tbuckley/cabot-search huggingface dataset:
Can we predict 2-year survival for radical radiation dosing schedules in advanced non-small cell lung cancer through a meta-analysis based predictive model?
Authors: W. Sharieff
Journal: Journal of Clinical Oncology (2010)

7089 Background: Total dose, dose per fraction, number of fractions, and treatment time are important determinants of the biological effect of a radiation dosing schedule. Biological effective dose (BED) based on the linear quadratic model is used to design new schedules prior to testing in randomized clinical trials (RCTs). Several RCTs have tested a variety of dosing schedules in advanced unresected non-small cell lung cancer (NSCLC); however, survival remains poor. Nevertheless, data from these RCTs could be used to optimize the dosing schedule for radical treatment of unresected NSCLC through a predictive model. Methods: 13 RCTs that compared various radiation schedules without chemotherapy were used to define the dose response relationship between radiation schedules and 2-year survival. Based on this relationship predictive models were developed. Predictions were compared with observations from radiation alone arms of 26 RCTs that compared various radiation schedules to the same schedules plus chemotherapy; scatter plots and pearson's correlation coefficient (r) were used for comparison. Uncertainty was quantified by computing 95% intervals around the estimates. Finally, based on predicted survival optimized schedule was searched. Results: Lower mortality was associated with the total dose (Odds ratio (OR)/5 Gy 0.68; 95% interval 0.56, 0.82), dose per fraction (OR/Gy 0.90; 0.79, 1.04), and number of fractions (OR/fraction 0.98; 0.93, 1.04); higher mortality was associated with total dose-squared (OR/5 Gy2 1.0; 1.0, 1.05), and treatment time (OR/week 1.25; 0.99, 1.54). The observed and predicted rates were similar (r = 0.75; 0.72, 0.77). Schedules that delivered higher total dose over a shorter time had higher survival rates compared to the standard (60 Gy, 30 fractions, 6 weeks). Conclusions: The developed model can better inform medical decision making through prediction of survival rates, compared to the BED model. This would help in designing new schedules for RCTs and would help in preventing futile research. This methodology can be applied to optimize chemotherapy regimens, and for other cancers such as head and neck, breast and prostate. No significant financial relationships to disclose.
RBC Transfusion Independence and Safety Profile of Lenalidomide 5 or 10 mg in Pts with Low- or Int-1-Risk MDS with Del5q: Results From a Randomized Phase III Trial (MDS-004).
Authors: Pierre Fenaux, Aristotle Giagounidis, Dominik Selleslag, Odile Beyne-Rauzy, Ghulam J Mufti, Moshe Mittelman, Petra Muus, Peter te Boekhorst, Guillermo Sanz, Consuelo del Cañizo, Agnes Guerci-Bresler, Brigitte Schlegelberger, Carlo Aul, Hans Kreipe, Gudrun Goehring, Robert Knight, John Francis, Tommy Fu, Eva Hellstrom-Lindberg
Journal: Blood (2009)
A phase I/II study of Xcellerated T Cells in patients with chronic lymphocytic leukemia
Authors: T. J. Kipps, W. G. Wierda, J. E. Castro, M. J. Keating, R. V. Boccia, R. Steis, J. Meyer, R. J. Berenson, M. W. Frohlich
Journal: Journal of Clinical Oncology (2005)

2511 Background: T cells from CLL pts can be activated & expanded ex vivo using the Xcellerate Process, in which peripheral blood mononuclear cells (PBMC) are incubated with anti-CD3 & anti-CD28 antibody-coated magnetic beads (Xcyte Dynabeads). With this process, anergic T cells from CLL pts can be activated, leading to upregulation of important immune molecules on leukemic B cells & leukemic cell apoptosis (Bonyhadi et al., J. Immunol, in press). Methods: A total of 17 pts with high risk or symptomatic/progressive intermediate-risk disease were divided into 3 cohorts which were treated with increasing Xcellerated T Cell (XTC) doses: 10 x 109(n=3), 30 x 109 (n=3), and 60–100 x 109(n=11). Results: Prior treatments included chemotherapy ± monoclonal antibody treatment (n=10), investigational vaccine (n=3), steroids (n=1), and no prior therapy (n=3). There was one serious adverse event (SAE) of atrial fibrillation, which occured 17 days post-infusion & was unlikely related to treatment. T cell counts increased in a dose dependent manner & increases in neutrophil, platelet, hemoglobin & NK counts were also observed. A ≥ 50% reduction in lymph node area was observed in 12 of 17 evaluable pts (71%), and ≥ 50% decrease in splenic enlargement was observed in 11 of 13 pts with enlarged spleens (85%). Treatment effects were sustained over the 12 week f/u period & observed at all dose levels of XTC administered. Decreases in leukemic cell counts were not observed. 6 pts received a 2nd infusion of XTC (median dose: 77.1 x 109; range: 68.7–96.4 x 109) a median of 10.3 mos (range: 5.8–11.0) following the 1st infusion. The 2nd infusions were well-tolerated, with no SAEs reported. 4 of 5 pts with measurable lymphadenopathy had reductions [median: -38%, range: -67% to +10%], & 2 of 3 pts with splenomegaly had reductions [median: -25%, range: -100% to +33%]. Conclusions: XTC were reproducibly manufactured & were well tolerated. Treatment led to increases in T cell & other blood counts, and significant decreases in lymphadenopathy & splenomegaly. Repeat treatment was well-tolerated, & led to subsequent decreases in lymphadenopathy & splenomegaly. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Xcyte Therapies Xcyte Therapies Xcyte Therapies Xcyte Therapies
Genetic correlations with chemotherapy-induced hepatic injury.
Authors: C. H. C. Pilgrim, K. Brettingham-Moore, A. Pham, W. Murray, E. Link, M. Smith, V. Usatoff, P. M. Evans, S. Banting, B. N. Thomson, M. Michael, W. A. Phillips
Journal: Journal of Clinical Oncology (2011)

3045 Background: Chemotherapy-induced hepatic injury (CIHI) represents a major cause of morbidity post-resection of colorectal liver metastases in patients treated with neoadjuvant chemotherapy. Prediction of patients at risk of developing CIHI may be possible by analysis of genes associated with forms of toxicity and chemotherapy drug metabolism. Methods: Two hundred twenty-two patients provided 234 tissue bank or pathology archive samples following hepatic resection, which were examined for CIHI and had DNA and RNA extracted for genetic analyses. CIHI subtypes were scored according to previously validated systems on haematoxylin eosin, and Masson trichrome slides of non-tumourous liver. Variants within genes relevant to damage neutralisation from oxaliplatin (nucleotide excision repair enzymes ERCC1 and ERCC2, and glutathione-S-transferase enzymes GSTM1 and GSTT1), and enzymes involved in metabolism of 5FU [thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD)] were examined by reverse transcriptase real time quantitative PCR for ERCC1, ERCC2, TS, DPD and TP, and multiplex PCR for null variants of GSTM1 and GSTT1. Associations between CIHI subtypes and genetic variants (present/null or highest expressing third vs. lowest third and continuous expression levels) were assessed by chi-square and t-tests. Results: High-grade steatosis, sinusoidal dilation and NASH were observed in 18%, 15% and 4%, respectively, of samples. Among all patients, development of steatosis was associated with DPD expression (low vs. high third OR=4.5 (95%CI 1.5–13.7) p<0.005, N=95) and sinusoidal injury was associated with GSTT1 null variant (OR=0.2 (0.0–0.8) p=0.007) and expression of ERCC1 (low vs. high third OR=0.3 (0.1-1.2) p=0.07) and ERCC2 (continuous expression levels 3x higher among those with no sinusoidal injury vs. injury, p<0.01, N=60). These associations were also present when restricted to the 60% of patients who had received chemotherapy. There were no further associations between injury patterns and other target variants. Conclusions: Predisposition to development of CIHI may be predictable based upon patient genetic signatures of enzymes related to metabolism of chemotherapeutic agents.
Diagnostic value of reverse-transcriptase polymerase chain reaction for <i>MAGE</i> families expression in malignant thoracic pleural effusions
Authors: G. Jiang, H. Wang, F. Yang, J. Wang
Journal: Journal of Clinical Oncology (2005)

9533 Background: The identification of malignant cells in effusions by conventional cytology is hampered by its limited sensitivity. Previous studies show that the MAGE genes families are only expressed in the malignant cells and not expressed in normal tissues except testis and placenta. The aim of this study was to improve tumor cell detection in effusions by reverse-transcriptase polymerase chain reaction (RT-PCR) for MAGE families expression. Methods: A total of 22 thoracic effusions from patients with lung cancer and 18 thoracic effusions from patients without an evidence of malignancy were included in this study. All effusion specimens were evaluated in parallel by cytology, RT-PCR for MAGE families expression and pleural biopsy under video assisted thoracoscopy. To improve the sensitivity of RT-PCR, we combined the results of RT-PCR for MAGE-1, 2, 3 and 4 expressions. Anyone of them expressed in the effusion was recorded as MAGE positive. Results: Tumor cell detection by cytology, RT-PCR for MAGE expression and pleural biopsy were negative in all of 18 effusions from patients with benign disease. In 22 effusions from patients with lung cancer, the sensitivities of tumor cell detection by cytology, RT-PCR for MAGE expression and pleural biopsy were 36%(8/22), 86%(19/22) and 100%(22/22), respectively. The corresponding specificities were all 100%. All the 8 effusions that were positive in cytology were positive in MAGE expression. Notably, 11 out of 14 effusions that were negative in cytology but positive in pleural biopsy were positive in MAGE expression. For the other 3 malignant effusions that were negative in both cytology and MAGE expression, RT-PCR for MAGE families expression on pleural biopsy samples were also negative which indicated the MAGE were not expressed in these tumors. Conclusions: RT-PCR for MAGE families expression is a highly sensitive and specific diagnostic tool for detecting malignant cells in effusions especially for the cytological negative effusions. No significant financial relationships to disclose.
Microwave ablation for hepatic malignancies: A multi-institutional analysis.
Authors: Ryan Thomas Groeschl, Charles Henry Caldow Pilgrim, Erin Marie Hanna, Kerri A Simo, Ryan Z Swan, David Sindram, John B Martinie, David A Iannitti, Mark Bloomston, Carl Richard Schmidt, Homan Khabiri, Lawrence Andrew Shirley, Robert C. G. Martin, Kathleen K. Christians, William S Rilling, T. Clark Gamblin
Journal: Journal of Clinical Oncology (2013)

218 Background: Although many hepatobiliary centers have moved from radiofrequency ablation to microwave ablation (MWA), the factors that influence local control with MWA are not well described. We hypothesized that tumor size, number of tumors, and tumor histology significantly affected MWA success and recurrence-free survival (RFS). Methods: Consecutive patients with hepatic malignancy treated by MWA were included from 4 high-volume institutions (2003-2011), and grouped by histology: hepatocellular cancer (HCC), colorectal metastases (CM), neuroendocrine metastases (NM), and other cancers. Independent significance of variables was established with logistic regression and Cox proportional hazards models. Results: Four-hundred seventy three ablation procedures were performed (139 HCC, 198 CM, 61 NM, and 75 other) for a total of 875 tumors. Median follow-up was 18 months. Complete ablation was confirmed for 839 of 865 tumors (97.0%) on follow-up cross-sectional imaging (Table). NM had greater odds of an incomplete ablation compared to other histologies (odds ratio: 3.07, 95% confidence interval [CI]: 1.08-8.67, p=0.035), however this was not significant in adjusted models. The local recurrence rate was 6.1% overall, and was highest for HCC tumors (10.3%, p=0.051). RFS did not vary significantly between histologies. In adjusted models, tumor size ≥3cm was the only variable predicting poorer RFS (hazard ratio: 1.60, 95% CI: 1.02-2.50, p=0.039). Independent predictors of poorer OS included age, number of tumors ablated, and tumor size ≥3cm. Conclusions: In this large dataset, patients with ≥3cm tumors showed a propensity for early recurrence, regardless of histology. Higher rates of local recurrence were noted in HCC patients, which may reflect underlying liver disease. Accounting for recurrence at any site, however, there were no significant differences in RFS between tumor histologies. [Table: see text]
Significance of definitive chemoradiotherapy and salvage surgery for squamous cell carcinoma of the esophagus.
Authors: M. Morita, K. Yoshinaga, H. Saeki, A. Egashira, T. Ohga, Y. Emi, Y. Kakeji, Y. Shioyama, Y. Maehara
Journal: Journal of Clinical Oncology (2010)

e14521 Background: Definitive chemoradiotherapy (CRT) has been recently administered for even resectable squamous cell carcinoma of the esophagus (ESCC). However, the clinical significance of definitive CRT as well as salvage esophagectomy is still unclear. Methods: Sixty-five patients with ESCC without organ metastasis received definitive CRT between 1998 and 2007. A total radiation dose of 50.4-71 Gy was combined with the administration of cisplatin (5 mg/m2/day) and 5-FU (700 mg/m2/day) 5 days per week for 6 weeks. Prognoses were compared retrospectively with 262 patients with ESCC who underwent an esophagectomy (excluding salvage esophagectomy) in the same period. Furthermore, the clinical results of 21 patients that underwent a salvage esophagectomy (group I) after definitive CRT were compared with those who received preoperative CRT (30-40 Gy, group II), and patients who underwent surgery alone (group III). Results: 1. Definitive CRT versus surgery: the 2 and 5-year survival of the patients received definitive CRT were 45 and 35%, respectively, which were worse than those who underwent a surgical resection (65 and 54 %, p < 0.01). The prognosis was similar between both group in cStage I and II, although a surgical resection was better than definitive CRT in cStage III (non-T4, p < 0.01) and T4/M1lym: The 5-year survival rates after definitive CRT were 88, 86, 40, and 9 %, while they were 84, 86, 12, and 25% after an esophagectomy, respectively. 2. Significance of salvage surgery: postoperative complications developed in 62, 40 and 26% of patients in group I, II and III, respectively (p < 0.05 between each groups). A multivariate analysis revealed that the odds ratios of postoperative complications for groups I and II were 3.5 and 1.7 compared to group III, respectively. The 2- and 5-year survival rates of group I were 64 and 55%, respectively, which were similar with those of group III (69 and 55%). Conclusions: Definitive CRT may compare with surgical resection in cStage I and II ESCC patient, when a salvage esophagectomy is performed for either remnant or recurrent disease. A salvage esophagectomy increases the morbidity and mortality, while long-term survival can be achieved after R0 resections. No significant financial relationships to disclose.
(−)-Epigallocatechin-3-Gallate (EGCG), Green Tea Component, Antagonize the Anti-Myeloma Activity of Proteasome Inhibitor PS-341 by Direct Chemical Interaction.
Authors: Tae Young Kim, Jongmin Park, Bora Oh, Hyun Jung Min, Tae-Sook Jeong, Jae Hoon Lee, Seung Bum Park, Dong Soon Lee
Journal: Blood (2007)
The Gleason score (GS) as a predictor of survival in stage D2 and D3 prostate cancer (PC).
Authors: B. Kasimis, V. T. Chang, M. L. Gonzalez, S. Srinivas, F. Zhong, L. Duque, M. McPherson, J. Einhorn, B. Crump, M. Blumenfrucht
Journal: Journal of Clinical Oncology (2011)

e15141 Background: The GS has been extensively proven to predict survival in early stages of PC for patients (pts) treated for cure. Limited information exists about its value as a predictor of survival for stages D2 and D3. We studied the relation between GS and survival for pts in stages D2 and D3. Methods: Retrospective analysis of 128 pts on stage D2 treated with LHRH analogs was performed in an IRB approved protocol. Of those 116 pts progressed to stage D3; 46pts (38%) were treated with chemotherapy. We studied the correlation between Hb, serum Alk Phos, Albumin, LDH, PSA levels, GS and survival when the pts were first diagnosed with stage D2 and D3 PC. All pts had failed surgery or radiation used while in earlier stages. Cox survival regression analyses were performed. Results: A. D2 stage:median(range), age 69 yr(47-92), Hb 13.1g/dl(6.9-16.8), AlkPhos 138U/l (28-2365), Albumin 3.9g/dl (2.1-4.7), LDH 194 IU/L (85-4554), PSA 138.5ng/ml (0.3-15906), GS 7(4-10). B. D3 stage: age 70 yr (50-84), Hb 12.3g/dl (6.1-15.6), AlkPhos 169U/L (51-2650), Albumin 3.8g/dl (1.9-5.1), LDH 197 IU/L (40-9960), PSA 95.9ng/ml (0.2-57643), GS 7(4-10). Caucasians were 65 pts (51%), African American 60 pts (47.6%) and others 1 pt (0.8%). Median stage D2 survival was 806 days (77-4565) and for stage D3 was 326 days (14-3221). Cox univariate and multivariate analyses for predictors of survival are presented in the Table. For pts who received chemotherapy the HR for GS was 1.1, p<0.1 and for those who did not receive chemotherapy the GS the HR was 1.1, p<0.19. PSA level was not a predictor of survival for either stage D2 or D3. Conclusions: Our data indicate that GS is an independent predictor for survival for patients with metastatic PC who have stage D2 and stage D3 disease and should be included in the nomogram prediction parameters. Gleason score is a predictor throughout the course of the disease. D2 D3 Univ Multi Univ Multi HR P HR P HR P HR P Hb 0.8 <0.0001 0.89 <0.09 0.2 <0.002 0.8 <0.002 Albumin 0.8 <0.001 0.68 NS 0.77 NS 0.78 NS LDH 1.00 <0.0001 1.006 <0.002 1.00 <0.0001 1.00 NS Alk Phos 1.001 <0.0001 1.00 NS 1.002 <0.0001 1.002 <0.0001 Gleason 1.5 <0.02 1.72 <0.032 1.98 <0.004 2.29 <0.007
Docetaxel plus FOLFOX4 compared with FOLFOX4 as adjuvant chemotherapy for gastric cancer.
Authors: Chun-Xia Du, Xiao-Yan Liu, Hong-Gang Zhang, Ai-Ping Zhou
Journal: Journal of Clinical Oncology (2015)

181 Background: To compare the efficacy of docetaxel plus FOLFOX4 to FOLFOX4 as adjuvant chemotherapy for gastric cancer patients. Methods: 320 patients with stage IB-IV (M0) gastric cancer were enrolled into the retrospective study. All patients received a total or subtotal gastrectomy with at least D1 lymph nodes dissection. 193 patients received FOLFOX4 as adjuvant chemotherapy. 127 patients received biweekly docetaxel plus FOLFOX4 (DOF regimen) as adjuvant chemotherapy. Docetaxel was administered at 40 mg/m2 on day 1, followed by FOLFOX4 regimen. Both of the regimens were repeated every 2 weeks for a maximum of 12 cycles. Results: In comparison with patients in FOLFOX4 group, patients in DOF group were relatively younger (p=.001), with more advanced disease in pN stage (p=.035) and pTNM stage (p=.031), received more cycles of adjuvant chemotherapy (p=.004), and had a higher percentage of adjuvant radiation (p =.002). After adjustment of unbalanced variables as mentioned above, no statistical difference was observed between DOF group and FOLFOX4 group in terms of 3-year disease-free survival (54% vs 69%, p = 0.100, HR 1.362, 95% CI (0.943-1.967)) and 3-year overall survival(70% vs 72%, p = 0.810, HR 1.049, 95% CI (0.711-1.548)). Stratified analysis according to clinicopathologic characters showed that there were almost no statistical differences of 3-year overall survival rates between two groups, except the primary site (middle 1/3) (p =.025) and pTNM stage (IIb stage) (p =.035) in favor of FOLFOX4 group. The incidences of grade 3/4 adverse events were obviously higher in DOF group than in FOLFOX4 group,including decreased appetite (18.1% V 10.4%, P = 0.046), diarrhea (4.7% V 0%, p=0.004 ), hypersensitivity reactions to oxaliplatin (3.1% V 0%, p=0.024) and neutropenia (47.3% V 31.6%, p=0.004). Conclusions: Compared to FOLFOX4 regimen, adjuvant docetaxel plus FOLFOX4 did not show significant survival advantages in gastric cancer patients. However, a more serious toxicity profile was observed in docetaxel plus FOLFOX4 arm. Further studies are needed to decide whether triplet regimen is appropriate as adjuvant chemotherapy of gastric cancer.
Salmonella enterica Remodels the Host Cell Endosomal System for Efficient Intravacuolar Nutrition
Authors: Viktoria Liss, A. Leoni Swart, Alexander Kehl, Natascha Hermanns, Yuying Zhang, Deepak Chikkaballi, Nathalie Böhles, Jörg Deiwick, Michael Hensel
Journal: Cell Host & Microbe (2017)
A predictive model to determine the likelihood of positive sentinel lymph node biopsy in thin melanomas.
Authors: S. S. Venna, S. Thummala, M. Nosrati, S. P. Leong, J. R. Miller, R. Sagebiel, M. Kashani-Sabet
Journal: Journal of Clinical Oncology (2010)

8549 Background: The rate of positive sentinel lymph node (SLN) biopsy among T1 melanoma patients is 5%-8%. Identifying which T1 patients are at increased risk for lymph node metastasis remains unclear. Methods: Retrospective analysis of 484 patients with T1 melanoma who underwent SLN biopsy. Clinical and histological factors were evaluated including Breslow's depth, ulceration status, tumor-infiltrating lymphocytes (TIL), age, sex, and anatomic site. The incidence of positive SLN biopsy was calculated and then factors predicting positive SLN biopsy were identified. Results: Of the 484 patients, 52.1% were T1a and 40.7% T1b. Seven percent had a positive SLN biopsy. The mean age of the cohort was 52.2 years with mean follow-up of 4.53 years. The majority of primary tumors were on the trunk (43.8%), followed by the lower extremity (19.8%), head and neck (19.6%), upper extremity (16.7%). Ulceration was present in 10.7% of primaries. Univariate logistic regression analysis showed the following 4 factors to be predictive of positive SLN biopsy: decreasing age, tumor 0.8 mm or greater, tumors on the lower extremity and trunk, and absent to few TIL. None of the patients with moderate to many TIL had a positive SLN biopsy. In a multivariate analysis, only decreasing age independently predicted SLN positivity. A predictive model was developed using these 4 factors. If 0-2 factors were present, the rate of positive SLN was 3%; if 3 factors were present this increased to 15% and if all 4 factors were present, the rate of positive SLN biopsy was 30%. Conclusions: A predictive model determining the risk of positive SLN biopsy in patients with T1 melanoma may be constructed using current clinical and histological parameters and may better identify those patients in the T1 cohort to undergo SLN biopsy. No significant financial relationships to disclose.