tbuckley/cabot-search huggingface dataset:
Application of very low dose-rate brachytherapy in gastrointestinal cancer.
Authors: Arnold M. Herskovic, Mark Rivard, Richard I Rothstein, Karen L Moodie, Kathleen Corcoran, Lynne Swanson, Claude Clerc
Journal: Journal of Clinical Oncology (2017)

201 Background: Despite treatment intensity escalation, the high local recurrence rate for esophageal cancer has frustrated clinicians for decades. Conventional High Dose Rate brachytherapy, particle therapies, and other sophisticated treatment methods are encouraging but often fiscally and/or biologically infeasible. Additionally, these technologies often burden patients with numerous hospital visits, decreasing patient quality of life. Very low dose-rate brachytherapy (vLDR), with sources emitting relatively low energy, can be more cost effective than conventional radiation treatments, particularly in underserved communities, and can replace many hospital visits with one procedure. The dose distribution advantages of vLDR are irrefutable, especially in regard to doses to other tissues. vLDR seeds are currently used regularly in the prostate and have been tested in several other anatomical sites with good safety results. In the present study, a radioactive(RA) stent platform was developed and tested to apply vLDR therapy to cancers of the gastrointestinal (GI) system. Methods: Monte Carlo simulations were used to guide design of a RA esophageal stent. A design was chosen that minimized surface dose variation while using commercially available RA seeds. RA stents loaded with 60 -125 Seed-in Carrier, GE Healthcare were endoscopically placed in the naïve esophagus of 3 Yucatan swine. Previously, mock treatments using dummy seeds were performed in three similar pigs. Stents were left in place for between 4 and 7 weeks and reaction of the mucosa was assessed macroscopically and histologically. Results: Porcine esophageal tissue received doses in the range of 132-160 Gy at the mucosal surface and 39-48 Gy at a distance of 5mm from the stent surface. Tissues were collected at 0, 1 and 10 weeks after stent removal. No macroscopic radiation damage was seen at autopsy and pathological analysis yielded no radiation-related damage in evaluable tissues. Conclusions: In this preliminary study, no local or systemic damage due to radiation was observed after treatment of normal esophageal tissue with a vLDR stent device. Ongoing research aims to determine dose tolerance in esophageal tissue and target application of vLDR in other locations in the GI tract.
Laboratory Monitoring of Non–Vitamin K Antagonist Oral Anticoagulant Use in Patients With Atrial Fibrillation
Authors: John W. Eikelboom, Daniel J. Quinlan, Jack Hirsh, Stuart J. Connolly, Jeffrey I. Weitz
Journal: JAMA Cardiology (2017)

The non-vitamin K antagonist oral anticoagulants (NOACs) apixaban, dabigatran, edoxaban, and rivaroxaban are administered in fixed doses without anticoagulant monitoring. Randomized trials show that unmonitored NOAC therapy is at least as effective as and safer than dose-adjusted warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. Subgroup analyses indicate that plasma drug levels or anticoagulant activity of the NOACs predict stroke and bleeding. This review examines the historical basis for anticoagulant monitoring, discusses methods to measure and interpret drug levels, and critically assesses the role of routine laboratory monitoring in the management of NOAC therapy.The predictable anticoagulant response of NOACs has provided the pharmacological basis for their administration in fixed doses without routine coagulation monitoring. Although it is possible to accurately measure NOAC drug levels, within-patient variability complicates interpretation of these results. Furthermore, patient characteristics, such as age and renal function, confound the association between NOAC drug levels and clinical outcomes. Information is lacking on the optimal drug level in particular patient groups (eg, elderly, the renally impaired, and those with high bleeding risk), the appropriate dose adjustment to achieve expected levels, and whether routine laboratory monitoring and dose adjustment will improve clinical outcomes. A benefit of a management strategy that incorporates routine therapeutic drug monitoring and dose adjustment over current standard-of-care metrics without such monitoring remains unproven.Robust evidence from patients with atrial fibrillation randomized to NOACs or warfarin demonstrates that unmonitored NOAC therapy is at least as effective and safe as monitored warfarin, with lower rates of intracranial hemorrhage and reduced mortality. Further research is required to determine whether routine laboratory monitoring might provide a net benefit for patients. Until such data are available, clinicians should continue to prescribe NOACs in fixed doses without routine monitoring.
Association of the activation of the mTOR pathway with prognosis in Chinese melanoma patients.
Authors: Yan Kong, Lu Si, Xiao wei Xu, Keith T. Flaherty, Zhi Hong Chi, Chuan Liang Cui, Xi Nan Sheng, Jie Dai, Long Liang, Qian Nan Zhang, Jun Guo
Journal: Journal of Clinical Oncology (2012)

8561 Background: mTOR is a ubiquitously expressed protein kinase and a validated target in the treatment of cancer. However, the characterization of mTOR pathway in Asian melanoma populations has not been reported. Methods: This study involved primary tumor samples from 173 melanoma patients (79 acral melanomas, 57 mucosal melanomas, 17 melanomas on skin with chronic sun-induced damage, 20 melanomas on skin without chronic sun-induced damage) in Peking University Cancer Hospital &amp; Institute. Clinical data were collected. Immunohistochemistry assays using antibodies against pmTOR, pS6RP, p4E-BP1 and pAKT were performed on formalin-fixed, paraffin-embedded specimens. Somatic mutations within the hotspot regions of frequently mutated genes in mTOR pathway (AKT1, TSC1, PI3K genes, etc) were analyzed by PCR amplification and Sanger sequencing. Results: Among the 173 samples, 26% of the cases (45/173) demonstrated positive staining with pmTOR. Expression of pS6RP was observed in 37% (64/173) of cases. Expression of p4E-BP1 was observed in 27% (46/173) of cases. pAKT was expressed by 22% (38/173) of cases. Somatic mutations in examined genes were detected. The median survival time for patients with expression of pmTOR was significantly shorter than patients with absence of pmTOR expression (25.3 vs 62.9 months, P =0.048). In addition, statistical differences were found for ulceration rates between melanomas with or without pS6RP (64.1%vs 35.9%, P= 0.049). Moreover, the median survival time for mucosal melanoma patients with pAKT expression was significantly shorter than for patients with absence of pAKT expression (20.4 vs 52.1 months, P =0.022). Conclusions: These data demonstrate that activation of the mTOR signaling pathway carries prognostic significance in Asia patients with melanoma. Targeted therapies to mTOR pathway may offer a therapeutic benefit for these melanoma patients.
Phase II study of induction chemotherapy with carboplatin, paclitaxel, and bevacizumab followed by surgery in patients with stage III nonsquamous non-small cell lung cancer: The Tokyo Cooperative Oncology Group trial (TCOG1002)
Authors: Toshihiko Iizasa, Ichiro Yoshino, Sakae Okumura, Makoto Suzuki, Yukitoshi Satoh, Koichi Yoshida, Norihiko Ikeda
Journal: Journal of Clinical Oncology (2014)

7542 Background: The clinical staging and treatment of locally advanced non-squamous non-small-cell lung cancer (NSCLC) remains controversial. We performed a phase II trial of induction chemotherapy with carboplatin, paclitaxel, and bevacizumab followed by surgery in patients with stage III non-squamous NSCLC. Methods: This study was a multicenter phase II trial (TCOG 1002). After staging N status by endobronchial ultrasonography or positron emission tomography, patients with stage III non-squamous NSCLC received induction chemotherapy with carboplatin (AUC6), paclitaxel (200mg/m2), and bevacizumab (15mg/kg) twice every 3 weeks, followed by carboplatin (AUC6) and paclitaxel (200mg/m2) 3 weeks later. Surgery was then performed. The primary endpoint was overall response rate. Results: Among 26 patients enrolled, 24 underwent surgery after induction chemotherapy. Their demographic characteristics were as follows: 12 men and 12 women, 42 to 73 years of age (mean 58.7 ± 8.3 years); 23 adenocarcinomas; stage IIIA, 22 patients and stage IIIB, 2 patients; performance status (PS) 0, 22 patients. Induction chemotherapy was completed according to the protocol in 21 (88%) of the 24 patients. The response rate was 62.5% (partial remission, 15 patients; stable disease, 9 patients). The most frequent grade 3-4 toxicities were neutropenia, 16 cases; leukopenia, 4 cases; liver dysfunction, 2 cases; hypertension 1 case; and febrile neutropenia, 1 case. Complete resection was performed in 20 (83%) of the 24 patients (17 lobectomies and 5 bilobectomies). There were no severe perioperative complications. The pathological response rate was 32% (complete response, 1; major response, 6; minor response, 15). Nodal downstaging was found in 6 patients (N0, 4; N1, 2). Conclusions: Induction chemotherapy with carboplatin, paclitaxel, and bevacizumab followed by surgery is safe and feasible in patients with stage III non-squamous NSCLC. Our results indicate that further studies are warranted to confirm the safety and efficacy ofthis treatment regimenin stage III non-squamous NSCLC. Clinical trial information: UMIN000004327.
Recurrence patterns in esophageal cancer patients undergoing curative trimodality therapy.
Authors: Edwin Chan, Catherine Vanderwater, Rachel Woo, Charles Cho, Jason Wong, Wei Xu, Qihuang Zhang, Geoffrey Liu, Beibei Zhang, Agnes Cheung, Alex Lee, Pravin Philip Chacko, Ehab Fadhel, Zahra Kassam
Journal: Journal of Clinical Oncology (2017)

195 Background: To document pattern of recurrence and its relationship to the radiation treatment volume in esophageal cancer patients treated with trimodality therapy. Methods: Patients with adenocarcinoma or squamous cell carcinoma (SCC) of the esophagus, T1-4N0-3 (AJCC 7 th Ed.) treated with chemoradiation (CRT) and esophageal resection between June 2010 and November 2015 participated in a prospective cohort study. Patients were planned using 4DCT and IMRT or VMAT. GTV and CTV were contoured on 4D exhale, inhale phases and voluntary exhale helical CT. CTV margins were 3-4cm superiorly and inferiorly, and 1cm circumferentially. CTVs were combined to form the ITV. PTV margin was 0.5cm. Site of first disease recurrence was classified as in-field (within 90% isodose), marginal (between 50-90%), or out-of-field (outside 50%). Results: Fifty-eight patients participated. Median age was 66 years (range: 40–78); 52 males: 6 females. 49 had adenocarcinoma, 7 SCC, and 2 mixed histology. 52 (90%) had clinically node positive disease. 31 received concurrent radiation 45-50Gy/25fr with Cisplatin/5FU and 27 received 41.4Gy/23fr with Carboplatin/Paclitaxel (CROSS protocol). 15 (27%) achieved a pathological complete response (pCR). Median follow up was 1.6 years (range: 0.2-4.8), 2-year overall survival 71%, disease-free survival 59%, median survival 4.4 years and median time to relapse 2.3 years. 17 patients (29%) had disease recurrence of which, at initial diagnosis, all were clinically node positive and 3 had pCR after CRT. Five developed locoregional recurrence (2 anastomatic, 3 locoregional nodes), 4 both locoregional and distant, and 8 distant recurrence alone. Of 9 patients with locoregional recurrence, 1 had in-field, 6 out-of-field and 2 had disease traversing in and out-of-field areas. 4 of 17 (24%) were treated with curative intent (1 surgery, 3 CRT) and all were alive at the latest follow up (time from first recurrence: 6 to 49 months). Conclusions: Survival and recurrence outcomes in this small cohort are similar to those reported in the literature. Only a small proportion of patients experienced in-field relapse. Of those who relapsed, 24% received curative salvage therapy.
Encryption algorithms are effective in maintaining security
Authors: D. A Agbamu
Journal: BMJ (1996)

EDITOR,—Many doctors know little about the Internet, and while David Sellu is right to be concerned about the security issues relating to the increasing use of the Internet by doctors and other health care workers, his short piece does not give a realistic picture of the situation.1

The suggestion that “Pentagon computers can be infiltrated by hackers almost to the point of starting a nuclear war” owes more to Hollywood than to any documented event. His …
Caregiving burden in head and neck cancer.
Authors: Amanda M. Sherrod, Barbara A. Murphy, Nancy L. Wells, Stewart M. Bond, Melody Hertzog, Jill Gilbert, Melissa Adair, Lindsey Parks, William M. Lydiatt, Russel B. Smith, Oleg Militsakh, Robert H. Lindau, Karen Schumacher
Journal: Journal of Clinical Oncology (2014)

e20678 Background: Head and neck cancer (HNC) presents family caregivers (FCs) with enormous challenges, yet this population remains understudied. Caregiving tasks include general tasks (e.g., providing emotional support and managing symptoms) and HNC-specific tasks (e.g., tube feeding and tracheostomy care). HNC caregiving is complex because FCs provide care in the context of functional changes unique to HNC cancer, such as speech and swallowing difficulties that affect communication and lifestyle. We are developing and testing the HNC Caregiving Task Inventory (HNC-CTI) to assess HNC caregiving burden. Herein we report descriptive results on frequently performed tasks and difficulty with task performance. Methods: Eligibility criteria included primary FCs of patients with HNC during and within 12 months of completing treatment. 56 FCs completed the HNC-CTI which includes 108 items in 11 domains. Questions are directed at the frequency and difficulty of specific caregiving tasks. Moderate to severe difficulty is defined as ≥ 3 (0-5 Scale). Results: FC characteristics: 80% female, 86% spouses, 29% ≥ 65 years old, 50% ≤ high school education. Results are reported as % who endorsed performing the specific task (% reporting moderate-severe difficulty): managing anxiety 60.7 (52.9), maintaining calories 76.8 (44.2), managing phlegm 35.7 (40), encouraging normal activities 83.6 (39.1), providing emotional support 90.9 (38.8), preparing foods 78.9 (37.7), helping to make medical decisions 82.1 (37.0), monitoring mental status 58.9 (33.4), communicating with insurers 58.9 (33.3), aiding mobility 26.8 (33.3), managing fatigue 60.7 (29.4), assisting with finances 73.2 (29.3), monitoring swallowing 75.0 (28.5), managing constipation 57.1 (28.1), knowing when to call doctor 85.7 (27.1), managing pain 66.1 (27.0), helping with medications 85.7 (22.9), tracheostomy care (n=11) 54.5 (16.7), managing PEG problems 52 (15.4), and ensuring safety 83.6 (4.6). Conclusions: HNC FCs engage in a vast range of caregiving tasks. Task burden was high overall. Some tasks were particularly difficult for FCs. Among the 11 domains, none dominated as a specific area for targeting intervention. Interventions for caregivers will likely need to be broad in scope.
Phase I study of volasertib (BI 6727) combined with afatinib (BIBW 2992) in advanced solid tumors.
Authors: Marc Peeters, Jean-Pascal H. Machiels, Korinna Pilz, Marina De Smet, Natalja Strelkowa, Dan Liu, Sylvie Rottey
Journal: Journal of Clinical Oncology (2013)

2521 Background: Volasertib is a potent and selective cell cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinases (Plk). Volasertib and afatinib, an irreversible ErbB family blocker, have shown single agent anti-tumor activity and manageable safety profiles in patients (pts) with advanced solid tumors. This dose escalation study was designed to determine the maximum tolerated dose (MTD) of two combination schedules of volasertib and afatinib in pts with advanced solid tumors refractory to or not amenable to standard therapy. Methods: In a 3 + 3 design, cohorts of 3–6 pts received volasertib 150–300 mg IV d1 Q3W + afatinib 30–50 mg PO QD d2–21 Q3W (Schedule A) or afatinib 50–90 mg d2–6 Q3W (Schedule B). Up to 12 additional pts were enrolled at the MTD. Primary endpoint was the MTD per schedule. Secondary endpoints included pharmacokinetics (PK), safety and efficacy (RECIST). Results: 57 pts (median 58 yr; ECOG PS 0/1/2: 35%/60%/5%) were treated (n=29, Schedule A; n=28, Schedule B). MTD was volasertib 300 mg/afatinib 30 mg (Schedule A) and volasertib 300 mg/afatinib 70 mg (Schedule B). Cycle 1 dose limiting toxicities (DLTs) were experienced by 5 (Schedule A) and 7 (Schedule B) pts. Most common DLTs were diarrhea (n=5), neutropenia (n=3), fatigue (n=2) and decreased ejection fraction (n=2) in Schedule A, and thrombocytopenia (n=6), neutropenia (n=5), diarrhea (n=4) and febrile neutropenia (n=3) in Schedule B. Most common grade 3/4 adverse events were neutropenia (n=8), thrombocytopenia (n=6), diarrhea (n=3) and febrile neutropenia (n=3). Volasertib exhibited multi-exponential PK behavior with a long half-life (130 hr), moderate clearance (900 mL/min) and large volume of distribution (Vss &gt;6000 L). Co-administration of volasertib and afatinib had no effect on the PK profile of either drug. Two pts in Schedule A (volasertib 300 mg/afatinib 30 mg) achieved partial responses (tumor types: NSCLC, head and neck). Conclusions: MTD of volasertib was 300 mg Q3W combined with afatinib 30 mg d2-21 (Schedule A) or afatinib 70 mg d2-6 (Schedule B). Both agents could be combined at previously shown active single agent doses. At the MTD, treatment was manageable and showed preliminary anti-tumor activity. Clinical trial information: NCT01206816.
Clinical characteristics, treatment, and survival outcomes in malignant pleural mesothelioma: A institution experience in Turkey.
Authors: Mehmet Kucukoner, Muhammed Ali Kaplan, Ali Inal, Zuhat Urakcı, Ozlem Abakay, Abdullah Tanrıkulu, Abdurrahman Abakay, Abdurrahman Senyigit, Abdurrahman Isikdogan
Journal: Journal of Clinical Oncology (2013)

e18544 Background: Malignant pleural mesothelioma (MPM) is a aggressive tumor that causes high mortality. Treatment of MPM remains disappointing, even new approaches are present today. Methods: The present study retrospectively examined the data related to 150 patients with MPM who were examined and treated in our center in Turkey from 2005 to 2012. The aims of this study were; to investigate clinicopathologic characteristics, treatment modalities and potential prognostic factors. Results: There were 87 males (58%) and 63 females (42%), 92 of the patients (61.3%) had an asbestos contact and this contact was generally environmental. Surgical resection (EPP or P/D) was used in 32 patients, 87 patients (58%) received only chemotherapy. The median progression free and overall survival (PFS and OS) for all patients were 10.6 and 14.8 months. There was no statistically significant difference between the patients who received pemetrexed/cisplatin (54 patients) and gemcitabine/cisplatin (28 patients) regimens in terms of the PFS and OS (p=0.145, p=0.244). The comparison between patients who were operated on and those who were not did not reveal any statistical difference in PFS and OS (p=0.416, p=0.095). There was no difference in both PFS and OS rates in comparison of patients who had P/D or EPP (p=0.87, p=0.652). Log rank analysis, ECOG performance status (p=0.018), histology (p&lt;0.001), stage (p&lt;0.001) and leukocytosis (p=0.005) were found to be significant prognostic factors in OS. At multivariate analysis, ECOG performance status (p=0.016), and stage (p&lt;0.001) remained independently associated with OS. Conclusions: In survival analysis revealed significant differences in terms of both the PFS and OS, performance status, histology, stage and leukocytosis. EPP or P / D surgical options did not provide difference in term of survival. Survival rates in patients who received combining platinum analogues with pemetrexed or gemcitabine as front-line chemotherapy were found similar.
Long-term results in multiple myeloma treated with high-dose melphalan and autologous peripheral stem cell transplantation and achieving complete remission.
Authors: Massimo Vincenzo Martino, Maurizio Postorino, Giuseppe Alberto Gallo, Giuseppe Irrera, Eugenio Piro, Giuseppe Messina, Santo Neri, Said Al Sayyad, Roberta Fedele, Caterina Musolino, Stefano Molica, Maura Brugiatelli, Francesco Nobile, Fortunato Morabito
Journal: Journal of Clinical Oncology (2012)

e18564 Background: Major progress has been made in the treatment of multiple myeloma (MM) in recent years, including the introduction of novel agents and transplant strategy. High-dose melphalan (HDM) followed by autologous haematopoietic stell cell transplantation (AHSCT) remains an integral component of upfront treatment strategy. Many studies stress the importance of achieving a deeper response as a surrogate for improved survival but, despite the improvements, MM remains incurable and long-term survival appears elusive. The aim of study is to establish the actual prognosis for the different response categories in the same original cohort of patients with MM treated with HDM and AHSCT after long-term follow-up. Methods: We evaluated a cohort of MM patients treated up-front in the Bone Marrow Transplant Unit of Reggio Calabria between 1994 and 2006. Disease response was assessed with the use of criteria from the European Group for Blood and Marrow Transplantation modified to include Complete Remission (CR) and near Complete Remission (nCR). Results: The study group was composed by 150 patients (age at 1st AHSCT M±SD 55±9 years, male 64%); 94 (63%) of them had 2 AHSCT. After treatments 22 (15%) patients have a CR, 32 (21%) a nCR and 90(64.0%) a PR. After a mean follow up of 50 months the cumulative probability of survival was 69% for patients with CR, 43% for those in nCR and 0% for patients in PR (log-rank test P PR vs nCR=0.006; CR vs nCR and nCR vs PR&lt;0.001 ). The estimate mean survival for patients with CR, nCR and PR was respectively 166, 81 and 46 months. For patients with CR the survival curves showed a plateau of cumulative probability of survival after 134 months. Conclusions: In MM achieving a CR after HDM and AHSCT is a central prognostic factor. The relapse rate is low in patients with &gt;11 years of follow-up, possibly signifying durable remission in patients in CR.