tbuckley/cabot-search huggingface dataset:
Characteristics and outcomes of patients with gallbladder cancer and cholangiocarcinoma referred to a phase I clinic.
Authors: Ishwaria Mohan Subbiah, Vivek Subbiah, Ahmed Omar Kaseb, Filip Janku, Jennifer J. Wheler, Aung Naing, Siqing Fu, Sarina Anne Piha-Paul, David S. Hong, Gerald Steven Falchook, Apostolia Maria Tsimberidou, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2012)

364 Background: The prognosis of cholangiocarcinoma (CC) and gallbladder carcinoma (GC) remains grim. The purpose of this study was to report the presenting characteristics and outcomes of patients with CC and GC treated on phase 1 clinical trials focused on targeted agents at a major cancer center. Methods: We reviewed the records of consecutive patients with GC and CC in the Phase I Clinical Trials Program at the M. D. Anderson Cancer Center from Nov 2004. We assessed the relationship between overall survival, patients' tumor types, and mutations, demographic and clinical characteristics. Results: Fifty-two patients were identified (7 with GC, 45 with CC). The median age was 58 yrs (range, 20-75 yrs). ECOG performance status (PS) was 0, 1, 2, and 3 in 9 (17%), 30 (58%), 7 (13%), and 6 (12%) pts, respectively. Median number of prior therapies was 3 (range 0-17). The median time from diagnosis of metastatic disease to primary Phase I clinic evaluation was 14.6 months. Of 52 patients, 17 (33%) were not enrolled on a Phase I trial due to decline in PS (n=13) or decision to pursue other treatments (n=4). Of 35 patients evaluable for response, 2 (6%) had a partial response (PR), and 3 (9%) had stable disease &gt; 4 months. Prognostic factors analyzed include Hg &lt; 10.5 g/dL, elevated CA 19-9 (&gt;47 ng/mL), ECOG PS &gt; 3, LDH &gt; 618 IU/L, albumin &lt; 3.5 g/dL, platelets &lt; 150 K/UL, and number of metastatic sites. Full analysis including the mutational analysis for PIK3CA, KRAS, BRAF, TP53 is in progress. Median survival since presentation to the Phase I clinic was 4.1 months (range 2.3 - 30.8 months). Median overall survival from diagnosis was 23.9 months. The median survival since enrollment in a Phase I trial was 4.6 months w the median time to disease progression on Phase I treatment was 2.2 months (range 0.6 - 25.6 months). Conclusions: Prognosis of pts with CC and GC referred for phase I studies remains poor. Further analysis including complete mutational profiles of CC and GC patients will be reported.
Risk of local relapse, second nonurinary neoplasms, and noncancer-related mortality after conservative management for invasive bladder cancer: A single-center experience.
Authors: I. Sullivan, J. P. Maroto, C. Martin, L. Robert, A. Sebio, P. Murata, A. Stradella, G. Sancho, G. Gomez de Segura, J. Palou
Journal: Journal of Clinical Oncology (2011)

e15091 Background: Patients with bladder tumors are at high risk of developing second urinary and non-urinary neoplasms. In addition, risk factors of cardiovascular and non-cardiovascular mortality such as smoking are common. We analyze the incidence of second tumors in conservatively managed patients with good prognosis invasive bladder cancer. Methods: From January 2000 to December 2010, 54 patients (9 women, 45 men) were treated with maximum transurethral resection (TUR). After TUR, 40 patients received either 3 cycles of chemotherapy (CT) with cisplatin 75 mg/m2 or carboplatin AUC 5, if creatinine clearance was below 55 mL/min, plus gemcitabine 1 gr/m2. 14 (26%) patients not candidates or not willing a cystectomy received concomitant chemoradiotherapy (CRT). A new TUR and biopsies were performed in all patients after completing the therapy and later biannually for the first year. Patients with cT4 tumors, other histology than transitional cell cancer and patients with hydronephrosis or multifocal carcinoma in situ were not included. Results: With a median follow-up of 32 months (m), 3 patients had a local relapse and were treated with cystectomy or concomitant chemo-radiotherapy. 9 (16%) patients presented a second tumor in the bladder. Of the second tumors, 3 were muscle-invasive and 6 superficial tumors. Median time to a second urinary tumor was 12 (5-93) m. 5-year no second urinary tumor free survival was 58%. A salvage cystectomy was necessary in 8 (15%) patients. 4 patients were diagnosed of a non-prostate second neoplasms (2 lung, 1 rectal, 1 unknown origin) and 2 patients had prostate cancer. Non-cancer related mortality affected 8 (15%) patients (1 patient an infectious disease, 5 cardiovascular disease, 1 COPD, 1 gastro-intestinal bleeding). Overall survival was 62 (45-102) m and disease specific (tumor) survival was 74 m. Conclusions: Cancer and non-cancer mortality in long-term survivors of bladder cancer treated conservatively is high. Specific management considerations should be considered for these patients.
Clinical decision support tools to improve quality and practice efficiency across a large network of oncology practices.
Authors: Debra A. Patt, Madeline Nubie, Denise R. Kazzaz, Aimee Arlen, Mark A. Sitarik, Asif Ahmad, Leslie T. Busby, Roy Beveridge
Journal: Journal of Clinical Oncology (2012)

294 Background: Electronic health records (EHR) provide opportunities for quality enhancements at various points in care. It can support electronic orders, meaningful use, progress notes, medication and allergy data, electronic prescribing, and vital-signs tracking. Clinical decision support tools (CDST) can facilitate high-quality performance and practice efficiency. These enhancements reduce error, improve quality, and drive practice efficiency. The oncology specific EHR (IKnowMed) incorporates CDST including physician driven level 1 pathways prescribing, chemotherapy regimen order entry, dose calculation, supportive care drugs, and guidelines for safe prescribing. Methods: To understand scope and utilization of CDSTs within a large network of individual oncology practices we characterized (qualitatively and quantitatively) common modalities in our EHR (iKnowMed). Treatment regimens were populated by the network collaborative-care committee. Physicians selected regimens pre-populated w/doses and pre-medications. Antiemetic regimens were pre-populated for emetagenic potential of the chemotherapy regimen. Results: Across the US Oncology Network, 952 physicians used the EHR to deliver services over a 5-month period. During that time, 69,448 cancer treatment regimens were ordered, pre-populated by drug, dose and pre-medications; and 68,268 chemotherapy regimens were pre-populated with antiemetic therapy to mirror emetagenic potential. Conclusions: By enhancing the EHR to include CDSTs, treatment and appropriate antiemetic regimens can be pre-populated across a large network of individual oncology practices that have aligned together using common IT and CDST to drive quality care for their patients. The network is using technology to enhance quality and efficiency in practice.
Phase I (Ph) safety, pharmacodynamic (PD), and pharmacokinetic (PK) trial of a pure MEK inhibitor (i), RO4987655, in patients with advanced /metastatic solid tumor.
Authors: S. Leijen, M. R. Middleton, P. Tresca, F. Kraeber-Bodere, V. Dieras, M. E. Scheulen, J. Tessier, Z. X. Xu, E. Shochat, A. Walz, J. Deutsch, S. Blotner, V. Lopez Valverde, V. M. Naegelen, J. H. M. Schellens, W. E. Eberhardt
Journal: Journal of Clinical Oncology (2011)

3017 Background: Mutations of Ras/Raf lead to a sustained and constitutive activation of ERK pathway. MEK1/2 is the only enzyme that activates ERK1/2; consequently MEK1/2 is a potential target to inhibit in cancers with an activated ERK pathway. RO4987655, a potent, highly selective ATP non-competitive MEK1i with an excellent selectivity profile, was tested in a 3+3 Ph1 study design. Objectives were determination of maximum tolerated dose (MTD), recommended Ph2 dose (RP2D), dose limiting toxicities (DLTs), safety/tolerability, PK/ PD and clinical activity. Methods: Patients (pts) with advanced/metastatic solid tumors received oral RO4987655 administered on a continuous daily dosing (QD) from 1-2.5 mg then twice daily (BID) from 3-21 mg total daily dose in 28 days (D) cycles. Blood PK samples were collected on cycle 1 (C1) [D 1, 8, 15 and 22]. Molecular target suppression was measured by pERKi in PBMC on C1 (D1, D15). Paired skin and tumor biopsies (optional) (baseline, C1D15) and sequential FDG-PET scans (baseline, C1D15, C3D1) were taken. Efficacy was measured as per RECIST. Results: 49 pts in 12 cohorts were enrolled at 4 sites. Mean age 52 y, ECOG 0-1, previous chemotherapy lines median 3 (0-10). Common tumor types included melanoma (27), CRC (11) and NSCLC (3). Four reversible DLTs were observed: CPK elevation (17 mg (n=1), 21 mg (n=2) and blurred vision (21 mg). MTD and RP2D were defined as 17 mg. Most commonly related adverse events included skin (91%), GI (57%), eye (26%) and CPK disorders (44%). PK profiles showed dose-linearity, a half-life of 4 to 6 hrs and drug accumulation ~ 2 fold at steady-state. High (mean 75%) and sustained (90% of time >IC50) pERKi was observed in PBMC at RP2D. FDG PET showed large decrease in SUV at RP2D (-47%, -90% to +29%) (mean, range) which correlated with PBMC pERKi in melanoma pts. PRs and SDs (>=4 mo) were observed in 2 and 5 melanoma, respectively. Conclusions: RO4987655 showed acceptable and manageable safety profile. PK was linear for the tested dose range with moderate inter-pt variability. PD activity in PBMC associated with large metabolic FDG-PET response and preliminary encouraging antitumor activity were demonstrated at the RP2D.
Utilizing a case management system to reduce the response time for symptom management calls in a high-volume practice.
Authors: Natalie R. Dickson, Larry Edward Bilbrey
Journal: Journal of Clinical Oncology (2016)

170 Background: A five physician, three nurse practitioner,community oncology clinic experiences high call volumes (average 352 daily), many of which are related to side-effects of chemo/biotherapy and health related issues. A study was completed to decrease the time for a patient symptom management call to be addressed and concluded. Methods: Initial primary data were collected over a four month period (April-August 2015) using the phone system and the Electronic Health Record (EHR) reporting capabilities, by cross-referencing the caller-ID data with the EHR patient demographics data; only documented symptom management calls within the EHR were included. Twenty-nine percent (202 of 691) of symptom management calls were identified for the sample. Secondary data were collected prospectively using a handwritten call log completed by triage nursing, detailing the purpose of every call routed to triage nursing. Changes were made in the daily telephone call process to include a full-time operator, additional triage nursing staff, and implementation of a structured case management system. Follow-up primary and secondary data were collected for six weeks (August-September 2015) utilizing the case management system. Of the calls routed to triage nursing, 100% were captured in the case management system; call response time and call purpose were recorded. Results: During the initial primary data collection, a baseline of 48% of symptom management calls being addressed within 2 hours was established. Staffing changes resulted in an improvement to 68%, and an additional improvement to 73% after implementation of the case management system. Secondary data collection at baseline showed that 35% of calls were inappropriately routed to triage nursing; this improved to under 1% after implementation of the case management system. Conclusions: The reallocation of staff to concentrate on patient call processes, and the use of a case management system, significantly improved symptom management call response time. The implementation of a case management system nearly eliminated all inappropriate calls routed to triage nursing.
Phase II trial of single agent oral vinorelbine in elderly (≥70 years) patients with advanced non small cell lung cancer and poor performance status
Authors: D. Amoroso, A. Camerini, O. Siclari, G. Tartarelli, C. Puccetti, S. Donati, M. Rondini, C. Valsuani, L. Amadei, P. Puccinelli
Journal: Journal of Clinical Oncology (2008)

19085 Background: Elderly patients with advanced non small cell lung cancer(NSCLC) with poor PS are a special population requiring particular attention. Single agent oral vinorelbine could be an attractive option. Methods: Patients with advanced NSCLC (IIIB-IV or any stage medically unfit for surgery) and ECOG PS ≥2. Oral vinorelbine was administered the dose of 60 mg/sm on day 1,8 every three weeks. Dose increase to 80 mg/sm was permitted in relation to pts tolerance. One previous platinum-based chemotherapy was permitted and 6 cycles were planned. Primary endpoints were response rate (according to RECIST criteria) and safety. Results: To date 31 pts (median age 76.5 yrs [range 70–84]; 28M) were enrolled. PS 2/3 distribution was 23/8. Pts received a median of 4 cycles (range 1–9). Response rate was 16.1% with 5 partial response, 12 (38.7%) stable disease lasting more than 12 weeks and 14 (45.2%) disease progression for an overall clinical benefit of 54.8%. Treatment was extremely well tolerated. On a total of 123 cycles we did not observe any G3/4 toxicity with the exception of a single not febrile G3 neutropenia. Regardless of severity, main toxicities observed were nausea and vomiting in 50% of pts, sensorial neuropathy in 10%, fatigue in 30%, leukopenia/neutropenia in 25%. There was no treatment related death. Median time to progression was 4 (range 2–22) months and median overall survival 5.5 (range 3–22) months. Conclusions: Single agent oral vinorelbine is moderately active and extremely safe in elderly pts with advanced NSCLC and ECOG PS ≥2 and may represent a valid option in this special population. No significant financial relationships to disclose.
Preliminary observations of blood-based (BB) molecular testing in a subset of patients with pancreatic cancer (PDA) participating in the Know Your Tumor (KYT) initiative.
Authors: Michael J. Pishvaian, Lynn Matrisian, Andrew Eugene Hendifar, Anitra Engebretson, Lola Rahib, William Arthur Hoos, Sameh Mikhail, Vincent M. Chung, Vincent J. Picozzi, Craig Heartwell, Kimberly Mason, Katelyn Varieur, Subha Madhavan, Emanuel Petricoin, Jonathan Robert Brody
Journal: Journal of Clinical Oncology (2016)

268 Background: Obtaining an adequate tissue sample for molecular profiling to guide therapy selection for patients with advanced cancers can be clinically difficult, and/or patients may not want to undergo a biopsy. There has been a growing interest in the use of BB tests, including cell free DNA (cfDNA) and exosome/circulating tumor cell based-analyses as surrogates for tumor tissue (TT) testing. Validation of BB tests in PDA is possible because &gt; 90% of PDAs harbor KRAS mutations – thus providing a reliable “internal control.” Methods: The Pancreatic Cancer Action Network (PanCAN) and Perthera initiated an IRB-approved registry trial for patients with pancreatic cancer wherein we facilitated commercially available, CLIA certified multi-Omic profiling including next generation DNA sequencing (NGS), immunohistochemistry, and phosphoproteomics on patient tumor samples. In a subset of these patients, we incorporated BB testing. Results: A KRAS mutation has been identified in 87% of KYT patients based on TT NGS in general. As of this report, 17 BB test results (cfDNA NGS) were available. In 8 patients we were able to compare the cfDNA NGS directly with TT NGS. BB testing identified a KRAS mutation in 1/8 compared to 8/8 from the tumor tissue. Of the 9/17 patients who did not have corresponding TT NGS, a KRAS mutation was found on BB testing in 3/9 samples. 4/17 BB cases overall revealed KRAS mutations, but when cases were filtered for patients with extensive metastatic disease and progressive disease at the time of blood sampling, the KRAS mutation rate increased to 2/5 overall. Actionable findings (i.e. linked to a specific therapeutic option) were identified in 6/17 cases, of which 3/17 had both an actionable mutation and a KRAS mutation. Conclusions: Although we are aware of the limitations of this study, we recommend that for patients who have biopsiable disease, a TT test should still be the gold standard for molecular profiling. For those without biopsiable disease, the KYT program presents an opportunity to determine the parameters that influence the probability of obtaining reliable molecular profiling information from a BB sample.
Biomolecular, biochemical, and radiologic evaluation of patients on anti-VEGF treatment for mCRC.
Authors: L. Rossi, E. Veltri, M. Di Seri, S. Vari, M. Colonna, D. Adua, F. Longo, F. Zoratto, M. Mottolese, S. Tomao
Journal: Journal of Clinical Oncology (2011)

556 Background: K-ras mutation is a negative predictor of clinical benefit (CB) from anti-EGFR treatment in mCRC. Bevacizumab combined with chemotherapy prolongs both PFS and OS in first-line treatment of mCRC. Previously data suggested that this results are independent of K-ras status. We conducted a study to investigate the CB of Bevacizumab in treatment of mCRC according to K-ras status and to evaluate timing of response to treatment trough the correlation between tumor markers values and clinical responses. Finally we evaluated CB in patients affected by mCRC with only hepatic metastases vs patients with multiple metastasis sites. Methods: 82 patients were enrolled and underwent first-line chemotherapy with Folfiri or FolFoX and bevacizumab. Tissue samples were analyzed for DNA sequencing in order to identify K-ras mutations in codons 12 and 13. Before therapy all patients were investigated with CT scan and with a blood sample to define tumor markers values; a new evaluation of tumor markers after 2 months of chemotherapy was performed and a CT scan after 3 months. Results: An overall objective response rate (RR) of 40% and a CB of 79% were obtained, with a correlation between tumor markers values and clinical response of 89%. 49% of population presented only hepatic metastases while other 51% showed multiple metastatic sites. RR in exclusive hepatic metastatic group was 45% vs 33% multiple metastatic sites group, CB was 90% vs 66% respectively. No grade 3 or 4 bevacizumab associated toxicity was showed in patients. K-ras mutations were investigated in 75 of 82 patients. 49 patients were wild-type (wt 65%) while 26 patients were mutated (mut 35%). RR in wt group was 45% vs 35% in mut group, while CB was 82% vs 81% respectively. Correlation between tumor markers values and clinical response was 90% in wt group vs 93% in mut group. Conclusions: RR in two K-ras groups was different with an advantage in K-ras wt group, but this difference does not observe in CB. Bevacizumab provides significant RR and CB after a short time of treatment and tumor markers values could be an optimal correlative parameters of early clinical response. Bevacizumab provides significant CB in patients with only hepatic metastases vs patients with multiple metastatic sites. No significant financial relationships to disclose.
Evolution of multimodality management of gastrointestinal stromal tumors of the stomach.
Authors: K. Y. Bilimoria, R. P. Merkow, J. D. Wayne, D. E. Abbott, J. N. Cormier, B. W. Feig, K. Hunt, P. W. Pisters, R. E. Pollock, D. J. Bentrem
Journal: Journal of Clinical Oncology (2011)

94 Background: Gastrointestinal stromal tumor (GIST) treatment has changed considerably with introduction of imatinib in 2001, initiation of ACOSOG adjuvant trial in 2002, and FDA adjuvant approval in 2008. However, little is known about how imatinib has been incorporated over time. Our objective was to examine the evolution of multimodality management of GISTs. Methods: Patients coded specifically as gastric GISTs were identified (n = 4,508; 443 hospitals) from the National Cancer Data Base (2001-2007). Changes over time were assessed with chi-squared test for trend. Separate multivariable regression models were developed to examine factors associated adjuvant and neoadjuvant practices. Results: Gastric GISTs reported to NCDB steadily increased: 463 in 2001 to 831 in 2007. 3,289 underwent resection: 78% partial/wedge, 6% total/near-total, and 14% multivisceral. From 2001 to 2007, use of adjuvant therapy increased from 29% to 47% (p &lt; 0.001), although patients were less likely to get adjuvant therapy if older, tumors &lt; 3cm, low grade, negative margins, or treated at low-volume hospitals (p &lt; 0.01). Adjuvant systemic therapy for lesions &lt; 3 cm also increased (17% to 25%, p = 0.001). For GISTs &gt; 6 cm, use of adjuvant therapy increased from 41% to 49% overall, with increases of 45% to 70% at high-volume centers and of 39% to 48% at low-volume centers (all p &lt; 0.001). Neoadjuvant therapy increased from 0% to 15% (p &lt; 0.001) with patients more likely to receive neoadjuvant treatment if size &gt; 6 cm, treated at high-volume centers, or treated in 2006-2007 (p &lt; 0.001). Multivisceral resections decreased over time (19% to 12%, p &lt; 0.001). The proportion of patients treated at high-volume centers increased slightly over time (22.2% to 26.9%, p = 0.006). Conclusions: Adjuvant systemic therapy use for GISTs was increasing and widespread prior to FDA approval of adjuvant imatinib, suggesting contemporaneous advances in advanced GIST management were being translated into the adjuvant setting more than expected. As relatively costly therapies are integrated into practice, more robust tracking systems are needed to follow and guide the incorporation of new treatments. No significant financial relationships to disclose.
High Rates of Early Donor Chimerism and Low Risk of Chronic GVHD Can Be Achieved in Poor Risk Patients Undergoing Unrelated Donor Stem Cell Transplantation Using a Reduced Intensity Conditioning Regimen Incorporating Fludarabine, Busulfan, and Rabbit ATG.
Authors: Mehdi Hamadani, Patrick Elder, Farrukh Awan, David Krugh, William Blum, Thomas Lin, Leslie Andritsos, Thomas Bechtel, Kristie Blum, Rebecca Klisovic, Steven M. Devine
Journal: Blood (2007)