tbuckley/cabot-search huggingface dataset:
Cardiovascular effects of rehabilitation in hormone-dependent breast cancer patient with the postcastration syndrome.
Authors: Oleg Ivanovich Kit, Yulia Yu. Arapova, Natalia N. Popova, Mikhail Yu. Rudenko, Alla Ivanovna Shikhlyarova, Tatiana P. Protasova, Vladimir E. Rostorguev
Journal: Journal of Clinical Oncology (2018)

e14530 Background: The treatment of hormone-dependent breast cancer (BC) involves, among other procedures, ovariectomy. This can result in the development of the postcastration syndrome (PCS) with early neurovegetative and vasomotor disorders in patients of the reproductive age. A high risk of the tension of the electrophysiological, energetic and bioadaptive status of the cardiovascular system (CVS) requires a rapid detection of the hemodynamic abnormalities. Our purpose was to study the effect of xenon on the phase tension dynamics and metabolism of CVS in patients with PCS in the early postoperative period. Methods: 20 patients of the reproductive age with hormone-dependent BC were examined. Patients of the main group (n = 10) received 5 xenon/oxygen inhalations every other day in the morning, starting from day 4 after ovariectomy; the controls (n = 10) did not receive xenon therapy. Parameters of the phase analysis of hemodynamics and energetic metabolism of the heart were recorded. Results: A marked tension of regulatory systems (stress index > 500 CU) were registered in patients of both groups after ovariectomy, as well as changes in the myocardial metabolism: a decrease in the oxygen and creatinine phosphate content with the lactate accumulation. In contrast with controls, patients of the main group demonstrated a decreased stress of regulatory systems ( < 500 CU) and the normalization of metabolic parameters. Conclusions: Monitoring of the phases of the cardiac function regulation and myocardial metabolism in patients with PCS allows assessing the effect of xenon. Xenon activates bioenergetic processes in the myocardium and limiting a stress effect on the body, and significantly reduces the risk of complications and facilitates the rehabilitation of breast cancer patients of reproductive age.
A complementary care program for improving quality of life of cancer patients during adjuvant radiotherapy and/or chemotherapy or outpatient aftercare.
Authors: Martin Domnick, Manju Domnick, Andre-Michael Beer, Karl-Rudiger Wiebelitz
Journal: Journal of Clinical Oncology (2016)

e21697 Background: Evidence for complementary therapies (CTs) as important strategies to relieve cancer treatment-associated symptoms and to improve physical and emotional well-being is increasing. Such CTs are used concomitant to the conventional treatments. To date, clinical studies evaluate single-procedure CTs, or have been performed on one cancer entity only. Also, these CTs mainly start at the end of adjuvant treatments, resulting in a long delay before the well-being of patients is addressed. Thus, this study, for the first time, aimed to evaluate a complex multimodal CT regimen for patients of different cancer entities conducted in parallel to adjuvant therapy and in proximity to patients’ homes. Methods: The LOTUS Care Cure Project (LCCP) included yoga, massage, art therapy, nutrition counseling etc. A single-center, randomized, controlled trial was conducted in 100 patients of various cancer entities and stages while on adjuvant chemotherapy and/or radiotherapy, or outpatient aftercare. Patients were randomized to receive either LCCP additionally (LCCP group, n = 50), or the conventional treatment alone (control group, CG). The CG was split in two groups, one with weekly talks (CG 1, n = 33), the other without (CG 2, n = 17). The primary endpoint was quality of life (QoL) after 3 months, represented by the global health status (via EORTC QLQ-C30). Secondary endpoints included among others cognitive and social function. Results: In the LCCP group, QoL significantly improved after 3 months compared to CG 2 (p = 0.022), but not compared to CG 1. At no time was any significant difference found in QoL between the two CGs. Other parameters showing a significant improvement were cognitive (p < 0.05, vs. CG 1 & 2) and social function (p < 0.05, vs. CG 2). Conclusions: This pilot study is the first to describe a multimodal CT program conducted in proximity to patients’ homes and in parallel to adjuvant conventional therapies and its power to significantly improve QoL and reduce treatment-associated side effects. Since the investigated cohort comprised different cancer entities, the effect seems to be global. To substantiate these data, multi-center trials are needed.
Delayed toxicities with anti-PD-1 and anti-PDL-1 immune checkpoint inhibitors (ICIs).
Authors: Neil J. Shah, Barbara T Ma, William J Kelly, Anas Belouali, Michael T Serzan, Sebastian Ochoa Gonzalez, Bradley Colton, Megan M Janni, Alice R Knoedler, Matthew Blackburn, Jeevan Puthiamadathil, Subha Madhavan, Pallavi P. Kumar, Stephen V. Liu, Geoffrey Thomas Gibney, Michael B. Atkins
Journal: Journal of Clinical Oncology (2018)

e15074 Background: ICI use is associated with immune-related adverse events (irAEs). Most irAEs occur early (within 3 months), but data regarding late toxicities is not well reported. Methods: Patients (pts) treated with ICIs (nivolumab [PD-1], pembrolizumab [PD-1], or atezolizumab [PDL-1]) were identified from pharmacy records across MedStar Health Network hospitals. The CTCAE 4.03 grading system was used to define irAEs. Pts who received distinct ICIs at separate time points were considered as separate events. We defined delayed toxicities as irAEs that developed 1 year after the first dose of ICI either on or off treatment (pts who did not receive subsequent therapies). Pts in whom irAEs developed during or after subsequent therapies were excluded from analysis. Results: We identified 325 pts who received 328 ICI therapies. 26% (n = 59) of pts developed any grade (grd) irAEs, with 8% (n = 26) of pts developing grd ≥3 irAEs. Of irAEs, 55% (n = 73) occurred within 3 months, 35% (n = 47) in between 3 to 12 months and 10% (n = 13) after 12 months. Of delayed irAEs, 46% (n = 6) of pts were on ICIs and 54% (n = 7) were off ICIs at the time of irAE onset. In the off treatment delayed irAE cohort, 70% of pts developed grd ≥2 irAEs, including colitis (grd 3, n = 1), joint pain (grd 3, n = 1), neurological toxicity (grd 2, n = 1), mucositis (grd 3, n = 1), and hypothyroidism (grd 2, n = 1). Of this cohort, five pts required systemic steroids. irAEs resolved within two weeks except one case in which colitis took 6 months to resolve. 12% (n = 40) of pts continued ICIs beyond 1 year, in which 15% (n = 6) developed delayed irAEs. These delayed irAEs were joint pain (grd 1, n = 1), pruritis (grd 1, n = 1), rash (grd 2, n = 1), hypothyroidism (grd 1, n = 1), hyponatremia (grd 1, n = 1) and colitis (grd 3, n = 1). Colitis required systemic steroid use and took 6 weeks to resolve, after which ICI was discontinued. In the pt with grd 2 rash, treatment with ICIs was continued. Conclusions: Findings from our retrospective study suggest that 15% of pts who continue ICIs beyond 1 year are at risk of developing delayed irAEs, which may require chronic immunosuppressive therapy. Delayed irAEs should be considered in discussions about treatment cessation in pts with major responses to ICIs.
Phase 1/2 study of safety/efficacy using trabectedin, ipilimumab and nivolumab triple therapy as first line treatment of advanced soft tissue sarcoma.
Authors: Erlinda Maria Gordon, Victoria S. Chua-Alcala, Katherine Kim, Shiva Sreenath Andrali, Marie Del Rosario, William W. Tseng, Seth Pollack, Sant P. Chawla
Journal: Journal of Clinical Oncology (2018)

TPS11591 Background: Sarcoma cells are most immunogenic at the onset of cancer when the immune system can recognize and destroy them (Schreiber 2011). Hence, immune checkpoint inhibitors would be most effective when given as first line therapy. Objectives: Primary: To investigate the maximum tolerated dose of trabectedin, an alkylating agent, when given sequentially with ipilimumab, a CTLA4 inhibitor, and nivolumab, a PD-1 inhibitor, in advanced STS. Secondary: To investigate the objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Exploratory: To correlate PFS with PD-L1 and other biomarker expression in patients’ tumors. Methods: Forty patients ≥18 years of age with advanced STS will be enrolled. This is an open label, dose-seeking phase ½ study using a defined dose of ipilimumab (1 mg/kg i.v. q 12 weeks), nivolumab (3 mg/kg i.v. q 2 weeks), and escalating doses of trabectedin (1.0, 1.3, 1.5 mg/m2 i.v. q 3 weeks). I. Dose Escalation Phase 1 (previously treated patients): The study will employ the standard “cohort of three” design. The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced DLT, with the next higher dose level having at least two patients who experienced DLT. II. Expansion Phase 2 (previously untreated patients): An additional 22-28 patients will receive trabectedin at the MTD and defined doses of ipilimumab and nivolumab to assess overall safety and potential efficacy in a greater number of patients. Patients may continue treatment until significant disease progression or unacceptable toxicity occurs. Statistical Considerations: NIH CTCAE v4.03 and RECIST v1.1 will be used. Categorical variables will be summarized by the n and percent in each category. Point estimates for efficacy endpoint incidences will be accompanied by a 2-sided 95% exact binomial CI. Time to event endpoints will be summarized descriptively using the KM method. The analyses of all study objectives will be descriptive and hypothesis generating, for planning Phase 2/3 studies. Clinical trial information: NCT 03138161.
The effect of the seleno-L-methionin, sodium selenite and cadmium chloride on telomerase activity of chick embryo neural tube cells
Authors: H. Akhavan, S.S. Hosseini-Asl, H. Abbasgholizadeh, M. Sagha
Journal: Annals of Oncology (2018)

Background: Telomerase is a ribonucleoprotein enzyme with reverse transcriptase activity, that more important in developmental processes including cell proliferation, differentiation, senescence and tumorigenesis. Selenium as a trace element for animals and human has been detected which can have anticancer properties, while cadmium (Cd) is a heavy metal in the natural environment and is very toxic. Purpose of this study was investigating the effects of Seleno-L-methionine, Sodium selenite and Cadmium chloride on the expression of telomerase activity in Chick embryo neural tube. Methods: Using quantitative and qualitative methods RTQ- TRAP and TRAP assay, the effect of the noted elements on the telomerase activity of Chick embryo neural tube was studied. Results: Unlike expected, seleno-L-methionine increased telomerase activity. Cadmium chloride had the greatest effect on telomerase activity, while the effect of Sodium selenite was lower than two others. However, the increasing effect has been determined. Conclusions: All three compounds at concentration of 5 μm and effect time of 6 hours had most impact on Chick embryo neural tube telomerase activity compared to the control groups. Cadmium chloride had greatest effect and sodium selenite were less effective. Legal entity responsible for the study: Ardabil University of Medical Sciences. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Association of glucocorticoid receptor expression with the treatment outcome of pemetrexed-based chemotherapy in NSCLC patients.
Authors: Xinmin Zhao, Jialei Wang
Journal: Journal of Clinical Oncology (2016)

e20525 Background: Pemetrexed is the preferred chemotherapy in the management of non-squamous non-small cell lung cancer (non-sq-NSCLC), yet in lack of biomarkers for predicting efficacy. Dexamethasone which is one of premedication of pemetrexated, may downregulate p53 through the glucocorticoid receptor (GR). The purpose of our study was to explore the effect of GR in peripheral blood mononuclear cell (PBMC) on pemetrexed efficacy. Methods: One hundred and twenty-two patients with stage IV non-sq-NSCLC who received first-line pemetrexed-containing chemotherapy were retrospectively reviewed. The expression of GR in PBMC were measured before treatment with pemetrexed using flow cytometry, and Real-Time PCR was used to detect the level of GRα and GRβ. Results: The response rate for all patients was 38.5%, with a median PFS of 5.9 months and OS of 14.3 months. In univariate analyses, patients with low level of GRα/GRβ ratio in PBMC had higher RR, better PFS, and better OS than those with high level of GRα/GRβ ratio(RR: 48.2% vs. 30.3%, p = 0.043; mPFS: 6.9 months vs. 4.0 months, p = 0.000; mOS: 18.7 months vs. 12.2 months, p = 0.005). The baseline GRα/GRβ ratio was an independent factor for RR (odds ratio [OR] = 0.451, 95%CI: 0.208-0.978, p = 0.044), PFS (HR = 1.584, 95%CI: 1.094-2.295, p = 0.015), and OS (HR = 1.761 , 95%CI: 1.195-2.595, p = 0.004). Conclusions: Baseline GRα/GRβ ratio detcteted by FCM is the same as RT-PCR in PBMC may predict the efficacy of first-line pemetrexed-containing chemotherapy in stage IV non-sqNSCLC patients.
Cataloguing depression among cancer patients by stage and source of malignancy.
Authors: Uri Goldberg, Michael Biglow, Damoun Safarpour, Neil Pasco, Benjamin Levron, Amy Fung, Atefah Kalantary, Byron Cary, Mario Hernandez, Hendy Jean, Neil Gupta, Ratesh Khillan, Madhumati R. Kalavar
Journal: Journal of Clinical Oncology (2016)

e21546 Background: The American Cancer Society reports that a quarter of cancer patients may suffer from depression. While depression is often under-diagnosed in the general population, the rate of under-diagnosis among cancer patients may be far higher. We seek to identify potential predictors of depression among an array of malignancy-related factors that may signal an enhanced need for the involvement of mental health services. Methods: This is an observational cross-sectional study evaluating depression among cancer patients in an outpatient setting. Over six months, 40 patients from our institutions’ affiliated cancer clinics were interviewed by study staff on questions related to social support and pain, and were administered the depression screening tool Patient Health Questionnaire 9 (PHQ-9). Data was collected and analyzed using Spearman’s rho. Results: The inclusion criterion was a confirmed cancer diagnosis; there were no exclusion criteria. Age ranged from 39 to 87 and women comprised 62% of participants. 25% of participants demonstrated mild depression, 12.5% moderate depression, and 7.5% moderate-severe depression. 72% of patients complained of pain. Age correlated negatively with the question of “Little…pleasure in doing things” (R = -0.52, P = 0.004) but positively with the question of “Thoughts that you would be better off dead…” (R = 0.49, P = 0.007). With respect to the latter question, stage of cancer correlated negatively (R = -0.45, P = 0.02). Finally, severity of pain correlated positively with the questions of “Poor appetite or overeating” and “Moving or speaking so slowly...Or the opposite — being so fidgety or restless...” (R = 0.41, P = 0.03; R = 0.40, P = 0.03, respectively). Conclusions: The effects of depression on cancer patients may contribute to life-shortening complications related to reduced compliance with treatment & lifestyle modifications, as well as the exacerbation of heart disease and other comorbid conditions. Our findings demonstrate that age, cancer stage, and pain may signal an elevated risk of depression and call for the swift involvement of mental health services. Such involvement may yield both quality of life benefits as well as improved health outcomes.
A phase II multicenter, randomized, placebo-controlled, double-blind study of CC-486 plus pembrolizumab (pembro) vs pembro plus placebo (PBO) in previously treated patients (pts) with locally advanced/metastatic non-small cell lung cancer (NSCLC).
Authors: Benjamin Philip Levy, Giuseppe Giaccone, Benjamin Besse, Damir Begic, Xiaoling Wu, Abderrahim Fandi, Luis Paz-Ares
Journal: Journal of Clinical Oncology (2016)

TPS9107 Background: Effective second-line chemotherapeutic treatment options for pts with NSCLC are limited. Pembro, a PD-1–blocking antibody, has demonstrated antitumor activity and proven second-line efficacy in pts with advanced NSCLC. Epigenetic modifying agents can enhance and lengthen responsiveness to subsequent anticancer therapies, including immunotherapeutic agents. The oral azacitidine CC-486 has shown promising activity when combined with cytotoxic chemotherapy in pts with relapsed/refractory solid tumors. This randomized phase II trial will evaluate the safety and efficacy of CC-486 .plus pembro vs pembro plus PBO in the second-line treatment of pts with locally advanced/metastatic NSCLC. Methods: ≈ 90 pts will be randomized 1:1 to receive oral CC-486 300 mg/day or PBO on days 1-14 plus pembro 200 mg intravenously (30-minute infusion) on day 1 of a 21-day cycle. Randomization will be stratified by histology (nonsquamous vs squamous). Pts will be treated until disease progression, start of new anticancer therapy, or study withdrawal. Eligibility criteria include stage IIIB/IV NSCLC (any PD-L1 status), 1 prior platinum-containing chemotherapy for advanced disease, Eastern Cooperative Oncology Group performance status ≤ 1, adequate organ function, no known EGFR and/or positive ALK mutation (nonsquamous histology only), and no prior treatment with azacitidine or other checkpoint inhibitor. Safety will be analyzed in the first 10 pts in each arm after the last enrolled pt has completed 1 treatment cycle. The primary endpoint is investigator-assessed progression-free survival (PFS). Secondary endpoints include disease control rate (DCR; stable disease ≥ 18 weeks, complete response, and partial response), overall survival, overall response rate (ORR), safety, and pharmacokinetics. Exploratory endpoints include immune-related efficacy (PFS, DCR, and ORR), tumor PD-L1 expression, tumor-infiltrating lymphocytes, and gene expression and DNA methylation analyses of tumors and/or blood. Twelve pts have been enrolled to date. NCT02546986. Clinical trial information: NCT02546986.
Neoadjuvant atezolizumab in resectable non-small cell lung cancer (NSCLC): Initial results from a multicenter study (LCMC3).
Authors: Valerie W. Rusch, Jamie E. Chaft, Bruce Johnson, Ignacio Ivan Wistuba, Mark G. Kris, Jay M. Lee, Paul A. Bunn, David J. Kwiatkowski, Karen L. Reckamp, David J Finley, Eric B. Haura, Saiama Naheed Waqar, Robert Charles Doebele, Edward B. Garon, Justin Blasberg, Alan Nicholas, Katja Schulze, See-Chun Phan, Mayank Gandhi, David Paul Carbone
Journal: Journal of Clinical Oncology (2018)

8541 Background: Platinum-based chemotherapy, before or after surgery, provides only a 5% benefit in 5yr. OS in locally advanced NSCLC. A recent pilot study (JCO 2017 35:15suppl, 8508) showed that preoperative immune checkpoint inhibitor therapy was well tolerated and yielded a clinically meaningful major pathologic response rate (MPR ≤10% residual viable tumor cells). This large multicenter trial tests the MPR rate and novel biomarkers of benefit using this novel neoadjuvant approach with atezolizumab (atezo) [NCT02927301]. Methods: Pts with stages IB -selected IIIB resectable NSCLC were to receive 2 cycles of atezo (1200 mg, days 1, 22) then undergo resection (day 40 +/- 10). Chest CT, PET obtained pre- and post atezo to assess clinical response. Primary tumor +/- node biopsies and blood samples were obtained before atezo and at surgery for biomarker studies. The primary endpoint was MPR. Secondary endpoints included safety, response by PD-L1, OS, and DFS. Results: For the prespecified initial safety analysis, the first 21 of 180 planned pts (67 pts currently on study) are reported: 13 males, median age 65 y, all ECOG 0-1; 4 current, 16 former smokers; 13 non-squamous NSCLC; clinical stages Ib/IIa/IIb/IIIa/IIIb = 4/2/6/5/4. Two pts received one dose of atezo due to treatment related AE (Gr 1 pyrexia, Gr 2 dyspnea) but underwent uncomplicated resection with MPR assessment. There were no Gr 5 AE, 5 Gr 3-4 AE (1 treatment related). By RECIST, 20 pts had SD, and 1 had PD. There were no major delays to surgery. 19 pts had MPR assessment: 1 pt discontinued atezo preop due to CNS mets and 1 pt had unresectable disease. MPR rate was 4/19 (21%, 95% CI 6-46). Excluding 2 pts who had known driver mutations (1 EGFR+, 1 ALK+), MPR rate was 4/17 (24%, 95% CI 7-50). 11/19 patients had ≤50% viable tumor. Conclusions: This first report of atezo in the neoadjuvant setting shows that preoperative treatment is feasible and well tolerated. MPR rate is encouraging. Clinical and pathological responses are often discordant. Safety and efficacy results from additional pts will be presented. Correlative analyses on pre- and post atezo tissues are ongoing. Preliminary correlative analyses in blood samples are included in a separate abstract. Clinical trial information: NCT02927301.
Evaluation of hematology/oncology patient and physician expectations for integrative oncology at a tertiary care center.
Authors: Damien Mikael Hansra, Stuart Sacks, Faheem Farooq, Jeremy Ramdial, Jorge Antunez de Mayolo, Eugene Ahn
Journal: Journal of Clinical Oncology (2016)

e18146 Background: We aim to compare how NCCN guideline recommended integrative services are valued between hematology/oncology physicians (MD) & patients (pts). Methods: IRB approval obtained. Pts & MDs at an academic tertiary care medical center were enrolled to complete a survey. Demographics include: age, gender, race, & ethnicity. Clinical info include: cancer subtype & treating MD. Survey consisted of 7 questions assessing opinions on integrative care asking: “In addition to standard care, it is important to incorporate/provide” nutrition services, exercise therapy, spiritual/religious counseling, supplement/herbal advice, support groups, music therapy, or other complimentary medicine services (acupuncture, massage, relaxation therapy). Answers recorded on a 5 point scale (1 = highly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = highly agree) & converted into 2 categories (1,2,3 = neutral/disagree vs. 4,5 = agree). Fisher’s exact test with 2 sided p-value used to compare significance between MD & pt responses. Results: 1008 pts and 55 MDs enrolled from June 2013 to October 2015. Pt mean age 55, range 18-88 with 45% male & 55% female. 62% of pts were Hispanic vs. 38% not Hispanic. 16% white, 14% black/African American, 2% Asian/Pacific Islander, & 6% other. 21% of pts had hematologic disorders (92% malignant 8% benign) vs. 79% of pts had solid malignancies. Significance disparities were demonstrated: 84% of pts agree that nutritional advice is important vs. 69% of MDs, p = 0.0077, exercise therapy (85% vs. 71%, p = 0.0120), spiritual/religious (68% vs. 47%, p = 0.0031), supplement/herbal therapies (85% vs. 44%, p < 0.0001), music (60% vs. 28%, p < 0.0001), &“other complementary services” (77% vs. 47%, p < 0.0001). Non statistical favoring of support groups by pts observed (71% vs. 66% respectively, p = 0.4377). Conclusions: With the exception of support groups, pts value integrative modalities more than MDs. It is expected that increased availability & utilization of integrative oncology modalities at tertiary hospital sites could improve pt satisfaction, quality of life, & other clinical endpoints.