tbuckley/cabot-search huggingface dataset:
Interferon-α (IFN), interleukin-2 (IL2) and 5-fluorouracil (5FU) vs IFN alone in patients with metastatic renal cell carcinoma (mRCC): Results of the randomised MRC/EORTC RE04 trial
Authors: M. E. Gore
Journal: Journal of Clinical Oncology (2008)

5039 Background: Until the recent introduction of the targeted agents, standard of care for patients with mRCC in Europe has included therapy with single agent IFN. Several phase II studies of the triple regimen IFN+IL2+5FU have shown high response rates with a suggestion of a survival advantage over other therapies. The RE04 study was set up to investigate the efficacy of the triple regimen in the context of a large randomised phase III trial. Methods: Patients with mRCC were randomised 1:1 to receive single agent IFN 10 MU tiw until progression or toxicity (Arm A) or a combination of IFN+IL2+5FU for 2 cycles (Arm B). A total of 1,006 patients were randomised over 5 years. Overall survival (OS) was the primary outcome measure with 90% power to detect a 3 month improvement in OS. Results: Accrual into Arms A and B was 502 and 504 patients, respectively. Pretreatment characteristics were well balanced with a median age of 57 years, 57% were WHO performance status 0 and 90% were nephrectomised. Median follow up was 27.8 months. There was no evidence of differences in median OS (18.7 vs 18.5 months, HR=1.05, 95% CI 0.89–1.23, p=0.57) or progression-free survival (PFS, 5.5 vs 5.3 months, HR=1.04, 95% CI 0.91–1.19, p=0.56). Best overall response was significantly higher in the triple therapy arm (24 vs 16%, p=0.004). Incidence of grade 3/4 toxicity was significantly higher (p<0.01) for diarrhoea, fever, hypotension, neutropenia and cutaneous skin reaction in patients receiving triple therapy. Quality of life analyses showed no important differences between treatment arms. Conclusions: RE04 is the largest randomised controlled trial yet performed in patients with mRCC. We have shown an advantage to triple therapy over single agent IFN in terms of response but not PFS or OS. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche, Schering-Plough Chiron, Roche, Schering-Plough Roche, Schering-Plough
Neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Predicting long-term outcomes based on response to treatment.
Authors: Kirsten Elizabeth Jean Laws, Christina Wilson, David McIntosh, Stephen Harrow
Journal: Journal of Clinical Oncology (2014)

621 Background: Neoadjuvant long course chemoradiotherapy is well recognised as a standard treatment in locally advanced, margin threatening rectal cancer, in order to downstage and reduce local recurrence. We investigated retrospectively whether long term outcomes could be predicted by response to neoadjuvant treatment, and which factors specifically seemed to predict a risk of poorer outcome. Methods: All patients treated with long course chemoradiotherapy between January 2008 and December 2009 were identified retrospectively. Patients were excluded if the treatment indication was for inoperable disease, postoperative, recurrence, or palliative intent. A total of 231 patients were analysed with retrospective analysis of all electronic records and case notes. The following information was collated: preoperative staging, chemoradiotherapy treatment planned and received, operation performed, postoperative pathology (including nodal status, margins, presence of LVSI, and evidence of response to neoadjuvant treatment), disease free survival, and overall survival. Results: Kaplan Meier curves are presented showing patients with either a complete or partial response to neoadjuvant treatment appear to have a statistically significant improvement in long term outcomes, compared to those with no response (Mean survival 55 months, 56 months and 43months respectively, p&lt;0.01). Furthermore, those who remain node positive or have evidence of LVSI following neoadjuvant treatment appear to have a statistically significant poorer outcome. Conclusions: Our study further develops on previous work looking at the prediction of outcomes following response to neoadjuvant treatment in rectal cancer. It appears that those who respond to initial treatment will have a better outcome than those who do not, including those who remain node positive or with LVSI following treatment. This study is limited because it is retrospective. Randomised controlled trial data is required to enable identification of poor risk imaging and pathology features that might suggest the need for adjuvant therapy following combined modality treatment with neoadjuvant chemoradiotherapy and surgery.
Flow Cytometric Leukemic Blasts Detection in Cerebrospinal Fuid of Children with Acute Leukemias
Authors: Alexander Popov, Tatiana Verzhbitskaya, Grigory Tsaur, Alexander Tomilov, Olga Khlebnikova, Olga Streneva, Egor Shorikov, Leonid Saveliev, Larisa Fechina
Journal: Blood (2011)
Progression-free survival (PFS) of first-line VEGF-targeted therapy as a prognostic parameter for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC).
Authors: C. Seidel, M. Fenner, C. W. Reuter, A. Ganser, V. Gruenwald
Journal: Journal of Clinical Oncology (2011)

4591 Background: Recent scoring systems for mRCC include laboratory markers, clinical course and performance status, without considering the response to systemic therapy. We therefore describe the validity of the PFS during first line VEGF-targeted therapy as an independent prognostic marker for the overall survival (OS) in mRCC. Methods: Medical records of 119 patients (pts.) treated with first line VEGF targeted therapy were retrieved and analyzed retrospectively. 91 pts. received sunitinib, 16 pts. sorafenib, 8 pts. axitinib and 4 pts. bevacizumab combined with either interferon-alfa or everolimus. The median OS and PFS were determined from start of first line VEGF-targeted therapy. Response to treatment was assessed according to response evaluation criteria in solid tumors (RECIST) 1.0. Log-rang test, Kaplan-Meier-, and Cox-regression analysis were employed to predict OS or PFS. Results: Best response to first line therapy consisted of stable disease in 46, partial remission in 18, complete remission in 6 and progressive disease in 25 pts. In 24 pts. best response was not evaluated. The median PFS of first line therapy was 8.1 months (range: 3.9-18.0) and was associated with a median OS of 22.7 months (range: 0.8-46.8). On univariate analysis, a PFS above 6 months (P <.0001), second line treatment (P=0.018), absence of osseous lesions (P=0.012), less than 3 metastatic organ sites (P=0.011), a good MSKCC score (P=0.011), clear cell histology (P=0.04), ECOG 0 (P=0.01), and achievement of complete response were associated with a prolonged OS. On multivariate analyses pts. with a PFS above 6 months (95% CI 0.145-0.438; HR 0.252), good MSKCC score (95% CI 0.072-0.530; HR 0.195), and pts. receiving second line treatment (95% CI 0.156-.674; HR 0.324) were identified as independent prognostic factors. The median OS in pts. with a PFS ≤6 or >6 months was 12 or 33 months, respectively. Conclusions: Our analyses describes first line PFS as an independent prognostic parameter in mRCC, suggesting that VEGF-responsiveness may play a key role for pts. prognosis and may serve as a selection criterion for subsequent therapy.
Lynch Syndrome diagnosis in Ireland: The impact of universal mismatch repair protein testing.
Authors: Lynda Corrigan, Catherine Clabby, Andrew J. Green, David Barton, David James Gallagher
Journal: Journal of Clinical Oncology (2016)

532 Background: It is estimated that approximately 2-4% of colorectal cancers (CRCs) are attributable to Lynch Syndrome (LS). Immunohistochemical testing for mismatch repair proteins is increasingly being performed on CRC specimens. In some centres all incident cases undergo this testing. An abnormal result should initiate a cascade of testing to determine if the loss of mismatch repair protein expression is sporadic or hereditary. We examined the pattern of cancer genetics referral for hereditary CRC diagnosed in Ireland under the age of 70 years. Methods: The number of patients with CRC diagnosed under the age of 70 between 2005 and 2013 was obtained from the National Cancer Registry of Ireland. The number of patients referred for cancer genetics work-up with a diagnosis of CRC &lt; 70 years of age was ascertained from the Department of Clinical Genetics, Our Lady’s Hospital, Crumlin (DCG), the only genetics laboratory in Ireland which processes such samples. The database of the DCG was searched for referrals for hereditary CRC syndromes; and the clinical reason for referral recorded. Results: Between 2005 and 2013, 10,334 patients were diagnosed with CRC less than 70 years of age. 85% were between 50 and 69 years of age (n = 8,736). 229 people under the age of 70 years were referred for cancer genetics work-up for LS with a diagnosis of CRC. Those referred for a non-CRC LS phenotypic manifestation and for predictive testing were excluded. For 41 individuals the reason for referral was not specified. Individuals with CRC were referred for one of the following reasons: diagnosis of CRC &lt; 70 years in 76 patients (33%), diagnosis of CRC &lt; 70 with a family history of LS-associated malignancy in 137 patients (60%), and diagnosis of CRC &lt; 70 with known familial genetic mutation in 16 patients (7%).This represents a referral rate of approximately 0.02% for CRC diagnosed under 70 years of age. Conclusions: 0.2% of colorectal cancer cases diagnosed at &lt; 70 years of age in Ireland over a nine year period were referred for cancer genetics opinion. Increased immunohistochemical testing for mismatch repair proteins should result in increased cancer genetics referral, which will require appropriate service provision within oncology management pathways.
Supportive Efficacy Analyses for the Phase 3 Study of Temsirolimus Versus Investigator’s Choice Therapy for the Treatment of Patients with Relapsed or Refractory Mantle Cell Lymphoma.
Authors: Jorge Romaguera, Bertrand Coiffier, Michael Crump, Raoul Herbrecht, Gregor Verhoef, Orysia Hanushevsky, Andrew Strahs, Becker Hewes, Anna Berkenblit, Georg Hess
Journal: Blood (2008)
Resection of primary tumor in patients who present with stage IV colon cancer may result in improved survival.
Authors: Aaron Lewis, Rebecca A. Nelson, Lily L. Lai
Journal: Journal of Clinical Oncology (2015)

726 Background: Resection of the primary cancer in patients with metastatic disease has been shown to result in improved survival in cancers such as renal cell carcinoma. Currently, the impact primary tumor resection has on survival in stage IV colon cancer patients is unknown. Methods: The SEER dataset was queried for patients who presented with histologically confirmed, stage IV colon cancer from 1998-2011. We excluded patients with rectal cancer, multiple primary tumors, age &lt;18 or &gt;90 years, diagnosis upon autopsy/death record, mortality within 30 days of diagnosis, or resection of other tumor sites (regional or distant). Cox proportional hazard models were used to assess demographic and clinical factors predictive of disease specific and overall survival. To limit group differences, a 1:1 matched analysis was also performed on patients who underwent primary resection compared to patients who did not. Results: A total of 28,068 stage IV colon cancer patients were evaluated, of which 70.3% underwent resection. Among the variables studied, multivariate models showed that patients who underwent primary tumor resection were at lower risk of disease-specific and overall mortality, with hazard ratios (HR) of 0.44 (0.43-0.46) and 0.45 (0.43-0.47), respectively. In the matched analysis (n=5,410 in each group), patients who underwent resection of the primary tumor remained at decreased risk of disease-specific and overall mortality, HR 0.48 (0.45-0.52) and 0.49 (0.46-0.53), respectively. The median survival and 3-year survival after matching was 17 and 9 months and 23% and 6% in the resection and nonresection groups, respectively, p&lt;0.0001. Conclusions: The majority (70.3%) of patients in the United States with stage IV colon cancer undergo resection of primary tumors. Analyses of SEER data suggests that resection of the primary tumor may result in improved DSS and OS in patients with stage IV colon cancer. A prospective, randomized trial is warranted to confirm a survival benefit.
Soluble mesothelin related peptides: A potential biomarker for malignant pleural mesothelioma
Authors: H. I. Pass, D. Wolaniuk, A. Wali, R. Thiel, I. Hellstrom, K. Hellstrom, N. Y. Sardesai
Journal: Journal of Clinical Oncology (2005)

9532 Background: At this time there are no biomarkers that can monitor therapy or predict asbestos-related malignant pleural mesothelioma (MPM). Fujirebio Diagnostics, Inc. developed MESOMARK™ a quantitative dual-monoclonal ELISA for soluble members of a family of proteins expressed by mesothelial cells called soluble mesothelin related peptides (SMRP). We assessed whether (1) SMRP levels in sera and pleural effusions (PE) differed between MPM, non-MPM tumors, asbestos-exposed non-MPM individuals (ASB) and normal volunteers (NL), and (2) SMRP could predict recurrence of MPM after surgery. Methods: Archived frozen serum from 26 ASB, 50 NLs, 54 MPMs, and 14 non-MPMs, and PE from 30 NL, 20 non-MPM tumors, and 45 MPMs were analyzed by MESOMARK™. Blinded longitudinal serum samples (preoperative to 47 month range) from 16 patients having cytoreduction and identical adjuvant therapy were investigated for post surgery SMRP levels and correlation with computerized tomographic (CT) follow-up scans. One-way ANOVA with post-hoc Tamhane test was used for statistical analyses. ROC curves were constructed for the serum and PE groups. Results: Serum SMRP levels were equivalent between ASB (1.166, range 0.004–2.821 nM), and NL (1.222, range 0.216–3.430 nM), but were significantly different from MPM (17.275, range 0.219–278.356 nM, p = 0.003). Stage I MPMs had higher levels of serum SMRP than ASB (p=0.046). Comparing the ASB and NL combined to MPMs, ROC curve analysis revealed an AUC of 0.793 (95%CI: 0.705 to 0.880). No differences were seen in the PE SMRP levels between non-MPM tumors and NL (p=0.521), however, MPM PE SMRP (65.573 nM, range 0.421–255.166) was significantly increased compared to NL PE SMRP (18.997 nM, range 0.291–140.121, p=0.003). The AUC under the PE ROC curve was 0.742 (95%CI: 0.637 to 0.847). SMRP levels decreased in 13/16 patients immediately following surgery, and increased significantly and preceded detection by CT in 10/13 patients who subsequently displayed postoperative progression. Conclusions: These data establish SMRP as a promising marker for MPM, and studies to further refine and validate these data in larger cohorts should be initiated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Fujirebio Diagnostics Fujirebio Diagnostics Fujirebio Diagnostics
Augmenting state cancer registry data for quality-of-care assessment: A Georgia-based application to evaluate receipt of adjuvant therapies for breast cancer and colorectal cancer.
Authors: Joseph Lipscomb, Kevin C. Ward, Kathleen Adams, Peter Joski, Douglas Roblin, Theresa Wicklin Gillespie, Juan Li
Journal: Journal of Clinical Oncology (2013)

6523 Background: The value of linking population-based cancer registry data with insurance claims files to assess quality of care has been demonstrated in numerous studies, including those using NCI’s linked SEER-Medicare database, covering patients age 65+ in fee-for-service plans, and studies linking registry data with Medicaid, private insurance, or managed care data covering the under-65 population. We describe a prototype program linking registry data with multiple data sources to assess quality of care for at-risk populations in a defined geographical area. Methods: Data exchange agreements were executed among the investigative site (Emory University), Georgia state government, and the claims data sources/vendors. We linked Georgia Cancer Registry (GCR) records for 1999-2005 incident cases of breast and colorectal cancer with enrollment and medical services records from Medicare, Medicaid, Kaiser Permanente of Georgia, and the State Health Benefit Plan (SHBP) which covers all state workers and dependents. Following data quality checks, algorithms based on National Quality Forum (NQF) endorsed breast and colorectal cancer quality measures were applied to each linked data set to assess performance. Results: The linked data sets included 60% of all breast and colorectal cancer cases in the GCR over the study period. Quality measure performance rates varied notably across payers. For example, the percent of Stage III colon cancer patients meeting the NQF standard for adjuvant chemotherapy in the linked GCR-Medicaid, GCR-Kaiser, and GCR-SHBP data were, respectively, 75%, 92%, and 92% (p&lt;0.05). The rates for breast cancer patients meeting standards for adjuvant chemotherapy were 86%, 84%, and 87% (p=NS), respectively. Patients in the linked GCR-Medicare data (all age 65+) generally had lower performance rates for each NQF measure. Conclusions: Linking state cancer registry data with multiple public and private sources of administrative data is technically feasible, and may represent a viable strategy for building a national cancer data system for quality improvement, as recommended in 1999 by the Institute of Medicine.
Impact of palliative care clinic (PCC) referrals on pain control in genitourinary (GU) cancer patients: Retrospective analysis at Roswell Park Cancer Institute (RPCI).
Authors: Neha Gupta, Shipra Gandhi, Sidra Anwar, Katy Wang, Yashodhara Satchidanand
Journal: Journal of Clinical Oncology (2014)

57 Background: Many cancer patients (pts) with GU cancer suffer from uncontrolled pain, and may benefit from more focused palliative care. We assessed the frequency and impact of specialist PCC referrals on pain management of our GU Medical oncology clinic (GUMOC) pts. Methods: 239 consecutive pts were collected from a retrospective review of GUMOC records from 12/1/2013 to 2/28/2014. This group of pts was used to assess the frequency of PCC referral. Pts were divided into two arms- Arm A= GUMOC pts referred to PCC; Arm B: GUMOC pts not referred to PCC. To be able to detect a 15% between the two arms at 95% significance, 37 additional pts (who were already being seen at GUMOC) were collected from retrospective review of PCC records over 9/1/2013 to 2/28/2014. Total 276 pts were divided into Arm A (n=49), Arm B (n=227 pts). Data for baseline pain score and 4-week follow up pain scores were collected. A palliative care screening tool (retrieved from Center to Advance Palliative care [CAPC] website) was used to assign palliative care screening score (PCSS) to all study pts. Chi square test and T-test were used for statistical analysis. Results: Out of the 239 initially collected GUMOC pts, 5% were referred to PCC. 10% (n=24) had PCSS score of ≥ 4, and 33% pts with PCSS ≥ 4 were referred to PCC. Arm A had worse baseline symptoms, ECOG status and more advanced cancer stage. 4-week pain score follow up revealed significant improvement in Arm A -2.74 vs. Arm B -0.13 (p&lt;0.01). Conclusions: GU cancer pts who are referred to PCC from medical oncology clinic have significant decrease in pain symptoms. Frequency of PCC consultation is still low in comprehensive cancer institutes, and not in congruence with the available palliative care screening tools criteria suggested by CAPC. Standardized tools should be developed to guide PCC referrals, and routine use of these tools will significantly help in pain control by seeking specialist palliative care.
A comparison of safety and efficacy of cytotoxic versus molecularly targeted drugs in pediatric phase I solid tumor oncology trials.
Authors: K. M. O. Dorris, T. R. Hummel, A. M. Ingle, M. Kim, J. P. Perentesis, M. Fouladi
Journal: Journal of Clinical Oncology (2011)

9543 Background: Prior reviews of phase I pediatric oncology trials involving primarily cytotoxic agents have reported objective response rates (ORR) and toxic death rates (TDR) of 7.9-9.6% and 0.5%, respectively. These data may not reflect safety and efficacy in phase I trials of often cytostatic, molecularly targeted drugs. Methods: A systematic review of pediatric phase I oncology trials in patients with refractory solid tumors published from 1990 to 2010 was performed. Publications were identified through a PubMed query for “phase I,” “pediatric” and “cancer” search terms. The published reports were evaluated for patient characteristics, toxicity information and response numbers. Additional data regarding disease response and stability, time to progression, and toxicity will be obtained from a subgroup of 18 published Children’s Oncology Group phase I trials for further analyses. Results: Eighty-nine phase I pediatric solid tumor clinical trials enrolling 2505 children were identified. Thirty trials investigated 26 molecularly targeted drugs; 59 trials evaluated 37 cytotoxic agents. The overall ORR (ie, complete, partial and minor responses) was 6.1% for cytotoxic drugs and 2.3% for molecularly targeted drugs (p<0.001). Rates of stable disease (SDR) for cytotoxic agents and molecularly targeted drugs were 19.6% and 25.5% (p=0.003), respectively. The likelihood of a dose-limiting toxicity (DLT) was 27.2% for cytotoxic trials and 18.3% for molecularly targeted drug trials (p<0.001). The TDR was 0.18% for cytotoxic trials and 0.14% for molecularly targeted drug trials (p>0.05). Conclusions: In phase I pediatric solid tumor trials, ORR were significantly higher for cytotoxic versus molecularly targeted agents. SDR were higher in molecularly targeted than cytotoxic drug trials. Although TDR were similar in both groups, patients treated with cytotoxic agents were more likely to experience a DLT than those patients receiving molecularly targeted drugs. These observations should help to guide future phase I/II pediatric oncology clinical trial designs for novel molecularly targeted drugs.