tbuckley/cabot-search huggingface dataset:
SORAVE trial: Phase I sorafenib and everolimus in solid tumors.
Authors: L. Nogova, M. Scheffler, I. Papachristou, C. Mattonet, R. Krais, I. Katay, P. Mallmann, U. Fuhr, M. Dietlein, J. Wolf
Journal: Journal of Clinical Oncology (2010)

TPS170 Background: Clinical efficacy of the multikinase inhibitor sorafenib is mainly based on its antiangiogenic properties mediated by VEGFR inhibition. The mTOR inhibitor everolimus also exerts antiangiogenic effects; additionally it may induce antiproliferative effects on the tumor cells by blocking the PI3K/AKT pathway. Treatment with both drugs simultaneously thus may enhance antitumor effects by combining (I) two differently acting antiangiogenic agents and (II) antiangiogenic and antitumor cell activity. This phase I study aims at demonstrating the safety of combination therapy with these two agents in patients suffering from relapsed solid tumors. Besides pharmacokinetic (PK) analyses for sorafenib and everolimus dynamic FDG-PET is used as pharmacodynamic parameter. A descriptive analysis of response is intended to gain first insight into efficacy of this treatment. Methods: A maximum of 24 patients with relapsed solid tumors is planned to be recruited for defining the MTD of everolimus in a cumulative 3+3 dose escalating scheme with 2.5-10 mg everolimus od. This treatment is combined with fixed dose sorafenib 400 mg bid after a two weeks run-in interval with everolimus monotherapy. Further 12 patients will be included in an extension phase treated with the MTD. Individual and population PK analysis will be based on the measurement of serum concentrations of both substances. FDG-PET will be performed before as well as 5 and 14 days after start of therapy. A comparison of standard uptake values (SUV) of glucose in target lesions with baseline imaging values serves for early assessment of pharmacodynamic response to therapy. After a period of 8 weeks of combination therapy response will be assessed by CT scan and comparison of previously defined target lesions with baseline findings according to RECIST criteria. Patients without clinical or radiological signs of progressive disease will continue treatment. An outcome analysis will measure RR, TTP, PFR, and OS. FDG-PET, clinical findings, and outcome parameters will be incorporated in a PK/pharmacodynamic model to optimize the treatment schedule. Currently 6 patients have been enrolled in this study with ovarian cancer (2), colorectal carcinoma (2), SCLC (1), and pancreatic cancer (1). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Bayer, Novartis Bayer, Novartis
Large-scale fast-track diagnostics in a comprehensive cancer center.
Authors: Sanne Heintzbergen, Wim van Harten, Nicolette Goedbloed, Marja van Wijngaarden, Arthur Dernison, Annelies H. Boekhout
Journal: Journal of Clinical Oncology (2013)

185 Background: In general, patients with a cancer suspicion visit the hospital multiple times before the diagnosis is completed. Using various “operations management” techniques a limited number of fast track diagnostic services were implemented in the Netherlands Cancer Institute (NKI) in 2006. Fast growing patient numbers and increasing process complexity, led to diminished service levels. To decrease the amount of patient visits and period of uncertainty, fast track diagnostics is implemented for 17 cancer types. The in benchmarks proven high efficiency, hardly any redundancy, and no capacity extension made this a large efficiency challenge. We report on the process of redesign, implementation, and first results. Methods: The throughput time (first visit to diagnosis conversation) was measured before redesigning the diagnosis process, and repeated after implementation of fast track diagnostics. In pre-measurement throughput time was retrospectively measured for 105 patients and 7 cancer types. The diagnosis process for 17 cancer types was redesigned by multidisciplinary teams. Input and process variation, slot use and constraints were analysed for all processes. In an eclectic approach, elements from lean management, theory of constraints, and mathematical analysis were used to organize slots for MRI, CT, PET, and echo with reservations turning into capacity available for short-term planning. Results: In premeasurement diagnosis was completed from 2 workdays onward to 58 (mean throughput time 13.3 workdays). It proved possible to design 15 of 18 tumors as a one-stop shop (Table). Through involvement of clinical and board leadership, massive communication efforts, commitment of physicians to reschedule their weekly activities was rather positive. In the post measurement the mean throughput time was 0.8 days (median 0 days). Conclusions: The involvement of physicians in redesigning and reorganizing their work was important: implementation of fast track diagnosis proved successful for 14 out of 17 cancer types. For 3 tumor types fast track diagnosis implementation is designed but not yet completed. Throughput time was considerably shortened after implementation of fast track diagnostics. [Table: see text]
Vascular Endothelial Growth Factor Expression in CD138+/CD19- and CD138+/CD19+ Plasma Cells in Monoclonal Gammopathies and Impact on Multiple Myeloma Prognosis
Authors: Catarina Geraldes, Ana Cristina Gonçalves, Raquel Alves, Emília Cortesão, Maria Leticia Ribeiro, José Nascimento-Costa, Ana Bela Sarmento-Ribeiro
Journal: Blood (2015)
Sequential chemotherapy with gemcitabine+carboplatin followed by gemcitabine+carboplatin+docetaxel for advanced upper-tract urothelial cancer.
Authors: Takahiro Yoneyama, Tendo Sato, Jotaro Mikami, Yuta Kojima, Naoki Fujita, Hiromichi Iwamura, Yuki Tobisawa, Tohru Yoneyama, Kazuyuki Mori, Atsushi Imai, Shingo Hatakeyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2016)

428 Background: Chemotherapy for advanced upper-tract urothelial cancer (UC) has not yet been established. Gemcitabine+cisplatin may be a promising regimen for advanced upper-tract UC as well as for advanced bladder cancer. However, cases with renal dysfunction are common in advanced upper-tract UC, and cisplatin often unfits for those patients. We retrospectively evaluated the effectiveness and adverse events (AEs) of a sequential chemotherapy with gemcitabine+carboplatin(GCarbo) followed by GCarbo+ docetaxel (GCarboD) for advanced upper-tract UC. Methods: We treated 74 patients (52 men and 22 women) with advanced upper-tract UC from September 2004 to December 2014. Mean age was 69.3 (43–89), and mean Ccr was 50.5 (11.6–99.3) ml/minute. Mean observation period was 24.0 (3–96) months. The patients received 2 courses of GCarbo consisted of 800mg/m 2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCarbo was performed. If this regimen did not induce any tumor size reduction, we switched to 2 courses of GCarboD (70mg/m 2 ) treatment as second-line treatment. Results: GCarbo regimen yielded 5 cases (6.8%) of CR, 32 (43.2%) of PR. GCarboD treatment was administered in 21 cases, and yielded two (9.5%) PR. The median survival period was 18.3 months with GCarbo/GCarboD regimens. Adverse events (AE) of grade 3 or higher occurred in 48 of those who had undergone the GCarbo therapy (64.9%). In GCarboD regimen, there were 20 (95.2 %) of G3/4 AEs. Conclusions: GCarbo and GCarboD chemotherapy can be administered safely to advanced upper-tract UC cancer, many of whom have renal dysfunctions. GCarbo regimen achieved high response rate (50.0%) in advanced upper-tract UC. However, GCarboD had limited effectiveness for non-responder of GCarbo.
The efficacy and safety of the capecitabine/temozolomide (CAPTEM) regimen in the treatment of well-differentiated neuroendocrine tumors with liver metastasis after failure of previous therapy: Columbia University Medical Center experience.
Authors: Paul Eliezer Oberstein, Anthony Paul Gulati, Benjamin A Krantz, Rebecca Anne Moss, Stephen M. Schreibman, Dawn Tsushima, Kelley B Mowatt, John Allendorf, Beth Schrope, James A Lee, William H. Sherman, John A Chabot, Robert Fine
Journal: Journal of Clinical Oncology (2013)

308 Background: We have observed efficacy and tolerability of the CAPTEM regimen in pNET. We conducted a retrospective review of patients with liver metastasis from any NET, including carcinoid, who were treated with this regimen at our institution between 2002-2008. Methods: We identified patients with neuroendocrine tumors who demonstrated progressive liver metastasis while on treatment with long-acting octreotide (up to 60mg/month) and were then treated with CAPTEM as per our institutional protocol. Patients received capecitabine for 14 days at 1000mg PO bid with temozolomide at 150 or 200mg/m2 in bid dosing on days 10-14 of each 28 day cycle. All patients had contrast enhanced CT or MRI, response was assessed by a radiologist utilizing RECIST 1.0 criteria. Results: We identified 18 patients (50% female, median age- 55), 9 had pNET (2 functional, 7 non-functional), 2 had MEN1, 4 had carcinoid (1 functional), 2 with gastrinoma and 1 with glucagonoma. All patients had Ki-67 &lt;10%, 11 patients (61%) had received previous chemotherapy (median of 2 regimens), and 50% had previous chemoembolization. Performance status at time of enrollment was 0-2 (5 patients, 28% with PS-2.)The response rate in the population was 61% (11/18) with 1 CR and 10 PR by RECIST 1.0 criteria. Stable disease was seen in 4 (22%) patients and clinical benefit (CR+PR+SD) in 83%. Response was noted in carcinoid patients (2 of 4, with 1 CR and 1 PR in this group) and in MEN1 patients (1 of 2 with PR). Median PFS was 14.0 months (range 4.2-18 months). Treatment was well tolerated; the most common grade 1/2 toxicities were lymphopenia (50%) and neutropenia (44%), 1 patient had hand-foot syndrome. Grade 3 thrombocytopenia was observed in 2 patients (11%), there was no other grade 3 or 4 toxicities. Conclusions: The CAPTEM regimen is well tolerated and is associated with a significant response in patients with liver metastasis from NET including the difficult to treat cases of carcinoid and MEN1. A prospective Phase II trial of this regimen is ongoing.
Biomarker assessment from EUS-guided biopsy to predict outcomes and treatment in pancreatic cancer.
Authors: Nam Q. Nguyen, Andrew Ruszkiewicz, David Chang, Jenna Bambrick, Andrew Victor Biankin
Journal: Journal of Clinical Oncology (2014)

182 Background: Current methods of pre-operative predicting outcome of pancreatic cancer and related pancreatectomy are limited. While several prognostic biomarkers, including S100A2 and S100A4, are associated with poor outcomes, these currently can only be assessed in operatively resected specimens. The amount of tissue from EUS guided fine needle aspirations is often insufficient for biomarker assessment. Procore needles aim to acquire larger volumes of tissue that may be suitable. We aim to (i) evaluate the feasibility of S100A2 and S100A4 assessment in EUS guided biopsy specimens using the Procore needle, and (ii) evaluate the relationship of these biomarkers with outcome. Methods: Clinico-pathological data from 79 patients (70 ± 2yrs; 44M:35F) with pancreatic ductal adenocarcinoma (PDAC) were prospectively acquired. All subjects had EUS guided biopsy with a 22G Procore needle and cell-block preparation was performed. Sections of cell-block material were assessed for S100A2 and S100A4 protein expression using immunohistochemistry. Results: Pre-operative biomarker assessments from EUS acquired specimens were possible in 90% (72/79) of patients, 14 of which then had pancreatectomy. Thirty-five (49%) of patients expressed S100A2 and S100A4, which were co-expressed in 97% of cases. Patients with S100A2/A4 tumours on EUS had a significantly shorter median survival (10.0 vs. 17.5 months, p=0.03). Among patients with S100A2/A4 expressing tumors, pancreatectomy (n=8) didn't lead to a survival benefit compared with those managed non-surgically (n=27) (12.5 vs. 10.0 months, p=0.70). Of patients who had pancreatectomy, those with S100A2/A4 expressing tumors (n=8) had shorter survival than those with S100A2/A4-negative tumors (n=6) (12.5 vs. 20.5 months; p = 0.04). Conclusions: Biomarker assessment from EUS guided biopsy specimens is feasible and successful in 90% of cases. The presence of S100A2 and S100A4 expression predicts both survival and response to pancreatectomy in patients with pancreatic cancer. These findings demonstrate a “proof-of-concept”, that pre-operative EUS guided biopsy could inform clinical decision-making, particularly with regard to selection for operative resection of PDAC.
Elevated pretreatment serum CA9 (carbonic anhydrase 9) and correlation with progression-free and overall survival in trastuzumab-treated metastatic breast cancer.
Authors: K. Leitzel, H. Y. Hou, U. Anyanwu, V. Shrivastava, M. S. Evans, S. M. Ali, W. Koestler, E. Fuchs, F. J. Esteva, W. P. Carney, A. Lipton
Journal: Journal of Clinical Oncology (2011)

563 Background: Approximately one-half of HER2-positive breast cancer patients will respond to first-line trastuzumab-containing therapy. However, in those patients with an initial trastuzumab response, most will progress within a year with acquired resistance. Since trastuzumab treatment is also now used in the HER2-positive adjuvant breast cancer setting, trastuzumab resistance will continue to be a recurring clinical problem, and better predictive and prognostic biomarkers are urgently needed. Methods: Serum HER2, tissue inhibitor of metalloproteinase-1 (TIMP-1), CA IX, and endoglin were measured using ELISA assays in 81 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. The HER2, TIMP-1, and CA IX ELISAs were from WILEX Inc./Oncogene Science, Cambridge, MA; and the endoglin ELISA was from R&D Systems, Minneapolis, MN. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with continuous pretreatment serum biomarker variables. Results: Pretreatment serum HER2 (p= 0.007), TIMP-1 (p< 0.0001), endoglin (p= 0.02), and CA IX (p <0.0001) were all significant as univariate continuous biomarkers for predicting PFS to first-line trastuzumab-containing therapy. In multivariate analysis for PFS with all biomarkers, only serum CA IX (p= 0.001) was a significant independent covariate. For OS, pretreatment serum HER2 (p= 0.007), TIMP-1 (p<0.0001), endoglin (0.014), and CA IX (p<0.0001) were all significant as univariate continuous biomarkers for prognosis. In multivariate analysis for OS with all biomarkers, serum CA IX (p<0.0001), TIMP-1 (p=0.026), and endoglin (0.045) were significant prognostic covariates (p=0.001). Conclusions: Elevated pretreatment serum CA IX (a marker of hypoxia) predicts reduced progression-free survival and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. These serum biomarkers deserve further study in larger trials of HER2-targeted breast cancer treatment. Supported by grants from Komen for the Cure, and the PA Breast Cancer Coalition.
Implementing independent double checks for patient-controlled analgesia (PCA) pump programming.
Authors: Nie Bohlen, Hannah Felton Lyons, Barbara J. Cashavelly, Inga Tolin Lennes
Journal: Journal of Clinical Oncology (2012)

153 Background: Pain is the most common symptom experienced by oncology patients. Up to 90% of all patients with advanced cancer experience pain and 50% of those describe their pain as moderate to severe. The patient controlled analgesia (PCA) is commonly used to treat pain on the acute care oncology unit at The Massachusetts General Hospital (MGH). The PCA pump can be programmed incorrectly, resulting in over or under dosing of patients with opiates. Both the Federal Drug Administration (FDA) and the Institute for Safe Medication Practice (ISMP) recommend an independent double check (IDC) be done on error prone processes like the use of high alert medications. An IDC involves two clinicians separately checking (alone and apart from each other, then comparing results) the infusion settings in accordance with the physician’s order. Methods: The nurses on the acute care oncology unit at MGH were surveyed to determine their baseline understanding of an IDC. Training was conducted and a process for documentation implemented. A second intervention included further education initiatives such as posters of key points and a web-based knowledge survey of the IDC definition, process, and documentation. Results: Prior to the initial implementation 80% (32/40) of the nurses provided a partially correct definition of an IDC, 17.5% (7/40) an incorrect definition of an IDC and only 2.5% (1/40) provided a correct definition of an IDC. After the initial educational activities, a second knowledge survey was administered. Performance improved with only 13.4% (7/52) of the nurses missing one or more of the three questions on survey. After the initial education, of the 126 opportunities to document an IDC 21.4% (27/126) were done correctly. Performance improved to 80.7% (67/83) after the second intervention. Conclusions: Prior to implementing this IDC education, nurses at MGH did not have a clear understanding of what is required for an IDC of a PCA. This pilot education module was effective in decreasing the knowledge gaps and improving performance. Education must be concise and repetitive to change practice. Successful implementation of an IDC process improves the safety of a high-alert medication for the patient.
Opioid use among prostate cancer patients with bone metastases.
Authors: Avin Yaldo, Lonnie Kent Wen, Augustina Ogbonnaya, Adriana Valderrama, Jonathan K Kish, Michael Eaddy, Charles Kreilick, Brian S. Seal
Journal: Journal of Clinical Oncology (2015)

278 Background: Bone metastases (mets) occur in ≥90% of men with castrate-resistant prostate cancer (PC), causing significant pain and resource use. Opioids are frequently used in managing pain throughout the course of care, but few studies have quantified the incremental use of opioids after the onset of bone mets. This study describes treatment patterns and incremental use of opioids among PC patients diagnosed with bone mets. Methods: Prostate cancer patients (ICD9=185.xx or 233.4) newly diagnosed with bone mets (ICD9=198.5) from 2006-2012 were identified from MarketScan databases. Patients were required to be ≥40 years, continuously eligible for medical and pharmacy benefits ≥12 months pre and ≥6 months postdiagnosis, and without evidence of other primary cancers during the study period. Patients were initially categorized as non-users of opioids (&lt;10 days use), short-term users (≥10 but &lt;60 days use), or long-term users (≥60 days use), and further by presence of skeletal-related events (SREs). Type of opioid therapy, proportion of time on opioids, morphine equivalent dose, and NSAID use were evaluated pre and postdiagnosis. Results: There were 4,476 patients identified for inclusion; 438 (9.8%) had an SRE. Mean age was 72 and 1.6% had chronic pain at baseline. The proportion of opioid users increased from 25.2% at baseline to 32.9% after diagnosis (P&lt;0.0001). Among opioid users, the proportion of long-term users increased from 29.9% to 45.5% (P&lt;0.0001). Use of monotherapy short-acting opioids decreased (pre 79.0% vs post 71.9%; P&lt;0.0001), with a corresponding increase in mixed-action opioids (pre 13.3% vs post 23.4%; P&lt;0.0001). Mean morphine equivalent dose (pre 7.1mg vs post 9.9mg; P&lt;0.0001) and proportion of time on opioid therapy also increased substantially (pre 28.3% vs post 54.7%; P&lt;0.0001). NSAID use decreased after bone met onset (pre 21.9% vs post 15.5%; P&lt;0.0001). Opioid use and radiation therapy were more evident in patients with SREs (opioids 21.9%, opioids + radiation 32.6%, radiation 29.5%), and mean morphine equivalent dose was 10.8mg. Conclusions: Long-term opioid use and dose significantly increased after bone met onset in PC. Novel strategies that mitigate bone pain and minimize opioid use should be evaluated in this population.
Lung toxicities encountered with gemcitabine in the treatment of lymphomas.
Authors: A. Jajeh
Journal: Journal of Clinical Oncology (2010)

e18561 Background: Gemcitabine is a diflourinted analogue of deoxycytadine which acts as antimetabolite. It is cell cycle specific and blocks cells in the G1/S interface. It is an active agent in the treatment of non-Hodgkin and Hodgkin lymphomas as a single agent or in combination with other active agents. Various form of lung toxicities encountered in certain patients with previous risk factors that predispose for such risk. Prior exposure to certain chemotheraputic drugs, total body radiation TBI, depressed cellular and humoral immunity and dosages used are very crucial in our analysis of sixty patients treated with this agent. Methods: Retrospective analysis of sixty patients with different type of lymphomas treated with gemcitabine as a single agent or in combination showed that five patients had developed serious lung toxicities identified by bronchoscopy and lung biopsy that is not related to the lymphomatous involvement. A total of sixty patients,twenty five with refractory or relapsed Hodgkin lymphoma, nineteen patient with refractory peripheral and cutaneous NHL and sixteen refractory/ relapsed B-cell NHL. Male:Female ratio 3:1, mean age 53 range 19-79. Blacks 45, whites 19, hispanics 34 and other 2 percent. Results: All patients had abnormal chest X-ray and were symptomatic. All patients developed dyspnea on exertion, cough and reduced room air arterial saturation. All patients had bronchoscopy and BAL. One patient had open lung biopsy. Two patients had prior exposure to TBI for autologous bone marrow transplant, one patient had Bleomycin. Gemcitabine dosages that exceed 1,200mg/m2 in each therapy for more than four cycles seen in two patients. All patients had reduced quantitative immunoglobulins and T cell depletion and low serum albumin. No infectious risk factors identified. Steroids and Immunoglobulins IV IgG therapy can ameliorate toxicity. Conclusions: Identification of above risk factors;TBI, Bleomycin,gemcitabine dosage above 1,000mg/m2,cellular T cell depletion, low humoral immunity and low albumin should be avoided. Initial and monitoring complete pulmonary fuction tests are very crucial preventive method in avoiding lung toxicities. No significant financial relationships to disclose.