tbuckley/cabot-search huggingface dataset:
<sup>68</sup>Ga-DOTA-Bombesin (<sup>68</sup>Ga-RM2 or <sup>68</sup>Ga-Bombesin) PET versus <sup>68</sup>Ga-PSMA PET: A pilot prospective evaluation in patients with biochemical recurrence of prostate cancer.
Authors: Andrei Iagaru, Ryogo Minamimoto, Steven Lee Hancock, Erik Mittra, Andreas Loening, Shreyas Vasanawala
Journal: Journal of Clinical Oncology (2016)

331 Background: Detection of prostate cancer (PC) after biochemical recurrence (BCR) remains a great challenge. RM2 is a synthetic bombesin receptor antagonist, which targets gastrin-releasing peptide receptors (GRPr). PSMA is a membrane antigen expressed on prostate cancer cells. Here we present a comparison of 2 novel PET tracers, 68 Ga-RM2 and 68 Ga-PSMA, in patients with BCR with prior non-contributory conventional imaging. Methods: Ten men (67-83 year-old; mean ± SD: 74.3 ± 5.9) with BCR PC were imaged with 68 Ga-RM2 and 7 of them also had 68 Ga-PSMA PET. The SUV max and SUV mean measurements were recorded in normal tissues and areas of uptake outside the expected physiologic biodistribution. Results: All 7 patients who had both scans had rising PSA (range: 3.5-36.5 ng/mL; mean±SD: 13.5 ± 11.5) and non-contributory conventional imaging (CT, MRI, 18 F FDG PET/CT, 18 F NaF PET/CT, 99m Tc MDP bone scan). 68 Ga-PSMA had the highest physiologic uptake in the salivary glands and small bowel, with hepatobiliary and renal clearance noted, while 68 Ga-RM2 had the highest physiologic uptake in the pancreas, with renal clearance noted. Uptake values uptake outside the expected physiologic biodistribution were not statistically different between 68 Ga-PSMA and 68 Ga-RM2. 68 Ga-PSMA localized in a lymph node and seminal vesicle in one patient with no abnormal 68 Ga-RM2 uptake. In 2 patients abdominal peri-aortic lymph nodes were more easily visualized by 68 Ga-RM2 due to lack of interference by radioactivity accumulation in the small intestine. Conclusions: 68 Ga-PSMA and 68 Ga-RM2 have distinct biodistribution in this small cohort of patients with BCR PC. High uptake in multiple areas outside the expected physiologic biodistribution suggests that both 68 Ga-PSMA and 68 Ga-RM2 are promising PET radiopharmaceuticals for localization of disease in patients with BCR PC and non-contributory conventional imaging. The differences in target density, biodistribution and clearance pathways may result in the superiority of one of the two tracers in different patients. 68 Ga-RM2 shows similar sensitivity to 68 Ga-PSMA and has the potential for being FDA-approved in the future. Clinical trial information: NCT02440308.
Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in non–anthracycline/cyclophosphamide (AC)-based moderately emetogenic therapy (MEC).
Authors: Daniel Powers, Paul Joseph Hesketh, Lee Steven Schwartzberg, Manuel R. Modiano, Sujata Arora, Ian D. Schnadig
Journal: Journal of Clinical Oncology (2015)

209 Background: Rolapitant, a novel NK-1 receptor antagonist, showed efficacy in CINV prevention in patients (pts) receiving MEC (anthracycline/cyclophosphamide (AC) and other regimens) in a global phase 3 trial. Recent anti-emetic guidelines consider AC based regimens to be highly emetogenic. In this post hoc analysis, the efficacy and safety of rolapitant was assessed in Cycle 1 in pts receiving non-AC MEC, and in the subset of pts receiving carboplatin-based MEC. Methods: In a double-blind, active-controlled study, pts were randomized to oral rolapitant 180 mg or placebo 1–2 hours before MEC. All pts received granisetron 2 mg oral on days 1-3 and oral dexamethasone 20 mg on day 1. Complete response (CR = no emesis + no use of rescue medication), no emesis, and no nausea were assessed in overall (0-120 h), acute (0-24 h), and delayed ( &gt; 24-120 h) phases. Results: CR was significantly (P &lt; 0.01) higher with rolapitant than active control in overall and delayed phases in the carboplatin subset and in all 3 phases in the non-AC population (Table). No emesis rates were significantly (p &lt; 0.05) higher with rolapitant in the carboplatin subset in the overall phase. No nausea rates were significantly (P &lt; 0.05) higher with rolapitant in the overall and delayed phases in carboplatin-based MEC. Incidences of treatment-related AEs in Cycle 1 with rolapitant vs. active control were 11.3% vs. 6.7% in the carboplatin-based subset. Most common AEs with rolapitant and active control were constipation, fatigue, and headache. Conclusions: Rolapitant was superior to active control in preventing CINV in pts receiving non-AC MEC, including in the subgroup receiving carboplatin. Rolapitant was well tolerated with low incidence of AEs. Clinical trial information: NCT01500226. [Table: see text]
Maternal CASPR2 antibodies and neurodevelopmental disorders in the offspring: epidemiological findings and an animal model
Authors: Ester Coutinho, David Menassa, Leslie Jacobson, Steven West, Joana Domingos, Teresa Moloney, Marianne G Pedersen, Michael E Benros, Bethan Lang, David Bennett, Paul J Harrison, Preben B Mortensen, Bent Nørgaard-Pedersen, David Bannerman, Angela Vincent
Journal: The Lancet (2017)
Adopting QOPI metrics into a continuous plan for learning across a five hospital network.
Authors: Diane Denny, Kathleen Dunn, Marjorie Hepler, Debra Kay Allen, Maurie Markman
Journal: Journal of Clinical Oncology (2016)

268 Background: Cancer Treatment Centers of America, Inc. (CTCA) is a national network of five hospitals that specialize in the treatment of patients fighting complex or advanced stage cancer. Utilizing metrics from the Quality Oncology Practice Initiative (QOPI), CTCA developed a “QOPI related continuous measures plan” from those areas of opportunity which fell greater than 10% below the QOPI aggregate score based upon its centers initial data abstraction efforts and findings. A total of 20 QOPI related measures were selected. The plan endorsed by clinical leaders and administration targeted at 50% improvement in these measures within 18 months. Methods: A crosswalk of metrics including patient inclusions and exclusions was developed for the continuous measures plan with data abstraction efforts based upon a review of new patients regardless of analytic or non-analytic status. As they progress through their treatment course, some measures are reported quarterly while others are reported semi-annually given volumes. A composite target of 71.2% was identified using T2 methodology, halving the distance between desired level of performance and the lowest facility baseline. Multiple educational efforts and strategies were deployed including efforts to redesign elements in the EHR. Results: The results are made visible in a number of different forums including a quality dashboard housing quarterly data and a monthly operations review process. A composite score in which data is rolled up from all 20 measures is reported as a key performance indicator across all five centers. Baseline composite through current performance is shown below by facility and in total. Conclusions: The QOPI related continuous measures plan is an evolving performance improvement process providing clinicians with an achievable goal for improving patient care. Team members anticipate surpassing the target through current and planned interventions. [Table: see text]
Analysis of ErbB/HER receptor pathways in formalin-fixed and paraffin-embedded cancer cell lines using multiplexed <i>eTag</i><sup>™</sup> assays
Authors: Y. Shi
Journal: Journal of Clinical Oncology (2005)

9565 Background: Immunohistochemistry (IHC) staining is the most commonly used method for assessing ErbB/HER receptor expression in formalin-fixed, paraffin-embedded (FFPE) tissues. IHC, however, is a non-quantitative method with limited sensitivity in detecting low levels of HER receptors. We have developed a multiplexed assay (eTag assay) that allows quantification of the HER targets and their activation status in FFPE samples. In this report, we present results obtained with the eTag system on FFPE samples derived from cancer cell lines. Method: FFPE samples of eight cancer cell lines with or without ligand treatment were prepared using standard protocols. eTag assays were performed in sample sections deparaffinized and rehydrated with xylene/ethanol/water protocols, and eTag signals were detected and quantified on capillary electrophoresis instruments. Concordance between the FFPE-based eTag assay and control methods (such as IHC, lysate-based eTag assays and immunoprecipitation/Western blot) was evaluated using the same cell lines. Results: The data obtained from the eTag assays and the control methods matched well for cell lines with different HER-1, HER-2 and HER-3 levels. Compared with the IHC approach, the eTag assays enabled differentiation of cell lines with low levels of HER receptors and more importantly, the detection and quantification of ligand-induced HER-1/1, HER-1/2, HER-2/3 and HER-1/3 dimerization and phosphorylation. Conclusion: The proximity-based eTag assays on FFPE samples provide unprecedented sensitive detection and quantification of the ErbB/HER receptor levels, homo- and hetero-dimerization and phosphorylation in cancer cell lines. This unique capability of the eTag assays has potential application in stratification of cancer patients based on their HER activation status for targeted therapies. No significant financial relationships to disclose.
Analysis of Outcomes Based on Response in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma Treated with Panobinostat or Placebo in Combination with Bortezomib and Dexamethasone in the Panorama 1 Trial: Updated Analysis Based on Prior Treatment
Authors: Jesús F San Miguel, Vânia TM Hungria, Sung-Soo Yoon, Meral Beksac, Meletios A. Dimopoulos, Ashraf Elghandour, Wieslaw W. Jedrzejczak, Andreas Guenther, Thanyaphong Na Nakorn, Noppadol Siritanaratkul, Robert L. Schlossman, Jian Hou, Philippe Moreau, Sagar Lonial, Jae Hoon Lee, Hermann Einsele, Monika Sopala, Bourras-Rezki Bengoudifa, Claudia Corrado, Florence Binlich, Paul G. Richardson
Journal: Blood (2015)
Feasibility and utility of influenza vaccination in hematology/oncology clinics.
Authors: Navjeet Uppal, Swanee Tobin, Jennifer Cape, Matthew Muller, Lisa K. Hicks
Journal: Journal of Clinical Oncology (2013)

166 Background: Seasonal influenza vaccination is recommended for cancer patients. However, many cancer clinics do not routinely offer flu shots. Early in January, 2013, Toronto experienced widespread influenza activity. Approximately 25% of hospitalizations on the hematology/oncology ward at St. Michael's Hospital (SMH) during this time were for suspected influenza. A large number of patients were noted to be unvaccinated. In-response, influenza vaccination was organized in parallel with regular hematology/oncology clinics at SMH. Aims: To determine the feasibility and utility of influenza vaccination in a cancer clinic. Methods: All patients seen in the SMH hematology/oncology clinic between January 14 and February 1, 2013, were eligible for influenza vaccination. A brief survey was administered to obtain vaccination history, willingness to receive flu vaccination, and beliefs about flu vaccination. Information regarding diagnosis, treatment, and family physician was obtained from the medical record. Univariate testing was completed with the Chi-squared and Fisher’s exact tests as appropriate. Results: 555 patients were seen during the period of interest; 206 completed the survey (37% response rate). Median age of respondents was 63 years, 42% were male, and 81% had cancer. 107(52%) of respondents had not received seasonal influenza vaccination of whom 41 (38%) accepted vaccination when offered. Among vaccinated patients, most received the flu shot from a family physician (70%). Reasons for not receiving the flu shot were personal preference (24%), belief that it was not necessary (19%), inconvenience (14%), concerns about side effects (8%), believe that it was contraindicated during chemotherapy (7%) and a perception that a medical practitioner advised against it (7%). Patients without a registered family physician were less likely to have received the seasonal flu shot (p=0.03). Patients with a malignant diagnosis and patients receiving IV chemotherapy tended to have lower rates of seasonal flu vaccination (p=0.09 and p=0.12 respectively). Conclusions: Administering influenza vaccination during hematology/oncology clinics is feasible and may address a care gap in this population.
A randomized phase II study of DTIC and interferon-α2a, with or without retinoic acid in metastatic melanoma-monitoring of immunopotentiation
Authors: G. Konjevic
Journal: Journal of Clinical Oncology (2005)

7567 Background: Combination of interferon-α2a (IFN) and dacarbazine (DTIC) with 13-cis retinoic acid (RA), as a biologic agent with antiproliferative, differentiating and immunomodulating potential, is being investigated within chemotherapy regimens. In this study immunological evaluation was performed in patients with metastatic melanoma (MM) receiving combined chemoimmunotherapy. Methods: Randomized MM patients who received DTIC (800 mg/m2 d1) and IFN (5x106 IU/m2 s.c., d2–6 (group A, n-25) and the same therapy supplemented with RA, 60 mg/d, d 1–10 (group B, n-28) have been serially monitored for NK cell activity, expression of activation antigen CD69 on NKcells and CD161, CD158a and CD158b on fresh NK cells and after predictive immunomodulating in vitro treatments, together with 39 healthy controls. Results: 53 patients were evaluable for tumor response, toxicity and immunological assessment. There was no significant difference in overall response (group A 32%, group B 21%), as well as in time to progression (median 3 mo) or toxicity between groups. Analysis of NK cell activity showed significantly decreased pretherapy levels in both groups, coinciding with decrease in CD161, as well as a significant increase, on day 6, after completion of IFN application. In comparison to pre-therapy values, responders had, repeatedly, a significantly higher percentage of increase of CD69 expression on CD56+ NK cells, although within groups the significant difference between non-responders and responders was only in group B, implicating immunopotentiating effect of RA that could be associated with RA in vitro induced decrease in CD158a, while RT-PCR analyses of interferon regulatory factor-1 expression in in vitro treatments suggest synergism of IFN and RA. Conclusions: In spite of certain favorable immunological changes in both groups there was no difference in clinical response.However, the type and dynamics of obtained immunomodulation suggest that possible changes in the dose and schema of administration of IFN and RA in these regimens could result in clinical benefit. No significant financial relationships to disclose.
Dissemination, implementation, and quality improvement research within the HMO Cancer Research Network.
Authors: Brian S. Mittman, James W. Dearing, Kathleen Mazor, James Nutter
Journal: Journal of Clinical Oncology (2013)

215 Background: The HMO Cancer Research Network, funded by the National Cancer Institute, provides infrastructure support to facilitate cancer research in non-profit integrated healthcare delivery systems. A key CRN goal to improve quality and outcomes through research and research-based methods for accelerating implementation of innovations in cancer care. Methods: The CRN is led by a Steering Committee and an Executive Committee. CRN Scientific Working Groups support activity within distinct areas; the CRN Communication and Dissemination Scientific Working Group (C&amp;D SWG) supports the design, conduct and reporting of research on (1) communication and decision makin in cancer care and (2) dissemination and implementation of cancer research findings and best practices. C&amp;D SWG activities include monthly calls presenting C&amp;D research resources, project ideas and funding opportunities; individual consultation and technical assistance to support CRN researchers developing funding applications and conducting research in relevant areas; and mentorship for CRN Scholars. General CRN resources to facilitate research to improve cancer care quality include a multi-institution Virtual Data Warehouse with accompanying query tools to facilitate preparatory-to-research and collaborative research studies and specific cancer-related data items; funding for Developmental and Pilot Studies; and an Outreach and External Collaborations Core to facilitate research collaborations among (a) CRN institution-based scientists, (b) scientists at other institutions, and (c) clinical and operations partners. Results: The CRN C&amp;D SWG continues to stimulate increased awareness and interest in conducting dissemination and implementation studies and quality improvement research in cancer care, and to support the development of new project ideas and funding applications and the successful completion and publication of such studies. Conclusions: CRN activities facilitate innovative multi-site, multi-disciplinary cancer studies in the integrated delivery system setting, and motivate continued evolution of CRN institutions as the nation's premier learning health care systems. Supported by U24 CA171524.
Defining radiation induced liver toxicity in the treatment of hepatocellular carcinoma: Which metric is most predictive for survival?
Authors: Tobias Robert Chapman, Stephen R. Bowen, Matthew J. Nyflot, Smith Apisarnthanarax
Journal: Journal of Clinical Oncology (2016)

361 Background: Radiation induced liver disease (RILD) is of critical concern in the treatment of hepatocellular carcinoma (HCC) with radiation therapy (RT). Variability exists in metrics used to define RILD with no consensus on which best predict for overall survival (OS) and RILD-specific survival (RILDSS). We examined the correlation between toxicity metrics and clinical outcomes in a heavily pre-treated population that received RT. Methods: The charts of 37 HCC patients treated from 2013 - 2015 were reviewed retrospectively. At baseline, 62% were Child-Pugh (CP)-A, 32% CP-B and 5% CP-C. The majority (59%) had prior liver-directed therapy (LDT), 43% received stereotactic body RT and 49% proton RT. Pre-treatment, toxicity ( ≤ 6 months from treatment) and outcomes data were collected. Deaths from RILD were scored. Pre-treatment factors and toxicity outcomes were assessed by univariate Cox models for association with OS and RILDSS. Statistically significant predictors formed the basis for stepwise multivariate Cox regression to retain independent predictors of survival. Results: At a median follow-up of 8 months, 14 patients had an increase in CP score ( ≥ 2, n = 7) and 3 had ≥ G3 RTOG transaminitis. There were 11 deaths, 5 from RILD. On univariate analysis (UA), tumor size, pre-treatment liver function, prior LDT and 5 toxicity metrics (CP score increases and transaminitis) were significantly associated with OS. An increase of ≥ 1 CP score (HR 22.7, p = 0.005), pre-treatment ALBI grade (HR 6.0, p = 0.02) and tumor size (HR 1.2, p = 0.01) were independent predictors of OS on multivariate analysis (MVA). Similar factors were associated with RILDSS on UA, including ≥ 2 CP score increase and ≥ G3 ALT elevation; however, only pre-treatment CP score (HR 4.0, p = 0.01) and tumor size (HR 1.5, p = 0.03) were independently predictive on MVA. Conclusions: Pre-treatment liver functional status and tumor size were highly predictive of OS and RILDSS, suggesting that baseline functional hepatic reserve is the primary determinant in developing fatal RILD rather than post-RT changes in liver function. Further work is needed to define dosimetric parameters and pre-treatment factors that predict RILD toxicity.
Rates and patterns of recurrence following complete resection of Hilar cholangiocarcinoma: Results from the U.S. Extrahepatic Biliary Consortium.
Authors: Harveshp Mogal, Sean O'Connor, Nora Fino, Cecilia Grace Ethun, Timothy M. Pawlik, George A. Poultsides, Thuy Tran, Kamran Idrees, Chelsea A Isom, Ryan C. Fields, Linda Jin, Sharon M. Weber, Ahmed I. Salem, Robert C. G. Martin, Charles Raben Scoggins, Carl Richard Schmidt, Eliza W Beal, Ioannis Hatzaras, Shishir Kumar Maithel, Perry Shen
Journal: Journal of Clinical Oncology (2016)

324 Background: Data for incidence and patterns of recurrence after surgical resection of Hilar cholangiocarcinoma have been derived largely from single institution series. We sought to assess factors associated with recurrence, recurrence patterns and their impact on outcomes. Methods: Patients with Hilar cholangiocarcinoma that underwent R0/R1 resection without 30-day mortality from surgery were analyzed from a 10-institution database. Results: 193 patients with recurrence data available were identified. Of these 95 (49%) recurred with median time to recurrence of 15.2 months and overall survival (OS) of 24.3 months. Univariate analysis identified age (HR 1.02, CI 1.004-1.036; p = 0.01), pre-op CA 19-9 (HR 1.02, CI 1.004-1.035; p = 0.02), positive lymph nodes (HR 1.72, CI 1.187-2.478; p = 0.004) and perineural invasion (HR 1.78, CI 1.125-2.802, p = 0.01) as factors predicting worse disease free survival. On multivariate analysis, only age (HR 1.032, CI 1.01-1.06, p = 0.007) and pre-op CA 19-9 (HR 1.02, CI 1.01-1.04, p = 0.013) remained significant. 67 patients (70.5%) had distant recurrence (DR) with or without locoregional recurrence (LR) while 28 patients (29.5%) had LR only. Of patients that had DR, 42 (63.6%) had liver, 23 (34.9%) had peritoneal, 8 (12.1%) had lung and 5 (7.6%) had other sites including distant nodal metastases. Median time to recurrence (13.6 vs 17.7 months, p = 0.07), time from recurrence to death (5.9 vs 4.5 months, p = 0.72) and OS (24.4 vs 25.3 months, p = 0.3), was not significantly different between patients who had LR or DR with or without LR. Among patients that recurred, tumor size, lymph node status, resection status (R0/R1), extent of resection and adjuvant therapy were not significantly associated with the type of recurrence. Conclusions: Hilar cholangiocarcinoma is an aggressive cancer with high rates of predominantly distant recurrence associated with poor survival. Further investigation is warranted to determine the role and potential type of adjuvant therapy in order to improve outcomes after surgical resection.
Method of treatment of destructive tuberculosis of single lung with extensively drug resistant mycobacteria tuberculosis
Authors: Irina Tabanakova, Aleksey Elkin, Mikhail Kobak, Nikolay Yakushenko
Journal: European Respiratory Journal (2011)

Treatment of patients with TB with total defeat of one lung and presence of destruction in the other, with a constant allocation of extensively drug resistant Myc.tuberculosis (XDR MBT), remains extremely weak. Under these conditions, the role of surgical and endoscopic therapies is rising.  Objective: To improve treatment of patients with fibrous-cavernous tuberculosis of a single lung with XDR MBT due to valvular lung volume reduction (VLVR) and local extrapleural thoracoplastic.  Material and methods: The treatment was performed in 13 patients (10 men, 3 women) of fibrous-cavernous tuberculosis of a single lung with XDR MBT. The patients9 age ranged from 30 to 54 years. Disease duration ranged from a half to 8 years, all patients were smear.  The essence of the proposed method is to use endobronchial non-return valve. Valve ensures the smooth discharge of air, sputum, bronchial content in the exhale, and cough. Inverse of air in the lung lesions did not occur. Thus, gradually hypoventilation was being reached, until atelectasis of lung tissue. VLVR performed during treatment with reserve anti-TB drugs. In 6 patients with VLVR was supplemented extrapleural thoracoplastic.  Results: Time that valve spent in the bronchus depended on the rate of cavity closure and cessation of bacteria and ranged from 7 to 274 days. Abacillation was achieved in 100% of patients, the cavity was closed in 76,9% of patients.  Conclusions: The proposed method of treatment of patients with tuberculosis enables us to reduce lung cavity and reach abacillation patients with XDR MBT in the absence of the effect of chemotherapy with reserve anti-TB drugs and a high risk of single lung resection.