tbuckley/cabot-search huggingface dataset:
Multimodal image and mapping guided focal salvage high-dose-rate brachytherapy for local recurrent prostate cancer.
Authors: Stephane Gilles Guerif, Ossama Didas, Jean Pierre Tasu, Odile Boissonnade, Catherine Cheze-Le Reste, Bertrand Debaene, Antoine Berger
Journal: Journal of Clinical Oncology (2017)

122 Background: Image guided brachytherapy and mapping biopsy could reduce the toxicity of the total salvage brachytherapy. This study evaluate the tumor control and the tolerance of a focal real time salvage high-dose-rate (HDR) brachytherapy to treat the local relapse as defined on transperineal mapping biopsy, multipara-metric MRI and Choline PETSCAN on the same treatment planning. Methods: Between October 2013 and June 2016, Twenty-nine patients with local relapse on Choline PET Scan after a primary irradiation had a salvage HDR Brachytherapy (2 fractions of 10 Gy within 4-6 hours in one implant) without hormone. One month before brachytherapy All patients had real time transperineal randomized European regions standardised magnetic resonance imaging (MRI) prostate biopsies and targeted biopsies with a fusion of T2 MRI sequence /CholinePETscan (50 % SUV) to intraoperative transrectal ultrasound one month before brachytherapy. We used Flex Focus 400 ultrasound machine BK, Vitesse 3.0 and 3 D navigation with EXII Stepper in order to use the result of mapping biopsy for real time HDR brachytherapy treatment planning study. Tumor control was measure with phoenix definition and Kaplan-Meier. The GU and GI toxicity were measure with CTCAE V 3. Results: 13 Low risk, 10 Intermediate risk, 8 High risk, initially treated with 3 Iodine brachytherapy ( 160 GY), 15 EBRT ≥ 78 Gy and 7 EBRT ≤ 70 gy were include. The number of biopsy (mean volume, 21 cm3; SD, 6.7). Prostate Volume (mean volume, 29.7 cm3; SD, 12.5). CTV Volume (mean volume, 13.3 cm3; SD, 6.7). Mean dose to 90% of the prostate was 11.4 Gy (SD, 1.45). Mean dose to 90% of the CTV was 21.1 Gy (SD, 1.45). Mean dose to 90% of the CTVmri was 27.6 Gy (SD, 3.4). The biologic disease free survival at 2 years is 65 % (Kaplan-Meier). Disease without hormone survival at 2 years is 86,5%. The chronic toxicity ( &gt; 6 mois) was 6 Gu and 4 GI for grade ≤ 2 and 1 GU grade 3 (total incontinence). Conclusions: Focal, mapping and multimodal image guided salvage HDR brachytherapy for recurrent prostate cancer is a feasible therapy. This approach has to be evaluated in multicenter cohort.
A discrete choice experiment to examine preferences and willingness to pay for prophylactic granulocyte colony-stimulating factors (G-CSF) in previously treated breast cancer patients.
Authors: Phaedra Johnson, Tim Bancroft, Richard L. Barron, Jason C. Legg, Xiaoyan Li, Holly Watson, Arash Naeim, Deborah Marshall
Journal: Journal of Clinical Oncology (2013)

e17509 Background: As patient-centered care becomes more prominent, a better understanding of patient preferences and tradeoffs amongst treatment alternatives and outcomes is needed. This study used a discrete choice experiment to examine the preferences and willingness to pay for prophylactic G-CSF to decrease the incidence of chemotherapy (CT)-induced febrile neutropenia in breast cancer patients who previously received CT. Methods: An online survey was developed with 16 paired treatment choice scenarios comparing 3 alternative G-CSF options (11 versus 1 or 6 versus 1 injections per CT cycle) with a follow-up “no treatment” option. Each scenario had 4 attributes: risk of disruption to CT schedule due to neutropenia, risk of infection requiring hospitalization, frequency of G-CSF administration, and total out-of-pocket (OOP) cost for G-CSF during a CT cycle. Patients’ preferences and willingness to pay (as OOP cost) were estimated using logistic regression. Results: Patients’ (n = 296) preferred G-CSF options with the lowest OOP costs, the fewest injections, and improved outcomes (lowest risk of disruption to CT schedule and lowest risk of infection requiring hospitalization). In the context of this discrete choice experiment, OOP costs and risk of disruption to CT schedule were the most important attributes to patients; risk of infection requiring hospitalization and frequency of G-CSF administration affected patients’ choice of G-CSF option to a smaller but similar degree. Patients were willing to pay OOP $1,076 per cycle to reduce the risk of disrupting the CT schedule from high to low, $884 per cycle to reduce the risk of developing an infection requiring hospitalization from 24% (high) to 7% (low), and $851 and $667 per cycle to decrease the number of G-CSF injections per cycle from 11 to 1 and 6 to 1, respectively. Conclusions: With a current focus on patient-centered approaches in decision-making, physicians need to consider patient preferences when making decisions about therapy, including supportive care agents.
Therapy of human solid tumor xenografts with CD74-targeted milatuzumab-SN-38 immunoconjugates.
Authors: David M. Goldenberg, Thomas M. Cardillo, Robert M. Sharkey, David V. Gold, Serengulam V. Govindan
Journal: Journal of Clinical Oncology (2012)

3091 Background: CD74 is commonly considered to be an antigen present in hematopoietic cancers, but it is also expressed in a number of solid tumors. The humanized anti-CD74 antibody, milatuzumab (hLL1), was previously shown to have exquisite internalization properties, making it an attractive carrier for drug delivery. In this study, we evaluated hLL1 conjugates of a potent topo I inhibitor, SN-38, for treating solid tumors. Methods: Two hLL1-SN-38 conjugates, possessing either a pH-sensitive linker (‘CL2A’ form) or a cathepsin-B-cleavable linker ("CL2E" form), were examined. In vitro analyses were carried out in the A-375 human melanoma cell line, and therapy experiments were performed in female athymic nude mice bearing established s.c. A-375 or s.c. human pancreatic adenocarcinoma (Capan-1) xenografts using specified doses (i.p.) at a twice weekly × 4 wks schedule; animals were sacrificed when tumor volumes (TVs) reached 1 cm 3 . Results: Both A-375 and Capan-1 cell lines tested positive for CD74 expression by IHC. In vitro, both SN-38 derivatives liberated free drug at the same rate when exposed to cathepsin-B at pH 5, while serum stabilities for CL2A and CL2E forms of the conjugates were ~ 1 d and &gt;10 d, respectively. In the A-375 melanoma cell line, IC 50 for the hLL1-SN-38 conjugates of CL2A and CL2E forms were 5 nM and 34 nM, respectively. In the aggressive A-375 s.c. model of melanoma, in nude mice (n =8; TV: 0.23 ± 0.06 cm 3 ) treated with 12.5 mg/kg protein dose (total 1.7 mg/kg SN-38 eq.) of specific or non-specific SN-38 conjugates of CL2A and CL2E forms, only hLL1-CL2A-SN-38 conjugate was efficacious (Log-rank: P&lt;0.009 vs. all controls), with a median survival time of 28 d vs. 10.5 d for untreated. Likewise, in mice bearing Capan-1 xenografts (n = 8-10; TV=0.27 ± 0.05 cm 3 ), two low doses of hLL1-CL2A-SN-38 (12.5 or 5 mg/kg) significantly improved survival in comparison to saline control mice (p&lt;0.035), whereas the CL2E form and a non-specific control demonstrated no efficacy. Conclusions: These results indicate the therapeutic potential of hLL1-CL2A-SN-38 conjugate and the importance of linker chemistry, and encourage additional testing in other CD74-positive solid cancers.
Association of idiotype vaccine-induced T-cell response with improved survival and time-to-next treatment (TTNT) in untreated mantle cell lymphoma (MCL).
Authors: Kieron Dunleavy, Sattva Swarup Neelapu, Larry W. Kwak, Cliona Grant, Carlos F. Santos, Mihaela A. Popa, Therese White, Barry Miller, Elaine S. Jaffe, Seth M. Steinberg, Wyndham Hopkins Wilson
Journal: Journal of Clinical Oncology (2012)

2528 Background: Murine models show Id-vaccines induce antitumor responses, possibly through Th1/Tc1 cytokines. We report an 11-year follow-up of Id-vaccine following DA-EPOCH-Rituximab in 26 untreated MCL patients. Methods: DA-EPOCH-R was administered q3 weeks × 6, followed 12 weeks later by 5 cycles of Id-vaccine. Id protein was made by hybridoma technology, conjugated to keyhole limpet hemocyanin (KLH) and administered with GM-CSF. Pre- and post-vaccine immune responses (IR) were tested in parallel: anti-Id and anti-KLH humoral responses (ELISA); anti-KLH cellular responses (intracellular cytokine assay); and anti-tumor cellular responses (cytokine induction, IFNγ ELISPOT). Results: Characteristics: median age 57 (r 22-73), blastoid variant 15%, and MIPI (low-65%; intermediate-16%; high-19%). With 122 mo median follow-up (r 111-132), the median PFS is 24 mo and OS is 104 mo. MIPI was associated with OS (p=0.0002); median OS: low (not reached), intermediate (84 mo) and high (44 mo). We found no association between OS and anti-KLH IR, anti-Id humoral response, IFNγ ELISPOT, or antitumor TNFα or IFNγ responses. Normalized antitumor T-cell GM-CSF response (median &lt;4.3 vs. &gt;4.3) was associated with OS of 79 mo vs. not reached, respectively (p=0.015 (unadj.) and p=0.045 (adj.)). MIPI (p=0.02) and GM-CSF (p=0.057) were independently associated with OS. TTNT (based on disease activity), correlated with antitumor GM-CSF response (p=0.018) but not MIPI and was independent of MIPI (GM-CSF; p=0.041). Correlation of pre-and post-treatment GM-CSF production suggested a priming effect. Tumor proliferation by GEP did not correlate with OS (n=14). Conclusions: Antitumor GM-CSF response was significantly associated with OS and TTNT, suggesting antitumor cellular immune response significantly delayed tumor growth. Antitumor GM-CSF response may serve as a surrogate biomarker for vaccine efficacy. Our results are consistent with recent data that T-cell GM-CSF production is required for breaking tolerance against self-antigens. Id vaccines may prolong survival of MCL following rituximab-based chemotherapy and should be further evaluated.
Concurrent radiotherapy with gefitinib in elderly patients with esophageal squamous cell carcinoma: Preliminary results of a phase II study.
Authors: Yaping Xu, Yuanda Zheng, Xinmin Yu, Wei Wu, Weimin Mao
Journal: Journal of Clinical Oncology (2015)

e15032 Background: Esophageal cancer has a very poor survival rate. This study investigated the efficacy of gefitinib in combination with radiation in 20 elderly patients with esophageal squamous cell carcinoma (ESCC) who were not eligible for platinum-based chemotherapy. Methods: A single center, non-randomized phase II study was conducted for open-label gefitinib with radiotherapy as a definite treatment for esophageal SCC in elderly patients at a daily oral dose of 250 mg gefitinib for 2 months and radiotherapy starting on day 1. Immunohistochemistry was performed to analyze EGFR expression, and the amplified refractory mutation system was used to detect EGFR mutations. Treatment response was assessed by endoscopy and computed tomography. Treatment toxicity was evaluated using the National Cancer Institute’s Common Toxicity Criteria. Results: The data showed that among these 20 patients, 5 experienced a complete response (CR), 13 a partial response (PR), and 2 had stable disease. The overall response rate (CR + PR) was 90%, the median overall survival (OS) was 14.0 months (95% CI, 10.0–17.9 months), and the median progression-free survival was 7.0 months (95% CI, 0–17.2 months). Patients with good Eastern Cooperative Oncology Group performance status, never smoking, and EGFR mutated tumors had the best OS (14.0, 14.0, and 17.0 months, respectively). Treatment-related grade 3/4 toxicity occurred in five patients. There were no patients with grade 3/4 impaired liver functions or hematological toxicity observed. Conclusions: Concurrent radiotherapy with gefitinib is effective and tolerable in elderly ESCC patients. (Trial registration: NCT01291823). Clinical trial information: NCT01291823.
Discordance of oncologic surgical classifications in COG studies.
Authors: Carol Morris, Lisa A. Teot, Mark L. Bernstein, Neyssa Marina, Mark D. Krailo, Doojduen Villaluna, Richard Greg Gorlick, R. Lor Randall
Journal: Journal of Clinical Oncology (2013)

10528 Background: “Wide resection” (a cuff of normal tissue) versus “radical resection” (the entire compartment) indicate very distinct oncologic surgical procedures and hence potential margin status. Distinguishing between these two oncologic classifications is important for understanding oncologic outcomes. Methods: We examined the available data for COG AOST0331: A Randomized Trial of the European and American Osteosarcoma Study Group to Optimize Treatment Strategies for Resectable Osteosarcoma Based on Histological Response to Pre-Operative Chemotherapy. We reviewed the surgical and pathology reports of patients considered to have received a wide or radical resection according to the investigator at the patient’s institution. Results: In 956 patients, the overall discordance rate was 43%. Of those patients reported to have had a wide excision by the reporting institution, only 5% of patients were reclassified to radical resection. However, of those patients reported to have undergone radical resection, 75% were reclassified to wide. In the absence of this re-review of the data, 56% of the patients would have been reported to have had a radical resection when in fact only 17% met the criteria for true radical resection. The greater number of patient reclassified to wide from radical is likely indicative of the influence and limits of the CPT coding system currently used for billing by surgeons; only CPT codes for radical resection currently exist. Conclusions: These discrepancies complicate subsequent data analysis, particularly assessing predictors of local recurrence. While this reporting problem is not unique to COG studies, we aim to use this example to raise awareness among our colleagues about the importance of accurate data reporting. Providing better training to those individuals responsible for submitting data may decrease the incidence of erroneous data entry and is essential to the successful completion of study objectives.
Daratumumab, Bortezomib and Dexamethasone Versus Bortezomib and Dexamethasone Alone for Relapsed or Refractory Multiple Myeloma Based on Prior Treatment Exposure: Updated Efficacy Analysis of Castor
Authors: Asher A. Chanan-Khan, Suzanne Lentzsch, Hang Quach, Noemi Horvath, Marcelo Capra, Roberto Ovilla, Jae-Cheol Jo, Ho-Jin Shin, Ming Qi, William Deraedt, Jordan Schecter, Himal Amin, Xiang Qin, Tineke Casneuf, Christopher Chiu, A. Kate Sasser, Pieter Sonneveld
Journal: Blood (2016)
Increasing colorectal cancer screening using a targeted, low literacy intervention
Authors: N. C. Dolan, M. R. Ferreira, N. S. Gorby, M. L. Fitzgibbon, A. Rademaker, D. Liu, T. C. Davis, B. P. Schmitt, M. S. Wolf, C. L. Bennett
Journal: Journal of Clinical Oncology (2004)

3596 Background: To evaluate whether a combined patient and physician intervention, targeted for a population with low literacy, increased adherence to colorectal cancer (CRC) screening. We also examined whether low literacy is associated with poorer knowledge and more negative attitudes towards CRC screening. Methods: Two VA Chicago general medicine firms were randomized to usual care or a combined patient-physician intervention. The patient component included a low literacy educational brochure and video. The physician component included an educational workshop and quarterly sessions with feedback on physician screening recommendations and patient adherence. Patients were male Veterans, age 50 and older, who had not received screening. A subset of patients was surveyed about knowledge and attitudes regarding CRC and their literacy level was assessed. Results: 979 patients were in the intervention firm, 941 patients in the usual care firm. Mean age was 67.8 years; 44% were white, 50% were African-American. Thirty-six percent of the 377 men surveyed had a literacy level ≤ 8th grade (inadequate literacy). Men with inadequate literacy were less likely to have heard about CRC (91.2% vs. 97.5%, p=0.006), and to know about screening tests (41.6% vs. 59.1%, p=0.0001), and were more likely to feel FOBT was messy (26.7% vs. 13.3%, p=0.008), or inconvenient (28.7% vs. 18%, 0.05). Overall, after 6–18 months of follow-up, there were higher rates of physican screening recommendations (76% vs. 70%, p=0.038) and completed screening (41% vs. 33%, p=0.008) in the intervention arm compared to the usual care arm. The intervention had a much greater effect on completion of screening among men with inadequate literacy (55.8% intervention vs. 32.1% control, p=0.007) compared to those with adequate literacy (40.2% intervention vs. 37.2% control, p=0.67). Conclusions: Low literacy is associated with poorer knowledge and more negative attitudes toward CRC screening and may be an overlooked screening barrier. This intervention, targeted to men with low literacy, significantly increased CRC screening among Veterans, especially those with inadequate literacy. No significant financial relationships to disclose.
Bevacizumab failure in glioblastomas.
Authors: Ghazaleh Tabatabai, Joerg Felsberg, Michael Sabel, Silvia Hofer, Manfred Westphal, Michael Weller, Guido Reifenberger
Journal: Journal of Clinical Oncology (2012)

2067 Background: Bevacizumab has been approved for the treatment of recurrent glioblastoma in various countries. The phase III registration trial assessing the addition of bevacizumab to standard chemoradiotherapy in newly diagnosed glioblastomas has completed recruitment. Salvage treatment of glioblastoma patients after bevacizumab failure, however, is commonly not successful. In the present study, we aimed at characterizing histological and molecular characteristics associated with glioma recurrence after bevacizumab. Methods: Paired tissue samples from primary and recurrent tumors obtained from 12 patients with glioblastoma (n=11) or anaplastic astrocytoma (n=1) before and after bevacizumab treatment, and 14 non-bevacizumab-treated patients as a reference group, were analyzed for histological features as well as molecular markers. Clinical records and magnetic resonance images were reviewed. Results: Histologically, recurrent tumors after bevacizumab showed more commonly a decreased blood vessel density and reduced glomeroloid microvascular proliferations when compared to recurrent tumors after conventional radiochemotherapy. In contrast, tumor cellularity and proliferation rate were similar. Distant relapse was more common in bevacizumab-treated patients. Molecular genetic studies of the respective tissue specimens are currently under way. Conclusions: Histological and molecular analyses of tumor tissue samples from glioma patients before and after bevacizumab treatment, combined with thorough clinical and radiological correlates, may provide hints for therapy escape mechanisms that can then be validated in preclinical models.
Global Epigenomic Analysis of Primary Human Pancreatic Islets Provides Insights into Type 2 Diabetes Susceptibility Loci
Authors: Michael L. Stitzel, Praveen Sethupathy, Daniel S. Pearson, Peter S. Chines, Lingyun Song, Michael R. Erdos, Ryan Welch, Stephen C.J. Parker, Alan P. Boyle, Laura J. Scott, NISC Comparative Sequencing Program, Elliott H. Margulies, Michael Boehnke, Terrence S. Furey, Gregory E. Crawford, Francis S. Collins
Journal: Cell Metabolism (2010)
Detection of EGFR mutations of serum circulating DNA.
Authors: Zongfei Li, Yaling Dou, Yong Qin, Weichen Xu, Zhen Yang, Yi Zhuang, Tao Wang, Yingchun Xu, Qiang Zeng
Journal: Journal of Clinical Oncology (2014)

11094 Background: As one of the EGFR-targeted drugs, EGFR tyrosine kinase inhibitors (TKI) play important roles in the treatment of NSCLC patients. It was established that EGFR mutation in tumor is a reliable marker for cancer response to EGFR-TKI. Herein, we assessed the concordance of EGFR mutations in serum circulating DNA (ctDNA) and tumor, and the possibility to predict the efficacy of EGFR-TKI by blood test. Methods: Samples (tissue and serum) from 404 NSCLC patients were analyzed retrospectively. EGFR mutations (exons 18-21) of tumor tissues and serum ctDNA were analyzed by sequencing and MCA-qASA assay respectively. MCA-qASA assay combines melting curve analysis and allele specific qPCR, which is expected to carry advantages of both. Results: We assess MCA-qASA assay first; the assay is capable to detect mutated DNA with low abundance (0.1 ng/μL) and low mutation rate (0.01%), probably the lowest ever. As summarized in the Table, among 123 tumor samples with EGFR mutations determined by DNA sequencing, we found 99 samples carrying EGFR mutations in their corresponding serum samples. We only found 15 serum samples carrying EGFR mutations among those whose corresponding tumor tissue samples did not carry EGFR mutations determined by DNA sequencing. The sensitivity and specificity for serum ctDNA EGFR mutation test using MCA-qASA assay as an alternative method for tumorous EGFR mutation test by DNA sequencing are 80.5% (99/123) and 94.7% (266/281) respectively. Kappa coefficient and Youden’s index are 0.767 and 75.2% respectively. Conclusions: EGFR mutation occurrences are consistent in serum ctDNA and tumor tissues, with Youden index as high as 75.2%, which is the highest reported ever, which is ascribed to the high sensitivity and specificity of the MCA-qASA assay. We propose ctDNA EGFR mutation test for NSCLC patients without tumor tissues before the medication of EGFR-TKI. Comparison of EGFR-mutation status of NSCLC tumor tissues and serum ctDNA. DNA sequencing - tumor Total Mutation-positive Wild-type MCA-Qaca - Serum Mutation-positive 99 15 114 Wild-type 24 266 290 Total 123 281 404
Randomized trial of a physical activity intervention in patients with metastatic breast cancer.
Authors: Jennifer A. Ligibel, Anita Giobbie-Hurder, Laura Shockro, Nancy Campbell, Ann H. Partridge, Sara M. Tolaney, Nancy U. Lin, Eric P. Winer
Journal: Journal of Clinical Oncology (2012)

9084 Background: Physical activity (PA) interventions improve fitness, functional capacity, and quality of life in patients with early-stage breast cancer. There are almost no data regarding the feasibility or potential benefits of PA in women with metastatic breast cancer (MBC). Our study evaluated the impact of a moderate-intensity PA intervention upon functional measures in patients with MBC. Methods: Participants were randomized 1:1 to a 16-week PA intervention or usual care control group. Eligibility included diagnosis of MBC, ECOG 0-1, and no active brain metastases. The intervention consisted of 4 weekly meetings with an exercise physiologist, followed by monthly in-person and weekly telephone-based meetings. The PA goal was 150 minutes per week. Baseline and 16-week evaluation included: modified Bruce treadmill test, 7-Day Physical Activity Recall Interview, and EORTC QLQ C-30 questionnaire. Results: 101 women enrolled between 9/06 and 3/11. Median age was 49 years, median time since diagnosis of MBC was 1.1 years, 48% of participants were on hormonal therapy and 42% on chemotherapy/biologic therapy. 69% completed all study measures (an additional 9% all but the final treadmill test). Attrition was higher in the intervention arm (30% vs. 16%, p=0.15). Outcome measures are shown in table below. Both groups experienced improvements in treadmill times. Intervention participants also reported improvements in physical functioning and increased minutes of weekly PA, with a trend toward significant differences between groups. Conclusions: Women with MBC participating in a PA intervention experienced consistent, but non-significant, trends toward improvements in functional measures. Our sample size was small, limiting power to evaluate the potential benefits of PA in women with MBC. Additional work is warranted, particularly since PA interventions appear feasible in this patient population. [Table: see text]