tbuckley/cabot-search huggingface dataset:
Patient–provider communication issues concerning fertility preservation with newly diagnosed cancer patients
Authors: S. T. Vadaparampil, G. P. Quinn, J. Lancaster, P. Jacobsen, D. Keefe, T. L. Albrecht
Journal: Journal of Clinical Oncology (2008)

6629 Background: Cancer patients of childbearing age may experience infertility as a result of either their diagnosis or the subsequent treatment. Studies report at least 40% of cancer survivors do not know their fertility status or did not discuss this issue prior to treatment. Sperm banking and embryo cryopreservation are two established methods of fertility preservation (FP) that may be available to patients who desire children. Methods: Twenty eight adult oncologists at two institutions and 26 pediatric oncologists throughout the state of Florida were interviewed via qualitative in-depth interviews to identify their knowledge, attitude and practice behaviors towards discussing FP with newly diagnosed cancer patients of child bearing age. Results: Adult oncologists were less knowledgeable than pediatric oncologists about FP options. Pediatric oncologists were more likely to discuss the issue with their post-pubertal patients than adults were with their patients of any age. Both pediatric and adult oncologists reported similar barriers to these discussions such as: lack of resources, insurance issues, inability for patients to delay cancer treatment to pursue options, and belief that FP is not a high priority. Conclusions: Pediatric oncologists discuss more regularly, but experience similar barriers to Adult Oncologists. Despite the recent American Society of Clinical Oncology guidelines suggesting all patients of childbearing age should receive information about FP, few oncologists are routinely discussing. Qualitative interviews provided greater depth to physician responses leading towards the development of a national survey of all US oncologists to clearly highlight communication barriers from the physician perspective. The prospective patient perspective is severely lacking on FP and could aid in creating motivation for physicians. No significant financial relationships to disclose.
Clinical experience of selective internal radiation therapy in combination with systemic chemotherapy as first-line therapy in patients with unresectable hepatic metastases from colorectal cancer
Authors: T. H. Tan, S. Kosmider, D. Yip, P. Gibbs
Journal: Journal of Clinical Oncology (2008)

15080 Background: For patients with colorectal cancer (CRC), the liver is the most common site of metastatic disease. Selective Internal Radiation Therapy microspheres (SIR-spheres) containing yttrium-90 are a novel and promising treatment for this group of patients. Trial data supports the use of SIR-spheres plus chemotherapy as first-line treatment. In routine clinical practice however SIR-spheres has typically been given to patients that have failed standard chemotherapy. Methods: We present a multi-centre Australian experience of SIR-spheres in patients with metastatic CRC that have not received prior treatment. Results: We identified 16 pts that had received SIR-spheres plus IV chemotherapy as initial therapy. Concurrent treatment was 5-FU in 6 cases and 10 received 5-FU plus oxaliplatin. The median patient age was 57 years (range 44–73). Eleven patients (69%) had no extra-hepatic metastases. There was one treatment related death due to hepatic failure. The most common toxicity from SIR-spheres was gastric ulceration, typically responding well to standard treatment. Thirteen patients (82%) achieved a response (2 CR/11 PR), with an additional patient having a complete response within the liver but progressive disease within lung. For all patients median progression free survival was 9.2 months and median overall survival 21.9+ months. Progression free and overall survival outcomes were significantly better in the patients with liver only disease. Conclusions: Consistent with published trial data, our findings suggest that SIR-spheres combined with systemic chemotherapy is an effective regimen for metastatic CRC in the first-line setting. Patients with liver only disease appear to derive the most benefit from this treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration SIRTEX Australia
Temozolomide-based chemoradiation in naïve pure and mixed anaplastic astrocytoma: Long term results of a phase II study.
Authors: S. Chiesa, G. Chiloiro, S. Manfrida, A. Mangiola, G. R. D'Agostino, G. Mantini, A. Albanese, P. De Bonis, C. Anile, M. Balducci
Journal: Journal of Clinical Oncology (2011)

2057 Background: This phase II study was performed to assess survival, local control and toxicity using concomitant chemo-radiotherapy (CRT) followed by adjuvant chemotherapy with temozolomide (TMZ) in patients affected by WHO III Gliomas [Anaplastic Astrocytomas(AA) and Anaplastic Oligo-Astrocytomas (AOA)] Methods: Patients (≥18 years) with histological diagnosis of of AA or AOA were enrolled. Written consensus was obtained After surgical resection, all patients received concomitant chemotherapy to RT. TMZ (75 mg/m2 daily) was administered from Monday to Friday for all time of radiotherapy (Total dose: 59.4 Gy). After a 4-weeks break, patients received also adjuvant chemotherapy with TMZ (150-200 mg/m2x 5 days ) for at least 6 cycles. Acute toxicity was evaluated according to RTOG criteria. The sample size of patients was assessed by the single proportion powered analysis. Results: From October 2000 to August 2010 59 patients (55.9% AA and 44.1% AOA) were enrolled. Median age was 41 years (range 18- 71 years). Thirty-five patients (59.3%) had a complete surgical resection and 23 patients (40.7%) presented a MR- proven residual tumor. Thirty-seven cases (63.1%) were classified as 1-3 RPA class and twenty-two (36.9%) as 4 RPA class. RTOG neurological toxicity G1-2 and G3 were 10.2% and 6.8%, respectively. RTOG haematological toxicity G1-2 and G3 was 16.9% and 10.1%, respectively. At a median follow-up of 55 months (range 3-123 months) 36 patients (61%) were alive. The median local control (LC) was 32 months and the 1 and 5-year LC was 90.8% and 42.3%, respectively. The median overall survival (OS) was 45 months (29 months for AA and not reached for AOA) and the 1 and 5-year OS was 66.3%, and 34.2%, respectively (for AA 86.8 and 28.1%, respectively; for AOA 95.7% and 56.5%, respectively [HR 4.1; 95%CI: 1.59-8.4]). A statistically significant difference in OS was found among patients with RPA class 1-3 (1 and 5-year OS 96.9%, and 70%) and those with RPA class 4 (1 and 5-year OS 79.9% and 7%). Conclusions: TMZ-based chemo-radiation for WHO grade 3 gliomas is well tolerated and seems to increase local control and survival; a randomized controlled study is necessary to confirm this data.
A phase II monocentric study of oxaliplatin (Ox) in combination with gemcitabine (Gem) (GEMOX) in patients (pts) with advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract
Authors: C. Theodore, F. Bidault, K. Fizazi, M. Di Palma, P. Wibault, N. Bouvet-Forteau, A. Laplanche
Journal: Journal of Clinical Oncology (2005)

4595 Background: Cisplatin (CDDP) based combinations induce approximately 50% of response rates (RR) as first-line chemotherapy in pts with advanced/metastatic TCC. However, they may also cause limiting renal and hematological toxicities and need be administered during hospitalisation. The GEMOX combination has been previously tried in pts with a variety of tumors on account of its potential efficacy and limited toxicity. Methods: Eligibility criteria: Histologically-proven locally advanced unresectable or metastatic TCC of the urothelial tract with at least one measurable target. Study Treatment: Gem 1500g/m2 followed by Ox 85 mg/m2 every 14 days in an outpatient setting. Endpoint: The activity of the combination based on the response rate (RR) (RECIST criteria). The 2-step modified Simon design was used for sample size determination. Results: No of patients enrolled: 30. Patient characteristics: male/female 25/5, median age: 65 yrs (range 41–83). PS 0/1: 4/26. locally advanced disease/metastaic disease: 14/16.Toxicity(NCI-CTC): grade (G) 3 and 4 neutropenia (N) in 3pts and 1 pt respectively, G 3 anemia in 3 pts, G 3 and 4 thrombocytopenia in 2 and one pt respectively, G 1, 2 and 3 peripheral neuropathy in 14, 11 and 2 pts respectively, G 2–3 fatigue in 13 and 7 pts respectively, G2 renal toxicity in one pt and G2 mucosal toxicity in 2pts. Hospitalisation due to N was required in 2 pts and transfusion in one pt. Activity: 3 Complete Responses (CR) and 11 Partial Responses (PR) [one of which was converted into a CR by additional chemo-radiotherapy] were observed in 29 evaluable pts, corresponding to an overall RR of 47% [95% CI:28%- 66%]. Median Overall Survival was 20 months. [95% CI: 7–59]. Conclusions: The GEMOX combination is active in pts with advanced/metastatic TCC of the urothelial tract with minimal renal and hematological toxicity. This combination needs to be compared with other regimens with evaluation of the risk/benefit ratio. No significant financial relationships to disclose.
Sentinel lymph node in prostate carcinoma: Methodology, feasibility, surgical, and oncological consequences: A prospective study about 93 patients.
Authors: Claude Soler, Yves Perraud, Eric Gremillet, Corine Armand, Benjamin Geissler, Aline Steiner, Frederic Levigne
Journal: Journal of Clinical Oncology (2013)

69 Background: There are few studies in the field of prostatic sentinel lymph node (SLN) procedure: in the literature at the most 10 publications are found. However the interest of urological surgeons is growing fast. We want to evaluate the rate of SLN SPECT-CT detection, the rate of SLN involvement, and the incidence of the SLN biopsy on the surgical and oncological management of patients. Methods: 93 patients with prostate cancer were included (gleason 6-9). All patients were elected for a radical laparoscopic prostatectomy. Nanocis* was intratumorally injected, guided by transrectal ultrosonography. 2 injections 0.6 ml in each lobe of the prostate were performed. Patient underwent planar imaging and SPECT-CT 2 hours after injections. Surgery was performed 18 hours after. Results: A lymphatic pelvic drainage was seen in 95,6 % (89/93) by SPECT-CT (external or internal iliac arteries areas). For 27 patients lymphatic drainage was on the right side, for 24 patients it was on the left side, for the 37 remaining patients migration was bilateral. The radioguided lymphadenectomy was assisted by a laparoscopic gamma-probe (Clerad, France), the SLN detection rate was 97.7% (87/89); the average number of resected radioactive nodes was 1.6 (range 1 to 5). By all the ways, a limited pelvic lymph node dissection was performed (including external iliac to common iliac arteries areas) in all 93 cases. An SLN involvement was found in 6 cases (5/87= 5.75%); in these 6 cases and in the 81 cases without SLN involvement, no metastatic involvement was found in the other lymph nodes, as well as in the 6 patients for which no SLN could be selectively resected (4 with no drainage seen and 2 not detected intra-operatively although visualized on lymphoscintigraphy). Conclusions: The low rate of lymphatic involvement is not surprising considering the Gleason score range 6 to 9 (low metastatic risk). So, the preliminary results are very attractive, especially for these patients that could have been falsely considered as N0. Our study is still in progress, and if these results are confirmed on a larger scale, then SLN procedure could be considered in the routine management of low risk prostatic carcinomas.
Standardizing patient-centered outcomes measurement in prostate cancer: An international, cross-disciplinary effort.
Authors: Neil E. Martin, Laura Massey, Caleb Stowell, Markus Graefen, Hartwig Huland
Journal: Journal of Clinical Oncology (2014)

271 Background: The prospective collection of standardized, patient-centered outcomes for men with prostate cancer will allow intra- and inter-institutional comparisons, patient education, self-assessment and dissemination of best practices. We lack recommended standardized sets of such outcomes. Methods: Through the International Consortium for Health Outcomes Measurement, a working group of urologists, radiation oncologists, registry representatives and patient advocates convened to develop a recommended minimum set of measures which institutions would collect on all prostate patients. Using a modified Delphi method over a series of in-person meetings and conference calls, a final set of recommendations was developed. Results: Approximately 30 experts in prostate cancer care from North America, Europe, Australia, and the Middle East participated in the process, representing academic centers, registries and patients. We defined the scope of this initial effort as outcomes related to the management of localized prostate cancer. The group recommended cross-disciplinary measures applicable to a variety of treatment approaches from surveillance to radiation and prostatectomy. Standards were identified for disease control definitions as well as baseline patient and disease-specific risk stratification factors. Domains of patient reported outcomes to be tracked in follow up were identified including urinary incontinence, urinary irritation, bowel irritation, sexual function, and symptoms related to hormonal therapy. Finally, specific tools to assess these domains and gaps in our current tools were identified. The final recommended set will be presented. Conclusions: Standardized outcome reporting is a necessary component in the movement towards high-value health care. Patient-centered outcomes related to toxicity and disease control can be identified and systemized by a multidisciplinary group of experts. The result of this project is an initial step in what will be an iterative process with the goal of improving the care of all men with prostate cancer. An international pilot project has been proposed based on implementing the final set of recommendations.
Phase I trial of escalating doses of the TLR9 agonist HYB2055 in patients with advanced solid tumors
Authors: D. J. Moore, J. Hwang, J. McGreivy, S. Park, S. Malik, R. R. Martin, T. M. Sullivan, S. Agrawal, J. Marshall
Journal: Journal of Clinical Oncology (2005)

2503 Background: HYB2055 (IMOxine) is a novel agonist of Toll-like receptor 9 (TLR9) and shows potent antitumor activity in mouse models. HYB2055 was well tolerated in a phase I multiple-dose volunteer trial. Methods: IMOxine was administered to 23 refractory cancer patients with advanced solid tumors by weekly subcutaneous injection. Treatment continued on a 4-w cycle based on tolerance and absence of disease progression as assessed by RECIST. Dose limiting toxicity (DLT) was grade 4 or grade 3 non-heme toxicity that prevented treatment for 2 weeks. Clinical/lab safety assessments, pharmacokinetics, leukocyte subsets, and serum cytokine levels were monitored. Results: 19 patients completed 4+ weeks of treatment, with 3+ patients at 0.04, 0.16, 0.32, 0.48, and 0.64 mg/kg/w. No DLTs occurred. Side effects included injection site reaction (78%), fever (61%), chills (57%), fatigue/malaise (57%), and myalgia (35%). Grade 3 toxicities possibly related to therapy were pain/nausea in one patient, hypoxia/chills in one patient (pre-existing COPD), and anemia in 2 patients. IMOxine regularly produced a lymphopenia 24 h after treatment consistent with cytokine-mediated lymphocyte margination. IMOxine typically increased the percentage of CD69+ T cells. Although plasma drug concentrations were dose proportional, immunology parameters appeared to plateau or decrease above 0.16 mg/kg/w. Nine patients had stable disease after 8 w of IMOxine treatment, and 4 had stable disease for at least 16 weeks. Of these 4, 1 with renal cell carcinoma had minor regression after 16 weeks and persisting currently through 40 weeks. Discontinuation in five patients was due to rapid disease progression after 1–5 doses of IMOxine, two were consent withdrawals, and three were symptomatic deterioration despite radiologically stable disease. Conclusions: IMOxine treatment was well tolerated at all doses. Effects were consistent with the immunological mechanism of action and clinical outcome was encouraging. A phase II monotherapy trial in renal cell carcinoma has been initiated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hybridon Hybridon
Continuous-dose regorafenib (REG) in hepatocellular carcinoma (HCC): Phase I safety and pharmacokinetic (PK) study.
Authors: Richard S. Finn, George R. Blumenschein, Anthony W. Tolcher, Stephen Leong, Oliver Boix, Konstanze Diefenbach
Journal: Journal of Clinical Oncology (2013)

300 Background: REG is a novel oral inhibitor of multiple kinases involved in angiogenesis, oncogenesis, and tumor microenvironment. A multicenter, open-label, single-arm phase I dose-escalation study evaluated REG given with a continuous schedule and established 100 mg once daily as the maximum tolerated dose. This study explored the safety and PK of this dose in an expanded cohort of advanced HCC pts. Methods: Adults with advanced treatment-refractory HCC (Child Pugh [CP] A or B) received REG 100 mg daily until tumor progression, unacceptable toxicity, or pt/investigator decision to stop. Safety and PK were primary endpoints. Tumor response was a secondary endpoint. Results: The HCC expansion cohort included 20 pts: male/female ratio: 14/6; 10 Asian, 4 white, 4 Hispanic, 1 black, 1 other; mean age: 56.8 ± 13.5 years; 16 CP A, 4 CP B; 2 stage II, 3 stage IIIA, 1 stage IIIC, 13 stage IV; 14 pts had disease progression at entry; 11 pts had 2+ metastatic sites; 19 pts had received prior sorafenib. Median duration of treatment was 42 days (range 23–329); 2 pts were still on treatment at data cutoff. Two pts died during the study (both due to disease progression). Drug-related AEs were reported in 18 pts (90%). The most common grade 3+ drug-related AEs were hypertension (n=4, 20%), fatigue (n=2, 10%), hand-foot skin reaction (n=2, 10%), pain (n=1, 5%), and hemoglobin, ALT, AST, lipase, and other metabolic/laboratory abnormalities (n=1, 5% each). Nine pts required REG dose modifications, and 2 pts stopped treatment permanently because of drug-related AEs. No drug-related serious AEs were reported. Single-dose PK data (cycle 1, day 1) were available from 18 pts, but only 1 pt was evaluable for steady-state PK samples. Single-dose analysis did not indicate any effect of CP status on REG PK. One pt had a partial response and 6 pts had stable disease; median time to progression was 36 days (range 28-237). Conclusions: Continuous-dose REG 100 mg once daily was well tolerated in pts with advanced HCC that progressed on prior sorafenib. PK data obtained after a single 100 mg dose did not indicate any effect of CP status on the PK of REG or its primary metabolites. Disease control was achieved in 7 pts. Clinical trial information: NCT01117623.
Discovery and validation of the nuclear export protein CRM1 (XPO1) as a new target for the treatment of renal cell carcinoma (RCC).
Authors: Hiromi Inoue Wettersten, Michael Kauffman, Sharon Shacham, Yosef Landesman, Joy Yang, Christopher Evans, Robert Weiss
Journal: Journal of Clinical Oncology (2013)

411 Background: The currently available targeted therapies for RCC have had limited success, so it is imperative to discover new therapeutic approaches for metastatic RCC. In a search for new such targets, we have identified inhibitors of CRM1 (XPO1, exportin1), the major karyopherin that mediates the export of most tumor suppressor proteins from the nucleus. To expand our initial work on the first generation of CRM1 inhibitors, we now evaluate KPT-330, an orally available Selective Inhibitor of Nuclear Export (SINE), the best tolerated among a series of CRM1 inhibitors that is currently in phase I clinical trials. Methods: The RCC cell lines (Caki-1 and 786-O) and a primary normal human kidney (NHK) cell line were treated with KPT-330, and MTT assays were performed. The cells were subjected to immunofluorescence and immunoblotting for appropriate proteins. Caki-1 xenograft mice were treated with KPT-330 for 15 days, and tumor volume was assessed. Results: KPT-330 selectively attenuated CRM1 levels and caused dose-dependent toxicity (EC50 &lt; 1 µM) through apoptosis in all RCC cells. In untreated RCC cells, p21 was localized in the nucleus, where it likely functions as a cell cycle arrest protein, and in the cytosol, where it functions as an anti-apoptotic protein. However, in NHK cells, p21 was confined to the nucleus. KPT-330 increased p53 and p21 and confined them to the nucleus in both NHK and RCC cells. KPT-330 given orally inhibited RCC growth in xenograft mice (85.3 % inhibition, p &lt; 0.001). Moreover, KPT-330 showed synergism with a Bcl-2 inhibitor ABT-737 in vitro, indicating the potential for combination therapy with a CRM1 inhibitor and Bcl-2 inhibitor. In vivo studies to test the combination of KPT-330 with Bcl-2 inhibitors are ongoing. Conclusions: We introduce a new therapeutic approach for RCC treatment based on the inhibition of the nuclear export of key tumor suppressors. Inhibition of CRM1 causes forced nuclear retention, and thereby activation, of several key p53-pathway proteins, leading to apoptosis in RCC cell lines in vitro and tumor growth inhibition in vivo.
Urinary metabolomics of gastric cancer.
Authors: Angela W Chan, Pascal Mercier, Dan E. Schiller, Dean Eurich, David Broadhurst, Michael B. Sawyer
Journal: Journal of Clinical Oncology (2015)

22 Background: Gastric cancer (GC) has 70-75% mortality, attributable to delayed diagnosis. There is no standard screening in North America. Metabolomics is a systems biology approach to measure low molecular weight chemicals (metabolites) in body fluids or tissues to provide a phenotypic “fingerprint” of disease etiology. In this preliminary study it was hypothesized that metabolic profiling of urine samples using 1 H-NMR spectroscopy could discriminate between resectable gastric adenocarcinoma (GC), benign gastric disease (BN), and healthy (HE) patients (pts). Methods: Midstream urine samples were collected, processed, and biobanked at -80°C, from 30 BN, 30 HE and 16 of 29 GC pts visiting three Edmonton clinics from August 2013 – January 2014. Thirteen of 29 samples were retrieved from a 2009-13 GC biobank. Samples were matched on age, gender and BMI. Using a validated standard operating procedure each sample was analyzed using high resolution 1 H-NMR spectroscopy. Resulting spectral traces were converted into annotated and quantified metabolite profiles of 58 metabolites. Univariate and multivariate statistical analysis uncovered a disease specific biomarker profile. Partial Least Squares Discriminant Analysis (PLS-DA) developed a GC vs. HE discriminative model. A Receiver Operator Characteristic (ROC) curve was constructed. Results: There was no significant difference in metabolite profiles between GC and BN pts. However, univariate analysis revealed 13 metabolites that differed significantly between GC and HE (p&lt;0.05). Correlation analysis, followed by PLS-DA produced a discriminative model with an area under ROC curve of 0.996, such that for a specificity of 100% the corresponding sensitivity was 93%. Conclusions: GC pts have a distinct urinary metabolite profile compared to HE controls; however in this study metabolic profiling was unable to discriminate GC from BN pts. This was probably due to sample size and phenotypic heterogeneity of BN patients. This preliminary study shows clinical potential for metabolic profiling for early GC detection.