tbuckley/cabot-search huggingface dataset:
Phase II study of a combination of radiofrequency ablation (RFA) and systemic chemotherapy for patients with colorectal liver metastases
Authors: C. Burkart, A. Raible, M. Fuchs, C. Bokemeyer, R. Teichmann, S. Clasen, J. T. Hartmann, P. L. Pereira
Journal: Journal of Clinical Oncology (2005)

3716 Background: More than 25% of patients (pts) with colorectal cancer (CRC) develop metastases confined to the liver (LM) without extra hepatic spread. In these pts surgery is the mainstay of treatment; however, not all pts are suitable for a surgical approach. This study has investigated the toxicity and efficacy of percutaneous RFA in combination with FOLFOX-4 chemotherapy in pts with inoperable LM of CRC. Methods: Pts with a maximum of 5 non-resectable LM up to a maximal size < 5 cm without extra hepatic spread were allocated to 12 cycles of systemic chemotherapy with FOLFOX-4 (every 2 wks: oxaliplatin 85 mg/sqm IV, D 1; folinic acid 200 mg/sqm IV over 2h and 5-FU 400 mg/sqm IV bolus followed by 600 mg/sqm IV 22h-infusion, D 1 and 2). Percutaneous RFA with internally cooled electrodes (Cool Tip, Valleylab, Boulder, Co) controlled by simultaneous CT or MRI guidance was performed after completion of 4 cycles and repeated if required. Follow-up investigations including dynamic MRI have been done after every 4 cycles of FOLFOX-4, and every three month after stop of treatment. Results: Thirteen pts have prospectively entered the study. Pts’ characteristics: m/f 9/4; median age 63 yrs (range, 44 - 78); primary tumor colon 9, rectum 4. Five pts were diagnosed with synchronous and 7 pts with metachronous LM with a median interval of 8 mos. AJCC classification at initial diagnosis: stage II/III/IV 4/4/5. Median no. of LM: 3 (range, 1 - 5), size range 7 - 48 mm. The median follow-up was 14.5 mos (range, 2 - 36). WHO Grade 4 leucocytopenia occurred in 1 pt; Grade 3 toxicity: diarrhoea 2 pts, infection 2 pts, peripheral NP 1 pt, pain 1 pt. Of the 12 pts, who have completed the protocol 8 pts achieved a complete remission (CR) lasting 9.5 mos (range, 2 - 32). 2 pts attained a partial remission and 1 pt had intrahepatic progressive disease. Conclusions: In a well defined subgroup of pts with LM of CRC origin the combination of RFA and systemic chemotherapy is a feasible approach with a low toxicity and complication rate. This combination therapy can achieve complete responses without an operative approach. Median duration of remissions warrants further investigation of a combined treatment approach in controlled clinical trials. No significant financial relationships to disclose.
Monitoring and switching patterns in chronic myelogenous leukemia (CML) pts treated with imatinib (IM): A chart review analysis.
Authors: Lei Chen, Annie Guerin, Clemence Aberki, Eric Q. Wu, Solveig Ericson, Elias Jabbour
Journal: Journal of Clinical Oncology (2012)

6594 Background: The objective of this study is to evaluate compliance to National Comprehensive Cancer Network (NCCN) and European LeukemiaNet (ELN) guidelines regarding monitoring frequency and switching practices in CML patients (pts) treated with IM in community practices. Methods: Physicians treating CML pts were selected from 28 community practices throughout the USA. Each physician reviewed and extracted up to 15 pt charts of CML pts in chronic phase not previously enrolled in clinical trials. Pts were required to have initiated 1st-line IM between 1/2006 - 10/2010. Data on 1st-line IM treatment response monitoring frequency and outcomes, and corresponding therapy switching patterns were extracted. Results: Information was collected on treatment monitoring and response from a total of 297 pt charts. Median IM duration was 320 days. Percentages of pts monitored according to both guidelines are reported. In addition, the proportion of pts who missed milestones and the proportion of pts who did not switch to a 2nd-line tyrosine kinase inhibitor (TKI) when they missed milestones are reported. Conclusions: There is considerable undermonitoring of CML pts receiving IM, which is likely to result in a significant portion of pts with suboptimal response left undetected. The switching rate to 2nd-line TKI among pts with suboptimal response to IM is much lower than recommended by either NCCN or ELN guidelines. [Table: see text]
Impact of prior chemotherapy on progression-free survival in patients (pts) with advanced pancreatic neuroendocrine tumors (pNET): Results from the RADIANT-3 trial.
Authors: R. F. Pommier, E. M. Wolin, A. Panneerselvam, S. Saletan, R. E. Winkler, E. Van Cutsem
Journal: Journal of Clinical Oncology (2011)

4103 Background: In the phase III RADIANT-3 trial, everolimus (EVE), an oral mTOR inhibitor, demonstrated superior progression-free survival (PFS) with a median of 11.0 vs 4.6 mo for placebo (PBO) (HR=0.35; 95% confidence interval, 0.27-0.45; P<0.0001) in pts with advanced pNET (ESMO 2010, Abstract #LBA9). An exploratory analysis of prior chemotherapy use and PFS from the RADIANT-3 trial is presented. Methods: Pts with progressive advanced low- or intermediate-grade pNET were randomized to EVE 10 mg/d orally (n=207) or PBO (n=203); both arms received best supportive care. The primary endpoint was PFS per central review (RECIST v1.0). Pts were stratified by use of prior vs no prior chemotherapy. Results: Overall, 206/410 (50%) pts received prior chemotherapy. Prior chemotherapy use was balanced in both arms: 104/207 (50%) EVE pts vs 102/203 (49%) PBO pts. No difference was observed in baseline characteristics (age, sex, race, tumor type, histologic grade) and baseline tumor biomarker levels for pts receiving prior chemotherapy vs those without. Time since initial diagnosis was >2 years for 147 (71%) pts with prior chemotherapy vs 98 (48%) pts without prior chemotherapy. A higher proportion of pts with prior chemotherapy also had received prior somatostatin therapy (54% prior chemotherapy vs 45% no prior chemotherapy). A positive treatment effect with EVE was observed in pts both with and without prior chemotherapy. EVE significantly prolonged PFS vs placebo in pts with prior chemotherapy (HR=0.34; P<0.0001) and those without prior chemotherapy (HR=0.42; P<0.001). Median PFS with EVE for pts with prior chemotherapy was 11.0 mo vs 11.4 mo for those without prior chemotherapy (HR=1.120; 95% CI, 0.768-1.634; P=0.56). Median PFS with PBO for pts with prior chemotherapy was 3.2 mo vs 5.4 mo for those without prior chemotherapy (HR=1.3; 95% CI, 0.990-1.828; P=0.054). Conclusions: EVE demonstrated significantly longer median PFS than PBO in pts with advanced pNET, regardless of prior chemotherapy use. These results suggest that EVE should be considered a treatment option for pNET pts, including those without prior chemotherapy.
A phase II study of afatinib in patients (pts) with metastatic human epidermal growth factor receptor (HER2)-positive trastuzumab refractory esophagogastric (EG) cancer.
Authors: Yelena Yuriy Janjigian, Geoffrey Yuyat Ku, David H. Ilson, Michelle S. Boyar, Marinela Capanu, Joanne F. Chou, David Paul Kelsen, Tooba Imtiaz, Michael F. Berger, Efsevia Vakiani
Journal: Journal of Clinical Oncology (2015)

59 Background: Trastuzumab combined with chemotherapy is the standard of care for pts with HER2+ EG cancer. Resistance to trastuzumab clearly emerges in this population. Afatinib, a potent ErbB Family Blocker, induced tumor regression in MSKCC HER2+ patient derived xenografts (PDX). This study assesses safety and preliminary efficacy of afatinib in patients with trastuzumab refractory EG cancer. Methods: Pts with HER2+ (IHC 3+ or FISH&gt;2.0) EG adenocarcinoma, after progression on trastuzumab, received oral afatinib 40 mg daily. Archival pre-trastuzumab tissue, tumor biopsy after progression on trastuzumab and after 1 week on afatinib is mandated on protocol for next generation sequencing (NGS), proteomics and establishment of PDX. The primary endpoint-overall clinical benefit at 4 months: stable disease (SD) or partial response (PR). Results: 20 pts treated with afatinib; median age 61, KPS 80; median 2 (1 to 4) prior trastuzumab regimens, 67% of tumors IHC3+; 33% IHC2+/FISH&gt;2.0. Common adverse events included: rash or dry skin (Grade 1/2:80%), diarrhea (Grade 1/2:60%), nausea/vomiting (grade 1/2:40%) fatigue (grade1/2: 25%). To date, 19 pts evaluable for response, 2 PRs and 6 SD, 42% disease stabilization rate (PR+SD) at 4months (4 to 13 mos). PDXs established from biopsies of 7 pts. EGFR amplification was detected in the tumor of 2 pts with PRs and 1 of 6 pts with SD. Recurrent PIK3CA, ERBB3 and MTORmutations were observed. Conclusions: Afatinib shows clinical efficacy and is well tolerated in patients with trastuzumab refractory, heavily pretreated EG cancer. Enrollment has now begun in an afatinib + trastuzumab cohort. Efforts to elucidate the mechanisms of trastuzumab resistance including validation of potential drivers of trastuzumab resistance using HER2+ PDXs are ongoing. Updated molecular and clinical data will be presented. Clinical trial information: NCT01522768.
Predictors of clinically significant bleeding in colorectal cancer: Results from a global prospective cohort study.
Authors: Davendra Sohal, Nicole Maria Kuderer, Frances A. Shepherd, Ingrid Pabinger, Giancarlo Agnelli, Howard A. Liebman, Eric Vicaut, Guy Meyer, Gary H. Lyman, Alok A. Khorana
Journal: Journal of Clinical Oncology (2014)

558 Background: Bleeding is an important complication among patients with colorectal cancer but its prevalence and predictors are incompletely understood. We evaluated data from a global prospective cohort study to define the incidence, predictors and consequences of bleeding in patients undergoing adjuvant or palliative treatment for colorectal cancer. Methods: CANTARISK was a prospective, non-interventional, international cohort study in patients with lung and colorectal cancer on chemotherapy, the patients were not on long term anticoagulation. Clinical data were collected at baseline, and at 2, 4, and 6 months. All data were compiled centrally and analyzed after the study had closed. Statistically significant univariable associations and a priori variables were tested in multivariable models; adjusted odds ratios (OR) with confidence intervals (CIs) are presented. Results: A total of 1,789 patients with colorectal cancer were enrolled from 2011-12. Median age was 62 years; 61% were male; 71% were Caucasian and 18% were Asian; 37% were from Europe, 28% from North America, 23% from Asia, and 12% from South America. Ninety-two (5.14%) patients experienced at least one bleeding episode during antineoplastic treatment, ranging from 1 to 5 episodes each, with a total of 109 episodes. The gastrointestinal tract was the source in 49 (45%) episodes. Approximately one-third of episodes (n=34, 31%) necessitated transfusion, but only 1 (0.9%) was fatal. In multivariate analysis, independent predictors of bleeding included presence of metastases (OR = 2.13, 95% CI=1.25-3.65) and surgery within prior 6 months (OR = 3.66, 95% CI=1.78-7.47) but not intact primary tumor (OR = 1.57, 95% CI=0.99-2.51). Notably, age, baseline blood counts, ECOG performance score, and anticoagulant use during study were not associated with bleeding. Conclusions: Bleeding is prevalent amongst patients with colorectal cancer receiving systemic chemotherapy. Post-surgical patients and those with metastatic disease appear to be at highest risk. Resection of the primary tumor does not appear to significantly alter risk.
Network meta-analysis (MA) of taxane-based neoadjuvant chemotherapy (NCT) for locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).
Authors: J. McGhie, E. Winquist
Journal: Journal of Clinical Oncology (2010)

5568 Background: Concurrent platinum-based chemoradiation (CRT) is a standard treatment for LA SCCHN based on results of the MACH-HN MA (Pignon, 2009). Cisplatin/5-fluorouracil (PF) NCT has shown less survival benefit. TPF combines a taxane with PF and has shown survival benefits as NCT in randomized trials (RCTs). A Network MA of TPF NCT in LA SCCHN was done to examine its relative benefits compared to CRT alone. Methods: A literature search for RCTs studying TPF NCT was done using electronic databases. Eligible RCTs compared TPF NCT+CRT with CRT alone or with PF NCT+CRT. Outcomes of interest included overall, progression-free and laryngectomy-free survival (OS, PFS, LGFS); overall and complete response rates (RR and CR); toxicity and health-related quality of life (QoL). The hazard ratio (HR) or odds ratio (OR) were used for statistical pooling. Pooled data comparing CRT alone or PF NCT+CRT to RT were available from the MACH-HN MA. TPF NCT+CRT was compared to RT alone by 2 independent routes using the method of Fisher et al (2001). Results: Six eligible RCTs providing 7 comparisons (n=1,994) were identified. Five were published and one was available as a meeting abstract only. Two RCTs compared TPF NCT+CRT to CRT: pooled OS HR 0.83 (0.61-1.11) and PFS HR 0.74 (0.60-0.92) favored TPF. Five RCTs compared TPF NCT+CRT to PF NCT+CRT: pooled OS HR 0.77 (0.64-0.86), PFS HR 0.66 (0.60 – 0.72) and LGFS HR 0.52 (0.43 – 0.64) (2 RCTs) favored TPF. Pooled toxic death rates were similar for TPF, PF, and CRT (2.0, 2.8, and 2.4%). RR with TPF was similar to PF (OR 1.2 [0.95–1.5]); however, CR rates before and after CRT were higher with TPF. TPF NCT+CRT was compared to RT alone using 2 independent routes of indirect comparison. OS HRs were 0.67 (0.46-0.96) and 0.69 (0.59-0.81). Conclusions: TPF NCT+CRT (HR 0.67-0.69) is associated with more OS improvement than CRT (HR 0.81) relative to RT alone. Larynx preservation rates are higher than with PF NCT+CRT and toxic death rates do not appear increased. These data support a strategy of TPF NCT+CRT in subgroups of LA SCCHN pts able to tolerate a more aggressive treatment approach who are at high risk for either cancer mortality or laryngectomy despite standard CRT. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
Towards intraoperative microCT imaging of breast cancer resections.
Authors: Phil Salmon, Alexander Sasov
Journal: Journal of Clinical Oncology (2015)

147 Background: MicroCT analysis of breast cancer resections was shown by Rong et al. [Tang R et al. (2013) The Breast Journal 19(5), 485-489; Tang R et al. (2013) Breast Cancer Research and Treatment 139(2), 311-316] to attain equivalence with pathology-histology in the assessment of positive margin. However, Rong et al. noted that the 14 minute scan cycle time–7 minutes scan, 7 minutes reconstruction–was a potential limitation. Methods: This paper reports the development of microCT instrumentation and software to address this and other technical challenges. These include (a) reducing the scan-reconstruction time, (b) a small desktop footprint, (c) reconciling optimal soft tissue contrast with minimizing artefacts from inserted metal wires and large calcifications, and (d) features to aid hospital workflow such as a barcode reader, an optical camera to photograph the specimen, and process automation. Scans were done with the purpose-built SkyScan1275 table-top microCT scanner, on frozen anonymous archived breast cancer resection samples. Results: Minimum scan time retaining acceptable image quality was 3 minutes. Reconstruction time was reduced to less than a minute by PC graphics accelerators. Scan-reconstruction cycle time can thus be &lt; 4 minutes. A small (105 x 64 cm) desktop footprint with a weight of 160 kg, requiring only a sturdy laboratory desk, has also been attained in this scanner. Artefacts from large calcifications and metal wires were reduced to non-obtrusive levels by scanning with 1mm aluminum filter and software techniques. An automated scan sequence was developed with sample holders recognized electronically in the scanner. On pressing a single button, the scanner automatically goes to the appropriate magnification and sample height, scans the sample, then reconstructs the scan with preset parameters, and finally opens the reconstructed dataset in software for interactive volume-rendered viewing. Sample barcode reading and optical photo taking can be included in this auto-scan sequence. Conclusions: These developments bring microCT nearer to realizing its potential as an intraoperative “back-table” technique in breast cancer surgery to obviate revisions and improve the surgery process and outcome.
Dignity therapy for advanced cancer patients.
Authors: Ann Marie Dose, Joleen Marie Hubbard
Journal: Journal of Clinical Oncology (2015)

225 Background: Recent guidelines promote simultaneous palliative care with active treatment for advanced/metastatic cancers, including interventions addressing all quality of life (QOL) domains. Dignity Therapy (DT) is an intervention demonstrating promising outcomes at end of life. It has not been offered earlier to cancer patients nor paired with a Life Plan (LP) intervention. The purpose of this phase I/II feasibility study was to determine the feasibility, acceptability and selected patient-reported outcomes (PROs) of the Dignity Therapy/Life Plan intervention and pilot study methods in advanced pancreatic cancer patients pursuing chemotherapy. Methods: DT is a brief psychotherapeutic intervention consisting a focused life review/values clarification delivered during 3 outpatient oncology clinic visits. Interviews were audiotaped, transcribed, and edited to produce a Generativity Document, which the patient can later share with family. Life Plan is a type of “bucket list”, where patients document future hopes/dreams. Feasibility was evaluated, distress measured with the Distress Thermometer (0-10 scale) and QOL measured with the Linear Analogue Self Assessment (LASA, 0-10 scale). Baseline scores of distress and QOL were compared with scores after the intervention, 4-6 weeks later (Time 2 [T2]). Results: Ten pancreatic adenocarcinoma patients enrolled, mean age 63. Two-thirds of those recruited enrolled; 90% completed all study procedures. Two-thirds were satisfied/very satisfied with DT/LP, and 78% found study participation worthwhile, DT/LP timing to be just right and would recommend DT/LP to others. QOL improved (baseline mean = 7.0; T2 = 7.25). Distress scores improved (Baseline mean = 6.13; T2 = 5.63). Conclusions: Distress and QOL modestly improved from baseline to T2. Baseline scores were collected before patients had begun any chemotherapy, therefore any improvements while undertaking aggressive chemotherapy are noteworthy. Participants felt the intervention was acceptable and better than they had expected. Conducting DT/LP in an outpatient oncology setting for newly diagnosed pancreatic cancer patients is both feasible and acceptable. Outcomes are encouraging for future larger scale trials. Clinical trial information: NCT02132325.
Updated phase I results of a phase I/II trial of BNC105P with everolimus in patients with metastatic renal cell carcinoma (mRCC).
Authors: Thomas E. Hutson, Long H. Dang, Richard C. Lauer, Alexander Starodub, Ralph J. Hauke, Matt D. Galsky, Kathryn A. Bylow, Charles Lance Cowey, David C. Bibby, Gabriel Kremmidiotis, Elizabeth E. Doolin, Tina C. Lavranos, Guru Sonpavde, Theodore Logan, Noah M. Hahn, Christopher Sweeney, John Sarantopoulos
Journal: Journal of Clinical Oncology (2013)

397 Background: BNC105P is an inhibitor of tubulin polymerization. In vivo exposure to BNC105P leads to selective damage of tumor vasculature in both primary and metastatic lesions, causing disruption of blood flow to tumors, hypoxia and associated tumor necrosis. BNC105P also has a direct anti-proliferative action on cancer cells. Up regulation of the mTOR pathway has been identified as a cellular response to hypoxic stress. The combined use of BNC105P with an agent active against mTOR may improve clinical outcome in patients with progressive mRCC who are refractory to VEGFR-directed tyrosine kinase inhibitors (TKI). Methods: A phase I/II study in mRCC patients who have received 1-2 prior TKIs was undertaken. The phase I component enrolled 12 subjects at 4 dose levels of BNC105P (4.2, 8.4, 12.6, 16 mg/m 2 ; IV infusion Days 1 and 8, 21-day repeating cycle). Everolimus was administered concurrently (10 mg p.o.). PK analysis was performed during cycle 1. Results: Updated results from the completed phase I component confirm the BNC105P/everolimus combination was well tolerated. No DLTs (drug-related, during cycle 1) were observed in any of the phase I subjects. Toxicities on study deemed to be drug-related (either single agent or combination) included single grade 3 events of anemia and pericardial effusion. Grade 2 events (more than 1 occurrence) of fatigue, anemia, and oral mucositis were also observed. 8 of the 12 phase I subjects achieved disease stabilization (7 of these subjects had a minimum time on therapy of 18 weeks, 6 cycles). Across all subjects a median of 6 cycles (range: 1-21) was administered, with removal from study predominantly due to disease progression. PK analysis confirmed no drug-drug interaction. The randomized phase II component of the study continues and will compare everolimus given concomitantly with BNC105P to a sequential approach (everolimus followed by BNC105P). Conclusions: BNC105P (16 mg/m 2 ) can be combined with full dose everolimus and is being evaluated in a randomized phase II study. Clinical trial information: NCT01034631.
Evaluation of panitumumab (pmab) plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) after first-line bevacizumab (bev) in patients (pts) with metastatic colorectal cancer (mCRC): A subgroup analysis of study 181.
Authors: M. Peeters, T. J. Price, A. H. Strickland, T. E. Ciuleanu, W. Scheithauer, S. O'Reilly, M. M. Keane, D. R. Spigel, Y. Tian, K. Krishnan
Journal: Journal of Clinical Oncology (2011)

3574^ Background: Pmab, a fully human monoclonal antibody targeting EGFR, has demonstrated activity in combination with FOLFIRI for second-line treatment of mCRC (study 181). Here, we describe the results of a prespecified subgroup analysis of study 181 to evaluate the efficacy of pmab plus FOLFIRI vs FOLFIRI alone in pts who received prior bev. Methods: Prior bev use for mCRC (yes vs no) was a predefined baseline covariate and stratification factor in study 181. A subgroup analysis was conducted to evaluate the treatment effect of pmab plus chemotherapy on progression-free survival (PFS), overall survival (OS), and tumor response rate in pts with wild-type (WT) KRAS tumors who received prior bev for mCRC. Results: 115 pts (from 20 countries) with WT KRAS tumors who had received prior bev were identified. Worst grade of 3 or 4 adverse events (AE) occurred in 73% of pts in the pmab+FOLFIRI arm vs 57% in FOLFIRI arm. Worst grade 3–4 AEs of interest included: skin toxicity (tox [35 vs 5%]); eye tox (7 vs 0%); nail tox (5 vs 0%); diarrhea (9 vs 8%); stomatitis/oral mucositis (7 vs 2%); pulmonary tox (0 vs 3% [and one grade 5 in the FOLFIRI arm]); vascular tox (2 vs 15%); hypomagnesemia (4 vs 0%); cardiac tox (0 vs 3%); and hypocalcemia (2 vs 0%). Grade 5 AEs occurred in 2% and 3% of pts, respectively. Median PFS and OS were numerically longer, and there was a significantly higher overall response rate (ORR) in the pmab+FOLFIRI arm vs FOLFIRI (Table). Conclusions: Pts with mCRC and WT KRAS tumors who progress after therapy with bev may benefit from second-line therapy with pmab+FOLFIRI. Pmab+FOLFIRI FOLFIRI Measure of risk N 55 60 Median PFS, months (95%CI) 5.8 (5.2–6.7) 3.7 (3.5–5.3) HR=0.712 (0.447–1.133) Median OS, months (95%CI) 15.7 (12.6–23.8) 12.5 (9.2–16.1) HR=0.680 (0.432–1.069) N* 53 57 ORR, n (% [95%CI]) 16 (30.19 [18.34–44.34]) 1 (1.75 [0.04–9.39]) OR=24.22 (3.40–1033.11) * Pts who had measureable lesion per central radiology review were included in the analysis of ORR. Abbreviations: CI, confidence interval; HR, hazard ratio; OR, odds ratio.
Gene Expression Profiling in AML with Normal Karyotype: A Multicenter Study Investigating Molecular Markers in 252 Cases
Authors: Alexander Kohlmann, Lars Bullinger, Christian Thiede, Markus Schaich, Susanne Schnittger, Konstanze Dohner, Martin Dugas, Hartmut Dohner, Gerhard Ehninger, Torsten Haferlach
Journal: Blood (2008)