tbuckley/cabot-search huggingface dataset:
Significance and clinical outcome of lymph node level assessment in biliary tract cancers.
Authors: Joaquina Martínez-Galán, Jesús Soberino, Cynthia S. González Rivas, Julia Ruiz Vozmediano, Lucia Portellano, Veronica Conde, Jose Antonio Ortega, Javier Garcia, Aranzazu González Vicente, Juan Ramon Delgado
Journal: Journal of Clinical Oncology (2013)

274 Background: Biliary tract cancers (BTCs) are relatively rare neoplasms encompass both cholangiocarcinoma (CC).The role of routine lymphadenectomy at the time of surgical resection remains poorly defined.We sought to identify factors associated with outcome following and examine the impact of lymph node (LN) assessment on survival. Methods: 43 pts who underwent curative intent surgery between 2000-10 were identified from a database.We calculated prognostic factors and impact lymph node assessment for survival. Results: A total 43 pts were identified with no metastatic BTCs.The median age was 65 years (29–82 years); PS0:33/43 (76%); PS1:8/43 (19%) and PS2:2/43 (5%) pts.A histological diagnosis of adenocarcinoma was confirmed in 100%.Surgical resection was performed in all patients.After resection 42% (18/43) had positive nodes.Adjuvant chemotherapy had 31/43(72%),preferred with gemcitabine and a median number of cycles 6. Grade 3 or 4 toxicities rarely occurred.During median follow-up of 6.6 years tumor recurrence or metastatic disease occurred in 63% with median survival global were 2 years and 1.5 years for disease free survival.For stage T, the median survival global rates were 58 months (95% CI 44.6-71.3) for T1-T2 and 35 months (95% CI 23.3-46.8) for T3-T4 p=0.015 and for median recidive-free survival were 23 months (95% CI 11.8-34) for T1-T2 and 14 months (95% CI 6.5-21) for T3-T4 p=0.05.For N stage, the median SG were 58 months (95% CI 50.5-65.4) for negative nodes and 26 months (95% CI 3.7-48.2) for positive nodes p=0.003 and for median recidive-free survival were 55 months (95% CI 31.7-57.5) for negative nodes and 10 months (95% CI 6.8-13) for positive nodes p=0.006.The pts who had nodal affectation in hepatic hilio had better recidive-free survival that those patients who had nodal affectation in celiac trunk p&lt;0.05. Conclusions: This represents a biliary cancer cohort with survival benchmarks obtained in the modern era of multidisciplinary care.Surgical resection and adjuvant QT offers the optimal treatment outcome in patients with ICC.From our results depth of tumor invasion (T),the presence the lymph node metastases (N) and level nodal affections are the strongest predictors of relapse and survival.
Discriminatory power of the 111-indium scan (111-In) in the prediction of altered biodistribution of radio-immunoconjugate in the 90-yttrium ibritumomab tiuxetan therapeutic regimen: Meta-analysis of five clinical trials and 9 years of post-approval safety data.
Authors: J. W. Kylstra, T. E. Witzig, M. Huang, C. E. Emmanouilides, A. Hagenbeek, G. F. Tidmarsh
Journal: Journal of Clinical Oncology (2011)

8048 Background: At the time of regulatory approval of 90-Y ibritumomab tiuxetan (Zevalin Z), 3 countries (USA, Switzerland, Japan) required labeling specifying that a 111-In imaging scan be performed 7-9 days before the therapeutic 90-Y Z dose, to guard against that the hypothetical risk that altered biodistribution (AB) of the radio-immunoconjugate cause unintended end organ damage; 42 other countries (incl. EU, Canada) approved Z without requiring 111-In. Methods: 1) Establishment of the false positive and true positive rate (positive predictive value) of the 111-In scan with data from 5 clinical trials that supported approval of Z for follicular lymphoma. Trials had subjected scans to both local- and secondary (expert) review. 2) Comparison of post approval safety surveillance data from countries that do- versus do not require 111-In as part of the Z therapeutic regimen. Results: In the 5 trials, 11 of 253 111-In scans (4.3%) were found to have AB based on local review. In only 3 of these, the local finding of AB was confirmed in central review. Of pts with 111-In scans reviewed by a trained reader in central review, 3/233 (1.3%) were found to have true AB and 7/233 (3%) were found to have had a false positive local judgement of AB. Three pts with true AB on central review who had proceeded with 90-Y Z treatment upon normal local review, showed safety and efficacy outcomes within the range of those shown by other patients on study. Comparison of post-marketing safety data between countries with (USA, CH, JP) and without (Rest of World) 111-In requirement did not reveal differences in the general pattern of safety signals, with Grade III/IV hematologic toxicity (bone marrow suppressive states) reported in 3% and 4% in the respective greographic clusters, and anaphylactoid reactions in 0.4% in both clusters. Conclusions: The 111-In scan shows poor discriminatory power in identifying cases of AB. Analysis of safety results of patients treated with 90-Y Z despite true AB does not indicate that removal of the 111-In requirement from the Z labeling would constitute a safety risk.
Association of race and socioeconomic status and outcomes with patients with rectal cancer.
Authors: J. R. Nitzkorski, A. I. Willis, J. M. Farma, S. J. Cohen, F. Zhu, D. M. Nick, E. R. Sigurdson
Journal: Journal of Clinical Oncology (2011)

376 Background: Few studies have evaluated disparities of race and SES with outcomes in RC patients. We hypothesize that disparities exist in treatment and outcomes of RC. Methods: Medical records were retrospectively reviewed of RC patients treated from 2000-2009 at an NCI cancer center and an urban academic center. SES was estimated using census data. Quartiles of income and education based on zip codes were calculated. Lowest vs. other quartiles were compared. Clinicopathologic variables included: initial stage, chemotherapy refusal, sphincter preservation, and overall survival (OS). Results: 748 patients were included (581 white, 135 black, 6 other, 26 unknown). Patients with Medicaid were more likely to present with advanced disease (Table). Initial stage did not differ by race, income, or education. Non-white (NW) patients and low education were more likely to refuse chemotherapy. 7 patients refused radiation. After excluding stage IVpatients; sphincter preservation was higher among those with higher income. Median OS for all stages was worse for NW patients (31 months vs. 50 months, p&lt;0.001), low income and education and most pronounced among NW patients with advanced disease. Insurance was not associated with survival difference. Advanced age, stage, and NW race (HR 1.49, 95% CI 1.10-2.02, p=0.01) were independent predictors of survival. Conclusions: Disparity exists in treatment acceptance and outcomes in patients with RC. NW race and lower SES is associated with advanced disease, lower rates of sphincter preservation, chemotherapy refusal, and worse OS in patients with RC. [Table: see text] [Table: see text]
Can excisional biopsy be avoided for papillary breast lesions with typical benign sonographic features and concordant core needle biopsy (CNB)?
Authors: Winnie Fu, David Motiuk, Tracy Elliot, Bobbie Docktor
Journal: Journal of Clinical Oncology (2012)

26 Background: The role of surgical excision in the management of papillary lesions remains controversial. Some studies have documented upgrade rates to malignancy or atypia as high as 17%. However, due to the inclusion of atypia or malignancy at percutaneous and other differences in methodology, these rates may have been over-estimated. This study was designed to determine sonographic features that can help to decide if a lesion warrants excision or standard follow-up. Methods: With institutional review board approval, we retrospectively reviewed 113 benign papillomas without atypia that were diagnosed at US-guided CNB at Foothills Medical Centre from 2005 to 2010. Surgical pathology for 62 of these lesions were assessed. Two radiologists who were blinded to the diagnosis reviewed the sonographic images to determine the likelihood of benignity. Statistical analysis was performed using chi-square and z-score tests. Results: In our study, 5.3% of benign papillomas were upgraded. The sonographic features associated with a higher likelihood of upgrade were intracystic type [LR+ 5.67, 95% CI (1.47,12)], non-periareolar location [LR+ 2.30, 95% CI (1.04,5.06)], complex echogenic pattern [LR+ 3.10, 95% CI (1.00,9.63)], and radiologist’s impression of unlikely benign (final BiRADS) [LR+ 1.48, 95% CI (1.01,1.90)]. Although no feature was statistically significant for greater likelihood of benignity, the sonographic features that may better predict benign pathology at excision include lesions &lt;1cm in size [LR- 0.52], homogeneously solid [LR- 0.63], smooth margin [LR- 0.69] and periareolar location [LR- 0.47]. Conclusions: The management of benign papillomas diagnosed with CNB remains controversial with a lack of agreement among published articles. Our study identifies characteristic sonographic features that are associated with higher likelihood of malignancy, warranting surgical excision. Conversely, it may not be unreasonable to place patients with lesions that are stratified as low risk into standard radiographic follow-up. As the confidence intervals span 1.00 for latter, further study is necessary to confidently recommend follow-up in place of excision.
Transient T-cell depletion causes regression of melanoma metastases
Authors: J. Chesney, M. Rasku, A. Clem, S. Telang, B. Taft, K. Gettings, H. Gragg, D. Cramer, S. Lear, K. M. McMasters, D. M. Miller
Journal: Journal of Clinical Oncology (2008)

9030 Background: Cognate immunity against neoplastic cells depends on a balance between effector T cells and regulatory T (Treg) cells. Treg cells prevent immune attack against normal and neoplastic cells by directly suppressing the activation of effector CD4+ and CD8+ T cells. We postulated that a recombinant interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; Ontak) may serve as a useful strategy to deplete Treg cells and break tolerance against neoplastic tumors in humans. Methods: We administered DAB/IL2 (12 mg/kg; four daily doses; 21 day cycles) to 16 patients with metastatic melanoma and measured the effects on the peripheral blood concentration of several T cell subsets and on tumor burden. Results: We found that DAB/IL2 caused a transient depletion of Treg cells as well as total CD4+ and CD8+ T cells (< 21 days). T cell repopulation coincided with the de novo appearance of melanoma antigen- specific CD8+ T cells in several patients as determined by flow cytometry using tetrameric MART-1, tyrosinase and gp100 peptide/MHC conjugates. Sixteen patients received at least one cycle of DAB/IL2 and five of these patients experienced regressions of melanoma metastases as measured by CT and/or PET imaging. One patient experienced a near complete response with the regression of several hepatic and pulmonary metastases coupled to the de novo appearance of MART-1-specific CD8+ T cells. A single metastatic tumor remained in this patient and, after surgical resection, immunohistochemical analysis revealed MART1+ melanoma cells surrounded by CD8+ T cells. Conclusions: Taken together, these data indicate that transient depletion of T cells in cancer patients may disrupt the homeostatic control of cognate immunity and allow for the expansion of effector T cells with specificity against neoplastic cells. Several T cell depleting agents are clinically available and this study provides strong rationale for an examination of their efficacy in cancer patients. No significant financial relationships to disclose.
Contrasting Rates of Molecular Evolution and Patterns of Selection among Gymnosperms and Flowering Plants
Authors: Amanda R. De La Torre, Zhen Li, Yves Van de Peer, Pär K. Ingvarsson
Journal: Molecular Biology and Evolution (2017)

The majority of variation in rates of molecular evolution among seed plants remains both unexplored and unexplained. Although some attention has been given to flowering plants, reports of molecular evolutionary rates for their sister plant clade (gymnosperms) are scarce, and to our knowledge differences in molecular evolution among seed plant clades have never been tested in a phylogenetic framework. Angiosperms and gymnosperms differ in a number of features, of which contrasting reproductive biology, life spans, and population sizes are the most prominent. The highly conserved morphology of gymnosperms evidenced by similarity of extant species to fossil records and the high levels of macrosynteny at the genomic level have led scientists to believe that gymnosperms are slow-evolving plants, although some studies have offered contradictory results. Here, we used 31,968 nucleotide sites obtained from orthologous genes across a wide taxonomic sampling that includes representatives of most conifers, cycads, ginkgo, and many angiosperms with a sequenced genome. Our results suggest that angiosperms and gymnosperms differ considerably in their rates of molecular evolution per unit time, with gymnosperm rates being, on average, seven times lower than angiosperm species. Longer generation times and larger genome sizes are some of the factors explaining the slow rates of molecular evolution found in gymnosperms. In contrast to their slow rates of molecular evolution, gymnosperms possess higher substitution rate ratios than angiosperm taxa. Finally, our study suggests stronger and more efficient purifying and diversifying selection in gymnosperm than in angiosperm species, probably in relation to larger effective population sizes.
Combining cetuximab with FOLFOX regimen as the first-line therapy of <i>KRAS</i> wild-type advanced gastric cancer.
Authors: Yung-Sung Yeh
Journal: Journal of Clinical Oncology (2014)

157 Background: Gastric cancer is one of the most common cancers worldwide with a high incidence in Asian countries, including Taiwan. For patients with recurrent or non-resectable advanced gastric cancer (AGC), chemotherapy or the combination of target and chemotherapy was chosen for therapy in AGC patients. We prospectively analyzed the safety and efficacy of cetuximab combined with FOLFOX4 as the first-line setting in patients with AGC. Methods: From January 2010 to January 2013, a total of 20 patients with histologically confirmed unresectable advanced/recurrent gastric cancer were enrolled into this study. Direct sequencing of KRAS mutation status was performed before the treatment. All patients received cetuximab 500 mg/m 2 every 2 weeks, and chemotherapy was administered with FOLFOX regimen of oxaliplatin at 85 mg/m2 plus leucovorin 200 mg/m2 on the first day of treatment, followed by 5-fluorouracil (5-FU) via a 24-hour continuous infusion of 1000 mg/ m2 5-FU on days 1-2 biweekly. Therapy was continued until disease progression or intolerable adverse events or receiving surgical resection. Results: All tumor tissues of 20 AGC patients were KRAS wild-type. With the median therapy of 6 cycles (4-8 cycles), clinical efficacy, according to RECIST criteria, showed an overall response rate of 55% (11/20), and 20% (4/20) of patients exhibited stable disease as well as 25% (5/20) who had progressive disease. Radical resection could be obtained in 30% (3/10) of unresectable patients as the neoadjuvant therapy. The median time to progress (TTP) was 8.3 months and the median overall survival (OS) was 12.2 months. The grade III-IV adverse events was observed in 4 of 20 (20%) patients, including 15% of neutropenia (3/20), 5% of skin rash (1/20), 10% of nausea and vomiting (2/20) as well as 15% of asthenia (3/20). Conclusions: Cetuximab combined with FOLFOX as the first-line therapy for KRAS wild-type AGC patients appears to have favorable efficacy and safety, and the possibility of conversion to radical resection. Grade 3-4 adverse events were relatively uncommon. Despite this preliminary favorable outcome; however, a long-term result and large scale clinical trial is mandatory to verify it.
Docetaxel, cisplatin, 5-flourouracil x 3 days (DCF3) compared to docetaxel, cisplatin, 5-flourouracil x 5 days (DCF5) chemotherapy for patients with metastatic or locally advanced, unresectable gastric carcinoma (MGC)
Authors: S. Z. Latifzadeh, V. Entezari, S. Akhavanfard
Journal: Journal of Clinical Oncology (2005)

4258 Background: Gastric carcinoma is a leading cause of death in Iran. Pts with MGC has poor prognosis and their median survival is 7–9 months. DCF regimen has succeeded to improve response rate and time to disease progression in MGC pts. Methods: in a prospective pilot study 21 pts (M/F: 15/6) with pathologically proven MGC and ECOG performance status I-II were enrolled. Fifteen (74.4%) pts were chemotherapy-nive and the liver was the most common site of metastasis. Pts received D: 75 mg/m2 IV d 1, C: 75 mg/m2 IV d 1, F: 750 mg/m2 24 hr IV infusion d 1–3 in DCF3 (n=15) and D: 75 mg/m2 IV d 1, C: 75 mg/m2 IV d 1, F: 750 mg/m2 24 hr IV infusion d 1–5 in DCF3 (n=6). The regiments were repeated every 3–4 weeks. Toxicity was evaluated by National Cancer Institute - Common Toxicity Criteria. The primary endpoint was pts response and complete response (CR), partial response (PR) and progressive disease (PD) were assessed with WHO criteria. toxicity per cycle was the main secondary endpoint.Results: A total 95 cycles were administered and 21 pts were available for response analysis. Overall responses rate (CR+PR) was 63.3 % (10/15) in DCF3 and 83.3% (5/6) in DCF5 and their difference was not statistically significant (P value = 0.37). The median survival and time to progression was 6.47 months and 4.53 months respectively and not statistically different between DCF3 and DCF5 (P value = 0.43 and 0.27). The most common grade III-IV toxicities per cycle were: alopecia (21%), anemia (9%) and diarrhea (4%) and these toxicities were significantly higher in DCF5 (table). There were no difference in other toxicities between DCF3 and DCF5.Conclusions: this is a pilot study and its findings support that DCF3 can be used for treatment of MGC with lower toxicity and comparable efficacy. Further conclusions should be confirmed by further large scale randomized trials. No significant financial relationships to disclose.
Safety results from a prospective study of concurrent radiosurgery and bevacizumab for recurrent malignant glioma.
Authors: K. C. Cuneo, A. R. Cabrera, J. H. Sampson, K. J. Allen, J. J. Vredenburgh, K. Peters, Z. Chang, J. E. Herndon, A. Desjardins, D. A. Reardon, J. Kirkpatrick
Journal: Journal of Clinical Oncology (2011)

2082 Background: Most patients with a malignant glioma recur after primary chemoradiation. Bevacizumab (BVZ) has been shown in phase II trials to improve disease-free survival in patients with recurrent glioma. Retrospective studies of stereotactic radiosurgery (SRS) for recurrent glioma have also suggested improved outcomes, particularly when BVZ is administered after SRS. Methods: Patients with a recurrent unifocal malignant glioma who were treated with chemoradiation at diagnosis and failed salvage chemotherapy were eligible for this IRB-approved study. MRI and CT imaging were used for SRS planning. The contrast-enhancing lesion on the T1-weighted MRI was expanded by 1 mm for the planning target volume. Lesions <2 cm and 2-2.9 cm in size were prescribed 24 and 18 Gy in a single fraction, respectively. Lesions measuring 3-5 cm were prescribed 25 Gy in 5 fractions. Subjects received BVZ 10 mg/kg the day of SRS and 14 days later. The primary endpoint of the study was toxicity. Secondary endpoints included survival, cognitive function, and quality of life. Adverse events were scored using the NCI Common Terminology Criteria. Patients underwent baseline cognitive testing which was repeated 1 week and 2 months after SRS using the Mini-Mental State Exam and Trail Making Test. Results: 15 subjects were enrolled between 1/2010 and 1/2011. Median age and KPS were 53 years (range 25-66) and 90 (range 80-100). Median time from primary diagnosis to salvage SRS was 19.6 months. There were 5 treatment-related grade 2 adverse events including neuropathy, cognitive disturbance, dizziness, and fatigue. One patient experienced grade 3 headache requiring hospitalization. No patient experienced a cerebrovascular accident or thrombotic event. No grade 4/5 adverse events were seen. Cognitive testing scores did not significantly decrease 1 week or 2 months following SRS compared to baseline. After a median follow up of 5.7 months 14 of the 15 patients are alive. Conclusions: Treatment with concurrent SRS and BVZ in heavily pre-treated patients with a recurrent malignant glioma appears well tolerated. Further follow up in this and a larger patient cohort is needed to test the efficacy of this approach.
Forced vital capacity (FVC) as a reproducible measure of pulmonary function (PF) in chemotherapy-pretreated patients with malignant pleural mesothelioma (MPM).
Authors: L. M. Krug, J. M. Arduino, X. Sun, H. L. Kindler, C. Manegold, D. Fennell, G. M. Lubiniecki, P. Baas
Journal: Journal of Clinical Oncology (2011)

7028 Background: MPM often results in a constrictive lung function. The most appropriate measure of pulmonary function to assess this constriction is Forced Vital Capacity (FVC). The reproducibility and validity of FVC is evaluated in chemotherapy-pretreated patients. Methods: The randomized, double-blind, placebo-controlled Phase III trial of vorinostat vs. best supportive care is the largest trial ever conducted in patients with MPM, and has completed accrual. FVC was measured in chemotherapy-pretreated patients prior to the start of study therapy and at follow-up visits. Reproducibility of FVC was evaluated using intraclass correlation coefficient (ICC) between 2 baseline assessments. Validity of FVC was assessed by whether baseline FVC correlated with: patient-reported disease-related symptoms and health-related quality of life (HRQOL) using the Lung Cancer Symptom Score-Mesothelioma; and Karnofsky performance status (KPS); using a Cox proportional hazard model controlling for number of prior therapies, histologic subtype and KPS. Results: Of the 660 target patients, pulmonary function data are available for 633 patients. Baseline characteristics for 633 patients are: median age of 64 years, 84% men, 87% Caucasian, 88% Stage III or IV, and 87% KPS ≥ 80%. The median baseline FVC is 2.37 liters (L) (intra-quartile range: 1.85 L to 2.9 L). In 216 patients with two baseline assessments of FVC measured between 3 to 16 days apart, acceptable reproducibility is demonstrated (ICC=0.87, 95% CI: 0.83, 0.90). A higher baseline FVC was associated with 1) higher baseline KPS (Median FVC for KPS 70%=1.89 L, KPS 80%= 2.25 L; KPS 90%=2.52 L, KPS 100%=2.79 L) (p-value<0.05); and 2) baseline patient-reported HRQOL (r=0.30, p<0.001) and interference with normal activity (r=0.31, p<0.001) scores. Conclusions: The reproducibility and validity of FVC is demonstrated in this study. These findings support the assessment of FVC in clinical trials of patients with MPM.