tbuckley/cabot-search huggingface dataset:
Executive functions in aging adult survivors of childhood leukemia.
Authors: K. R. Krull, N. Jain, Z. Pan, K. Shine, D. K. Srivastava, D. Stewart, C. Jones, L. L. Robison, M. M. Hudson
Journal: Journal of Clinical Oncology (2010)

9011 Background: Survivors of childhood ALL are at risk for deficits in basic cognitive skills (e.g. attention, processing speed and working memory), typically beginning within five years of diagnosis and associated with cranial radiation therapy (CRT). The degree of impairment in very long-term survivors is unknown. Methods: We evaluated complex neurocognitive functions (i.e. executive functions [EF]), in 285 adult survivors of childhood ALL (mean [range] of current age = 35.0 yrs [20.4 – 49.9], age at diagnosis = 6.0 yrs [0.2 – 18.8], and time since diagnosis = 28.9 yrs [12.0 – 45.3]. Survivors completed a comprehensive neuropsychological evaluation. Age-adjusted standard scores were calculated using national norms, with clinical impairment defined as scores ≤ 10th percentile. Analysis of variance and regression was used to examine associations between executive functions and CRT, sex, and age at diagnosis, as well as educational and vocational outcomes. Results: 72.6% of survivors demonstrated impairment on at least one measure of EF. Rates of impairment were higher measures of cognitive fluency (28%), flexibility (34%), and working memory (39%) compared to basic intelligence (14%) and processing speed (15%). CRT was associated with impairment on measures of EF (p's < .01), and basic cognitive skills (p's < .005). Female sex was associated with impairment on basic cognitive skills (p's < .01), but not measures of EF. Younger age at diagnosis was associated with poor cognitive flexibility (p = .007) and problem solving (p<.0001), as well as intelligence (p = .004). Survivors with impaired EF were less likely to graduate college (RR = 1.76, 95% CI 1.28 – 2.64, p = 0.005) and were less likely to be currently employed fulltime (RR = 1.68, 95% CI 1.28 – 2.19, p<0.0001). Conclusions: Survivors of childhood leukemia continue to be at risk for neurocognitive impairment well into adulthood. Compared to basic cognitive skills and intellect, impairment appears more common in complex executive functions such as fluency, flexibility, and problem solving, functions which typically develop throughout adolescence. Impairment on these executive functions is related to educational and vocational outcomes. No significant financial relationships to disclose.
Dosimetic quality and evolution of edema after prostate brachytherapy for small prostates: Implications for the use of newer isotopes.
Authors: Konstantin Kovtun, Luciant D. Wolfsberger, Thomas Niedermayr, Emily Neubauer, Yonina R. Murciano-Goroff, Clair Beard, Anthony Victor D'Amico, Neil E. Martin, Peter F. Orio, Paul Linh Nguyen
Journal: Journal of Clinical Oncology (2013)

232 Background: Prostate brachytherapy is often avoided in men with small prostate volumes (PV) due to concerns about suboptimal dosimetry. We characterized prostate swelling and dosimetry in patients with small PVs compared with large PVs. Methods: We studied twenty-five patients with PV &lt;25 cc (range 15.1-24.8) and sixty-five patients with PV &gt;=25 cc (range 25.0-66.2) who underwent brachytherapy. Gland size was based on the contoured volume on a 3D transrectal ultrasound before the procedure. Ultrasound-guided brachytherapy was performed under intra-operative planning with loose Iodine-125 seeds to a prescription dose of 145 Gy. Patients underwent CT and MRI scans on post-implant Days 1 and 30 for dosimetric study. MRI was used to contour the prostate and then fused with the CT for dosimetry. Results: Small PVs had greater Day 1 post-implant swelling than patients with large PVs (32.5% increase in volume vs. 23.7%, p=0.04) but Day 30 swelling was minimal and not significantly different (4.4% increase in volume vs. 1.6%, p=0.44) for small and large PVs respectively. Small PVs had greater seed and needle density at implant (p&lt;0.001). Small PV patients had larger Day 1 hot spots in the prostate at (V150 = 59.6% vs. 53.0, p=0 .022) which resolved by Day 30 (V150 = 70.9% vs. 67.1, p=0.20). Rectal and urethral doses were nearly identical by Day 30 (Small PV RV100 = 0.32 cc, Large PV RV100 = 0.33 cc, p=0.99; small PV UV150 = 0.20, large PV UV150 = 0.20, p=0.91). Day 1 swelling created cold areas (rate D90&gt;140 Gy = 88.0% and 90.6% for the small and large PV groups respectively, p=0.71), but day 30 dosimetry was excellent (rate D90&gt;140 Gy = 100% for both groups). Conclusions: While smaller prostates have more immediate post-operative swelling, good Day 30 dosimetry can be achieved in small prostates, which makes them excellent candidates for treatment with I-125 seeds (t ½ = 60 days). Due to the increased short-term swelling, small prostates may be suboptimal candidates for implants done with shorter half-life sources such as cesium-131 (t ½ = 9.7 days), where the majority of the dose may be delivered to an edematous gland.
Intra-individual genetic heterogeneity among liver metastases in metastatic colorectal cancer.
Authors: Anita Sveen, Inger Marie Loes, Sharmini Alagaratnam, Gro Nilsen, Maren Høland, Ole Christian Lingjaerde, Halfdan Sorbye, Kaja Christine Graue Berg, Arild Horn, Jon-Helge Angelsen, Stian Knappskog, Per Eystein Lonning, Ragnhild A Lothe
Journal: Journal of Clinical Oncology (2016)

555 Background: Almost 50% of patients with colorectal cancer (CRC) develop liver metastases, often as multiple simultaneous metastatic deposits. Up to 25% of the patients are eligible for partial liver resection, but 70% will relapse after surgery and there are currently no good criteria to select patients who will benefit from the treatment. Genetic heterogeneity among metastatic deposits has great potential impact on disease progression, but has not been well described. Methods: Totally 134 liver metastatic deposits were collected from 45 patients undergoing partial liver resection for metastatic CRC according to a prospective study protocol. All deposits were analyzed for high-resolution DNA copy number variation using the Affymetrix SNP Array 6.0. A novel bioinformatic approach was used to measure intra-individual genetic heterogeneity among the metastatic deposits. Results: The patients showed a large variation in the level of intra-individual metastatic heterogeneity, and heterogeneity was independent of the number of liver metastases analyzed per patient. Heterogeneity was a strong and independent prognostic factor in multivariate analysis with known clinicopathological prognostic factors. Patients with a high level of heterogeneity (above the median) had a three-year overall survival rate of 18%, compared with 66% for patients with a low level (hazard ratio, HR = 3.7, P = 0.007). The corresponding survival rates for progression-free survival were 6% and 24% (HR = 2.6, P = 0.01). Conclusions: A high level of intra-individual genetic heterogeneity among liver metastatic deposits is associated with poor survival after partial liver resection in patients with metastatic CRC.
Impact of postoperative complications on pancreatic cancer survival and recurrence.
Authors: Masahiro Asari, Toru Aoyama, Yusuke Katayama, Masaaki Murakawa, Koichiro Yamaoku, Amane Kanazawa, Akio Higuchi, Manabu Shiozawa, Makoto Ueno, Manabu Morimoto, Makoto Akaike, Tsutomu Hayashi, Naoto Yamamoto, Takashi Oshima, Takaki Yoshikawa, Yasushi Rino, Munetaka Masuda, Soichiro Morinaga
Journal: Journal of Clinical Oncology (2015)

446 Background: We investigated the impact of postoperative complications on pancreatic cancer survival and recurrence after curative surgery. Methods: This study included 164 patients who underwent curative surgery for pancreatic cancer between 2005 and 2014. The patients were classified into those with postoperative complications (C group) and those without postoperative complications (NC group). The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. Results: Postoperative complications were found in 61 of the 164 patients (37.2%). The RFS rate at five years after surgery was 10.6% in the C group patients and was 21.0% in the NC group patients. The RFS tended to be worse in the C group than in the NC group (p=0.1756). The OS rate at five years after surgery was 7.4% in the C group and 22.8% in the NC group, which was significantly different (p=0.0189). The multivariate analysis demonstrated that postoperative complications and lymphatic invasion were significant independent risk factors for the RFS and OS. Conclusions: The development of postoperative complications was a risk factor for a decreased overall survival and for disease recurrence in patients who underwent curative surgery for pancreatic cancer. The surgical procedure, perioperative care and the surgical strategy should be carefully planned to avoid complications.
Serum fatty acid synthase as a marker of gastric neoplasia.
Authors: T. Ito, H. Orita
Journal: Journal of Clinical Oncology (2011)

e14543 Background: It is a well-known fact that anaerobiotic metabolism is accelerating in many cancer cells. Lipids seem to be undertaking the important roles of ontogeny and progression. Lipid is made from triglyceride and fatty acid by fatty acid synthase. Fatty acid synthase (FAS) is overexpressed in many human cancers and is considered to be a promising target for therapy. We have reported that enzyme is overexpressed not only in tissue, but also in serum levels in many cancers. This time, we investigated: (1) the expression of this candidate target in gstric cancer, and (2) the serum level of this enzyme, and considered the possibility of this enzyme for a tumor marker. Methods: (1) Using immunohistochemistry, we evaluated the expression of FAS protein in32 gastric cancers. (2) By using the ElISA kit, we measured the serum level of FAS in 32 patients, who underwent surgical resection ofgastric cancer in Juntendo shizuoka hospital, and 153 normal patients whose samples were provided by cardiologist, Dr. Shimada’s research group. And we considered the relationship with pathological stage and clinical data. Results: (1) We discovered significantly higher levels of FAS expression in 77% of gastric cancers. (2) The serum FAS levels were also significantly higher control (patient’s average is 23.0 ug/mL, and control is 2.3ul/mL). There is no significant correlation with clinicopathological data. Conclusions: Similar to several other common types of human cancer, FAS is expressed at very high levels in gastric cancer. The serum FAS level is also expressed at significantly high levels in human gastric carcinomas. It appears that the FAS serum level will be a tumor marker candidate.
Clinical features and treatment outcomes of angioimmunoblastic T-cell lymphoma.
Authors: B. Pro, G. F. Perini, L. Feng, J. E. Romaguera, M. A. Rodriguez, P. McLaughlin, F. B. Hagemeister, L. Fayad, T. M. Kadia
Journal: Journal of Clinical Oncology (2010)

8048 Background: Angioimmunoblastic T-cell lymphoma (AITL) accounts for up to 15-20% of all peripheral T-cell lymphomas. Typically, the disease follows an aggressive course with systemic symptoms and an overall poor prognosis. The primary objectives of this analysis were 1) to assess the association between complete response status after first-line chemotherapy and the other known prognostic factors; 2) to estimate the overall survival (OS) and progression-free survival (PFS) by patients' prognostic factors. Methods: Sixty-three patients diagnosed with AITL between 1996 and 2009 were included in the study. Patients characteristics were: 57% male, median age 65 (range: 35- 83), 94% stage III-IV, 46% IPI of ≥3. Eighty percent of the patients presented with B symptoms and 18% of them had a history of previous chemical exposure. Most of the patients were initially treated with anthracycline-based chemotherapy (87%) and 11 (17%) patients received rituximab in combination with chemotherapy. Results: Overall response rate to initial chemotherapy was 78% with 65% of patients achieving a CR. The only factor associated with achievement of CR was low IPI (p= 0.05). With a median follow-up of 20 months (range: 2-152), the 5-year and 10-year OS rates of all patients were 47% and 23% respectively. The 5-year and 10-year PFS rates were 18% and 15% respectively. Performance status and IPI were both predictive prognostic factors for survival (p=0.005 and 0.04 respectively) whereas only IPI was predictive for PFS (p=0.03). The presence of EBV RNA detected by in-situ hybridization was associated with a better PFS (p=0.02). Conclusions: This study confirms the poor prognosis of patients with AITL when treated with standard anthracycline-based chemotherapy regimens. IPI remains the strongest predictive factor for both OS and PFS. Novel therapies are needed to improve the outcome of this disease. No significant financial relationships to disclose.
RNA-based molecular tumor typing and immunological infiltrate as response predictors to neoadjuvant chemotherapy: Prospective validation in the GeparQuinto-PREDICT substudy.
Authors: C. Denkert, R. Kronenwett, S. Loibl, V. Nekljudova, S. Darb-Esfahani, B. Gerber, B. Sinn, C. Petry, I. Bauerfeind, J. Budczies, M. Rezai, M. Dietel, I. Schrader, G. Kunz, G. Von Minckwitz
Journal: Journal of Clinical Oncology (2011)

10526 Background: We have recently developed a standardized system and defined cutoffs for assessment of molecular tumor subtype based on RNA expression of ESR1 and HER2 in FFPE tissue. (Müller et al. Diagn Mol Pathol 2011). Furthermore we described intratumoral and stromal lymphocytes as well as lymphocyte-predominant breast cancer (LPBC) as new predictors of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) (Denkert et al. J Clin Oncol 2010). Methods: The PREDICT substudy of the GeparQuinto trial (von Minckwitz et al. SABCS 2010) included a prospective independent validation of these 5 markers. RNA was extracted from 192 HER2neg FFPE breast cancer core biopsies using a fully-automated robot-based system. Expression of ESR1 and HER2 mRNA as well as control genes was determined by quantitative RT-PCR using predefined cutoffs. Test results were available in all cases before the patient underwent surgery. Results: 112 luminal tumors and 80 triple-negative (TNBC) tumors were defined by RNA-based subtyping. pCR rate was 40% in TNBC compared to 7.1% in luminal tumors. TNBC was predictive for response to NACT in logistic regression analysis (p<0.001) with an OR of 8.67 (95%CI [3.72-20.2]). LPBC had a pCR rate of 41%, compared to 14% for non-LPBC tumors (p<0.01). Intratumoral lymphocytes (p=0.005), stromal lymphocytes (p<0.005) and LPBC (p<0.005) were predictive for pCR in univariate logistic regression analysis. TNBC were more likely to contain an increased lymphocytic infiltrate compared to luminal tumors (p=0.001). Conclusions: This is the first report of a validated diagnostic test for mRNA based molecular subtyping. Distinct molecular subgroups according to the predefined cutoffs showed statistically significant different pCR rates. This standardized approach might be helpful to reliably define TNBCs as target population for clinical trials investigating new agents.
FCR (Fludarabine, Cyclophosphamide, Rituximab) Followed By 90yttrium Ibritumomab Tiuxetan for the Treatment of Relapsed Grades 1 and 2 Follicular Lymphoma. Long Term Efficacy and Safety Results of 9 Cases
Authors: Francesco Pisani, Maria Laura Dessanti, Diana Giannarelli, Ramy Kayal, Francesco Marchesi, Rosa Sciuto, Sandra Rea, Carlo Ludovico Maini, Mirella Marino
Journal: Blood (2014)
Multi-institutional evaluation of the prognostic significance of altered mammalian target of rapamycin (mTOR) pathway biomarkers in upper-tract urothelial carcinoma (UTUC).
Authors: Aditya Bagrodia, Laura-Maria Krabbe, Bishoy A. Gayed, Payal Kapur, Oussama M. Darwish, Ira Bernstein, Xian-Jin Xie, Christopher G. Wood, Richard Zigeuner, Alon Z. Weizer, Jay D. Raman, Mesut Remzi, Cord Langner, Marco Roscigno, Christian Bolenz, Karim Bensalah, Arthur I. Sagalowsky, Shahrokh F. Shariat, Yair Lotan, Vitaly Margulis
Journal: Journal of Clinical Oncology (2014)

323 Background: Alterations in the MTOR and HIF pathways may have prognostic significance in bladder carcinoma. We evaluated the predictive value of altered MTOR-pathway biomarkers in upper tract urothelial carcinoma (UTUC). Methods: Multi-institutional review of clinicopathological data on patients receiving extirpative surgery for UTUC from 1990-2008. Immunohistochemistry for phosphorylated-S6, mTOR, phosphorylated-mTOR, PI3K, p4E-BP, phosphorylated-AKT, PTEN, HIF-1a, Raptor and Cyclin D was performed on tissue microarrays from radical nephroureterectomy specimens. Predictive markers were identified by regression analyses. Significance of altered markers was assessed with Kaplan-Meier and Cox regression analysis. Results: 620 patients with a mean age of 69 years were included. 37% of patients had non-organ confined (T3/T4 and/or N+) disease. 74% of patients had high-grade disease and 22% had LVI on final pathology. Over a median follow-up of 27.3 months, 24.6% of patients recurred and 21.8% died of UTUC. On multivariable analysis, PI3K (OR 1.28, p=0.001) and Cyclin D (OR 3.45, p=0.05) were significant predictors of clinical outcomes. Cumulative marker-score was defined as low-risk (zero/one altered marker) or high-risk (Cyclin D AND PI3K altered). Patients with high-risk marker-score had a significantly higher proportion of high-grade disease (91% vs. 71%, p&lt;0.001), non-organ confined disease (61% vs. 33%, p&lt;0.001), LVI (35% vs. 20%, p=0.001), and lymph node metastases (22% vs. 6%, p&lt;0.001). Kaplan-Meier analysis demonstrated a significant difference in CSM based on risk groups. On multivariable analysis for CSM incorporating non-organ confined disease, grade, LVI, tumor architecture, and marker-score, high-risk biomarker-score was an independent predictor of CSM (HR 1.5, 95%CI 1.04-2.3, p=0.03). Conclusions: Alterations in MTOR pathway correlate with established adverse pathologic features and independently predict inferior oncologic outcomes. Incorporation of MTOR-based marker profiles may allow for enhanced patient counseling, risk stratification, and individualized treatment regimens.
Growth of tumorspheres from peripherally circulating tumor cells.
Authors: Dorothea Zimon, Monica Pizon, Ulrich A. Pachmann, Katharina Pachmann
Journal: Journal of Clinical Oncology (2012)

2 Background: Even after the complete resection of a malignant tumor the menace remains, that cells that have dissociated from the tumor might resettle in distant organs and grow into life-threatening metastases. Therefore we have developed an approach (maintrac) to detect and monitor the circulating tumor suspect epithelial cells in blood. However, the question arises whether these cells have the potential to grow into metastases. Methods: Using a nondissipative approach with only one enrichment step of red blood cell lysis, the cells from the pellet, containing the white blood cells together with the putative tumor cells were cultured under conditions favoring the growth of epithelial cells. At 7, 14, and 21 days the cultured cells were stained with anti-EpCAM antibody and inspected for the appearance of epithelial antigen positive spheroids. Results: Peripherally circulating cells from patients with malignant tumors in different stages of disease were analyzed for the presence of circulating epithelial tumor suspect cells and the frequencies of tumorspheres. Tumorspheres could so far be grown from all of 20 patients in whom more than 2000/ml epithelial tumor suspect cells were detected. Fractions of tumorspheres varied from less than 1% of the epithelial tumor suspect cells in patients with primary breast cancer to up to 70% in a patient with an aggressively growing metastatic colon cancer. The size of the spheres increased from day 7 to day 21 but already had reached the size of day 21 colonies after seven days in the patient with the metastatic colon cancer. Conclusions: Here, we demonstrate that the tumor suspect cells, detected in our approach contain a subpopulation with stem cell-like properties capable of growing into tumorspheres. The frequency and growth potential of cells capable of forming spheres seems to be dependent from the properties of the primary tumor. The possibility to grow tumorspheres from peripherally circulating tumor cells may open up a new field, where the relevant cells with stem cell properties from individual patients can now be specifically analysed further for genetic endowment, transcriptional activity, heterogeneity, and stem cell markers.
First line chemotherapy with oral vinorelbine (oV) in elderly hormone-refractory prostate cancer (HRPC) patients (pts)
Authors: N. Caristi, G. Altavilla, R. Maisano, A. Pollicino, V. Adamo, G. Chiofalo, M. Picciotto, F. La Torre, A. Mafodda
Journal: Journal of Clinical Oncology (2005)

4749 CT regimens for HRPC are often burdened with heavy toxicity in elderly pts. A ≥ 50% PSA reduction, for at least four weeks, during a CT is considered a significant prognostic factor for survival. Intravenous Vinorelbine has shown to be active and safe in HRPC; oV has been employed in breast and lung cancer treatment with similar response and a more favourable toxicity profile, compared to i.v. form. The aim of this trial is to evaluate safety, PSA response and clinical benefit in elderly CT-naive HRPC pts treated with oV. Men aging ≥ 70 years, with histologically confirmed HRPC, KPS ≥ 50%, no prior radionuclide treatment, adequate metabolic and bone marrow function were entered into study to receive oV 60 mg/m2 on days 1 and 8 of a 21-day cycle. All were off antiandrogenic drugs, while LH-RH analogues were mantained. On the first day of each cycle PSA and QoL (FACT-P instrument) status were assessed. Toxicity was evaluated according to NCI-CTC. Response was defined by a ≥ 50% PSA decline from baseline or by ≥ 50% volume reduction of measurable lesions. To date, 18 pts with median age 77 years (70–84) received a total of 75 cycles, with a median of 4 cycles (2–8). 13 had only bone metastases, 5 both bone and soft or visceral measurable metastases. 2 pts received less than 3 cycles due to early PD. The main toxicity was haematological (anemia G2 in 2 pts; neutropenia G2 in 3 pt and G3 in 1 pts). Mild nausea was registered in 5 pts and G2 diarrhea in 2 pts. 4 pts delayed therapy for toxicity and 3 had dose reduction. No CR was observed. PSA response occurred in 6 pts in a median time of 3 weeks (1–12) with a median duration of 15 weeks (9–28). 5 pts had a significant improvement of QoL, not closely related to PSA changes. Our preliminary data suggest that oV is a safe and moderately active option in the palliation of elderly HRPC pts. No significant financial relationships to disclose.