tbuckley/cabot-search huggingface dataset:
Usefulness of whole body FDG-PET for the prediction of pathologic response after neoadjuvant chemoradiotherapy in locally advanced resectable esophageal cancer
Authors: S. Y. Song, J. H. Kim, J. S. Ryu, E. K. Choi, G. H. Lee, S. B. Kim, S. I. Park, H.-Y. Song, K.-J. Jo
Journal: Journal of Clinical Oncology (2004)

4075 Background: To assess the efficacy of the whole body FDG-PET (PET) for predicting pathologic response and restaging of locally advanced esophageal cancer which was treated with neoadjuvant chemoradiotherapy in prospective phase II study, PET were checked before and after neoadjuvant chemoradiotherpay which was followed by esophagectomy. Methods: From July 2001 to December 2003, PET was checked in 20 patients with locally advanced resectable esophageal cancer before and after neoadjuvant chemoradiotherapy in prospective phase II study. Ivor-Lewis esophagectomy was performed after restaging studies (PET, esophagogastroduodenoscopy, esophagogram, chest CT and/or EUS) and pathologic response was compared to those of PET and conventional diagnostic work-ups. Complete remission on PET was defined as maximal SUV lower than 2.5 in primary esophageal tumor and as no visible increased uptake lesion in regional lymph node. Results: All of the 20 patients completed neoadjuvant treatment and had surgical resection. Pathologic complete response (pCR) was achieved in 9 patients, microscopic residual disease (mRD) in 1 patient, and gross residual tumor (gRD) was observed in 10 patients. In the primary tumor site of esophagus, pCR was observed in 14 patients, mRD in 2 patients, and gRD in 4 patients. For detecting residual tumor, the sensitivity, specificity and accuracy of PET were 50.0%, 92.9%, and 80.0% respectively, where as those of conventional modalities were 100.0%, 28.6%, and 50.0%. Total 206 regional nodal groups were dissected during esophagectomy in 20 patients, and 17 of them had residual tumor cells. The results in regional lymph nodes were 17.6%, 68.8%, and 55.4% respectively with PET, and 23.5%, 47.9%, and 41.5% with conventional modalities. Conclusions: PET was superior to conventional response evaluation modalities especially in the prediction of pCR in both primary site and regional lymph nodes after neoadjuvant chemoradiotherapy. It can give us more information when used with conventional modalities for response evaluation after neoadjuvant treatment. No significant financial relationships to disclose.
MYC gene copy number (GCN) and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC).
Authors: Armida D'Incecco, Lorenza Landi, George Fountzilas, Konstantine T. Kalogeras, Ravit Geva, Severine Kako, Caroline M. Robb, Milo Frattini, Elisa Rossi, Jessica Salvini, Vienna Ludovini, Lucio Crinò, Federico Cappuzzo, Marileila Varella-Garcia
Journal: Journal of Clinical Oncology (2012)

e21018 Background: Monoclonal antibodies against Epidermal Growth Factor Receptor (EGFR) demonstrated efficacy in mCRC patients without mutations in the KRAS gene. Previous data in breast and lung cancer suggested that MYC GCN affects sensitivity to anti-EGFR agents. Methods: This retrospective study was conducted in a cohort of 303 mCRC patients treated with cetuximab/panitumumab, either alone (N=24) or in combination with chemotherapy (N=279). MYC GCN was assessed by fluorescence in situ hybridization (FISH) in primary colorectal cancer tissue samples. Results: In the study population response rate (RR) was 28%, median progression-free survival (PFS) 5.6 months and median overall survival (OS) 11.8 months. MYC was successfully evaluated in 298 cases and was amplified in 17 patients (5.7%). Individuals with MYC amplification showed a trend for a lower RR (7.7% versus 28.9%, p=0.12), shorter PFS (3.0 months versus 5.8 months, p=0.22) and shorter OS (11.3 months versus 12.6 months, p=0.15) than patients with non-amplified tumors. A Receiver Operating Characteristic (ROC) analysis was also performed in order to verify whether a better MYC GCN cut-off could discriminate between anti-EGFR sensitive and resistant cases. In this analysis, patients with mean MYC GCN ≥2.53 (N=199, 66.8%) had a significantly higher RR (32.2% versus 19.1%, p=0.02), a longer PFS (5.8 months versus 4.5 months, p=0.06) and a longer OS (12.3 months versus 11.4 months, p=0.59) than patients with mean GCN &lt;2.53 (N=99, 33.2%). In order to assess the potential confounding effect of KRAS and BRAF status, we further analyzed the outcome of the 81 KRAS/BRAF wild-type patients according to MYC GCN. In this subset, a trend for improved RR (42% versus 20%, p=0.05), PFS (8.6 months versus 4.2 months, p=0.16) and OS (13.5 months versus 9.7 months, p=0.51) favored MYC FISH GCN ≥2.73 patients. Conclusions: MYC amplification is a rare event in mCRC, not significantly reducing sensitivity to anti-EGFR agents. A trend for better outcome was observed in presence of increased MYC GCN.
A phase I dose-escalation trial with the new redox activated compound sodium trans-[tetrachlorobis(1 H-indazole)ruthenate(III)]/indazolhydrochloride (1:1.1) (FFC14A) in patients with solid tumors - a CESAR study
Authors: M. E. Scheulen, B. Kynast, U. Jaehde, R. A. Hilger, E. Scheuch, V. Arion, P. Kupsch, M. M. Henke, C. Dittrich, B. K. Keppler
Journal: Journal of Clinical Oncology (2004)

2101 Background: A phase I trial was initiated with the new ruthenium(III) complex FFC14A, which was selected for clinical trials due to its differential profile regarding antitumor activity and toxicity in animal models compared to several other new ruthenium compounds. The unique biological characteristics of FFC14A are based on its ability to use transferrin, the natural iron transport protein, for a targeted delivery of the agent towards transferrin receptor over-expressing tumor cells in vivo and subsequently higher concentrations accumulating in the target tissue. Furthermore, the mechanism of action of this new agent can be attributed to its induction of apoptosis and a change of the mitochondrial membrane potential. Methods: FFC14A is under investigation in patients with advanced solid tumors. It is administered as intravenous infusion twice a week over three weeks. The clinical trial started with a dose of 25 mg. Dose escalation will be performed according to an accelerated dose titration design with dose escalation of 100 % during the early phase of the trial. Ruthenium (Ru) concentrations in plasma were determined by atomic absorption spectrometry (AAS). Results: Preclinically, the MTD after intravenous administration was determined in mice and rats to be 58.8 mg/kg and 42.0 mg/kg, respectively. The no-observed-adverse-effect-level (NOAEL) in the 28-day toxicity study was determined to be 0.84 mg/kg FFC14A in rats and 1.05 mg/kg (3.36 mg/kg) in male (female) mice, respectively. The first patient treated with 25 mg FFC14A tolerated the six applications well without any side effect. The preliminary evaluation of the pharmacokinetic parameters in a 2-compartment-model resulted in a terminal half-life (t1/2) of 78 h at a volume of distribution at steady state (Vss) of 32 L for protein-bound Ru in plasma. Conclusion: Long t1/2 and low Vss may reflect a long circulation of a FFC14A-transferrin-complex in plasma which will be analyzed within the ongoing study. No significant financial relationships to disclose.
Predicting the extent of invasive disease by MRI to enhance the use of minimally invasive techniques in the management of early stage breast carcinoma
Authors: R. S. Davidson, M. Chaudhry, R. Localio, M. D. Schnall, S. M. Domchek
Journal: Journal of Clinical Oncology (2004)

610 Background: With the advent of minimally invasive procedures such as radio-frequency ablation and vacuum-assisted core biopsy for managing early-stage invasive breast carcinoma, the ability to predict invasive disease by pre-procedure imaging is essential to achieving an adequate margin and for guiding adjuvant therapy. Magnetic resonance imaging (MRI) is a sensitive modality used in the detection of breast pathology and may provide the anatomic resolution necessary to predict the extent of invasive disease. Methods: A retrospective review was conducted on MRI and pathologic data from 24 (63%) of 38 patients with focal, invasive breast carcinoma enrolled in an ongoing multi-modality imaging study between 3/02 and 10/03. Patients were selected on the basis of the following criteria: 1) 1 or 2 suspicious focal lesions per breast detected on MRI, 2) 1 or 2 pathologically-proven foci of invasive carcinoma per breast, and 3) no chemotherapy between MRI and definitive surgery. Largest tumor dimension as measured by MRI, performed prior to definitive surgery, was compared to the largest pathologic tumor dimension. Results: Median age of selected patients was 52.0 y (range 37.9–71.1). 25 lesions were evaluated. Histology revealed 20 (80%) invasive ductal carcinomas, 3 (12%) invasive lobular carcinomas, and 2 (8%) mixed lesions. Seven patients underwent reexcision due to positive margins with no further invasive carcinoma identified. Median lesion size by MRI was 2.0 cm (0.7–3.4). Median lesion size by pathology was 1.9 cm (0.8–4.0). For lesions ≤ 2 cm by pathology (n =16), MRI size was equal to or greater than pathologic size for 14 lesions (88%) and the difference between MRI and pathologic size was within 0.5 cm in 12 lesions (75%). Conclusion: MRI was effective at estimating invasive breast carcinoma dimension in lesions less than 2 cm. MRI avoided underestimation of pathologic size in small lesions, making it a potentially safe means of identifying the target for minimally invasive techniques. No significant financial relationships to disclose.
Circulating tumor cells monitored over time in lung cancer patients
Authors: M. S. Luttgen, D. Marrinucci, D. Lazar, M. Malchiodi, P. Clark, E. Huynh, K. Bethel, L. Bazhenova, J. Nieva, P. Kuhn
Journal: Journal of Clinical Oncology (2009)

11025 Background: Circulating tumor cell (CTC) detection and enumeration is a valuable tool for monitoring cancer patient status and outcome. While many current techniques employ immunomagnetic-enrichment based protocols focused on the importance of a particular CTC number as the indicator of patient status or outcome, we employ a cytometric, enrichment free approach using an immunofluorescent protocol to monitor CTC counts in patients with non-small cell lung cancer (NSCLC) over the course of treatment. Methods: Eligible patients had progressive stage IV NSCLC. The histological subtypes in the 42 cases for which the data was available included adenocarcinoma (22/42), squamous cell carcinoma (6/42), large cell undifferentiated carcinoma (3/42), and non-small cell lung carcinoma not further described, poorly differentiated, or with a mixed pattern (11/42). Blood samples were collected 3 wks, 3 mo, 6 mo, 9 mo, and 1 yr after the initial sample. CTCs were identified via immunofluorescence and cytometric analysis. Patient response to therapy was determined by RECIST every 3 months between time 0 and time 12 mo. Results: 80 of 109 patient samples have CTCs (73%) and all of the 52 patients tested have CTCs. 13 of 52 patients have CTC data for time 0 and 3 wks. Only 4 of these patients (30.8%) show a correlation linking CTC count change between time 0 and 3 wks and clinical assessment. 13 patients have CTC data for time 0 and 3 mo, 10 of whom show a correlation linking CTC count change between time 0 and 3 mo and clinical assessment. 7 of the 8 patients (87.5%) showing stable or partial response at 3 mo show a decrease in CTC count between time 0 and 3 mo. Five of the 6 patients (83.3%) clinically showing progressive disease at the 3 mo time point show an increase in CTC count between time 0 and 3 mo. The patients that do not show a correlation linking CTC count change between time 0 and 3 mo and clinical assessment at 3 mo show a correlation at the 6 mo time point. Conclusions: CTCs can be effectively enumerated in metastatic NSCLC patients, with the majority demonstrating CTCs in the setting of progressive disease. The change in CTC count at 3 mo, but not at 3 wks, correlates with radiographic response to chemotherapy. Further follow-up will determine the predictive value of CTC enumeration on survival. No significant financial relationships to disclose.
Current use and attitudes toward the use of information technologies in health care among cancer patients.
Authors: Anne Girault, Marie Ferrua, Aude Fourcade, Guillaume Hebert, Jonathan Lapointe, Claude Sicotte, Muriel Mons, Sophie Beaupere, Naima Mezaour, Francois Lemare, Anne Montaron, Michel Ducreux, Charles Guepratte, Mario Di Palma, Etienne Minvielle
Journal: Journal of Clinical Oncology (2014)

e20652 Background: The patient-perceived usefulness of IT in oncology and the current utilization by patients could be strong predictors for the success of a coordinated care pathway (patients, cancer center, primary care) relying on IT. According to the literature, some patient characteristics could influence the responses. The goal of this study was to identify which of them had an impact to adjust the pathway according to patient preferences. Methods: A questionnaire-based survey was conducted in June 2013, over seven days within seven outpatient departments of Gustave Roussy, a comprehensive cancer center near Paris (≈160 000 consultations yearly). The sample was representative of the outpatient population. We computed descriptive statistics and performed correlation analysis to investigate patients' IT usage and attitudes in relation to age, gender, socioeconomic status, social isolation, and place of living. We conducted multinomial logistic regressions using R. Results: The participation level was 85% (n=1371). 70% of respondents were females. The median age was 53.4. 71% used a mobile phone everyday and 68% connected to the Internet every day. Age and socioeconomic status were negatively associated with the use of IT (p<0.001). Regarding patients' expected benefits (see table), a significant majority valued its use in health care, and especially, the possibility to enhance communication with providers. 84% of patients reported feeling comfortable with the use of IT but age and socioeconomic status had a significant influence. Otherwise, no significant gap between attitudes among the different patient groups could be identified. Conclusions: Most patients were connected to IT every day. Overall, patients advocated for an extended use in oncology. Differences in perceived ease of use according to age and socioeconomic status have to be addressed. Perceived benefits of IT applications. IT applications Useful/very useful Neutral Not useful/rather not useful N/A Schedule an appointment 71% 6% 22% 1% Communicate via emails with your physician 75% 5% 18% 2% Get help with medication monitoring 61% 12% 26% 1% Get information about disease 69% 12% 18% 1% Get access to external contacts 66% 13% 20% 1%
A Phase II trial of imatinib mesylate in patients (pts) with malignant mesothelioma (MM)
Authors: J. L. Villano, A. N. Husain, W. M. Stadler, L. L. Hanson, N. J. Vogelzang, H. L. Kindler
Journal: Journal of Clinical Oncology (2004)

7200 Background: Platelet derived growth factor (PDGF) is a potent mitogen for normal mesothelium. PDGF is composed of 2 subunit polypeptides: the A and B chains. The c-sis proto-oncogene encodes the B chain of PDGF, which is co-expressed with the PDGF receptor (PDGF-R) in MM. This results in an autocrine growth-stimulating loop. In vitro, transduction of a ribozyme against PDGF-B mRNA into MM cells significantly decreases cell growth. PDGF may thus be an appropriate target for therapy of MM. Imatinib (Gleevec) is a tyrosine kinase inhibitor that inhibits PDGF-R. We performed a phase II trial of imatinib in MM pts. Methods: Eligible pts had histologically proven, unresectable MM, unidimensionally measurable disease, PS 0–1. Imatinib 600 mg was given daily for 28 days; CT scans were obtained every 2 cycles. Baseline expression of PDGF, PDGF-R and KIT-R were determined by immunohistochemistry; plasma levels of PDGF isoforms were obtained at baseline and every 8 weeks. 17 pts enrolled 12/02–8/03. Pt characteristics: median age 71 years (range 56–82); males 65%; prior chemotherapy 94% (range 0–3, median 2); PS 0/1 30%/70%; histology: epithelial 80%, biphasic 20%; site of origin: pleura 94%, peritoneum 6%; thrombocytosis 30%. Results: 41 cycles of imatinib were given (median 2, range 0–6). Grade 3/4 toxicities: nausea, dyspnea: 12% each; leukopenia, neutropenia, fatigue, edema, rash: 6% each. 5 pts required dose reduction to 400 mg; 2 pts stopped drug after 2 weeks. There were no objective responses. Progression-free survival was 7.4 weeks (range 2–24, 95% CI 6.9–13.9). Median survival has not been reached; 1-year survival was 62% (95% CI 28–83%). Baseline plasma levels of PDGF isoforms demonstrate greater expression of AB followed by AA and BB (p<0.01) that does not correlate with time to progression (p=0.4) or thrombocytosis. Conclusions: Imatinib is inactive in MM; the 600 mg dose is poorly tolerated. Baseline PDGF levels do not correlate with time to progression. Further data on biologic correlates will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Photodynamic therapy (PDT) with mTHPC in the palliation of advanced head and neck cancer in patients who have failed prior therapies and are unsuitable for radiotherapy, surgery or systemic chemotherapy
Authors: W. Rauschning, I. B. Tan, G. Dolivet
Journal: Journal of Clinical Oncology (2004)

5596 Background: A previous clinical trial showed that the novel PDT drug, mTHPC, is effective in improving quality of life in patients with advanced head and neck cancer. This current, ongoing, multinational, open-label study is being conducted to confirm that finding. Methods: Patients with advanced squamous cell carcinoma of the head and neck, who have failed prior therapies, and are unsuitable for curative therapy, are being enrolled in this single-arm, palliative care study. Each patient has a tumour that is accessible for unrestricted laser light illumination and is no greater than 10 mm in depth. The primary endpoint of the study is the overall tumour response rate. In addition, quality of life, an important measure in this end-stage population, is being assessed. Patients receive a 0.15-mg/kg intravenous dose of mTHPC followed 96 hours later by illumination of the tumour with a diode laser (light dose 20 J/cm2, irradiance 100 mW/cm2, wavelength 652 nm). Results: To date, 10 patients have been treated in the study. The mean age of patients is 61 years (range, 44 to 82 years). Interim data indicate that 5 patients (50%) have achieved a complete tumour response and 2 patients a partial response (using WHO criteria), thus 7 of 10 patients (70%) have experienced an overall tumour response. The adverse events observed so far in the study are typical of those seen with mTHPC, and include pain, oral necrosis, and trismus. Investigators involved in the study have commented upon the ability of mTHPC to preserve functional and anatomical integrity, which in turn affords patients an improved quality of life. Conclusions: The results, based on these interim data, confirm the effectiveness of mTHPC in reducing tumour mass, and therefore suggest that mTHPC may indeed improve or maintain quality of life. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biolitec Pharma Biolitec Pharma Biolitec Pharma
Safety of infusing ipilimumab (ipi) over 30 minutes (min).
Authors: Parisa Momtaz, Vivian Park, Katherine Panageas, Joyce Diana Guillen, Michael Andrew Postow, Margaret K. Callahan, Jedd D. Wolchok, Paul B. Chapman
Journal: Journal of Clinical Oncology (2015)

9046 Background: The approved dose of ipi is 3mg/kg infused over 90 min. In clinical trials, however, 10mg/kg has also been infused over 90 min. At 10mg/kg, patients (pts) receive 3mg/kg within the first 27 min of treatment. We sought to determine if the standard 3mg/kg dose could be safely infused over 30 min. Methods: We first retrospectively reviewed the incidence of infusion-related reactions (IRRs) to ipi at our institution in melanoma pts receiving either 3mg/kg or 10mg/kg doses infused over 90 min. Our findings led to a change in institutional guidelines for ipi infusion time from 90 min to 30 min. We then prospectively reviewed the 30 min infusion of ipi. Results: Between 4/1/08 and 6/30/13, 595 pts received ipi infused at either 3mg/kg (n = 457) or 10mg/kg (n = 138) over 90 min. There was no significant difference in the incidence of IRRs between pts receiving 10mg/kg (4.3%) vs. 3mg/kg (2.2%) of ipi over 90 min (p = 0.22). 120 pts were then treated prospectively with 3 mg/kg ipi infused over 30 min. 7 pts (5.8%) had an IRR (p = 0.06 compared to 10/457 (2.2%) in the 3 mg/kg 90 minute infusions). All IRRs occurred at dose 2; 6 were grade 2, one was grade 3. Five IRRs occurred during the infusion, two occurred after (one 30 min after and the second immediately after completion of infusion). All 7 pts received subsequent doses of ipi safely administered over a range of 30-90 min. 5/7 pts received subsequent doses with pre-medication (diphenhydramine, steroids) without incident. One of the 2 pts who did not receive pre-medication at dose 3, experienced an IRR at dose 3, received pre-medication for dose 4, and did not experience an IRR at dose 4. Conclusions: Ipi at 3mg/kg can be infused safely over 30 min with an acceptably low incidence of IRRs. Dose 2 is most commonly associated with an IRR. After an IRR, patients can safely receive additional doses of ipi with premedication. It is unclear from our data whether subsequent infusions need to be administered more slowly. It may be reasonable to observe patients for a short period of time after the infusion. A 30 min infusion time enhances patient convenience and allows more efficient use of outpatient infusion facilities.