the treatment of esophageal cancer (EC). The status of the immune system, such as, the lymphocyte count, is now considered to be an important biomarker for ICI treatments. Recognition of the significant impact of the lymphocyte count on the survival of patients with EC in the era of immunotherapy has revived interest in understanding the causes of lymphopenia and in developing strategies to predict, prevent and eliminate the adverse effect of lymphopenia. Here, we review what we have learned about lymphopenia in EC, including the prognostic and predictive value of lymphopenia in patients with EC, the predictors of lymphopenia, and the strategies to ameliorate the effect of lymphopenia in patients with EC.
Micro1278 Leads to Tumor Growth Arrest, Enhanced Sensitivity to Oxaliplatin and Vitamin D and Inhibits Metastasis via KIF5B, CYP24A1, and BTG2, Respectively
Authors: Lin Weidong , Zou Heng , Mo Jinggang , Jin Chong , Jiang Hao , Yu Chengyang , Jiang Zufu , Yang Yusha , He Bin , Wang Kunpeng
Published: March 2021

Colorectal cancer (CRC) is the most common cancer type in the digestive tract. Chemotherapy drugs, such as oxaliplatin, are frequently administered to CRC patients diagnosed with advanced or metastatic disease. A better understanding of the molecular mechanism underlying CRC tumorigenesis and the identification of optimal biomarkers for assessing chemotherapy sensitivity are essential for the treatment of CRC. Various microRNAs, constituting class of non-coding RNAs with 20-22 nucleotides, have served as oncogenes or tumor suppressors in CRC. We analyzed miR-1278 expression in clinical samples by qRT-PCR. We then explored the role of miR-1278 in CRC growth in vitro and in vivo as well as sensitivity to oxaliplatin via RNA-seq and gain- and loss-of-function assays. We found that miR-1278 was downregulated in CRC samples, correlating with advanced clinical stage, and overexpression of miR-1278 led to tumor growth arrest and increased sensitivity to oxaliplatin via enhanced apoptosis and DNA damage. Suppression of KIF5B by miR-1278 through direct binding to its 3′UTR was the mechanism for the miR-1278-mediated effects in CRC, miR-1278 inhibits metastasis of CRC through upregulation of BTG2. Additionally, we also found that the expression of CYP24A1, the main enzyme determining the biological half-life of calcitriol, was significantly inhibited by miR-1278, according to data from clinical, RNA-seq and functional assays, which allowed miR-1278 to sensitize CRC cells to vitamin D. In summary, our data demonstrated that miR-1278 may serve as a potential tumor suppressor gene and biomarker for determining sensitivity to oxaliplatin and vitamin D in CRC.
Patients With Short PFS to EGFR-TKIs Predicted Better Response to Subsequent Anti-PD-1/PD-L1 Based Immunotherapy in EGFR Common Mutation NSCLC
Authors: Liu Sangtian , Wu Fengying , Li Xuefei , Zhao Chao , Jia Yijun , Jia Keyi , Han Ruoshuang , Qiao Meng , Li Wei , Yu Jia , Zhou Fei , Xiong Anwen , Chen Bin , Fan Jue , Ren Shengxiang , Zhou Caicun
Published: March 2021

Background

Despite disappointing outcomes from immuno-monotherapy, studies reported that NSCLC patients with EGFR mutation may possibly benefit from combined immunotherapy. Whether the response to prior EGFR-TKI has association with the outcomes of subsequent immunotherapy remains unclear.

Patients and Methods

Advanced NSCLC patients with resistance to EGFR-TKIs and received ICI treatment from January 2016 to June 2019 were retrospectively analyzed. Single cell sequencing and flow cytometry were conducted to explore the difference of cell components in tumor microenvironments (TME). A 1:3 matched case–control study was conducted to compare the clinical effects of combined immunotherapy with standard chemotherapy as second-line treatment.

Results

Fifty-eight patients treated with anti-PD-1/PD-L1 based immunotherapy behind EGFR-TKI treatment were enrolled. Correlation analysis showed TKI-PFS had a significantly negative association with corresponding IO-PFS (r = −0.35, p = 0.006). TKI-PFS cutoff 10 months had the most significant predictive function for posterior immunotherapy and was validated to be an independent predictor by uni- and multivariate analyses. Kaplan–Meier analysis showed that patients with TKI-PFS less than 10 months had significantly prolonged IO-PFS and higher ORR than those with long (median PFS, 15.1 vs 3.8 months; HR, 0.26, p = 0.0002; ORR, 31.8 versus 10%, p = 0.04). Single cell RNA-seq revealed that the cell components were varied among patients after treatment with EGFR-TKI. Patients with short TKI-PFS demonstrated a relatively higher proportion of CD8 effector cells and lower ratio of M2 like macrophage to M1 like macrophages, which was validated by flow cytometry. Case–control study demonstrated that combined immunotherapy achieved significantly longer PFS (HR, 0.51, 95% CI: 0.31–0.85, p = 0.02), longer OS (HR, 0.48, 95% CI: 0.26–0.89, p = 0.05) and higher ORR (33.3 vs 10.0%, p = 0.02) than traditional chemotherapy for patients with short TKI-PFS.

Conclusion

Patients with short TKI-PFS conferred better response to immunotherapy than those with long. The status of TME were different among those two populations. Combined ICI treatment could promisingly be a better choice than classical chemotherapy in second-line setting for patients with short TKI-PFS and no T790M mutation. Underlying mechanisms need to be further explored.
CRISPR Gene-Editing Models Geared Toward Therapy for Hereditary and Developmental Neurological Disorders
Authors: Wong Poh Kuan , Cheah Fook Choe , Syafruddin Saiful Effendi , Mohtar M. Aiman , Azmi Norazrina , Ng Pei Yuen , Chua Eng Wee
Published: March 2021

Hereditary or developmental neurological disorders (HNDs or DNDs) affect the quality of life and contribute to the high mortality rates among neonates. Most HNDs are incurable, and the search for new and effective treatments is hampered by challenges peculiar to the human brain, which is guarded by the near-impervious blood-brain barrier. Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR), a gene-editing tool repurposed from bacterial defense systems against viruses, has been touted by some as a panacea for genetic diseases. CRISPR has expedited the research into HNDs, enabling the generation of in vitro and in vivo models to simulate the changes in human physiology caused by genetic variation. In this review, we describe the basic principles and workings of CRISPR and the modifications that have been made to broaden its applications. Then, we review important CRISPR-based studies that have opened new doors to the treatment of HNDs such as fragile X syndrome and Down syndrome. We also discuss how CRISPR can be used to generate research models to examine the effects of genetic variation and caffeine therapy on the developing brain. Several drawbacks of CRISPR may preclude its use at the clinics, particularly the vulnerability of neuronal cells to the adverse effect of gene editing, and the inefficiency of CRISPR delivery into the brain. In concluding the review, we offer some suggestions for enhancing the gene-editing efficacy of CRISPR and how it may be morphed into safe and effective therapy for HNDs and other brain disorders.
COVID-19 in Children With Liver Disease
Authors: Di Giorgio Angelo , Hartleif Steffen , Warner Suzan , Kelly Deirdre
Published: March 2021

Background: The global pandemic caused by novel Coronavirus SARS-CoV-2 disease (COVID-19) is a major threat to the general population and for patients with pre-existing chronic conditions. We report data concerning SARS-CoV-2 infection in children with chronic liver disease (CLD).

Methods: A literature review using the online database PubMed was performed to summarize available findings on the association between pre-existing liver disease and COVID-19 infection in children.

Results: Children with COVID-19 have preserved effector and immunosuppressive components resulting in a milder disease compared to adults. The most common hepatic manifestation is an elevation of hepatic transaminases. Liver damage may be directly caused by viral infection of liver cells, by medications or by the chronic hypoxia seen in COVID-19 patients. A multicenter study reported that the majority of children with a CLD remained healthy during the outbreak. Similarly, studies reported that children on immunosuppressive treatment, including patients with autoimmune liver disease (AILD) and liver transplantation (LT), maintained good health during the outbreak without experiencing major complications even if infected with COVID-19.

Conclusion: COVID-19-related liver injury presents with a mild elevation of transaminases, although its clinical significance is unclear. Children with CLD, including those with AILD and post-LT, do not have an increased risk for severe disease course of SARS-CoV-2 infection with little or no liver dysfunction. These data highlight the necessity to ensure normal standards of care while adhering to national Covid-19 guidelines, and particularly to maintain immunosuppressive medication to prevent relapse or rejection. Further research is required to evaluate the differences in clinical course between immunosuppressed adults and children and in particular whether asymptomatic infection is a concern.
An Open Access Database of Licensed Cancer Drugs
Authors: Pantziarka Pan , Capistrano I Rica , De Potter Arno , Vandeborne Liese , Bouche Gauthier
Published: March 2021

A global, comprehensive and open access listing of approved anticancer drugs does not currently exist. Partial information is available from multiple sources, including regulatory authorities, national formularies and scientific agencies. Many such data sources include drugs used in oncology for supportive care, diagnostic or other non-antineoplastic uses. We describe a methodology to combine and cleanse relevant data from multiple sources to produce an open access database of drugs licensed specifically for therapeutic antineoplastic purposes. The resulting list is provided as an open access database, (http://www.redo-project.org/cancer-drugs-db/), so that it may be used by researchers as input for further research projects, for example literature-based text mining for drug repurposing.
Solution to the Modified Helmholtz Equation for Arbitrary Periodic Charge Densities
Authors: Winkelmann Miriam , Di Napoli Edoardo , Wortmann Daniel , Blügel Stefan
Published: March 2021

We present a general method for solving the modified Helmholtz equation without shape approximation for an arbitrary periodic charge distribution, whose solution is known as the Yukawa potential or the screened Coulomb potential. The method is an extension of Weinert’s pseudo-charge method [Weinert M, J Math Phys, 1981, 22:2433–2439] for solving the Poisson equation for the same class of charge density distributions. The inherent differences between the Poisson and the modified Helmholtz equation are in their respective radial solutions. These are polynomial functions, for the Poisson equation, and modified spherical Bessel functions, for the modified Helmholtz equation. This leads to a definition of a modified pseudo-charge density and modified multipole moments. We have shown that Weinert’s convergence analysis of an absolutely and uniformly convergent Fourier series of the pseudo-charge density is transferred to the modified pseudo-charge density. We conclude by illustrating the algorithmic changes necessary to turn an available implementation of the Poisson solver into a solver for the modified Helmholtz equation.
Shear Wave Elastography Based on Noise Correlation and Time Reversal
Authors: Brum Javier , Benech Nicolás , Gallot Thomas , Negreira Carlos
Published: March 2021

Shear wave elastography (SWE) relies on the generation and tracking of coherent shear waves to image the tissue's shear elasticity. Recent technological developments have allowed SWE to be implemented in commercial ultrasound and magnetic resonance imaging systems, quickly becoming a new imaging modality in medicine and biology. However, coherent shear wave tracking sets a limitation to SWE because it either requires ultrafast frame rates (of up to 20 kHz), or alternatively, a phase-lock synchronization between shear wave-source and imaging device. Moreover, there are many applications where coherent shear wave tracking is not possible because scattered waves from tissue’s inhomogeneities, waves coming from muscular activity, heart beating or external vibrations interfere with the coherent shear wave. To overcome these limitations, several authors developed an alternative approach to extract the shear elasticity of tissues from a complex elastic wavefield. To control the wavefield, this approach relies on the analogy between time reversal and seismic noise cross-correlation. By cross-correlating the elastic field at different positions, which can be interpreted as a time reversal experiment performed in the computer, shear waves are virtually focused on any point of the imaging plane. Then, different independent methods can be used to image the shear elasticity, for example, tracking the coherent shear wave as it focuses, measuring the focus size or simply evaluating the amplitude at the focusing point. The main advantage of this approach is its compatibility with low imaging rates modalities, which has led to innovative developments and new challenges in the field of multi-modality elastography. The goal of this short review is to cover the major developments in wave-physics involving shear elasticity imaging using a complex elastic wavefield and its latest applications including slow imaging rate modalities and passive shear elasticity imaging based on physiological noise correlation.