tbuckley/cabot-search huggingface dataset:
<i>CHK1</i> promoter polymorphism predicts survival in cancer
Authors: K. Riemann, C. Hasenbein, G. Wieker, H. Rübben, K. W. Schmid, G. Iliakis, W. Siffert
Journal: Journal of Clinical Oncology (2008)

11053 Background: Checkpoint kinase 1 (CHK1) plays an essential role in checkpoint control. After DNA damage it is activated and induces cell cycle arrest to allow DNA repair, thereby ensuring genomic integrity. However, CHK1 expression is altered in a variety of cancers. Thus, damaged DNA can accumulate which induces genomic instability. Since polymorphisms are known to influence gene expression, this study aimed to investigate whether a CHK1 promoter polymorphism is functional and influences the course of cancer. Methods: The -1143G>T single nucleotide polymorphism (SNP) was identified by systematic sequencing. Genotypes were determined in the normal population (n=315) as well as cancer samples and associated with survival in patients with urothelial (n=229) and mamma carcinoma (n=330). Functional analysis included reporter assays with the overexpressed transcription factor GABP. Genotype- dependent CHK1 expression was determined using quantitative real-time PCR. Checkpoint activity according to the genotype was determined by damage assessment of metaphase chromosomes of cultured peripheral lymphocytes of healthy volunteers (n=27) after 1 Gy ionizing radiation. Results: Overall survival of patients with bladder cancer was dependent on the -1143G>T genotype (p=0.042). Patients carrying the homozygous T allele displayed a higher risk for death than G allele carriers (HR: 2.6; p=0.010). In patients with breast cancer, however, the G allele displayed the worst survival (p=0.017) and was associated with a higher risk for death (HR: 4.6; p=0.004). Multivariate analysis revealed that the CHK1 SNP was an independent risk factor. Reporter assays showed an allele-dependent difference in the ability of GABP to bind to the CHK1 promoter with a stronger activity of the G allele (p=0.012). CHK1 expression in tumor tissues of bladder cancer patients with GG genotype was significantly increased (p=0.024). Furthermore, strongest G2 checkpoint activity was observed in GG genotype carriers as demonstrated by a reduced number of chromosome breaks following irradiation (p=0.003). Conclusions: The functional promoter SNP in CHK1 described here might serve as a molecular marker for survival of cancer patients. In addition, this polymorphism bears the potential to predict the response to irradiation. No significant financial relationships to disclose.
Prevalence of radiologic evidence of metastatic pancreatic ductal adenocarcinoma (PDAC) at first post-operative restaging studies in patients (pts) undergoing pancreatic cancer surgery with curative intent.
Authors: Sofia Palacio, Peter Joel Hosein, Joe U Levi, Jaime R. Merchan, Jorge Monge, Lorraine Portelance, Isildinha M. Reis, Caio Max S. Rocha Lima
Journal: Journal of Clinical Oncology (2016)

225 Background: Surgical resection is the only potentially curative modality for PDAC. However, even after a successful surgical resection outcomes are poor due to both local and distant disease recurrence. Patients with early recurrence likely derive no benefit from surgery and could be considered for a non-surgical approach as initial therapy. Since the incidence of recurrent/metastatic disease at first post-operative staging scan is not well documented, our aim was to determine this incidence. Methods: This IRB-approved analysis identified all pts diagnosed with resectable PDAC that underwent surgery with intent to cure at the University of Miami/Sylvester Comprehensive Cancer Center between 2010 and 2012. Patients with imaging before and within 6 months after surgery were included. All post-operative CT scans performed within 3 months after surgery were reviewed for the presence of recurrent and/or metastatic disease. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Results: Data from105 pts were analyzed. Mean age was 61, 63% were male, 91% had adenocarcinoma, 84% had disease in the head of the pancreas. 11 out of 85 (13%) pts had recurrent/metastatic disease detected on first post-operative CT scan; 64% stage IIB and 73% had positive lymph nodes. 54 out of 105 (51%) had disease progression. 60% had local recurrence, 40% had distant metastasis. The mean time from preoperative CT scan to surgery was 35 days. Patients with early and late recurrence had similar OS from diagnosis (median 27.7 and 27.1 months, respectively) but worse than those with no disease recurrence (median not reached, OS rate 78% at 36 months). Conclusions: The relatively high incidence (13%) of early recurrence in this retrospective cohort suggests that further studies aimed at improving patient selection for surgery are warranted and provides a strong rationale for the use of neoadjuvant therapy to select patients with early disease progression who would not have benefitted from surgery.
Retrospective evaluation of the Adjuvant! for breast cancer after 5 years of adjuvant tamoxifen (AAT) and other factors for prediction of recurrences (OFPR) following 5 years of adjuvant tamoxifen (AT).
Authors: A. Barzi, L. A. Rybicki, B. A. Sisk, C. Yu, M. W. Kattan, G. T. Budd
Journal: Journal of Clinical Oncology (2011)

e11068 Background: AAT is a computer model that predicts 5 year (yr) relapse rate (PRR) for patients (pts) with estrogen receptor positive breast cancer after AT. We used the Cleveland Clinic surgery database to validate the PRR of AAT and investigate OFPR. Methods: 744 Pts surgery 1/1995–12/1999 were reviewed (Table), and 292 were included. Demographic, pathology, staging, and treatment data were entered into AAT and PRR was calculated. Observed outcome (OO) in each pt (no R, local R, systemic R, death due to breast cancer (BC)/non-BC and unknown causes) was recorded for each pt. The association between AAT, PRR and OO were assessed with Cox proportional hazards analysis (CA), concordance index (CI), and calibration plots (CP). CI was calculated as a measure of discrimination for ATT PRR. CP was visually assessed. Deaths from other causes were treated as competing risks for recurrence. Results: Pts characteristics: median age 62, ductal histology 83%, median tumor size 1.5 cm, and median number of nodes 0. Median PRR was 7.5 (range 3.8-51.9). 33 pts recurred (11.4%), 18 within 5 yrs of AT. Median time to recurrence was 3.9 years after AT. Recurrence was local in 12, systemic in 19, and both in 2. There are 33 patients who died from other causes. PRR did not predict recurrence in CA. After adjusting for competing risks, the CI in the entire cohort was 0.569 (95% CI 0.472-0.670). CP revealed that the predictions appear to be reasonably accurate for lower adjuvant online scores, but not as accurate for higher scores. In CA histology, tumor size and progesterone receptor status were predictive of recurrence with p value of 0.017, 0.048, and 0.033 respectively. In multivariate analysis (MVA) histology and progesterone receptor (PR) status remained significant (p<0.05) in prediction of recurrence. Conclusions: The OO was not well predicted by AAT. In the pts with higher scores, the risk score overestimated the recurrence probability. Histology and PR were predictive of recurrence in MVA. Exclusion reason Less than 5 ys f/u 231 Incomplete 5 ys of AT 153 Presented with recurrent disease 59 Recurrence while on AT 9
Oral vinorelbine (NVBo) + CDDP and radiotherapy (RT) in stage III non small cell lung cancer (NSCLC) patients (pts)
Authors: M. Flentje, R. Fietkau, R. Huber, G. Beckmann, B. Poellinger, D. Aubert, A. Fittipaldo
Journal: Journal of Clinical Oncology (2005)

7302 Background: Standard treatment for inoperable stage III NSCLC consists on chemotherapy (CT) in combination with RT. In this setting, vinorelbine i.v. has demonstrated to be effective and safe together with CDDP and RT (CALGB 9431). A new oral formulation (NVBo) recently showed similar efficacy in stage IV NSCLC. The present phase I has been performed in order to establish the recommended dose of NVBo in combination with CDDP and RT. Methods: Histological or cytological proof of NSCLC, untreated stage IIIA (only N2) or IIIB (supraclavicular N3 were excluded). The CT regimen consisted of 2 cycles (cy) of 28 day of CDDP 20 mg/m2 d 1–4 together with NVBo administered on d1,8,15 q4 w at 3 different levels (L): L1 40 mg/m2; L2 50mg/m2 and L3 60 mg/m2. Total dose of RT 66 Gy (2Gy fr/day) with a maximum irradiation of 20 Gy to no more than 30% of both lungs volume. Main end point was to determine the maximal recommended dose of NVBo. After the concomitant treatment, 2 additional cy were administered to all pts as consolidation CT with NVBo 60 mg/m2 d1,8 at the first cy and 80 mg/m2 d1,8 at the 2nd and CDDP 80 mg/m2 d1 per 2 cy q3w. Results: 11 stage IIIB pts (L1 3pts; L2 3pts; L3 5pts) received a total of 37 cy; the median number of cy per pt was 4. Median age 59; 82% PS 0–1. Grade 3–4 toxicity per pt and per L included neutropenia (1pt L2; 3 pts L3); oesophagitis (4 pts L3); gastritis (1 pt L3); pain (1 pt L3) and febrile neutropenia (1pt L3). Dose limiting toxicity (DLT) for CT-RT was oesophagitis, reported at NVBo L3. Nine pts received consolidation CT. Neutropenia (2 pts G3; 1pt G4) (33%) and thrombocytopenia (1pt G3) (11%) were the only toxicities present during consolidation CT. ORR in ITT pts: 64%. The 3 patients treated at the recommended dose (L2) responded to the treatment (2 pts PR, 1pt CR). Conclusion: NVBo 50 mg/m2 d1,8,15 and CDDP 20mg/m2 D1–4 both q4w (L2) is the recommended dose to be used with RT at 66 Gy, without any DLT. This dose will be used as concomitant CT in a phase III trial testing the efficacy of consolidation CT in patients not progressing to CT-RT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Institut de Recherche Pierre Fabre Institut de Recherche Pierre Fabre Institut de Recherche Pierre Fabre Insititut de Recherche Pierre Fabre
Validation of hepatectomy for elderly patients with hepatocellular carcinoma.
Authors: Norihiro Kishida, Taizo Hibi, Osamu Itano, Masahiro Shinoda, Minoru Kitago, Hiroshi Yagi, Yuta Abe, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2014)

380 Background: Hepatectomy for hepatocellular carcinoma (HCC) and its outcomes in the elderly population have yet to be defined. We aimed to validate our current strategy to determine surgical indication regardless of age. Methods: A single-center, retrospective cohort study was conducted for 104 patients who underwent hepatectomy for HCC from 2005 to 2010. The patients were divided into 2 groups according to age; i.e. &lt;75 years (non-elderly cohort; n=82) and ≥75 years (elderly cohort; n=22), and short-/long-term results were compared. Results: In the elderly cohort, the prevalence of ECOG performance status 1 preoperatively (p&lt;0.001) and HCV or non-HBV/non-HCV were higher than in the non-elderly cohort (p=0.04). Otherwise, patient/tumor characteristics were comparable between the 2 groups. The elderly cohort suffered postoperative complications more frequently (42% vs. non-elderly, 16%, p=0.01) but the length of hospital stay was equivalent. Ninety-day mortality occurred in 1 case each (elderly, respiratory failure; non-elderly, liver failure; p=0.38). During a median follow-up period of 47 months, unadjusted 5-year disease-free and overall survivals were comparable per log-rank comparison (elderly, 25% and 80% vs. non-elderly, 33% and 79%, p=0.96 and 1.00, respectively). Cox univariate analyses on recurrent HCC showed hypertension, Child-Pugh grade B, tumor size, recurrent/multiple tumors, preoperative alpha-fetoprotein level, moderate/poor differentiation, portal invasion, intrahepatic metastases, and positive margins to have p values &lt;0.20. After adjustment, the hazard ratio of recurrent HCC at 5 years in the elderly cohort was 0.87 (95% CI, 0.40-1.91; p=0.74). Tumor size, alpha-fetoprotein level, and intrahepatic metastases emerged as independent predictors of diminished 5-year disease-free survival in the entire cohort. Conclusions: Although postoperative complications develop more frequently, hepatectomy in the elderly patients affords comparable short- and long-term prognoses to the non-elderly patients. Surgical strategy for HCC should be based on tumor factors and hepatic reserve and not by age alone. Perioperative management needs to be individualized according to coexisting disorders.
Exploring patient-provider communication about cancer survivorship care in community-dwelling survivors.
Authors: Guadalupe R. Palos, Katherine Ramsey Gilmore, Paula A. Lewis-Patterson, Patricia Chapman, Maria Alma Rodriguez
Journal: Journal of Clinical Oncology (2016)

86 Background: Patient-provider communication about survivorship care and care plans is a core tenet of quality cancer care. Our objective was to examine gaps in communication about maintaining health, importance of follow-up care, and unmet information needs in community-based survivors. Methods: A convenience sample of adult survivors attending a community-based cancer survivorship conference were eligible to take this survey. Consenting adult survivors completed a self-administered survey with selected questions from the NCI Follow-Up Care Use among Survivors Survey. Participants were informed that survey completion was voluntary and confidential. Descriptive statistics were used to summarize and analyze data. Results: 284 surveys were distributed and 169 surveys returned, resulting in a response rate of 59.5%. After excluding Spanish-language surveys and respondents not diagnosed with cancer, 109 surveys were included in this sub-analysis. Most survivors were female (77.7%), college-educated (86.1%), married (58.4%) and diagnosed with breast cancer (47.5%). Over half (55.5%) reported experiencing pain that interfered with their daily routine yet, 83.2% reported being in good to excellent health. The primary reason for receiving follow-up care was to check for recurrence (66.2%). Most survivors (78.5%) reported having no to some patient-provider discussions about the late effects associated their treatment. 47.6% reported not receiving information about a written care summary from their provider, 94.8% would have liked to have received a written summary, and 73.1% preferred more information about the benefits of a personalized care plan. Survivors also reported in the past 2 years, their providers did not discuss topics related to emotional concerns (35.3%), alcohol consumption (35.1%) and types of foods to eat (33.8%). Survivors wanted more information on self-management techniques such as how to improve energy (83.2%), manage fatigue (72.9%), or improve sleep (69.3%) Conclusions: Our findings highlight the need for further examination on the impact of inadequate patient-provider communication on survivors’ outcomes and providers’ practice.
Selection of Patients With Multiple Sclerosis to Undergo Autologous Hematopoietic Stem Cell Transplantation
Authors: Michael K. Racke, Jaime Imitola
Journal: JAMA Neurology (2017)

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First quality-of-life data of a sequential dose-dense regimen in advanced ovarian cancer: A multicenter phase II study of the Northeastern German Society of Gynecological Oncology.
Authors: G. Oskay-Özcelik, R. Richter, K. Pietzner, H. Hindenburg, H. L. Sommer, R. Chekerov, O. Camara, E. Keil, J. Einenkel, W. Lichtenegger, J. Sehouli
Journal: Journal of Clinical Oncology (2011)

5071 Background: The objective of this study was to examine the impact of a sequential dose dense schedule of carboplatin and paclitaxel on quality of life (QoL). Methods: In this multicenter phase II trial patients with advanced ovarian cancer received four cycles of carboplatin followed by 12 cycles of weekly paclitaxel after primary radical surgery (abstr. 5533; J Clin Oncol 2007). QoL (QLQ-C30; QLQ-Ov28) was analyzed regarding the effect of carboplatin and paclitaxel separately at end of treatment (EOT) and 6, 12, and 24 months later. Results: Overall 87 out of 104 eligible patients (84%) participated for at least one QoL-assessment during the treatment, but only 24 patients did likewise 2 years after EOT. At baseline all QLQ-C30 scales and symptoms were significantly worse on average than age adjusted expected values of the general population. From then QoL improved in general. During chemotherapy with paclitaxel most functioning scales and symptoms worsened slightly but not significantly. But peripheral neuropathy and chemo side-effects increased with clinically important differences. After EOT most QoL scores were similar wih those of general population, but physical functioning and fatigue were worse, sexual functioning remained very low. Worries about future health and peripheral neuropathy were rated problematic for some patients. Conclusions:QoL was generally favorable and was mainly affected by the paclitaxel weekly schedule. During chemotherapy and after EOT QoL was improved. Therefore the QoL data support a dose dense regimen.
Institutional implementation of a clinical pathway in rectal cancer: The advantages of standardization of protocols.
Authors: F. Lopez-Lara, E. Una Cidon
Journal: Journal of Clinical Oncology (2010)

e16536 Background: Rectal cancer (RC) is a relevant cancer.The absence of specific clinical protocols implies a significant/unjustifiable variability. Purpose: Development of Clinical Pathway (CP) based on the process analysis/adaptation to organizational characteristics/availability of resources. The aims: reducing variability in diagnosis/treatment (TR), increasing clinical effectiveness/patient satisfaction (S). Methods: Creation of a multidisciplinary team. Holding of periodic meetings. Project developed according to “Guide of Best Clinical Practices (GBP) for CRC” (published by the Counseling of Health of our Community) and consensus of specialists involved. CP begun after capturing a patient with suggestive symptoms/asymptomatic with probable diagnosis. Eligible: all patients ≥ 18 years included in CP. Results: N 48. Before CP: wide time interval colonoscopy-first TR, according to quality criteria considered by GBP. Appropriate complete diagnosis <40%. Locoregional staging not accurate: Magnetic Resonance (MR) in 9%. Neoadjuvant treatment and anal sphincter saving surgery low (Table, part 1). Patient S. was also evaluated (Table, part 2). Conclusions: CP guides diagnostic/TR, homogenized attitudes and allows establishing responsibilities of professionals, ensures optimal use of resources, reduces timeouts between phases, achieves better coordination between disciplines involved in RC. CP has improved all aims including S. Pathology report Before CP (%) After CP (%) Differences Poor information Histological grade 23 0 +* Size 58 0 + Margins 41 0 + TNM 69 0 + Vascular invasion 79 0 + Nodes analyzed No mentioned 16 0 + Isolated 19 0 + <12 87 90 - ≤ 3 31 0 + Induction TR Hypofractionated radiotherapy (R) 31 0 + Chemoradiotherapy 2 71 + A. interval time (t)/test/procedures t to colonoscopy 20 100 + t to results after biopsy 18 100 + t to first TR 27 100 + t to surgery after ending R 43 100 + t to end diagnostic tests 23 44 + MR 9 90 + Anal sphincter saving 40 65 + Survey Yes (%) N Appropriate (A.) timeout to first TR 80 48 S. with information 60 48 A. time of hospital admission 100 48 A. of attention 80 48 S. with attention 80 48 +* Differences in favor of CP No significant financial relationships to disclose.
Excess bone marrow mast cells constitutively express CD154 (CD40 ligand) in Waldenstrom's macroglobulinemia and may support tumor cell growth through CD154/CD40 pathway
Authors: O. Tournilhac, D. Ditzel Santos, A. Branagan, Z. Hunter, R. Manning, Y.-T. Tai, J. L. Kutok, N. Munshi, K. C. Anderson, S. P. Treon
Journal: Journal of Clinical Oncology (2004)

6555 Background: Excess mast cells (MC) have been described in Waldenstrom's macroglobulinemia (WM), though the frequency of detection of MC and their role in the pathogenesis of WM remains to be clarified. Methods: BM biopsies of 188 patients diagnosed with an IgM monoclonal gammopathy at our institution were reviewed. Excess MC were observed in 123/171 (71.9%) cases of WM, but not in IgM MGUS (n=14), IgM myeloma (n=3), or in 5 healthy donors. To determine if WM patient MC were activated and expressed ligands which could support the growth of WM cells, we used multicolor flow cytometry, immunohistochemistry, and/or RT-PCR to examine BM MC (CD117+ FceRI+) for expression of CD154 (CD40 ligand) and CD153 (CD30 ligand). BM LPC were also evaluated for expression of CD30 and CD40, the signaling receptors for CD154 and CD153. BM LPC proliferation by CD40 stimulation was also evaluated by 3H-thymidine uptake. The secretion of cytokines which could support the growth and survival of MC was also evaluated by ELISA. Results: CD154 and CD153 were expressed on BM MC from 14/15 (93.3%) and 6/6 (100%) patients with WM, respectively, but not on normal donor BM MC. Immunohistochemistry and/or RT-PCR analysis further confirmed expression of CD154 and CD153 on WM MC, but not normal donor MC. Bright CD40 expression was observed on LPC in most patients, whereas CD30 was weakly positive in 3/12 patients. Given the above, we next evaluated purified BM LPC for growth induction by CD40 stimulation, and demonstrated dose dependent uptake of 3H-thymidine. Lastly, in an evaluation of mast cell growth factors, we observed elevated levels of IL-3, but not IL-4, IL-5, IL-6, IL-9, IL-13, IL-15 and SCF in patients with WM (n=41) versus healthy donors (n=20) (p=0.01). Conclusions: The results suggest that MC may play a central role in the growth of WM tumor cells through the CD154/CD40 pathway. Moreover, WM tumor cells may provide support for MC growth and survival by secretion of IL-3. These data provide the rationale for targeting MC-WM tumor cells interactions in the treatment of WM. No significant financial relationships to disclose.