tbuckley/cabot-search huggingface dataset:
Prognostic role of interleukin-1B and interleukin-1-receptor antagonist polymorphisms in localized gastric cancer.
Authors: E. Goekkurt, G. Folprecht, S. Lehmann, L. Obermann, M. Kramer, A. Rentsch, S. Wilop, G. Ehninger, T. H. Brummendorf, J. Stoehlmacher-Williams
Journal: Journal of Clinical Oncology (2011)

10623 Background: Interleukin-1b (IL1b) and interleukin-1 receptor antagonist (IL1-RN) polymorphisms have been suspected to play a role in prognostication of advanced gastric cancer (GC). Here, we sought to determine the prognostic role of these polymorphisms in localized GC. Methods: 62 patients (pts) were enrolled in this prospectively planned analyses. Pts were treated with peri-operative neoadjuvant and adjuvant chemotherapy between 2006 and 2010. All pts signed written informed consent for genetic analyses. DNA for genotyping was extracted from whole blood samples. Genotyping was performed using PCR-based methods. The primary objective was to analyze the association between genotypes and clinical outcome measured by overall survival (OS). Results: Median age was 59 years. Majority of pts were male (81%). 86% of pts were treated with epirubicine in combination with cisplatin or oxaliplatin and 5-fluorouracil or capecitabine. 14% were treated without epirubicine. Pts were assigned to receive peri-operative treatment consisting of 3 neoadjuvant and 3 adjuvant chemotherapy cycles. Median OS of the whole study population was 32.0 months [95%CI (28.0;35.9)]. IL1bC-511T, IL1bT-31C and IL1-RN polymorphisms were in strong linkage disequilibrium. In fact, the wildtype genotype IL-1b-511CC genotype was observed exclusively in combination with the wt IL1b-31TT and vice versa and a strong correlation with the IL1-RN L/L genotype was observed. Wildtype genotypes were associated with favourable median OS. Multivariate cox regression analyses revealed following factors as independent prognosticators of OS: presence of N2 status with a HR of 5.6 [95%CI (1.5;21.1); p=0.01], age with a HR of 1.6 [95%CI (1.2;2.1); p<0.001] and presence of the IL1-RN L/L genotype with a HR of 0.2 [95%CI (0.1; 0.5), p=0.001]. Median OS in pts with the homozygous wt genotype IL1-RN L/L was not reached whereas median OS in 2/L or 2/2 pts was 32 months [95%CI (18.1;45.9); p=0.09; log-rank test]. Conclusions: Our results confirm the prognostic role of IL1b and IL1RN polymorphisms in localized GC. These polymorphisms might play a crucial role in the guidance of multimodal treatment of localized GC.
A clinical parameters-based predictive model to predict early efficacy for rectal cancer patients with neoadjuvant chemotherapy alone: Subgroup efficacy analysis of a phase II study.
Authors: Jianwei Zhang, Yue Cai, Huabin Hu, Ping Lan, Jianping Wang, Meijin Huang, Liang Kang, Yanhong Deng
Journal: Journal of Clinical Oncology (2015)

716 Background: To avoid the damage of radiotherapy for a part of patients, we have an ongoing phase II study comparing Neoadjuvant FOLFOX6 chemotherapy with or without radiation in Rectal Cancer. To define the population who could obtain benefit from neoadjuvant chemotherapy alone, we aimed to develop a model in which clinical parameters are used to predict early efficacy of neoadjuvant chemotherapy for rectal cancer, including tumor regression grade (TRG) and ypTNM down-staging. Methods: Until now, 116 patients were enrolled into FOLFOX6 chemotherapy alone group. All the clinical parameters were collected, including gender, age, tumor location and size by MRI imaging, blood routine test, blood biochemistry and serum tumor markers, TRG and ypTNM staging. 96 patients were used to be training set and another 20 patients was the validation set. Binary logistic regression was used to analyze the effect of all clinical factors on TRG and ypTNM stage. Clinical variables were incorporated into the Cox models for multivariate analysis. Results: Among the 116 patients, 9 patients had TRG 0 (complete regression), 26 patients with TRG 1 and 81 patients with TRG 2 to 3 (poor regression). 47 (40.5%) patients had good down-staging with ypTNM stage 0 and stage I. The optimal multivariable predictive model for TRG (0-1 vs. 2-3) was a four-variable model consisting of age, ApoA1, tumor length and tumor encircle size (AUC=0.732, 95% CI, 0.614–0.849). The model for ypTNM (stage 0-I vs. II-III) was also the four parameters (AUC=0.725, 95% CI, 0.615–0.835). Patients with younger age, shorter tumor length, smaller encircle size and higher ApoA1 had better outcome with chemotherapy. Applying the four clinical parameters model to the validation cohort, a good performance (AUC=0.792, 95% CI, 50.54–0.95) was obtained. Conclusions: With this predictive model, the patients who might obtain good efficacy from neoadjuvant FOLFOX6 chemotherapy could avoid radiotherapy damage. And better suggestion would be provided for patients who might be high risk with chemotherapy alone.
Early experience with Puerto Rico: Effective use management of bone agents.
Authors: Kenneth Wurtz, Dinah Faith Q. Huff, Lourdes Feliciano, Charles L. Bennett, Kevin Knopf, William J. Hrushesky, Anna DiMarco, Michael Baum
Journal: Journal of Clinical Oncology (2016)

130 Background: Oncology Analytics is a cancer care decision support group recently entering the Puerto Rican cancer care marketplace. Bone agents are used in metastatic cancer management to delay the progression of lytic bone metastases. These agents are also used for the treatment of demonstrated osteoporosis with bone densitometry (DEXA scan). Oncology Analytics has found these agents are sometimes used in the absence of lytic metastases or osteoporosis. When this is discussed with treating physicians, practice patterns promptly improve. Beginning our work: The following work focuses entirely upon use among patients with bone mets. There is modest use of bone agents for bone mets among PR oncologists. A statistically significant decreasing and sustained trend in the inappropriate utilization of bone agents and especially the use of denosumab in the PR market is closely associated with recent initiation of OA decision support. Methods: We analyzed data from oncology drug preauthorization requests for bone modifying agents for the management of metastatic bone disease submitted by providers to payers serving in Puerto Rico from Jan 1, 2015 through September 30, 2015. Results: Within the 9 months, non-compliant zoledronic acid use diminished by one-third; pamidronate by 40%; and denosumab use was decreased by 75%. Quarterly dynamics demonstrates a statistically significant downward trend in the unnecessary use of these agents among PR oncologists (p,0.05). Conclusions: Oncology Analytics presence in a new market enhances cancer care quality and cancer care value quickly, while at the same time conserving substantial resources.
Phase I trial of zirconium 89 (Zr89) radiolabeled J591 in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Michael J. Morris, Neeta Pandit-Taskar, Jorge A. Carrasquillo, Joseph A. O' Donoghue, John Humm, Serge K. Lyashchenko, Eric C. Haupt, Neil Harrison Bander, Scott T. Tagawa, Jason P. Holland, Peter M. Smith-Jones, Jason Stuart Lewis, Stephen Barnett Solomon, Howard I. Scher, Steven M. Larson
Journal: Journal of Clinical Oncology (2013)

31 Background: Presently, there are no means of accurately and reproducibly imaging bone metastases for patients with mCRPC. We are investigating a prostate-specific imaging method that can directly visualize metastases using PSMA as a target and Zr89 radiolabeled anti-PSMA antibody J591 as a tracer. Following the FDA roadmap for biomarker development, we report the first human data on the tracer and its preliminary analytic validation. Methods: 5 mCi of Zr89-J591 was administered intravenously and 4 serial PET/CT scans were obtained within the following time intervals post-injection: 2-4 hours, 18-30 hours, 2-5 days, and 6-7 days. Pharmacokinetic (PK) sampling occurred at 5, 30, and 60 minutes post-injection, and at each PET scan. Patients underwent standard cross-sectional imaging, bone scintigraphy, and FDG PET scanning. Metastatic sites were biopsied in order of preference: Zr89-J591 and FDG positivity, then Zr89-J591 and FDG mismatch, and lastly standard imaging and any PET mismatch. Results: Ten patients were scanned, 132 Zr89-J591 positive sites were detected, and 12 lesions (5 bone, 6 node, 1 lung) in 8 patients were biopsied. Tissue correlation: 12/12 biopsies were positive for cancer. 11/12 biopsied lesions (5 bone, 5 node, 1 lung) were positive on Zr89-J591 imaging. 10/12 were positive by standard scans or FDG. 1 lesion was negative by Zr89-J591 PET, but positive by other modalities. Immunokinetics: Blood clearance T 1/2α : 7 +/- 4.5 h (1.1-14 h); T 1/2β : 62 +/- 13 h (51-89 h); Whole body clearance T 1/2 : 219 +/- 48 h (153-317 h). Dosimetry: Maximum retention in liver 8 +/- 1.5 SUV; Kidney 4.1 +/- 0.8 SUV; Tumor 8.2 +/- 6.5 SUV (mean SUV in bone 11.13 +/- 7.57 vs. soft tissue 4.31 +/- 2.59). Optimal time for patient imaging after injection, in terms of tumor to background ratios was 7 +/- 1 days. Conclusions: Zr89-J591 imaging demonstrates excellent tumor localization, pathology correlation, and can demonstrate the presence of tumor even when lesions are negative by standard imaging or FDG PET imaging. PK properties of the tracer have been defined. Use of Zr89-J591 to direct biopsies of metastases provides excellent yield. Further studies to examine reproducibility and post-treatment effects are planned. Clinical trial information: NCT01543659.
Assessment of the effectiveness of a prechemotherapy teaching session: A Brown University Oncology Group study.
Authors: Nathan Connell, Anthony E. Mega, Jorge J. Castillo, Mary Anne Fenton, Carolyn Bartley, Anne Kaplan, Benjamin Murphy, Jenna Iannuccilli, Lindsey Stobie, Currie Touloumtzis, Andrew Schumacher, Susan Korber, Katherine E. Faricy-Anderson, Pamela Bakalarski, William M. Sikov, Howard Safran, Anthony George Thomas, Debora Isdale, Kayla Rosati
Journal: Journal of Clinical Oncology (2012)

260 Background: Pre-chemotherapy teaching sessions, often coordinated by nursing personnel, are an opportunity to educate patients on treatment side effects, schedule, medications for toxicities such as nausea, and how to contact the oncology team if adverse events develop. Our institution provides a structured 60-minute nurse-coordinated pre-chemotherapy teaching session. The aims of this study were to evaluate whether pre-chemotherapy teaching sessions improve patient knowledge, preparedness, and anxiety in relation to chemotherapy. Methods: Patients were offered the opportunity to participate in the study after their medical oncologist had reviewed their treatment regimen. After informed consent was obtained, participants were administered a 10-question survey assessing knowledge of treatment adverse effects, treatment schedule, management of complications, accessing their medical team, and patient anxiety. Subjects then participated in a pre-chemotherapy teaching session with an oncology nurse. The survey was readministered when patients returned on day 1, cycle 1 of treatment and on day 1, cycle 2. The questionnaire used a 1 to 4 rating scale (1=no knowledge, 2= minimally informed, 3= reasonably informed, 4= well informed). A pre-defined mean change of 1 on the rating scale was considered to be clinically significant. Paired one-sided t-tests were performed to evaluate the mean change in groups between each of the three surveys. p values &lt;0.05 were considered statistically significant. Results: At the time of analysis, 78 patients had completed a pre-chemotherapy teaching session and all three surveys. After participating in a teaching session, there was an increase in patient’s perceived knowledge of side effects (mean score 2.3 vs. 3.5, p&lt;0.001), knowledge of the treatment schedule (mean score 2.4 vs. 3.5, p&lt;0.001) and medications to prevent nausea (mean score of 1.4 vs. 3.1, p &lt;0.001). There was also a statistically significant reduction in patient anxiety in relation to treatment, p&lt; 0.001. Conclusions: These results show that a nurse-coordinated, pre-chemotherapy teaching session increases patient knowledge and reduces anxiety regarding their upcoming treatment.
Evaluation of p53 mutation as a predictive biomarker for outcome to chemotherapy in ovarian cancer.
Authors: A. H. Calvert, J. C. Jackson, C. Hutton, A. M. Swart, W. Qian, C. Kwakye, R. Fossati, A. Lissoni, P. G. Harper, N. Colombo, R. J. Edmondson, J. Lunec
Journal: Journal of Clinical Oncology (2011)

10522 Background: There is increasing evidence that patients (pts) with wild type p53 have higher response rates to single agent carboplatin and may gain no benefit from the addition of paclitaxel chemotherapy. We tested two hypotheses in the context of a controlled clinical trial: 1) Tumours with wild-type p53 are more sensitive to platinum based chemotherapy than those with mutant p53, so will survive longer; 2) Pts whose tumours have mutant p53 benefit from the addition of paclitaxel to treatment, whilst those with wild type p53 do not. Methods: We collected 265 archival diagnostic tissue samples from pts that took part in the UK Medical Research Council ICON3 ovarian cancer trial comparing carboplatin or CAP (cyclophosphamide, doxorubicin, cisplatin) vs carboplatin plus paclitaxel. We examined the tissue for p53 mutations by genomic DNA sequencing of the coding exons and adjacent splice sites. Overall survival (OS) was updated for this study. A Cox regression model was applied in the analysis. Results: Mutations of p53 were detected in 130/265 (49.1%) pts tumour samples. With a median follow up of 12 years, a total of 214 (84%) pts had died. In univariate analysis, the presence of p53 mutations was associated with worse OS for pts who received single agent carboplatin [HR (95%CI)=1.72(1.14-2.60), p=0.0099, n=121] and p53 status retained independent prognostic significance after adjusting for age, stage, residual bulk, grade and histology [HR (95% CI)=1.89 (1.20-2.93), p=0.0059]. For the second hypothesis (n=265), pts whose tumours had mutant p53 showed greater benefit from the addition of paclitaxel to their treatment [HR (95%CI)=0.64(0.43-0.95) p=0.027] compared to patients with wild-type p53 tumours [HR (95%CI)=1.02(0.68-1.54) p=0.92]. Conclusions: We conclude that p53 is an independent prognostic biomarker for OS in ovarian cancer, particularly for patients receiving single agent carboplatin. Furthermore, the addition of paclitaxel shows OS benefit for pts with p53 mutant tumours, but not for those with wild-type p53 tumours.
A web-based program to engage informal caregivers to support patients through chemotherapy.
Authors: Maria Silveira, CW Given, Alla Sikorskii, Barbara Ann Given, Kemp Bailey Cease, John D Piette
Journal: Journal of Clinical Oncology (2015)

90 Background: Most interventions to improve cancer symptoms rely on patient self-management, which can be challenging for some. "Cancer CarePartners" is a system designed to engage informal caregivers to support patients' quality of life as they receive chemotherapy. The system provides weekly, automated telephonic symptom assessment to patients, and symptom alerts plus tailored advice to their caregivers. We conducted a randomized control trial to test the efficacy of this program in controlling symptoms and improving adherence to chemotherapy. Methods: Consenting patients with solid tumors undergoing chemotherapy that reported any symptom at ³3 (out of 10) and had a consenting caregiver were randomly assigned to 10 w of either Cancer CarePartners or an attention control. Arms were balanced for lung cancer and caregiver type. Subjects were surveyed at 0, 10, and 14 weeks; charts were reviewed at 14 weeks. We tracked patient and caregiver use of the system. Results: 834 patients were referred to the study and 371 (45%) met eligibility criteria. Among the 151 (41%) patients who consented, 91% entered the study and 82% completed the trial. Patients completed assessments for most weeks on study (mean 7.7 intervention vs. 8.3 control). Intervention caregivers logged into the Website an average of 4.1 times over 10 weeks (range 0-10). At 10 weeks, intervention patients experienced lower summed symptom severity than controls (mean 19.5 vs. 23.2), but this was not statistically significant after adjusting for baseline symptoms (P = 0.107). They also experienced fewer inpatient stays (mean 0.19 vs. 0.34, P = 0.1814) and phone calls with providers (mean 0.46 vs. 0.62, P = 0.3019) than controls did. They received more chemotherapy (# agents per cycle 3.6 vs. 3.1 P = 0.0395; # agents per infusion 2.2 vs. 2.0 P = 0.0054). Intervention caregivers reported less depression (CESD Coef -1.08, P = 0.094, 95% CI -2.35 to 0.19), and similar burden as controls. Conclusions: Cancer CarePartners enhances caregiver support for patients and improves their symptom management and adherence with chemotherapy as a result, while adding little burden to the caregiver. One limitation of the study is that recruitment was less than expected. Clinical trial information: IIR 08-309.
A multicenter phase II study of sorafenib in Japanese patients with hepatocellular carcinoma and Child Pugh A or B cirrhosis.
Authors: Eiichiro Suzuki, Shuichi Kaneko, Takuji Okusaka, Masafumi Ikeda, Kensei Yamaguchi, Michihisa Moriguchi, Tosiya Sato, Junji Furuse
Journal: Journal of Clinical Oncology (2014)

354 Background: Sorafenib has been used as the first-line treatment for advanced hepatocellular carcinoma (HCC), however, its efficacy and safety in Japanese patients (pts), especially those with Child-Pugh (CP) B cirrhosis, have not yet been fully examined. This study was conducted to evaluate the efficacy and safety of sorafenib in Japanese pts with HCC and CP B or CP A cirrhosis. Methods: The eligibility criteria were patients 1) with pathologically or clinically proven HCC, 2) with an ECOG performance status 0 to 2, 3) aged 20 to 79 years, 4) with measurable lesions, 5) with adequate hematological, renal and Child Pugh class A or B liver functions. Sorafenib was administered orally at the dose of 400 mg twice daily. Administration was continued until the detection of disease progression or appearance of unacceptable toxicity. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints included objective response, overall survival (OS), and toxicity. Results: Forty CP A pts and 12 CP B pts were enrolled between April 2010 and January 2012. The median PFS in the CP A pts was 3.3 months (M) and that in the CP B pts was 3.2 M. Among the pts with CP A, there was one patient with confirmed complete response (2.5%), 3 pts with partial response (7.5%), and 19 pts (47.5%) with stable disease (SD). Among the pts with CP B, there were no treatment responses, and 8 (66.7%) pts had SD. The median overall survival in the CP A pts was 13.4 M and that in the CP B pts was 7.4 M. With regard to toxicities, fewer CP A pts experienced grade 3/4 toxicities than CP B pts (77.5% vs. 91.6%). The grade 3/4 toxicities in the CP A and B pts, respectively, included thrombocytopenia (10% and 25%), hand foot skin reaction (27.5% and 16.7%), Erythema multiforme (0% and 16.7%), and upper gastrointestinal bleeding (0% and 16.7%). There were no treatment-related deaths in either group of patients. Conclusions: This study shows that sorafenib is effective and well-tolerated in Japanese patients with HCC and Child Pugh class A liver cirrhosis, consistent with previous reports. The outcome was poorer and severe toxicities were more frequent in patients with Child Pugh B cirrhosis than in those with Child Pugh A cirrhosis. Clinical trial information: 000002972.
Toward a rational strategy for prostate cancer screening based on long-term risk of prostate cancer metastases and death: Data from a large, unscreened, population-based cohort followed for up to 30 years.
Authors: H. Lilja, C. Savage, A. Gerdtsson, T. Bjork, J. Manjer, P. Nilsson, A. Dahlin, A. Bjartell, P. T. Scardino, D. Ulmert, A. J. Vickers
Journal: Journal of Clinical Oncology (2011)

4512 Background: Prostate-specific antigen (PSA) testing remains controversial due to high number of men need to be screened to prevent one death. Current screening recommendations are based on few data. We analyzed PSA in archived blood plasma collected in 1974–92 as part of the Malmö Preventive Project. This is a large, representative cohort of Swedish men not subject to screening, chiefly accruing at age 44-50 (i.e. shortly before PSA is recommended to begin in US) and followed for up to 30 years. The study is a unique “natural experiment” to understand the association between early PSA and long-term risk of prostate cancer morbidity and mortality. Methods: We conducted a case control study nested within a cohort of 12090 men providing blood in 1974-86 and 4999 providing a repeat sample 6 years later and an independent cohort of 1,167 men with blood provided at age 60. 252 men with carefully ascertained evidence of prostate cancer metastasis or death were matched 3:1 with controls. Anti-coagulated plasma was analyzed using methods shown to give highly accurate PSA values. Results: PSA was strongly associated with risk of prostate cancer death or metastasis up to 30 years later (AUC 0.70, 0.76 and 0.90 at age 44-50, 51-55 and 60 respectively, p<0.005). At age 44-50, 44% of cancer deaths occurred in men with PSA >1.6 ng/ml (top 10%) at a median follow up of 27 years. PSA at median at age 44-50 did not rule out risk of metastases or death but did so in older men: 28%, 18% and 0.5% of metastases occurred in men with PSA at median (<0.7, <0.8 and <1.1 ng/ml at age 44-50, 51-55 and, 60 respectively). The risk of prostate cancer metastasis by 15 years for men with PSA at median was never greater than 0.3% at any age. Conclusions: PSA is highly predictive of long-term risk of prostate cancer morbidity and mortality. Close to half of all deaths could be prevented by intense surveillance of a small proportion of men with the highest PSA levels at age 44-50. For men with lower PSA, testing at age 51-55 and age 60 is sufficient to capture risk of prostate cancer metastases or death 10+ years in advance. This strategy would allow 50% of men to have only three lifetime PSA tests.