tbuckley/cabot-search huggingface dataset:
Determination of the rates of neurological toxicity associated with the use of dose-dense (DD) paclitaxel-containing schedules in patients with early breast cancer
Authors: S. J. Nicum, S. Sutherland, I. E. Smith, S. Ashley, S. Johnston
Journal: Journal of Clinical Oncology (2008)

620 Background: The taxanes have been shown to be potent agents in the management of patients with early breast cancer, including sequential or combination regimens in the neoadjuvant setting which have led to enhanced clinical and pathological response rates. In practice neurotoxicity associated with dose-dense (DD) 2-weekly 175 mg/m2 paclitaxel can be a significant problem for some patients. We wished to determine the rates of grade 1–4 neurotoxicity associated with the use of 2 weekly DD paclitaxel. Methods: A retrospective analysis of 186 patients (pts) receiving chemotherapy for early breast cancer between January 2005 and May 2007 was performed at the Royal Marsden Hospital, UK. Neoadjuvant treatment consisted of 4 cycles of doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) administered at 3 weekly intervals followed by 4 cycles of DD paclitaxel. Neurotoxicity was determined prior to each cycle of chemotherapy. For grade (Gr) 1/2 toxicity treatment continued, but for Gr3 toxicity affecting daily activity treatment was either stopped, or replaced with 3 weekly docetaxel. Results: 101 pts received adjuvant and 85 pts neoadjuvant AC followed by DD paclitaxel chemotherapy. 91% pts completed 4 cycles of AC, and 82% pts completed 4 cycles of DD paclitaxel. Overall 57% pts developed some neuropathy (37% Gr1, 17% Gr2, 3% Gr3, nil Gr4). In 20%, 19%, 15% and 3% of pts neuropathy developed after cycle 1, 2, 3 and 4, respectively. Of the 6 pts with Gr3 toxicity, 3 have persistent neuropathy affecting activities of daily living more than 6 months after completing treatment. 32 pts (18%) discontinued treatment with DD paclitaxel (17 due to neuropathy; 5 due to a lack of neoadjuvant response, and 10 for other toxicities such as myalgia / allergic reactions). Of the 85 pts receiving neoadjuvant AC - DD paclitaxel, 14 (17%) achieved a pathological complete remission. Conclusions: A significant proportion of early breast cancer patients treated with AC - DD paclitaxel experienced mild Gr1/2 neurotoxicity. Rates of Gr3 neurotoxicity were low (3%), and comparable to the previous CALGB-9741 study (4%). Whilst DD-paclitaxel may improve outcome in patients with early breast cancer, neurotoxicity can be problematic for some patients. No significant financial relationships to disclose.
Isolation and characterization of spontaneous spheroid aggregates within human colon carcinomas
Authors: V. Dangles-Marie, P. Validire, S. Richon, L. Weiswald, M. Briffod, A. Pecking, B. Gayet, D. Bellet
Journal: Journal of Clinical Oncology (2007)

14515 Background: In vitro spheroid model using cancer cell lines is widely admitted to mimic in vivo micro tumors, including micrometastases. Floating spheroid cell cluster culture has been recently used for normal and cancer stem cell expansion. Spontaneously spheroids generated in vivo have been only studied in ovarian cancer ascites while organoid aggregates have been sometimes observed in the establishment of human colon cancer cell lines. In this study, we investigated whether spontaneous spheroid aggregates from colon cancer could be isolated and characterized. Methods: 127 colorectal primary tumor specimens have been collected and mechanically dissociated into small fragments, which were then shortly cultured on cell plastic flask. Production of spheroid- like structures, referred to as colospheres, was examined at Day 1 and colospheres were gathered for phenotypic characterization. Results: Colospheres were successfully generated from 67 surgical specimens (53%). The capacity to form colospheres was strictly restricted to tumor tissue: dissociated normal colon mucosa never generated colospheres and colospheres were formed exclusively by cancer cells. The ability to generate colospheres was demonstrated to be significantly related to tumor aggressiveness, according to nodal status and AJCC’s stages (Chi-2 test, p&lt;0.05). Immunohistochemical studies showed that cells forming colospheres were frequently positive for Ki67, and displayed often a disturbed expression of the epithelial caretaker E-cadherin. Peripheral cells of colospheres were able to migrate into Matrigel in absence of any chemoattractant. Conclusions: Collectively, the morphology of these colospheres derived directly from tumoral tissues and made up exclusively of cancer cells, their potential capacity to acquire an epithelial-to-mesenchymal transition phenotype and their in vitro migration ability could be aligned with the collective migration properties of carcinomas. Consequently, these ex vivo spherical structures might form an in vitro cell system for micrometastasis studies, at the very time when mortality among colorectal cancer patients continues to be attributed to metastasis development. No significant financial relationships to disclose.
Randomized, Double-Blind Study of Sonidegib (Lde225) in Patients (Pts) with Advanced Basal Cell Carcinoma (Bcc)
Authors: R. Dummer, A. Guminski, R. Gutzmer, L. Dirix, K. Lewis, P. Combemale, R. Herd, M. Kaatz, C. Loquai, A. Stratigos, H. Schulze, R. Plummer, T. Yi, A.L.S. Chang, F. Cornélis, R. Kudchadkar, U. Trefzer, J. Lear, D. Sellami, M.R. Migden
Journal: Annals of Oncology (2014)
An initial analysis of an allele-specific quantitative PCR (Q-PCR) assay which detects minimal residual disease (MRD) in the peripheral blood of follicular lymphoma (FL) patients
Authors: T. Theriault, N. Kautz, K. Mason, D. Ingolia, D. W. Denney
Journal: Journal of Clinical Oncology (2006)

17541 Background: MyVax Personalized Immunotherapy is an active immunotherapy that targets the idiotype of surface immunoglobulin (Ig) on malignant B cells and is currently in a pivotal Phase 3 trial. Idiotype vaccines have shown promising results in early phase clinical trials. The monitoring of circulating tumor cells in peripheral blood lymphocytes (PBLs) may provide important information regarding disease status and response to therapy. A standard method of assessing MRD in FL is by PCR amplification of the t(14:18) translocation at the major breakpoint region (MBR) locus. Studies have shown that 35–50% of FL tumors are not detected by the MBR assay. Circulating non-malignant cells that carry the t(14:18) translocation may complicate MBR analysis. We have developed an allele-specific oligonucleotide (ASO) Q-PCR assay that detects unique Ig heavy chain sequence. This patient-specific ASO assay has the ability to monitor tumor in PBLs of all patients. Methods: Three TaqMan assays were performed on each sample analyzed: 1) ASO; 2) MBR; 3) albumin. The MBR and albumin assays were standard for all patients. The ASO assay was developed for each patient based on amplification using patient-specific primers and TaqMan probes that span the CDR2/CDR3 region of each patient Ig heavy chain. The Ig heavy chain sequences identified during the production of MyVax Personalized Immunotherapy were used to develop patient-specific primers and probes. MBR and ASO counts were normalized using the results of the albumin assay. Assays were performed on DNA samples isolated from PBLs collected before and 6 months after chemotherapy and following MyVax Personalized Immunotherapy. Results: Q-PCR data were grouped into MBR positive and MBR negative sets. We were able to monitor tumor-specific cells present in peripheral blood by the ASO assay in all patients. ASO values appear to correlate with MBR values. Both the ASO and MBR assays allowed detection of 1 tumor cell in 10 4 to 10 5 PBLs with reaction efficiencies of 1.80 or higher. Conclusions: The ASO assay is broadly applicable for detecting MRD in both MBR positive and MBR negative FL patients. [Table: see text]
Cetuximab (C) and bevacizumab (B) in patients with recurrent or metastatic head and neck squamous cell carcinoma: An updated report
Authors: M. K. Gibson, M. Kies, S. Kim, P. Savvides, A. Kotsakis, G. Blumenschein, F. Worden, H. Chen, J. Grandis, A. Argiris
Journal: Journal of Clinical Oncology (2009)

6049 Background: Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) represent important therapeutic targets in SCCHN. Cetuximab (C), an IgG1 monoclonal antibody against EGFR, has single agent activity in SCCHN. Upregulation of VEGF has been associated with C resistance, thus, combined targeting may enhance anti-tumor activity. We designed a phase II trial of bevacizumab (B), an anti-VEGF humanized monoclonal antibody, with C to evaluate this hypothesis. Methods: Eligible patients have recurrent or metastatic SCCHN, measurable disease (RESIST), ECOG performance status (PS) 0–2, and no history of bleeding or thrombosis. Up to 1 regimen (without an EGFR inhibitor) for recurrent or metastatic disease and prior chemoradiotherapy with curative intent are allowed. Treatment consists of weekly cetuximab, 250 mg/m 2 (after a loading dose 400 mg/m 2 ) and bevacizumab, 15 mg/kg given intravenously every 21 days, until disease progression. The primary endpoint is the objective response rate. Sample size is 45 eligible patients. Specific biomarkers relating to EGFR and VEGFR signaling will be evaluated in tumor tissues and blood samples. Results: 28 patients enrolled (27 eligible). Median age 60 years (range 33–92); male 19; PS 0 (7 pts), PS 1 (18), PS 2 (2). All had prior RT, and 26 had chemotherapy. A median of 4 cycles were given (range, 1–12). Best response in 25 evaluable patients: 5 (20%) PR (1 was uncomfirmed), 14 (56%) SD, and 6 (24%) PD. Progression-free survival was 2.8 months and median overall survival was 8.1 months. Grade (G) 3 adverse events included: hemorrhage (from a benign neck ulcer), 1; hypertension, 2; infection, 2; rash, 2; dysphagia, 4; hypophosphatemia, 1; and fatigue, 1. G 4 AEs: proteinuria, 1. One pt died of aspiration pneumonia, with possible cardiac ischemia of uncertain relationship to study drugs. Conclusions: Preliminary results show that cetuximab and bevacizumab is an active regimen in SCCHN with rare serious toxicities. In particular, our results establish the safety of this bevacizumab-based regimen in regards to bleeding complications in SCCHN. Study accrual continues and biomarker analysis is planned. (Supported by U01 CA099168–01 and P50 CA097190) No significant financial relationships to disclose.
Correlation among [18-F] FDG-PET/CT, tumor marker CA 27.29, and circulating tumor cells in metastatic breast cancer
Authors: A. A. Saad, S. Rikhye, A. Kanate, A. Sehbai, G. Marano, G. Hobbs, J. Abraham
Journal: Journal of Clinical Oncology (2007)

10533 Background: Both tumor marker CA 27.29 and combined [18-F]-fluorodeoxyglucose-positron emission tomography/computed tomography scan (PET/CT) are used to follow up response to treatment and disease progression in patients with metastatic breast cancer (MBC). Recently, circulating tumor cell testing (CTC) has been used in this context. It is not known if one of the three tests can be a surrogate for the other 2 tests. Methods: We analyzed the database of 35 patients with MBC. There were 173 time points (at least 6 weeks apart), when at least 2 of these tests were done. CA 27.29 test (chemiluminescent immunoassay by Bayer Advia Centaur) was either high or normal (&lt; 38.6 U/ml). Circulating tumor cells cell test (Cell Search by Quest Diagnostics, Nichols Institute, Chantilly, VA) was either high or normal (0 cells detected). Results: PET/CT scan results were compared to CA 27.29 at 163 time points. There was statistically significant correlation between both groups (P value: 0.02), however, sensitivity of CA 27.29 to detect metastatic disease seen in PET/CT scan was 59%. The positive predictive value (PPV) of CA 27.29 was 90%, while the negative predictive value (NPV) was only 24%. PET/CT scan results were compared to CTC at 100 events, where there was statistically significant correlation between both groups (P value: 0.0002), however, sensitivity of CTC to detect metastatic disease shown in PET/CT scan was 55%. The positive predictive value of CTC was 98% while the negative predictive value was only 33%. CTC test was more specific (94% Vs 67%) than CA 27.29 to rule out metastatic disease that is seen in PET/CT scan. CA 27.29 results were also compared to CTC at 93 events, where there was statistically significant correlation between both groups (P value: 0.0002). However, only 64 % of those with high CA 27.29 had abnormal CTC. Conclusion: Our data shows correlation among PET/CT scan, CA 27.29, and CTC. However, both CA 27.29 and CTC had poor sensitivity and negative predictive value to detect metastatic disease seen in PET/CT scan. Normal CA 27.29 test or CTC has to be interpreted cautiously in patients with MBC. No significant financial relationships to disclose.
Prospective cohort study of quality of care (QC) and quality of life (QL) of palliative cancer patients in three different situations: In-patient hospitalization (IN), palliative care unit (PA) and home care (HO). Final analysis
Authors: G. Chvetzoff, D. Pérol, P. Rebattu, Y. Devaux, P. Saltel
Journal: Journal of Clinical Oncology (2008)

20670 Background: The aim of the study was to assess QC and QL in advanced cancer patients receiving palliative care during (i) in-patient hospitalization in a comprehensive cancer center, (ii) in-patient hospitalization in a palliative care unit, (iii) home-care. Methods: After giving informed consent, the patient chose one of the three possibilities. QC was assessed by the STASS questionnaire, QL by the EORTC QLQ-C30, mood disturbance by Spielberger questionnaire and pain by VAS. The impact on family members was assessed by semi- structured interviews. Evaluations were conducted at days 0, 15, 30 and then monthly until death (max four months). Results: 51 men and 49 women were included (median-age: 61 years). The choices expressed by the patients were IN 14%, PA 20% and HO 66%. The type of care actually provided was IN 26%, PA 19%, HO 55%. At the end of the study (85% patients died before 4 months), the distribution was IN 50%, PA 24% and HO 26%. Symptom evaluation was consistent between patients and care-givers. QC, QL and pain assessment were similar between the three cohorts. IN nurses were more anxious and considered that patients had a better estimation of their prognosis. The level of anxiety among patients and families was lower in HO. Re hospitalization was correlated with Karnofsky index alteration but not with pain, patient or family anxiety. Conclusions: The majority of patients choose home hospitalization, but families frequently find it difficult to cope. Even if the family agrees with the patient’s choice, re-hospitalization is frequently required at the end of life. Physical and psychological symptoms are frequent but under control and do not differ between the three cohorts. Home palliative care demands special attention and specific support for family members. No significant financial relationships to disclose.
Are men with larger prostates and bothersome voiding symptoms less likely to have significant prostate cancer?
Authors: C. R. Porter, J. Wright, L. Borden, K. Jason, K. Latchemsetty
Journal: Journal of Clinical Oncology (2006)

4656 Background: Gleason Sum (GS) predicts clinically significant prostate cancer (CAP) and prostate specific antigen (PSA) survival in men undergoing prostatectomy for CAP. BPH can also elevate PSA. Objective: evaluate prostate gland volume (PV) and American Urologic Symptom Score (AUASS) in men undergoing prostate needle biopsy (PNB) to detect CAP. Analysis endpoints: 1) CAP and 2) GS ≥7. Methods: From 1/2000–7/2005, 1,078 men undergoing PNB were prospectively examined. Urinary voiding symptoms were measured by AUASS. All men were examined by 1 surgeon: DRE and Transrectal Ultrasound (TRUS) were given levels of suspicion (LOS) from 1 = low suspicion (smooth DRE, homogeneous TRUS) to 5 = high suspicion (hard DRE, hypoechoic lesion). LOS ≥3 was abnormal. Prebiopsy parameters: PSA, DRE, age, race, biopsy history, prostate volume (PV), TRUS lesion, and AUASS. All men had 10-core biopsy. 1) Predictors for CAP were evaluated by Univariate (UVA) and multivariate (MVA) analysis (logistic regression) for 1,078 men. 2) Predictors for GS≥7 were evaluated in men with no prior biopsy (NOPB). Results: Median PSA = 5.4 ng/ml (mean 10.4), 38% and 52% had abnormal TRUS &amp; DRE respectively. Mean patient age = 64 years. Mean AUASS = 10.4. Positive biopsy rate = 38%. AUASS: 47% had low symptoms scores (&lt;7), 39% had moderate scores (8–19), and 14% had severe scores (20–35). UVA &amp; MVA (N = 1,078) showed that PSA was not an independent predictor of CAP (p = 0.18), but abnormal DRE, age, low AUASS, no prior biopsy (NOPB), race (AA), abnormal TRUS, and low PV were all independent predictors (p &lt; 0.03). Subset MVA analysis of men in PSA range of 2.5–10 (N = 738), demonstrated that low AUASS (p = 0.05) &amp; low PV (p = 0.00001) were predictors of CAP, while DRE, NOPB, and age were also independent predictors. MVA of men with NOPB (N = 790), indicated that low PV, PSA, DRE, and Age were independent predictors for CAP (p &lt; 0.0001). The multivariate risk of having GS ≥7 on biopsy was independently associate with both low PV (p = 0.001) and abnormal DRE (p = 0.001). The relationship between PV and GS ≥7 showed that for every 1 cc increase in gland volume the risk of GS ≥7 CAP decreases by 2.2%. Conclusions: Men with smaller prostates are more likely to have cancer and are more likely to have significant disease. No significant financial relationships to disclose.
Daptomycin therapy for gram-positive infections in cancer patients
Authors: H. L. Hogan, I. Raad, K. V. I. Rolston
Journal: Journal of Clinical Oncology (2005)

8193 Background: Daptomycin is a novel cyclic lipopeptide antibacterial agent approved for the treatment of skin and skin structure infections caused by susceptible gram-positive organisms. Clinical data in cancer patients are limited. Methods: Retrospective review of daptomycin usage for documented and/or suspected gram-positive infections in cancer patients at a comprehensive cancer center. Results: Twenty-one patients, 9 men and 12 women, were treated. Five (21%) patients received 6 mg/kg/day and 16 patients received 4 mg/kg/day. Eleven (52%) had hematological malignancies and 10 (48%) had solid tumors (acute leukemia, lymphoma and breast cancer were the most common). The average age was 49 years (range 27–56). Six (29%) were neutropenic. The infections treated were cellulitis-12 (57%), abscess-3 (14%), bacteremia-5 (24%), and urinary tract infection-1 (5%). The organisms isolated were S. aureus (8, including 4 MRSA), Enterococcus spp. (4, including 2 VRE), and coagulase negative staphylococci- (3). Five patients (24%) had failed vancomycin (3 cellulitis, 2 bacteremia) and 2 linezolid therapy (l cellulitis, 1VRE bacteremia). All isolates from clinical failures were susceptible to prior antimicrobial regimens. The overall response to daptomycin (19 of 21 patients) was 90%. Five of the six neutropenic patients responded to daptomycin therapy. The mean duration of therapy was 11 days. No toxicity was observed, including no CPK elevations. The 2 patients who failed to respond to daptomycin (both leukemics with cellulitis/abscess) responded to alternative agents. Conclusions: Daptomycin appears to be a promising agent for the treatment of gram-positive infections in neutropenic and non-neutropenic cancer patients and needs further clinical evaluation in this setting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cubicin Cubicin
The identification of discrete prognostic groups in low grade non-Hodgkin's lymphoma
Authors: R.C.F. Leonard, R.L. Hayward, R.J. Prescott, J.-X. Wang, N.C. Allan, A. Barrett, S.N. Das, A.A. Dawson, A. Heppleston, A.M. Lessells, N.P. Lucie, H.H. Lucraft, M.J. Mackie, K.S. MacLaren, A.C. Parker, S.J. Proctor, T.K. Sarkar, T. Sheehan, M. Soukop, W.P. Steward, J.M. White
Journal: Annals of Oncology (1991)
Validation of proteomic classifier for clinical benefit from erlotinib as first line treatment for advanced non-small cell lung cancer (ECOG 3503)
Authors: B. J. Solomon, H. Roder, R. Robert, F. Taguchi, J. Brahmer, S. H. Joan, M. W. Duncan, F. R. Hirsch, P. A. Bunn, D. P. Carbone
Journal: Journal of Clinical Oncology (2007)

7508 Background: In this study we tested the ability of our serum mass spectrometry classifier of clinical benefit from gefitinib to classify pre-treatment sera and plasma samples from non-small cell lung cancer (NSCLC) patients treated first line with erlotinib in ECOG E3503. Methods: Pretreatment serum and plasma samples were available from 73 of the 96 previously untreated advanced NSCLC patients treated with single agent erlotinib on ECOG protocol 3503, 13 subjects had only serum samples, and 10 had only plasma samples. All of these samples analyzed in replicate by MALDI mass spectrometry (MS). A prediction algorithm we established based on a training cohort of 139 patients treated second or third line with gefitinib was used to classify these patients for survival and time to progression, and results obtained from serum and plasma were compared when both were available Results: We found that the signals for the 8 distinct mass-to-charge (m/z) features used in our classifier were highly concordant between serum and plasma samples from the same patient, and that there was no difference in the classification of the patients between serum and plasma when both were available. Therefore we classified all 96 patients using serum if available, and plasma if not. The classification algorithm very successfully classified patients into groups with good and poor survival (median survival of 306 days vs 107 days, p = 0.0007). With the available follow-up, the time to progression was also statistically significant in this group (p = 0.007, data not shown). In a Cox multivariate analysis including the most significant univariate parameters PS (0 vs. 1 vs 2), number of involved sites (=3 vs &gt;3) and prior weight loss (&lt;5% vs = 5%), the MALDI MS classification algorithm retained independent significance at p = 0.03, with a hazard ratio of 0.53. Conclusions: This multi-institutional ECOG study demonstrates that MALDI MS can assist in the pre-treatment selection of a subgroup of NSCLC patients who are likely to show improved survival after treatment with first line erlotinib. No significant financial relationships to disclose.