tbuckley/cabot-search huggingface dataset:
Effect of radioimmunotherapy-based conditioning for autologous stem cell transplantation on poor-risk molecular profiling in diffuse large B-cell lymphoma.
Authors: Tanya Siddiqi, Ni-Chun Tsai, Joycelynne Palmer, Stephen J. Forman, Amrita Y. Krishnan
Journal: Journal of Clinical Oncology (2012)

6547 Background: Gene expression profiling has improved risk stratification of diffuse large B-cell lymphoma (DLBCL) in the first line setting as shown by DNA microarray analysis and immunohistochemistry (IHC). 5-year overall survival (OS) for germinal center B-cell-like (GCB) DLBCL is significantly better than that for non-GCB DLBCL in newly diagnosed patients. However, in the relapsed/refractory setting, autologous stem cell transplant (ASCT) appeared to overcome the poor prognosis of cell of origin as defined by IHC using CD10, Bcl6 and MUM1 and there was no difference in survival between GCB and non-GCB groups. Ibritumomab tiuxetan (Z)-BEAM conditioning regimen for ASCT in DLBCL has produced promising response rates and progression free survival (PFS). The role of poor risk molecular markers in predicting outcome with the novel conditioning regimen Z-BEAM is unknown. Methods: We evaluated cell of origin (GCB, non-GCB) using IHC in 36 patients undergoing ASCT with Z-BEAM conditioning from 2002 to 2010. Median age of the patients was 54.5 years. There were 12 females and 24 males. 6 patients were in 1 st CR/PR ( 17%), 12 had induction failure disease (33%), 9 were in 1 st relapse (25%), 1 in 2 nd relapse (3%) and 8 were in ≥2 nd CR (22%). 27 patients had chemosensitive disease (75%) and all had prior rituximab exposure. Median number of prior treatments was 2. IPI at transplant was mainly low risk (78%). 22 patients had GCB (61%) and 14 (39%) had non-GCB DLBCL. Results: Median follow up is 25.6 months. 12 patients relapsed (33%) and 9 died (25%). The major cause of death is relapse/disease progression. At 2 years, median OS is 79% and median PFS is 64%. No significant difference in 2 year OS and PFS is noted between the GCB and non-GCB groups (p=0.07 and 0.06 respectively). Conclusions: Z-BEAM conditioning for ASCT may overcome the poor prognostic effect of non-GCB DLBCL in relapsed/refractory disease. Further evaluation of cell of origin using new markers like GCET1, LMO2 and FOXP1 could confirm these results as there seems to be better concordance of these markers with DNA microarray analysis.
On the role of nicotine in head and neck cancer.
Authors: Norbert H. Kleinsasser, Marzell Semmler, Ulrich A. Harreus, Elmar Richter
Journal: Cancer Research (2006)

5223  Nicotine is the tobacco plant specific alkaloid commonly accused for the addictive potential of tobacco smoke. Although the carcinogenic effect of smoking has been ascribed mostly to other constituents of tobacco smoke such as polycyclic aromatic hydrocarbons, nitrosamines and arylamines, in recent studies a possible contribution of nicotine is discussed. In the present study genotoxic effects of nicotine were evaluated in human lymphocytes and cells of human lymphatic tissue of the palatine tonsils as well as in mini organ cultures of human nasal epithelium. Using the comet assay, DNA single strand breaks, alkali labile and incomplete excision repair sites were examined after exposure to nicotine. To monitor for possible artefacts, lymphatic tissue cells and lymphocytes were incubated with nicotine probes of high purities from two different suppliers were tested and in a medium in which the pH was left either unadjusted at increasingly alkaline conditions with increasing nicotine concentrations or adjusted to neutral pH. With mini organs repetitive nicotine exposures with consecutive repair phases were performed. One hour exposure to nicotine at 0.125, 0.25, 0.5, 1, 2, 4 mM induced a dose dependent increase of DNA migration up to 3.8-fold and 3.2-fold in lymphatic tissue cells and lymphocytes, respectively. The lowest concentration eliciting significant DNA damage was 0.5 mM nicotine There were neither relevant differences concerning the source of nicotine nor at neutral versus increasingly alkaline pH of the medium. In mini organs, one hour exposure to 2 and 4 mM nicotine on day 7 of culture caused a dose-dependent significant 3.3- and 5.6-fold increase of DNA damage compared to solvent controls. Although no significant repair was evident within 24 h recovery, DNA damage was not further increased by a second and third 1 h incubation with nicotine on days 9 and 11. However, at higher concentrations and after prolonged exposure up to 24 h increased DNA migration could be observed. In conclusion, the data indicate significant direct genotoxic effects of nicotine in human target cells in vitro. Therefore, a tumor initiating effect of nicotine in head and neck cancer cannot be excluded. Supported by a grant from Imperial Tobacco Ltd.
Dose-dense first-line chemotherapy in advanced ovarian cancer: How to select the patients?
Authors: Alexandra Tjulandina, Marina Stenina, Ilya Pokataev, Mikhail Fedyanin, Alexey Tryakin, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2013)

e16509 Background: First line dose-dense (dd) regimens improve PFS in patients (pts) with advanced ovarian cancer, but also increase hematological toxicity, peripheral neuropathy and usage of G-CSF. Nowadays it is unknown which pts benefit from this treatment. Methods: The analysis included 156 pts with ovarian carcinoma stages Ic-IV, who received paclitaxel (Ptx) and platinum agents in first line chemotherapy (CT) from 1996 to 2010 in our center. Retrospective group contained 91 pts, who were administered standard regimens (Ptx 175 mg/m 2 + Carboplatin (C) AUC5-6 /Cisplatin (DDP) 75 mg/m 2 every 3 weeks). Prospective group included 65 pts. Forty of them received 9 cycles Ptx 150 mg/m 2 +DDP 50 mg/m 2 every 2 weeks, 25 pts were given 6 cycles Ptx 80 mg/m 2 1,8,15 days + C AUC6 every 3 weeks. Results: Median PFS in the dd (12.5 months) and the standard arms (13.3 months) were not statistically significantly different (p = 0.6, HR 0.9; 95% CI 0.61-1.37). Multivariate analysis revealed the optimality (p=0.006) and time (p = 0.008) of cytoreduction were found as the strongest factors exerted on PFS and could take effect on choice of CT regimen. Median PFS was longer in pts with primary optimal cytoreduction (26.3 months) than in group with primary non optimal, interval debulking or without any surgery treatment (10.9 months) (p &lt; 0.0001, HR 0.28; 95% CI 0.23-0.55). The dd regimens prolonged PFS in comparison with the standard arm in pts with favorable prognosis (primary optimal cytoreduction): median was not reached vs 15.1 months respectively (p = 0.02, HR 0.36; 95%CI 0.13-1.2). Meanwhile, median PFS in unfavorable prognostic group was not different between 2 arms: 10.3 vs 11.5 months respectively (p = 0.4 HR 1.26; 95% CI 0.8-2.02). Conclusions: First-line dd statistically significantly prolong PFS in pts with primary optimal cytoreduction comparing with standard conventional CT. It is necessary to validate this predictive factor in prospective trial.
A phase II study of oral metronomic combination therapy in relapsed epithelial ovarian cancer.
Authors: Sudeep Gupta, Gautam Goyal, Jaya Ghosh, Bharatsinha Baburao Bhosale, Jyoti Bajpai, Amita Maheshwari, Rajendra Kerkar, Kedar Deodhar, Bharat Rekhi, Santosh Menon, Shripad Banavali
Journal: Journal of Clinical Oncology (2013)

5554 Background: Etoposide (E), cyclophosphamide (C) and tamoxifen (T) have been used as single agents in relapsed epithelial ovarian cancer (EOC) patients. We tested a low dose, continuous, daily, oral metronomic regimen that combined these 3 agents. Methods: This single centre prospective study included patients of relapsed EOC with exposure to at least 2 prior lines of chemotherapy (CT) and at least partial as the best response to most recent regimen. Study regimen comprised daily oral administration of E (50 mg/m2) and C (50 mg/m2) for 21 of a 28 day cycle plus T (20 mg/m2, twice per day) continuously. The primary endpoint was serological (CA-125) progression-free survival (PFS) as per Rustin Criteria and secondary endpoints were radiological (RECIST) PFS, overall survival (OS), duration of response (DOR), response rates and toxicity. The data cut-off date was 15 Jan 2013. Results: 26 patients with a median age of 48 years were accrued, of whom 21 had received 2 prior lines of CT and 5 had received 3 lines. 25 patients who were evaluable for analysis received a median of 6 (1-19) cycles of metronomic regimen. The median delivered relative dose intensities of E, C and T were 0.71, 0.71 and 0.97 respectively. 13 (52%) patients needed dose reduction after a median of 3 (1-9) cycles. Most common grade 3 or 4 toxicities included anemia, neutropenia, febrile neutropenia, nausea, vomiting and diarrhea in 44%, 36%, 12%, 16%, 16% and 12% patients respectively. 19 (76%) patients had serological CR or PR with a median time to response (TTR) and DOR of 1.8 (0.83-2.96) and 7.0 (95% CI, 5.8-8.2) months respectively. 11 (45.8%) of the 24 evaluable patients achieved radiological CR or PR with median TTR and DOR of 3.7 (1.8-7.2) and 5.5 (95% CI, 3.9-7.2) months respectively. 17, 18 and 7 patients have respectively experienced serological progression, radiological progression and death at the time of analysis. The median serological PFS, radiological PFS and OS are 7.9 (95% CI 7.2-8.6), 7.97 (95% CI, 5.95-9.98) and 22.3 (95% CI, 17.4-27.3) months, respectively. Conclusions: The oral metronomic combination of E, C and T has substantial and durable activity in relapsed EOC and is worthy of further evaluation in a larger randomized study.
Circulating tumor cells as a prognostic marker in metastatic non-small-cell lung cancer patients receiving chemotherapy.
Authors: Yuichi Sakamori, Young Hak Kim, Hiroshige Yoshioka, Masataka Hirabayashi, Koichi Onaru, Motonari Fukui, Toshiki Hirata, Michiaki Mishima
Journal: Journal of Clinical Oncology (2013)

11041 Background: Radiographic response remains the gold standard for assessment of the chemotherapy effect and has been used as a surrogate endpoint in clinical trials. Recently, circulating tumor cells (CTC) have emerged as a novel prognostic marker in many types of cancer; however, their significance has not been fully examined in patients with non-small-cell lung cancer (NSCLC). Methods: We conducted a prospective study to evaluate the clinical significance of CTC in metastatic NSCLC patients treated with chemotherapy. Peripheral blood samples were collected for CTC analysis before chemotherapy, after 1 cycle of chemotherapy, and after 2 cycles of chemotherapy. CTC analysis was performed using CellSearch (Veridex). Results: One hundred and forty-eight patients wereenrolledbetween August 2009 and January 2012, and 121 patients were eligible for the analysis. CTC was positive (CTC ≥1) in 30.6% (37/121) before chemotherapy, in 21.0% (26/118) after 1 cycle of chemotherapy, and in 21.6% (24/111) after 2 cycles of chemotherapy, respectively. CTC counts were higher in patients with N3 lymph node metastases (vs. N0-2, p = 0.0001), M1b status (vs. M1a, p = 0.0081) or ≥2 metastasis sites (vs. 1 metastasis site, p = 0.0342). Although not statistically significant, a positive trend was observed between the radiographic response and the dynamic change of CTC counts (p = 0.0734). In multivariate analysis, including the radiographic response (responder vs. non-responder), baseline CTC was a significant negative predictive factor for PFS (HR = 1.867; p = 0.0080) and OS (HR = 2.753; p = 0.0006). Considering pre- and post-treatment time points (before and after 2 cycles of chemotherapy) together, CTC-positive patients at either time point experienced significantly worse PFS (HR = 1.747; p = 0.0143) and OS (HR = 2.031; p = 0.0123) than those who were CTC negative at both time points. Conclusions: CTC was an independent prognostic factor in patients with metastatic NSCLC who was treated with chemotherapy.
Oligo-guanidyl targeted bioconjugates forming rod shaped polyplexes as a new nanoplatform for oligonucleotide delivery
Authors: Alessio Malfanti, Anna Scomparin, Sabina Pozzi, Hadas Gibori, Adva Krivitsky, Rachel Blau, Ronit Satchi-Fainaro, Francesca Mastrotto, Paolo Caliceti, Stefano Salmaso
Journal: Journal of Controlled Release (2019)
APOL1 Kidney Risk Variants and Cardiovascular Disease: An Individual Participant Data Meta-Analysis
Authors: Morgan E. Grams, Aditya Surapaneni, Shoshana H. Ballew, Lawrence J. Appel, Eric Boerwinkle, L. Ebony Boulware, Teresa K. Chen, Josef Coresh, Mary Cushman, Jasmin Divers, Orlando M. Gutiérrez, Marguerite R. Irvin, Joachim H. Ix, Jeffrey B. Kopp, Lewis H. Kuller, Carl D. Langefeld, Michael S. Lipkowitz, Kenneth J. Mukamal, Solomon K. Musani, Rakhi P. Naik, Nicholas M. Pajewski, Carmen A. Peralta, Adrienne Tin, Christina L. Wassel, James G. Wilson, Cheryl A. Winkler, Bessie A. Young, Neil A. Zakai, Barry I. Freedman
Journal: Journal of the American Society of Nephrology (2019)

Two coding variants in the apo L1 gene (APOL1) are strongly associated with kidney disease in blacks. Kidney disease itself increases the risk of cardiovascular disease, but whether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results.We conducted a two-stage individual participant data meta-analysis to assess the association of APOL1 kidney-risk variants with adjudicated cardiovascular disease events and death, independent of kidney measures. The analysis included 21,305 blacks from eight large cohorts.Over 8.9±5.0 years of follow-up, 2076 incident cardiovascular disease events occurred in the 16,216 participants who did not have cardiovascular disease at study enrollment. In fully-adjusted analyses, individuals possessing two APOL1 kidney-risk variants had similar risk of incident cardiovascular disease (coronary heart disease, myocardial infarction, stroke and heart failure; hazard ratio 1.11, 95% confidence interval, 0.96 to 1.28) compared to individuals with zero or one kidney-risk variant. The risk of coronary heart disease, myocardial infarction, stroke and heart failure considered individually was also comparable by APOL1 genotype. APOL1 genotype was also not associated with death. There was no difference in adjusted associations by level of kidney function, age, diabetes status, or body-mass index.In this large, two-stage individual participant data meta-analysis, APOL1 kidney-risk variants were not associated with incident cardiovascular disease or death independent of kidney measures.
Use of Bleeding Assessment Tools in the Diagnosis of Von Willebrand Disease: Are We Asking the Right Questions?
Authors: Jordan Spradbrow, Sasha Letourneau, Julie Grabell, Yupu Liang, James Riddel, Wilma Hopman, Victor S. Blanchette, Margaret L. Rand, Barry S. Coller, Andrew D. Paterson, Paula D. James
Journal: Blood (2017)
Nodal status after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer: Prognostic evaluation of number of resected lymph nodes (LNs), metastatic resected LNs, and LN ratio in the National Cancer Institute of Brazil.
Authors: Fernando Meton Vieira, Rodrigo Otavio Araujo, Ana Paula Victorino, Maria de Lourdes Oliveira, Carlos G. M. Ferreira
Journal: Journal of Clinical Oncology (2013)

e14568 Background: For accurate colon cancer staging, 12 or more LNs must be resected. However, in rectal cancer, preoperative CRT can decrease the number of evaluable LNs, and the cutoff for a minimum number of LNs retrieved is unclear, as well as the prognostic value of LN ratio. Methods: We evaluated all locally advanced rectal cancer that received CRT followed by standard surgery (TME) from 2002 to 2009. External radiotherapy consisted of 45 to 50.4 Gy in 5 weeks and concomitant chemotherapy was bolus 5-Fu/LV. Pre-treatment staging included abdominal and pelvic CTs, chest RXs, CEA, and physical examination. Clinical data was collected from medical records and surgical specimens were pathologically evaluated accordingly to Quirke's method. LN ratio was defined as the ratio of the number of positive LN and total number of LN examined. Kaplan-Meier overall survival (OS) and disease free survival (DFS) curves were obtained and compared using the Long-rank test. Categorical variables were assessed using Fish's exact test. Results: Of 202 patients included, 125 (62%) were low rectal cancers (5cm or less from anal verge). Surgery was performed in a mean time interval from CRT of 3.95 months (0.28-24), and the type of resection was a low anterior resection in 139 (64%) and abdominoperineal resection in 63 (36%). Only 42.5% received postoperative chemoterapy. LN metastasis at the vascular stump level were more frequent in cancers lying more than 5 cm above the anal verge (p=0.02). Median number of LNs found in the specimens was 12 (0-56). The number of resected LNs had no impact in prognosis within the cutoff levels of 7 or 12, neither when considering only ypN0 cases. A LN Ratio &gt;0.15 was found in 33% of our patients, and associated to a decrease in OS (p&lt;0.001) and DFS (p=0.01), and was the only variable associated to distant metastasis (p=0.048). Conclusions: Positive LNs after CRT severely impaired prognosis in patients treated with rectal cancer. A prognostic cutoff value for LN dissection were not achieved, but a LN ratio &gt;0.15 seems to be a strong predictor of recurrence and cancer related death.
Global Consultation on Cancer Staging: promoting consistent understanding and use
Authors: James Brierley, Brian O’Sullivan, Hisao Asamura, David Byrd, Shao Hui Huang, Anne Lee, Marion Piñeros, Malcolm Mason, Fabio Y. Moraes, Wiebke Rösler, Brian Rous, Julie Torode, J. Han van Krieken, Mary Gospodarowicz
Journal: Nature Reviews Clinical Oncology (2019)

Disease burden is the most important determinant of survival in patients with cancer. This domain, reflected by the cancer stage and codified using the tumour-node-metastasis (TNM) classification, is a fundamental determinant of prognosis. Accurate and consistent tumour classification is required for the development and use of treatment guidelines and to enable clinical research (including clinical trials), cancer surveillance and control. Furthermore, knowledge of the extent and stage of disease is frequently important in the context of translational studies. Attempts to include additional prognostic factors in staging classifications, in order to facilitate a more accurate determination of prognosis, are often made with a lack of knowledge and understanding and are one of the main causes of the inconsistent use of terms and definitions. This effect has resulted in uncertainty and confusion, thus limiting the utility of the TNM classification. In this Position paper, we provide a consensus on the optimal use and terminology for cancer staging that emerged from a consultation process involving representatives of several major international organizations involved in cancer classification. The consultation involved several steps: a focused literature review; a stakeholder survey; and a consultation meeting. This aim of this Position paper is to provide a consensus that should guide the use of staging terminology and secure the classification of anatomical disease extent as a distinct aspect of cancer classification.
Outcomes after treatment of resectable, node-negative esophageal cancer: A risk-adjusted analysis of the Surveillance, Epidemiology, and End Results registry.
Authors: Jeremiah Thomas Martin, Mathias Worni, Joseph Bertram Zwischenberger, Ricardo Pietrobon, Thomas A. D'Amico, Mark Francis Berry
Journal: Journal of Clinical Oncology (2012)

e14562 Background: Esophageal cancer has poor prognosis even in early stages. We examined survival for patients with resectable tumors in the absence of nodal disease in order to assess the benefits of surgery and radiation. Methods: Patients with T1-T3N0M0 squamous cell or adenocarcinoma of the mid or distal esophagus were identified using the SEER database from 1998-2008. The Kaplan-Meier approach and risk-adjusted Cox proportional-hazard models were used to assess 5-year overall survival. Survival risk among treatment modality subgroups (surgery only (SO), radiotherapy only (RO), combined surgery and radiotherapy (CT), and local tumor resection (LR)) was evaluated for the overall patient cohort and stratified among T-stage. SEER does not record chemotherapy use, which therefore wasn’t analyzed. Results: Overall 5-year survival for 4,251 patients identified (mean age 67.7±11.4 years, 966 (22.7%) female) was 37.6% (95% CI: 35.8-39.4). Survival correlated with T-stage: T1N0 48.0% (45.4-50.6); T2N0 29.8% (26.1-33.5); and T3N0 25.8% (22.9-28.7), p&lt;0.001. For T1N0 patients, risk-adjusted survival was better with SO compared to CT (HR: 0.84, CI: 0.74-0.96, p=0.01) while LR and SO were not significantly different (p=0.24) (Table). Treatment with SO or CT had better survival compared to RO for T2N0 and T3N0 patients. The addition of radiation to surgery (CT vs. SO) improved survival for T3N0 patients (HR 0.79, CI 0.65-0.97, p=0.03) but not T2N0 patients (HR: 1.05, CI: 0.81-1.37, p=0.71). Conclusions: Surgical resection without radiation therapy is adequate for T1N0 esophageal cancer, but combined radiation and surgery has the best outcomes for T3N0 patients. Prognoses of T2N0 cancers are more similar to T3N0 cancers than T1N0 cancers, but no survival benefit to adding radiation to surgery for T2N0 patients was seen in this study. [Table: see text]
The impact of reducing the frequency of prostate specific antigen (PSA) testing among men on active surveillance for prostate cancer.
Authors: Matthew R. Cooperberg, Lisa F. Newcomb, Elissa C. Brown, Shanshan Zhao, Ziding Feng, James D. Brooks, Daniel W Lin
Journal: Journal of Clinical Oncology (2013)

5092 Background: Active surveillance is a management strategy for men with low risk prostate cancer. Most surveillance regimens include routine PSA assessments, typically performed q 3 mos, although recent studies have questioned the utility of short-term PSA kinetics. Moreover, frequent PSA assessments may be associated with repeated intervals of anxiety around the time of testing, decreasing overall quality of life and potentially leading to avoidable interventions. We hypothesized that PSA assessment q 6 mos rather than q 3 mos would yield similar PSA kinetics calculations. Methods: We analyzed data from the Prostate Active Surveillance Study (PASS), a prospective, multicenter cohort accruing data and biospecimens from men on surveillance at 9 sites across North America. In PASS, PSAs are measured q 3 mos, with high completeness of data. We included data from men who had at least 5 PSA assessments after diagnosis, separated by ≥6 months (most had 10 PSAs separated by 3 months). PSA doubling time (PSADT) was calculated as ln(2) divided by the slope of a regression line drawn through the 5 PSAs. PSADT3 and PSADT6 were defined as the PSADT calculated from q 3 mos and q 6 mos data, respectively; for PSADT6, PSAs between each 6-month measurement were ignored. In each case, PSADT of 0-3 years defined progression, and PSADT &gt; 3 years or declining PSA defined non-progression. Results: 161 men had sufficient PSA followup for analysis. 133 had no progression by either PSADT3 or PSADT6, and 16 progressed by both PSADT calculations. 4 and 8 men, respectively, progressed only by the PSADT3 or PSADT6 calculation but not by the other calculation. The κ score for agreement of progression ascertainment between PSADT3 and PSADT6 was 0.68, and McNemar’s test indicated no statistically significant difference between the two assessments (p=0.39). Conclusions: Calculating PSADT using 6-month rather than 3-month PSA assessments does not significantly change ascertainment of PSA progression in men on surveillance. Our finding suggests that surveillance protocols may reduce the frequency of PSA testing, potentially reducing unnecessary biopsy procedures and patient anxiety due to more frequent PSA measurements.