tbuckley/cabot-search huggingface dataset:
Abstract 16915: Mortality And Safety Outcomes of Various Catheter-based Treatment Modalities in Patients With High-risk Pulmonary Embolism: A Meta-analysis
Authors: Navkaranbir S Bajaj, Rajat Kalra, Sameer Ather, Jason Guichard, William J Lancaster, Fabio Raman, Pankaj Arora, Trey Clark, David C McGiffin, Mustafa I Ahmed
Journal: Circulation (2015)

Background: Catheter-based treatments (CBTs) are diverse set of techniques aimed at relieving pulmonary arterial obstruction in patients with high-risk pulmonary embolism. Multiple modalities are currently available. The mortality and safety outcomes have not been studied among these different modalities. Hypothesis: We conducted this investigation to determine the mortality and safety of individual modalities. Methods: We searched SCOPUS since inception to November 2014 using predefined criteria. Studies including massive PE or a combination of massive and submassive PE, as defined by the American Heart Association, were included. In-hospital mortality rates and pooled safety complication rate (defined as a composite of peri- and post-procedural cardiac arrest, minor access site bleeding, major access site bleeding, and bleeding at other sites) were estimated using standard meta-analytic methods and compared among six different groups namely aspiration thrombectomy, intrapulmonary thrombolysis (IP), mechanical fragmentation (MF), rheolytic thrombectomy (RT), ultrasound-accelerated thrombolysis (USAT) and multiple simultaneous modalities. Results: In 54 eligible studies with 1,333 patients, 1,357 CBT procedures were performed. Patients undergoing USAT had the lowest in-hospital mortality rate whereas patients undergoing RT had the highest in-hospital mortality rate (p = 0.011, Table). Intrapulmonary thrombolysis had the highest pooled rate of safety outcome whereas MF had the lowest rate among various techniques (p = 0.034, Table). Conclusion: There is significant heterogeneity in mortality and safety outcomes between various CBT modalities. Our analysis is limited by variance in study quality and baseline characteristics. More investigation is required to determine the optimal type of CBT for high-risk PE.
Amid Osteoporosis Treatment Crisis, Experts Suggest Addressing Patients’ Bisphosphonate Concerns
Authors: Jennifer Abbasi
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Utility of dedicated breast positron emission tomography as a tool for predict malignancy grade and staging of breast cancer.
Authors: Norio Masumoto, Takayuki Kadoya, Eri Suzuki, Satoshi Sueoka, Noriko Gohda, Shinsuke Sasada, Keiko Kajitani, Akiko Emi, Rumi Haruta, Tsuyoshi Kataoka, Morihito Okada
Journal: Journal of Clinical Oncology (2018)

e12550 Background: Dedicated breast positron emission tomography (DbPET) provides detailed high resolution images of the breast. We focused on breast cancer present with heterogeneous intratumoral distribution of 18F-fluorodeoxyglucose (FDG). This study aimed to evaluate correlation between the intensity of FDG uptake for DbPET and tumor characteristics of breast cancer, and aimed to analyze clinicopathological features of breast cancer which showed heterogeneous intratumoral distribution of FDG on DbPET. Methods: We evaluated 195 consecutive patients with invasive breast cancer who underwent preoperative concurrent WBPET and DbPET from January 2016 to March 2017. The relationships among standard uptake values (SUV) of Db- and WB-PET or heterogeneous intratumoral distribution of FDG on DbPET and clinicopathological factors (clinical T/N stage, nuclear grade: NG, Ki67 proliferation index, ER status HER2 status) were evaluated. Results: The SUVs for DbPET were significantly correlations with clinicopathological factors (clinical T, p< 0.001; Clinical N, p< 0.001; NG, p< 0.001; Ki67 proliferation index, p< 0.001; ER status, p= 0.006; HER2 status, p= 0.044). The breast cancer cases with heterogeneous intratumoral distribution of FDG on DbPET were significantly associated with tumor size (p< 0.001), LN-positive (p= 0.002), high NG (p< 0.001), higher Ki67 proliferation (p< 0.001). Conclusions: The SUV of DbPET correlates with clinicopathological factors, and can be applied as a prognostic factor in the same manner as WBPET. Furthermore, the presence of heterogeneous intratumoral distribution on DbPET can provide excellent predictive value for high-grade malignancy and might help to determine appropriate therapeutic strategies.
PTU-022 Comparison of two multi band mucosectomy devices for endoscopic resection of barrett’s related neoplasia
Authors: D Alzoubaidi, C Magee, R Hamoudi, M Rodriguez-Justo, M Novelli, L Lovat, R Haidry
Journal: Gut (2017)

Introduction  Oesophageal adenocarcinoma carries a poor prognosis and therefore treatment of early neoplasia arising in the precursor condition Barrett’s Oesophagus (BE) is desirable. Visible lesions arising in BE need endoscopic mucosal resection (EMR) for accurate staging and removal. Resection modalities include a cap based system with snare and custom made multiband mucosectomy (MBM) devices (Duette, Cook Medical Ltd). A new MBM device has been launched (Captivator, Boston Scientific Ltd). Aim: A retrospective study to compare the efficacy, safety, specimen size and histology of EMR specimens resected with two MBM devices (Cook Duette and Boston Captivator) in treatment naive patients undergoing endoscopic therapy for BE neoplasia.  Method  All procedures were carried out by a single experienced endoscopist in a single unit. All visible lesions were marked and resected using 1 of the 2 MBM devices. Identical diathermy settings and suction pressures were used and all lesions were resected without submucosal injection. All samples were fixed to cork by the same endoscopy nurses. All resected specimens were analysed by the same two experienced pathologists. The resected specimens in both groups were analysed for length mm (max diameter), width mm (min diameter) and surface area SA mm2.  Results  This study included 20 patients [18M+2F; mean age=74 (range:53–85)] in the Duette group and 19 [16M+3F; mean age=72(range:48–87) in the captivator group with a mean max length of BE of 5.7 cm (Range:0–15) and 5.4 cm (Range:1–15) respectively (P=NS). Successful resection in 100% of the cases with a total of 58 specimens resected in the duette and 61 in the captivator group. There were no reported perforations. There was 1 delayed bleeds in both groups requiring endoscopic therapy (P=NS). First follow up endoscopy showed 2 strictures post EMR in the duette group and 1 in the captivator. Fifty percent of the cancer cases in the duette group showed SM invasion, in comparion to 21% in the Captivator (P=NS). Lengthm, width and surface area of Captivator EMRs were larger than the Duette (surface area 135 vs 114mm2, p=0.005).  Conclusion  Both MBM devices are safe and effective at resecting visible lesions in patients with BE neoplasia.The EMR Captivator device appears to resects specimens with a larger surface area in the oesophagus when compared with the Duette device. A possible advantage of this is in situations where en bloc resection is wanted for larger lesions (>10 mm) and where fewer resections per lesion size is desirable in larger lesions. A further randomised trial would be needed to confirm these findings.  Disclosure of Interest  None Declared
Assessment and management of bone health in women treated with adjuvant anastrozole in the DATA study.
Authors: Irene Van Hellemond, Carolien H. Smorenburg, Petronella Peer, Astrid Swinkels, Caroline M. Seynaeve, Maurice Van Der Sangen, Judith R. Kroep, Hiltje de Graaf, Aafke H. Honkoop, Frans Erdkamp, Franchette van den Berkmortel, Maaike De Boer, Wilfred de Roos, Sabine C. Linn, Alexander Imholz, Vivianne C. Tjan-Heijnen
Journal: Journal of Clinical Oncology (2018)

534 Background: The phase III DATA study (NCT00301457) investigates the efficacy of 6 versus 3 years of adjuvant anastrozole (AI) after an initial 2-3 year treatment with tamoxifen in postmenopausal women with breast cancer. In a planned side study, we assessed patterns of care in detection and treatment of osteopenia/osteoporosis and linear trends over time in bone mineral density (BMD). Methods: BMD measurements and bisphosphonate use in the DATA study were left to the treating physician. We registered all BMD measurements and start of bisphosphonate-use. BMD was measured by a dual-energy x-ray absorptiometry (DEXA) scan of the lumbar spine and/or the hip and transformed to a T-score. Time to osteopenia or osteoporosis was analysed by reverse Kaplan Meier methodology. For the linear trend in BMD T-score, linear mixed models with random effects for patient were used. Results: Of the 1860 eligible patients in the DATA study, 910 (48.9%) had a BMD measurement at the start of anastrozole (baseline). In 417 (45.8%) patients the baseline measurement indicated a normal BMD, in 408 (44.8%) osteopenia, and in 85 (9.3%) osteoporosis. In patients with a normal baseline BMD, osteopenia was observed in 53.5% of patients in the 6-year group, and 55.4 % in the 3-year group (p = 0.18), while none developed osteoporosis within 6 years after randomization. Of the patients with osteopenia at baseline, 24.4 % developed osteoporosis in the 6-year group and 20.4% in the 3-year group (p = 0.89). The yearly BMD change in the lumbar spine showed a decline of the mean T score of 0.075. When bisphosphonates were added the decline became 0.047 per year (p < 0.001), and when the AI was stopped and bisphosphonates continued the BMD increased yearly with 0.047. Conclusions: In postmenopausal women who had been treated with 2-3 years of adjuvant tamoxifen, BMD measurement showed osteopenia in 44.8% of women and osteoporosis in 9.3%. Although subsequent AI-use was associated with a further decrease of BMD, none of the patients with a normal BMD at baseline developed osteoporosis regardless of treatment arm. Clinical trial information: NCT00301457.
Challenges and perspectives in obstructive sleep apnoea
Authors: Winfried Randerath, Claudio L. Bassetti, Maria R. Bonsignore, Ramon Farre, Luigi Ferini-Strambi, Ludger Grote, Jan Hedner, Malcolm Kohler, Miguel-Angel Martinez-Garcia, Stefan Mihaicuta, Josep Montserrat, Jean-Louis Pepin, Dirk Pevernagie, Fabio Pizza, Olli Polo, Renata Riha, Silke Ryan, Johan Verbraecken, Walter T. McNicholas
Journal: European Respiratory Journal (2018)

Obstructive sleep apnoea (OSA) is a major challenge for physicians and healthcare systems throughout the world. The high prevalence and the impact on daily life of OSA oblige clinicians to offer effective and acceptable treatment options. However, recent evidence has raised questions about the benefits of positive airway pressure therapy in ameliorating comorbidities.An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5 years, discussed the current challenges in the field, and proposed topics for future research on epidemiology, phenotyping, underlying mechanisms, prognostic implications and optimal treatment of patients with OSA.The group concluded that a revision to the diagnostic criteria for OSA is required to include factors that reflect different clinical and pathophysiological phenotypes and relevant comorbidities (e.g. nondipping nocturnal blood pressure). Furthermore, current severity thresholds require revision to reflect factors such as the disparity in the apnoea-hypopnoea index (AHI) between polysomnography and sleep studies that do not include sleep stage measurements, in addition to the poor correlation between AHI and daytime symptoms such as sleepiness. Management decisions should be linked to the underlying phenotype and consider outcomes beyond AHI.
A phase 2, multicenter, open-label study of trastuzumab deruxtecan (DS-8201a) in subjects with HER2-positive, unresectable and/or metastatic breast cancer previously treated with T-DM1.
Authors: Jose Baselga, Kenji Tamura, Toshinari Yamashita, Shanu Modi, Eriko Tokunaga, Yoshinori Ito, Hiroji Iwata, Mahmoud Charif, Caleb C. Lee, Masahiro Sugihara, Takahiro Jikoh, Fabrice Andre
Journal: Journal of Clinical Oncology (2018)

TPS1102 Background: There is no standard of care for HER2-positive breast cancer refractory to T-DM1. DS-8201a is a novel HER2-targeted antibody-drug conjugate with a humanized HER2 antibody attached to a topoisomerase I inhibitor payload by a cleavable peptide-based linker (deruxtecan), and with a high drug-to-antibody ratio of 7 to 8. In the ongoing phase 1 DS8201-A-J101 trial, DS-8201a showed a manageable safety profile and promising antitumor activity in HER2-positive breast cancer subjects previously receiving T-DM1 (confirmed objective response rate [ORR] of 61.4%; Oct 2017 data cutoff) (Modi et al, SABCS 2017). In August 2017, the FDA granted breakthrough therapy and fast track designations. Methods: The phase 2, open-label, multicenter, 2-part, DESTINY-Breast01 study will assess the efficacy and safety of DS-8201a in subjects with HER2-positive (confirmed by centralized testing) unresectable and/or metastatic breast cancer previously treated with T-DM1. Part 1 will enroll 120 subjects and includes pharmacokinetic (PK) and dose finding stages to identify the recommended phase 2 dose (RP2D). The PK stage will randomize 60 subjects (1:1:1) to 1 of 3 DS-8201a doses (7.4, 6.4, and 5.4 mg/kg; once every 3 weeks). In the dose finding stage, an additional 60 subjects will be randomized (1:1) to 1 of 2 doses selected in the PK stage. Part 2a will continue to enroll approximately 100 subjects at the RP2D. Part 2b will enroll an open-ended number of subjects who discontinued T-DM1 for reasons other than progressive disease. Overall, enrollment of ≥100 subjects with a history of prior pertuzumab treatment for metastatic breast cancer is planned at the RP2D. The primary endpoint, ORR, will be assessed in all subjects enrolled in parts 1 and 2a who received the RP2D and who had baseline measurable tumors assessed by an independent central imaging facility. Secondary endpoints include duration of response, disease control rate, progression-free survival, and overall survival. Enrollment began in August 2017. As of Feb. 12, 2018, 35 of approximately 230 subjects have been enrolled. Clinical trial information: NCT03248492.
A combination of anti-PD-L1 mAb plus Lm-LLO-E6 vaccine to suppress tumor growth and metastasis in HPV-infected cancers.
Authors: Po Lin Lin, Yun Yen, Huei Lee
Journal: Journal of Clinical Oncology (2017)

e23175 Background: PD-1/PD-L1 immunotherapy is viewed as having clinical benefits in advanced cancers but is effective in only a few patients, suggesting that an efficient combination approach is needed to improve efficacy for certain non-small cell lung cancer (NSCLC) patients. Methods: PD-L1 and E6 oncoprotein expressions in lung tumors from 122 NSCLC patients were examined by immunohistochemistry and their prognostic value was evaluated by Kaplain-Meier and Cox regression analysis. HPV16-postive and negative TL-1 and TL-4 lung cancer and SiHa and C33A cervical cancer cells were used to test whether PD-L1 expression could be regulated by E6, not by E7 oncoprotein. Immune deficiency nude mice were used to test the possibility that combining anti-PD-L1 mAb with Lm-LLO-E6 vaccine could have a higher antitumor activity compared with anti-PD-L1 mAb or Lm-LLO-E6 vaccine alone. Results: Immunohistochemistry analysis indicated that PD-L1 expression was correlated with the E6 expression in tumors from 122 lung cancer patients. The poorest survival occurred in PD-L1-positive/E6-positive tumor. PD-L1 expression was increased by the expression of E6, but not the E7, oncoprotein in lung and cervical cancer cells. PD-L1 expression was responsible for E6-mediated colony formation and soft agar growth. Therefore, PD-L1 secreted from tumor cells may directly promote tumor progression, particularly in E6-positive tumors. A greater antitumor activity was obtained with anti-PD-L1 mAb+Lm-LLO-E6 vaccine than with anti-PD-L1 mAb or Lm-LLO-E6 alone in subcutaneous and metastatic tumors induced by TL-1 and SiHa cells. The longest survival time for nude mice was observed in the anti-PD-L1 mAb+Lm-LLO-E6 vaccine group. Conclusions: An anti-PD-L1 mAb+Lm-LLO-E6 vaccine may be an efficient treatment for suppression of tumor growth and metastasis induced by HPV-infected cells.
Percentages of post-mastectomy patients presenting with perinodal extension or inadequate axillary dissection in STAGE I and II carcinoma breast.
Authors: Maitrik Mehta, Ankita Parikh, Shikha Dhal, Unikrishnnan Suryanarayan
Journal: Journal of Clinical Oncology (2018)

e12618 Background: Purpose of the study is to assess patients with Stage I and II Carcinoma breast presenting with perinodal extension and inadequate axillary dissection following modified radical mastectomy in Radiotherapy department. Methods: We retrospectively reviewed 130 patients of Stage I and II postmastectomy tumors of Carcinoma Breast presented to department of radiation oncology. Patients have been sent for assessment for radiotherapy. Results: Between August 2015 to December 2017, 130 patients were evaluated. 3 patients had Stage I, 22 patients had Stage IIA (T0-1N1M0, T2N0M0) , 105 patients had Stage IIB (T2N1M0, T3N0M0) disease. In patients with T1N1M0 status – 3, 6 and 4 patients had 1, 2, 3 nodal positivity respectively. In patients with T2N1M0 status – 29, 40 and 20 patients had 1, 2 and 3 nodal positivity respectively. 60 (46.2%) patients had lymph node positivity with perinodal extension (Stage IIA – 4, Stage IIB - 56). In patients with T1N1M0 stage, 2, 2 and 0 patients with 1, 2 and 3 nodes involvement respectively and in patients with T2N1M0 stage, 11, 27 and 18 patients with 1, 2 and 3 nodes involvement respectively had lymph node positivity with perinodal extension. 26 (20%) patients had inadequate axillary dissection (Stage I – 1 , Stage IIA – 11, Stage IIB – 14). So, total 86 (66.2%) patients out of 130 had perinodal extension or inadequate axillary dissection, which ultimately needs loco-regional treatment. Also, out of 130 patients, 103 (79.2%) patients had nodal metastasis and out of 103 patients with nodal metastasis, 60 (58.2%) had perinodal extension. Conclusions: Large majority of cases with nodal metastasis shows extranodal spread. These findings show extensive and advanced stage in our patients even in early stage of breast cancer. We combined both of these factors to see that how many patients in early stage breast cancer will require adjuvant Loco-regional Radiotherpy treatment. Stage TNM No. of patients No. of involved nodes Nodes with Perinodal extension Inadequate axillary dissetion I T1N0 3 - 0 1 IIA T0N1 1 1 0 1 T1N1 3 1 2 1 6 2 2 2 4 3 0 2 T2N0 8 - 0 5 IIB T2N1 29 1 11 8 40 2 27 3 20 3 18 0 T3N0 16 - 0 3 130 60 (46.2%) 26 (20%) 103 (nodes positive) 60 (58.2%)
Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer
Authors: Pranavi Koppula, Yilei Zhang, Li Zhuang, Boyi Gan
Journal: Cancer Communications (2018)

Abstract Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs, and to maintain redox homeostasis. One nutrient transporter frequently overexpressed in human cancers is the cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11; also known as xCT). SLC7A11 promotes cystine uptake and glutathione biosynthesis, resulting in protection from oxidative stress and ferroptotic cell death. Recent studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells. This review discusses the roles of SLC7A11 in regulating the antioxidant response and nutrient dependency of cancer cells, explores our current understanding of SLC7A11 regulation in cancer metabolism, and highlights key open questions for future studies in this emerging research area. A deeper understanding of SLC7A11 in cancer metabolism may identify new therapeutic opportunities to target this important amino acid transporter for cancer treatment.
Precision neoadjuvant therapy (P-NAT): A planned interim analysis of a randomized, TNBC enrolling trial to confirm molecular profiling improves survival (ARTEMIS).
Authors: Stacy L. Moulder, Kenneth R. Hess, Rosalind P Candelaria, Gaiane M Rauch, Lumarie Santiago, Beatriz Adrada, Wei Tse Yang, Michael Z Gilcrease, Lei Huo, Michael Charles Stauder, Banu Arun, Rachel M. Layman, Rashmi Krishna Murthy, Senthil Damodaran, Naoto T. Ueno, Alastair Mark Thompson, Bora Lim, Elizabeth A. Mittendorf, Jennifer Keating Litton, William Fraser Symmans
Journal: Journal of Clinical Oncology (2018)

518 Background: ARTEMIS is a double blind, randomized trial to determine if P-NAT impacts rates of excellent pathologic response [Residual Cancer Burden (RCB) 0-I]. P-NAT used a CLIA-certified chemosensitivity mRNA gene signature (GES) and subtyping of triple negative breast cancer (TNBC) by immunohistochemistry (IHC) to select targeted therapy (TT) trials for chemo insensitive tumors. Methods: ARTEMIS planned to randomize 360 TNBC patients (pts) 2:1 to 'know' vs. 'not know' P-NAT results using a group sequential design with one-sided O'Brien-Fleming boundaries and two interim tests for futility and superiority; overall α set at .05 with 80% power to detect improved RCB 0-1 rate from 50% to 64%. After biopsy, pts began a planned 4 cycles of Adriamycin-based chemo (AC). Volumetric change by ultrasound (US) upon completion of AC (or at progression) combined with GES results (if known) determined sensitivity using a protocol defined algorithm. Pts with sensitive disease received subsequent taxane-based (T) therapy. Pts with insensitive disease were offered phase II trials (TT; table) using IHC results, if known. To gauge impact of TT independently from GES, pts having < 50% volumetric reduction by US to AC were evaluated (US-resistant cohort). Results: The first interim analysis (n = 133 pts with RCB status) revealed a RCB 0-1 rate of 56% (know P-NAT) v 62% (not know P-NAT); p = 1.0; thus, randomization was discontinued for futility. In total 232 pts were enrolled; 168 evaluable for RCB. In the US-resistant cohort (n = 43), RCB 0-I rates were higher in pts treated with TT (n = 30) v AC-T (n = 13); (30% v 8%; odds ratio = 5.1 with 95% CI = (0.6-45.7); Fisher's exact test 1-sided p-value = 0.11). Conclusions: GES failed to improve rates of RCB 0-I in TNBC; however, in pts with resistant disease identified by US after AC, RCB 0-I rates were higher in pts treated with targeted therapy compared to chemo alone. Clinical trial information: NCT02276443.Regimen Entry criteria (IHC) # pts treated Atezolizumab + nab-paclitaxel None 19 Panitumumab + paclitaxel + carboplatin None 14 Liposomal doxorubicin + bevacizumab + everolimus Vimentin > / = 50% or metaplastic 12 Enzalutamide + paclitaxel Androgen receptor > / = 10% 11 AC-T None 153