tbuckley/cabot-search huggingface dataset:
Total bilirubin as a predictive marker for irinotecan-induced toxicity in patients with gastrointestinal cancer.
Authors: Katsuya Makihara, Sayaka Azuma, Hiroko Hasegawa, Masataka Ikeda, Kazumasa Fujitani, Hideyuki Mishima, Toshimasa Tsujinaka
Journal: Journal of Clinical Oncology (2014)

68 Background: Irinotecan (CPT-11) is widely used for the treatment of patients with gastrointestinal cancer. However, CPT-11 can cause severe neutropenia and diarrhea.It has been reported that the AUC of SN-38, an active metabolite of CPT-11, correlated with Pre-treatment serum total bilirubin level (PTB), but there is no criteria of dose setting based on the PTB. Therefore, we retrospectively searched the PTB which can serve as an indicator for dose setting of CPT-11. Methods: We investigated the incidence of neutropenia and diarrhea at the first 28 days in patients with gastrointestinal cancer who were administered CPT-11 alone in Osaka National Hospital from June 2006 to July 2013. Correlation between PTB and grade 3-4 neutropenia or diarrhea were assessed. When toxicity of correlation exists, ROC (receiver operating characteristic) analysis was conducted to explore the cut-off value of the PTB. In addition, the incidence of febrile neutropenia (FN) in the cut-off value was compared. Results: 87 patients were analyzed. Of these, 65 were gastric cancer, 22 were colorectal cancer. Although PTB was significantly higher in patients who experienced grade 3-4 neutropenia than those who didn’t (p&lt;0.001), PTB was not associated with grade 3-4 diarrhea. As the results of ROC analysis, cut-off value of PTB associated with grade 3-4 neutropenia was determined to 0.8 mg/dL. The incidence of FN was significantly higher in 20% of patients with PTB ≥ 0.8 mg/dL compared with 1.6% of patients with PTB &lt; 0.8 mg/dL (OR: 15.5, p=0.01). On the other hand, in subgroup analysis showed no difference in the incidence of FN and neutropenia in patients whose dose was less than 100 mg/m². Conclusions: PTB was a predictive marker for CPT-11-induced severe neutropenia and FN. Results of this study suggested needs of dose reduction to less than 100 mg/m 2 in patients with PTB ≥ 0.8mg/dL.
Neoadjuvant chemoradiotherapy with 5-fluorouracil, (5-FU), carboplatinum (C) and paclitaxel (T) dramatically improves survival in patients with clinical stage 2 and 3 adenocarcinoma of the distal esophagus and GE junction compared to surgery alone
Authors: E. L. Rosato, S. V. Daluvoy
Journal: Journal of Clinical Oncology (2005)

4204 Intro: The prognosis of adenocarcinoma of the distal esophagus & GE junction remains poor. Attempts to improve survival have been made using combined modality induction therapy with chemoradiotherapy (CRT) followed by surgery. Methods: A retrospective review of patients with adenocarcinoma of the GE junction or distal esophagus undergoing CRT followed by surgery or surgery alone from 1996 to 2003 was performed at Thomas Jefferson University Hospital. A total of 41 patients underwent induction CRT with concurrent C/T/5-FU and 45 Gy external beam radiation followed by surgery as part of an in-house Phase II protocol of stage II & III patients. This was compared with 26 patients who underwent surgery alone in the same period. Data collected included gender, age, race, clinical & pathologic stage (AJCC staging-5th Ed), and overall survival. Survival curves were calculated using Kaplan-Meier methods and compared using log-rank statistics. Results: The mean age in the CRT group was significantly lower than in the surgery alone group (58 v 67 years, p=0.0015). There was no difference in race between the 2 groups. Clinical stage in the CRT group was evenly distributed between stage II and III (n=20 and 21), while patients in surgery alone arm had stage I (n=12), II (n=8), or III (n=6). 13 patients achieved a pathologic complete response (pCR-32%), and they had a 5-yr survival of 70% compared to 45% survival for those with residual tumor (p=0.19). Patients with clinical stages II & III had significantly improved survival after induction CRT plus surgery compared to surgery alone (Table). Conclusion: Induction of CRT with C/T/5-FU followed by surgery in esophageal & GE junction adenocarcinoma is well tolerated and results in a 32% pathologic complete response rate and a 70% 5-yr survival in patients with no residual tumor. No significant financial relationships to disclose.
Carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in very platinum-sensitive ovarian cancer patients: Results from a subset analysis of the CALYPSO phase III GCIG trial.
Authors: S. Mahner, W. Meier, A. Du Bois, C. Brown, D. Lorusso, A. Ferrero, J. Cretin, H. Havsteen, P. Bessette, L. Angleitner-Boubenizek, I. B. Vergote, P. A. Vasey, V. Gebski, B. Slama, J. Herrstedt, L. Kaizer, A. Georgoulopoulos, N. Reed, U. Wagner
Journal: Journal of Clinical Oncology (2011)

5059 Background: CALYPSO is a randomized trial that showed superiority of carboplatin-pegylated liposomal doxorubicin (C-PLD) over carboplatin-paclitaxel (C-P) in relapsed ovarian cancer (ROC). Because the optimal management of patients with "very platinum-sensitive relapse" (>24 months platinum-free interval) is unclear, we performed a subset analysis of this CALYPSO population. Methods: Randomized, phase III, open-label, non-inferiority trial, enrolling 976 women with ROC that relapsed >6 months following first- or second-line therapy with platinum and paclitaxel. Patients were stratified by treatment-free interval (TFI) among other factors and randomized to C-PLD or C-P for a minimum of 6 cycles in the absence of progression or unacceptable toxicity. Patients with a TFI of >24 months were evaluated in this subset analysis for progression-free survival (PFS), the primary endpoint of CALYPSO, response and safety. Results: A total of 259 very platinum-sensitive patients were included (n=131, C-PLD and n=128, C-P). The median number of cycles was 6 in each arm. Median follow-up for PFS endpoint was 21 months. Median PFS times were 12.0 months (C-PLD) and 12.3 months (C-P), hazard ratio 1.05 (95% confidence interval [CI]: 0.79, 1.40; p=0.73 for superiority). Overall response rates were 42% and 38% for C-PLD and C-P, respectively (p=0.46). Worst toxicities were more common with C-P versus C-PLD and mimicked that of the overall CALYPSO population. Conclusions: Carboplatin-PLD and carboplatin-paclitaxel are equieffective in patients with very platinum-sensitive relapsed ovarian cancer previously treated with platinum and paclitaxel. However, carboplatin-PLD has a superior risk/benefit profile compared to carboplatin-paclitaxel which is of particular importance in this subgroup of patients with favourable prognosis.
Subgroup analyses of a phase III trial comparing tivozanib hydrochloride versus sorafenib as initial targeted therapy for patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Thomas E. Hutson, Dmitry Nosov, Timothy Eisen, Oleg N. Lipatov, Piotr Tomczak, Anna Alyasova, Mihai Harza, Mikhail Kogan, Boris Y. Alexseev, Cezary Szczylik, Andrew Louis Strahs, Brooke Esteves, Anna Berkenblit, Robert John Motzer
Journal: Journal of Clinical Oncology (2013)

354 Background: Tivozanib hydrochloride (T) is a potent, selective, tyrosine kinase inhibitor of all 3 VEGF receptors with a long half-life. T has shown tolerability and has extended progression-free survival (PFS) compared with sorafenib (S; median 11.9 months vs. 9.1 months; p =0.042) in a phase III trial (TIVO-1) as initial targeted therapy for pts with mRCC. We report results of PFS subgroup analyses from TIVO-1. Methods: Pts with clear-cell mRCC, prior nephrectomy, and ≤1 prior treatment for mRCC were randomized to T (n=260) or S (n=257). Cox proportional hazards model was used to evaluate PFS. Results: Significant improvement in PFS by T vs. S was observed for the following prespecified subgroups: white, Eastern Cooperative Oncology Group (ECOG) performance status 0, ≥1 year since diagnosis, no prior treatment, ≥2 metastatic sites, North America/Western Europe, baseline systolic blood pressure (SBP) ≤140 mm Hg, and baseline diastolic BP (DBP) ≤90 mm Hg. Exploratory subgroup analysis showed a similar significant improvement by T vs. S in Memorial Sloan-Kettering Cancer Center (MSKCC) favorable prognostic group, and pts who developed hypertension on study had significantly longer PFS than pts with normal BP. The improvement in PFS by T vs S was more marked for the subgroups that developed hypertension (selected subgroups shown in the table). Conclusions: PFS subgroup analyses showed a consistent advantage with T vs. S for mRCC. Clinical trial information: NCT01030783. [Table: see text]
Phase II study of irinotecan (CPT-11) plus doxorubicin (DXR) for early recurrent (&lt;12 months) (ER) or refractory (R) ovarian cancer (OC)
Authors: N. Umesaki, H. Tsuda, S. Nishimura, Y. Hashiguchi, K. Kokawa, R. Nishimura, S. Kamiura, O. Ishiko, K. Hasegawa
Journal: Journal of Clinical Oncology (2005)

5172 Background: There is no standard chemotherapy regimen for R-OC and ER-OC. CPT-11 (a DNA topoisomerase I inhibitor) is active against OC. A combination of CPT-11 and DXR (a topoisomerase II inhibitor) may inhibit both DNA and RNA synthesis, resulting in synergistic cytotoxicity. In a previous phase I study, the RD of CPT-11/DXR was 50 mg/m2 (days 1, 8, and 15)/40 mg/m2 (day 3) (Negoro et al., Anal Oncol 11, 2000). This is an interim analysis to evaluate the efficacy and toxicity of CPT-11 and DXR combination for R-OC and ER-OC. Methods: A multicenter study in pts with R-OC or ER-OC with measurable disease, or non-measurable disease and rising CA125. Eligibility criteria: Histologically verified OC, age 20–75 years, ECOG ≤2, adequate bone marrow, hepatic, and renal function, and written informed consent. CPT-11 (50 mg/m2) was administered on days 1, 8, and 15, plus DXR (40 mg/m2) on day 3. This regimen was repeated every 4 weeks. Toxicities were assessed according to NCI-CTC, and responses were assessed according to WHO or Rustin criteria. Results: Seventeen pts were enrolled and assessable for both toxicity and response. The median age was 52 years (41 to 71 years), and the histology was 8 serous and 9 non-serous. The interval since primary chemotherapy was <6 months in 13 pts and 6 to <12 months in 4 pts. Forty-six cycles were administered and 16 of 17 pts received at least 2 cycles (median of 2 cycles (1–7)). Gr3/4 toxicities were neutropenia (52.9%/35.2%), including 1 febrile neutropenia; thrombocytopenia (5.9%/17.6%), anemia (17.6%/0%), and diarrhea (5.9%/0%). The overall response rate was 23.5% (4/17), with 1 CR (5.9%) and 3 PR (17.6%). Conclusions: CPT-11 plus DXR is tolerable and promising for R-OC and ER-OC. We continue to enroll patients in this trial. No significant financial relationships to disclose.
<i>TGFBR1</i>*6A is somatically acquired at high frequency in cancer and switches TGF-β responses
Authors: B. Pasche, T. Knobloch, Y. Bian, J. Liu, V. Kaklamani, L. Baddi, D. Rosman, A. de la Chapelle, C. Weghorst
Journal: Journal of Clinical Oncology (2005)

9511 Background: TGFBR1*6A is a common variant of the type I Transforming Growth Factor Beta receptor (TGFBR1). Epidemiological studies suggest that TGFBR1*6A may act as a common tumor susceptibility allele. How TGFBR1*6A contributes to cancer development is largely unknown. Methods: To determine if TGFBR1*6A is somatically acquired by primary tumors and metastases during cancer development, we genotyped tumor and non-tumor tissues from 531 patients with a diagnosis of head and neck, colorectal or breast cancer. We determined whether the three amino acid deletion that differentiates TGFBR1*6A from TGFBR1 is part of the mature receptor or part of the signal sequence. We stably transfected cancer cells with TGFBR1 and TGFBR1*6A to determine whether TGFBR1*6A acts as a dominant allele in cancer cells. Results: TGFBR1*6A is somatically acquired in 43% of colorectal cancer metastases and in 2% of colorectal and head and neck primary tumors. TGFBR1*6A somatic acquisition is not associated with loss of heterozygosity, microsatellite instability or a mutator phenotype. The signal sequences of TGFBR1 and TGFBR1*6A are cleaved at the same site resulting in identical mature receptors. TGFBR1*6A acts a dominant allele that switches TGF-beta growth inhibitory signals into growth stimulatory signals in cancer cells. Conclusions: TGFBR1*6A is somatically acquired at high frequency in cancer and bestows cancer cells with a dramatic growth advantage in the presence of TGF-β. The functional consequences of this conversion are mediated by TGFBR1*6A signal sequence rather than by the mature receptor. The results highlight a new facet of TGF-β signaling in cancer and suggest that TGFBR1*6A may become a therapeutic target in cancer. No significant financial relationships to disclose.
Prognostic impact of C-reactive protein (CRP) in metastatic prostate cancer (MPC): A systematic review and meta-analysis.
Authors: Gurudatta Naik, Charity Morgan, Pedro Filipe Simoes da Rocha, Arnoud J. Templeton, Gregory Russell Pond, Guru Sonpavde
Journal: Journal of Clinical Oncology (2014)

43 Background: Serum C-reactive protein (CRP), a marker of inflammation, appears to demonstrate a prognostic impact in small studies of metastatic prostate cancer (MPC). We conducted a meta-analysis to better quantitate its prognostic impact. Methods: A systematic review was conducted to identify publications and presentations exploring the association of baseline serum CRP and overall survival (OS) in MPC, both castration-sensitive and castration-resistant. The hazard ratio (HR) and 95% confidence interval (CI) with P values were pooled. HRs were selectively extracted from multivariable analyses. Estimates of HRs were weighted and pooled using the generic inverse variance and random-effect models. Heterogeneity among trials was assessed using Cochrane’s Q statistic and the I 2 statistic was used to quantify inconsistency among trials. The assumption of homogeneity was considered invalid for P&lt;0.1. All statistical tests were two-sided, and P&lt;0.05 was considered significant Results: Six studies comprising 659 evaluable patients were eligible. The first authors were Prins (N=119), Pond (N=112), Ito (N=80), Nakashima (N=126), Beer (N=160), and McArdle (N=62). The Nakashima and McArdle studies evaluated castration-sensitive men, while the remaining four studies evaluated castration-resistant men receiving docetaxel-based chemotherapy. The primary endpoint was OS except the McArdle study, which used cancer specific survival. All HRs were derived from multivariate analyses except the Pond study, which was a bivariate analysis. Men with higher CRP had significantly worse OS than those with lower CRP (HR = 1.42, P&lt;0.001, 95% CI: 1.17 to 1.73; I 2 = 72.6%, p = 0.003). In trials of castration-sensitive men receiving hormonal therapy, high CRP yielded a HR = 1.92 (P=0.005, 95% CI: 1.22 to 3.03; I 2 = 0). In castration-resistant men receiving chemotherapy, high CRP yielded HR=1.35 (p=0.003, 95% CI: 1.11 to 1.65; I 2 = 79%), P for subgroup difference=0.20. Conclusions: This meta-analysis suggests a strong prognostic impact for CRP on OS in men with both castration-sensitive and castration-resistant prostate cancer. Prospective validation is justified, given the affordability, ready availability and large dynamic range of CRP.
A randomized controlled trial of primary tamoxifen versus mastectomy plus adjuvant tamoxifen in fit elderly women with breast carcinoma of high estrogen receptor content: Long-term results at 20 years of follow-up.
Authors: S. J. Johnston, F. S. Kenny, B. M. Syed, J. F. R. Robertson, S. Pinder, L. Winterbottom, I. O. Ellis, R. W. Blamey, K. Cheung
Journal: Journal of Clinical Oncology (2011)

536 Background: Long-term analysis of a randomized controlled trial (RCT) in Nottingham comparing surgery with tamoxifen as initial treatment demonstrated that, in unselected cases, surgery achieves better local control. However, it was also suggested that for patients with oestrogen receptor (ER) rich tumours, local control rates may be comparable. We now present long-term follow-up of a further RCT designed to clarify this group. Methods: Between 1989-1996, 153 fit elderly (≥70 years) women of mean age 78 years (range 70-93) with clinically node negative primary breast carcinoma <5cm of high ER content (H-score ≥ 100) were randomised to primary tamoxifen (n=100) or mastectomy with adjuvant tamoxifen (n=53). Randomization was 2:1 in favor of tamoxifen in order to detect the events in this group. Results: With a median follow-up of 78 months (range 6-237) there was no significant difference in breast cancer specific survival, metastatic status or regional recurrence between the treatment arms; however, local control was markedly inferior on primary tamoxifen. Conclusions: Irrespective of ER positivity, primary tamoxifen led to progression in a large proportion of cases. Thus surgery remains the treatment offering the lowest chance of local failure. However, there was excellent and similar breast cancer specific survival in both treatment groups, even at 10 years. Primary tamoxifen could be considered in those who are
Associations between hospice use and end-of-life (EOL) care outcomes in patients with advanced cancer.
Authors: Pallavi Kumar, Laura Hatfield, Alexi A. Wright, Jennifer S. Temel, Nancy Lynn Keating
Journal: Journal of Clinical Oncology (2015)

53 Background: There are few data examining the association between hospice care (HC) and the quality of advanced cancer patients’ EOL care. We explored associations between HC and family-reported relief of patients’ symptoms, quality of EOL care, and concordance with patients’ previously expressed wishes for EOL care and place of death. Methods: We surveyed 2,307 family members of deceased patients with advanced lung cancer (LC) or colorectal cancer (CRC) who were enrolled in the Cancer Care Outcomes Research and Surveillance (CanCORS) study (a national prospective, observational cohort study). We used propensity score matching to compare family-reported outcomes for patients who did or did not receive HC, including prevalence and relief of common symptoms (pain, dyspnea, depression or anxiety), quality of EOL care, and concordance with wishes for EOL care and place of death. Results: In 985 matched pairs, patients with LC or CRC who received HC had higher pain, distress from pain, and depression and/or anxiety, but more appropriate relief of pain and dyspnea (Table). HC was associated with a higher family-reported quality of EOL care, greater concordance with patients’ EOL care wishes, and higher likelihood of death in a preferred place. Conclusions: Patients receiving HC had greater symptoms compared to non-hospice enrollees, but had more appropriate symptom relief. HC for patients with LC or CRC is also associated with higher quality of EOL care, and concordance with wishes for EOL care and place of death as reported by bereaved family members. These data demonstrate the need to improve hospice utilization for advanced cancer patients. [Table: see text]
A new noninvasive blood-test for the early detection of colorectal cancer.
Authors: Iradj Sobhani, Roberto Incitti, Jean-Pierre Roperch
Journal: Journal of Clinical Oncology (2013)

348 Background: Colorectal cancer (CRC) remains a major medical problem in the world. Its early detection impacts the prognosis and the cost of treatment. Fecal occult blood test is a current noninvasive screening method for CRC detection in asymptomatic average risk individuals. It detects less than 50% of cancers and yields a high number of “normal” colonoscopies. The dysregulation of DNA methylation has been recognized as playing a crucial role during CRC development. The aim of the study was to develop a CRC-specific methylated DNA test in serum. Methods: First, the GoldenGate Methylation microarray containing 1,505 CpG loci within 807 cancer-related genes was used to study methylation patterns in CRC patients. We performed such assays on 9 tissues (4 CRC, 4 normal autologous tissues, 1 polyp), 17 blood and urine pooled samples (7 CRC, 6 polyps, 4 normal) and 20 stool samples (7 CRC, 3 polyps, 10 normal). The clinical status of each sample was assessed by colonoscopy and/or pathology findings. Among methylated genes detected in tumour tissue, stools, and blood, NPY, PENK and WIF1 genes were selected taking into account their high degree of methylation. We then carried out a clinical validation by quantitative multiplex methylation-specific PCR (QM-MSP) in two phases: firstly on 30 tissues (15 CRC, 15 homologous normal tissues) and secondly on 193 serum samples (32 CRC, 161 normal). Results: For to obtain the best accuracy of QM-MSP test, we defined for both biological sources a cumulative methylation index (CMI) by adding of the methylation percentage of each gene. At the CMI of 20.0% on tissues, our QM-MSP test allows to diagnose the CRC with the highest accuracy (100% of specificity and 100% of sensitivity). From sera, the CMI has been standardized at 2.0% giving a sensitivity and specificity for detecting CRC of 94.4% and 59.4% respectively (NPV of 92.1% and PPV of 67.8%). Conclusions: We developed a QM-MSP-based analysis of NPY, PENK, and WIF1 methylated genes in serum. This test classified correctly and with a high accuracy the healthy individuals and colon cancer patients. We propose here new sensitive serum-based epigenetic biomarkers as an effective and simple new noninvasive test for CRC screening in the average and high risk populations.
Average breast cancer stage in patients with various insurances and incomes.
Authors: Sehr Haroon
Journal: Journal of Clinical Oncology (2012)

278 Background: Worsening global economy is increasing uninsured vs. other insurance (private, medicare, Medicaid, VA). Average stage of breast cancer is likely higher in uninsured vs. other insurance. Methods: Individuals diagnosed with breast cancer (diagnosed 2000- 2009) were reported to the National Cancer Database (NCDB). Variables of insurance status (uninsured, private, Medicaid, Medicare, and VA), stage of diagnosis (0:carcinoma in situ- 4:metastatic disease), and income level (&lt;$28k, $28k-32,999, $33k-38,999, $39k-48,999, $49k+) were analyzed. Results: From 2000-2009, the privately insured percentage decreased by 39.4%, with 134.3% increase in Medicaid insured. Average stage in uninsured was 1.8, statistically significant compared to 1.2 for privately insured, and 1.5 for Medicare. This was untrue of VA and Medicaid insured. Significant differences exist between uninsured and Privately insured for every income. At $28K/yr, average stage of breast cancer was 1.9 in uninsured,1.5 in privately insured. When income &gt;49K/yr, average stage was 1.7 in uninsured, 1.3 in privately insured, while VA insured remained 1.4. Conclusions: Uninsured patients had worse stage than privately insured. For private and Medicare insured, increasing income correlated significantly to earlier stage of diagnosis4, which was untrue for uninsured, VA, and Medicaid insured. Highest stage was in lowest income uninsured, whereas lowest stage was in highest income, privately insured. Income did not effect average stage of VA. [Table: see text]