tbuckley/cabot-search huggingface dataset:
Clinical outcome for continuous versus intermittent chemotherapy for unresectable metastatic colorectal cancer: Comparative analysis after first-line therapy.
Authors: Nadine Abdallah, AMR Mohamed, Hibah Ismail, Wei Chen, Alaa Akhras, Hyejeong Jang, Daryn W. Smith, Anteneh A. Tesfaye, Philip Agop Philip, Anthony Frank Shields
Journal: Journal of Clinical Oncology (2018)

825 Background: Colorectal cancer (CRC) is the third most common and second most lethal cancer in the U.S, with almost 50% of patients developing metastatic disease. Although survival of metastatic CRC (mCRC) has improved significantly, current treatment strategies are associated with many adverse effects. With no prospect of cure, goals of treatment should consider both quantity and quality of life. Interruption of chemotherapy after induction can represent a means to achieve this balance. Methods: The primary objective of this meta-analysis is to assess the effect of continuation vs interruption of systemic therapy in terms of survival in patients with unresectable mCRC after first line treatment. Among 15 prospective studies published from 2009-2017, 9 qualified for inclusion. Random-effect model was used for pooled effects within two main categories: continuous chemotherapy vs chemotherapy-free interval after first line induction. Studies with maintenance fluoropyrimidine and/or bevacizumab were excluded. Primary endpoint was median progression free survival (PFS) and secondary endpoint was median overall survival (OS). z statistics were used for comparing subgroups. All statistical tests were two-sided. P values &lt; 0.05 were considered significant. Results: 1366 patients (55% males) were included in the final analysis. Induction treatment was 5-FU or capecitabine-based chemotherapy with either oxaliplatin or irinotecan with or without bevacizumab. After stratifying for induction status, there was no statistically significant difference in median PFS between continuous vs chemotherapy free interval [Median PFS 4.74-month (95% CI 3.87-5.61) vs 3.52 month (95% CI 2.97-4.07), z-test adjusted p value 0.1383]. No significant difference in median OS between both groups [Median OS 16.95-month (95% CI 15.40-18.50) vs 18.35 month (95% CI 15.17-21.54)]. Conclusions: In mCRC patients, the superiority of continuous chemotherapy was not demonstrated. Further studies should shed light on patient and tumor characteristics most likely to benefit from continuous chemotherapy to limit delivery of cytotoxic therapy to this subset of patients.
The Combination of Duvelisib, a PI3K-δ,γ Inhibitor, and Romidepsin Is Highly Active in Relapsed/Refractory Peripheral T-Cell Lymphoma with Low Rates of Transaminitis: Results of Parallel Multicenter, Phase 1 Combination Studies with Expansion Cohorts
Authors: Steven M. Horwitz, Alison J. Moskowitz, Eric D Jacobsen, Neha Mehta-Shah, Michael S Khodadoust, David C. Fisher, Patricia Myskowski, Erica B.K. Wang, Marianne Tawa, Theresa Davey, William Blouin, Helen Hancock, Nivetha Ganesan, Natasha Galasso, Evan Marzouk, Alexandra Bahgat, Hallie Jester, Sophia Fong, Abeer Butt, Ahmet Dogan, Youn H. Kim, David M Weinstock
Journal: Blood (2018)
Safety and Tolerability of Omalizumab: A Randomized Clinical Trial of Humanized Anti‐IgE Monoclonal Antibody in Systemic Lupus Erythematosus
Authors: Sarfaraz Hasni, Sarthak Gupta, Michael Davis, Elaine Poncio, Yenealem Temesgen‐Oyelakin, Elizabeth Joyal, Alice Fike, Zerai Manna, Sungyoung Auh, Yinghui Shi, Diana Chan, Philip Carlucci, Ann Biehl, Barbara Dema, Nicolas Charles, James E. Balow, Meryl Waldman, Richard M. Siegel, Mariana J. Kaplan, Juan Rivera
Journal: Arthritis & Rheumatology (2018)

Objective Autoreactive IgE antibodies have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). We hypothesize that omalizumab, a monoclonal antibody binding IgE, may improve SLE activity by reducing type I interferon (IFN) production by hampering plasmacytoid dendritic cells and basophil activation. This study was undertaken to assess the safety, tolerability, and clinical efficacy of omalizumab in mild to moderate SLE. Methods Sixteen subjects with SLE and a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI‐2K) score of ≥4 and elevated autoreactive IgE antibody levels were randomized to receive omalizumab or placebo (2:1) for 16 weeks, followed by 16 weeks of open‐label treatment and a 4‐week washout period. The SLEDAI‐2K score, British Isles Lupus Assessment Group index (BILAG 2004) score, and physician's global assessment of disease activity were recorded at each visit. The type I IFN–induced gene signature was determined using quantitative polymerase chain reaction. Results Omalizumab was well tolerated with no allergic reactions, and mostly mild adverse events comparable to those experienced with placebo treatment. SLEDAI‐2K scores improved in the omalizumab group compared to the placebo group at week 16 ( P = 0.038), as well as during the open‐label phase in subjects initially receiving placebo ( P = 0.02). No worsening in BILAG scores or the physician's global assessment was detected. There was a trend toward a reduction in IFN gene signature in subjects treated with omalizumab ( P = 0.11), especially in subjects with a high baseline IFN signature ( P = 0.052). Conclusion Our findings indicate that omalizumab is well tolerated in SLE and is associated with improvement in disease activity. Larger randomized clinical trials will be needed to assess the efficacy of omalizumab in patients with SLE.
Tolerable Dose of 6-Mercaptopurine and Prognostic Impact of NUDT15-Deficient Genotype in Childhood Acute Lymphoblastic Leukemia
Authors: Yoichi Tanaka, Motohiro Kato, Takaya Moriyama, Yuki Arakawa, Daisuke Hasegawa, Junya Fujimura, Dai Keino, Atsushi Sato, Takahiro Ueda, Yuichi Taneyama, Masatoshi Takagi, Masaki Yamamoto, Masaki Matsuoka, Moeko Hino, Hiroki Hori, Katsuyoshi Koh, Allen Eng Juh Yeoh, Jun J. Yang, Atsushi Manabe
Journal: Blood (2018)
Impact of IKZF1 Deletions and IKZF1 Plus in Pediatric Acute Lymphoblastic Leukemia Outcome
Authors: Maria Sara Felice, Patricia Laura Rubio, Myriam Ruth Guitter, Jorge Gabriel Rossi, Jorge Alberto Digiorge, Maria Constanza Guardia, Maria Angelica Fernández Barbieri, Gladys Gutierrez, Ezequiel Recondo, Maria Soledad Vides Herrera, Vanina Livio, Cristina Noemi Alonso
Journal: Blood (2018)
Assessing concordance with Cancer Care Ontario guidelines for safe administration of systemic therapy.
Authors: Esther Green, Leonard Kaizer, Victoria Zwicker, Zahra Ismail, Vicky Simanovski, Erin Rae, Tory Andrien, Reena Tabing
Journal: Journal of Clinical Oncology (2014)

e17670 Background: The delivery of chemotherapy in a way that optimizes patient safety depends on the vigilance of a health care team and the integration of system checks and balances to recognize and prevent medication errors before they occur. Nurses, as the primary clinician responsible for delivering chemotherapy, are key players in this endeavor. In 2012, Cancer Care Ontario (CCO) released Part 1 of the Safe Administration of Systemic Cancer Therapy Guideline that outlined recommendations on the planning and preparation phases of chemotherapy delivery. A survey was developed to assess concordance with the recommendations, identify areas for local and provincial quality improvement and review the role of nurses in ensuring patient safety during systemic treatment. Methods: The survey focused on the areas in the guideline that reflected nursing practices in chemotherapy suites: patient identification, checklists, patient assessment prior to treatment and written treatment plans. Nurses were identified at the 14 Regional Cancer Centres (RCCs) to complete the survey. Results: All 14 RCCs completed the survey (100% response rate). All centres complied with the guideline recommendation to use at least two patient identifiers, with 11 centres using patient wristbands as recommended. Concordance to the recommendations to have a written protocol for patient pretreatment assessment and the use of safety checklists was low, as most centres did not implement these tools systematically. Six centres cited routine use of formal written plans of care that are included in patient records. Nine centres indicated that documented care plans are available to nurses involved with the delivery of chemotherapy. While all centres employ methods to ensure patient safety, the results indicate that there are opportunities for improvement in the majority of nursing practice domains. Conclusions: CCO’s Safe Administration Guideline provides recommendations to improve patient safety and drive widespread practice changes to prevent chemotherapy errors. Increased awareness of the guideline and the implementation of recommended tools such as checklists can support guideline concordance and increase patient safety.
A Randomized, Double-Blind Efficacy and Safety Study of PF-05280586 (a Potential Rituximab Biosimilar) Compared with Rituximab Reference Product (MabThera®) in Subjects with Previously Untreated CD20-Positive, Low Tumor Burden Follicular Lymphoma (LTB-FL)
Authors: Jeff Sharman, Anna Marina Liberati, Rodrigo Santucci Silva, Igor Aurer, Jeffery Robbins, Julie Ann Rosenberg, Tahira Khan, Ann Alcasid
Journal: Blood (2018)
Do patients achieving pathologic complete response (pCR) following neoadjuvant treatment for locally advanced rectal cancer (LARC) need adjuvant chemotherapy?
Authors: Anis Hamid, Jeremy David Shapiro, Paul McMurrick, Stephen Bell, Ian Porter, Peter Carne, Andrew Mark Haydon
Journal: Journal of Clinical Oncology (2014)

3577 Background: Optimal treatment for locally advanced rectal cancer (LARC) includes neoadjuvant short-course radiotherapy (SCRT) or long-course chemoradiotherapy. One advantage of long-course treatment is potential for tumour downstaging to pathologic complete response (pCR) in 10-15%, a sub-group with an excellent long-term prognosis. Uncertainty exists regarding the need for post-operative chemotherapy in such patients. We aimed to review the treatment and outcomes of all consecutive patients achieving pCR following neoadjuvant treatment for LARC. Methods: All patients undergoing neoadjuvant treatment for LARC at two academic centers between 1999-2012 were identified and their resection histopathology reports reviewed to identify patients with pCR. These cases were reviewed for initial stage, pre- and post-operative treatment, local and distant recurrences as well as OS. Results: There were 53 (15.5%) of 342 consecutive patients undergoing curative-intent surgery achieved pCR (ypT0N0). 2/41 (4.9%) undergoing SCRT, and 51/301 (16.9%) undergoing long-course radiotherapy (LCRT) had pCR. Of 53 pCR patients, 46 were staged T3/T4 pre-operatively, all remaining were T2, node-positive except 2 patients who were T2, node-negative. Between patients who did and did not achieve pCR, there was no significant difference in age, Eastern Cooperative Oncology Group (ECOG) (0 vs 1+), the proportion undergoing SCRT versus LCRT (2/53 vs. 39/289 respectively, p=0.06) or the time from completing LCRT to surgery (p=0.32). 63% of pCR patients received adjuvant 5-FU. These patients were younger (mean age 54 vs 71 years; p<0.001), however there was no difference in ECOG. No pCR patients developed local recurrence and only 2 distant recurrences occurred. 5-year OS was 91%, and no difference in RFS or OS was seen between those who did and did not receive adjuvant 5-FU. Conclusions: Our findings support previous studies showing excellent outcomes (>90% 5-year DFS and OS) for patients with pCR after neoadjuvant treatment for LARC. We further demonstrate no significant difference in OS or RFS between pCR patients who did and did not receive adjuvant 5-FU. This data adds to growing evidence suggesting that there may be no advantage in administering adjuvant 5-FU to this patient population.
Neurotrophins and glial cell line-derived neurotrophic factor in the ovary: physiological and pathophysiological implications
Authors: Hsun-Ming Chang, Hai-Cui Wu, Zhen-Gao Sun, Fang Lian, Peter C K Leung
Journal: Human Reproduction Update (2018)

Neurotrophins [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4)] and glial cell line-derived neurotrophic factor (GDNF) are soluble polypeptide growth factors that are widely recognized for their roles in promoting cell growth, survival and differentiation in several classes of neurons. Outside the nervous system, neurotrophin (NT) and GDNF signaling events have substantial roles in various non-neural tissues, including the ovary. The molecular mechanisms that promote and regulate follicular development and oocyte maturation have been extensively investigated. However, most information has been obtained from animal models. Even though the fundamental process is highly similar across species, the paracrine regulation of ovarian function in humans remains poorly characterized. Therefore, this review aims to summarize the expression and functional roles of NTs and GDNF in human ovarian biology and disorders, and to describe and propose the development of novel strategies for diagnosing, treating and preventing related abnormalities. Relevant literature in the English language from 1990 to 2018 describing the role of NTs and GDNF in mammalian ovarian biology and phenotypes was comprehensively selected using PubMed, MEDLINE and Google Scholar. Studies have shown that the neurotrophins NGF, BDNF, NT-3 and NT-4 as well as GDNF and their functional receptors are expressed in the human ovary. Recently, gathered experimental data suggest putative roles for NT and GDNF signaling in the direct control of ovarian function, including follicle assembly, activation of the primordial follicles, follicular growth and development, oocyte maturation, steroidogenesis, ovulation and corpus luteum formation. Additionally, crosstalk occurs between these ovarian regulators and the endocrine signaling system. Dysregulation of the NT system may negatively affect ovarian function, leading to reproductive pathology (decreased ovarian reserve, polycystic ovary syndrome and endometriosis), female infertility and even epithelial ovarian cancers. A comprehensive understanding of the expression, actions and underlying molecular mechanisms of the NT/GDNF system in the human ovary is essential for novel approaches to therapeutic and diagnostic interventions in ovarian diseases and to develop more safe, effective methods of inducing ovulation in ART in the treatment of female infertility.
The impact of PET-CT on staging, management, and prognostication of small-cell lung cancer.
Authors: Alona Zer, Yael Rapson, Meital Nadam, Dov Flex, Aaron Allen, Salomon M. Stemmer, David Groshar, Hanna Bernstine
Journal: Journal of Clinical Oncology (2014)

6611 Background: Although frequently used, there is no randomized data assessing the role of PET CT in the staging process of SCLC patients, or its impact on patients’ management. We aimed to review the utility of PET-CT in patients diagnosed with SCLC in a single tertiary medical center. Methods: All patients diagnosed with SCLC for 5 consecutive years were included, either staged by PET-CT or not. We retrieved clinical data, staging procedures, PET parameters (SUVmax and TLG) progression free survival (PFS) and Overall Survival (OS). In the group of patients who underwent PET CT during initial evaluation, re-assessment staging was performed by two independent radiologists: one according to PET-CT findings, and the other according to chest, abdomen and pelvic contrast-enhanced CT scan findings (with bone scan results if available) and blinded to the PET results. Results: 108 patients were identified. 2 patients were excluded from the analysis for lack pathology or staging procedure data and 10 patients were excluded since their PET imaging was not accessible. Out of 96 patients, 54 had a PET-CT done as part of their staging procedure. PET-staged patients had significantly less staging procedures (including FDG-PET scan, CT scans, MRIs, Bone Scans, BMBs) done than non-PET-staged patients (24% underwent 3-4 staging procedures versus 62%, p=0.04). PET altered management in 19 patients (35%), with 13 patients with suspected metastatic disease, who benefited from down-staging by PET. Treatment was delayed in PET-staged patients by 4 days; 30 vs 26 days from diagnostic procedure to treatment (p=0.04). High TLG level predicted poorer survival (HR=3.38, p=0.007). Conclusions: PET-CT adds to SCLC patients’ management by reducing the amount of staging procedures and possibly down staging patients who otherwise would have been treated for palliative intent. In the setup of a public health system, waiting for the PET to be done and reported could result in treatment delay. TLG appears to be a new promising prognostic biomarker in small cell lung tumors. Prospective randomized trials are warranted to properly evaluate sensitivity, specificity and influence on management.
Does auto-PAP work in patients with acute quadriplegia and sleep-disordered breathing?
Authors: Abdulghani Sankari, M. Safwan Badr
Journal: Thorax (2019)

Patients living with spinal cord injury or disease (SCI/D) face numerous hurdles to accessing high-quality care for sleep disorders, from inadequate recognition of sleep health among patients with SCI/D and their providers, to erroneous attribution of daytime symptoms, limited access to sleep diagnostic services and difficulties using medical devices needed to treat sleep-disordered breathing (SDB). The treatment of choice for SDB is positive airway pressure (PAP), which improves sleep quality, metabolic function and quality of life while reducing sleepiness in able-bodied adults. For example, the Apnea Positive Pressure Long-term Efficacy Study (APPLES) trial,1 which recruited from both sleep clinics and the general population, demonstrated that PAP therapy was associated with significant improvement in subjectively and objectively measured sleepiness, but without a significant impact on short-term or long-term cognitive function. Even in able-bodied adults with SDB, adherence to PAP remains a major challenge that requires individualised and intensive education, monitoring and support. There is evidence that patients with SCI/D are less adherent to PAP therapy than able-bodied individuals.2 Reasons for poor adherence include mobility impairment to adjust the mask, increased awakenings due to autonomic dysfunction, nasal congestion, inadequate support and inconvenience due to the presence of other comorbidities.3

SDB in patients with SCI/D combines features of obstructive and central SDB. For example, increased upper airway collapsibility is noted in all patients with SCI4 and the use of opioid analgesics may increase the risk of central SDB. In addition, …
Acalabrutinib in Treatment-Naive (TN) Chronic Lymphocytic Leukemia (CLL): Updated Results from the Phase 1/2 ACE-CL-001 Study
Authors: John C. Byrd, Jennifer A. Woyach, Richard R. Furman, Peter Martin, Susan M. O'Brien, Jennifer R. Brown, Deborah M. Stephens, Jacqueline C. Barrientos, Stephen Devereux, Peter Hillmen, John M. Pagel, Dih-Yih Chen, Ahmed Hamdy, Raquel Izumi, Priti Patel, Min Hui Wang, Nitin Jain, William G. Wierda
Journal: Blood (2018)
Role of wnt/ß-catenin pathway in myeloid neoplasms with 5q deletion: A new therapeutic target.
Authors: Nupur Mittal, Amber Dawn Seba, Vitalyi Senyuk, Zhijian Qian
Journal: Journal of Clinical Oncology (2014)

7076 Background: 5q deletion (del 5q) is a recurring cytogenetic abnormality present in around 10% of de-novo and 40% of therapy related myelodysplastic syndrome (MDS)/ Acute myeloid leukemia( AML). These patients often are relatively resistant to conventional therapies and have unfavourable outcome. Del 5q is associated with haplo-insufficiency of APC gene in hematopoietic stem cells (HSCs) which leads to MDS like disease in mice (Blood 2010). APC regulates the function of HSCs largely through β-catenin dependent mechanisms ( Blood 2013). We have shown previously that Indomethacin induced β-catenin inhibition leads to growth suppression in human myeloid leukemia cells with del 5q (UoCM1) but has non-specific targets in addition to β-catenin. Methods: Our objective is to show effects of blocking Wnt/β-catenin pathway by specific β-catenin inhibition in del 5q myeloid leukemia. Lentiviral particles expressing a control empty backbone or β-catenin targeting inhibitory shRNA were transduced into UoCM1 and REH (Leukemia cell line with no del 5q) achieving specific β-catenin knockdown. Growth , proliferation and apoptosis of the transduced cells was assessed by flow cytometry and In vitro colony forming assay. Results: Western Blot confirms higher β-catenin expression in UoCM1 vs REH line. UoCM1 cells transduced with β-catenin shRNA showed 60% growth inhibition compared to control vector. In contrast, REH demonstrated comparable growth in control and β-catenin shRNA transduced cells. There was significant decrease in the fractions of cells in S and G2/M phase and increase in apoptosis (p <0.05) in UoCM1 cells with β-catenin inhibition compared to control. REH showed no difference in distribution in cell cycle and similar frequency of apoptosis in β-catenin inhibited and control cells. Decrease in colony formation was observed in UoCM1 cells with β-catenin inhibition. Conclusions: 5q del in myeloid leukemia cell line leads to up-regulation of β-catenin. Blockade of Wnt pathway by specific β-catenin inhibition suppresses cell growth and induces apoptosis in a human myeloid leukemia cell line with 5q del. This discovery paves the way for new therapeutic strategies targeting β-catenin and improving survival in 5q del AML/MDS.