tbuckley/cabot-search huggingface dataset:
Level of scientific evidence underlying palliative care recommendations arising from the National Comprehensive Cancer Network (NCCN) clinical practice guidelines.
Authors: Felipe Melo Cruz, Fernando Mauro Lima Prearo, Daniel Iracema Cubero, Auro Del Giglio
Journal: Journal of Clinical Oncology (2012)

e19537 Background: The palliative care NCCN recommendations are classified according to the level of scientific evidence in four groups: category I, high level of evidence with uniform consensus; category IIA, lower level of evidence with uniform consensus; category IIB, lower level of evidence without a uniform consensus but with no major disagreement; and category III, any level of evidence but with major disagreement. Palliative care guidelines have not yet been judged as to the relative content of each of the aforementioned types of recommendations. Methods: We analyzed the distribution of categories of evidence cited in the 10 supportive care NCCN guidelines, version 2.2011. Results: Of the 2,537 recommendations found in the 10 guidelines, the proportion of category I, IIA and IIB recommendations were 2.9%, 95.7%, 1.4%, respectively. There wasn’t any category III recommendation (table 1). The fields with a higher rate of category I recommendations were fatigue (14.3%) and chemotherapy induced nausea and vomiting (12.7%). No category I recommendations were found on Senior Adult Oncology, Cancer and Chemotherapy induced Anemia and Adult Cancer Pain. Conclusions: : Palliative care NCCN recommendations are largely based on lower level of evidence, but with uniform expert opinion. This data show the urgent need to expand palliative care research in oncology. [Table: see text]
Efficacy and tolerability of lenalidomide (LEN) in patients (pts) 75 and older versus those younger than 75 with RBC transfusion-dependent low/int-1-risk MDS and del 5q.
Authors: Pierre Fenaux, Agnes Guerci-Bresler, Petra Muus, Mikkael A. Sekeres, Aristoteles Giagounidis, H Joachim Deeg, Peter Greenberg, Barry Skikne, Xujie Yu, Alan F. List
Journal: Journal of Clinical Oncology (2012)

6522 Background: LEN is the approved treatment for pts with RBC transfusion-dependent Low/Int-1-risk MDS and del 5q. In 2 multicenter trials (MDS-003/-004) LEN lead to RBC transfusion independence (TI) for ≥ 26 wks in 35–58% of pts and cytogenetic response (CyR) in 25–73%. Most common grade (G) 3–4 adverse events (AE) were neutropenia and thrombocytopenia, a safety concern in elderly pts. We evaluated efficacy and tolerability of LEN in pts ≥ 75 y vs &lt; 75 y in MDS-003/-004 trials. Methods: Pts received LEN 5 mg × 28 d, 10 mg × 21 d, or 10 mg × 28 d (all 28 d cycles). Dose reductions were required for G4 neutropenia (both trials) and platelet counts &lt; 30 x 10 9 /L (MDS-003) or &lt; 25 x 10 9 /L (MDS-004). Results: 32% of the 286 pts were ≥ 75 y. Baseline (BL) characteristics, LEN treatment, and optional G-CSF use are shown in Table. In pts ≥ 75 y vs &lt; 75 y: RBC-TI ≥ 26 wks was 39 vs 47% (P = NS); CyR was 64 vs 54% (P = NS); 2-y AML progression rates were 10 vs 19% (P = NS); 2-y overall survival rates were 62 vs 73% (P = .001); G3–4 AE: neutropenia (63 vs 76%; P = .024), thrombocytopenia (56 vs 49%; P = NS), infection (36 vs 20%; P = .003); median time to recovery to ANC &gt; 1 x 10 9 /L was 0.7 vs 0.7 mo (P = NS) and to platelet counts &gt; 100 x 10 9 /L was 3.3 vs 1.7 mo (P = NS). 59% pts ≥ 75 y and 49% pts &lt; 75 y discontinued LEN due to AE (33 vs 26%; P = NS), lack of effect (32 vs 49%; P = NS), or death (15 vs 6%; P = NS). Dose reduction and discontinuation rates are shown in Table. Conclusions: Pts ≥ 75 y and &lt; 75 y had comparable response and AML progression rates. In pts ≥ 75 y, LEN appears to be well tolerated but the higher infection rate justifies close follow-up. [Table: see text]
A phase III, multicenter, randomized trial of maintenance versus observation after achieving clinical response in patients with metastatic breast cancer who received six cycles of gemcitabine plus paclitaxel as first-line chemotherapy (KCSG-BR 0702, NCT00561119).
Authors: Young-Hyuck Im, Yeon Hee Park, Kyung Hae Jung, Seock-Ah Im, Joo Hyuk Sohn, Jungsil Ro, Sung-Bae Kim, Jin-Hee Ahn, Do Youn Oh, Sae-Won Han, Soohyeon Lee, In Hae Park, Keun-Seok Lee, Jee Hyun Kim, Seok Yun Kang, Moon Hee Lee, Hee Sook Park, Jin Seok Ahn
Journal: Journal of Clinical Oncology (2012)

1003 Background: Chemotherapy provides a survival benefit in patients with metastatic breast cancer (MBC), but the optimal duration of chemotherapy remains controversial. Primary purpose of the study was to evaluate whether the maintenance chemotherapy with gemcitabine/paclitaxel (GP), which is one of the two regimens which showed a survival gain from a randomized trial, is superior to observation in terms of progression free survival (PFS) in responding patients with MBC after 6 cycles of GP as first-line treatment. Methods: This study is a prospective, randomized, multi-center, phase III study. Patients who achieved response (CR+PR+SD) following 6 cycles of GP chemotherapy (gemcitabine 1250 mg/m 2 on day 1 and 8 plus paclitaxel 175 mg/m 2 on day 1 every 3 weeks) randomized to maintenance till progression or observation arm. The trial was conducted by the Korean Cancer Study Group (KCSG). Results: Among total 324 patients enrolled between 2007 and 2010 from 10 centers, 231 responding patients to were randomly assigned to maintenance chemotherapy (n=116) or observation (n=115). Median age was 49 (range 28-76). The numbers of hormone receptor (HR)+ve and HR-ve patients were 172 (74.5%) and 59 (25.5%), respectively. The median No. of chemotherapy cycles in maintenance group was 12 (range 6-32). During median 33 months of follow-up, median PFS was superior in maintenance than in observation (12.0 vs. 8.3 months, p=0.030). Patients &lt; age 50 years (hazard ratio 0.50, p=0.001) and HR-ve patients (hazard ratio 0.52, p=0.019) received more benefit from maintenance chemotherapy in terms of PFS. Median OS was superior in maintenance than in observation (36.8 vs 28.0 months, p=0.047). Neurotoxicity (≥ grade 2) was more common in maintenance than in observation without statistical significance (41.7% vs 33.3%, p=0.210). Serial assessment of Quality of Life (QoL) did not show any significant difference between two groups. Conclusions: Maintenance GP chemotherapy for responding patients with MBC showed clinical benefit in terms of PFS and OS without impairment of QoL.
BRCA1 methylation status in high-grade serous ovarian cancer (HGSOC) patients (pts).
Authors: Ilary Ruscito, Elena Ioana Braicu, Pierluigi Benedetti Panici, Radoslav Chekerov, Desislava Dimitrova, Ram N. Ganapathi, Ines Vasconcelos, Filippo Bellati, Christina Fotopoulou, Werner Lichtenegger, Sven Olek, Jalid Sehouli
Journal: Journal of Clinical Oncology (2012)

5070 Background: Mutations in BRCA1/2 genes contribute to increase risk for breast and ovarian cancer (OC).Hypermethylation of CpG islands in gene promoter regions is considered a frequent mechanism associated with inactivation of tumor suppressor genes which contributes to oncogenic transformation. Studies identified methylation changes in OC pts. Most of the studies analyzed a small cohort and combined different histological subtypes. HGSOC is a special entity of OC associated with poorer OS. Aim of this study was to analyze the clinical impact of BRCA1 promoter gene methylation status in HGSOC. Methods: The cohort comprised 127 HGSOC treated by cytoreduction followed by platinum-based chemotherapy at Department of Gynecology, Charité Medical University Berlin, Germany. Fresh frozen OC tissues provided by TOC were examined to access the tumoral tissue quality. Samples presenting at least 50% of tumour area were included within this study. DNA was extracted followed by sodium bisulfite conversion, and assessment of BRCA1 gene promoter methylation rate was determined by PCR. Statistical analisys has been carried out using SPSS software. Results: In our study, 14.2% of the pts presented a hypermethylation of the BRCA1 promoter gene. The hypermethylation of BRCA1 promoter gene was significantly more frequently encountered in the younger pts (&lt;59 yrs: 77.8% in the Hypermethylation Group vs 47.7% in the Hypomethylation Group, p=0.022). No differences in methylation status between primary and metastatic tissue from OC pts could be observed. Also no correlation with FIGO stage was observed. Optimal tumor debulking could be reached in most of the pts (57.5%), without significant differences between both groups. Platinum response rates were similar between both groups. No differences in PFS and OS could be observed. Conclusions: The study shows that HGSOC pts presenting the BRCA1 gene promoter in the methylated status, developed the disease significantly earlier with respect to OC patients with unmethylated BRCA1 gene promoter. The clinical outcome was similar in HGSOC independently from BRCA1 methylation status.
Persistent Cytotoxic T Lymphocyte Expansions after Allogeneic Hematopoietic Stem Cell Transplantation: Kinetics, Clinical Impact and Absence of STAT3 Mutations
Authors: Julia Muñoz-Ballester, Tzu Hua Chen-Liang, Ana María Hurtado, Pastora Iniesta, María Dolores García-Malo, José Bartolomé Nieto, José Padilla, Raul Teruel Montoya, Maria del Mar Osma, María Luisa Lozano, Felipe de Arriba, Francisco José Ortuño, Inmaculada Heras, Vicente Vicente, Cristina Castilla-Llorente, Andres Jerez
Journal: Blood (2015)
Influence of the department on the resection rate in palliative treatment of metastatic colorectal cancer (CRC)
Authors: A. Wein, T. Liersch, R. Hofheinz, J. Fahlke, J. Wilke, W. M. Brueckl, G. Maennlein, F. Boxberger, R. Kohnen, E. G. Hahn, W. Hohenberger
Journal: Journal of Clinical Oncology (2006)

13528 Background: During the last years due to the application of Irinotecan, Oxaliplatin and “biologicals” for the first- and secondline treatment of CRC in palliative situation the efficacy of palliative treatment has considerably improved with an acceptable toxicity. The achievements of secondary metastatic resection after downsizing by palliative treatment have increasingly become the focus of interest in palliative patients and opened up new ways in terms of curative options (Folprecht et al. 2005; Wein et al. 2001). Here, we analyse the influence of different departments on the resection rate after palliative treatment. Methods: A prospective phase III trial in metastatic CRC with systemic treatment by 5-FU/sodium FA as a 24h-infusion (AIO) versus AIO plus Oxaliplatin followed by secondary metastatic resection. Trial start: 2000; end of trial: 2005. Randomized patients: n = 240 by 5 centers experienced in clinical trials. In order to achieve a homogeneous patient group, non-resectability of distant metastases was required according to pre-defined criteria. Stratification characteristics: In accordance to the participating departments; ECOG index 0.1 vs 2. Involvement of the hepatic tumour extension 25% vs other localisation; organ manifestation 1 vs &gt; 1. Inclusion criteria: Definitively non-resectable metastases. Palliative first-line treatment: Histologically proven adenocarcinoma of the colon or rectum, unambiguous enlargement of metastatic masses in objective imaging procedures. At least one bidimensionally measurable tumour lesion. Age: &gt; 18, &lt; 75 years. Exclusion criteria: Concomitant treatment with other anti-neoplastic substances. Sensoric neuropathy. Results: Resected/randomized patients of 176 currently evaluable patients, both treatment groups combined: department (dep.) 01: 0/26 (0%), dep. 02: 10/27 (37.0%), dep. 03: 21/68 (30.9%), dep. 04: 8/43 (18.6%), dep. 05: 1/12 (8.3%), total: 40/176 (22.7%). Although in the total population, a remarkable resection rate could be achieved, the variation between the departments is high (p=.0043 for differences between departments). Conclusions: The resection rate after palliative CRC treatment essentially depends on the department. No significant financial relationships to disclose.
Glucose metabolism and bladder cancer.
Authors: Eugene K. Lee, Karim Pirani, Jeffrey M. Holzbeierlein, Paige Martin, Parthasarathy Rangarajan, Jill Hamilton-Reeves, Shrikant Anant
Journal: Journal of Clinical Oncology (2017)

359 Background: To understand and evaluate the role of glucose metabolism in bladder cancer growth, in the identification of disease, and development of potential treatment strategies. Methods: UMUC3, T24 and 253JBV cells were grown in varying glucose concentrations (25, 100 and 200mg/dl) and cell proliferation assay with Vi-Cell was performed. Next, we used Qiagen PCR array of glucose metabolic pathway of the UMUC3 cell line under different glucose concentrations. PKM2 is a driver of glycolysis and exists in an inactive dimer or active tetramer. Dimer PKM2 also known as Tumor M2-PK was measured in urine samples of bladder cancer patients using a commercially available ELISA kit (ScheBo Biotech AG). Lastly, Shikonin, a PKM2 inhibitor was evaluated as an inhibitor of bladder cancer cell proliferation using Vi-Cell. Results: Increased glucose concentration 200mg/dl leads to increased proliferation in bladder cancer cells while decreased concentration of glucose; 25mg/dl reduces proliferation compared to control (100). PCR array demonstrates genes in the glycolytic pathway genes are upregulated in cells that are grown in 200mg/dl glucose media and the TCA cycle genes are upregulated in cells that are subjected to the 25mg/dl glucose media when compared to control (100mg/dl). The enzyme pyruvate kinase M2 (PKM2) controls the transition from the glycolytic pathway to TCA cycle. We have found that 9/10 (90%) of bladder cancer urine samples show elevated levels of tumor M2-PK (&gt;104) compared to urine from two normal subjects (~30 units ) using a commercially available ELISA kit. Conclusions: Increased glucose concentration 200mg/dl leads to increased proliferation in bladder cancer cells while decreased concentration of glucose; 25mg/dl reduces proliferation compared to control (100).
Sentinel lymphadenectomy guided complete lymph node dissection improves loco-regional disease control in early-stage head and neck melanoma
Authors: J. H. Lee, R. Essner, L. Wanek, D. Morton
Journal: Journal of Clinical Oncology (2004)

7552 Introduction: The utility of lymphatic mapping (LM) and sentinel lymphadenectomy (SL) in head and neck (H&N) melanoma is still debated. The purpose of this study is to determine the therapeutic efficacy of LM/SL-directed surgical clearance of tumor-involved lymph node (LN) basins in early-stage cutaneous H&N melanoma. Methods: Database query identified all cutaneous H&N melanoma patients who were seen at our institution within first 3 months of diagnosis and underwent surgery between 1974 - 2002. Inclusion criteria were stage I - III, wide local excision (WLE) only, WLE/SL ± complete lymph node dissection (CLND), and at least 1-year of follow-up. Exclusion criteria were mucosal melanoma and stage III with palpable LNs. Group 1 underwent WLE only, whereas Group 2 underwent WLE/SL + CLND if sentinel node contained metastatic tumor. Patients from each group were matched for Breslow thickness (0 - 1 mm, 1.01 - 2 mm, 2.01 - 3 mm, 3.01 - 4 mm, > 4 mm), primary site (face/nose, scalp, ear, neck), and gender. 5-year disease free survival (DFS), loco-regional recurrence (LRR), and times to LRR were measured. χ2 and log-rank tests were used to determine statistical significance. Results: Of 604 eligible patients, 176 patients from each group (total of 352) were matched for above prognostic factors. Distribution of Clark level (p = 0.16) and % of patients with ulceration (p = 0.63) were not different. 5-year DFS rates were not statistically different (65 ± 4% for Group 1 vs. 71 ± 4 for Group 2; p = 0.287). However, the difference in LRR was statistically significant (Group 1: 20% vs. Group 2: 6.3%; p = 0.0001). Despite differences in median follow-up times (99 vs. 51 months), the median/mean times to LRR were not different (Group 1: 12/26 months vs. Group 2: 13/36 months; p = 0.56). Conclusions: Our data indicate that LM/SL-directed surgical clearance of melanoma-involved LN basins decreases the incidence of LRR for early-stage cutaneous H&N melanoma. Its therapeutic superiority in controlling loco-regional disease, when compared to WLE alone, provides a de-facto evidence of validity for application of LM/SL in early-stage cutaneous H&N melanoma. No significant financial relationships to disclose.
Incidence and outcomes of hospitalized patients with gastrointestinal malignancies and <i>Clostridium difficile</i> infection: A nationwide analysis.
Authors: Arjun Gupta, Raseen Tariq, Nivedita Arora, Ryan D. Frank, Muhammad S. Beg, Darrell S. Pardi, David H. Johnson, Sahil Khanna
Journal: Journal of Clinical Oncology (2017)

704 Background: Inpatients with gastrointestinal (GI) malignancies are at a high risk for Clostridium difficile infection (CDI) but the impact of CDI on outcomes in these patients needs elucidation. We analyzed the incidence of CDI and its impact on outcomes in GI cancer patients using the National Hospital Discharge Survey (NHDS) database from 2001 - 2010. Methods: NHDS collects clinical information on patients dismissed from non-Federal short-stay United States hospitals. Demographics, diagnoses (GI malignancies, CDI and comorbidities), length of stay (LOS), and dismissal information were abstracted using ICD-9 diagnosis and procedure codes. Weighted analyses were performed using SAS version 9.4. Results: Of an estimated 317.9 million unique hospitalizations; 4.6 million had a diagnosis of a GI malignancy (1.4%); median age 68 years, 46.1% female. CDI was more common in patients with GI malignancies compared to patients with no GI malignancy (1.05% vs 0.69%, aOR 1.16, 95% CI 1.15- 1.17, p &lt; 0.0001). There was a significant increase in CDI incidence in GI cancer patients over the 10-year study period (72.7 in 2001-2002 to 109.1 in 2009-2010, per 10,000 discharges, p &lt; 0001). In multivariable analysis, compared to GI cancer patients without CDI, GI cancer patients with CDI had a longer mean LOS (3.94 more days, 95% CI 3.31-4.56) and dismissal to a care facility (adjusted OR, 1.75; 95% CI, 1.71-1.79), but lower all-cause in-hospital mortality (adjusted OR, 0.76; 95% CI, 0.74-0.79), all p &lt; 0.0001 Conclusions: In this national database of hospitalized patients, an increasing incidence of CDI in patients with GI malignancies was noted over the study period. CDI prolonged hospitalization, and was associated with increased dismissal to a care-facility. Lower rates of in-hospital mortality may represent early diagnosis due to vigilance or a milder form of CDI. Despite increased attention over the last few decades, CDI remained a serious infection in GI cancer patients, and merits appropriate prevention, management and follow-up.
Cyclin D1 expression in breast cancer patients and tamoxifen therapy
Authors: M. Filipits, M. Rudas, M. Lehnert, E. Kubista, O. Dietze, R. Greil, S. Lax, H. Samonigg, R. Jakesz, M. Gnant
Journal: Journal of Clinical Oncology (2007)

523 Background: Adjuvant tamoxifen therapy improves survival of hormone receptor-positive breast cancer patients, but there is a subset of patients who fails to respond or develops resistance to tamoxifen. Cyclin D1 plays a central role in cell cycle regulation, directly affects the estrogen receptor and may predict outcome of tamoxifen therapy. Methods: We determined expression of cyclin D1 in formalin-fixed, paraffin-embedded surgical breast cancer specimens by means of immunohistochemistry. The patients had been enrolled in the Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 5 (test set) or ABCSG Trial 6 (validation set). Comparison of cyclin D1 expression with clinical parameters and survival of the patients was performed with cyclin D1 as a continuous variable and as a dichotomized variable. The median value of the percentage of cyclin D1-positive tumor cells was a priori chosen as cut-off point to classify cyclin D1- positive and cyclin D1-negative tumors. The cutpoint was established in the test set and validated in the validation set. Overall survival and relapse-free survival were analyzed with Cox models adjusted for clinical and pathological factors. Results: Cyclin D1 was positive (&gt;10% cyclin D1-positive tumor cells) in 140 of 253 (55%) tumors of the test set and in 569 of 948 (60%) tumors of the validation set. A benefit from adjuvant endocrine therapy was associated with absence of cyclin D1 in both cohorts. Overall survival was significantly shorter in patients with cyclin D1-positive tumors as compared to patients with cyclin D1-negative tumors (adjusted hazard ratio for death [test set], 2.47, 95% confidence interval [1.08–5.63] P=0.03; adjusted hazard ratio for death [validation set], 1.91, [1.45–2.51] P&lt;0.001). Relapse-free survival was also shorter in patients with cyclin D1-positive tumors than in patients with cyclin D1-negative tumors (adjusted hazard ratio for recurrence or death [test set], 2.73, [1.50–4.96] P=0.001; adjusted hazard ratio for recurrence or death [validation set], 1.60, [1.19–2.16] P=0.002). Conclusions: Women with early-stage, hormone receptor-positive breast cancer and cyclin D1-negative tumors benefit more from adjuvant tamoxifen therapy than women with cyclin D1-positive tumors. No significant financial relationships to disclose.
Phase II trial of epothilone B analogue BMS-247550 in advanced carcinoma of the urothelium (E3800): A trial of the Eastern Cooperative Oncology Group
Authors: R. Dreicer, S. Li, J. Manola, N. Haas, B. Roth, G. Wilding
Journal: Journal of Clinical Oncology (2006)

4543 Background: Patients (pts) with advanced urothelial carcinoma who progress following first line therapy have limited effective therapeutic options. The epothilones are a class of antineoplastics with a broad range of antitumor activity. We evaluated BMS-247550 in pts with advanced urothelial cancer having received 1 prior systemic therapy regimen. Methods: Pts with TCC or mixed histologies containing TCC received BMS-247550 40 mg/m 2 IV over 3 hours on day 1 of a 3-week cycle. Dose modifications occured for low granulocytes and/or platelets, mucositis, sensory neuropathy, and other Grade 3 or 4 toxicities. Pts remained on treatment until disease progression or unacceptable toxicity. Standard ECOG response criteria were used. Results: Total accrual (allowing for ineligible pts) was 45 pts, of whom 17 had received prior taxanes. One pt was ineligible (2 prior regimens) and was excluded from this analysis. Sixteen pts are still being evaluated for eligibility. The pt cohort was 82% male and 86% Caucasian. The median age was 63 (range 37–81), 70%, 7% and 23% had 1, 2 and 3 MSKCC risk factors respectively. Eighty-two % of pts had distant metastatic disease at study entry. A median of 2 cycles were administered (range, 1–8). The most common reasons for discontinuing treatment were progressive disease (65%) and toxicity (25%). Twelve pts experienced grade 4 toxicity, including leukopenia (n = 5), neutropenia (n = 9), ventricular arrhythmia, hypotension, DIC, stomatitis, elevated bilirubin, dyspnea, febrile neutropenia, hypoxia, acidosis, and elevated creatinine (n = 1 patient each). One pt died of cardiac failure following numerous grade 4 toxicities, including neutropenic infection. Two other deaths due to progressive disease occurred while pts were receiving treatment. Response information is available for 37 of 44 potentially eligible pts. There have been 5 partial responses, 3 among pts who had previously received taxanes, 17 pts had stable disease for at least 6 weeks. Conclusions: BMS-247550 has modest activity in pts with previously treated advanced TCC of the urothelium, but at the cost of modest-significant toxicity. Activity in pts previously treated with paclitaxel is of interest, however its ultimate utility remains undefined. [Table: see text]