tbuckley/cabot-search huggingface dataset:
Outpatient oncology massage self-reported outcomes in cancer patients and their caregivers.
Authors: Gabriel Lopez, Kathrin Milbury, Sat-Siri Sumler, Curtiss M Beinhorn, Qi Wei, Amy Spelman, Eduardo Bruera, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2016)

e21627 Background: Massage as a manual therapy has shown benefit for symptomatic relief in cancer patients and their caregivers. We explored the impact of a single massage session on self-reported symptoms in an outpatient clinic at a comprehensive cancer center. Methods: Data were reviewed from massage sessions (30 or 60-min duration) at our Integrative Medicine Center outpatient clinic from Sep 2012-Jan 2015. Participants completed a modified Edmonton Symptom Assessment Scale (ESAS; 0-10 scale, 10 most severe) pre- and post-massage. ESAS subscales analyzed included Physical Distress (PHS), Psychological Distress (PSS), and Global Distress (GSD). We used paired t-tests with a Bonferroni correction (i.e., p < .001) to examine pre/post massage self-reported symptoms. Results: Initial massage visits for 164 patients and 39 caregivers were analyzed. Highest symptoms burden (means) at baseline for patients were Sleep 3.93, Fatigue 3.70, and poor sense of Well-Being 3.62; for caregivers Distress 4.14, Sadness 3.43, and Sleep 3.21. Although patients reported significantly more physical symptoms (F = 27.56, P < .0001) compared to caregivers at baseline, groups did not differ in regard to psychological symptom burden (P = .75). Massage therapy was associated with significant improvements in PHS, PSS, and GSD for both patients and caregivers at P < .0001. Including participants with symptom report greater or equal to 1, massage resulted in a clinically significant improvement (reduction > or equal to 1) in pain, fatigue, sleep, distress, dry mouth, sadness, numbness, anxiety, wellbeing for patients; pain, fatigue, distress, sadness, numbness, anxiety, wellbeing for caregivers. Regarding massage duration, there were no significant effects for 30 vs 60-min duration on pre/post ESAS difference scores. Conclusions: A single 30- or 60-min massage session resulted in acute relief of self-reported symptoms in patients and caregivers. Further study is warranted regarding optimal massage dose and frequency.
Phase II randomized study of first line avelumab with carboplatin-gemcitabine versus carboplatin-gemcitabine alone in patients with metastatic urothelial carcinoma ineligible for cisplatin-based therapy.
Authors: Alejo Rodriguez Vida, Begona Mellado, Xavier Garcia del Muro, Alvaro Taus, Rafael Morales Barrera, Pablo Maroto, Teresa Bonfill, Montserrat Domenech, Alvaro Pinto, Begona Perez Valderrama, Miguel A. Climent, Javier Puente, Jose Luis Perez-Gracia, Enrique González-Billalabeitia, Federico Vazquez, Susana Galtes, Barbara Pons, Sonia Macia, Daniel E. Castellano, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2018)

TPS4591 Background: Cisplatin-based chemotherapy is standard first line treatment for metastatic urothelial carcinoma (mUC). However, around 50% of patients are ineligible for cisplatin due to poor performance status or comorbidities. For these cases, carboplatin-based combinations are valid alternative options, although they are associated with inferior survival. Additional new strategies for cisplatin-ineligible patients are therefore urgently needed. Recently, excellent clinical activity has been reported with immune checkpoint inhibitors as monotherapy for cisplatin-ineligible patients. The purpose of this study is to test the safety and efficacy of avelumab (anti PD-L1 therapy) given pre-emptively and combined with carboplatin-gemcitabine (carbo/gem) followed by maintenance avelumab. Priming the chemotherapy response giving immunotherapy first could enhance the overall response of the combination and prevent the detrimental effect of chemotherapy on immune cells. Up regulation of PD-L1 by chemotherapy could also enhance the immunotherapy efficacy. Methods: This is a multicenter, randomized, open label phase II study evaluating safety and efficacy of sequencing 2 cycles of induction avelumab prior to combining carboplatin-gemcitabine plus avelumab for 6 cycles, followed by avelumab maintenance, compared to carbo/gem alone. Eligibility criteria include patients with mUC, no prior systemic therapy, ineligibility for cisplatin and adequate organ function. Patients will be stratified by the presence/absence of visceral metastasis and ECOG 0-1 versus 2. Primary endpoint of the study is objective response rate (ORR). Secondary endpoints include progression free survival, overall survival and safety. Exploratory endpoints include potential immunologic and genomic predictive biomarkers. For sample size calculation, we hypothesized that the ORR with the combination will be ≥45%, compared to 30% with standard carbo/gem. A sample of 80 patients will provide a probability of 0.9 of confirming our hypothesis, based on a Simon randomised phase II design. The trial is open to accrual. Clinical trial information: NCT03390595.
Communication near the end of life (EoL) between oncologists and patients with advanced cancer in Mexico.
Authors: Jacqueline Alcalde-Castro, Enrique Soto Perez De Celis, Alfredo Covarrubias-Gómez, Africa Navarro-Lara, Paulina Quiroz, Sofia Sanchez, Yanin Chavarri Guerra
Journal: Journal of Clinical Oncology (2018)

e22192 Background: Timely communication about prognosis is relevant for patients with late-stage cancer to ensure quality of life near the EoL. Conversations about EoL care help patients set appropriate goals, and potentially avoid intensive medical treatments and in-hospital deaths. ASCO has encouraged integration of communication into standard oncology care at the EoL through a palliative care checklist. However, even in developed nations, many patients are misinformed or misunderstand treatment/prognosis, and others have difficulty coping with illness. We reviewed current communication practices between oncologists and patients/caregivers at the EoL in a cancer center in a developing country. Methods: All patients with newly diagnosed advanced solid tumors seen at the National Institute of Medical Science and Nutrition in Mexico City from 10/2015 to 03/2016 were included. Demographic, clinical characteristics and data regarding communication coaching (prognosis, preferences, treatment goals and patient/caregiver understanding) were retrospectively obtained from chart reviews within the 1st year after diagnosis. Frequencies, summary statistics and Xi2 were utilized. Results: 76 patients were included. Median age was 62 years (range 19-88; 55% male). 53% had gastrointestinal, 21% genitourinary, and 16% other tumors. 85% of cases had a change in treatment/prognosis during the 1st year. Oncologists assessed literacy in 12%; patient/caregiver role preferences in 10.5%; understanding of diagnosis/illness and prognosis in 29%; and offered to clarify treatment goals at least once in 51% of cases. 41% of patients died during follow-up, of which 39% did so at the hospital. Clarifying treatment goals was associated with fewer in-hospital deaths (p = 0.04). Conclusions: Communication between oncologists and patients near the EoL was incomplete in a substantial proportion of cases. Better communication could lead to improved shared-decision making, better EoL care and less in-hospital deaths. Novel strategies are needed to improve effective communication and coping strategies for cancer patients in developing countries.
Baseline mutation profiling of circulating cell-free DNA from healthy individuals to improve the detection accuracy of circulating tumor DNA in cancers.
Authors: Geng Tian, Ligang Xia, Zhoufang Li, Xiaohua Li, Feiyue Xu, Chaoyu Liu, Jiankui He
Journal: Journal of Clinical Oncology (2017)

e23057 Background: Cell-free circulating tumor DNA (ctDNA) has emerged as an effective blood-based biomarker for clinical diagnostics in cancers, improving the accuracy and efficiency of cancer treatment for clinic. However, the somatic mutations originated from inheritance or normal biological metabolism in circulating cell-free DNA (cfDNA) in plasma can largely interfere with the detection of ctDNA. The baseline for ctDNA evaluation is urgently needed for accuracy identification of ctDNAs in patients. Methods: Averagely 20 ml blood samples were collected from more than 1200 individuals including healthy volunteers, lung cancer, colorectal cancer, pancreatic cancer, gastric cancer patients, etc. Genomic DNA from white blood cells and cfDNA from plasma were extracted and constructed as sequencing libraries using a panel contains 50 cancer-associated genes, respectively for each sample. Then they are subjected to ultra-deep sequencing with average depth &gt; 40000 folds covering ~21K nucleotide regions. Results: The background somatic mutation frequencies were detected in genomic DNA and cfDNA in healthy controls. The results showed that most of mutations in cfDNA were consistent with those in genomic DNA. Using data from 1200 individuals, we generated the baseline mutation profiling of cfDNA, which was referred in the ctDNA determination in cancer samples, which significantly improved the accuracy of ctDNA detection compared with tissue biopsy. Conclusions: Our studies demonstrated the importance of sequencing both cfDNA and genomic DNA for ctDNA detection in cancers. We also determined the baseline mutation profiling of circulating cfDNA from more than 1200 healthy individuals and confirmed the value of it by comparing with DNA sequencing data in cancer tissue. Our work offers clue on how to improve the detection accuracy of circulating tumor DNA in early cancer diagnosis.
Neuroendocrine carcinoma of the uterine cervix: A retrospective monocentric study.
Authors: Morgane Creoff, Simon Thezenas, Ariane Lapierre, Angelique Ducteil, Celine Bourgier, David Azria, Christine Kerr
Journal: Journal of Clinical Oncology (2018)

e17502 Background: Neuroendocrine cervical carcinoma (NECC) is a very aggressive and rare disease. To date, only 2 prospective studies with scarce patient numbers have been reported in the literature. Here we studied a NECC patients (pts) cohort treated with current anticancer treatment modalities. Methods: All pts with NECC were retrieved from 1996 to 2013 in our institute (n = 14). 3D-conformal radiation therapy combined to concomitant chemotherapy (RT-CT) was performed to all pts. Chemo- regimen (CT) was cisplatin plus etoposide or carboplatin plus etoposide. Mean total dose to clinical target volume (CTV) was 48 Gy. Results: Pts and treatments characteristics. Mean age was 48.5 years old. Most of pts had a loco regional disease (n = 11): stage IA (n = 1), IB (n = 1), IIA (n = 2) and IIB (n = 7); 3 pts were stage IVB. Pelvic and/or lombo-aortic lymph nodes involvement was observed in 42.8 % pts (n = 6). Among them, 3 pts were treated with an extended lombo-aortic radiation field. Among the entire cohort, 2 treatment modalities were distinguished: (i) most of pts were treated with neoadjuvant CT followed by concurrent RT-CT (n = 9). Either pulsed-dose rate (PDR) brachytherapy (n = 4) or colpo-hysterectomy ( = 3) was performed according to tumor response. Adjuvant CT was performed to 3 pts in this subgroup (mean number of cycle: 3); (ii) colpo-hysterectomy followed by concomitant RT-CT and PDR brachytherapy (n = 1), adjuvant CT delivered to 1 patient (3 cycles). Pts outcome. Median follow up was 10 years (range, 0.3-11.2). Median overall survival (OS) was 1.9 years; (IC95% [0.8 –NC]); 1-, 2- and 5-y OS were 79%, 48% and 40% respectively. Median progression free survival (PFS) was 11.7 months (IC95% [6 - 59]); 1-, 2- and 5- y PFS were 50%, 29% and 21% respectively. At the time of study analysis, 5 pts were still alive without any progression disease and are considered as long patient survivor (follow up at least more than 6 years) Conclusions: Despite the small number of pts in our study, pts outcome was consistent with the literature. This study showed a large variety of treatment modalities. To date, there is no consensus on how to treat these pts. However, owing to poor pts outcome, aggressive treatment modalities are probably required.
Efficacy of PD-1 inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) with KRAS or EGFR T790M mutations.
Authors: Nitika Sharma, Chipman Robert Geoffrey Stroud, Paul R. Walker, Sulochana Devi Cherukuri, Mahvish Muzaffar, Cynthia R. Cherry, Teresa Parent, Jessica Hardin
Journal: Journal of Clinical Oncology (2017)

e20513 Background: Immune checkpoint blockade(ICB) has revolutionized the treatment of progressive NSCLC with its durable benefit when compared to cytotoxic agents. In the era of personalized medicine, there is a need to identify effective predictive biomarkers to detect exceptional responders to ICB. Immune modulating interventions with cytotoxic or biologic agents can maximize clinical responses from ICB in poorly immunogenic tumors. KRAS mutations are a negative prognostic factor for survival and generally lack targeted therapies. The T790M mutation in EGFR is the most common cause of acquired resistance to first line TKIs. As a group, patients with EGFR mutations generally do not derive clinical benefit from ICB versus cytotoxic chemotherapy. Preclinical data suggests that mutations like T790 m are associated with higher immunogenicity leading to avid stimulation of antigen specific T-cells (Ofuzi et al, 2014) and better response to ICB (Yamada, 2013). However, the efficacy of ICB by specific molecular mutations remains poorly defined. Methods: We reviewed data for 83 pts with recurrent or progressive metastatic lung cancer treated with nivolumab from June 2015-Dec 2016. All pts were treated with ICB as a second or subsequent line of treatment. The patients were assessed for pathology, mutational status and overall survival. Mutational status was checked on either tissue biopsy or serum samples submitted for proteomic veristrat/genestrat (Biodesix Inc., Boulder, CO, USA) assay. Results: Of the 83 patients treated with nivolumab, 65 patients were found to have NSCLC. Eleven pts were found to have KRAS mutation which was further subdivided as: 6 pts with KRAS G12C, 4 with KRAS G12V, 1 with KRAS G12D. Two pts were found to have T790M mutation. 81%(9/11) pts with KRAS mutation died. Median survival in pts with KRAS G12C mutation was 10 weeks and KRAS G12V was 12 weeks (p = 0.17). Median survival was not reached for patients with T790M mutation. Conclusions: KRAS mutations tend to have a shorter overall survival with ICB as compared to patients with EGFR T790M mutations. Further studies are necessary to isolate poorly immunogenic subtypes of NSCLC and develop novel treatment approaches to optimize outcomes.
A Bayesian randomized phase II study of guadecitabine (SGI-110) based regimens comparing guadecitabine 5 days (SGI5), 10 days (SGI10), 5 days + idarubicin (SGI5 + Ida), 5 days + cladribine (SGI5 + Clad), in untreated patients ≥ 70 years with acute myeloid leukemia (AML).
Authors: Kiran Naqvi, Graciela M. Nogueras-Gonzalez, Cora M. Cheung, Naveen Pemmaraju, Elias Jabbour, Guillermo Garcia-Manero, Courtney Denton Dinardo, Maro Ohanian, Nitin Jain, Koichi Takahashi, Yesid Alvarado, Marina Konopleva, Xuelin Huang, Jorge E. Cortes, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2017)

7019 Background: Guadecitabine is a next generation hypomethylating dinucleotide of decitabine and deoxyguanosine resistant to degradation by cytidine deaminase. This allows prolonged exposure of leukemia cells to its active metabolite, decitabine. We aimed to compare the efficacy and safety profile of guadecitabine in untreated ≥ 70 years AML patients. Methods: Untreated patients ≥ 70 years with AML were randomized in a phase 2 Bayesian design in one of the 4 arms: guadecitabine 60mg/m 2 /daily x 5 (SGI5), guadecitabine 60mg/m 2 /daily x 10 (SGI10), SGI5 + Ida (6mg/m 2 /daily x 2), or SGI5 + Clad (3mg/m 2 /daily x 5). The Bayesian design evaluated response and toxicities simultaneously. Primary objective was complete remission (CR) rate and remission duration. Survival was estimated using the Kaplan-Meier method. Results: Between June 2014 and Nov 2016, we treated 34 patients: 8 in SGI5; 9 in SGI10; 8 in SGI5 + Ida and 9 in SGI5 + Clad. Median age was 75 years. 38% had complex karyotype. Median follow-up was 8.3 months. Overall response rate (ORR= CR + CRi) was 53%, shown in the table below. Median remission duration was 7.4 months. 4 week mortality was 3%. Median survival is 13.1 months. A trend for superior survival was observed with SGI5 + Ida (median survival not reached; p=0.22). Common G3/4 toxicity included febrile neutropenia (48%), thrombocytopenia (26%), leukopenia (22%) and anemia (11%). Conclusions: Guadecitabine is clinically active and safe as single agent and in combination in elderly patients with untreated AML. A separate previously reported multicenter study showed no difference between SGI5 vs SGI10 in 103 treatment naïve elderly AML patients (Kantarjian et al. Blood 2015 126:458). CR and ORR were lower with SGI5 + Clad. Based on these findings, the study continues now comparing SGI5 vs SGI5 + Ida. [Table: see text]
Effects of MRX34, a liposomal miR-34 mimic, on target gene expression in human white blood cells (hWBCs): qRT-PCR results from a first-in-human trial of microRNA cancer therapy.
Authors: Heidi J. Peltier, Kevin Kelnar, Andreas G. Bader
Journal: Journal of Clinical Oncology (2016)

e14090 Background: Each microRNA (miRNA) modulates the expression of hundreds of genes across distinct cellular pathways, giving miRNA-based therapy the potential to simultaneously repress multiple oncogenic processes in the tumor microenvironment, including growth and proliferation, resistance, cancer stem cells, metastasis, and immune evasion. The naturally occurring tumor suppressor miR-34a has been shown to down-regulate the expression of > 30 oncogenes (eg, MET, MEK1, PDGFR-α, CDK4/6, BCL2, WNT 1/3, NOTCH1, CD44), as well as genes involved in tumor immune evasion (eg, PD-L1, DGKζ). MRX34, a liposome-encapsulated miR-34a mimic, is a potential first-in-class miRNA therapy for cancer. Methods: In the MRX34-101 phase I trial (NCT01829971), patients with advanced malignancies under dexamethasone premedication received IV infusions of MRX34 daily for 5 d in week 1 with 2 weeks rest in 21-d cycles (QDx5 schedule). Whole blood was collected pretreatment and at multiple times after the first and during subsequent infusions. Total RNA from hWBCs (LeukoLOCK method) was isolated (mirVana kit) and assessed for quality (Agilent 2100 Bioanalyzer). qRT-PCR was used to measure and compare the relative expression levels of selected direct miR-34a target genes in the RNA from pre- and post-dose samples. Results: Expression of miR-34a target genes was repressed in hWBCs 24 hrs after the start of MRX34 dosing. The effect was dose-dependent such that the depth of repression increased at higher MRX34 doses corresponding to increased exposure to and uptake of miR34a in hWBCs. In contrast, expression of p21 (CDKN1A), a tumor-suppressor gene specifically induced by miR-34a, was increased. Conclusions: This qRT-PCR analysis of hWBCs samples obtained from patients treated with MRX34 in a first-in-human clinical trial of miRNA cancer therapy showed dose-dependent modulation of expression in target genes directly regulated by miR-34a. Our work suggests that MRX34 effectively delivers active miR-34a mimics to hWBCs in pts with cancer, and provides a potentially useful method to evaluate biomarkers of response to MRX34 therapy.
Adjuvant ipilimumab compared with observation in completely resected Merkel cell carcinoma (ADMEC): A randomized, multicenter DeCOG/ADO study.
Authors: Jürgen C. Becker, Jessica Cecile Hassel, Christian Menzer, Katharina C. Kähler, Thomas K. Eigentler, Friedegund Elke Meier, Carola Berking, Ralf Gutzmer, Peter Mohr, Felix Kiecker, Martin Kaatz, Christiane Windemuth-Kieselbach, Claudia Lorenz-Schlüter, Lisa Zimmer, Selma Ugurel, Dirk Schadendorf
Journal: Journal of Clinical Oncology (2018)

9527 Background: Merkel cell carcinoma (MCC) is a rare, immunogenic, and highly aggressive skin cancer. Almost 40% of patients with completely resected MCC will relapse within the first two years after initial diagnosis. Currently, there is no accepted adjuvant systemic therapy for MCC. This study was conducted to determine if an immune modulating therapy with ipilimumab improves the disease-free survival (DFS) of MCC patients. Methods: Within 12 weeks after complete resection of primary or locoregional metastatic MCC, patients were randomly assigned to four doses of 3mg/kg ipilimumab i.v. every 3 weeks or observation. The primary end point of the study was DFS; secondary endpoints included adverse events and overall survival at 12 months. Futility analysis was performed after screening 20% of the planned patient number. Results: At the time of futility analysis, 47 patients had been screened and 40 patients enrolled. Four patients had to be excluded after randomization due to protocol violations or withdrawal of informed consent (ipilimumab = 1; observation = 3). Median follow-up was 22.3 months. Groups were well-balanced with regard to demographics, histology, and tumor stage. DFS was not significantly different between ipilimumab and observation (hazard ratio, 1.8; CI, 0.3 to 10; P = 0.48). However, patients in the treatment arm had a significantly increased incidence of adverse events by 4-fold, i.e. in more than 80% of the patients, compared to the observational arm, which was most relevant for adverse events of grade > = 3. Conclusions: Given the lack of efficacy of ipilimumab in preventing disease progression of MCC together with the pronounced toxicity, it was decided to stop enrollment of further patients into this study because a significant survival benefit was unlikely to be achieved as predicted by the futility analysis even across the originally planned cohort. Adjuvant ipilimumab should not be considered in MCC patients. Currently adjuvant nivolumab is tested in comparison to observation to improve DFS. Clinical trial information: NCT02196961.