tbuckley/cabot-search huggingface dataset:
Outcomes associated with anemia in chemotherapy-treated cancer patients
Authors: A. Ben-Jacob, M. Fridman, D. Lubeck
Journal: Journal of Clinical Oncology (2004)

6142 Background: The prevalence of anemia in patients (pts) treated in community oncology practices and associated resource utilization is not well documented. This study evaluated presence of anemia in chemotherapy (ctx)-treated cancer pts and associated outcomes.Methods: Chart data were abstracted, retrospectively, from 1025 oncology pts at 35 US community oncology practices. Data from pts who had received ctx for at least 60 days from January 2001 to January 2002 were included. Standard data collection forms were completed at all sites including all ctx, laboratory, and associated visit information during the entire treatment course. Anemia was defined as a hemoglobin (Hb) value of <11 g/dL at any point during ctx. Results: Anemia was present in 669 (65.3%) pts. Mean age of anemic pts was 62.9 years (SD=13.1) while non-anemic pts averaged 60.5 years (SD=13.1; p=0.005; t-test). There were no statistically significant differences in gender (67% female overall), ethnicity (86% Caucasian overall), cisplatin-containing ctx (29.4% overall) or tumor type (breast [33.4%], colorectal [14.2%], and non-small cell lung [13.1%]). Anemic pts were significantly more likely to receive red blood cell transfusions than non-anemic pts (15.4% [95%CL=12.5–18.0] vs. 0.8%,[95% CL=0.0–1.8], respectively; p<0.0001; chi-square) and more likely to be hospitalized (33.4% [95% CL=30.8–38.1] vs. 12.6%[95% CL-9.2–16.2], respectively; p<0.0001; chi-square). Anemia was also associated with an earlier time to admission (mean 65.9 [SD=49.3] days vs 70.9 [SD=46.1] days, respectively) and a longer length of stay (mean of 8.2 [SD=8.9] days vs. 7.2 [SD=7.9] days, respectively). Anemia was also associated with a greater chance of a break in ctx treatment (31.4% of anemia pts did not complete planned ctx vs. 21.1%, respectively; p<0.001) and increased likelihood of progressive cancer (23.5% vs.12.4%, respectively; p<0.001). Conclusions: Anemia was prominent in this study sample and potentially has an adverse effect on outcomes and resource utilization. Early treatment should be instituted to reduce the risk of anemia and its associated adverse outcomes. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Inc. Amgen, Inc. Amgen, Inc. Amgen, Inc.
Analysis of pre-treatment O<sup>6</sup>-alkylguanine transferase (AGT) levels in patients (pts) with hematologic malignancies receiving VNP40101M (101M)
Authors: S. L. Gerson, S. O’Brien, J. Donze, V. Karsten, J. Karp, D. Rizzieri, G. Verhoef, S. Daenen, M. Sznol, F. Giles
Journal: Journal of Clinical Oncology (2005)

6542 Background: 101M is a novel DNA cross-linking alkylating agent that preferentially attacks the O6 position of guanine. In preclinical studies, resistance to 101M is related to increased cellular levels of AGT, the enzyme that removes the chloroethyl group from the O6 position of guanine prior to formation of the DNA cross-link (Finch et al., Cancer Research 2001). We postulated that AGT activity measured in peripheral blood (PB) or bone marrow (BM) samples obtained prior to 101M treatment would correlate with clinical response. Methods: Samples were analyzed in 30 of 41 advanced leukemia pts entered to CLI-034, a phase I study of escalating doses of 101M (200–600 mg/m2) in combination with araC 1.5 gm/m2 IVCI days 1–4, and 31 of 107 pts enrolled to CLI-033, a phase II of 101M 600 mg/m2 for high risk MDS or acute myeloid leukemia (AML). Eligibility in the latter trial was restricted to pts > 60 years without prior induction chemotherapy, or AML in 1st relapse and 1st complete response (CR) duration < 12 months. AGT was measured in PBMC samples according to published techniques (Spiro et al, Cancer Research 1999). Results: Median AGT activity was 11.57 fm/μg DNA (range 1–131) in the entire population; for studies CLI-034 and CLI-033 it was 8.28 (1–131), and 14.9 (2.96–36.23), respectively. A significant difference was found in the response rates above and below the median AGT activity (p=0.0023). Response and demographic information for evaluable patients are provided in the table below. Conclusions: 101M is an active agent in leukemia. Responses are observed in some pts with poor prognosis and/or progression after standard therapy. AGT activity appears to be an independent predictor for response to 101M and may be valuable in selecting patients for future clinical trials. We recently initiated a phase I trial for patients with advanced heme malignancies in which temozolomide is used to deplete AGT prior to 101M administration. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Vion Vion
Homocysteine (HC) level as possible predictor of pemetrexed efficacy
Authors: J. Symanowski, L. Simms, A. Melemed
Journal: Journal of Clinical Oncology (2006)

20078 Background: Pemetrexed is a novel anticancer agent clinically active in several solid tumors, including malignant pleural mesothelioma (MPM), non-small cell lung cancer (NSCLC), and breast cancer. Pemetrexed’s anticancer activity is believed to be related to its inhibition of 3 enzymes involved with folate metabolism and DNA synthesis. Some side effects associated with its clinical activity are more pronounced if a patient (pt) has a folate deficiency and high HC levels (Niyikiza et al, Ann Oncol 1998). Given this connection, we hypothesized that high HC levels might predispose a pt to pemetrexed anticancer activity. In a related question, we examined if baseline HC levels varied among different cancers. Methods: To investigate these hypotheses, plasma HC levels were examined from pts in the pemetrexed-containing arm of a phase III MPM trial (N = 226; Vogelzang, JCO 2003); a phase III NSCLC trial (N = 265; Hanna, JCO 2004); and a phase II breast cancer trial (data pooled from 600 and 900 mg/m 2 groups) (N = 92; Llombart, ASCO 2006). For each study, HC (high vs low) was used as a prognostic indicator variable for overall survival (OS) and progression-free survival (PFS). Different cut points distinguished pts with high vs low HC, and final analysis results were based on the optimal cut point that yielded the largest Wald chi-square value (smallest p-value). Results: Average baseline HC levels were similar for each trial: 11.0, 10.6, and 10.6 μmol/L for the MPM, NSCLC, and breast trial, respectively. The MPM data suggested that high HC pts had longer OS (all hazard ratios [HRs] &lt;1). The NSCLC data showed comparable OS times regardless of HC level. MPM and NSCLC data for PFS was similar to OS results. PFS from the breast cancer study was also similar for both HC groups (HR ∼1). Conclusions: Average baseline HC level did not suggest differences in nutritional status of the 3 pt populations. Data examination from the 3 studies yielded contradictory results, suggesting that high HC level is not a predictor of a better efficacy response to pemetrexed. [Table: see text] [Table: see text]
SCCRO/DCUN1D-gene family is commonly dysregulated in non-small cell lung cancers
Authors: C. C. Bommeljé, C. T. Stock, B. J. Golas, S. Bains, C. Towe, V. W. Rusch, Y. Ramanathan, B. Singh
Journal: Journal of Clinical Oncology (2008)

22058 Background: SCCRO1/DCUN1D1 is a novel oncogene mapped to 3q26.3, a locus known to be amplified in a wide range of human cancers. SCCRO1 amplification is associated with an aggressive clinical course. In silico analyses identified four highly conserved SCCRO1 paralogs mapped to chromosomal loci known to be aberrant in malignancies, including non-small cell lung cancer (NSCLC). The aim of this study is to assess the status of the SCCRO/DCUN1D family in NSCLC by gene expression analysis and correlate with histological subtypes of NSCLC, clinical parameters and outcome. Methods: RNA was extracted from snap frozen primary lung cancer from 56 patients undergoing definitive resection following institutional guidelines and after obtaining informed consent (n=27 adenocarcinomas (ADC); n=30 squamous cell carinomas (SCC)). Specific primer pairs were designed. Gene expression analysis was performed using RT-PCR. GEnorm identified B-actin as the most stable housekeeping gene which was used as control. Change in gene expression was determined for each tumor relative to its matched normal tissue. All statistical comparisons were performed using non-parametric measures. Results: Four of the five SCCRO-family genes (SCCRO1, SCCRO2, SCCRO4 and SCCRO5) were overexpressed in NSCLC. Overexpression of these genes was significantly more common in SCC (57%, 23%, 7% and 47% respectively) relative to ADC (4%, 11%, 0% and 7% respectively), with 70% of SCC having at least one of these genes dysregulated. There was a postitive correlation for overexpression and history of smoking (p<0.05) and outcome (P=0.05) in SCC. The expression of SCCRO3R was significantly reduced in both ADC (48%) and SCC (57%), but showed no correlation with clinical or outcome variables. Conclusions: The SCCRO family of genes are overexpressed in a significant number of lung SCC, but not ADC. Overexpression is correlated with a history of tobacco exposure, implicating it as a putative tobacco-related event. Interestingly, there was a significant loss in expression of SCCRO3R in both ADC and SCC. Biochemical characteristization of SCCRO3R suggest it may act as an antagonist of the other SCCRO family members, suggesting its function as a tumor suppressor. The dysregulation of SCCRO in NSCLC may have diagnostic and therapeutic implications. No significant financial relationships to disclose.
Patient evaluation of a physician conveying a more optimistic versus a less optimistic message: A randomized controlled trial.
Authors: Kimberson Tanco, Wadih Rhondali, Pedro Emilio Perez-Cruz, Silvia Tanzi, Gary B. Chisholm, Walter F. Baile, Amy Sisson, Joseph Arthur, Eduardo Bruera
Journal: Journal of Clinical Oncology (2014)

88 Background: Information regarding treatment options and prognosis is essential for patient decision making near end of life. However, physicians are frequently reluctant to deliver bad news due to multiple factors, including fear of being perceived as less compassionate. This randomized controlled double blind trial aimed to examine the patient’s perception of physician compassion after being exposed to a more optimistic vs. a less optimistic message. Methods: 100 patients were randomized to observe 2 standardized videos, depicting a physician discussing treatment and prognostic information (more optimistic message and less optimistic message) with a patient with advanced cancer. Both physicians displayed identical number of empathetic statements (5) and posture. Three sets of surveys were completed including the Physician Compassion Questionnaire (0=best, 50=worst). Actors and patients were blinded to the purpose of the study. Investigators were blinded to the video observed by the patient. Results: Patients reported significantly better compassion scores after watching the more optimistic video as compared to the less optimistic video [median (Q1-Q3): 15 (5-23) vs. 23 (10-31), p=0.0002]. Results were equally significant after parallel analysis of first video only and after cross-over analysis. There was also an order effect with compassion scores (p=0.0002) favoring the second video. Univariate analysis showed that degree of trust in the medical profession, ESAS fatigue, ESAS anxiety and ESAS depression had significant association with compassion perception independent of message observed. After applying Bonferonni correction, only degree of trust in the medical profession reached the corrected p value of p=0.0014 (p=0.0002). Conclusions: A more optimistic message resulted in a physician being perceived as more compassionate by the patient. The physician seen in second order is also perceived to be more compassionate. More research is needed to better understand patient perception of compassion in communication with physicians.
Differential protein expression profiling by iTRAQ-2DLC-MS/MS of human bladder cancer EJ138 cells transfected with the metastasis suppressor KiSS-1 gene
Authors: L. Grau, I. Ruppen, M. Gil, J. M. Piulats, J. Bellmunt, K. Ashman, T. Ecke, M. Sanchez-Carbayo
Journal: Journal of Clinical Oncology (2009)

e16043 Background: The use of isobaric tags for relative and absolute quantization (iTRAQ) followed by multidimensional liquid chromatography (LC) and tandem mass spectrometry (MS/MS) analysis is emerging as a powerful methodology for biomarker and drug target discovery. KiSS-1 is a metastasis suppressor gene reported to be involved in the progression of several solid neoplasias. The loss of KiSS-1 expression has been shown to be inversely correlated with increasing tumor stage and poor overall survival in bladder tumors. In order to identify the molecular pathways associated with the metastasis suppressor role of KiSS-1 in bladder cancer, we carried out a proteome discovery analysis using an iTRAQ approach. Methods: Bladder cancer cells (EJ138) were transiently transfected with a vector encompassing the full length KiSS-1 gene. Protein extracts collected after 24h and 48h transfection were fractionated, digested with trypsin and treated with iTRAQ reagents. The labelled peptides were separated through Strong Cation Exchange (SCX) and Reversed Phase LC and analysed by MALDI TOF/TOF MS. Several software packages were utilized for data analysis: ProteinPilot, Protein Center for gene ontology (GO) analysis and Ingenuity Pathway. Results: Comparative analysis among transfected, mock and empty vector exposed cells have identified more than 800 proteins with high confidence (&gt;99%), showing high correlation rates among replicates (&gt;70%). The involvement of the identified proteins in biological networks has served to characterize molecular pathways associated with KiSS-1 expression and to select critical candidates for validation analyses by Western Blot using independent transfected replicates. As part of complementary clinical validation strategies, inmunohistochemical analyses performed in metastatic bladder tumours spotted onto tissue microarrays (n = 175) have revealed the role of KiSS-1, ezrin and filamin in bladder cancer progression. Conclusions: Our proteomic study not only has served to reveal molecular mechanisms associated with the metastasis suppressor role of KiSS-1 in bladder cancer, but also to identify novel potential metastatic biomarkers for patients affected with bladder tumors. No significant financial relationships to disclose.
Satraplatin, an oral platinum analog, is active and synergistic with paclitaxel and docetaxel in prostate carcinoma models
Authors: L. Lamphere, F. Obermayr, M. Caligiuri, G. Unteregger, M. S. Rudoltz, K. Wosikowksi, A. M. Casazza
Journal: Journal of Clinical Oncology (2006)

14620 Background: Satraplatin is a novel oral platinum analog with potent cytotoxic and antitumor activity in preclinical models. Satraplatin showed activity in hormone refractory prostate cancer (HRPC) and other tumor types in Phase II trials. A pivotal Phase III trial evaluating satraplatin as 2 nd -line therapy for HRPC completed accrual of &gt; 900 patients in 2005. Satraplatin’s activity, safety profile and ease of administration make it attractive for combination regimens. Methods: Satraplatin and its active metabolite JM-118 were tested in vitro as single agents in the androgen-sensitive LNCaP and the androgen-insensitive PC-3 and DU-145 human prostate carcinoma (ca.) cell lines. For in vitro combination studies, PC-3 cells were treated with satraplatin or JM-118 either prior to, after, or concomitantly with paclitaxel or docetaxel. The PC-3 cell line was used for in vivo xenograft experiments in nude mice. Paclitaxel was given intravenously on Day 1, satraplatin orally on Days 2 to 6, and paclitaxel again on Day 8. Results: Satraplatin and JM-118 as single agents inhibited the growth of all three prostate ca. cell lines in vitro in a dose dependent fashion. IC 50 values for JM-118 were &lt; 1μM. Strong synergism was noted when PC-3 tumor cells were treated in vitro with paclitaxel or docetaxel followed by satraplatin or JM-118. Satraplatin administered orally inhibited the growth of PC-3 xenografts in nude mice. Treatment of advanced PC-3 tumors with paclitaxel (40 mg/kg) and satraplatin (35 mg/kg) was well tolerated and resulted in a Tumor Growth Delay equivalent to 3 Log Cell Kill, an effect superior to that of the single agents. Conclusions: In vitro, satraplatin and its metabolite JM-118 are active as single agents against human prostate ca. cells, and are synergistic with taxanes. In vivo, treatment with paclitaxel followed by satraplatin showed synergism without increased toxicity. These preclinical data support ongoing Phase I and II clinical trials that are evaluating combinations of satraplatin with paclitaxel or docetaxel. [Table: see text]
Outcomes after chemoradiation alone for adenocarcinoma of the esophagus and gastroesophageal junction.
Authors: Anthony Pham, Karyn A. Goodman, David H. Ilson, Yelena Yuriy Janjigian, Geoffrey Yuyat Ku, Nabil P. Rizk, Abraham Jing-Ching Wu
Journal: Journal of Clinical Oncology (2015)

138 Background: Definitive chemoradiation (CRT) is a standard treatment for esophageal cancer (EC), particularly squamous cell carcinoma (SCC). However, data for nonsurgical treatment of adenocarcinoma (AC) is limited, and response rates to CRT are lower in AC vs. SCC. Therefore, trimodality therapy is often preferred for AC. However, some patients with AC achieve clinical complete response (cCR) after CRT and decline surgery, or are medically inoperable. We therefore reviewed outcomes after CRT alone for esophageal AC. Methods: All patients receiving full-dose (≥ 50 Gy) CRT without surgery for Stage I-III AC of the esophagus or gastroesophageal junction (GEJ) from 2007-2012 at our institution were included. Complete clinical response (cCR) was defined as negative post-CRT biopsy, or SUVmax ≤ 3 on post-CRT PET if no biopsy was obtained. Local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: 105 patients were included. 11 patients (10%) had T1-2N0 disease; the rest had T3+ or N+ disease. Median follow-up was 49 months. 85 patients (81%) received induction chemotherapy prior to CRT. Median OS was 25 months, with 3/5 year OS of 35% and 20% respectively. 67 patients (64%) had cCR, with median OS of 33 months and 3/5 year OS of 48% and 30%, compared to 15 months in incomplete responders (p&lt;0.001). There were no long-term survivors among incomplete responders. 31 (46%) of cCR patients developed local failure, with 3 and 5 year LRFS of 53% and 46%. Median DMFS was 33 months in cCR patients. Of 10 patients who developed isolated local failure, 6 had salvage surgery, 3 had brachytherapy and 1 had laser ablation. Of these, 3 are alive and 2 are free of disease. Conclusions: This is the largest reported series of CRT alone for esophageal AC. In cCR patients, CRT alone is associated with long-term survival comparable to that expected with trimodality therapy. However, local recurrence still occurs in nearly half of patients with cCR. More study is needed to define which patients with cCR will benefit from immediate surgery after CRT, and improvements in therapy are needed to reduce local failure in patients not eligible for surgery.
The reported rate of radiation-induced cardiac toxicity in patients with breast cancer: Impact of treatment era and follow-up duration
Authors: S. Demirci, J. Nam, J. L. Hubbs, L. B. Marks
Journal: Journal of Clinical Oncology (2008)

11595 Background: Cardiac toxicity following breast radiotherapy (RT) has been widely described in ‘older’ RT trials (i.e. those using higher fraction sizes, wide RT fields and orthovoltage energy). More ‘modern’ RT techniques reportedly reduce cardiotoxicity. Comparisons between older and modern trials are confounded by the longer follow-up in the older trials. We systematically assess the impact of treatment era and follow-up on the reported rates of cardiac mortality associated with RT. Methods: The English-language literature was surveyed using Pubmed to identify studies with key words of ‘breast cancer’ and ‘radiotherapy’ and ‘heart’ and ‘morbidity/mortality’. The relative risk (RR) or hazard ratio (HR) of RT-associated cardiac mortality was extracted from each study. Studies were grouped based on study era and median follow-up duration. The reported RR/HR were averaged for each group. Results: 23 published reports of patients treated from 1949–2001 were analyzed (1 meta-analysis, 8 randomized controlled trials, 14 multicenter tumor registry and database studies). Higher RR or HR were reported in trials conducted prior to 1970 vs more modern studies (see table). Both the older and modern studies have low HR/RR at short follow-up durations (6–10 years). The relatively high HR/RR associated with older studies was apparent only at >11–15 years of follow-up. The modern studies obviously lack longer follow-up. Conclusion: Modern RT techniques appear to lessen the short-term risk of RT-associated cardiac mortality. Additional follow-up is needed to ensure that modern methods effectively prevent cardiac toxicity. Continued diligence to minimize cardiac exposure remains prudent. Acknowledgement: This work was supported by grant from International Atomic Energy Agency (IAEA, TUR/07003). Treatment era (Median Start Year) RR/HR for RT-associated cardiac mortality; average and range Median Follow-up Duration (years) 6-10 11-15 16-20 21-25 1940-1960 1.43 1961-1970 2.46 1971- 1980 1.06 (1.03-1.09) 1.69 (1.65-1.74) 1.56 (1.23-2.5) 1.58 1981-1990 1.00 (0.4- 2.1) 1.38 (1.27-1.5) 1.41 (1.1-1.99) 1991-2000 0.99 No significant financial relationships to disclose.