tbuckley/cabot-search huggingface dataset:
Breast cancer genetic risk evaluation and referral for assessment.
Authors: Mary Anne Fenton, Tara Szyamnski, Kimberly Perez, Cindy Benson, Chanika Phornphutkul
Journal: Journal of Clinical Oncology (2013)

75 Background: ASCO Quality Oncology Practice Initiative (QOPI) provides tools for oncology practices to assess quality and adherence to clinical guidelines. Following each data submission a QOPI measures summary report is published providing practices the opportunity to compare themselves to QOPI Aggregates. In 2011, QOPI initiated a more stringent evaluation of family history documentation, which would improve rates of referral to genetic counseling for breast and colon cancer. Methods: A review of QOPI measure summary reports is performed by Rhode Island Hospital’s (RIH) Comprehensive Cancer Center Quality Improvement Team after each round of chart abstraction. Following review of QOPI practice results for genetic evaluation in 2011, our interventions included development and implementation of a 3 generation maternal and paternal family history intake form, genetics referral form with criteria to refer patients for genetic evaluation and initiation of a Genetics Clinic on site at the Cancer Center. Results: Presented is a summary of QOPI results for the Breast Cancer measures of complete family history documented and Genetic testing addressed appropriately. Conclusions: Our interventions included a patient intake form, genetics referral form with criteria to refer patients and a Genetics Clinic on site at the Cancer Center. The institution of a patient intake form resulted in a 19-fold improvement in complete family history documentation. The genetics referral form and establishment of an on-site Genetics clinic resulted in a 10% increase in referrals for genetic risk assessment. In spite of these interventions review of our Genetic Risk Evaluation data is notable for a 39% no show rate for the genetic risk assessment appointments. [Table: see text]
Phase II study of combination with irinotecan and S-1(IRIS) for inoperable recurrent advanced colorectal cancer(HGCSG0302). Final analysis
Authors: S. Yuki, Y. Komatsu, I. Iwanaga, H. Fukushima, M. Kudo, M. Tateyama, T. Meguro, M. Watanabe, M. Asaka, Y. Sakata
Journal: Journal of Clinical Oncology (2008)

15112 Background: We planned to conduct a phase II study of combination with irinotecan and S-1. We reported the interim reports of this study in colorectal cancer patients at ASCO 2007. Methods: The response rate(RR) was the primary endpoint, while the safety, progression-free survival time, and median survival time were the secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer aged 20–75 years. Irinotecan was administered at a dose of 100 mg/m2 (on days 1 and 15) as an intravenous infusion over 90 minutes, and oral S-1 (40 mg/m2) was administered after breakfast and dinner and then withdrawn for 2 weeks. Results: Forty patients were enrolled in the present study. There were 23 men and 17 women. The median age was 62 years (range: 34 to 74 years). Four patients showed grade 4 neutropenia, but the next course could be given safely after dose reduction. Six patients had grade 3 diarrhea, but this therapy could be continued with addition of an antidiarrhea drug. No other serious adverse reactions occurred (either hematological or non-hematological), and all patients could receive therapy safely on an outpatient basis. Forty patients are evaluable for efficacy: RR was 52.5% (CR 1, PR 20, SD 17, PD 2, 95% CI, 37–68%) and Disease Control Rate (CR+PR+SD) was 95.0%. Progression Free Survival of this regimen was 262 days. Median Survival Time will be final-analized in January 2008. Conclusions: IRIS therapy achieved a high response rate and could be given safely. These findings suggest that the therapy has potential as first-line treatment for inoperable advanced recurrent colorectal cancer. It seems that IRIS is a good treatment equal to FOLFIRI. Our next new trial, IRIS plus Bevacizumab (NCT00569790), was planned, and it has been already started now. The final data will be reported at this meeting. No significant financial relationships to disclose.
A prospective monitoring study on the value of LDH and protein S-100B as indicators of progressive disease during adjuvant interferon a treatment in melanoma
Authors: A. Hauschild, W. Hitschler, M. Weichenthal
Journal: Journal of Clinical Oncology (2005)

7542 Background: Despite adjuvant interferon treatment, a significant number of patients with high-risk melanomas will develop progressive disease within the following years. Currently, the recommendations for blood tests in the follow-up of these patients are inconsistent. Methods: A prospective evaluation compared the value of lactate dehydrogenase (LDH) and protein S-100B serum tests (Sangtec 100 LIA mat) as indicators of progressive disease. Therefore, blood samples from 98 melanoma patients were taken 3-monthly and the upper institutional limits (LDH 240 U/l; S-100B 0,20 μg/l) were considered as cut-off points. A total of 1273 sera were analyzed. All patients belonged to prospective-randomized phase III trials (Dermatologic Cooperative Oncology Group; DeCOG) and were treated either if clinically lymph node negative (n=53) with two different Interferon a2b schedules or if clinically lymph node positive (n=54) in another interferon-based trial with observation controls. Results: During the median observation period of 30 months 52 out of 98 patients (53.1%) progressed to either stage III or IV according to the new AJCC melanoma classification. Neither S-100B nor LDH represented indicators of in-transit metastases. The detection of clinically apparent lymph node metastasis by abnormal serum values was feasible in only 11.8% (LDH) and 35.3% (S-100B) of the patients, respectively. Whereas S-100B elevations led to the detection of early distant metastasis (stage IV) in half of the patients (50.0%), only 15.4% of the patients demonstrated abnormal LDH concentrations. The rate of false-positive serum levels in currently disease-free patients did not differ between the two serum markers (S-100B: 13.0%, LDH: 10.9%). Conclusions: Now as before, loco-regional relapses in high-risk melanoma patients have to be detected by clinical examinations and lymph node ultrasound. However, S-100B serum tests are superior to LDH assessments as indicators of early distant metastasis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration DiaSorin DiaSorin
A phase II study of arsenic trioxide (ATO) in patients with advanced hepatocellular carcinoma (HCC).
Authors: H. A. Rodgers, S. F. Katta, A. K. Malani, M. Willis, A. B. Markowitz
Journal: Journal of Clinical Oncology (2010)

e14686 Background: Hepatocellular carcinoma (HCC) is the 3rd leading cause of cancer death globally with most deaths occurring within 1 year of diagnosis. Arsenic trioxide (ATO) has proven activity in the treatment of both solid and hematologic tumors. ATO cytotoxicity and apoptosis induction has been demonstrated in vitro with numerous human cancer cell lines including HCC. Methods: Patients with advanced measurable HCC, no more than one prior systemic treatment or no treatment, ECOG PS 0-2 and Child-Pugh class A received ATO 0.35 mg/kg on days 1, 8, 15, and 22 of each 28-day cycle. The primary endpoints were the feasibility of administering this regimen and the qualitative and quantitative toxicities of treatment. Secondary endpoints were response to treatment, duration of progression-free survival, patterns of failure, and survival. Results: 9 patients were enrolled from 10/13/04 to 9/5/07. Median age of patients was 57 years (range 50-62 years) and included 8 males and 1 female. No patients had previous systemic therapy. 3 patients did not complete the first cycle and were not evaluable for response. 6 patients had progressive disease on therapy. 1 patient received 8 cycles of therapy, achieved a partial response lasting 8 months and is still alive. Most common adverse effects (AEs) were fatigue and QTC prolongation and all AEs were less than grade 3. No patients had APL differentiation syndrome. Conclusions: Although ATO demonstrated 1 partial response in this trial, ATO appears to be less active than sorafenib which is FDA approved for treatment of advanced HCC. Given the complexity of therapy and potential cardiotoxicity, further development of ATO in this setting appears unwarranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cepahlon, GlaxoSmithKline, Lilly Cepahlon
Targeted analysis of progressive metabolic perturbations in colorectal cancer in colorectal adenoma: Potential for a serum metabolomics-based colorectal cancer screening test.
Authors: Farshad Farshidfar, Aalim Weljie, Karen A. Kopciuk, Hans J. Vogel, Robert Hilsden, Elizabeth McGregor, Oliver F. Bathe
Journal: Journal of Clinical Oncology (2014)

426 Background: Colorectal cancer (CRC) could be resected and cured if detected at an early stage. A serum metabolomics-based screening test would represent a rapid and convenient means to identify adenoma and early CRC. However, changes in the metabolome with such minimal disease may be too subtle if the usual high throughput discovery approach were taken. We postulated that adenoma-associated metabolic changes could be better identified by targeting our analysis to metabolites that changed in a progressive manner with sequential stages of disease. Methods: Sera from patients with locoregional (LR CRC) and metastatic (mCRC) disease (stage I n=21, stage II n=30 , stage III n= 35, stage IVa n=67) and matched controls (n=121) were analyzed by gas chromatography-mass spectrometry (GC-MS). After normalization, batch correction and autoscaling, 249 features were selected. Metabolites that characterized CRC were filtered by identifying those metabolites that increased or decreased in a progressive manner with higher disease stage. Subsequently, sera from 31 adenoma patients and 31 matched controls, collected under standardized conditions prior to colonoscopy and polypectomy, were analyzed by GC-MS. "The variable importance” of metabolites identified in the first analysis were studied. Results: Products of fatty acid metabolism (dodecanoic acid, 2-amino butanoic acid, isocaproic acid, hexadecanoic acid) and urea were among metabolites that were altered more markedly in advanced disease stages. A number of metabolites that changed in this progressive fashion were found to change to a more subtle degree in adenoma. Conclusions: A targeted analysis of metabolites that change in a progressive fashion as CRC progresses represents a means to identify the subtle changes in the serum metabolome that accompany adenoma. This demonstrates the feasibility of developing a serum metabolomics-based screening test for CRC. In addition, extension of this selection approach can be used in other applications where minimal disease is challenging to detect with conventional statistical methods.
FDA evaluation of hepatotoxicity related to tyrosine kinase inhibitors.
Authors: J. Chang, M. Rand, G. M. Blumenthal, P. Cortazar, C. Kulick, E. Hausman, S. Chang, R. Pratt, B. Habtemarium, Y. Chen, J. Bullock, R. Charlab Orbach, I. Zineh, R. L. Justice, R. Pazdur
Journal: Journal of Clinical Oncology (2011)

3106 Background: Tyrosine kinase inhibitors (TKIs) interfere with several critical signal transduction pathways in cancer. Nine TKIs have been FDA approved to treat a variety of malignancies. TKIs have been associated with severe liver injury (SLI). Whether this liver injury is a class effect, or specific to certain TKIs is being investigated. Methods: Analyses included evaluation of postmarketing reports of SLI associated with 9 TKIs (imatinib, dasatinib, nilotinib, erlotinib, gefitinib, lapatinib, sorafenib, sunitinib, and pazopanib) from FDA's Adverse Event Reporting System (AERS) and literature review. SLI is defined as acute liver injury (elevated LFTs, bilirubinemia, or jaundice) in combination with one of the following events: death, liver transplantation or placement on liver transplant list, hepatic encephalopathy, coagulopathy or renal impairment. Clinical toxicity data, demographics, drug metabolism, laboratory, pharmacokinetic and exposure data were reviewed from new drug application (NDA) submissions. Results: Of 497 AERS reports of SLI associated with TKIs, 55 cases with causality assessment of possible or likely were identified in 8 of 9 TKIs across a number of oncologic indications. 37 cases of SLI were reported in the literature associated with 5 of 9 TKIs. Investigations as to the mechanistic basis for bilirubin and liver enzyme elevation properties of the TKIs are ongoing. Conclusions: Once at risk-populations and mechanisms for TKIs-associated liver injury are identified, FDA can better communicate the risks relative to benefits of TKIs. Possible risk minimization strategies include: 1) careful monitoring of liver function tests, 2) increased prescriber and patient awareness through risk communication such as incorporation of hepatotoxicity warnings in the label and 3) exclusion of patients at risk. Mechanisms for TKI-associated liver injury are unknown and should be properly investigated including possible dysregulation of biliary homeostasis and impaired liver regeneration.
Short-course stereotactic radiotherapy with high fraction doses for advanced intra-abdominal malignancies
Authors: V. Vinh-Hung, J. de Mey, M. Voordeckers, J. van de Steene, G. Soete, D. van den Berge, G. Storme
Journal: Journal of Clinical Oncology (2005)

4237 Background: Historically radiotherapy (RT) plays a minor role in the management of unresectable liver metastases and abdominal tumors. There are few studies (Dawson, Herfarth, Blomgren…) on high fraction dose RT. We report our single institution experience with the stereotactic RT system Novalis. The primary objective is to evaluate overall survival (OS), local progression free survival (PFS) and time to response (TTR). Use of implanted intra-tumoral positioning markers to improve precision was introduced end 2003: the secondary objective is to evaluate their impact. Methods: Patients treated with stereotactic RT were selected if they presented metastatic abdominal localisations, or inoperable local-regional recurrence of abdominal carcinomas. Comparison of survival estimates used logrank test. Multivariate analysis used Cox models with age, gender, tumor size, treatment duration, fraction dose and total RT dose. Results: In 2000–2004, there were 91 cases: 56 liver localizations, 7 pancreas, 28 nodes or abdominal masses. Mean tumor diameter was 6.4 cm (range 1.8–12.5). Mean number of treated tumors was 1.5 (range 1–6). A marker was placed in 23 cases. A fraction dose of 4–10 Gy was delivered in 3–10 sessions for 42 patients, lower dose in others. Median treatment duration was 6 days (range 2–48). Median OS was 25 months, PFS 13 months, TTR 10 months. Marker had no impact on OS, but improved PFS and TTR (Table). In Cox models, a larger total RT dose was most significantly associated with improved OS (p=0.001), PFS (p<0.001), and TTR (p=0.007), and a smaller number of fractions with improved PFS (p=0.05) and TTR (p=0.07). Discussion: The dose-survival relationship suggests that in metastatic cases with multiple localizations, control with RT might be worthwhile considering. Markers were associated with faster and increased percentage of responses, suggesting the potential added utility of improved precision in palliative situations. No significant financial relationships to disclose.
Sequential therapies with sorafenib and sunitinib in advanced or metastatic renal cell carcinoma.
Authors: E. Herrmann, N. Marschner, M. Grimm, C. H. Ohlmann, U. Hutzschenreuther, F. Overkamp, M. Groschek, K. Blumenstengel, T. Steiner
Journal: Journal of Clinical Oncology (2011)

e15061 Background: There is increasing evidence to suggest that patients with metastatic renal cell carcinoma (mRCC) benefit from sequential therapies with the tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib. Our goal was to compare overall progression-free survival (PFS) and overall survival (OS) between mRCC patients who were treated with sorafenib followed by sunitinib and patients who received the reciprocal sequence. Methods: 89 patients were treated in nine German centres between 2002 and 2009. The TKI sequence started as first-, second- or third-line therapy after prior chemo- or immunotherapy. When progression was diagnosed, treatment was switched to the second TKI until further progression. Results: Overall progression-free survival (PFS) of patients receiving sunitinib followed by sorafenib shows no statistically significant difference to patients receiving sorafenib followed by sunitinib (15.4 vs. 12.1 months). The secondary use of sorafenib resulted in a median PFS of 3.8 months if the TKI sequence had been started as a first-line treatment, and of 3.5 months if the TKI sequence had been started second-line. The secondary use of sunitinib resulted in a median PFS of 3.4 and 4.0 months, respectively. OS was 28.8 months for all patients, without a statistically significant difference between the two groups. Conclusions: This study endorses the notion of a clinical benefit of the sequential use of sorafenib and sunitinib and supports observations from previous studies. In terms of the optimal succession of the two TKIs, the study does not allow a definite answer.
Correlation of pretreatment p63-positive subtype of gastroesophageal adenocarcinoma (GEAC) with pathologic complete response (pathCR) in patients receiving preoperative chemoradiation.
Authors: Elena Elimova, Soo-Mi Kim, Xuemei Wang, Yusuke Shimodaira, Bo Hwa Sohn, Heath Devin Skinner, Jeffrey H. Lee, Brian Weston, Manoop S. Bhutani, Bruce D. Minsky, David C. Rice, Jun Eul Hwang, Stephen Swisher, Wayne Lewis Hofstetter, Mariela A. Blum, Dipen M. Maru, Jaffer A. Ajani, Ju-Seog Lee
Journal: Journal of Clinical Oncology (2016)

51 Background: Biomarker or biomarker signature(s) is needed to help optimize therapy of GEAC patients undergoing multimodality therapy. p63 is a transcription factor important in the development of squamous epithelial lineage and mediating ectodermal-mesenchymal interactions. Methods: Primary objective of this study was to study the predictive value of p63-associated subtype for pathCR. Other outcomes were also studied. Results: Unsupervised cluster analysis of gene expression data from 185 GEAC patients uncovered two distinct subtypes of GEAC with differences in expression of p63 mRNA: p63-positive and p63-negative. All patients had chemoradiation and surgery. Most were men (88%), all had adenocarcinoma, and most were p63-negative (69%). 25% of patients achieved a pathCR. The median follow-up for all patients was 3.9 years (range, 0.1 – 11.5). p63-positive subtype was associated with pathCR in both a univariate and multivariate analyses (p = 0.04 and p = 0.02, respectively). Female patients with p63-positive subtype, lower no. of ypNodes, and low grade GEACs had a higher probability of pathCR. However, p63-positive subtype was not prognostic (PFS, p = 0.26 or OS, p = 0.80). The median OS for all patients was 4.8 years (95% CI, 3.3 – 6.7 years). Higher no. of ypNodes, higher histologic grade, and mid- or higher esophageal primary were associated with shorter OS (with p-values of &lt; 0.0001, 0.0004 and 0.0001, respectively). Conclusions: Our data suggest that pretreatment p63-positive subtype of GEAC highly correlates with pathCR. Further refinement/validation and combination with other biomarkers is warranted.
High response rate but significant toxicity with sequential high-dose ifosfamide (I), carboplatin (C), and etoposide (E) with rituximab for relapsed Hodgkin’s (HD) and large cell non-Hodgkin’s lymphoma (NHL)
Authors: T. C. Shea, D. Rizzieri, D. Gabriel, J. Serody, N. Chao, J. Gockerman, C. Lindley, G. Rey, M. J. Lehman
Journal: Journal of Clinical Oncology (2005)

6700 Background Ifosfamide, Carboplatin and Etoposide (ICE) are commonly used for the treatment of recurrent HD and NHL prior to autologous stem cell transplantation (ASCT). Since maximizing the single agent dose intensity of each component of a combination regimen has led to improved outcomes in breast cancer, we studied such an approach in lymphoma by developing a regimen in which patients received the dosage equivalents of 3 cycles of combination ICE therapy as sequential single agent treatments. Methods 22 patients (21 evaluable) with relapsed or refractory Hodgkin’s (9) or non-Hodgkin’s Lymphoma (12) received 15 g/m2 I with hydration and mesna, followed by 900 mg/m2 E, followed by C at an AUC of 15 every 21 days. NHL pts received 375 mg/m2 of R with each cycle. Pts received E as the second agent and stem cell apheresis following count recovery prior to receiving C. CR, PR, or SD pts then proceeded to ASCT with CBV (9 pts) or BEAM (6 pts). Prophylactic antibiotics and G-CSF were administered with each cycle of therapy. Results Severe toxicity consisted of 7 episodes of hospitalization for F&N, one large pleural effusion, one pt with transient grade 4 neurotoxicity and irreversible grade 4 renal failure and one pt with grade 3 renal failure. Following institution of a mandatory 12-hour interval between R and I, no serious renal toxicity was observed in the next 13 pts. Two treatment deaths occurred; one from sepsis in the pt on dialysis and a 2nd pt who died of neutropenic sepsis following C. One pt died during transplant of diffuse pulmonary thrombosis. Four pts achieved CR, 9 PR, 2 SD, 4 PD pre-ASCT. Three pts were not evaluable for response due to either early death (1), withdrawal due to AE (1), or missing data (1). 11 of 15 transplanted pts achieved CR; 7 (47%) remain in CR at a median f/u of 27 months. Conclusions This regimen has significant activity, but is more toxic than when administered in a conventional manner. The current remission rate post SCT is encouraging in these advanced disease pts but it is unclear if it is greater than that achieved with standard salvage regimens followed by ASCT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen, Bristol-Myers Squibb