tbuckley/cabot-search huggingface dataset:
Long-term quality of life (QoL) for stage II/III rectal cancer survivors in the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS).
Authors: Mary E. Charlton, Karyn Beth Stitzenberg, Chi Lin, Grelda Yazmin Juarez, Thorvardur Ragnar Halfdanarson, Jane F. Pendergast, Elizabeth A. Chrischilles, Robert B. Wallace
Journal: Journal of Clinical Oncology (2014)

584 Background: Standard therapy for stage II/III rectal cancer includes surgery, radiation, and chemotherapy. Multiple trials demonstrated neoadjuvant chemoradiation (CRT) provides better local control and decreased morbidity compared to adjuvant CRT, though differences in overall survival and long-term QoL have not been demonstrated. We examined impact of treatment (pre-op CRT/post-op CRT/no CRT) on long-term QoL. Methods: CanCORS patients with survey/medical record data diagnosed in 2003-2005 with stage II/III rectal (non-rectosigmoid) cancer had resection and survived &gt; 7 years were included. QoL (SF-36, EQ-5D) measures and defecation problems were derived from surveys at 14 months and 7 years post-diagnosis. Mean scores were adjusted for the following when significant: age, gender, stage, sphincter preservation, comorbidities, and baseline self-reported health status and QoL scores. Results: Of 119 patients, 53% received pre-op CRT, 23% post-op CRT, and 24% no CRT. Of 114 patients with 14-month follow-up, Pre-op CRT and No CRT groups had better EQ-5D adjusted mean scores but worse defecation scale (DS) scores compared to the Post-op CRT group. Of 49 disease-free survivors with 7 years follow-up, there were no differences among groups in QoL scores, but the No CRT group had better DS scores than other groups. Conclusions: No major differences were detected in long-term QoL based on treatment aside from the DS, though sample sizes became small. Regardless of treatment, long term (7y) mental health and vitality were generally comparable to U.S. norms, while physical health and overall health status (EQ-5D) were somewhat lower. [Table: see text]
A Prospective Randomized Phase I/II Study of Lenalidomide, Melphalan, Prednisone and Thalidomide (RMPT) for Relapsed/Refractory Multiple Myeloma Patients.
Authors: Federica Cavallo, Alessandra Larocca, Maria Teresa Petrucci, Vincenzo Federico, Antonietta Pia Falcone, Grazia Sanpaolo, Letizia Canepa, Monica Crugnola, Mario Boccadoro, Antonio Palumbo
Journal: Blood (2009)
Quantitative density evaluation of liver metastases on CT scan: A new tool to evaluate early the benefit of bevacizumab plus chemothrapy regimen.
Authors: E. Assenat, B. Gallix, M. Ducreux, A. Rene, C. Mollevi, A. Adenis, B. Chauffert, E. Boucher, E. Francois, J. Pierga, S. Nougaret, T. Mazard, M. Ychou
Journal: Journal of Clinical Oncology (2011)

e14015 Background: The standard criteria used to evaluate tumor response (RECIST), were developed to assess tumor shrinkage after cytotoxic chemotherapy and may be limited in assessing response to biologic agents, which have a cytostatic mechanism of action. The aim of this study is to validate novel tumor response criteria based on tumor density early changes observed on computed tomography (CT) in patients with colorectal liver metastases treated with bevacizumab-containing chemotherapy regimens. Methods: We performed a centralized review of the 145 patients included in ACCORD 13 clinical trial (NCT00423696). Seventy one patients were excluded of the analysis because of the absence of liver metastasis (n=19), images data not available or incomplete (n=30), CT delay time not respected (n=7), CT acquisition protocol not respected (n=15). The final study population was 74 patients treated by FOLFIRI + bevacizumab (n= 46) or XELIRI + bevacizumab (n=28), with a median follow-up of 34.1 months [2.8-47.5 months]. Tumor size (RECIST) and density were determined objectively using a semi- automatic segmentation tools (Myran, Intrasense) at the portal phase. We analyzed changes in tumor size and density, in patient who underwent a CT scan before and 2 months after starting treatment. Results: There was no significant difference between the entire clinical trial population study (ACCORD 13) and the analysed patient group in terms of age, sex, PFS and OS. At the first CT evaluation (2 months), objective RECIST response was not predictive of the PFS (p= 0.559). At the same evaluation, decrease in tumor density (p=0.027), and decrease in tumor density normalized to the liver ratio (p=0.012) were predictive of the PFS. Hazard ratio was 0.50 [0.30 – 0.83] for a tumor to liver ratio density response (p=0.009). We performed the same analysis in a control population (n=70) treated in first line with chemotherapy and without bevacizumab for a metastatic colorectal cancer: nor RECIST evaluation and nor changes in tumor density were correlated with PFS. Conclusions: A change in tumor density on CT seems to be an accurate method to early predict the benefit of chemotherapy + bevacizumab treatment.
Differential HER2 expression in resected gastric cancer: Is there prognostic value?
Authors: Sarah B. Fisher, Kevin E. Fisher, Malcolm Hart Squires, Sameer H. Patel, David A. Kooby, Charles A. Staley, Alton B. Farris, Shishir K. Maithel
Journal: Journal of Clinical Oncology (2013)

54 Background: For advanced gastric cancer, the ToGA trial established HER2 as an important therapeutic target in the 20% of patients whose tumors exhibited HER2 overexpression or gene amplification. Others have reported that HER2-positive tumors are associated with poor survival in advanced disease. The expression profile and prognostic value of HER2 in resectable gastric cancer are unknown. Methods: 111 pts underwent curative intent resection of gastric adenocarcinoma between 1/00-6/11 and had tissue available for analysis. Immunohistochemistry (IHC) for HER2 was performed on banked tumor specimens and graded by two pathologists blinded to outcomes utilizing ToGA trial criteria. An IHC score of 0+ or 1+ was regarded as negative, 3+ as positive. Fluorescence in-situ hybridization (FISH) for HER2 was performed on equivocal (2+) IHC samples. Primary outcome was differential expression, secondary outcome was overall survival (OS). Results: Median age was 64 years, 54% were male. Median tumor size was 4 cm, 7.2% had a positive margin, 67.6% were poorly differentiated, 23.4% had perineural invasion, 35.1% had lymphovascular invasion, and 61.3% had nodal metastases. 24 patients had stage I disease (21.6%), 32 stage II (28.8%), and 55 stage III (49.6%). Mean follow-up was 28.9 months, median OS was 27.2 months. HER2 expression by IHC was negative in 61 (55%), equivocal in 37 (33.3%), and positive in 13 (11.7%). Of the 37 equivocal cases, FISH was positive in 8, for a total of 21 HER2-positive cases (18.9%) and 90 HER2-negative cases (81.1%). HER2 status did not correlate with T or N stage, tumor size or location, tumor grade, or perineural or lymphovascular invasion. HER2 status was not associated with OS (p=0.36). Conclusions: Resectable gastric cancer exhibits differential expression of HER2, similar to that of advanced disease. Despite reports suggesting HER2 positive status is associated with aggressive disease and worse outcomes in the advanced setting, HER2 status is not associated with adverse pathologic factors or survival in resectable disease. Although not prognostic, the predictive value of HER2 status for response to trastuzumab in the adjuvant setting requires further investigation.
Magnetic resonance (MR) perfusion imaging to differentiate early progression from pseudoprogression following chemoradiotherapy for glioblastoma (GBM).
Authors: J. J. Graber, R. J. Young, A. Gupta, A. D. Shah, T. A. Chan, Z. Zhang, W. Shi, K. Beal, A. M. P. Omuro
Journal: Journal of Clinical Oncology (2011)

2009 Background: Patients with glioblastoma (GBM) treated with temozolomide and radiotherapy (RT) may experience early progressive disease (PD) or pseudoprogression (PsP) due to radiation effects, both of which appear as contrast-enhancing lesions on MRI. Currently, there is no reliable way to differentiate between PD and PsP, posing a common diagnostic and treatment dilemma since patients with PD have a poor prognosis, while PsP usually resolves without changes in therapy. Methods: We retrospectively identified 71 GBM patients with new or enlarging enhancing lesions on initial MRI following temozolomide and RT. In twenty patients, dynamic susceptibility (DSC) MR perfusion had been performed, including relative cerebral blood volume (rCBV), relative peak height (rPH) and peak signal recovery (PSR) of the enhancing lesions. Two independent reviewers unaware of results of DSC MR perfusion imaging assigned patients to either PD or PsP based on review of clinical data and follow up or results of biopsy of the enhancing lesions (if available). Two-sided Wilcoxon rank-sum tests were used to evaluate associations between DSC parameters and PD or PsP status. Results: The PsP group had significantly lower median rCBV compared to PD (1.5 vs 2.8, p=0.009) and rPH (1.3 vs 3.0, p<0.001), with higher PSR (1.0 vs 0.8, p=0.039). Receiver operator characteristic analysis revealed an optimal rCBV threshold of ≤1.80 to detect PsP with 100% sensitivity and 75% specificity (AUC=0.938). To maximize specificity, an rCBV threshold of ≤2.40 achieved 69% sensitivity and 100% specificity to detect PsP. Conclusions: DSC MR perfusion imaging of new or enlarging enhancing lesions immediately after completion of RT and temozolomide successfully identified patients with PsP versus those with PD, which has important implications for clinical treatment.
Final results of phase II trial of pegylated arginine deiminase (ADI-PEG20) in metastatic melanoma (MM).
Authors: L. G. Feun, M. You, C. Wu, M. Wangpaichitr, M. T. Kuo, A. Marini, A. Jungbluth, N. Savaraj
Journal: Journal of Clinical Oncology (2010)

8528 Background: ADI-PEG20 catabolizes arginine (Arg), a nonessential amino acid in human adults, to citrulline and ammonia. Tumor cells which lack argininosuccinate synthetase (ASS) are unable to synthesize Arg which can lead to cell death. A phase I/II trial of ADI- PEG20 showed activity in MM (JCO 23:7660) and the optimum biologic dose (OBD) was considered to be 160 IU/m2/week which lowered blood Arg to nondetectable levels. In this phase II study, we obtained tumor samples, when accessible, for ASS staining prior to therapy in patients (pts) with MM and correlated the ASS staining with tumor response. Methods: MM pts were treated with ADI- PEG20 (provided by Polaris, Inc.) at 160-320 IU/m2 I.M. weekly. Tumor measurements were done every 8 weeks. Pretreatment tumor samples were available in 26 pts for ASS staining by immunohistochemistry and/or real time PCR. Results: 36 pts were evaluable for response. 4 (11%) had tumor shrinkage at > 30%, 4 had minor response (< 30% shrinkage), 2 had stable disease and 4 had mixed response. ASS staining correlated with tumor response: for the 16 pts with ASS(−) tumors, 3 (19%) had response and clinical benefit (partial response, minor response and stable disease) was noted in 8 (50%). Including mixed responses, 10/16 (63%) with ASS (−) tumors showed some evidence of antitumor effect, while only 1 of 10 pts had stable disease when tumor was ASS (+) (P value = 0.01). Response also correlated with the dose of ADI-PEG20, independent of ASS staining. Of 20 pts treated with 320 IU/m2/week, 4 had response, while no pt had response when dosage was < 320 IU/m2/week. Toxicity was uncommon, consisting mainly of discomfort at the injection site. Repeat biopsies were done in 2 ASS(−) pts and found to be positive at the time of relapse. This finding also was seen in the laboratory in certain melanoma cell lines in which ASS can be induced upon repeated exposure to ADI-PEG20/Arg deprivation (MCT 12:3223,2009). Conclusions: This is the first study using Arg depleting therapy with ADI-PEG20 to show correlation of response with ASS (−) staining. Future studies with ADI-PEG20 should target only MM pts with ASS(−) tumors. Furthermore, the dose required for response in certain MM pts may exceed the OBD. Supported by RO1CA109578. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Polaris
Comparison of the efficacy between the gemcitabine/cisplatin (GP) and capecitabine/cisplatin (XP) for the advanced biliary tract cancer: Retrospective analysis in a single institution.
Authors: Ji Eun Lee, Myung Ah Lee, Tae Ho Hong, In Seok Lee, Young Kyoung You
Journal: Journal of Clinical Oncology (2012)

365 Background: Bile duct cancers (BTC) are known to be the chemotherapy resistant cancer, and more common in old-age group. Gemcitabine and cisplatin (GP) has been widely used as first line treatment for unresectable BTC. Capecitabine and cisplatin (XP) combination chemotherapy has been also used as another option treatment. We retrospectively compared the efficacy of GP and XP for advanced BTC. Methods: Between Jan, 2009 and Jun, 2011, Fifty five patients who were diagnosed with unresectable BTC at Seoul St. Mary’s hospital were enrolled for analysis of the efficacy in the present study. All the patients had recurrent disease or metastatic cancer, confirmed by histologically adenocarcima. In GP group, gemcitabine was given with 1,000mg/m2, I.V for 30min on d1 and d8, and cisplatin was injected with 75mg/m2, d1, repeated every 21 days. In XP group, capecitabine was administered by orally 2,000mg/m2, divided dose d1-14, and cisplatin was administerd with 75mg/m2, d1, repeated every 21 days. Response evaluation with CT scan was taken after 2 cycles. Results: Of the 55 patients enrolled, 28 patients were treated with GP and 27 patients were treated with XP. Median age was 69 years old in GP, 65 years old in XP. Median number of cycle was 2.5 in both groups. There was no difference in patients’ characteristics between two groups in terms of sex, age, number of cycle and disease status. In analysis of the response rate, Partial response rate was 38.5% in XP, and 7.1% in GP, and stable disease was achieved in 23.1% in XP, 42.9% in GP (p=0.004). Median time to progression was 2.0 mon in GP, and 4 mon in XP (P=0.147). However, median survival time was 6 months vs. 4. 3months in GP and XP, respectively (p=0.510). There was no difference in toxicity between two groups. Conclusions: GP and XP showed similar clinical outcome, such as TTP or OS, although XP had significantly better response rate. These two regimens had modest activity, but not effective in terms of TTP or OS. Median number of cycles was only 2.5 in both groups because most patients were over 65 years old, and had poor performance status. Development of new effective regimens in advanced BTC should be warranted.
Postoperative modified Glasgow prognostic score as an independent predictor of overall survival in clinically localized clear cell renal cell carcinoma.
Authors: Lindsey Allison Herrel, Caroline Gar-Ling Tai, Ruth Westby, Ken Ogan, Daniel Canter, John Pattaras, Peter Nieh, Viraj A. Master
Journal: Journal of Clinical Oncology (2013)

456 Background: Renal cell carcinoma (RCC) demonstrates heterogeneous behavior. Approximately 30% to 40% of patients with clinically localized RCC will later metastasize. Current tools are imperfect for predicting who will have distant spread of disease. The utility of the modified Glasgow Prognostic Score (mGPS) calculated from C-reactive protein (CRP) and albumin levels, has been well-studied as a pre-operative predictive tool in patients with various solid organ malignancies, including clear cell renal cell carcinoma. This score has not been used in the post-operative setting, and we hypothesized that mGPS can be a powerful tool to predicting overall survival. Methods: Patients undergoing nephrectomy for clinically localized RCC from 2005 to 2010 were studied. Inclusion criteria required clear cell histology and no nodal or metastatic disease at the time of surgery. Additionally, only patients with post-operative C-reactive protein and albumin recorded were included in the analyses. Demographic and clinico-pathological variables were analyzed as categorical variables with the exception of age and tumor size, which were analyzed as continuous variables. Patients were assigned an mGPS score of 0, 1, or 2 based on post-operative data (0 = CRP ≤ 10 mg/l, 1 = CRP&gt;10 mg/l and 2 = CRP&gt;10 mg/l and albumin&lt;3.5 g/dL). Survival analyses utilized Kaplan-Meier and multivariate Cox regression models. Results: Study criteria were met in 142 patients. Mean age was 59 years and 61% were men. No patients had T4 disease while 25% had T3, 9% had T2, and 66% had T1 disease. A post-operative mGPS of 0, 1, and 2 was assigned to 69%, 13% and 18% of the study population, respectively. Multivariate analysis identified post-operative high mGPS (mGPS = 2) as an independent predictor of overall survival (HR 5.591; CI 95% 1.508, 20.734; p = 0.010). Conclusions: In patients with clinically localized clear cell renal cell carcinoma, post-operative mGPS score is an independent predictor of overall survival. Accordingly, mGPS may be a useful tool to monitor disease progression in this patient population.
Cancer screening distress in a clinic-based population of BRCA mutation carriers
Authors: B. Karlan, L. B. Wenzel, K. Osann, R. Kurz, L. McClure
Journal: Journal of Clinical Oncology (2008)

20570 Background: Knowledge of BRCA1/2 carrier status has been linked with increased distress and health concerns in this population. Mutation carriers receive recommendations for more intensive cancer screening, which may create added stress. The purpose of this study is to identify whether there are differences in distress associated with the screening process depending on completion of prophylactic surgery (PS), and to determine whether this distress changes over time. Methods: A longitudinal design was utilized to survey 90 physician-referred women who had previously received notice that they were BRCA1/2 mutation carriers. Patient-reported surveys were collected during the first clinic visit, and at one year follow-up for 55 women. Cancer screening distress was measured by the Impact of Event Scale. Statistical analyses included t-tests and analyses of variance for continuous variables, and chi-square tests for categorical variables. Results: Among 90 BRCA1 (69%) or BRCA2 (30%) carriers, 40% had a cancer history. The majority of participants were nonHispanic White women (98%) of Ashkenazi Jewish descent (76%). 37% of the total study population reported clinically significant levels of distress associated with screening, driven largely by the BRCA1 mutation carrier cohort. Those considering PS evidenced significantly more distress associated with cancer screening (p=0.05) compared to those who were not opting for PS, or those who had already had it. Within the three groups, clinically significant levels of distress were noted in 26% who did not have PS, 39% for those who had PS, and 53% for those considering a procedure. At follow-up one year later, cancer screening distress decreased only for those who had considered and subsequently underwent PS. Quality of life did not change over time. Conclusions: Distress associated with the screening process was greatest for those considering surgery, but decreased sharply after the PS. Cancer screening was least distressing for those who were not considering a prophylactic procedure. Interventions should be targeted at those at greatest risk for distress. No significant financial relationships to disclose.
Epigenetic field effect markers as indicative of occult high-grade prostate cancer.
Authors: Sandra Marlene Gaston, Jihad E Hayek, Gaetan Otto, James Yen, Joseph Bigley, Leander Van Neste, Gary P Kearney
Journal: Journal of Clinical Oncology (2013)

116 Background: Epigenetic changes through DNA methylation can serve as biomarkers for the presence of prostate cancer (PCa). Gene methylation in histologically benign tissue adjacent to PCa can provide “field effect" biomarkers to detect cancer missed due to sampling errors. Such errors may also result in underestimates of PCa stage or grade, complicating decisions about Active Surveillance. We previously showed increased field effect methylation in GS 7 over GS 6 subjects in a small patient cohort. Here, established methylation markers of PCa (GSTP1, APC and RASSF1) were tested in a larger cohort to compare histologically benign biopsy cores from patients diagnosed with no cancer, low volume GS 6 cancer and GS 7 cancer. The objective was to confirm that epigenetic field effects may be useful for detecting occult high grade malignancies in diagnostic and prognostic settings. Methods: DNA was extracted from prostate biopsy tissue prints and used for multiplex methylation-specific PCR (MSP) assays of the 3 genes. All testing was done blinded. Each of 12 tissue cores was tested from a series of 76 biopsy patients: 34 diagnosed with GS 6 PCa, 22 with GS 7 PCa, and 20 no-cancer controls. Results: In 19 of the 22 GS 7 cases (86%), epigenetic markers were positive for field effects in one or more adjacent benign cores; 12 (54%) were positive for all 3 epigenetic markers. In contrast, only 9 of 34 cases (26%) GS 6 cases were positive for all 3 markers. We again observed that robust marker expression in histologically benign cores from cases diagnosed with low volume GS 6 PCa was associated with higher grade cancer at radical prostatectomy (upgrading). APC showed the best performance as a single marker “field effect” test for adjacent high grade PCa. Conclusions: GSTP1, APC and/or RASSF1 gene promoter methylation was observed to be more prevalent in histologically benign cores from biopsy patients diagnosed with GS 7 PCa, as compared with low volume GS 6. This study confirms previous findings in a larger cohort of subjects that these “field effect” biomarkers can be useful for detecting cancer adjacent to histologically negative biopsies and may be indicative of occult aggressive PCa.
Pathways impact on chemotherapy administration before death.
Authors: Marcus A. Neubauer, Jody S. Garey, Brian Turnwald, Josh Howell, Robyn K. Harrell, Jad Hayes, Debajyoti Bhowmik, J. Russell Hoverman, Barry Don Brooks
Journal: Journal of Clinical Oncology (2013)

86 Background: Continuing IV chemotherapy (chemo) in patients (pts) with advanced cancer near death does not extend survival or improve quality, but does increase costs. Pathways (PW) programs have compared treatment (tx) costs but have not evaluated the impact on chemo given near death. The primary goal is to evaluate IV chemo administered in the last 14 and 30 days of life in pts treated On vs. Off-PW. Methods: Eligibility: in US Oncology’s (USO) iKnowMed (iKM) EHR 7/1/09-6/30/12; diagnosis (dx) of breast, colon, NSCLC, SCLC or pancreas cancer; &gt;/=3 visits to a USO clinic; assessed for Level I PW compliance in the last 12 mths of life; and a date of death. IV chemo received in the last year of life was assessed. Pts were defined On-PW if all tx was On-PW or if pts did not receive IV chemo 12 mths before death (best supportive care). Pts were Off-PW if any tx received was Off-PW. PW-status, age, sex, dx, and last line of therapy (LOT) received were assessed. Multivariate logistic regression analysis was used to assess if PW status predicted likelihood of chemo within 14 and 30 days of death. Results: 12,551 pts met inclusion criteria. PW status was independently associated with chemo 14 and 30 days before death. Pts treated Off-PW had 2-fold higher odds of receiving IV chemo within 14, 30 days of death vs. pts treated On-PW (OR: 2; 95% CI: 1.8-2.3, OR: 2.2, 95% CI: 2-2.4), see Table. Findings were similar for each dx. Tx for pts On-PW vs Off-PW showed lower mean last LOT overall (1 vs. 2) and by dx. Conclusions: Pts On-PW were less likely to receive IV chemo within 14 and 30 days of death and had fewer LOT. This suggests adherence to Level I PWs is associated with improved quality metrics. [Table: see text]