tbuckley/cabot-search huggingface dataset:
Endomicroscopy for Computer and Robot Assisted Intervention
Authors: Siyang Zuo, Guang-Zhong Yang
Journal: IEEE Reviews in Biomedical Engineering (2017)

Endomicroscopy is a new technique that allows human tissue to be characterized in vivo and in situ, circumventing the need for conventional biopsy and histology. Despite increased application and growing research interests in this area, the clinical application of endomicroscopy, however, is limited by difficulties in ergonomic control, consistent probe-tissue contact, large area surveillance, and retargeting. Recently, advances in high-speed imaging, mosaicing, and robotics have aimed to address these difficulties. The development of robot-assisted devices in particular has shown great promises in extending the clinical potential of endomicroscopy. Issues related to miniaturization, adaptation to tissue deformation, control stability, force and position compensation, cost, and sterility are being pursued by both research and commercial communities. In this review, recent clinical and technical developments in different aspects of computer and robotic assisted endomicroscopy interventions including instrumentation, multiscale integration, and high-speed imaging techniques are presented. We further address emerging trends and new research opportunities toward more widespread clinical acceptance of robotically assisted endomicroscopy technologies.
A phase I study of cediranib (NSC #732208) in combination with cisplatin and pemetrexed in chemonaive patients with malignant pleural mesothelioma (SWOG S0905).
Authors: Anne S. Tsao, James Moon, Ignacio Ivan Wistuba, Nicholas J. Vogelzang, Gregory Peter Kalemkerian, Mary Weber Redman, David R. Gandara
Journal: Journal of Clinical Oncology (2013)

7527 Background: The VEGF/VEGFR and PDGF/PDGFR pathways are potential therapeutic targets in mesothelioma. Cediranib, a VEGFR/PDGFR inhibitor, showed anti-tumor activity in a salvage monotherapy study S0509. Methods: S0905 combined cediranib (2 dose cohorts 30 mg and 20 mg daily) with cisplatin and pemetrexed for 6 cycles followed by maintenance cediranib in unresectable chemo-naïve MPM patients. Results: A total of 20 patients (7 to cohort 1 - 30 mg, 13 to cohort 2 - 20 mg) were enrolled. In first cohort, 2 patients reported grade 3 DLTs of diarrhea and fatigue. Cohort 2 DLTs included 2 patients with grade 3 hyponatremia/dehydration and mucositis. For all cycles, 12 patients reported Grade 3 AEs, the most common being diarrhea (4), dehydration (3), fatigue (3) and neutropenia (3). Two grade 4 thrombocytopenia were reported with 1 treatment-related death (cohort 2) due to pneumonia/sepsis. Based on the toxicity profile, a decision was made to proceed with cediranib 20 mg daily for the remaining phase I/II trial. Two radiographic response measurements were utilized (RECIST 1.1, modified RECIST). 18/20 patients were evaluable for response by RECIST 1.1 (7 - 30 mg cohort, 11 - 20 mg cohort). The RECIST 1.1 RR was 22% (95% CI: 6% - 48%) and median PFS was 14 months (95% CI: 8 – 17). Two patients had inadequate assessments and are classified as non-responders. There were 19 patients measurable by modified RECIST with RR 53% (95% CI: 29%-76%) and median PFS 10 months (7-13). For all patients, the median OS was 16 months (95% CI: 11-19). One patient in the 30 mg cohort remains on trial after 25 cycles of therapy; 2 patients at the 20 mg cohort remain on trial on cycles 19 and 15 of therapy. Conclusions: Cisplatin-pemetrexed-cediranib shows significant clinical activity and acceptable toxicity with cediranib 20 mg/day. The randomized phase II portion of the trial is ongoing. Clinical trial information: NCT01064648. [Table: see text]
Window of opportunity trial of HPV E7 antigen-expressing <i>Listeria</i>-based therapeutic vaccination prior to robotic surgery for HPV-positive oropharyngeal cancer.
Authors: Brett Miles, Sacha Gnjatic, Michael Donovan, Eric Michael Genden, Krzysztof Misiukiewicz, Rosemarie Krupar, Yvonne M. Saenger, Elizabeth G Demicco, Marshall R. Posner, Andrew Gregory Sikora
Journal: Journal of Clinical Oncology (2015)

TPS6088 Background: The incidence of human papilloma virus-associated oropharyngeal cancer (HPVOPC) has rapidly risen over the past two decades. Foreign viral antigens make HPVOPC an attractive target for immunotherapy. One exciting approach is the use of live attenuated Listeria monocytogenesbioengineered to express the HPV16 E7 protein (LmE7) and elicit a vigorous immune response. We designed a phase II “window of opportunity” trial with robust correlative endpoints to determine the effect of LmE7 vaccination on anti-tumor immunity in the tumor microenvironment and peripheral blood, as well as safety and tolerability in the HPVOPC population. Methods: Trial Design: Non-randomized single-arm phase II clinical trial utilizing a Simon’s two-stage design. HPVOPC patients receive two cycles of LmE7 over 5 weeks prior to standard-of-care transoral surgical resection of their tumor with or without neck dissection. The primary objective is to determine the rate of post-vaccination T cell responses by measuring the pre- and post-treatment mean frequency of peptide-specific IFN-γ expressing T cells in the peripheral blood by ELISPOT. We will conclude that LmE7 is likely highly immunogenic and worth further investigation if post-treatment responses are seen in > 75% of patients. Inclusion Criteria:Previously untreated surgically-resectable stage II-IV HPVOPC, HPV-positive by PCR-based testing. Exclusion Criteria:Prior history of cancer within 3 years, or any history of systemic cancer therapy; immunosuppressive disorder or medications; medical contraindications to therapy. Correlative Studies:The pattern of immunocyte infiltration in the tumor and draining lymph nodes will be assessed by multiplex immunofluorescence; expression profile of immune-related genes assessed by nanostring; and T cell receptor diversity by deep sequencing. These tissue-based changes will be correlated with comprehensive analysis of immune changes in the peripheral blood Status: Open, actively accruing. 8 of a maximum 22 (9 in first stage, 13 in second stage) vaccinated patients, and 0 of a maximum 10 untreated observational cohort patients have been enrolled. Clinical trial information: NCT02002182.
Physician toxicity attribution in phase I trials: Evaluating the effect of dose on the frequency of 11,909 toxicities.
Authors: Anne Eaton, Alexia Iasonos, Mrinal M. Gounder, Erika Pamer, Alexander E. Drilon, Diana Vulih, Gary L. Smith, Percy Ivy, David R. Spriggs, David Michael Hyman
Journal: Journal of Clinical Oncology (2015)

e17674 Background: Accurate classification of toxicity in Phase I trials as related or unrelated to study drug is critical. Attribution in Phase I has not been widely studied and assessing it is complicated by the lack of a gold standard. We examined dose-toxicity relationships as a function of physician-assigned attribution to evaluate for evidence of toxicity misattribution. Methods: Individual patient records from 1,156 patients enrolled to 38 Phase I studies between 2000-2010 were used. Dose was defined as percent of maximum dose administered on each study. Relationships between dose and patient-level toxicity were explored graphically and with logistic regression. All p-values were two-sided. Results: 11,909 unique toxicities were analyzed. A broad range of drug classes were represented. Only 4% and 12% of toxicities were assigned ‘definitely’ or ‘probably’ related, respectively. ‘Possibly’ related accounted for 30% of all toxicities. Using a simplified binomial attribution system, unrelated toxicity was not associated with dose (p = 0.0920 grade ≥ 3, p = 0.4194 grade ≥ 1) while related toxicity increased with dose (p < 0.0001, both grade ≥ 3 and ≥ 1). Similar relationships were observed within specific toxicity categories. The increase in toxicity rate with dose was steepest for constitutional, hematologic and gastrointestinal toxicities. In the 5-tier system, toxicities attributed as ‘possibly’, ’probably’, or ‘definitely’ related were associated with dose (all p < 0.0001) while toxicities attributed as ‘unlikely’, or ‘unrelated’ were not (all p > 0.1). Conclusions: We did not observe an association between unrelated toxicity rate and dose, something which could only have been explained by physician misattribution. These findings confirmed our expectation that related toxicity rate increases with dose while unrelated toxicity occurs at a constant rate across dose levels. The similarity of dose-toxicity relationships between ‘unrelated’ and ‘unlikely’ related toxicities and ‘possibly’, ‘probably’ and ‘definitely’ related toxicities support moving towards a simplified binomial attribution system for classifying the relatedness of treatment-emergent events.
Analysis of patients with esophageal cancer following trimodality therapy: Pathological complete remission (PathCR) versus non-PathCR.
Authors: Mariela A. Blum, Lianchun Xiao, Arlene M. Correa, Roopma Wadhwa, Elena Elimova, Heath Devin Skinner, Ritsuko Komaki, Jeffrey H. Lee, Manoop S. Bhutani, Brian Weston, Zhongxing X. Liao, David C. Rice, Stephen Swisher, Wayne Lewis Hofstetter, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2015)

4041 Background: Trimodality therapy (chemoradiation followed by surgery) continues to be the cornerstone treatment for localized esophageal cancer; predictive models for pathCR have been not been clinically validated. The purpose of this study was to determine the association of pathCR with baseline clinical factors, overall survival (OS), and recurrence free survival (RFS) in a large population. Methods: We analyzed the data of 911 consecutive patients treated for esophageal cancer with trimodality therapy. Logistic regressions were used to identify independent baseline factors associated with pathCR. We applied log rank testing and univariable and multivariable Cox models to determine the association between pathCR and the time-to-event outcomes (OS and RFS). Results: Of 911 patients studied, 218 (23.9%) achieved pathCR. Lower clinical T stage (T1/T2) was more likely to achieve pathCR (p = 0.0006). Advanced age (OR = 0.984, p = 0.0297), poorly differentiated tumors ((OR = 0.48), p = < 0.0001), and signet ring cell histology (p = < 0.0001) were associated with lower rate of pathCR. OS and PFS rates were higher for pathCR patients (p = 0.0021 and p = 0.0011). The estimated median OS was 71.28 (95% CI: 51.71-91.63) months in pathCR patients and 35.87 (95% CI: 31.23-42.19) months in non-pathCR patients. Distant recurrences were less common in pathCR patients (p = 0.0036). Conclusions: Poor prognostic indicators associated with decreased rate of pathCR and OS were: older age, poorly differentiated tumors, and the presence of signet ring cell histology. Our data is the largest data set showing that pathCR confers better prognosis in patients with esophageal cancer. While recurrences were still seen in pathCR patients, distant metastases were more common in non-pathCR patients. Further biomarker-based approach might help to identify patients who are more likely to achieve pathCR.
Radiosensitive effect of gemcitabine on nasopharyngeal carcinoma CNE-1 cell line
Authors: Y. Chen, X. Yu
Journal: Journal of Clinical Oncology (2006)

20105 Background: To observe the effect and mechanism of gemcitabine-induced radiosensitization on CNE-1 nasopharyngeal carcinoma cell line. Methods: The cell survival curves were obtained with clonogenic assay. The cell cycle phases were measured with flow cytometric analysis. Results: No cytotoxic effect was observed in 0.1 μM and 2 μM gemcitabine alone group. The radiosensitivities were observed in the groups treated with radiation and gemcitabine exposed in different consistencies and times. The SER were 1.35,1.82; 1.55 and 2.16 respectively. The G1 cell cycle phase block was observed in the two consistency groups after exposing to gemcitabine for 24 hours. D q were rather lower in 2 μM groups especially that exposed for 24 hours. Conclusions: The radiosensitivity was obviously observed in the groups treated with two consistencies of gemcitabine. The effect was more obviously as the consistency and the exposing time increased. The block of cell cycle from G1 to S and the decrease of sublethal damage repair might be contributed to the mechanism. No significant financial relationships to disclose.
A multidisciplinary clinic to mitigate the toxicity of therapy for newly diagnosed metastatic prostate cancer undergoing chemohormonal therapy: A feasibility study.
Authors: Jeffrey Hough, Tammy J. Rodvelt, Miles Thomas, Brian Ma, Michael W. Rabow, Rami Weinberg, Greta Macaire, Nancy Shepard, June M. Chan, Erin Van Blarigan, Gonzalo Choque-Gonzales, Mina Lee, Terence W. Friedlander, Won Kim, Charles J. Ryan, Eric Jay Small, Rahul Raj Aggarwal
Journal: Journal of Clinical Oncology (2017)

153 Background: Chemohormonal therapy is standard of care for newly diagnosed metastatic prostate cancer (mPC) patients (pts) but is associated with significant adverse effects and negative metabolic changes. We performed a pilot study to investigate whether participation in a multi-disciplinary clinic to mitigate adverse effects of treatment is feasible. Methods: Pts with recently diagnosed mPC who were planning to start or had recently started chemohormonal therapy were prospectively enrolled in a multi-disciplinary clinic that included individualized monthly counseling from a physical therapist, oncology dietitian, and palliative care specialist on a rotating basis for 12 months. Patients were assessed quarterly for changes in % body fat, weight, serum levels of 25-OH vitamin D, fasting lipids/glucose/insulin, and quality of life (QOL). DXA bone density scans were performed at baseline and end of 12 months. The primary endpoint was the completion rate of scheduled visits. Results: 7 pts were enrolled between September 2015 and June 2016. All patients had extensive disease ( &gt; 4 bone metastases and/or visceral metastases) at the time of study entry, and all 7 patients completed six cycles of docetaxel-based chemotherapy, and remained on hormone therapy for the duration of study. The percentage of completed visits was 98% (54/55 planned visits). The percentage of completed assessments including QOL questionnaires was 81%. No skeletal-related complications were observed. Median percent increase from baseline in body weight and % body fat was 3.51% and 20%, respectively. Four of the seven patients had osteopenia at baseline. Patient reported satisfaction was high and positive impact on psychosocial well-being was observed. Conclusions: Participation in a multi-disciplinary clinic by men receiving intensive chemohormonal therapy for metastatic prostate cancer was feasible. Patients are at risk for adverse metabolic and bone toxicity with therapy, underscoring the potential positive impact of a multi-disciplinary clinic. A randomized study to detect objective improvements in health outcomes is underway. Clinical trial information: NCT02168062.
Reduced PU.1 expression underlies aberrant neutrophil maturation and function in β-thalassemia mice and patients
Authors: Panjaree Siwaponanan, Jurre Ynze Siegers, Razi Ghazali, Thian Ng, Bradley McColl, Garrett Zhen-Wei Ng, Philip Sutton, Nancy Wang, Isabelle Ooi, Chayada Thiengtavor, Suthat Fucharoen, Pornthip Chaichompoo, Saovaros Svasti, Odilia Wijburg, Jim Vadolas
Journal: Blood (2017)
Phase I/II trial of bortezomib plus docetaxel in patients with advanced androgen-independent prostate cancer
Authors: R. Dreicer, B. Roth, D. Petrylak, D. Agus, M. Meyers, D. Esseltine, D. Rodriquez, P. Oppedisano, K. Wang, A. Boral
Journal: Journal of Clinical Oncology (2004)

4654 Background: Docetaxel is a microtubule stabilizing agent with documented clinical activity in patients with advanced prostate cancer. Bortezomib (Velcade, formerly PS-341) is a small molecule that is a potent and reversible proteasome inhibitor with evidence of anti-tumor activity in prostate cancer models. Following completion of the phase I portion of this study during which MTD was not reached, we evaluated two dose levels in expanded phase II cohorts. We report the results from the low expanded cohort. Methods: From 6/02 to 4/03, 31 patients (pts) were enrolled. Eligible pts had androgen-independent prostate cancer with radiologic and/or biochemical evidence of progression following antiandrogen withdrawal with castrate testosterone levels, KPS ≥ 60% and adequate organ function; prior systemic therapy was permitted. Docetaxel with standard dexamethasone premedication was given at 40 mg/m2 IV over 30 minutes on days 1 and 8. Bortezomib was given 24 hours after docetaxel at of dose of 1.3 mg/m2 IV push on days 2 and 9. Treatment was repeated every 21 days. Results: Median age was 67 (53–81), median KPS was 85% (60–90%), and median pre-therapy PSA value was 270. Nineteen pts had prior chemotherapy, 14 with a taxane containing regimen. Therapy was well tolerated with grade 3 diarrhea, peripheral neuropathy, hyperglycemia, neutropenia and fatigue seen in less than 5% of patients. Twenty-two patients are currently evaluable for response. Eight of 22 (36%) (90% CI 20–56) had a ≥ 50% decline in PSA from baseline and 5 of the 8 had a 90% or greater decline. Two of 12 (17%) patients with measurable disease achieved a partial response. Conclusions: Docetaxel + bortezomib was well tolerated at this dose and schedule, and showed promising activity in this population. Evaluation of a cohort receiving docetaxel at 40 mg/m2 + bortezomib 1.6 mg/m2 is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis; Millennium Pharmacueticals Glaxo Aventis; Celgene AstraZeneca; Aventis; Genentech; Millennium
A randomized, multicenter phase III study of lobaplatin/etoposide versus cisplatin/etoposide as first-line therapy in patients with extensive-stage small-cell lung cancer and circulating tumor cells (CTCs) as an exploratory biomarker.
Authors: Ying Cheng, Yun Fan, Xiaoqing Liu, Yunpeng Liu, Jiwei Liu, Dong Wang, Yan Yu, Shukui Qin, Wei Liu, Cheng Huang, Helong Zhang, Jun Liang, Jianhua Shi, Lijun Sheng
Journal: Journal of Clinical Oncology (2014)

7595 Background: Cisplatin plus etoposide (EP) is conventional regimen to treat small cell lung cancer (SCLC), however the toxicities of cisplatin limited its efficacy. Here, we showed the results of a phase III clinical trial using lobaplatin, a third-generation platinum compounds, in combination with etoposide (EL) in comparison to EP for extensive SCLC (ES-SCLC). Methods: A total 234 Chinese patients with newly diagnosed ES-SCLC were randomized into two groups: (1) the EL Group (n=122): 6 cycles of lobaplatin (30 mg/m2/day on day 1) and etoposide (100 mg/m2/day on days 1-3, every 21 days) and (2) EP Group (n=112): 6 cycles of cisplatin (80 mg/m2/day on day 1) and etoposide. The primary end point was progression-free survival (PFS); secondary end points included toxicity, QOL and overall survival (OS). Eighty five ES-SCLC patients were tested for circulating tumor cells (CTCs) (CELLSEARCHÒ) prior to treatment, at 2 cycles after therapy and disease progression. Results: For EL and EP group, the median PFS and the disease control rate (DCR) was 5.37 versus 5.99 months (P=0.1638), and 82.64% versus 83.78% (P=0.8618), respectively. In terms of toxicities, the incidence of nephrotoxicity in the EL group was significantly lower than that in the EP group (2.48% vs 11.71%, P=0.0079), as well as incidences of nausea and vomiting (22.31% vs 36.04%, P=0.0292, and 14.05% vs 25.23%, P=0.0453, respectively). At baseline as well as 2 cycles after chemotherapy, the median OS was significantly lower in patients with ≥5 CTCs than those with <5 CTCs (baseline: 23 months vs >26 months, P <0.0028 and 2 cycles: 23 months vs >26 months, P <0.0124). Conclusions: EL regimen is not inferiority to EP regimen in terms of PFS. The tolerance and QOL with EL regimen are better than that with EP regimen. Thus EL regimen provides an alternatively new choice for first-line ES-SCLC treatment in China. The study is the first worldwidely prospective clinical study using CTCs as a biomarker monitoring SCLC therapeutic effects. Clinical trial information: ChiCTR-TRC-10001047.
Grip strength and timed get-up-and-go: Associations with symptoms among women taking adjuvant endocrine therapy.
Authors: Andrea Phillips Sitlinger, Rebecca A. Shelby, Heidi K White, Sara N. Edmond, Hayden B Bosworth, Francis J Keefe, Gretchen Genevieve Kimmick
Journal: Journal of Clinical Oncology (2015)

e11564 Background: Little is known about the relationship between endocrine therapy side effects and measures of function in women with breast cancer. We examined the association of function and symptoms experienced by breast cancer patients on endocrine therapy. Methods: Eligible women were postmenopausal, had hormone receptor positive, stage I-IIIA breast cancer, completed surgery, chemotherapy, and radiation, and were on adjuvant endocrine therapy. At a routine follow-up visit, women (N = 107) completed standardized symptom measures: Brief Fatigue Inventory, Brief Pain Inventory, Menopause Specific Quality of Life Questionnaire, Functional Assessment of Cancer Therapy Neurotoxicity scales. Analyses were performed with an overall symptom composite score. Function was assessed by grip strength (Jamar dynamometer; n = 71) and timed get-up-and-go (TUG; n = 103). Correlations were performed to determine univariate associations. Regression analyses were also performed. Results: Participants had mean age 64 (range 45-84), 87% white, 84% on an aromatase inhibitor, and on endocrine therapy for mean 35 months (range 0.1-130 months). Dominant hand grip strength correlated inversely with symptoms (r = -.29, p < .05), specifically pain intensity (r = -.30, p < .05) and neurotoxicity (r = -.25, p < .05). In multivariate analysis, controlling for age, education, months on endocrine therapy, and endocrine therapy type, weaker dominant hand grip strength was significantly associated with greater symptoms by symptom composite (b = -.27, t = 2.42, p = .02). TUG correlated inversely with comorbidity level (r = .36, p < .05) and symptoms by symptom composite (r = .24, p < .05), specifically pain (r = .38, p < .05) and fatigue (r = .21, p < .05). In regression analyses, controlling for age, marital status, education, race, and comorbidity, slower TUG was associated with symptoms by symptom composite (b = .18, t = 1.97, p = .05). Conclusions: Weaker dominant hand grip strength and slower TUG were significantly associated to greater pain and overall symptoms. Endocrine therapy side effects, therefore, may be associated with worse functional performance. Further studies are needed to explore these associations.