bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: A symptom assessment study in patients >65 years old.
Authors: Eraj Salman Ali , Jomaa Mona K , Rock Crosby Douglas , Mohamed Abdallah , Garden Adam S. , Sturgis Erich M. , Hutcheson Kate A. , Lu Charles , Frank Steven J. , Morrison William H. , Rosenthal David Ira , Fuller Clifton David , Gunn Gary Brandon ,   MD Anderson Head and Neck Cancer Symptom Working Group
Published: September 2018

e21611 Background: Given the potential for older patients (pts) to experience exaggerated toxicity and symptoms, this study was performed to characterize pt reported outcomes (PROs) in older pts following definitive radiation therapy (RT) for oropharyngeal cancer (OPC). Methods: Disease-free head and neck cancer survivors ( > 6 mos. since tx) were eligible for participation in a questionnaire-based study. Participants completed the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Those who had been treated for OPC with definitive RT (w/ or w/o systemic therapy) and were > 65 y/o at time of RT were included. Individual and overall symptom severity and clinical variables were analyzed. Results: Of the 79 participants analyzed, 82% were male, 95% white, 41% T3/4 disease, 39% RT alone, 27% induction chemotherapy, 52% concurrent, and 18% both, and 96% IMRT. Median age at the time of RT was 71 yrs. (range: 65-85); median time from end of RT to MDASI-HN completion was 46 mos. (2/3 > 24 mos.). The top 5 MDASI-HN items rated most severe in terms of mean (±SD) ratings (0-10 scale) were dry mouth (3.48±2.95), taste (2.81±3.29), swallowing (2.59±2.96), mucus in mouth/throat (2.04±2.68), and choking (1.30±2.38) reported at moderate to severe levels (≥5) by 35, 29, 29, 18, and 13%, respectively. Thirty-nine % reported none (0) or no more than mild (1-4) symptoms across all 22 MDASI-HN symptoms items, and 38% had at least one item rated as severe (≥7). Hierarchal cluster analysis resulted in 3 patient groups: 1) ~75% with generally no to moderate symptom burden, 2) ~25% with moderate to severe ratings for a subset of classically RT-related symptoms (e.g. dry mouth, mucus, swallow, taste), and 3) only 2 pts with severe ratings of nearly all items. Subgroup comparisons will be presented. Conclusions: The overall long-term symptom burden seen in this older OPC cohort was largely favorable, yet a higher symptom group (~25%) with a distinct pattern of mostly local symptoms was identified. We have implemented the routine use of symptom assessment tools as part of OPC survivorship programs and plan to explore age-dose-modeling of symptoms identified and associated normal structures.
Evaluation of nutritional parameters in prechemotherapy of oncology patients in a service of the Unified Health System.
Authors: Graziani Silvia Regina , Vital Carolina Graziani , Fernandes Hezio Jadir , Naime Fauzia de Fátima , Fonseca Ricardo Oliveira Da , Dias Carla Andressa Rodrigues , Almeida Ligia Rabello De , Neto Raphael Francisco Azuaga , Yamada Karina Emi , De Abreu Maria Stella Sa Granja , Pontes Tatiana Caldeira , D'Alvia Thiago , Ferreira Rafael Sanches , Eyzaguirre Velasquez Arianne Renata , Orias Valéria Urresti , Vanderlinde Fabiano Garcia , de Almeida Leandro Maritan , Diniz Paula Calixto Batistela , Van Eyll Brigitte M. , Costa Cassia 
Published: September 2018

e21628 Background: Pre-chemotherapy nutritional evaluation is fundamental strategy as predictive factor for the possibility of response to oncological treatment and treatment-related toxicity. As in the Unified Health System patients usually arrive for evaluation with advanced disease, we believe that medical evaluation of the nutritional parameters is important in the therapeutic decision. Methods: From October 2015 through July 2016, we evaluated 210 patients referred for cancer treatment at the Arnaldo Vieira de Carvalho Cancer Institute in São Paulo (Brazil), which is an Institution that exclusively serves the Unified Health System. We evaluated the clinical parameters of weight and height, for estimation of BMI; evaluation the muscle of the fold of the thumb; and laboratory parameters as hemoglobin, lymphocytes, albumin, PCR (C-reactive protein) levels. We included 54 patients with gastrointestinal tract carcinoma; 32 colorectal carcinoma, 14 gastric carcinoma, 8 esophageal carcinoma, 12 lung carcinoma, 16 head and neck carcinomas, 38 breast carcinoma, 6 cervical carcinoma, 4 uterine carcinoma, 6 ovarian carcinoma, 4 malignant melanoma carcinoma, 2 soft tissue sarcomas, 10 prostate carcinoma, and 4 bladder carcinoma. Results: We found significant changes in the clinical nutritional parameters in patients with gastric, esophageal, lung and head and neck carcinomas, whose hemoglobin levels were among the mean normal values of 8.9 g/dL (6.5-10.3 g/dL), the lymphocytes levels were 850/mm3 (450-1200/mm3), the albumin levels were 3.2 g/dL (2.3-3.8 g/dL), the PCR levels were 126 mg/L (80-620 mg/L) and the Adductor muscle of the thumb were < 1 mm. Although all the evaluated patients presented advanced stages in diagnosis, the tumors of breast, prostate, uterine body, malignant melanoma and bladder did not present any significant alterations in the nutritional state. Conclusions: Our strategy shows that nutrition evaluation is an easy-to-use instrument, and opens the possibility of using in the therapeutic decision in patients with severe mal nutrition and compromising the general condition, since palliative chemotherapy has no impact on the overall survival of this population.
Online yoga as a non-pharmacologic symptom management approach in myeloproliferative neoplasms.
Authors: Huberty Jennifer , Eckert Ryan , Gowin Krisstina L. , Ginos Brenda F. , Kosiorek Heidi E. , Dueck Amylou C. , Larkey Linda , Mesa Ruben A. 
Published: September 2018

e21704 Background: Patients with myeloproliferative neoplasms (MPN) have difficult symptom burden (i.e. fatigue, pruritus, night sweats) not resolved by current medical therapies including jak inhibitor therapy. We hypothesize that on-line (at home) yoga might alleviate MPN symptoms and complement medical therapy. Methods: MPN patients, recruited by social media, were asked to complete 60 min/week of online yoga (designed for MPN patients) for 12 weeks and completed online self-report surveys (weeks 0,7,12 and 16) on participation (Qualtrics), disease features, and symptom burden (MPN Symptom Assessment Form; NIH PROMIS measures of pain, anxiety, depression, sleep, and sexual function). Results: Two hundred and forty-four MPN patients completed the eligibility survey, 134 were eligible, 55 completed the informed consent, and 38 MPN patients completed the 12-week intervention. The majority of participants were diagnosed with either PV (n = 16) or ET (n = 16), with MF being less common (n = 6). Approximately 37% (n = 14) of study participants averaged ≥60 min/week of yoga (i.e., demand). Yoga participation averaged 50.8±36.2 min/week. Overall, 68% of participants were satisfied with online yoga and 75% felt that is was helpful for coping with MPN-related symptoms (i.e., acceptability, practicality). Additionally, 75% of participants felt safe from injury while participating in online yoga. Only one adverse event was reported (irritated enlarged spleen). From week 0 to week 12 (n = 38), there were significant improvements in total symptom burden (effect size [ES] in standard deviation units = -0.36, p = 0.004), anxiety (ES = -0.67, p = 0.002), depression (ES = -0.41, p = 0.049), sleep (ES = -0.58, p < 0.001), and fatigue (ES = -0.33, p = 0.04). These improvements remained significant at follow-up week 16 (n = 28) for all outcome measures with a trend for maintained fatigue improvement (ES = -0.34, p = 0.06) (see Table 1). There were no significant differences in outcomes between those that averaged < 60 min/week of yoga compared to those that averaged ≥60 min/week of yoga. Conclusions: A 12-week online yoga intervention is feasible (i.e., accepted, practical) for MPN patients and merits a randomized trial as complementary therapy.
Acupuncture for breast cancer related lymphedema: A randomized controlled trial.
Authors: Bao Ting , Van Zee Kimberly J. , Cassileth Barrie R. , Coleton Marci , Li Qing Susan , Mehrara Babak , Vertosick Emily , Vickers Andrew J. , Mao Jun J. 
Published: September 2018

e21706 Background: Up to 20% of breast cancer survivors develop breast cancer related lymphedema (BCRL), and current therapies are limited. In a previous single armed study, acupuncture appeared to reduce BCRL. In this study, we compared our specific protocol of acupuncture (AC) to usual care wait list control (WL). Methods: Women with moderate persistent BCRL were randomized to AC or WL. The AC protocol included twice-weekly manual acupuncture over 6 weeks. The primary endpoint was change in circumference difference between affected/unaffected arms. Responders were defined as having > 30% improvement in arm circumference difference between arms. We also evaluated the change in difference between affected/unaffected arm bioimpedance. We used analysis of covariance for circumference and bioimpedance measurements and Fisher’s exact test for proportion of responders. Results: Among 82 patients, 73 (89%) were evaluable for the primary endpoint (36 in AC and 37 in WL). The median age in AC was 65 (IQR 54, 71) and 58 (IQR 49, 70) in WL. Most patients in both arms had undergone mastectomy (74%) and axillary lymph node dissection (96%), and had a history of prior lymphedema treatment (96%). Median duration of lymphedema was 2.2 years in AC (IQR 1.3, 3.0) and 2.5 years in WL (IQR 1.4, 3.4). We found no evidence of a difference in either arm circumference difference improvement (β -0.38cm, 95% CI -0.89, 0.12, p = 0.14) or bioimpedance difference improvement (β -1.06, 95% CI -7.85, 5.72, p = 0.8) between AC and WL at Week 6. There was also no difference in proportion of responders: 17% AC vs. 11% WL (6% difference, 95% CI -10%, 22%, p = 0.5). No severe adverse events (AE) were reported. Grade 1 treatment-related AEs such as bruising (58%), hematoma (2%), and pain (2%) were reported in patients receiving AC. Among the 837 acupuncture treatments provided, one possibly related grade 2 skin infection was reported. Conclusions: Although it appears to be safe and well tolerated, our acupuncture protocol did not offer additional clinically meaningful reductions in BCRL compared with usual care among patients who had received lymphedema treatment. This regimen should not be recommended for breast cancer survivors with persistent BCRL. Clinical trial information: NCT01706081.
Sarcoma tumor size (T) staging: Are radiology or pathology measurements more appropriate?
Authors: Pang Angela , Carbini Mariana , Demicco Elizabeth , Maki Robert G. 
Published: September 2018

e22522 Background: In the AJCC version 7 TNMG staging of soft tissue sarcomas (STS), the longest dimension (1D) of the primary tumor at pathology analysis is the gold standard for tumor size (T) staging. However, measurements may differ between scans and actual tissue measurement, due to tissue elasticity, deformation, and/or formalin fixation. Thus, tumor size may change compared to preoperative imaging. Should STS T stage be defined by imaging or by direct tumor measurement? We examined the variability of the measurements between radiology and pathology data, examining 1D, cross sectional area (2D), and tumor volume (3D) to assign a T stage. Methods: We reviewed all patients (pts) with extremity STS who had surgery at Mt Sinai Hospital New York (2010-2015). MRI or CT and resected gross tumor measurements were available for 79 pts. After eliminating 10 samples with grossly irregular shapes and 11 samples with incomplete data, 58 tumors had complete 3D measurements. We calculated Pearson correlation coefficients for paired variables (radiology vs pathology size in 1D, 2D and 3D). Results: Imaging measures correlated well with direct tumor measurements. Pearson correlation coefficients for 1D, 2D and 3D measurements were 0.93, 0.72 and 0.78, respectively (all p < 0.01). The SEM (radiology/pathology size) = 0.13, i.e. 13% for 1D measurements. Thus, T stage could be incorrectly assigned in up to 13% of samples near 5 cm in size; this proportion decreases the further the tumor is from the 5 cm cutoff. Conclusions: As shown previously in the rationale for RECIST, 1D measures provide the smallest variance between radiology and pathology. The situation is made more complex in AJCC version 8, with four T categories. It remains unclear how to stage the 10-15% of primary STS with irregular shapes. These data support the use of nomograms for risk assessment rather than using bins created by the AJCC tumor staging system. 3D tumor volumes, if used at all, may play a greater role when assessing therapy responses or contending with tumors of irregular shape, rather than for routine STS staging.
miR-106b-5p, miR-17-5p to predict recurrence and progression in breast DCIS model based on TGFβ paradox.
Authors: Lee Jieun , Yim Kwangil , Kim Dong-Min , Song Young-Seok , Lee Ahwon 
Published: September 2018

e23019 Background: Ductal carcinoma in situ (DCIS) is a well-known precursor of invasive ductal carcinoma (IDC). Part of patients show disease recurrence as DCIS or IDC after local treatment, but there are no established markers for prediction of recurrence. Methods: Authors analyzed 30 patients diagnosed as pure DCIS, recurrent DCIS, and IDC progressed in DCIS background. miRNA was extracted from archival tissue, and hierarchical clustering of miRNA microarray was performed. We selected highly expressed miR-17-5p and miR-106b-5p as marker for recurrence of DCIS. Two miRNAs were transfected to MCF-12 and MCF-7 cell line. Cell proliferation assay and Western blot analysis was performed for analyzing the interaction between cell proliferation and TGFβ downstream pathway. Results: miR-106b-5p single and combined miR-106b-5p and miR-17-5p transfected MCF-12 cell line showed increased proliferation index compared to un-transfected cell line. In MCF-7, miR-106b and miR-17-5p transfected cell line showed inferior proliferation index compared to un-transfected cell line. Western blot analysis showed minimal increased expression of SMAD4, phosphorylated SMAD2 (pSMAD2) in miR-106b-5p and miR-17-5p transfected MCF-12 cell line. However, decreased expression of TGFBR2 and no interval change of SMAD4 and pSMAD2 was detected in miR-106b-5p and miR-17-5p transfected MCF-7 cell line. Conclusions: miR-106-5p, miR-17-5p showed increased expression in recurrent DCIS or IDC based on miRNA hierarchical microarray. miRNA transfected MCF-12 cell line showed increased proliferation index and activated TGFβ downstream pathway. miRNA transfection might have made normal cell line to pre-cancerous cell line and TGFβ pathway might have influenced to promote tumor proliferation, based on TGFβ paradox hypothesis.
ctDNA detection of EGFR mutations in NSCLC patients using TargetSelector.
Authors: Beerkens Frans , Kim Chul , Hasan Syed P. , Subramaniam Deepa Suresh , Liu Stephen V. , Arnold Lyle , Vibat Cecile Rose T. , Singh Veena M. , Giaccone Giuseppe 
Published: September 2018

e23037 Background: EGFR mutations are the most frequent targetable genomic alterations in non-small cell lung cancer (NSCLC) patients (pts). While tissue biopsy remains the standard for assessing of EGFR mutation status, it is invasive and not always feasible. Liquid biopsy is a minimally invasive alternative. Biocept’s proprietary TargetSelector system evaluates circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in blood. We aimed to clinically validate the accuracy of EGFR-specific TargetSelector in NSCLC pts. Methods: At three time points (T0: baseline before TKI, T1: during EGFR-TKI therapy, T2: after progression), blood samples were collected in Biocept OncoCEE BCT validated to preserve DNA up to 8 days. These samples were interrogated for three EGFR mutations: exon 19 deletions (Del 19), L858R, and T790M. The objectives are to assess detection sensitivity of liquid biopsy using EGFR mutation status vs the tissue as gold standard and to evaluate whether the detection sensitivity changes with EGFR-TKI therapy. Results: A total of 53 study pts were enrolled (male, 21; female, 32). The mean age was 70.6 (range: 46 – 90). Most pts had stage IV disease (43, 81.1%) and lung adenocarcinoma (48, 90.6%). 26 (49.1%) pts had EGFR mutations in tumor tissue: Del 19, 13; L858R, 8; T790M, 6; other, 8. Detection sensitivity for sensitizing EGFR mutations (Del 19 and L858R) at T0, T1, and T2 was 60.0% (6/10), 33.3% (5/15), and 33.3% (1/3), respectively. There was no statistical difference in CTC counts between activating EGFR mutation-positive and -negative pts (mean CTC count: 10.5 vs 20.1; p = 0.11 by two-sided t-test). Detection sensitivity for T790M was 33.3% (2/6) and 5 of 6 pts were receiving T790M directed therapy (3, rociletinib; 2, osimertinib) at the time of blood draw. Two pts – one patient before initiation of EGFR-TKI and the other during treatment with erlotinib – were found to have T790M mutations only in blood and not in tissue. Conclusions: Activating EGFR mutation detection may decrease during the course of TKI therapy, possibly due to treatment response. Further research with an expanded sample size and serial collections are needed to evaluate this finding, and to investigate possible implications of the presence of T790M only in blood.
PDL1 test to assess the dynamic range of mRNA expression from platelet enriched plasma in patients with NSCLC.
Authors: Mellert Hestia S. , Jackson Leisa , Pestano Gary Anthony 
Published: September 2018

e23063 Background: Therapeutic options for patients with non-small cell lung cancer (NSCLC) continue to expand with the advent of immunotherapies. Lack of tissue and drawbacks with IHC have increased the need for blood-based diagnostics that measure continuous variables. Thus these tests are of increasing relevance for clinical testing. Methods: We focused on mechanisms of blood-based testing for the sensitive measurement of circulating RNA using ddPCR. Specifically, we optimized methods for the detection of PD-L1 and cytokeratin 19 (CK19) transcripts recovered from plasma. Specimens included tumor derived cell-lines, activated and resting immune cells, normal donor plasma and NSCLC (stages 1-4) donor plasma. Results: Assessing PD-L1 in circulation is complicated by its expression in both immune and cancer cells. Analytic performance was initially evaluated with cancer cell lines and activated lymphocytes and monocytes expressing variable levels of cytokeratins and PD-L1. A preliminary threshold was defined based on CK19 expression levels in normal donor plasma (n = 35). Of the 79 NSCLC donors tested 49% expressed CK19 above the threshold, indicating they contained sufficient circulating RNA derived from tumor. These donor samples tested either positive for EGFR del19 E746-A750 or L858R (n = 13), negative for EGFR (n = 10) or positive for KRAS G12C/V (n = 16). We found no differentiation in PD-L1 levels on the basis of EGFR sensitizing and EGFR wild-type status. We observed only three donors that expressed PD-L1 at high levels, and this was regardless of EGFR mutation status. In contrast, 30% of KRAS mutation-positive donor samples were above the pre-defined PDL1 threshold (n = 6 of 16 samples tested). These data are consistent with tissue-based studies that report trends of higher PD-L1 expression in KRAS positive NSCLC patients. Conclusions: We have developed sensitive and specific methods to measure the dynamic range of PD-L1 in circulation and have shown utility of these methods by evaluating key immune and cancer-specific RNAs.
Anticancer applications of allosteric inhibitors of proteasome.
Authors: Osmulski Pawel A. , Cropper Jodie , Giletto Matt , Jones Corey , Killer Caleb , Jiang Shoulei , Tepe Jetze , Chatterjee Bandana , Huang Tim , Gaczynska Maria E 
Published: September 2018

e23066 Background: Proteasome as a hub protease of the ubiquitin proteasome pathway is an established anticancer drug target. Several drugs that inhibit proteasome are currently used to successfully treat aggressive blood cancers. These drugs are based on their competition with protein substrates of proteasome. However, efficacy of these drugs toward solid cancers is inadequate. Besides, the side effects and developing drug resistance are increasingly hampering the therapy. Therefore, there is an unmet challenge to develop new types of proteasome targeting compounds that are efficient against solid cancers and utilize other mechanisms to stop proteasome. Here we present a compound with a novel molecular mechanism, potentially bypassing limitations of the available drugs. Methods: We rationally designed and synthesized a series of small molecule “B” compounds, derivatives of a binding domain of seco-rapamycin that noncompetitively interfere with peptidase activities of proteasome. We tested effects of the compounds in vitro on purified proteasome, in cellulo with selected cancer cell lines and in a xenograft mouse model of prostate cancer. Results: We found that compound B1 binds to the catalytic core of proteasome far from the catalytic sites, destabilizes assembly of the 26S proteasome responsible for digest of polyUb substrates and allosterically inhibits its proteolytic activities. Molecularly, B1 impedes the gating mechanism responsible for substrate uptake as found with AFM. Tryptophan fluorescence indicates that B1 changes proteasome fold and the binding mode of competitive inhibitors. B1 substantially decreases viability of selected cancer cell lines and shifts their mechanical phenotype toward noncancerous status. B1 synergizes with bortezomib decreasing the IC50 5-10 fold. In a xenograft hormone resistant prostate cancer model, B1 treatment leads to shrinkage of the tumor size, decreases enumeration of aggressive, EpCAM+ CTCs and shifts the macrophage profile toward predator M1 type. Conclusions: B1 compounds constitute a new class of noncompetitive allosteric inhibitors of proteasome that could be useful to develop to treat aggressive prostate cancers alone or in synergy with competitive inhibitors.