tbuckley/cabot-search huggingface dataset:
Study on the relationship between radiation-induced lung injury and chemotherapy in the patients with non-small cell lung cancer (NSCLC) treated by three-dimensional conformal radiotherapy (3D-CRT)
Authors: J. Xing, J. B. Li, J. M. Yu, F. Shi, M. Xu, S. Y. Tian, Q. Shao, T. Y. Fan, C. Q. Liang, Y. J. Zhang
Journal: Journal of Clinical Oncology (2008)

7602 Background: To explore he relationship between radiation-induced lung injury and chemotherapy in the patients with non-small cell lung cancer (NSCLC) treated by three-dimensional conformal radiotherapy (3D-CRT) and to find out the liminal value of chemotherapy for the the prediction of radiation-induced lung injury. Methods: One hundred sixty-nine patients with stage I∼III of NSCLC who were treated by 3D-CRT and followed by CT scan for more than six months after 3D-CRT were selected, and all the patients were divided into five grades (grade 0 to grade 4) based on the CT image appearance of radiation-induced lung injury. The chemotherapy characters were reviewed to analyze the relationship between radiation-induced lung injury and chemotherapy factors. Results: In this study, the positive rate of CT appearance was significantly higher in the chemoradiotherapy group than in the radiotherapy group (72.73% vs. 45.83%, P=0.001). In different subgroups of chemoradiotherapy based on different regimens, no statistically significant difference of the positive rate of CT appearance is found (P=0.952). And in different subgroups of chemoradiotherapy based on different combination with radiation, the positive rate of CT appearance was significantly highest in the concurrent chemoradiotherapy group (94.74%) and lowest in the group treated with chemotherapy firstly and then with radiotherapy (50.19%), with the P value of 0.001. Conclusions: Chemoradiotherapy can increase the occurrence of radiation-induced lung injury after 3D-CRT for patients with NSCLC, especially in concurrent chemoradiotherapy. No significant financial relationships to disclose.
Classification procedure of the German version of the Cancer Fatigue Scale (CFS-D)
Authors: M. Reif, M. Kröz, F. Schad, H. von Laue, G. Feder, H. Matthes, M. Girke
Journal: Journal of Clinical Oncology (2009)

e20608 Background: Fatigue severely reduces quality of life in many cancer patients. Cancer related fatigue (CRF) occurs with anaemia, during and after chemo- or radiotherapy and in advanced tumour states. The Cancer Fatigue Scale (CFS) is a well validated 15-item, 3-dimensional inventory (physical, cognitive, affective). Our classification procedure of its German version aimed at best separation of fatigue in cancer patients from healthy controls. Methods: CFS-D study data was combined from two studies that included CSF-D evaluations: a) 21 breast cancer (BC) and 7 colorectal cancer (CRC) patients (from a group of 57 cancer patients) and all 57 matched-pairs healthy controls (C); b) 41 BC and 25 CRC patients with chemotherapy. Analysing repeated ratings, four groups were found to significantly differ in global CFS-D (N female/male): C 65/27, CRC with (+) viscum album (VA) 27/34, BC + VA 110/0, BC without (-) VA 30/0. In cut-off analyses of sum- and subscales we iteratively categorized the data using moving thresholds and calculated their chi-square (X 2 ) statistics when crossed with the study groups. CFS-D values were chosen as cut-off thresholds that yielded maximum X 2 values when tested in 2x2-, 3x4-, and 4x4-tables. We plotted ROC curves to check for congruency of cut-off and ROC values. Results: Global CFS-D median (min.-max.) were: C 18 (2–38), CRC 22 (1–46), BC + VA 27 (0–54), and BC - VA 29.5 (7–48). For global CFS-D, cut-off and ROC analyses indicated ‘unclear’ CRF starting at 23 and ‘probable’ at 30. Subscale results were less definite; maybe with categories ‘unclear’/‘probable’ for dimensions ‘physical’: 9/15, ‘cognitive’: 9/11, ‘affective’: 6/8. Conclusions: The CFS-D is a highly reliable and valid global CRF questionnaire indicating categories ‘probable’ &gt;= 30, ‘unclear’ at 23–29 and ‘none’ &lt; 23. Thresholds for CFS-D subscales are less clear-cut and can not simply be calculated as proportional fractions of the total scale. No significant financial relationships to disclose.
Effect of EGFR inhibition with cetuximab on the efficacy of paclitaxel in previously treated metastatic urothelial cancer.
Authors: Y. Wong, S. Litwin, E. R. Plimack, D. J. Vaughn, W. Song, S. M. Cohen, J. W. Lee, M. B. Dabrow, H. Tuttle, G. R. Hudes
Journal: Journal of Clinical Oncology (2011)

243 Background: The benefit of salvage chemotherapy such as weekly paclitaxel (TAX) is modest in metastatic (met) urothelial ca, with median TTP of ≤3 months and ORR of 10% (95% CI 4-18% [combined results, Vaughn 2002; Joly, 2009]). Cetuximab (CET) is a monoclonal antibody against the epidermal growth factor receptor (EGFR). High-grade urothelial cancer overexpress EGFR. We conducted a multicenter randomized, noncomparative phase II study to measure the efficacy of CET ± TAX in patients (pts) with previously treated met urothelial cancer. Methods: Pts with met urothelial cancer who received one line of chemotherapy in the adjuvant, neoadjvuant, or met setting were enrolled. Pts were randomized to CET 250mg/m 2 (after 400 mg/m 2 load) ± TAX 80 mg/m 2 weekly. A cycle was 4 weeks (wks). Response (RECIST) was assessed by imaging every 8 wks. We used early progression to assess futility (Litwin Stats Med 2007). Either arm would close if 7 of the initial 15 pts in that arm progressed at the first disease evaluation. Either arm would be considered promising if ≥9/28 patients had PFS&gt;16 wks (90.4% power to detect an improvement in Median [Med] PFS from 8 to 16 wks with a 7.1% type 1 error). Results: We enrolled 39 evaluable pts (30 male). Median age was 69 years (range 49-79). All pts received prior platinum-based chemotherapy. CET arm closed after 9 of the first 11 pts progressed by 8 wks (ASCO GU 2009). CET-TAX arm completed full accrual (28 pts), of which 11 had visceral disease and 13 received chemo for met disease. 10/28 pts had PFS&gt;16 wks. Overall RR was 28.5%, (8/28 pts, 95% CI 13-49%) (2 CR, 6PR). 4 additional pts had unconfirmed PR. 2 pts have maintained PR 3 and 4 months after discontinuing CET-TAX. Med PFS for the CET-TAX was 115 days (16 weeks)(95% CI 58-174 days). Med PFS for pts with visceral disease was 84 days (95%CI 50-NR). Med PFS for pts who received prior chemo for met disease was 142 days (95% 58-NR). Med number of cycles for the CET-TAX was 3 (range 0-25). Grade 3 AEs occurring in more than 2 pts were rash (5), fatigue (4), anemia (4), low magnesium (3). Conclusions: EGFR inhibition with CET appears to augment the antitumor activity of TAX in pts with previously treated urothelial cancers. The CET-TAX combination merits further study to establish its role in treatment of urothelial cancers. [Table: see text]
Differential release and deposition of S100A8/A9 proteins in inflamed upper airway tissue
Authors: Koen Van Crombruggen, Thomas Vogl, Claudina Pérez-Novo, Gabriele Holtappels, Claus Bachert
Journal: European Respiratory Journal (2015)

Intracellular Ca(2+)-binding S100A8/A9 proteins gain novel functions when released during inflammation. The exact outcome of their extracellular function depends on the local tissue environment in which they are released; both anti-inflammatory and pro-inflammatory responses are described, modulating the immune system by binding Toll-like receptor (TLR)-4 or the receptor for advanced glycation end-products (RAGE). However, the contribution of the proteins in the pathophysiology of chronic rhinosinusitis (CRS) remains unclear.Homomeric S100A8 and S100A9, and heteromeric S100A8/A9 proteins were evaluated in CRS with/without nasal polyps (CRSw/sNP) and controls. Functional responses were assessed in polyp tissue stimulated with S100 proteins in the presence of TLR-4 and RAGE blocking antibodies.S100A8, S100A9 and S100A8/A9 protein levels were significantly higher in CRSwNP patients, showing increased deposition on extracellular matrix (ECM) structures of CRSwNP tissue in contrast to CRSsNP and controls. In the presence of Staphylococcus aureus, S100A8/A9 is released from neutrophils and from the ECM. Extracellular S100A8 and S100A9 proteins induced increased levels of diverse inflammatory mediators via TLR-4 engagement.The inflammatory/remodelling characteristics of CRSwNP specifically allow increased retention of S100A8, S100A9 and S100A8/A9 proteins in the ECM of CRSwNP tissue. Upon release, homodimeric proteins act as a local danger signal inducing inflammatory mediators, predominantly via TLR-4 activation.
Adjuvant multipeptide vaccination in high-risk renal cell carcinoma.
Authors: S. Feyerabend, C. Gouttefangeas, S. Stevanovic, D. Wernet, J. Hennenlotter, J. Bedke, A. Droege, K. Laske, H. Rammensee, A. Stenzl
Journal: Journal of Clinical Oncology (2010)

e15051 Background: We conduct an immunotherapy-based adjuvant phase I/II clinical trial using individual multi peptide vaccination in advanced or metastatic renal cell carcinoma after R0 resection. Both MHC-class I and –class II binding peptides derived of various tumor-associated antigens (TAA) are applied in order to activate CD8+ and CD4+ T-cell effectors in vivo. Study endpoints are side effects and disease free survival. Methods: Peptide cocktails of TAA are selected according to the HLA-typing and applied subcutaneously combined with either GM-CSF or Montanide ISA51 as adjuvant for 12 months or until progression. HLA-A1+, A2+, A3+, B7+ and B8+ patients receive a fixed peptide mix containing between 3 to 10 HLA-class I epitopes and ligands. Patients expressing other HLA-class I alleles are never the less treated with an individual peptide mix. Additionally, all patients receive HLA-DR-restricted epitopes. Imaging is performed every three months to evaluate progression-free survival. T-cell activity and specificity are tested with Elispot assay and by flow cytometry with intracellular cytokine staining or HLA-multimer staining after in vitro sensitization. Results: 21/40 patients have terminated the treatment so far. No adverse event greater than I° CTCAE 3.0 occured. 10 stage III patients have a median progression-free survival of 44 months (range 7-75) so far and 2/10 experienced progression after 7 and 16 months. 8/11 stage IV patients have progressed during treatment after a median of 13 months (range 4-29) after the most recent metastasectomy. Progression free survival of 11 stage IV patients is 16 months (range 4-29) at interim data analysis. In the majority of the patients tested so far, a strong induction or increase of CD4+ T cells specific for 1 to 3 of the HLA-class II injected peptides is observed after vaccination. A good proportion of HLA- A2+ patients develop specific CD8+ T cell responses with Cyclin D being recognized frequently. Conclusions: The immune modulating approach shows no side effects. The results may indicate that in patients with low tumor burden stage III disease multi peptide vaccination is promising. No significant financial relationships to disclose.
Pediatric and AYA invasive cutaneous melanoma: Population-based study comparing adult melanoma cases
Authors: P. Cinar, J. A. Zell, T. H. Taylor, L. S. Sender, H. Anton-Culver
Journal: Journal of Clinical Oncology (2008)

9071 Background: Prior studies have reported possible survival differences between pediatric, AYA and the adult population with invasive cutaneous malignant melanoma (MM). However, none have analytically compared these different age groups. We set out to determine differences in incidence and survival for MM by age group for each stage by using the population-based California Cancer Registry (CCR) database. Methods: We performed a retrospective, case-only analysis of MM cases in the CCR database (1993–2003). Cases were grouped according to the diagnosis age: <15, 15–19, 20–30 and >30 years. Age-specific incidence rates for these age groups were calculated using the standardized population for California. For ages ≤30 and >30, overall survival (OS) and melanoma-specific survival (MSS) was calculated by univariate analyses using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios. Results: 38,996 incident MM cases were analyzed (<15 years: 61 cases, 15–19 years: 257 cases, 20–30 years: 1,976 cases, >30 years: 36,702 cases). Incidence rates per 100,000 cases were higher for females than males for age 15–19 years (1.15 and 0.75) and age 20–30 years (4.07 and 2.23). However, for age >30 years, the incidence rate was higher for males compared to females (21.89 and 14.68). After adjustment for gender, histology, AJCC stage, anatomic site and SES, a statistically significant decreased risk of death was observed for females compared to males in both age groups (Table 1). In the adjusted analyses, high SES quintile was associated with improved survival only for cases >30 years of age. Conclusions: Among cases aged 15–30 years, incidence of MM is higher among females than males; after age 30, incidence is higher among males. Females in all age groups are observed to have decreased risk of death compared to males. Cases ≤30 years at diagnosis have improved survival compared to older cases and SES differences do not independently predict survival among this young age group. Adjusted Cox Models of Melanoma-Specific Survival in Patients with Invasive Melanoma, 1993–2003 ≤30 years old >30 years old Female 0.49 (0.32- 0.75) 0.74 (0.68-0.81) Stage II 10.65 (6.34-17.87) 5.07 (4.61-5.58) Stage III 17.98 (10.62-30.43) 11.95 (10.67-13.38) Stage IV 26.27 (6.80-101.36) 45.52 (38.41-53.94) Second Lowest SES 0.67 (0.32-1.43) 0.92 (0.79-1.07) Middle SES 0.76 (0.38-1.53) 0.82 (0.71-0.95) High SES 0.57 (0.28-1.15) 0.72 (0.63-0.83) Highest SES 0.70 (0.34-1.44) 0.66 (0.57-0.76) Reference groups: Male (Gender), Stage I (AJCC Stage), Lowest SES Quintile (SES) No significant financial relationships to disclose.
Assessment of early response to imatinib 800 mg after 400 mg progression by 18f-fluorodeoxyglucose positron emission tomography in patients with metastatic gastrointestinal stromal tumor.
Authors: A. Rodriguez Espíndola, M. Chacon, M. Eleta, E. Roca, G Mendez, S. Rojo, C. Puparelli, R Chacon
Journal: Journal of Clinical Oncology (2010)

10081 Background: Imatinib is the standard first-line therapy for advanced GIST patients. 18 F- fluorodeoxyglucose positron emission tomography (FDG-PET/CT) shows a faster response than CT in nonpretreated patients. After disease progression on imatinib 400 mg, FDG-PET/CT scans were performed to evaluate early response to imatinib 800 mg. Methods: After disease progression on imatinib 400 mg, 16 patients had their dose escalated to 800 mg and tumor response was evaluated by FDG-PET/CT on days 7 and 37. Objective assessment was performed according to the recommendations of the European Organization for Research and Treatment of Cancer (EORTC) PET Study group. The primary objective was to correlate early metabolic response with progression-free survival (PFS). Secondly, metabolic assessment, Response Evaluation Criteria in Solid Tumors (RECIST) and Choi criteria were compared. Ninety-five lesions were assessed in 46 FDG-PET/CT. Results: Early metabolic assessment by FDG-PET/CT scan was not predictive of PFS in advanced GIST patients treated with imatinib 800 mg daily. Median PFS was 5.3 months. Gastric primary site and previous exposure to imatinib 400 mg for over 12 months were statistically significant positive predictive factors for PFS (p 0.02). Three partial responses were observed on day 7 FDG-PET/CT but time to progression was 2 months (range 2-3). No objective responses according to RECIST criteria were observed on Day 7 or 37. There was a trend towards an earlier identification of partial responses or disease progression with PET and Choi than RECIST. In this group of patients, OS was only influenced by gastric primary site (p 0.05). Metabolic response or other clinical-molecular variables did not impact in OS. Conclusions: The assessment of early metabolic response by FDG-PET/CT in advanced GIST patients exposed to imatinib 800 mg was not predictive of PFS or OS. No significant financial relationships to disclose.
BIG 1–98: A randomized double-blind phase III study comparing letrozole and tamoxifen given in sequence vs. alone as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer
Authors: H. T. Mouridsen, A. Keshaviah, L. Mauriac, J. Forbes, R. Paridaens, M. Castiglione-Gertsch, R. Gelber, I. Smith, B. Thuerlimann, A. Goldhirsch
Journal: Journal of Clinical Oncology (2006)

LBA528 Background: The Primary Core Analysis (PCA) of BIG 1–98 comparing letrozole (L) to tamoxifen (T) as initial adjuvant endocrine therapy showed that L significantly prolonged disease-free survival (DFS), particularly reducing the risk of relapse in distant sites, compared with T for postmenopausal women with endocrine-responsive breast cancer (BC). The aim of the Second Primary Analysis (SPA) is to compare L and T given in sequence vs. alone. On Mar 15, ‘06, the Data Safety Monitoring Committee (DSMC) will review the results of the 2nd interim analysis of the SPA. We will present safety and efficacy data from this analysis if the DSMC recommends release of the results. Methods: 8028 women were randomized upfront to Tx5 years (yrs) (A), Lx5 (B), Tx2→Lx3 (C), or Lx2→Tx3 (D); 1835 to the 2-arm option of the study (arm A vs. B; Mar ’98 - Mar ‘00) and 6193 to the 4-arm option (arm A vs. B vs. C vs. D; Apr ’99 - May ‘03). The primary endpoint was DFS (time from randomization to first occurrence of invasive BC recurrence, invasive contralateral BC, second non-breast malignancy, or death from any cause). The SPA is comprised of two pair-wise comparisons: arm A vs. C and B vs. D. Only 4-arm patients (pts) alive and disease-free at 2 yrs after study entry (corresponding to the treatment switch for arms C and D) are included. These analyses will determine if the risk of an event beyond 2 yrs is reduced by switching agents. Additional exploratory analyses based on all events and follow-up (FU) for 4-arm pts will be conducted, including the comparison of arm B vs. C. The final SPA is planned for Feb ‘08, after 662 events. In Jan ‘05, the 1st interim efficacy analysis was presented to the DSMC, after 162 events among 3641 pts (excluding those who had an event within 2 yrs or did not yet have at least 2 yrs of FU). The median SPA FU (from 2 yrs after study entry) was 11.1 months. The 2nd interim efficacy analysis will be presented to the DSMC on Mar 15, ‘06 based on data received as of a Dec 21, ‘05. Results: Conclusions: No significant financial relationships to disclose.
Neoadjuvant chemotherapy improves outcomes of chemoradiation therapy for locally advanced pancreatic cancer
Authors: V. Rana, S. Krishnan, J. L. Abbruzzese, H. Q. Xiong, G. R. Varadhachary, L. Ho, N. A. Janjan, D. B. Evans, R. A. Wolff, C. H. Crane
Journal: Journal of Clinical Oncology (2006)

4036 Background: Two-thirds of all pancreatic cancer patients have radiographically detectable metastatic disease at the time of diagnosis. Most of the remaining patients have locally advanced, unresectable disease that is typically treated with either chemoradiation or chemotherapy alone. We explored the possible benefit of the use of consolidative chemoradiation after induction chemotherapy. Methods: Between December 1993 and October 2005, 318 patients with locally advanced, non-metastatic, pancreatic cancer were treated at our institution with concurrent chemoradiation therapy. All patients underwent CT staging and biopsy confirmed adenocarcinoma. 245 patients received chemoradiation (CR) as initial treatment while 73 patients received a median of 2.5 months of induction chemotherapy prior to chemoradiation (CCR). Radiosensitizers included 5FU (42%), gemcitabine (39%) and capecitabine (19%) and most patients (88%) received 30 Gy of radiation therapy. The most common induction chemotherapy regimens were gemcitabine and cisplatin (73%) and gemcitabine alone (15%). Results: All statistics are actuarial and calculated from date of initial treatment. Median follow-up was 5.5 months (range 1–63 months). For all patients, overall survival was 9.0 months and 2-year survival was 8%. Age, gender, histology, grade, radiation fractionation and concurrent chemotherapy regimen had no impact on outcomes on univariate analysis. However, overall survival was 8.5 months in the CR group and 11.9 months in the CCR group (p = 0.0004). Median time to local progression was 6.0 months in the CR group and 8.4 in the CCR group (p = 0.0055). Median time to distant progression was 5.8 months in the CR group and 9.5 months in the CCR group (p=0.0136). Conclusions: In one of the largest series of locally advanced pancreatic cancer patients, the use of induction chemotherapy followed by chemoradiation seems to prolong median survival over initial treatment with chemoradiation. By excluding patients who progress rapidly during induction chemotherapy, this approach presumably selects patients most likely to benefit from a local treatment modality. This strategy merits prospective evaluation. [Table: see text]
Magnitude of HER2 amplification as a predictive factor for HER2-overexpressing metastatic breast cancer treated with weekly paclitaxel plus trastuzumab as first-line chemotherapy
Authors: H. Han, J. Kim, S. Im, J. Park, S. Oh, D. Oh, J. Kim, K. Lee, T. Kim, Y. Bang
Journal: Journal of Clinical Oncology (2008)

1053 Background: Trastuzumab is an active agent for HER2 overexpressing metastatic breast cancer (MBC). We evaluated the efficacy and safety of weekly paclitaxel plus trastuzumab as a first line chemotherapy in women with HER2-overexpressing MBC. Furthermore, we analyzed the role of HER2 amplification ratio as a predictive factor for this regimen. Methods: Fifty-four patients of HER2- overexpressing MBC were treated with weekly pacllitaxel plus trastuzumab as first-line chemotherapy by preformed chemotherapy protocol. HER2 overexpression defined as 3+ by IHC or as HER2/CEP17 ratio of ≥ 2.0 by FISH. Treatment consisted of weekly paclitaxel at 80mg/m2, immediately followed by trastuzumab at 4mg/kg as a loading dose, and 2mg/kg i.v. given weekly thereafter. Clinicopathologic parameters were analysed. Results: From Feb 2004 to Dec 2006, 54 patients with HER2-overexpressing MBC were enrolled and 51 patients are evaluable. The overall response rate was 84.3% (95% CI, 70.9 to 92.5), 9 patients achieved complete response, 34 patients partial response. At the median follow-up of 28 months, the median time to progression (TTP) was 17.7 months (95% CI, 7.3 to 28.2) and the median overall survival was 25.6 months (95% CI, 21.8 to 27.3). Therapy was generally well tolerated, although three patients (5.9%) had reversible, symptomatic heart failure. When the patients classified by HER2/CEP17 ratio ≤ 4.0 and > 4.0 cut-off value, there was a statistically significant difference in TTP; 10.8 and 23.2 months, respectively (P= 0.034) and HER2/CEP 17 ratio > 4.0 was a significant predictive marker for TTP in multivariate analysis (P=0.032). Conclusions: The combination of weekly paclitaxel plus trastuzumab as a first-line chemotherapy was a well tolerated and effective regimen for patients with HER2-overexpressing MBC. The magnitude of HER2 amplification was an independent predictive factor for TTP in HER2-overexpressing MBC confirmed by FISH. No significant financial relationships to disclose.