tbuckley/cabot-search huggingface dataset:
Acupuncture versus cognitive behavioral therapy for cognitive impairment in cancer survivors with insomnia: Implications for personalized medicine.
Authors: Jun J. Mao, Kevin Liou, James Root, Qing Susan Li, Ting Bao, Sheila N. Garland, Tim Ahles
Journal: Journal of Clinical Oncology (2019)

11522 Background: Cognitive impairment is a prevalent condition among cancer survivors that lacks effective treatment and can be maintained and exacerbated by poor sleep. This study explored whether treating insomnia with acupuncture or Cognitive Behavioral Therapy for Insomnia (CBT-I) improves subjective and objective cognitive functions in cancer survivors. Methods: We analyzed cognitive outcomes from a pragmatic randomized trial comparing acupuncture versus CBT-I for cancer survivors with insomnia. Analysis was limited to those reporting cognitive impairment at baseline. Acupuncture and CBT-I were delivered over 8 weeks. Perceived cognitive ability was assessed using the Brown Attention-Deficit Disorder Scale (BADDS). Objective cognitive function was evaluated with the Buschke Selective Reminding Test (BSRT). All outcomes were evaluated at baseline, Week 8 (end of intervention), and Week 20 (12 weeks post-intervention). Results: Among 99 cancer survivors, mean age was 60.4 years, 56.6% were women, and 26.3% were non-white. The most common cancer types were breast (31.3%) and prostate (19.2%). Perceived cognitive ability improved in both acupuncture and CBT-I groups at weeks 8 and 20 relative to baseline (all P &lt; 0.001). No significant between-group differences were noted in BADDS total score (p = 0.28), but the CBT-I group demonstrated a better BADDS attention subscale score than the acupuncture group at weeks 8 and 20 (p = 0.031). With regards to objective cognitive functions assessed by BSRT, acupuncture improved attention (p = 0.017), learning (p = 0.040), and memory (p = 0.0020) at Week 8, whereas CBT-I only improved attention at Week 20 (p = 0.0002); between-group differences were not statistically significant. Conclusions: Among cancer survivors with insomnia, both acupuncture and CBT-I improved cognitive impairment relative to baseline, but their relative effects differed: the CBT-I group showed slightly better subjective attention, whereas the acupuncture group may have improved objective memory. Further investigation of these two therapies may lead to effective and personalized interventions for cancer survivors. Clinical trial information: NCT02356575.
Clinical implications of discrepancy in the diagnosis of primary myelofibrosis between referral and tertiary center.
Authors: Ghayathri Jeyakumar, Cecilia Ysabel Arana Yi, Pedro Medina, Jorge E. Cortes, Sherry Pierce, Mark Brandt, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2013)

7115 Background: Primary Myelofibrosis (PMF) is a stem cell-derived clonal disorder with broad disease spectrum and the diagnosis is based on a combination of clinicopathological criteria. The aim of the study is to evaluate the frequency of diagnostic discrepancies between the referring center and a tertiary center and the impact in clinical outcomes in patients with PMF. Methods: 560 patients (pts) with Primary Myelofibrosis (PMF) referred to MD Anderson Cancer Center from January 2007 to December 2011 were evaluated. Results: 70 (12.5%) pts were discordant and 490 (87.5%) were non-discordant. The median age was 67 years (range, 32-88): 39 (56%) discordant versus 326 (67%) non-discordant pts were older than 65 years (p&lt;0.075). Cytogenetics in the discordant group were favorable in 40 (57%) and unfavorable in 27 (39%) and in the non-discordant group 309 (63%) and 162 (33%) respectively (p&lt;0.36). The DIPSS-plus score in the discordant group was low in 3 (4%), intermediate-1 in 11(16%), intermediate-2 in 27 (39%), and high in 26 (37%), and in the non-discordant group 12 (2%), 63(13%), 251 (51%) and 161 (33%) respectively (p &lt; 0.33). JAK2V617F was positive in 46 (66%) cases of discordant group and in 381 (78%) of the non-discordant group (p&lt;0.027). Peripheral blasts &gt;1% were present in 378 (77%) non-discordant and in 36 (51%) discordant cases (p&lt;0.001). The referring diagnosis for discordant cases were MPN unclassified in 18(26%), PV in 12 (17%), ET in 7 (10%), CML in 5 (7%), MDS/MPN unclassified in 15 (21%), BCR-ABL negative CML in 2 (32%), CMML in 2 (3%) and MDS in 8 (11%) cases. The median OS in the non-discordant group versus discordant group after the appropriate diagnosis were 44.6 and 36.6 months respectively (p&lt;0.069). Conclusions: The results confirm that the diagnosis of PMF is complex. The rate of discrepancy is high confirming the need for complete evaluation in a tertiary center. The presence of peripheral blasts and JAK2 mutation appear to helped in making proper diagnosis before referral.
Physical symptoms and psychological distress in head and neck cancer patients.
Authors: Lara Anne Trevino, Joseph Roscoe, Jennifer S. Gewandter, Gary R. Morrow
Journal: Journal of Clinical Oncology (2012)

e16056 Background: Little is known about the relationship between psychological distress and physical symptoms in head and neck cancer (HNC) patients undergoing radiation therapy (RT), and how these relationships may change over the course of treatment. We conducted exploratory analyses, on a previously published descriptive study examining the occurrence and severity of physical symptoms during RT. The purpose of this secondary analysis was to determine the relationship over time between psychological distress and physical symptoms in HNC patients. Methods: Ninety HNC patients receiving RT completed a Symptom Inventory (SI) weekly for five weeks, beginning with the week prior to the start of treatment. The SI assesses the presence and severity of 12 symptoms, including, pain, fatigue, nausea, disturbed sleep, feeling distressed, shortness of breath, memory, lack of appetite, drowsiness, vomiting, skin problems, and urination difficulty. Change scores in symptom severity between baseline and weeks 2, 3 and 4 were calculated, and Pearson’s correlations were used to determine the associations between psychological distress and physical symptoms. Results: Changes in psychological distress between baseline and week 2 of treatment were significantly correlated with changes in fatigue (r = 0.35, n=52, p = 0.01) and skin problems (r = 0.40, n=36, p = 0.02). Changes in psychological distress between baseline and week 3 of treatment were significantly correlated with changes in fatigue (r = 0.42, n=42, p = 0.006), shortness of breath (r = 0.48, n=42, p = 0.001), memory (r=0.36, n=42, p = 0.02), and lack of appetite (r = 0.53, n=42, p = 0.001). Changes in psychological distress between baseline and week 4 of treatment were correlated with changes in fatigue (r = 0.57, n=40, p=0.001), memory (r=0.48, n=39, p=0.002), and lack of appetite (r=0.49, n=40, p=0.001). Conclusions: Fatigue, memory, shortness of breath, and lack of appetite are significantly related to psychological distress in HNC patients undergoing RT. Additional research is needed to determine how psychological distress affects physical symptoms and if improvements in psychological distress may attenuate physical symptoms in HNC patients receiving RT.
Factors affecting survival of patients with Masaoka stage IV thymic epithelial tumors (TET).
Authors: Yaman Suleiman, Milan Radovich, Luis Rojas, Ryan Frederick Porter, Madison Conces, Kristen Leigh Shirar, Robert P Nelson, Aaron John Spittler, Bilal Karim Siddiqui, Matthew Burns, Sunil S. Badve, Bryan P. Schneider, Patrick J. Loehrer
Journal: Journal of Clinical Oncology (2012)

7107 Background: Thymoma and thymic carcinoma (TC) are rare tumors, but represent the most common neoplasms of the anterior mediastinum. The vast majority of TET present in early stages with little data existing on factors influencing survival in patients with advanced or stage IV disease. Methods: A retrospective analysis was performed on patients with confirmed TET (histology and with tissue blocks) seen at IUSCC diagnosed between 1976 and 2011. Patient demographics including Masaoka stage, histology, and sites of metastasis were linked with progression free survival (PFS) and overall survival (OS). Results: Our analysis included 102 patients with stage IV TET: 50 presented de novo and 52 developed stage IV disease following primary treatment. When stratified by tumor histology (thymoma or TC), patients with TC had considerably poorer PFS (p=1.87x10 -7 ) and OS (p=7.72x10 -8 ). The median PFS for TC was 13 months (range 4 to 39) and the MST was 36 months (range 4 to 115). PFS at 5-years was 21% and 0% but the five-year OS was 84% and 29% for thymoma and TC, respectively. Ten year OS was 55% for patients with thymoma and 0% for those with TC. Pleural (&gt;3 vs. &lt;3) metastases were significantly associated with a better PFS (p=0.036) and OS (p=0.0003). The PFS and OS of patients with lung nodules trended with those with pleural metastasis. Patients with pleural metastasis and lung nodules sites did considerably better than those with visceral disease (PFS, p=0.004, OS, p=2.09x10 -5 ). Conclusions: Patients with TC have significantly poorer PFS and OS when compared to thymoma confirming that TC is a distinct clinical entity from thymoma. Patients with thymoma may have prolonged survival, despite having residual disease. Although current staging places patients with pleural metastasis (Masaoka stage IVA) and those with lung nodules (stage IVB) as separate categories, our data would suggest that those with lung nodules have similar survival with those who have pleural metastasis.
Long-lasting blood pressure lowering effects of nitrite are NO-independent and mediated by hydrogen peroxide, persulfides, and oxidation of protein kinase G1α redox signalling
Authors: Martin Feelisch, Takaaki Akaike, Kayleigh Griffiths, Tomoaki Ida, Oleksandra Prysyazhna, Joanna J Goodwin, Nicholas D Gollop, Bernadette O Fernandez, Magdalena Minnion, Miriam M Cortese-Krott, Alessandra Borgognone, Rosie M Hayes, Philip Eaton, Michael P Frenneaux, Melanie Madhani
Journal: Cardiovascular Research (2019)

Abstract Aims Under hypoxic conditions, nitrite (NO2−) can be reduced to nitric oxide (NO) eliciting vasorelaxation. However, nitrite also exerts vasorelaxant effects of potential therapeutic relevance under normal physiological conditions via undetermined mechanisms. We, therefore, sought to investigate the mechanism(s) by which nitrite regulates the vascular system in normoxia and, specifically, whether the biological effects are a result of NO generation (as in hypoxia) or mediated via alternative mechanisms involving classical downstream targets of NO [e.g. effects on protein kinase G1α (PKG1α)]. Methods and results Ex vivo myography revealed that, unlike in thoracic aorta (conduit vessels), the vasorelaxant effects of nitrite in mesenteric resistance vessels from wild-type (WT) mice were NO-independent. Oxidants such as H2O2 promote disulfide formation of PKG1α, resulting in NO- cyclic guanosine monophosphate (cGMP) independent kinase activation. To explore whether the microvascular effects of nitrite were associated with PKG1α oxidation, we used a Cys42Ser PKG1α knock-in (C42S PKG1α KI; ‘redox-dead’) mouse that cannot transduce oxidant signals. Resistance vessels from these C42S PKG1α KI mice were markedly less responsive to nitrite-induced vasodilation. Intraperitoneal (i.p.) bolus application of nitrite in conscious WT mice induced a rapid yet transient increase in plasma nitrite and cGMP concentrations followed by prolonged hypotensive effects, as assessed using in vivo telemetry. In the C42S PKG1α KI mice, the blood pressure lowering effects of nitrite were lower compared to WT. Increased H2O2 concentrations were detected in WT resistance vessel tissue challenged with nitrite. Consistent with this, increased cysteine and glutathione persulfide levels were detected in these vessels by mass spectrometry, matching the temporal profile of nitrite’s effects on H2O2 and blood pressure. Conclusion Under physiological conditions, nitrite induces a delayed and long-lasting blood pressure lowering effect, which is NO-independent and occurs via a new redox mechanism involving H2O2, persulfides, and PKG1α oxidation/activation. Targeting this novel pathway may provide new prospects for anti-hypertensive therapy.
Relationship between EGFR Intron-1 CA SSR 1 polymorphism and skin rash in patients treated with cetuximab.
Authors: Sergiusz Nawrocki, Monika Rucinska
Journal: Journal of Clinical Oncology (2013)

e22087 Background: EGFR inhibiting drugs do not work equally effectively in cancer patients. We were looking for potential genetic factors which could help to select patients who benefit from treatment with cetuximab. One of established clinical factors is skin rash, which correlate with clinical response to EGFR inhibitors. Our hypothesis was that rash intensity depends on genetic polymorphisms of gene encoding EGFR, especially on Intron-1 CA SSR 1 polymorphism. The number of CA repeats in Intron-1 may affect the level of preRNA synthesis. Methods: The prospective study included 62 patients (colon cancer, head and neck, non-small cell lung cancer and gastric cancer) who were treated with cetuximab together with chemotherapy. 4 weeks after the start of treatment with cetuximab, rash intensity was assessed according to NCI CTAEv.3.0. criteria. DNA for analysis was isolated from 5 ml of peripheral blood. Using the PCR reaction with specific primers (polymorphic DNA segment was amplified. The obtained DNA fragments were analysed by GenScan to determine their lengths. Results: Patients with 15-18 “CA” repetitions were classified as having a short allele “S”, while patients with 19-22 “CA” repetitions have been marked as having a long allele “L”. The relationship between the rash intensity and the CA-polymorphism was assessed (Table). The analysis showed that there is tendency to more intensive rash in patients with pair of “short” alleles (SS), than in patients with “short-long” (SL) and “long” (LL) allelles (p&lt;0,1 chi-square test). Conclusions: There is a relationship between the EGFR Intron-1 CA-polymorphism and the rash intensity in patients treated with cetuximab which warrants further prospective clinical investigation. [Table: see text]
Timing and severity of skin-related adverse events in a phase II trial of sorafenib (BAY43-9006) in patients with advanced thyroid cancer.
Authors: Raya D. Terry, Stephen Michael Keefe, Carolyn Marie Grande, Larisa Zifchak, Marcia S. Brose
Journal: Journal of Clinical Oncology (2013)

e17009 Background: We previously conducted a phase II study of sorafenib (BAY43-9006) in advanced thyroid cancer. Rash and Hand-Foot Skin Reaction (HFSR) were two of the most common adverse events (AEs). Because these skin-related AEs affect quality of life, we further explored their time course and management. Methods: Fifty-five patients were treated on UPCC 03305, a phase II study of sorafenib in patients with advanced thyroid cancer from 2006 to 2011. AEs were recorded using CTCAE v.3.0 and reported here if relation to the drug was deemed “possibly-related” or greater. Cycle length was four weeks. Results: No grade 4 or 5 skin toxicity was observed. Forty-nine patients (89%) experienced rash. Thirty-one patients had a maximum severity of grade 1 (56%), eight had grade 2 (15%), and nine had grade 3 (18%). Fifty patients (91%) had HFSR. Thirteen patients had a maximum severity of grade 1 (24%), 33 had grade 2 (60%), and four had grade 3 (7%). The severity of rash peaked at cycle 1 (19% grade 2,3) and declined by cycle 3 (4% grade 2,3). The severity of HFSR peaked at cycle 2 (39%, grade 2,3) and declined by cycle 6 (10% grade 2,3). The timing and severity of rash and HFSR by cycle are reported in the Table. Following cycle 12 the severity and prevalence of skin AEs reached a steady state. Of the 55 patients, 30 patients (55%) required dose-reduction, and nine of those patients (31%) resumed full dose by the end of study date. Nine patients (16%) were dose-reduced for rash, 17 patients (31%) were dose-reduced for HFSR, and three patients (5%) were dose-reduced for both rash and HFSR. Conclusions: The severity of skin toxicity peaked by cycle 1 for rash and cycle 2 for HFSR. The severity improved dramatically for rash by cycle 3 and for HFSR by cycle 6. Our data support the close supervision of skin-related AEs in the first six cycles of treatment with sorafenib. However, the sustained high prevalence of rash and HFSR requires all patients receive ongoing skin care for the duration of therapy. Clinical trial information: NCT00095693. [Table: see text]
Synthetic Lethal Screening Identifies CHK1 Inhibition As an Exploitable Vulnerability in EZH2 Deficient T-ALL
Authors: Theresa E. Leon, Tanya Rapoz-D'Silva, Sunniyat Rahman, Michael Magnussen, Nadine Farah, Jose A. Guerra-Assunção, Rajeev Gupta, Elisabeth P. Nacheva, Javier Herrero, David C. Linch, Marc R. Mansour
Journal: Blood (2017)
Nivolumab-Associated Pulmonary and Bone Sarcoidosis in a Patient With Melanoma of Unknown Primary
Authors: Rima I. Tulbah, Steven P. Rowe, Lilja B. Solnes, Mehrbod S. Javadi
Journal: Clinical Nuclear Medicine (2019)

Abstract A 57-year-old man with stage IIIB malignant melanoma of unknown primary presented for pretherapy FDG PET/CT that demonstrated metastatic left cervical lymph node with no other site of involvement. Following left neck dissection, nivolumab was initiated. Follow-up FDG PET/CT 3 months after initiation of nivolumab demonstrated extensive radiotracer-avid chest lymphadenopathy and multiple bone lesions. Ultrasound-guided endobronchial biopsy of the mediastinal lymph nodes demonstrated sarcoidosis.
Utilization and outcomes of primary tumor surgery for stage IV colon cancer in the United States: A population-based study.
Authors: Yvonne Sada, Zhigang Duan, Hashem El-Serag, Jessica Davila
Journal: Journal of Clinical Oncology (2012)

3542 Background: Stage IV colon cancer treatment may include resection of the primary tumor. Current use of primary tumor surgery (PTS) in clinical practice is unknown. This study examined utilization and determinants of PTS and evaluated its effect on survival. Methods: Using national Surveillance, Epidemiology, and End Results registry data, stage IV colon cancer patients diagnosed from 1998-2008 were identified. Data on demographics, PTS, and tumor features were collected. Temporal changes in receipt of PTS were examined over 3 periods (1998-2000, 2001-2004, 2005-2008). Multiple logistic regression was used to identify significant determinants of PTS. 1- and 3-year cancer-specific survival was calculated in PTS and non-PTS patients. Cox proportional hazards models examined the effect of PTS on mortality risk. Results: 16,029 patients were identified. Median age was 69 (IQR: 57-78), and 50% were male. Approximately 67% of patients received PTS. Receipt of PTS significantly declined from 72% in 1998-2000 to 68% in 2001-2004, and 63% in 2005-2008 (p&lt;0.01). Results from the logistic regression analysis showed that patients who were younger, white, married, had right sided cancer and higher tumor grade were more likely to receive PTS (all p&lt;0.01). The 1- and 3-year survival was higher in patients who received PTS compared with those who did not (1-year: 55% (95% CI: 54-56) vs. 24% (95% CI: 23-26); 3-year: 19% (95% CI: 19-20) vs. 4% (95%CI: 3.4-4.9)). Adjusted for demographics and tumor features, risk of mortality was 54% (HR=0.46; 95% CI: 0.44-0.48) lower in patients who received PTS than those without PTS. Recent year of diagnosis (HR=0.88; 95% CI: 0.75-0.80) and being married (HR=0.90, 95% CI: 0.86-0.95) were associated with lower mortality. Older age (HR=1.48; 95% CI: 1.39-1.56), black race (HR=1.09; 95% CI: 1.03-1.15), right sided cancer (HR=1.21; 95% CI: 1.17-1.26), and poorly differentiated tumors (HR= 1.62; 95% CI: 1.46-1.80) were associated with increased mortality. Conclusions: PTS utilization for stage IV colon cancer has significantly declined, yet survival was higher in patients who received PTS. However, these findings are limited by the absence of co-morbidity and chemotherapy data.
Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial
Authors: Charlotte E L Klaver, Daniel D Wisselink, Cornelis J A Punt, Petur Snaebjornsson, Johannes Crezee, Arend G J Aalbers, Alexandra Brandt, Andre J A Bremers, Jacobus W A Burger, Hans F J Fabry, Floris Ferenschild, Sebastiaan Festen, Wilhelmina M U van Grevenstein, Patrick H J Hemmer, Ignace H J T de Hingh, Niels F M Kok, Gijsbert D Musters, Lotte Schoonderwoerd, Jurriaan B Tuynman, Anthony W H van de Ven, Henderik L van Westreenen, Marinus J Wiezer, David D E Zimmerman, Annette A van Zweeden, Marcel G W Dijkgraaf, Pieter J Tanis, Caroline S. Andeweg, Vivian P. Bastiaenen, Willem A. Bemelman, Jarmila D.W. van der Bilt, Johanne Bloemen, Frank C. den Boer, Djamila Boerma, Daan ten Bokkel Huinink, Walter J.A. Brokelman, Huib A. Cense, Esther C.J. Consten, Geert-Jan Creemers, Rogier M.P.H. Crolla, Jan-Willem T. Dekker, Jennifer Demelinne, Marc J. van Det, Karin K. van Diepen, Marjolein Diepeveen, Eino B. van Duyn, Esther D. van den Ende, Pauline Evers, Anna A.W. van Geloven, Erwin van der Harst, Jeroen Heemskerk, Joost T. Heikens, Daniel A. Hess, Bas Inberg, Jan Jansen, Frank W.H. Kloppenberg, Thomas J.M. Kootstra, R.T.J. Kortekaas, Maartje Los, Eva V.E. Madsen, H.C.J. van der Mijle, Linda Mol, Peter A. Neijenhuis, Simon W. Nienhuijs, Loes van den Nieuwenhof, Koen C.M.J. Peeters, Sebastiaan W. Polle, Jolien Pon, Pieter Poortman, Sandra A. Radema, Bert van Ramshorst, Philip R. de Reuver, Koen P. Rovers, Roderick F. Schmitz, Nina Sluiter, Dirkje W. Sommeijer, D.J.A. Sonneveld, T.C. van Sprundel, Sanne C. Veltkamp, Maarten Vermaas, Victor J. Verwaal, Emma Wassenaar, Johannes A. Wegdam, Johannes H.W. de Wilt, Marinke Westerterp, Fennie Wit, Arjen J. Witkamp, Karlijn van Woensdregt, Edwin S. van der Zaag, Mandy Zournas
Journal: The Lancet. Gastroenterology & hepatology (2019)