tbuckley/cabot-search huggingface dataset:
Response and survival in oesophageal cancer patients following neoadjuvant chemotherapy assessed by FDG-PETCT imaging and corelation to pathologic response.
Authors: Y. Manikyam, S. J. Hughes, C. Harrison, D. McManus, C. Boyd, C. L. Ng, P. D. Carey, J. A. Kennedy, K. McManus, M. M. Eatock
Journal: Journal of Clinical Oncology (2010)

e14571 Background: Combined positron emission tomography with computed tomography(PETCT) using [18F] 2-fluoro-2-deoxy-D-glucose (FDG) is an important modality for staging oesophageal cancer and may also predict pathological response to chemotherapy. We therefore conducted this retrospective review to assess the relationship between metabolic response measured by FDG-PETCT imaging following neoadjuvant chemotherapy in oesophageal cancer and survival. Methods: Oesophageal cancer patients presenting to Northern Ireland Cancer Centre between January 2003 to December 2008, who had FDG-PETCT assessment for staging and also following neoadjuvant chemotherapy before surgery were included. Routine FDG-PETCT findings were collated and metabolic response (≥ 35% reduction in the tumour standard uptake values[SUV]), evaluated. Pathologic response was assessed and stratified into five histological tumour regression grades (TRG1-5). TRG 1 and 2 groups were classified as pathological responders. Overall survival and event-free survival were obtained. Results: 81 patients with a median age of 66 years (28-77) were identified. 66 (81%) had oesophageal carcinoma and 15 (19%) had Siewart type I or type II oesophageal-gastric junction (OGJ) carcinomas. Metabolic response was identified in 67 (82.3%) of patients. After a median follow up of 25.0 months, the median overall survival in metabolic responders has not been reached. In the metabolic non responders the median overall survival was 15.7 months (p 0.005), (HR = 2.66, 95%CI 1.31-5.41) and median event-free survival was also 15.7 months (p 0.023), (HR = 2.14, 95%CI 1.09-4.21). Pathological response was seen in 14 (17.9%) and this correlates poorly with metabolic response. There is no statistically significant relationship between pathologic response and survival. Conclusions: Metabolic nonresponse to neoadjuvant chemotherapy measured by FDG-PETCT appears to be associated with a poor survival. Further work will seek to identify a molecular signature for lack of response to preoperative chemotherapy in order to minimise exposure of patients to toxic treatment where they are unlikely to benefit. No significant financial relationships to disclose.
Dose-finding study using oxaliplatin (Ox) in combination with fixed dose gemcitabine (Gem) and radiotherapy (RT) in patients with locally advanced pancreatic or biliary tract cancer (PBCa)
Authors: M. Peeters, T. Boterberg, E. Monsaert, I. Borbath, A. Demols, M. Polus, P. Scalliet, F. Berrevoet, T. Derre, J. Van Laethem
Journal: Journal of Clinical Oncology (2006)

14028 Background: Prognosis of inoperable PBCa is poor. Large randomized studies in pancreatic cancer showed a better survival in patients (pts) with locally advanced (LA) in comparison with metastatic disease. Data on radiochemotherapy are scarce in pts with LA disease. Therefore, we performed this multicenter, phase I study on the combination of radiotherapy and Gem/Ox. This regimen showed superior activity to Gem alone in pancreatic cancer (Louvet C et al. JCO 2005;23:3509–16.) Methods: After signed informed consent, pts with LA pancreatic cancer (n = 14) or biliary tract cancer (n=1) were included. They received two cycles of Gem/Ox 1 followed by 5 weeks of RT (25 fractions of 1.8 Gy up to a total dose of 45 Gy) in combination with a weekly fixed dose of Gem (300 mg/m 2 in 30’) and an escalating weekly dose of Ox (levels: 40/50/60 mg/m 2 ). NCI-CTC 2.0 was used weekly to score treatment-related toxicity in all pts. Results: Today, 15 pts. with a median age of 61 y (range: 44–74), median Karnofsky performance score 90 (range: 70–100) and M/F = 8/7 were included. Upto 60 mg/m 2 Ox, no disease limiting toxicity (DLT) occured. Grade 3 toxicity included nausea (n = 1), neutropenia (n = 3) and thrombocytopenia (n = 1). This latter patient was treated with 40 mg/m 2 Ox and subsequently also experienced a grade 4. One patient receiving 50 mg/m 2 Ox developed a grade 4 thrombocytopenia. Most frequent grade 1/2 toxicity was nausea (n = 8, 53%), thrombocytopenia (n = 5, 33%) and diarrhea (n = 5, 30%). Fourteen out of 15 received the full course of radiotherapy. Median time to progression (TTP) is 6.7 months (95% CI: 3.7–13.5). Thirteen out of 15 pts. are still alive. Conclusions: Combination of radiotherapy and Gemcitabin/Oxaliplatin in pts with LA pancreaticobiliairy cancer is feasible and well-tolerated. The long TTP underlines the potential activity of this regimen. As no DLT has been reached, we will use a dose of 60 mg/m 2 Ox for further evaluation. [Table: see text]
Survival in women with breast cancer having children with pediatric tumors—-A nationwide cancer register study
Authors: H. Olsson, A. Bladström
Journal: Journal of Clinical Oncology (2006)

20071 Background: Breast cancer is a heterogenous disease with a minoruty of cases having a hereditary background. Hereditary factors could affect disease prognosis and it has been postulated that breast cancer patients having p53 germline mutations have an especially bad prognosis. In the present study survival has been compared in women with breast cancer with and without having a child with a pediatric tumour. Methods: Using and linking the population based fertility registry and cancer registry the offspring of all women with breast cancer diagnosed between 1961–1999 was traced in Sweden. All women with breast cancer with a pregnancy were included. Further all childhood cancer cases &lt; 21 years of age were identified among the offspring. Likewise using census data the women’s overall survival was followed. Results: Patients with breast cancer having a child with a childhood malignancy (n = 254) had a significant worse survival compared with other women with breast cancer (n = 74,781), RR = 1.25, 95% CI 1.02–1.55, p &lt; 0.04, adjusted for age at diagnosis, year of diagnosis, parity and time since last pregnancy. Mothers with children with pediatric sarcomas or acute myeloid leukemias seemed to be strongest associated with a worse survival in the mother (RR = 1.38 and RR = 1.69). The worse survival of the mother was present regardless if the breast cancer diagnosis was before or after 50 years of age. Conclusion: The results suggest that genetic syndromes such as the Li-Fraumeni syndrome and possibly other childhood/adult cancer syndromes if present worsens the survival for breast cancer patients. This familial factor may be of importance for future treatment stratification. It is unknown whether other tumor diseases in the mother may be associated with a worse survival if their children have had cancer. No significant financial relationships to disclose.
An evaluation of FDG-PET as a predictor of metabolic response to chemotherapy in metastatic colorectal cancer patients (mCRC).
Authors: N. Van Damme, S. De Bruyne, J. Mertens, C. Van de Wiele, W. P. Ceelen, P. Smeets, L. Ferdinande, S. Laurent, K. Geboes, M. Peeters
Journal: Journal of Clinical Oncology (2011)

e14057 Background: Limited information is available on the role of FDG-PET in the management of patients with mCRC. Bevacizumab prolongs overall survival and progression-free survival (PFS) when added to standard chemotherapy in mCRC patients. The purpose of the study was to explore the possible role of FDG-PET as response predictor for bevacizumab treatment in liver mCRC patients. Methods: Eighteen mCRC patients (7 women and 11 men), were treated with FOLFOX (n=12) or FOLFIRI (n=6) and bevacizumab (5 mg/kg). FDG-PET scans were performed before treatment (baseline) and median 15 days after cycle 5 (follow-up). PET scans were read by a nuclear medicine physician, blinded to the results of clinical parameters. The most representative liver lesion was used as target lesion. PET results were quantified by calculating the maximum standard uptake value (SUVmax) at baseline and follow-up. PFS was defined as the time from start of treatment to the date of first documented disease progression. Results: Median PFS was 10 months (95% CI: 8.51-11.49). The median baseline SUVmax was 5.18 (IQR: 3.61-8.42) and the median follow-up SUVmax was 2.93 (IQR: 2.15-5.94; p=0.025). Following the EORTC criteria, FDG-PET revealed a complete metabolic response in 8 patients (44%), partial metabolic response in 3 patients (17%), stable metabolic disease in 3 patients (17%) and progressive metabolical disease in 4 patients (22%). Correlation between metabolic response and radiological response according to RECIST was as follows: 6 of the 8 patients with radiological response had metabolic response (sensitivity 75%) and 5 out of 10 patients with radiological stable or progressive disease were metabolic non-responders (specificity 50%). Using the Cox proportional hazards model, the follow-up SUVmax (HR 1.33, 95% CI 1.000-1.776, p=0.05) showed a trend towards significant prediction of PFS. The Kaplan-Meier log rank test showed a PFS benefit for patients with >30% reduction in their SUVmax (p=0.02). Conclusions: The use of FDG-PET for therapy monitoring is clinically feasible and the follow-up SUVmax seems to be a promising predictor of PFS.
Do molecular markers predict when to implement aromatase inhibitor therapy in invasive breast cancer
Authors: S. Tovey, B. Dunne, C. J. Witton, A. Forsyth, T. G. Cooke, J. M. S. Bartlett
Journal: Journal of Clinical Oncology (2005)

9559 Background: Data from the ATAC & IES trials suggest that differences exist in the molecular profile of patients who response to early or delayed treatment with aromatase inhibitors. PR-ve patients derived greater benefit from initial aromatase inhibitor treatment compared to tamoxifen (ATAC) than those treated after 2–3 years tamoxifen (IES). We show that HER1–3 positive/PR negative patients are significantly more likely to relapse on tamoxifen treatment at an early stage but that HER/PR status has no impact on the likelihood of later recurrences. Methods: 402 ER+ve surgical patients treated between 1983–1999 who received adjuvant tamoxifen and adjuvant chemo/radiotherapy according to protocols at the time. IHC staining for EGFR, HER2 and HER3 & PR was performed and scored using the Herceptest or Histoscore method. Statistical calculations were performed using Kaplan-Meier log rank testing of breast cancer related relapse on tamoxifen over 2 time periods; throughout the duration of tamoxifen (ATAC) treatment or after 3 years of tamoxifen therapy (IES). Results: Both HER1–3+ve (28%) and PR-ve (37.9%) patients demonstrated increased relapse rates on tamoxifen (p=0.0060 and p=0.0017 respectively). Patients PR-ve and/or HER1–3+ve (53%) were significantly more likely to relapse on tamoxifen in univariate analysis (p<0.0001) and in Cox multivariate regression analysis, along with nodal status, grade and size (p=0.0026). However in patients who survived 3 years of tamoxifen (as in the IES study) no significant effect of PR/HER1–3 expression on recurrence rates in univariate (p=0.09) or multivariate analysis was observed p=0.2478). Conclusions: This data suggests that HER1–3 and PR are time dependent variables related to breast cancer recurrence. Critically, these results may be invoked to explain the observed differences in the predictive value of PR, and potentially HER1–3 expression between the ATAC and IES studies and to predict when to implement AI treatment. In ATAC ER+ve/PR-ve cases showed higher rates of relapse on tamoxifen vs AIs a finding not repeated in the IES study which randomised patients surviving 3 years tamoxifen. This hypothesis could be tested in the remodelled TEAM study in the near future. No significant financial relationships to disclose.
FOLFOXIRI plus bevacizumab (BEV) in patients (pts) with previously untreated metastatic colorectal cancer (mCRC): Preliminary safety results from the OPAL study.
Authors: Alexander Stein, Djordje Atanackovic, Bert Hildebrandt, Patrick Stuebs, Claus-Christoph Steffens, Wolfram Brugger, Gunnar Hapke, Gerald Illerhaus, Ernst Bluemner, Carsten Bokemeyer
Journal: Journal of Clinical Oncology (2013)

515 Background: The addition of BEV to standard doublet chemotherapy (CT) improves outcomes vs CT alone in pts with mCRC. Use of more intensive triplet CT may prolong overall survival (OS), progression-free survival (PFS), increase response rates and improve resectability rates but at the expense of greater toxicity. The OPAL study examined the effect of BEV + FOLFOXIRI on PFS in pts with previously untreated unresectable mCRC. Here we report preliminary safety findings. Methods: Eligible pts had histologically confirmed mCRC, ECOG PS ≤1 and were 18–70 years old. Pts received ≤12 cycles of FOLFOXIRI (infusional 5-fluorouracil [FU] 3200 mg/m 2 , folinic acid [FA] 200 mg/m 2 , oxaliplatin 85 mg/m 2 , irinotecan 165 mg/m 2 ) + BEV 5 mg/kg q2w (induction phase) followed by ≤40 cycles of 5-FU/FA + BEV q2w (maintenance phase). PFS was the primary endpoint; secondary endpoints included OS, proportion of pts achieving resectability and safety. Results: 96 pts were enrolled. Of these, 90 received study medication and formed the safety population: 64 male, 26 female; median age 58 (range 28–71) years; ECOG performance status 0/1 in 49/41 pts. All pts have completed induction treatment and the study is ongoing. In total, 61 serious AEs occurred in 34 pts (38%). AEs resulting in death occurred in 3 pts (3%); these were not considered treatment-related by the investigators. The incidence of AEs of special interest with BEV was low. Main AEs reported during the induction phase are summarised in the table. Conclusions: BEV + FOLFOXIRI was generally well tolerated in this mCRC pt population. The incidence of AEs was as previously reported [Falcone et al. ASCO 2010] and there were no new safety signals. Clinical trial information: NCT00940303. [Table: see text]
Evaluation of C-reactive protein and YKL-40 as risk factors for incident cancer and early death after a diagnosis of cancer.
Authors: K. H. Allin, S. E. Bojesen, J. S. Johansen, B. G. Nordestgaard
Journal: Journal of Clinical Oncology (2010)

1531 Background: Elevated plasma levels of C-reactive protein (CRP) and YKL-40 are each associated with increased risk of cancer in the general population and with early death in patients with cancer. We examined whether CRP and YKL-40 levels combined are better at predicting these risks than either one alone. Methods: We studied 8,706 participants from the Copenhagen City Heart Study which is a prospective cohort study of the Danish general population. At study entry, plasma CRP was determined by using a high-sensitivity turbidimetry assay and plasma YKL-40 was determined by using a commercial two-site sandwich- type enzyme-linked immunosorbent assay. We examined the risk of lung, gastrointestinal, or any cancer during the first five years of follow-up and the risk of early death during the first five years after a diagnosis of cancer. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results: HR of lung cancer for a doubling of CRP levels was 1.35 (95% CI, 1.17 to 1.56) and indifferent to adjustment for YKL-40 levels. HR of gastrointestinal cancer for a doubling of YKL-40 levels was 1.37 (95% CI, 1.17 to 1.61) and indifferent to adjustment for CRP levels. HR of early death after a diagnosis of cancer for a doubling of CRP levels was 1.12 (95% CI, 1.05 to 1.18) and indifferent to adjustment for YKL-40 levels, whereas HR of early death after a diagnosis of cancer for a doubling of YKL-40 levels was 1.09 (95% CI, 1.02 to 1.16), but this estimate was attenuated after adjustment for CRP levels. Conclusions: Elevated CRP levels were associated with increased risk of lung cancer and early death in patients with cancer, independently of YKL-40 levels. Elevated YKL-40 levels were associated with increased risk of gastrointestinal cancer, independently of CRP levels. No significant financial relationships to disclose.
Identifying variables that predict poor tumor biology and suboptimal outcomes in patients treated with cytoreduction and HIPEC.
Authors: Smit Singla, Valerie Francescutti, John Michael Kane, Joseph J. Skitzki
Journal: Journal of Clinical Oncology (2015)

709 Background: Cytoreduction with HIPEC has improved survival in select group of patients with peritoneal carcinomatosis. Despite rigorous selection criteria, some patients invariably perform worse than others and are presumed to conceal poor tumor biology. Methods: A single institution analysis of all patients presenting with peritoneal carcinomatosis between 2003 and 2014. All patients who underwent CRS with HIPEC were included in the analyses. Clinical variables deemed high risk for poor outcome were categorized as ‘poor tumor biology’ and analyzed using the multivariate association for survival outcomes. Results: Based on pre-defined criteria, 160 patients (M: 68, F: 92; median age, 53 years) were identified and included in this study. The most common site of tumor origin was appendix (n=73, 45.6%), and the most common histology subtype was adenocarcinoma (n=91, 56.9%). Patients presenting with ascites (n=39, 24.3%, p&lt;0.001) and perforation (n=18, 11.2%, p=0.036) performed poorly, while age (young versus old), gender and the timing of surgery from diagnosis did not affect survival outcomes (p&gt;0.05). Patients who received pre-operative chemotherapy (n=77, 48%, p=0.007), complete cytoreduction (n=115, 71.9%, p=0.02) and fewer number of gastrointestinal anastomoses (=&lt;1, p=0.005) during surgery performed better; however, patients who developed intra-abdominal abscess, anastomotic leak, fistula and bowel obstruction in the immediate peri-operative period (n=30, 18.8%, p&lt;0.001) saw significant decline in survival outcome. The median overall survival and progression free survival in our patient cohort were 68.0 months (CI, 46.8-NR) and 19.3 months (CI, 14.7-37.4), respectively; but patients with colorectal adenocarcinoma, ascites, perforation and bowel complications performed poorly and were assumed to harbor poor biology. Conclusions: A thorough understanding of the presenting symptoms and peri-operative clinical variables can identify patients with poor tumor biology. These patients are unlikely to have significant improvement in outcome, and cytoreduction with HIPEC can be considered palliative in these patients.
Dihydropyrimidine dehydrogenase (DPD) single nucleotide polymorphisms (SNP) in Thai patients treated with 5-FU based regimens
Authors: T. Reungwetwattana, E. Sirachainan, N. Trachu, Y. Wisetpanit, S. Mahasirimongkol, R. Panvichian, T. Sirisinha, V. Ratanatharathorn, T. Ativitavas
Journal: Journal of Clinical Oncology (2008)

14537 Background: DPD deficiency is a genetic disease caused by molecular defects in the DPD gene (DPYD). Cancer patients with DPD deficiency developed severe toxicity after receiving 5-FU based chemotherapy. The objective of this study is to determine the extent of DPYD gene polymorphisms of Thai cancer patients who received 5-FU based chemotherapy regimens. Methods: We conducted a molecular analysis to determine the polymorphisms of DPYD gene in 116 Thai cancer patients. 76 patients developed severe (grade 3–4) toxicities after receiving the first or second cycle of 5-FU based chemotherapy. The other subject group consisted of 40 patients without severe toxicity. The clinical characteristics (sex, age, diagnosis, regimen and dosage) of both groups were recorded. We isolated genomic DNA from buffy coat of their peripheral blood samples then performed PCR. The DNA sequencing of every amplicon was done to identify 11 mutations as reported in Asian population. The actual change of absolute neutrophil count (ANC), hematocrit, platelet and percentage of neutrophil were compared in each SNP using Mann Whitney U test. Results: We detected 13 SNPs which 6 SNPs were found in exons; 967G>A, 1011A>T, 1236G>A, 1774C>T, 1896T>C and 1627A>G. The other 7 SNPs were found in introns but only IVS14+1G>A is the intron splice site. There have never been report in 10 SNPs; 967G>A, 1011A>T, 1236G>A, 1774C>T, IVS8–118A>G, IVS8–17A>C, IVS11–15T>C, IVS14–68T>G, IVS14+19C>A and IVS14+134G>T. We found homozygous GG of 1627A>G in 4 patients who had severe toxicities. Statistic significant in actual ANC change and percentage of neutrophil change in homozygous GG (p=.011 and .009) were found. The median nadir ANC of homozygous GG is 399.6 cells/mm3. This SNP cause the amino acid change from isoleucine to valine. Novel heterozygous SNPs (967G>A, 1774C>T) that cause the amino acid change were found in two patients with severe toxicities. Conclusions: 1627A>G, 967G>A, 1774C>T and IVS14+G>A may be the cause of DPD deficiency in Thai patients. The further study needs to establish the functional DPD protein in this population. Ten novel SNPs were discovered in our study. No significant financial relationships to disclose.
Insulin-like growth factor (IGF)-I, IGF-binding protein (IGFBP)-3 and breast cancer (BC) risk: A synthetic case-control study
Authors: Z. Kahan
Journal: Journal of Clinical Oncology (2004)

9610 Background: Correlation between levels of IGF-I, and IGFBP-3, and BC risk have been explained by the mitogenic antiapoptotic, and hormonal effects of IGF-I. Methods: Since February 2002 attendants to the national mammography-screening program and patients with screen-detected early BC without diabetes, malignancy, or HRT within the last 6 month were included in the study. Demographic data (body mass index, age at menarche, menopause, parity, past hormone exposure, and family history) in addition to blood samples were collected from 1755 healthy individuals, and 104 mammography screen-detected BC patients. Plasma IGF-I, IGFBP-3, 17β-estradiol, estrone, testosterone, androstenedione, sex hormone binding globulin (SHBG) were determined with RIA in the BC patients (cases), and 168 matched controls. Results: Demographic data did not differ between controls and cases. Plasma IGF-I concentrations were 167.9±13.6, and 198.2±21.9 ng/ml in premenopausal controls (n=49) and BC patients (n=22), respectively (p=0.23). In postmenopausal controls (n=119), and cases (n=82) IGF-I levels were 113.2±7.2, and 153.2±9.3 ng/ml, respectively (p=0.0007). Levels of IFGBP-3, estrogens, or SHBG did not differ between the control and BC groups. Testosterone concentrations were significantly higher in BC than control postmenopausals (p=0.0005). A linear regression model of IGF-I by case or control status was used to estimate the relative risks. Ranges of IGF-I values of <120, 120–220, and >220 ng/ml were used following sensitivity analysis. There was a positive association between IGF-I concentrations and BC risk in postmenopausal women as follows: OR=2.61 (95% CI: 1.15–5.95, p=0.022) and OR=2.03 (95% CI: 1.08–3.82, p= 0.027) comparing high and medium ranges with the low one, respectively. No such effect was found among premenopausal women. No strong correlation between IGF-I and other hormones were found. Conclusions: A positive relation between IGF-I and BC risk among postmenopausal women was demonstrated. Recruitment of additional premenopausal cases into the study is needed. No significant financial relationships to disclose.
Abstract 12444: Low Levels of Serum N-3 Polyunsaturated Fatty Acids are Associated with Worse Heart Failure Free Survival in Patients with Acute Myocardial Infarction
Authors: Masahiko Hara, Yasuhiko Sakata, Sen Matsumoto, Masaya Usami, Shinichiro Suna, Daisaku Nakatani, Toshimitsu Hamasaki, Hiroshi Sato, Masatsugu Hori, Takahisa Yamada, Yasuji Doi, Shinsuke Nanto, Issei Komuro
Journal: Circulation (2012)

Background: Intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is associated with a lower risk of atherosclerotic...