tbuckley/cabot-search huggingface dataset:
Neoadjuvant chemoradiotherapy versus chemotherapy and surgery for patients with locally advanced esophageal squamous cell carcinoma.
Authors: Daxuan Hao, Xue Li, Yuanyuan Yang, Yougai Zhang, Xiaoyuan Wu, Yongshun Chen, Chunyu He, Wen Wang, Jinsong Liu, Jianhua Wang
Journal: Journal of Clinical Oncology (2016)

91 Background: Neoadjuvant chemoradiotherapy (nCRT) combined with surgery has been recommended as the standard treatment for locally advanced esophageal cancer in western countries. However, in clinical practice, neoadjuvant chemotherapy (nCT), rather than nCRT, is preferred for a large cohort of patients with locally advanced esophageal squamous cell carcinoma (ESCC) for fear of increasing the odds of postoperative morbidity in China. The aim of this study is to compare the clinical efficacy of nCRT and nCT in terms of postoperative morbidity, tumor pathology and survival in patients with locally advanced ESCC. Methods: A total of 111 patients with locally advanced ESCC (T2-4N0-1M0) received neoadjuvant treatment at our institution from January 2009 through January 2014.Among these patients, 53 cases received one cycle of neoadjuvant chemotherapy with concurrent radiotherapy while the remaining 58 cases received two cycles of neoadjuvant chemotherapy only before surgery. Results: pCR was observed in 15 patients in nCRT group (28.3%) and 8 patients in nCT group (13.8%, P= 0.060). Postoperative morbidity was 32.1% in nCRT group and 37.9% in nCT group (P= 0.660). Disease-free survival rates at 1, 2, 3 years were 73.1%, 66.7%, 53.6% in nCRT group and 73.7%, 60.4%, 52.2% in nCT group (P= 0.848). Overall survival rates at 1, 2, 3 years were 88.5%, 78.0%, 59.5% in nCRT group and 89.5%,72.9% and 56.2% in nCT group(P= 0.749). No significant differences were found in recurrence rate between two groups (P= 0.836). Conclusions: Neoadjuvant CRT may achieve higher pCR rate than neoadjuvant CT without increasing the odds of postoperative morbidity. Both neoadjuvant CRT and CT can prolong survival in patients with locally advanced ESCC. Further study is needed to prove which one is better.
Management of growing teratoma syndrome: Aachen University experience.
Authors: David J. K. P. Pfister, Daniel Porres, Andrea K. Thissen, Charlotte Piper, Axel Heidenreich
Journal: Journal of Clinical Oncology (2014)

385 Background: Growing teratoma syndrome (GTS) is an infrequent clinical phenomenon. GTS is defined as an enlarging metastatic mass during systemic chemotherapy for advanced nonseminomatous germ cell tumors (NSGCT) despite decreasing serum tumor markers. Complete surgical resection of the mass is mandatory to achieve a favourable outcome. We report on our single center experience in the management of GTS. Methods: Between January 2000 and August 2009 postchemotherapeutic retroperitoneal lymph node dissection (PCRPLND) was performed in 162 patients (pts) with advanced NSGCT. Fourteen pts (4.9%) fulfilled the criteria of a GTS: enlarging metastatic mass in the retroperitoneum or visceral organs during systemic chemotherapy with normalized or regredient tumor markers. In all cases of GTS a complete radical bilateral PCRPLND including the resection of adjacent visceral and vascular structures was performed. Results: Median patient age was 24.5 (18 to 52) years. All patients exhibited NSGCT with a good or intermediate prognosis according to IGCCCG; in all cases the primary tumor contained predominantly (greater than 50%) mature teratoma; 10 and 4 patients presented with clinical stage IIC and III, resp. Median tumor diameter at time of surgery was 6,5 (3,0-35)cm. Tumor markers were normalized in 12 out of 14 patients and markers plateauted in 2 out of 14 patients. Tumor masses were localized in the retroperitoneum in 12 pts.; two patients had additional pulmonary metastases which were resected in a second approach. Median time from start of chemotherapy to surgery was 4.8 (1.5 to 26.5) months Median surgical time was 265 (165 to 585) minutes, and median blood loss 650 (450 to 2,000) ml. Four pts required resection of the inferior vena cava or abdominal aorta with implantation of a prosthetic graft; adjunctive nephrectomy was performed in three pts. After a median follow-up of 4.2 years two pts developed recurrent disease; the remainder are alive without evidence of disease. Conclusions: GTS is a rare phenomenom among pts with advanced NSGCT and necessitates complete surgical resection of all masses with curative intention. Surgery should be considered at time of progression to facilitate complete removal of the mass. Due to the complex surgery, treatment should be performed at specialized centers.
Clergy religious beliefs and ICU utilization at the end of life.
Authors: Michael Balboni, Adam Sullivan, Rebecca Quinones, Tyler J. Vanderweele, Tracy A. Balboni
Journal: Journal of Clinical Oncology (2015)

223 Background: High religious community spiritual support is associated with greater aggressive interventions at the end of life (EOL). At EOL, half of U.S. patients are visited by clergy. The relationship of clergy religious beliefs about EOL care to dying congregants’ EOL medical decisions is unknown. Methods: This is an NCI-funded study of 1,665 U.S. clergy randomly-selected from a comprehensive database of 368,408 U.S. congregations and administered a survey 8/2014-2/2015; 1,005 responded (60%). Clergy reported endorsement of religious beliefs about congregants’ EOL care (RBEC), including miracles, sanctity of life, divine sovereignty, and redemptive suffering. Clergy reported on their last experience in spiritual caregiving to a dying congregant, including congregant’s care location in the final week. The primary outcome was any ICU care in the final week of life. Multivariable analyses (MVA), controlling for clergy age, gender, race, region, and congregational income, assessed the relationship of clergy RBEC to any congregant ICU care in the last week. Results: Most (86%) clergy affirmed belief in a miraculous cure; 54% agreed that the congregant should accept every medical treatment out of religious obligations. A minority of clergy affirmed that belief in divine sovereignty relieved congregants of future medical decisions (28%) and that they should endure medical procedures because suffering is God’s test (27%). In MVA, higher RBEC scores were associated with a greater likelihood of any ICU utilization in the last week (AOR=1.28, p=.02), with belief in divine sovereignty being the strongest predictor (AOR 2.1, p=.005). Predictors of having greater RBEC scores included being Hispanic (AOR=3.35, p&lt;.001) or black (AOR=3.0, p&lt;.001), as compared to white, and being Pentecostal (AOR=3.54, p&lt;.001) or Evangelical (AOR=2.12, p&lt;.001) as compared to clergy self-identified as liberal. Conclusions: A majority of clergy endorse religious beliefs regarding their dying congregants’ EOL medical care; these beliefs are associated with greater ICU care in the final days of life for congregants. Future research is needed to determine religiously-consistent approaches to clergy EOL education to mitigate aggressive interventions at the EOL.
Pharmacodynamic activity demonstrated in phase I for PLX3397, a selective inhibitor of FMS and Kit.
Authors: S. P. Anthony, I. Puzanov, P. S. Lin, K. B. Nolop, B. West, D. D. Von Hoff
Journal: Journal of Clinical Oncology (2011)

3093 Background: PLX3397 is a novel, oral small molecule that potently and selectively inhibits i) FMS, Kit, and Flt3‐ITD kinases, which regulate key components of the tumor microenvironment (macrophages, microglia, osteoclasts, and mast cells), and ii) oncogenic variants of these kinases that drive certain tumors. Anti-tumor benefits may be achieved via reduced tumor growth, angiogenesis and metastasis, with the potential to confer an overall survival benefit. Methods: This phase I dose escalation study was designed to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of PLX3397 administered by continuous daily oral dosing in four week cycles in sequential cohorts of 3-6 patients (pts) with solid tumors. Results: In 5 dose escalation cohorts, 26 pts with advanced solid tumors were treated with PLX3397 doses of 100-900 mg daily. PK data reveal dose-dependent systemic exposure (R2=0.99) that, based on in vivo pharmacology data, exceeds the EC90 for Fms inhibition. An elimination half-life of 20 hrs enables a once-daily dosing regimen. PLX3397 was generally well tolerated, with drug-attributable toxicities (mostly grade 1) of anemia, fatigue, nausea, and rash. PD biomarkers are consistent with robust target inhibition, including a pronounced reduction in a defined subset of circulating monocytes (CD14dim/CD16+), and at higher PLX3397 systemic concentrations, a marked increase (up to 10-fold) in serum CSF-1, an activating ligand of FMS. A reduction in circulating tumor cells (CTC) has been demonstrated in 3 of 4 pts who had baseline levels ≥ 5 per 7.5 mL blood. These CTC reductions were accompanied by reduced narcotic use (n=2) and skin metastasis inflammation (n=1). Additionally, hair depigmentation has been observed in 4 pts treated at 600 or 900 mg/day, indicating substantial Kit target inhibition. Conclusions: PLX3397 represents a novel therapeutic approach for cancer, showing dose-proportional systemic exposure clearly reaching an efficacious range for both FMS and Kit inhibition. The selectivity of PLX3397 has translated into a favorable safety profile. The first of several planned phase II trials in selected indications has been initiated in refractory Hodgkin lymphoma.
A novel patient-aimed visual tool to aid in decision making in oncology.
Authors: Cristian Zanartu, Fernando J. Camacho, Benjamin Martin
Journal: Journal of Clinical Oncology (2015)

21 Background: With up to 15% of Medicare patients receiving chemotherapy during the last two weeks of life, improving specialist-patient communication is a priority. The Help-Hurt Tool (2015) is a very simple patient-language visual aid for decision-making. It consists of two scales, a blue one labeled “from 1 to 5 how much could this therapy help me” and a red one with the same statement ending in “…hurt me”. The tool is held by the specialist and shown to the patient while arrows are moved to a particular point below each scale. That way, two values are given to the patient for the degree of benefit and of harm respectively expected from an offered treatment. Each number corresponds to an outcome in patient-language (i.e. a ‘help’ score of 2 is “small chance of making me feel better...” and of 4: “big chance of making me live at least a year longer”. A ‘hurt’ score of 2 is “likely non-dangerous side effects” and of 5: “likely life threatening therapy”). Methods: Feasibility study in an oncology clinic at an urban area in New York. Adult cancer patients without dementia whose disease had progressed through a previous treatment and were being offered a new line of therapy were enrolled. Results: Thirty encounters were enrolled. The tool was successfully used in 29 of them (96.7%); one patient was confused and could not follow at all. In more than 70% of encounters patients stated that the tool helped them understand their disease and treatments (‘helpful’: 32.3%, ‘very helpful’: 38.7%), and in 90% of encounters patients stated wanting to be approached with a tool like this again. Importantly in 60% of encounters patients were able to recall either the Help or Hurt score, and in 33.3% of encounters both values were perfectly recalled by patients. In 83.3% of encounters oncologists declared that the tool had a positive effect (‘helpful’ (40%) or ‘very helpful’ (43.3%)) in their interactions with the patient. Conclusions: This first-of-its-kind tool is promising for enhancing communication between specialists and patients at the time a therapy is being offered. Future steps for this tool would include a randomized trial to explore if its use can further affect outcomes like use of chemotherapy in the last two weeks of life, earlier hospice enrollment and quality of life, among others.
Antidepressant effects of a yoga program in breast cancer patients undergoing conventional treatment: A randomized controlled trial
Authors: B. S. Ajaikumar, R. M. Raghavendra, S. Patil, D. B. Ravi, S. B. Srinath, K. S. Gopinath, R. Nagarathna
Journal: Journal of Clinical Oncology (2008)

9556 Background: Depression is common among breast cancer patients and warrant clinical attention because of their adverse effects on quality of life in cancer patients. We compared the effects of a yoga program with supportive therapy on self-reported symptoms of depression in breast cancer patients undergoing conventional treatment. Methods: Thirty-eight stage II and III breast cancer outpatients were randomly assigned to receive yoga (n = 18) or brief supportive therapy (n = 20) over a 24-week period during which they underwent surgery followed by adjuvant radiotherapy and chemotherapy. Intervention consisted of yoga sessions lasting 60 minutes daily while the control group was imparted supportive therapy during their hospital visits as a part of routine care. Primary outcome measure was self reported Beck’s Depression Inventory and secondary outcomes were symptom checklist quality of life assessed using modified version of Memorial symptom assessment scale and Functional living index of cancer respectively. Assessments were done at baseline, after surgery, before, during, and after radiotherapy and chemotherapy. Results: A GLM repeated measures ANOVA showed overall decrease in depression (p < 0.001) in yoga group as compared to controls. However, there was no significant group by time interaction effects. Post hoc tests using Bonferroni correction showed significant decreases in depression following surgery (p = 0.01), during radiotherapy (p = 0.005) and during chemotherapy (p < 0.001) in yoga group as compared to controls. There was a positive correlation between depression score with symptom severity and distress during conventional treatment intervals and negative correlation with quality of life. Conclusions: The results suggest that yoga can be used for managing self reported depressive symptoms in breast cancer patients undergoing conventional treatments. No significant financial relationships to disclose.
Overcoming cisplatin resistance with mTOR inhibition in small cell lung cancer: A phase I-II trial design
Authors: B. R. Bastos, C. Wu, M. Wangpaichitr, L. G. Feun, C. Robles, N. Savaraj
Journal: Journal of Clinical Oncology (2008)

14673 Background: Small cell lung cancer (SCLC) patients treated with Cisplatin and VP-16 alone have a median survival of 12 months. Results with salvage therapy remains poor. The introduction of new anticancer agents for SCLC has been disappointingly slow, thus development of novel approaches and therapeutic agents are needed. We hypothesize that in order to survive cisplatin, SCLC cells have to synthesize repair proteins, antiapoptotic proteins and growth signaling proteins, through over expression of ribosomal proteins(RP) and elongation factor(elF). Reviewing array data indicate that one common biochemical abnormality in these resistant cells is the increase of cDNA which encodes for RP and elF. Thus, by blocking their translation, one should be able to restore cisplatin sensitivity. We have studied the role of CCI- 779, which inhibits translation by disabling mTOR, in restoring cisplatin sensitivity in a panel of cisplatin resistant cell lines. Methods: We propose a Phase I-II pilot study that will include patients with relapsed/resistant SCLC with prior exposure to platinum based regimens. We include patients with: partial response after cycle 1–2 of treatment and no further improvement after cycle 3–4; stable disease after cycle 1–2; progression of disease and relapsed patients. The pharmacodynamic effects of CCI-779 will be measured in mononuclear cells with a p70s6 kinase assay. Patients will receive CCI-779 at a dose of 25 mg intravenously weekly concomitant with the prior platinum based regimen. Results: Our in vitro data show that CCI-779 possess antiproliferative effects in both cisplatin sensitive and resistant cell lines. Importantly, CCI-779 at 10 ng/ml (less that 10% of the growth inhibitory effect) can increase the growth inhibition of cisplatin by 2.5–6 folds. Moreover, CCI-779 also enhances the apoptotic effect of cisplatin in cisplatin resistant cell lines. In these resistant cells, adding CCI-779 decreases the amount of 4E-BP phosphorylation and p-70S6 kinase phosphorylation as well as lower the amount of elF while cisplatin alone has no effect. Conclusions: CCI-779 is able to restore cisplatin sensitivity in SCLC resistant cell lines. These findings will be further explored in this phase I-II clinical trial design. No significant financial relationships to disclose.
Comprehensive CYP2D6 genotyping in a multiracial population shows differences in allele frequencies between races.
Authors: W. J. Irvin, K. E. Weck, C. M. Walko, W. K. Chiu, P. Rubin, O. A. Olajide, S. G. Moore, R. E. Raab, D. R. Carrizosa, S. W. Corso, G. Schwartz, S. M. Anderson, K. J. Friedman, E. C. Dees, D. Flockhart, J. M. Peppercorn, H. L. McLeod, J. P. Evans, L. A. Carey
Journal: Journal of Clinical Oncology (2011)

e11095 Background: CYP2D6 genotyping has been investigated to avoid suboptimal response to tamoxifen, and although current data do not support routine genotyping in postmenopausal women, there is a need for further evaluation in multiracial populations. As part of a clinical trial evaluating genotype-guided tamoxifen dosing, we comprehensively examined CYP2D6 allele frequencies in women of heterogeneous ethnicity taking tamoxifen. Methods: As part of a multi-institution prospective clinical trial (LCCC 0801), patients on tamoxifen ≥ 4 months and not on potent CYP2D6 inhibiting medications were genotyped for CYP2D6 using the CYP450 AmpliChip. Tamoxifen dose was increased in patients with any intermediate or poor metabolizing (IM or PM) alleles [but not in patients homozygous for extensive metabolizing (EM) alleles]. Here we report the allele frequency data. Results: 499 evaluable patients participated in the study: 82 (16%) African-Americans (AA), 391 (78%) non-Hispanic whites, 11 Asians (2%), 13 Hispanics (3%), 1 American Indian, and 1 Pacific Islander. Genotyping revealed 152 (31%) EM/EM, 6 (1%) EM/UM (ultra-rapid), 104 (21%) EM/IM, 115 (23%) EM/PM, 28 (6%) IM/IM, 50 (10%) IM/PM, 31 (6%) PM/PM, 2 UM/PM, 2 UM/IM and 9 (2%) unknown. Allele frequencies are shown in the table. Of the 27 variant alleles evaluated, all were present in our population except *7,* 8, *11,*15, *19, *20, *36, *40, and *10XN. The odds ratio of an AA patient having a reduced metabolism allele was 2.0 (95% CI, 1.4-2.9) times higher than for white patients. Conclusions: AA women have a higher prevalence of reduced metabolism CYP2D6 alleles. Although the clinical impact of variations in tamoxifen metabolism is uncertain, it is possible that previously unrecognized racial pharmacogenetic heterogeneity contributes to breast cancer outcome disparities. CYP2D6 allele frequencies. Allele frequencies *1, *2 (EM) *35 (EM) *3-6 (PM) *9 (IM) *10 (IM) *17 (IM) *29 (IM) *41 (IM) Other Total patients (n=499) 0.50 0.04 0.22 0.02 0.02 0.03 0.02 0.11 0.04 African American patients (n=82) 0.34 0 0.15 0.01 0.02 0.16 0.09 0.14 0.09 Non-African American patients (n=417) 0.53 0.04 0.24 0.03 0.02 0.01 0 0.11 0.02
The Epstein-Barr Virus (EBV) Encoded Oncoprotein LMP1 Mediates Down Regulation of Shelterin Proteins, Formation of Telomere Aggregates and Multinuclearity.
Authors: Valérie Lajoie, Bruno Lemieux, Bassem Sawan, Daniel Lichtensztejn, Zelda Lichtensztejn, Martin Rowe, Raymund Wellinger, Sabine Mai, Hans Knecht
Journal: Blood (2010)
Learning from and engaging patients/families during the implementation of a new medical record system.
Authors: Stephen Flaherty, Kathleen Horvath, Patricia Jahoda Stahl
Journal: Journal of Clinical Oncology (2016)

66 Background: Dana-Farber Cancer Institute implemented a new medical record system to improve clinical and revenue cycle services. Through the formation of a Patient Experience (PX) committee we thoughtfully and methodically revised materials and processes putting patient and family perspectives first. Methods: Formed PX committee with PFAC members, executive leadership, Patient/Family Relations (PFR), Volunteer Services, Management operations, and Quality/ Patient Safety representation. Created and vetted plan for measuring and mitigating patient experience/satisfaction during a hospital-wide EHR roll-out. Involved patient and families in every committee meeting; presented with plans and ideas for their input and approval before implementation and updated post. Deployed volunteers (composed of former/current patients and families) in increased numbers during system roll out to help patients navigate changes in hospital processes, to answer questions about the roll-out, including wait times. Staff/Ambassador rounding implemented for month 1 of roll out to gather real-time patient concerns. Manager, director or nurse leader were involved in the completion of every service recovery. Modified communication tools, volunteer and staffing patterns, and service adjustment plans. Identified and prioritized patient satisfaction questions for longitudinal analysis. These questions and associated personal comments were tracked and presented as Institutional success metrics. Results: No formal filing of patient or family complaints related to this implementation. Service Recovery costs were minimal. Volunteer Services facilitated a 33% increase in volunteer hours from same time period the previous year. Patient Satisfaction scores for the outpatient service saw one month positive impact, followed by one month negative impact followed by recovery to normal. Conclusions: Working with patients and families to ensure a seamless and smooth roll-out of a new EHR is imperative. Implementation is felt by patients as work flows for all hospital employees are impacted by initial utilization of a new system. The impact of implementation to patients was mitigated through work done by our committee.
Induction of REMISSION with Clofarabine IN CHILDREN with Relapsed Acute LYMPHOCYTIC Leukemia.
Authors: Maria M Moschovi, Georgios G Trimis, Kaliopi Karamolegou, Niki Tourkantoni, Maria Tzanoudaki, Anna Divane, Eleni Botsa, Elias Bouzios, Eleftheria Koultouki, Fotini F Tzortzatou-Stathopoulou
Journal: Blood (2009)