tbuckley/cabot-search huggingface dataset:
Randomized trial of amifostine in locally advanced non-small cell lung cancer (NSCLC) patients receiving chemotherapy and hyperfractionated radiation (HRT): Long-term survival results of Radiation Therapy Oncology Group (RTOG) 9801
Authors: B. Movsas, J. Moughan, C. Langer, M. Werner-Wasik, N. Nicolaou, R. Komaki, M. Machtay, C. Smith, R. Axelrod, R. Byhardt
Journal: Journal of Clinical Oncology (2007)

7529 Purpose: This analysis was conducted to address the potential antitumor effect of amifostine (AM) in NSCLC patients enrolled on RTOG-9801. The long-term survival results of RTOG-9801 are presented here. Methods: 243 patients (pts) with stage II/IIIAB NSCLC received induction paclitaxel (P) 225 mg/m 2 IV days 1, 22 and carboplatin (C) AUC 6 days 1, 22 and then concurrent weekly P (50 mg/m 2 ) and C (AUC 2) and HRT (69.6 Gy at 1.2 Gy BID). Pts were randomly assigned to AM 500 mg IV 4x/week or no-AM during chemoradiation. Treatment differences for overall and disease-free survival (OS &amp; DFS) were analyzed with the log-rank test; Gray's test was used for time to progression (TTP). Results: 118 pts were randomly assigned to receive AM and 121 to no-AM (4 pts were ineligible). The median follow-up for pts still alive is 52.3 months (mo) for the AM-arm and 58.3 mo for the no-AM arm (16.6 vs 17.9 for all pts). There are no significant differences in OS, DFS or TTP between arms. The median survival, 3-yr, and 5-yr OS are 17.1 mo, 27% and 17% (AM-arm) vs 18.4 mo, 28% and 16% (no-AM arm) (p=0.97). Grade 3/4/5 late-RT toxicities are similar (11%/3%/2% AM-arm vs 14%/4%/2% no-AM arm). Conclusion: While an earlier publication reported that amifostine did not reduce objective measures of severe esophagitis in RTOG-9801, patient-reported outcome analyses suggested a possible advantage to AM with decreased pain and swallowing symptoms (J Clin Oncol 23:2145–2154, 2005). This long-term follow-up analysis on survival shows no evidence of tumor radioprotection due to amifostine. The promising 5-yr OS suggests that induction paclitaxel/carboplatin (P/C) followed by concurrent RT and weekly low-dose P/C is comparable to other regimens using cisplatin doublets at higher dosages every 3–4 weeks. Research supported by NCI and Medimmune Oncology. No significant financial relationships to disclose.
Superiority of tirapazamine-containing chemoradiation in head and neck cancers showing evidence of hypoxia on <sup>18</sup>F-misonidazole (FMISO) pet scanning
Authors: R. Hicks, D. Rischin, R. Fisher, D. Binns, J. Corry, S. Porceddu, M. Grossi, C. Okane, L. Peters
Journal: Journal of Clinical Oncology (2004)

5520 Background: 45 patients were enrolled on a hypoxic imaging sub-study of a larger TROG trial in which patients with Stage III or IV SCC of the head and neck were randomized to radiotherapy (70Gy/35fx/7weeks) plus either cisplatin and infusional 5FU during weeks 6 and 7 (CIS/5FU) or the hypoxic cytotoxin, tirapazamine and cisplatin in weeks 1, 4 and 7 and tirapazamine alone in weeks 2 and 3 (CIS/TPZ) (Proc ASCO 22: 495, 2003). The objective was to determine the association between tumor hypoxia, treatment regimen and local-regional failure (LRF). Methods: Pretreatment FMISO PET was performed 2 hours after tracer administration with qualitative scoring of uptake in both primary tumours and nodes. Scores of 2 (mild) or grade 3 (moderate-high) were deemed positive for the presence of hypoxia. Results: 32 (71%) patients had detectable hypoxia in either or both primary and nodal disease. Hypoxia was present in the primary tumours of 17 of 45 (38%) patients and in the nodes of 21 of 35 (60%) node positive patients. In patients who received the CIS/5FU regimen, 1/10 without any PET evidence of hypoxia had LRF compared to 8/13 of those with hypoxia: time to LRF was significantly shorter in hypoxic patients (exact logrank P=0.038; hazard ratio (HR)= 7.1). In patients with hypoxic tumours who received the CIS/TPZ regimen, only 1/19 patients had LRF: time to LRF was significantly shorter in CIS/5FU patients with hypoxia (P=0.001; HR=15). Results at the primary site alone were as follows: in patients treated with CIS/5FU, 1/14 without hypoxia failed locally, compared to 6/9 of those with a hypoxic primary: time to primary failure was significantly shorter for hypoxic patients (P=0.018; HR=8.9). For patients with hypoxic primaries treated with CIS/TPZ 0/8 failed locally compared with 6/9 with CIS/5FU (P = 0.011). Conclusions: Hypoxic PET imaging can identify patients most likely to benefit from treatment with this tirapazamine containing chemoradiation regimen. The decreased LRF rate in patients with hypoxic tumors who received CIS/TPZ supports the hypothesis that tirapazamine acts by specifically targeting hypoxic tumour cells. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo Sanofi-Synthelabo Sanofi-Synthelabo
The profile of platelet-derived growth factor receptor alpha (PDGFRA) gene alterations in GIST patients (pts) from Brazil
Authors: D. A. Braggio, E. Braggio, I. Á. Small, C. E. Bacchi, L. F. Lopes, M. Valadão, S. Portella, S. Romano, D. P. Guimarães, C. G. Ferreira
Journal: Journal of Clinical Oncology (2008)

10561 Background: Oncogenic activation mutations of the PDGFRA gene have been identified in a small subset of GIST that lack KIT mutations (WT-KIT). Most of the PDGFRA mutations occur in exon 18 and the site of mutation may influence response to tyrosine kinase inhibitors (TKIs). Further, Brazilian population is characterized by a very heterogeneous genetic background. Our goal was to evaluate PDGFRA gene alterations in WT- KIT GIST pts from Brazil. Methods: Eight-one pts with completely resected GISTs CD117+ from Jan 1990 to Apr 2003 were included. WT-KIT (exons 9, 11, 13 and 17) GISTs were examined for mutation in PDGFRA gene (exons 12, 14 and 18) by direct sequencing. Clinical and pathologic data were retrieved from medical records. Tumors were classified according to the risk into very low-, low-, intermediate-, and high-risk based on tumor size and mitotic index (Fletcher et al, Hum Pathol 2002). Results: Out of 81 GIST pts included, mutation analysis was feasible in 55 pts. Median age was 55 (9–77); Male/female 40/60 %. Eleven (20.0%) pts had very low-risk tumors, 12 (21.8%) had low-risk, 12 (21.8%) had intermediate risk and 14 (25.5%) had high-risk tumors. Six (10.9%) pts had metastasis at the time of surgery and were classified as overtly malignant. Primary tumor sites were stomach (47.3%) and others (52.7%). Overall, KIT mutations were found in 40/55 (72.7%) tumors examined (exon 11, 38/55 (69.1%); exon 9, 2/55 (3.6%)). We found PDGFRA mutations in 4/55 (7.3%) cases including 3 missense mutations and 1 deletion. There was a predominance of exon 12 mutations, 3/55 (5.5%) compared to mutations in exon 18, 1/55 (1.8%). All GISTs carrying PDGFRA mutations were gastric tumors of very low- or low-risk and 3 were histologically epithelioid. Three genomic sequence alterations without changing amino acid of the PDGFRA protein were seen in 6/15 (40.0%) WT-KIT GISTs (2472 C>T; 1701 G>A; IVS17–50insT). Conclusions: Of note, in contrast to published data the region encoding juxtamembrane domain (exon 12) of PDGFRA gene was the most common site of mutation in our population. Once data is confirmed in a larger pts population this may have implications for pts selection to TKIs. Further, we found three polymorphisms in our WT-KIT tumors with still unknown biologic significance. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Brazil S.A.
Lung deposition of aerosolized anticancer drugs with a novel inhalation system: AKITA
Authors: E. Hofstetter, H. Ehlich, B. Muellinger, G. Scheuch
Journal: Journal of Clinical Oncology (2006)

12037 Background: Inhalation of anticancer drugs might be a helpful route of delivery in cancer therapy, particularly for lung tumors and metastasis in the lungs. In this experimental setup 12 different drugs (including antineoplastic drugs and immunotherapeutics) were nebulized with two different jet nebulizer systems. Aerosol particle size (MMD) and mass output were characterized. Methods: MMD was measured using a laser diffraction system (Sympatec, Clausthal-Zellerfeld, Germany). Mass output measurements were performed after CEN Standard using a Flow/volume simulator with radiolabelled (99m Tc) solution/suspension. The amount of radioactivity on the filters was detected with a scintillation counter. For aerosolization two nebulizer systems were used: Pari LC Plus with Pari compressor (PARI) and Pari LC Star with AKITA compressor (AKITA). To determine lung deposition a lung deposition model (International Commission of Radiological Protection, ICRP66, 1994) was used, taking into account: mass output, particle size and breathing pattern of patients. The AKITA guides the patient with a positive pressure through the inhalation maneuver, it is breath activated and delivers the medication only during inspiration. The PARI nebulizes continuously and the patient inhales with different individual breathing pattern. Results: MMD with PARI was found to be 4.2 ± 0.4 μm compared to 3.40 ± 0.3 μm for AKITA. After filling 2.5 ml into the nebulizers we found 1.4 ml residual volume with PARI and 1.0 ml for AKITA. The output rate was 0.15 ± 0.02 ml/min for PARI and 0.29 ± 0.03 ml/min for AKITA. Lung deposition relative to the emitted dose was determined to be 28 ± 10% for PARI and 85 ± 4% for AKITA. This is because the AKITA nebulizes only during inspiration and guides the patient through the inhalation maneuver, where as the PARI is running continuously and patients inhale with different breathing pattern. The result is that from 2.5 ml filled into the nebulizer, on average 0.3 ml will be deposited in the lungs with the PARI and 1.3 ml with the AKITA. To deposit 1 ml in the lungs with AKITA it will take 7 min, with PARI about 24 min. Conclusions: By use of modern inhalation devices with controlled inhalation lung deposition for cancer therapy can be optimized. [Table: see text]
A phase I study of hepatic arterial infusion of nab-paclitaxel in patients with predominant hepatic metastases.
Authors: S. Fu, A. Naing, S. L. Moulder, G. S. Falchook, K. S. Culotta, Y. Zhang, D. C. Madoff, C. S. Ng, J. Lim, R. Kurzrock
Journal: Journal of Clinical Oncology (2010)

e13044 Background: Previous studies with hepatic arterial infusion (HAI) have demonstrated tumor regressions in patients with refractory cancer and predominant liver metastases. We therefore performed a phase I trial to ascertain tolerance and activity of HAI nab-paclitaxel (nanoparticle albumin-bound paclitaxel). Methods: Cohorts of 3–6 patients with predominant hepatic metastases with serum bilirubin less than 2.0 mg/dL received an escalating dose of HAI of nab-paclitaxel (ranging from 180 mg/m2 to 260 mg/m2 over 1 hour) once every 3 weeks (q3w). Some patients received a first course administered IV for pharmacokinetic comparison in individuals with paired studies (IV versus HAI) in order to determine peak concentrations and the effect of first-pass hepatic extraction. Results: Of 35 enrolled patients, toxicities and responses were evaluated at 3 dose levels and at dose expansion. DLT was not observed and the patients tolerated the treatment well. Common adverse events included alopecia, fatigue, myelosuppresion, nausea, and vomiting. Two (5.7%) patients achieved a PR (1 cervical cancer, 18+ cycles, n=1; and 1 breast cancer, 7 cycles, n=12) and 3 (8.6%) achieved SD (1 esophageal cancer, 10+ cycles, n=3; 1 ovarian cancer, 7 cycles, n=1; and 1 carcinoid tumor, 9 cycles, n=1). Pharmacokinetic analyses revealed lower peak concentrations (about 50%) with greater hepatic extract (about 41%) by the use of HAI nab-paclitaxel when compared to IV nab-paclitaxel. Conclusions: HAI nab-paclitaxel at < 260 mg/m2 q3w was well tolerated with 5 patients (14.3%) achieving SD or PR. Pharmacokinetics showed saturated hepatic extract at the dose level for 1 hour as described in this trial. Studies are ongoing to determine if levels of SPARC (secreted protein acidic and rich in cysteine) correlate with responses. Because of excellent tolerance, further study with increased dosages of HAI nab-paclitaxel, with prolonged infusion time up to 24 hours for greater hepatic extract, as well as in combination with other agents, may be worthwhile. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience
General epidemiology and survival rate of malignant and non-malignant brain and central nervous system tumors in Nice area (France)
Authors: E. Chamorey, C. Lebrun, D. Fontaine, F. Vandenbos, J. Michiels, P. Paquis, M. Frenay
Journal: Journal of Clinical Oncology (2007)

17078 Background: The aim of this cohort study was to produce descriptive epidemiological data from the Group of Neuro- Oncology of Nice (GNON) database. Data were collected from the Comprehensive Cancer Center and the University Hospital of Nice (France). Methods: All cases that have been discussed during multidisciplinary meetings of neuro-oncology were entered. Data were compared with the Central Brain Tumor Registry of the United States (CBTRUS) report taken as reference tool. Follow-up information was obtained from the patient medical chart and from the national death registry. Results: 1,395 patients (718 males, 677 females) were registered in the data base. There were 938 tumors of neuroepithelial tissue (percentage of all reported cases in our study: 67.9%, median age in our study; 58 yrs, percentage in CBTRUS report: 43.6%, median age in CBTRUS report: 53 yrs), 55 tumors of cranial and spinal nerves (4.0%, 53 yrs; 8%, 52 yrs), 270 tumors of meninges (19.5%, 59 yrs; 31.4%, 63 yrs), 54 lymphoma and hemopoietic neoplasm (3.9%, 68 yrs; 3.1%, 60 yrs), 16 germ cell tumors, cysts and heterotopias (1.2%, 17yrs; 0.6%, 16yrs), 12 craniopharyngioma (0.9%, 50 yrs; 0.7%, 48 yrs), 9 chordoma/chondrosarcoma (0.6%, 65 yrs; 0.2%, 48 yrs), 27 unclassified tumors (2.0%, 46 yrs; 6.1%, 68 yrs). The table shows the survival rates at one, three and five years respectively for some selected brain and central nervous system tumors (results from the CBTRUS report in parentheses). Conclusions: A comparison between results from the CBTRUS and GNON data base showed some similarities and didn't point out any major unexplainable discrepancy. [Table: see text] No significant financial relationships to disclose.
The Long-Term Outcome Of Adult Patients With Acute Myeloid Leukemia NPM+ and FLT3/ITD- Is Not Significantly Improved By The Application Of An Allogeneic Stem Cell Transplantation
Authors: Tamara Intermesoli, Marco Frigeni, Elena Oldani, Pamela Zanghì, Orietta Spinelli, Alberto Bosi, Filippo Marmont, Giuseppe Rossi, Sergio Cortelazzo, Alessandro Levis, Daniele Mattei, Maria Pogliani Enrico Maria, Anna Maria Scattolin, Massimo Bernardi, Giacomo Gianfaldoni, Ernesta Audisio, Arianna Masciulli, Renato Bassan, Alessandro Rambaldi
Journal: Blood (2013)
Evidence in bronchoalveolar lavage for third type immune reactions in hypersensitivity pneumonitis
Authors: A Pesci, G Bertorelli, P P Dall'Aglio, G P Neri, D Olivieri
Journal: European Respiratory Journal (1990)

during the entire follow-up in patients who be regularly exposed.Patients who continagricultural en~runents but witho~t ~er specific anugens at work exh1b1ted a CP4+ cells, a decrease rn CD8+ cells, and of CD4/CD8 ratio to the nonnal range six the first observation [8J.~iqtoJIORIIcat analysis.at fli'St evaluation, showed ... u. ....... _n of lung parenchyma by CD8+ cells ~hl!eOI~cut immunohistological observations f!CU:ii~'J""' CD8+ infiltrate in the group of continued to ~ regularly exposed, and of CD4+ cells after 6 months in the lungs of were not.indicate that alveolitis in RP patients is a and its intensity might be modulated by to relevant antigens, amount of antigen of sensitization, thus explaining the BAL lymphocytosis observed in patients exposed to the specific antigens compared are noL Increased cells with supprcssor/cyin the lung of these patients is related to a local immunological response .These mechanisms may be relevant in the pathogenesis of HP.Acbtowkdg•merrts: We wish to thank Drs. G. Marcer, A. Cipria.
Acute myeloid leukemia (AML) patients' understanding of prognosis and treatment goals: A mixed-methods study.
Authors: Thomas William LeBlanc, Catherine T Bloom, Debra M. Davis, Susan C. Locke, Karen E. Steinhauser, Peter A. Ubel, James A. Tulsky, Amy Pickar Abernethy
Journal: Journal of Clinical Oncology (2014)

221 Background: Patients with AML face complex information about the risks and rewards of pursuing treatments of varying intensity. Little is known about what patients understand or value in the decision-making process. Methods: AML inpatients receiving induction chemotherapy completed weekly electronic surveys about their prognosis and treatment goals, along with a baseline semi-structured, qualitative interview exploring their understanding of illness. Their oncologists (MDs) completed baseline surveys about prognosis and treatment goals. We followed a mixed-methods approach to analysis, applying standard statistical methods to survey data, and a constant-comparative qualitative approach to the interview data to enrich our understanding of survey results. Results: We enrolled 13 dyads (a patient and MD pair). Mean patient age was 65.5, and all had high-risk disease due to either age &gt;60, complex cytogenetics, secondary AML, or relapsed disease. At baseline, mean MD-rated chance of cure was 27% (SD 17.6), while patients’ rating was 54% (SD 34.7; p=0.02). Only 2 patients’ estimates of cure matched their MD’s rating, yet MDs rated their patients’ prognostic understanding as high (mean 7.2 on an 11-point scale). MDs reported an average of 3.1 available treatment options, but patients recalled just 1.5. Most MDs gave a specific treatment recommendation (11 of 13), and most patients received the recommended treatment (10 of 11). Agreement about treatment goal was markedly worse than expected by chance (kappa -0.41; 95% CI -0.88-0.07). Qualitative analysis suggests that patients often viewed treatment decisions as binary “life-or-death” propositions, rather than choices between options with differing goals and intensities. Patients also significantly underestimated the risks of induction chemotherapy. Conclusions: AML patients receiving induction chemotherapy have a poor understanding of their prognosis, treatment goals, and risks of induction chemotherapy, but their oncologists are not aware of this. These findings suggest the need for an intervention to improve patient understanding of their illness and treatment options.
Response to second-line chemotherapy in patients with hormone refractory prostate cancer (HRPC) receiving two sequences of mitoxantrone (M) and taxanes (T)
Authors: W. K. Oh, J. Manola, V. Babcic, N. Harnam, P. W. Kantoff
Journal: Journal of Clinical Oncology (2005)

4616 Background: Treatment options for HRPC patients are limited. Trials show a survival benefit for initial T-based chemotherapy, but little data exist regarding the value of second-line chemotherapy. Methods: We retrospectively identified all patients treated at one institution who received at least 2 chemotherapy regimens for HRPC: one M-based and one T-based. T-based regimens included docetaxel or paclitaxel, given weekly or q3 wks. Patients may have received concurrent steroids, estramustine, carboplatin, or investigational agents. Patients progressed after castration and were evaluable by PSA Working Group criteria. PR = PSA decline ≥50% from baseline. SD = PSA decline < 50% or rise ≤ 25%. PD = PSA rise > 25%. Results: 68 patients were analyzed: M→T (n=33) and T→M (n=35). Median age: 66 and 58 yrs, respectively. Median PSA: 23 and 24 ng/ml, respectively. Median time from diagnosis to chemo: 78 and 56 wks, respectively. TABLE shows response to 1st and 2nd chemotherapy in each group. Response to T-based chemo was higher whether used 1st or 2nd (p<0.0001). No differences were seen between groups in Gleason score, TNM stage, or local therapy. Progression-free survival (PFS) was longer with T-based chemo compared with M, whether used 1st or 2nd. However, total PFS from start of 1st regimen to progression on 2nd regimen was 39.9 and 38.7 wks, respectively (p=.67). Overall survival (OS) was 15.2 and 17.1 mos, respectively (p=.96). Multivariable analysis indicated that age and time from diagnosis to chemo did not influence differences in PFS. Conclusions: T-based chemotherapy is active whether used before or after M. Though PFS is longer with T-based chemo, total PFS and OS after either M→T or T→M was equivalent. This suggests that T-based chemo remains active even if delayed. Though PRs and SD were seen with M after T-based chemotherapy, PFS is short and new agents are needed in patients who progress after taxanes. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
Genes that mediate colon cancer metastasis to liver
Authors: Q. Ding, X. Xie, S. Wang, u. Jer-Yan Yang, Alice Zhang, Dung-Fang Lee, Sunny K
Journal: Journal of Clinical Oncology (2008)

15049 Background: Metastasis is a complex series of steps in which cancer cells leave the original tumor site and migrate to a distant organ. Certain cancers tend to spread to specific organ sites. For example, colorectal cancer commonly metastasizes to the liver. The appearance of liver metastases has long been regarded as an ominous sign and is a leading cause of colorectal cancer-related morbidity and mortality. In one-third of patients who die of colorectal cancer, metastatic disease is found only in the liver_meaning that it is imperative to uncover the underlying mechanism of liver metastasis and then to further exploit effectively treating methods. Methods and Results: We firstly established a mouse model of liver metastasis through orthotopic inoculation of parental colon cancer cell line in mouse colon. Metastatic activity was assayed by bioluminescence imaging of luciferase-transduced cells. After two generations of inoculation, we got a stable mouse model of liver metastasis and two colon cancer cell lines with high tendency of liver metastasis. To compare the patterns of gene expression between parental and liver metastatic colon cancer cell lines, transcriptomic microarray was performed. A total of 73 unique genes were found to be overexpressed in colon cancer cell with high tendency of liver metastasis. The top 10 genes (including LERK, Calbindin, S100, et al) with at least a ten-fold change in expression level were selected and confirmed by quantitative PCR and Western Blotting. These genes were either overexpressed by retroviral system in parental cells, or downregulated by RNAi technique in cells with high tendency of liver metastasis. We found that they not only could enhance tumor cell migration and invasion in vitro, but also are required for the liver metastasis of colon cancer cells in animal experiment. Finally, we investigated the gene signature in 40 human samples of metastatic liver tumor and primary colon tumor. Conclusion: Taken together, our results indicated that the 10 genes are not only molecular makers but also functional mediators of liver-specific metastasis, which might provide the plausible molecular targets to overcome liver metastasis, resulting in a huge difference for many patients with colon cancer. No significant financial relationships to disclose.