tbuckley/cabot-search huggingface dataset:
A feasible and time-efficient adaption of the neurosafe intraoperative frozen section technique to robotic-assisted radical prostatectomy.
Authors: Burkhard Beyer, Pierre Tennstedt, Katharina Boehm, Jonas Schiffmann, Thorsten Schlomm, Thomas Steuber, Markus Graefen, Alexander Haese
Journal: Journal of Clinical Oncology (2014)

147 Background: In robotic-assisted radical prostatectomy (RARP) intraoperative frozen sections are often avoided due to suspected difficulties in harvesting the prostate during this procedure, loss in pneumoperitoneum, increased blood loss and lacking impact on functional outcome. We demonstrate the technique, feasibility and beneficial impact of our NeuroSAFE technique on the rate of nerve-sparing (NS) in RARP and analyse the oncological outcome. Methods: We analyzed 1,570 consecutive patients undergoing RARP from 2004 to 2012. NeuroSAFE was done in 1,178 pts. We compared OR-time, blood loss, frequency of nerve-sparing (NS) and PSM in non-NeuroSAFE versus NeuroSAFE-RARP. The prostate was intraoperatively harvested via an extension of the camera trocar incision without undocking the system. Instrument arms were not undocked. Blood spillage from the dorsal vein complex due to loss of pneumoperitoneum was avoided by upward traction on the transurethral catheter. After prostate removal, pneumoperitoneum was reestablished by closing the extended incision and repositioning of the optical trocar. NeuroSAFE-procedure consisted of intraoperative bilateral frozen sections covering the entire contact area of the prostate and the neurovascular bundles. Results: There was no significant difference in blood loss (253.5±204.4 ml vs. 265.8±246.7 ml, p=0.49) and OR-time. (220 min ± 51 vs. 224 min ± 64, p=0.22). No complications associated with specimen harvesting occurred. NS-rate increased significantly with vs. without NeuroSAFE (overall 97% vs. 81%, pT2 99% vs. 90%, pT3a 94% vs. 74%, pT3b 91% vs. 30). PSM rate dropped significantly with NeuroSAFE (overall 16% vs. 24%, pT2 8% vs. 15%, pT3a 22% vs. 39%, pT3b 49% vs. 67%, all p&lt;0.05). Conclusions: We demonstrate a time-efficient adaption of the NeuroSAFE without patient side cart undocking, easy harvesting process, no increased blood loss or OR-time increased rate of nerve-sparing frequency and reduction of PSMs.
Are we systemically under treating cisplatin-eligible patients with muscle invasive bladder cancer (MIBC) who are undergoing bladder preservation by chemoradiotherapy?
Authors: Srikala S. Sridhar, Shaheena Bashir, Peter W. M. Chung, Alexandre Zlotta, Neil Eric Fleshner, Robert G. Bristow, Girish S. Kulkarni, Miriam Teich, Nimira S. Alimohamed, Gregory Lo
Journal: Journal of Clinical Oncology (2016)

417 Background: Neoadjuvant chemotherapy (NC) improves survival in MIBC pts regardless of local management-cystectomy or chemoradiation. NC use with chemoradiation has been limited as these pts are often elderly, frail and cisplatin-ineligible. But, as more fit, cisplatin-eligible pts opt for chemoradiation it is critical that we re-evaluate the feasibility and outcomes of giving NC followed by chemoradiation. Methods: We reviewed 25 MIBC pts with cT 2-4 N 0-1 M 0 , undergoing chemoradiation between 2008-2014 at the Princess Margaret and Durham Regional Cancer Centers. All pts received NC with gemcitabine-cisplatin (2-4 cycles) then external beam radiation (median dose 60Gy) with concurrent cisplatin. Toxicities were recorded using CTCAE v 3.0. Response and outcomes were assessed by cystoscopy and imaging. Median follow-up was 29.7 mos and 6 pts had &lt; 2 yrs of follow-up. Kaplan Meier analysis was used for survival. Results: Main reasons for a chemoradiation approach were pt preference 15/25 (60%) and comorbidities 10/25(40%). At diagnosis, median age was 69 (49-85), 76% were male, all were ECOG PS 0/1, median CrCl was 58.5 ml/min and 7/25 (28%) had hydronephrosis. CIS was seen in 10/25 (40%), LVI in 3/25 (12%) and node positivity in 2/25 (8%). All but 1 patient completed planned NC, where main Grade 3/4 toxicities as expected were neutropenia and infection. All planned radiotherapy and 83% of planned concurrent chemotherapy was given. Maximal TURBT was done in 76%. Cystoscopically post NC, 12/15 (80%) had a CR, 1/15 (7%) had CIS, and 2/15 (13%) had residual disease. Of the 12 pts with a CR, radiologically 4/12 had a CR, 2/12 had a PR and 6/12 had SD. Four pts required salvage cystectomy for local recurrence, 4 pts developed metastases and have died. Median OS was not reached, but the 2 yr OS rate was 73.8% (95% CI 50.3-87.4%). Conclusions: NC followed by chemoradiation, showed cystoscopic CR rates of 80% post NC and 2 yr OS rates of 73.8% suggesting this approach should be considered in cisplatin-eligible MIBC pts undergoing chemoradiation. Comparing outcomes between matched MIBC pts receiving NC and then chemoradiation or cystectomy also appears warranted.
A risk model for first cycle febrile neutropenia in cancer patients receiving systemic chemotherapy
Authors: G. H. Lyman, J. Crawford, D. A. Wolff, E. Culakova, M. S. Poniewierski, D. C. Dale
Journal: Journal of Clinical Oncology (2005)

8122 Introduction: Myelosuppression remains the major dose-limiting toxicity of cancer chemotherapy. A prospective, nationwide study was undertaken to develop and validate a risk model for febrile neutropenia (FN) in cancer patients receiving chemotherapy. Methods: More than 2,300 patients with cancers of the breast, lung, colon and ovary or lymphoma initiating a new regimen have been prospectively registered at 137 randomly selected sites. Data on at least 1 cycle of chemotherapy are available on 2,106. A standard regimen has been defined in 1,464 patients permitting an estimation of planned dose intensity (PDI). A logistic regression model for cycle 1 FN in those with known PDI was developed and test performance characteristics estimated. Results: Of 222 patients experiencing FN events, 125 (56%) did so in cycle 1 with prophylactic growth factors reported in only 3.5%. Major independent clinical factors in the risk model include: anthracycline chemotherapy (OR=7.80;P=.001); immune disorders (OR=5.14;P=.014); pretreatment neutropenia (OR=4.00;P<.001); elevated bilirubin (OR=3.73;P=.009); ECOG PS ≥2 (OR=2.84;P=.010); stage 1–2 disease (OR=2.66;P=.009); pretreatment lymphopenia (OR=2.51;P=.001); elevated alkaline phosphatase (OR=2.15; P=.012); pretreatment thrombocytopenia (OR=1.5;P=.024), and anemia (OR=1.43;P=.069). The risk model was adjusted for practice, planned dose intensity, BSA and patient demographics. The risk model accounted for over 80% of the variability (R2=0.829) with a c-statistic of 0.874 [0.847,0.902](P<.0001). Model discrimination was optimized for an estimated risk ≥5% distinguishing high and low risk groups with average cycle 1 FN risks of 20% and 1%, respectively. The model was associated with a sensitivity[±95%CL] of 93%[86–96], specificity of 66%[63–68], predictive value + and - of 20%[17–24] and 99%[98–100], respectively and diagnostic odds ratio of 22[12–43]. Discussion: Based on excellent test performance characteristics, the risk model identified patients at increased risk for first cycle FN for possible targeted prophylaxis with filgrastim or pegfilgrastim. Validation of the model in phase 2 of this ongoing registry study is currently underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen
Phase III trial comparing long-term versus short-term androgen deprivation combined with high-dose radiotherapy for localized prostate cancer: GICOR protocol DART01/05.
Authors: A. Zapatero, A. Guerrero, X. Maldonado, A. Alvarez, C. González San Segundo, A. Cabeza, V. Macías, F. Casas, A. Pedro-Olivé, S. Villa, A. Boladeras, M. L. Vazquez de La Torre, C. Martin de Vidales, F. A. Calvo
Journal: Journal of Clinical Oncology (2011)

4580 Background: Hormone therapy plus radiotherapy significantly decreases recurrences and mortality of patients affected by locally advanced prostate cancer (PCa). Controversy remains about the optimal duration of androgen deprivation (AD) when associated to high-dose radiotherapy (HDRT). This trial was designed to determine whether long-term AD (LTAD) is superior to short-term AD (STAD) in the setting of HDRT Methods: Eligibility included patients with cT1c-T3aN0M0 adenocarcinoma of prostate with intermediate and high risk factors according to NCCN criteria and PSA less than 100 ng/ml. All patients received 4 months of neoadjuvant and concomitant AD (STAD) + HDRT (minimum dose to the prostate 76 Gy) before randomization to adjuvant gosereline (LTAD) for two years. Stratification was performed according to risk group (intermediate risk [IR] versus high risk [HR]). Study endpoints included overall survival (OS), metastasis free survival (MFS), disease free survival (DFS) and biochemical-disease free survival (bDFS). Initial analysis of results is reported. Results: A total of 361 men were registered, of whom 180 were randomly assigned to STAD (97 HR and 83 IR) and 181 to LTAD (94 HR and 87 IR). Median isocenter radiation dose to the prostate was 78.0 Gy for both groups. Elective pelvic radiotherapy was administered in 28 patients treated with STAD and in 20 patients with LTAD. Demographic data, tumour and treatment characteristics were evenly distributed in the two arms. After a median follow-up of 30 months, 9 patients in the STAD group (2 intermediate risk and 7 high risk PCa) and none in the LTAD group had biochemical failure according to Phoenix definition (p=0.002). The median time to biochemical relapse was 28 months. Four patients developed distant metastasis (all of them in the STAD arm) and 3 patients have died from causes other than PCa. Grade ≥ 2 radiation related adverse effects in both arms were not statistically significant. Conclusions: Although preliminary, the results of the present study suggest that LTAD could be superior to STAD in patients with unfavourable PCa treated with HDRT.
Migratory and specific antitumoral immunostimulatory capacities of new dendritic cells generated with IL-3 and IFNβ in melanoma patients
Authors: M. Trakatelli, M. Toungouz, D. Blocklet, L. Gordower, M. Laporte, L. Mortier, S. Goldman, P. Coulie, M. Goldman, T. Velu
Journal: Journal of Clinical Oncology (2005)

2524 Background: Although some encouraging results were obtained with the standard dendritic cells (DC) generated with GM-CSF and interleukin (IL)-4, further improvements are clearly needed. DC generated with type-I interferon were found to have interestingly high expression of MHC and costimulatory molecules, of migration-enhancing CCR7 chemokine receptor, of Th-1 response-promoting IL-15 cytokine, and of IFN-α in response to poly I:C. They were shown to induce efficient T cell responses against tumor antigens in vitro. Herein, we investigated the ability of DC generated in interferon (IFN)-β and IL-3 (DC I3) and activated by poly I:C to migrate and to induce CD8+ T cell responses against the NA17-A2 tumor peptide in patients (pts) with stage III or IV melanoma. Methods: DC were generated from adherent PBMC by a 6-day culture with IL-3 and IFN-β followed by overnight maturation with poly I:C and loading with NA17.A2 peptide. 9 HLA-A2 pts with stage III or IV NA17+ melanoma received 3 DC I3 vaccines (weeks 0, 3, 6) (20x10E6 i.d./s.c. and 2.5x10E intranodal). Anti-NA17-A2 CD8+ T cell responses were measured using mixed lymphocyte-peptide culture under limiting dilution conditions followed by enumeration of cells stained with NA17-HLA-A2 tetramers. DC labeling with In-111 enables to study cell migration after injection. Results: We found that the DC I3 vaccine was well tolerated with only minor and transient flu-like symptoms and local inflammatory reaction at the site of injection. In 7 out of the 9 pts, isotopic imaging documented DC migration from the injection site to draining lymph nodes. Anti-NA17-A2 CD8+ T cell responses were found in 4 out of 7 pts: from <0.6 (min pre-vaccine) to 21 (max post-vaccine) specific T cells/10E6 CD8+ lymphocytes. Among 4 pts with no evidence of disease (NED), 3 remained free of disease at >9, >11 and >13 months, and among 5 pts with evaluable lesions, one had stable disease (SD) (>6mo). All of these patients with stable NED (but one pt) and SD were in the T cell responder group. Conclusions: DC generated in type-I IFN might represent an interesting alternative to DC generated in IL-4 and GM-CSF for the development of more efficient cellular vaccines against melanoma. No significant financial relationships to disclose.
Stimulation of the B-Cell Receptor (BCR) Induces Successive Activation of STAT3 and Nuclear Factor-Kappa-B in CLL Cells
Authors: Uri Rozovski, David M. Harris, Ping LI, Zhiming Liu, Alessandra Ferrajoli, Jan A Burger, Philip Thompson, Nitin Jain, William Wierda, Michael Keating, Zeev Estrov
Journal: Blood (2015)
The ZOTECT study: Effect of intravenous zoledronic acid on bone metabolism in patients with metastatic bone disease in prostate cancer (PC) and breast cancer (BC).
Authors: P. Hadji, M. Ziller, T. Maurer, M. Muth, A. Ruebel, C. May, K. Birkholz, J. E. Gschwend
Journal: Journal of Clinical Oncology (2011)

4614 Background: Approximately 75% of patients (pts) with advanced BC or PC will develop bone metastases (BM), which influence bone metabolism and increase the incidence of skeletal related events (SREs). Therapy with zoledronic acid (ZOL) reduces the incidence and delays the onset of SREs. As recent studies showed strong correlations between the level of bone markers and SREs, the primary objective of this study was to access the course of several bone markers under therapy with ZOL and the correlation with disease outcomes. Methods: This prospective, single arm, open-label study investigated the effect of ZOL 4 mg IV q4wks given for 4 months on bone markers (CTX, PINP, RANKL, OPG) in PC and BC pts with BM. After 12 months a final follow-up was conducted. Secondary objectives included the relationship between metastatic sites assessed by bone scan and the level of bone markers at study entry, pain assessment (VAS) and analgesics score, the relationship between pain and SREs and the course of bone markers, SRE rate, quality of life (EORTC QLA-30/BR-23), Estradiol and PSA changes. Results: 99 BC pts and 301 PC pts were recruited at 98 German sites between May 06 and August 08. The course of OPG and RANKL was not significantly influenced by ZOL, however the level of PINP and CTX significantly decreased to stable values (p<0.0001). No significant differences between BC and PC pts were observed. Pts with high EOD (extension of disease) score had higher PINP and CTX baseline values and also showed a reduction in PINP and CTX. Average PSA values of PC pts were reduced from 168.5 to 92.5 µg/l. A total of 13 SREs occurred in 11 pts. Quality of life was not influenced under therapy. A slight pain reduction with correlation to the bone markers was detected. ZOL was generally well tolerated and adverse events were in accordance with the known safety profile of ZOL. Conclusions: 4 months therapy with ZOL significantly reduced the level of PINP and CTX in 400 BC and PC pts with BM. This result confirms the reduction of bone metabolism under ZOL resulting in prevention of SREs. This is the first study which investigated the effect of ZOL on OPG and RANKL and it showed no significant effect on these markers.
Processes of discontinuing chemotherapy for metastatic non-small cell lung cancer at the end of life.
Authors: William F. Pirl, Joseph A. Greer, Kelly Irwin, Inga Tolin Lennes, Vicki A. Jackson, Elyse R. Park, Daisuke Fujisawa, Alexi A. Wright, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2014)

96 Background: Administration of chemotherapy close to death is widely recognized as poor quality care. The goals of this study were to describe the processes of how chemotherapy is discontinued and examine their relationships with timing before death, hospice referrals, and terminal hospitalizations. Methods: We reviewed electronic health records of a prospective cohort of 151 patients with newly diagnosed metastatic non-small cell lung cancer (NSCLC) who participated in a randomized trial of early palliative care. Chemotherapy treatment during the final regimen was qualitatively analyzed, identifying categories of discontinuation processes. We then quantitatively investigated predictors and outcomes of the discontinuation process categories. Results: 144 patients had died, with 81 and 48 receiving intravenous (IV) and oral chemotherapy as final regimens, respectively. Five discontinuation processes were identified: definitive decisions; deferred decisions (breaks); disruptions for radiation therapy; disruptions due to hospitalizations; and no decisions. For patients receiving IV chemotherapy, definitive decisions were least frequent (19.7%), while disruptions due to hospitalizations were most frequent (27.2%). The different processes occurred at significantly different times before death; and often hospice referrals occurred months after chemotherapy discontinuation. Deferred decisions, or “breaks,” occurred at the longest interval before death, but definitive decisions resulted in greatest hospice utilization. Among patients receiving oral chemotherapy, 83.3% were switched from IV to oral as their final regimen, sometimes concurrent with or even after hospice referral. Conclusions: Patients with metastatic NSCLC stop their final chemotherapy regimen via different processes, which significantly vary in time before death and in subsequent end-of-life care.
Concordance between patient and family caregiver reports of quality of colorectal cancer care.
Authors: Rachel D. Havyer, Michelle van Ryn, Patrick Wilson, Joan M. Griffin
Journal: Journal of Clinical Oncology (2016)

187 Background: Patient-reported evaluations of interpersonal quality of care are essential elements of quality of cancer care assessment. At times, patients may be unable to report themselves on their care experience and systems may rely on proxy reports. The validity of this approach is dependent on the degree to which family caregiver assessments are concordant with patient assessments. Methods: A VA cohort of colorectal cancer (CRC) patients and their caregivers both completed a self-administered questionnaire on the quality of VA cancer care in 3 specific domains: surgery, chemotherapy overall and chemotherapy nursing care, all measured on a 5-point Likert scale. Because the kappa statistic penalizes skewed distributions which are commonly seen in patient satisfaction reports, agreement between patients and caregivers on perceptions of quality care were measured using Gwet’s AC2 statistic. Stratified analyses on caregiver burden, race, education, and age as well as patient’s stage of disease were used to assess variation in agreement. Results: 417 caregiver-patient dyads completed the survey (70% response rate), of whom 362 (86.8%) had surgery and 195 (46.8%) had chemotherapy. Overall agreement was high for the 3 quality of care domains: AC2 (95% CI): 0.870 (0.838, 0.903) for surgery, 0.835 (0.786, 0.884) for chemotherapy overall and 0.906 (0.868, 0.944) for chemotherapy nurses. Stratified analyses of agreement showed particular populations of higher or lower agreement; however the findings were inconsistent across the three domains and most were not statistically significant. Patients with lower stage (I-II) had higher agreement than higher stages (III-IV) (AC2: 0.967 and 0.879 respectively, P = 0.006) but only in the chemotherapy nurses domain. For the surgery domain, age was the only significant difference in agreement (0.816, 0.912, and 0.838 for &lt; 50, 51-65, and &gt; 65 respectively, P = 0.03). Conclusions: Family caregiver reports on the quality of CRC care were highly concordant with patient reports. Therefore, family caregivers may be able to provide reasonable proxy report on measures of quality of cancer care when patient reports are unavailable.
Comparing accuracy of digital rectal exam finger patterns.
Authors: T. S. Floyd, G. C. Bailey, C. Kowalik, A. Lee, G. J. Gerling, T. L. Krupski
Journal: Journal of Clinical Oncology (2011)

e12011 Background: As prostate cancer is the second leading cause of cancer mortality in men, mastering the digital rectal exam (DRE) should be part of a physician’s skill set. The Virginia Prostate Exam Simulator (VPES) is designed to train health care practitioners to master the DRE. The VPES presents disease scenarios of varying difficulty and provides feedback on finger patterns. We sought to discover if there is uniformity in finger patterns used and, if so, the accuracy of these disparate DRE patterns. Methods: Three groups of participants (18 NP students (NPS), 16 resident physicians (RP), and 11 urologists (US)) participated in an IRB approved psychophysical methods of limits experiments with the VPES. During methods of limits testing designed to authenticate the tactile realism of simulated prostate abnormalities, the VPES recorded participant finger pattern and pressure. Each participant was blinded to the recording while performing DREs on four simulated pathology scenarios. The VPES recorded the global finger patterns (GFP) and local finger patterns (LFP) employed by the examiners. Variations in GFP were divided into four main categories: U, V, L, and line patterns. LFP was parsed into three discrete categories: tapping, vibration, and sliding. The patterns and accuracy of each participant group were compared. Results: The GFP of NPS were the V (44%) and line (35%) patterns. RP predominantly employed the line (42%) but were equally likely to use the V (28%) or L (28%) patterns. US used a line GFP almost exclusively (95%). In terms of LFP, NP students used vibration (48%) and tapping (35%). The dominant LFP of RP was the vibration (50%) while tapping and sliding were each used 25% of the time. The LFP of US could not be identified 45% of the time. When a pattern was identified, it was the vibration (55%) pattern. NPS, RP, and US accurately detected abnormalities 28%, 42%, and 26% of the time, respectively. Conclusions: Urologic surgeons showed less variation in the GFP. This suggests a degree of uniformity in DRE technique within the most experienced group of participants. It is unclear, however, whether this is the most accurate technique. More work is necessary to determine the optimal DRE technique that should be used as a model for instructing health care practitioners.