tbuckley/cabot-search huggingface dataset:
Traditional versus up-front 18FDG PET staging of non-small cell lung cancer (NSCLC): A Dutch Co-operative randomized study
Authors: G. J. Herder
Journal: Journal of Clinical Oncology (2004)

7000 Background: diagnostic work-up of patients (pts) with suspected NSCLC can be complicated, time-consuming and requires multiple diagnostic tests of poor to moderate specificity. If applied late in the diagnostic approach, PET prevents unnecessary surgery. We investigated whether application of PET immediately after first presentation might simplify staging without losing accuracy, as compared to the traditional strategy in routine clinical setting. Methods: at first presentation (history, phys exam, chest X-ray and bronchoscopy), pts without overtly disseminated NSCLC were randomized to traditional work-up (TWU) or PET. TWU was performed according to international guidelines. PET arm consisted of PET followed by verification of PET positive lesions suspect for distant metastasis (M1) or lymph node (N) involvement (CT if indicated). In case of FDG avid, non-central tumors without suspicion of M1 or ≥ N2 involvement at PET, clinicians were advised to proceed directly to thoracotomy. Follow up (FU) in presumed benign lesions was ≥12 months. Clinical stage prior to thoracotomy/other therapy was compared to peroperative stage and 6 months FU after apparently curative surgery. To investigate substitution, the number (non)invasive (staging and functional) procedures to achieve clinical TNM staging was measured. Results: from 09–1999 to 06–2001, 465 pts (233 TWU, 232 PET) were enrolled by 23 hospitals (20% of eligible pts). Mean age 64 (sd ± 10); 67% male and 96% WHO performance score ≤1. Accuracy of clinical staging was similar (p=0.073) in the two arms (Kappa 0.85 (95%CI 0.80–0.90) TWU and 0.78 (95%CI 0.72–0.84) PET). This measurement does not take any severity of misclassifications into account. Conclusion: application of FDG PET up-front in staging of pts with (suspected) NSCLC carries similar overall accuracy as compared to TWU, with limited impact on test substitution. No significant financial relationships to disclose.
Breast imaging two years post-breast conserving therapy (BCT): Do more frequent mammograms (MMG) yield benefits?
Authors: Jingjing Hu, Madhavi Latha Reddy Kambam, Wilson C. Mertens, Grace Makari-Judson, Jane Garb
Journal: Journal of Clinical Oncology (2014)

9602 Background: High level evidence defining the optimal timing and frequency of MMG surveillance (6-monthly vs. annually) after breast-conserving therapy (BCT) is lacking. The purpose of this retrospective study was to determine the value of 6-monthly MMG in detecting cancer events after BCT. Methods: AJCC stage 0 to IIIC breast cancer and ductal carcinoma in-situ (DCIS) patients (n=492) treated with BCT from 2005-2009 who had two years of surveillance MMG were selected. MMG-associated events, additional imaging and biopsies (Bx) triggered by abnormal mammograms, and tumor recurrences were analyzed by time intervals. A 6-monthly MMG group (n=400) was compared with annual MMG group (n=92). MMG yield was defined as MMG detected events divided by total MMG. We analyzed results using simple frequencies and Fisher’s exact test. Results: Of 1591 total MMG, 144 were pre-radiation; 69 additional imaging tests (38 ultrasounds, 22 magnification MMG and 9 MRIs) were performed. 1407 and 182 MMGs were performed in 6-monthly MMG group and annual MMG group respectively. 44 biopsies were triggered by abnormal MMGs (table). At 24 months after BCT, MMG detected 3 ipsilateral invasive cancers and 2 contralateral DCIS; 1 ipsilateral regional and 5 distant cancer events were found clinically. Two-year MMG yield was 0.31% (95%CI: 0.04-0.59%); First-year MMG yield was 0.10% (95%CI: 0-0.4%) and second- year MMG yield was 0.66% (95%CI: 0.02%-1.3%). MMG yields were 0.21% (95%CI: 0-0.45%) for the 6-monthly group and 1.0% (95%CI: 0-4.0%) for the annual group with no significant difference (p=0.11). Conclusions: The addition of 6-monthly MMG over annual screening did not significantly increase cancer detection, but was associated with unnecessary images and biopsies. Interval after BCT(mos.) Positive ipsilateral MMG- triggered Bx (n) Ipsilateral MMG- triggered Bx (n) Positive contralateral MMG- triggered Bx (n) Contralateral MMG- triggered Bx (n) Total positive MMG- triggered Bx n,(%) Positive non-MMG triggered Bx 6-12 0 17 1 6 1,(4.4%) 2 13-18 3 8 0 0 3,(37.5%) 0 19-24 0 11 1 2 1,(7.7%) 4 First 24 mo. 3 36 2 8 5,(11.4%) 6
Treatment of metastatic uveal melanoma with adoptive transfer of tumour-infiltrating lymphocytes: a single-centre, two-stage, single-arm, phase 2 study
Authors: Smita S Chandran, Robert P T Somerville, James C Yang, Richard M Sherry, Christopher A Klebanoff, Stephanie L Goff, John R Wunderlich, David N Danforth, Daniel Zlott, Biman C Paria, Arvind C Sabesan, Abhishek K Srivastava, Liqiang Xi, Trinh H Pham, Mark Raffeld, Donald E White, Mary Ann Toomey, Steven A Rosenberg, Udai S Kammula
Journal: The Lancet Oncology (2017)
An exploratory clinical trial of bortezomib in patients with lower risk myelodysplastic syndromes
Authors: May Daher, Juliana Elisa Hidalgo Lopez, Jasleen K. Randhawa, Kausar Jabeen Jabbar, Yue Wei, Naveen Pemmaraju, Gautam Borthakur, Tapan Kadia, Marina Konopleva, Hagop M. Kantarjian, Katherine Hearn, Zeev Estrov, Steven Reyes, Carlos E. Bueso‐Ramos, Guillermo Garcia‐Manero
Journal: American Journal of Hematology (2017)

Abstract Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis and an increased risk of transformation. Few effective therapies are available for lower risk MDS patients, especially after the failure of hypomethylating agents. MDS progenitor cells are dependent on the nuclear factor‐κB (NF‐κB) for survival, which makes it an attractive therapeutic target. As a proteosomal inhibitor, bortezomib is thought to have inhibitory activity against NF‐κB. We designed a proof‐of‐principle study of subcutaneous (SC) bortezomib in lower risk MDS patients with evidence of NF‐κB activation in their bone marrow. Fifteen patients were treated, their median age was 71 (range 56–87), 33% were low and 67% int‐1 by IPSS, median number of prior therapies was 2, all patients were transfusion dependent. Baseline median pp65 percentage was 31% and 11 patients had evidence of ring sideroblasts (RS). SC bortezomib was safe, well tolerated with no excess toxicity. Three patients out of the 15 (20%) had evidence of response with hematologic improvement (HI‐E). Bortezomib caused a decrease in pp65 levels in 7 out of 13 evaluable patients (54%, P = .025). Of interest, unexpectedly, we observed a significant decrease in RS in 7 out of 10 (70%) evaluable patients during treatment. In conclusion, this study suggests that NF‐κB activation, measured by pp65 levels, may be a useful biomarker in MDS. Bortezomib is safe in this patient population but has modest clinical activity. The role of the proteasome in the genesis of RS needs further study.
Folate cycle enzyme MTHFD1L confers metabolic advantages in hepatocellular carcinoma
Authors: Derek Lee, Iris Ming-Jing Xu, David Kung-Chun Chiu, Robin Kit-Ho Lai, Aki Pui-Wah Tse, Lynna Lan Li, Cheuk-Ting Law, Felice Ho-Ching Tsang, Larry Lai Wei, Cerise Yuen-Ki Chan, Chun-Ming Wong, Irene Oi-Lin Ng, Carmen Chak-Lui Wong
Journal: Journal of Clinical Investigation (2017)

Cancer cells preferentially utilize glucose and glutamine, which provide macromolecules and antioxidants that sustain rapid cell division. Metabolic reprogramming in cancer drives an increased glycolytic rate that supports maximal production of these nutrients. The folate cycle, through transfer of a carbon unit between tetrahydrofolate and its derivatives in the cytoplasmic and mitochondrial compartments, produces other metabolites that are essential for cell growth, including nucleotides, methionine, and the antioxidant NADPH. Here, using hepatocellular carcinoma (HCC) as a cancer model, we have observed a reduction in growth rate upon withdrawal of folate. We found that an enzyme in the folate cycle, methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L), plays an essential role in support of cancer growth. We determined that MTHFD1L is transcriptionally activated by NRF2, a master regulator of redox homeostasis. Our observations further suggest that MTHFD1L contributes to the production and accumulation of NADPH to levels that are sufficient to combat oxidative stress in cancer cells. The elevation of oxidative stress through MTHFD1L knockdown or the use of methotrexate, an antifolate drug, sensitizes cancer cells to sorafenib, a targeted therapy for HCC. Taken together, our study identifies MTHFD1L in the folate cycle as an important metabolic pathway in cancer cells with the potential for therapeutic targeting.
Measuring adaptation in colonic cancer patients' concepts of quality of life (QL) using multilevel models: Should we reconsider use of QL instruments which ignore adaptation?
Authors: A. Lowy, J. Bernhard
Journal: Journal of Clinical Oncology (2004)

6008 Background: If psychological adaptation to disease brings about major changes in what is important to the patient's quality of life (QL), most instruments in common use are poorly suited to longitudinal QL measurement, especially over periods encompassing substantial life changes such as occur during the course of many cancers. Little is known about this, and there is a lack of suitable methods for assessing its importance. We introduce a new application of multilevel models which directly addresses this question, and present results from colonic cancer patients in a phase III clinical trial. Methods: 126 colonic cancer patients summarised domains of QL and overall QL using linear analogue scales after three months of adjuvant treatment or observation, and again 21 months later. Changes in importance of domains were estimated using multivariate multilevel models. Results: There was strong evidence of a change in the relative importance of the measured domains to patients' QL (p=0.001); functional performance decreased markedly in importance and energy increased in importance, whereas the importance of pain did not change. Conclusions: The factors which these patients considered most relevant to their QL changed profoundly during the course of disease. Conventional QL instruments which apply a fixed set of weights to domain scores assume that no such changes occur. By ignoring adaptation, they might seriously misrepresent changes in subjective QL in these patients. If this effect is also found among other cancer patients, QL instruments which allow for adaptation should be favoured over those which ignore it. Multilevel models offer a simple, transparent way to study this phenomenon, and can readily be applied to existing QL datasets collected for other purposes. No significant financial relationships to disclose.
Differential phenotypes of memory CD4 and CD8 T cells in the spleen and peripheral tissues following immunostimulatory therapy
Authors: Gail D. Sckisel, Annie Mirsoian, Christine M. Minnar, Marka Crittenden, Brendan Curti, Jane Q. Chen, Bruce R. Blazar, Alexander D. Borowsky, Arta M. Monjazeb, William J. Murphy
Journal: Journal for ImmunoTherapy of Cancer (2017)

<h3>Background</h3> Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative of immune responses occurring at metastatic sites following immunotherapy. <h3>Methods</h3> Phenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype. <h3>Results</h3> Here we reveal that, similar to what occurs in the spleen and lymph nodes, CD4-T cell numbers decreased while CD8-T cells expanded at these peripheral sites. In contrast to having differential expression of PD-1 as occurs in the spleen, both CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver and lungs. Further analysis correlated PD-1 expression to CD62L<sup>low</sup> (T effector/effector memory,T<sub>E/EM</sub>) expression which are more prevalent in CD4-T cells in general as well as CD8-T cells in peripheral organs. Similar elevated PD-1 expression on T<sub>E/EM</sub> cells was observed in patients undergoing systemic high-dose IL-2 therapy. <h3>Conclusions</h3> These data highlight PD-1 expressing and/or T<sub>E/EM</sub> subsets of T cells in circulation as more representative of cells at immune sites and underscore the importance of valuation both in lymphoid as well as target organs when making determinations about immune status. <h3>Trial registration</h3> ClinicalTrials.gov NCT01416831. Registered August 12, 2011.
American Society of Clinical Oncology Position Statement: Strategies for Reducing Cancer Health Disparities Among Sexual and Gender Minority Populations
Authors: Jennifer Griggs, Shail Maingi, Victoria Blinder, Neelima Denduluri, Alok A. Khorana, Larry Norton, Michael Francisco, Dana S. Wollins, Julia H. Rowland
Journal: Journal of Clinical Oncology (2017)

ASCO is committed to addressing the needs of sexual and gender minority (SGM) populations as a diverse group at risk for receiving disparate care and having suboptimal experiences, including discrimination, throughout the cancer care continuum. This position statement outlines five areas of recommendations to address the needs of both SGM populations affected by cancer and members of the oncology workforce who identify as SGM: (1) patient education and support; (2) workforce development and diversity; (3) quality improvement strategies; (4) policy solutions; and (5) research strategies. In making these recommendations, the Society calls for increased outreach and educational support for SGM patients; increased SGM cultural competency training for providers; improvement of quality-of-care metrics that include sexual orientation and gender information variables; and increased data collection to inform future work addressing the needs of SGM communities.
"Interferon- release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis." M. Sester, G. Sotgiu, C. Lange, C. Giehl, E. Girardi, G.B. Migliori, A. Bossink, K. Dheda, R. Diel, J. Dominguez, M. Lipman, J. Nemeth, P. Ravn, S. Winkler, E. Huitric, A. Sandgren and D. Manissero. Eur Respir J 2011; 37: 100-111.
Authors: C Hewson, J Haas, N Bartlett, S Message, V Laza-Stanca, T Kebadze, G Caramori, J Zhu, M Edbrooke, L Stanciu, O Kon, A Papi, P Jeffery, M Edwards
Journal: European Respiratory Journal (2012)
CCT6A suppresses SMAD2 and promotes prometastatic TGF-β signaling
Authors: Zhe Ying, Han Tian, Yun Li, Rong Lian, Wei Li, Shanshan Wu, Hui-Zhong Zhang, Jueheng Wu, Lei Liu, Junwei Song, Hongyu Guan, Junchao Cai, Xun Zhu, Jun Li, Mengfeng Li
Journal: Journal of Clinical Investigation (2017)

Paradoxically, during early tumor development in many cancer types, TGF-β acts as a tumor suppressor, whereas in the advanced stages of these cancers, increased TGF-β expression is linked to high metastasis and poor prognosis. These findings suggest that unidentified mechanisms may function to rewire TGF-β signaling toward its prometastatic role in cancer cells. Our current study using non-small-cell lung carcinoma (NSCLC) cell lines, animal models, and clinical specimens demonstrates that suppression of SMAD2, with SMAD3 function intact, switches TGF-β-induced transcriptional responses to a prometastatic state. Importantly, we identified chaperonin containing TCP1 subunit 6A (CCT6A) as an inhibitor and direct binding protein of SMAD2 and found that CCT6A suppresses SMAD2 function in NSCLC cells and promotes metastasis. Furthermore, selective inhibition of SMAD3 or CCT6A efficiently suppresses TGF-β-mediated metastasis. Our findings provide a mechanism that directs TGF-β signaling toward its prometastatic arm and may contribute to the development of therapeutic strategies targeting TGF-β for NSCLC.
Use of supportive measures to improve outcome and decrease toxicity in docetaxel-based antiangiogenesis combinations in metastatic castrate resistant prostate cancer (mCRPC).
Authors: Fatima H. Karzai, Ravi Amrit Madan, Andrea Borghese Apolo, Yangmin M. Ning, Howard L. Parnes, Philip M. Arlen, Melony A. Beatson, Nancy Harold, Anna Couvillon, John Joseph Wright, Clara Chen, Nancy Ann Dawson, James L. Gulley, William Douglas Figg, William L. Dahut
Journal: Journal of Clinical Oncology (2013)

e16017 Background: We have completed accrual of 63 patients (pts) to our study combining lenalidomide (L), with bevacizumab (B), docetaxel (D), and prednisone (P) (ART-P) in mCRPC. Due to the lack of improved survival and the increased toxicity of anti-angiogenic docetaxel combinations in the MAINSAIL and CALGB 90401 trials, we attempted to compare and contrast our studies with these failed phase III trials. Methods: Among the first 52 pts on ART-P, 3 received L 15 mg daily, 3 received 20 mg daily, and the others received 25 mg daily for 14 days of every 21−day cycle (C). We then enrolled 11 pts at L 15 mg. All pts received D 75 mg/m2 and B 15 mg/kg on day 1 with P 10 mg and enoxaparin daily. Pegfilgrastim was given on day 2. Patients on CALGB 90401 received D 75 mg/m2 and B 15 mg/kg on day 1, with P 10 mg. On MAINSAIL, pts received D 75 mg/m2, L 25 mg daily for 14 days of every 21−day cycle with daily P. Patients on CALGB 90401 and MAINSAIL did not receive enoxaparin or pegfilgrastim prophylactically. Results: The median number of Cs on ART-P is 18 (1-52). Median PFS is 19.1 months. Twenty-seven pts had a PR, and one pt with measurable disease had a CR. Two patients (3%) had deep vein thromboses. Of 1,334 Cs given, 14 cycles were complicated by febrile neutropenia (FN) (1%). There were no treatment related deaths. In comparison, median number of Cs in MAINSAIL L+DP arm was 6, with a PFS of 45 weeks and an OS of 77 weeks. Thirty-four pts (6.5%) developed pulmonary emboli and there were 2 deaths due to toxicity in the experimental arm. Nearly 12% of Cs were complicated by FN. In the experimental arm of CALGB 90401 trial, median OS was 22.6 months with median PFS of 9.9 months. The median number of Cs were 8 and 19 pts developed thrombosis/emboli (3.6%). In addition, 37 patients developed FN and treatment related deaths were reported at 4%. Conclusions: The use of supportive care allowed longer treatment duration with the ART-P combination as compared to D+L (MAINSAIL) and D+B (CALGB 90401), potentiating a longer PFS, RR and possibly OS with an improved safety profile. This data demonstrates the potential importance of supportive measures and is hypothesis generating for future combination studies. Clinical trial information: NCT00942578.
Factors affecting quality of life in patients with vitiligo: a nationwide study
Authors: J.M. Bae, S.C. Lee, T.H. Kim, S.D. Yeom, J.H. Shin, W.J. Lee, M.‐H. Lee, A.‐Y. Lee, K.H. Kim, M.B. Kim, C.J. Park, S.H. Lee, D.H. Kim, H.J. Lee, D.Y. Lee, C.W. Choi, Y.C. Kim, H.Y. Kang, S. Haw, Y.B. Lee, S.J. Yun, S.‐K. Yun, S.P. Hong, Y. Lee, H.J. Kim, G.S. Choi
Journal: British Journal of Dermatology (2017)

Little is known about factors affecting the quality of life (QoL) of patients with vitiligo, and previous studies have shown conflicting results. To explore the QoL of patients with vitiligo and to identify factors affecting QoL. A nationwide questionnaire‐based study was conducted with 1123 patients with vitiligo recruited from 21 hospitals in Korea from July 2015 to June 2016. Data were collected using a structured questionnaire for demographic information and the Skindex‐29 instrument. Mild or severely impaired QoL in patients with vitiligo was assessed according to each domain (symptoms, functioning and emotions) of Skindex‐29. Multivariate logistic regression analyses were performed to determine the factors associated with QoL. Of the enrolled participants, 609 were male and 514 female, with a mean age of 49·8 years (range 20–84). The median duration of disease was 3·0 years (range 0–60). Using multivariate logistic regression modelling, the involvement of visible body parts and a larger affected body surface area were consistently associated with QoL impairment in all three domains of Skindex‐29. Additionally, the QoL of patients aged 20–59 years, who potentially had a more active social life than older patients, was associated with functional impairment. Furthermore, a higher educational background was associated with emotional impairment. A multitude of factors significantly influence the QoL of patients with vitiligo. A better appreciation of these factors would help the management of these patients.
Pattern of systemic relapse and outcome of patients (pts) with ocular melanoma (OM) after curative local therapy (Rx): Results of an active surveillance strategy.
Authors: Niamh Coleman, Giuseppe Gullo, Ciara Marie Kelly, Megan Greally, Barry Power, Susan Kennedy, Emir Hoti, Noel Horgan, John P Crown
Journal: Journal of Clinical Oncology (2015)

e20091 Background: Despite optimal local Rx 35-50% of pts with OM develop metastasis (MM), most frequently in the liver. Systemic Rx for MM is very unsatisfactory and the median overall survival (OS) is approximately 6 months. In this study, we aimed to assess the pattern of systemic relapse and outcome of pts with OM referred to our institution after curative local Tx. Methods: We conducted a retrospective analysis of a prospectively maintained medical oncology database of all OM cases referred to our institution. The database started accruing in September 2009 and all pts entered an active surveillance program with oncology review, physical examination and dedicated liver imaging (computed tomography or ultrasound) every 6 to 12 months. Results: 120 pts were included in our database and analysed. Pts characteristics: male 66 (55%), median age 54yrs (range 24–85), median OM thickness: 4.85mm, median OM diameter: 11.4mm, definitive local Tx: plaque brachytherapy 81 (67.5%), enucleation 33 (27.5%), proton/external beam RT 6 (5%). Median follow-up (FU) is 30 months (range 3-144 months). 16 pts (13%) developed relapsed MD during FU, 15 of whom (94%) in the liver. MM was diagnosed on surveillance imaging in 13/16 pts (81%), 3/16 pts (19%) had imaging because of symptoms. Six pts had resectable liver disease and underwent surgery, 10 pts were unresectable and received systemic Tx. At a median FU of 10mos (1-38), 4/6 pts (67%) are alive in the resectable group (2 disease-free: 2+, 8+ months from surgery), 3/10 (30%) in the non-resectable group (1+, 6+, 12+ months from diagnosis). Pts received multiple lines of systemic Tx which included ipilimumab (n = 12), pembrolizumab (n = 2), systemic chemotherapy (CT) (n = 4) and Delcath intrahepatic CT (n = 2). Conclusions: (1) Metastatic relapse rate in our series is lower than published literature, possibly related to relatively short median FU. (2) Liver was the first site of MM in the vast majority of pts. (3) Implementation of an active surveillance strategy after curative local Rx results in diagnosis of asymptomatic MM in liver, allowing for early resection of disease. (4) Managing metastatic OM remains a significant challenge.