tbuckley/cabot-search huggingface dataset:
Treatment of small-cell lung cancer with an alternating chemotherapy regimen given at weekly intervals: a Southwest Oncology Group pilot study.
Authors: C W Taylor, J Crowley, S K Williamson, T P Miller, S A Taylor, T G Giri, R L Stephens, R B Livingston
Journal: Journal of Clinical Oncology (1990)

We designed an intensive, weekly treatment regimen for patients with small-cell lung cancer (SCLC) using six of the most active chemotherapeutic agents for this disease (doxorubicin [DOX], cyclophosphamide [CTX], vincristine [VCR], etoposide [VP-16], cisplatin [CDDP], and methotrexate [MTX]). The goal of this program was to gain rapid, repetitive exposure to multiple, active drugs. Treatment was administered weekly for a total of 16 weeks. Seventy-six SCLC patients (limited disease, 34; extensive disease, 42) were treated. The overall complete plus partial response rate was 82%. Complete response rates of 47% and 38% were observed in patients with limited (LD) and extensive disease (ED), respectively. The median survivals for patients with LD and ED were 16.6 and 11.4 months, respectively. Toxicities were tolerable and were primarily hematologic. Twenty-six patients had one or more transient life-threatening toxicities, but only one patient developed a fatal toxicity. Eighty-four percent of the patients received 80% or greater of the intended protocol dosages over the entire 16-week treatment period. We conclude that this intensive, short-duration treatment regimen is at least as good as other "standard" regimens, and we are encouraged aged by the complete response rate and median survival in patients with ED SCLC.
Correlates of local therapy for women with DCIS
Authors: S. J. Katz, P. Lantz, N. Janz, A. Fagerlin, K. Schwartz, L. Liu, D. Deapen, M. Morrow
Journal: Journal of Clinical Oncology (2005)

739 Background: Concerns have been raised about the quality of treatment for women with DCIS because persistent high rates of mastectomy suggest over-treatment; while low rates of radiation therapy after BCS suggest under-treatment. We conducted a population-based survey of women with DCIS to address correlates of local treatment decisions with regard to clinical factors, characteristics of patient-surgeon communication, and patient attitudes. Methods: All women aged 79 and younger diagnosed with DCIS in 2002 based on initial pathology reports and reported to the Detroit and Los Angeles metropolitan SEER registries were surveyed shortly after receipt of surgical treatment (response rate 81.9%, N=817). Analyses were restricted to patients with DCIS based on SEER summary stage (N=659). Results: Only 14.0% of patients at lowest risk of recurrence (based on tumor size and histological grade) received a mastectomy compared to 22.8% and 52.6% of patients at intermediate and highest risk (p<.001). Only 7.9% of patients who were not/slightly influenced by concerns about recurrence received mastectomy versus 61.4% of women who were greatly influenced by this concern (p<.001). Fewer patients in Los Angeles received radiation compared to patients in Detroit (61.4% vs 79.2% in Detroit, p<.001). Between-site differences were greater for lowest risk women (38.9% in Los Angeles vs 70.5% in Detroit) versus highest risk women (80.2% in Los Angeles vs 85.9% in Detroit; p=.051 for interaction between risk and site). Between-site differences in use of radiation after BCS were consistent with patient recall of surgeon discussions. For example, the proportion of women in the lowest recurrence risk group who reported a surgeon recommendation for radiation therapy was 59.1% in Los Angeles compared to 81.5% in Detroit; while these figures were 90.5% and 89.8% for highest recurrence risk women in Los Angeles and Detroit, respectively (p=.048). Conclusion: Surgeons are tailoring their recommendations for local therapy options for DCIS based on important clinical factors. Patient attitudes play a powerful role in treatment decisions. The significant influence of both surgeon opinion and patient attitudes should temper concerns about the quality of treatment decisions for women with DCIS. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NCI
Impact on quality of life (QoL) of FEC-T compared with FEC or E-CMF: UK Taxotere as Adjuvant Chemotherapy Trial (TACT) 2-year follow-up
Authors: P. Hopwood, A. Ridolfi, S. Russell, C. Peckitt, J. M. Bliss, E. Hall, L. Johnson, P. Barrett-Lee, P. Ellis, D. A. Cameron
Journal: Journal of Clinical Oncology (2008)

548 Background: TACT randomized 4,162 early stage breast cancer patients (pts) to FEC x4 →docetaxel x4 (FEC-T) v control (FEC x8 or epirubicin x4→CMF x4). The primary endpoint was disease-free survival; pts reported QL a secondary endpoint. Methods: Pts at participating sites completed EORTC QLQ-C30, BR23 and HADS questionnaires (Q) at baseline (Bs), end of chemotherapy (CT) cycles (C) 4 and 8, plus toxicity diary cards (DC) at C1, C5 and C8; both Q+DC at 9, 12, 18 and 24 months (M). Mean change in scores from Bs were compared at each later time point; changes of ≥10 points were considered clinically relevant. Standard clinical thresholds for HADS were applied. P value 0.01 allowed for multiple testing. Results: 829 (418 FEC-T; 411 Control) pts entered QL study; Q compliance at Bs, C8 and 24M was 99%, 83% and 78%, respectively. Analyses based on pts who completed Bs before starting CT (796 - 401 FEC-T; 395 Control): median age 49yrs (range 27–71). Increases in BR23 systemic therapy side effects and decreases in body image and sexual enjoyment during CT for both regimens were comparable and clinically relevant. At C8, worse global QL (p=0.01), decreased physical (p<0.01), emotional (p=0.008), social (p=0.003) and role function (p=0.001), and increased pain (p=0.01) and fatigue (p=0.006) were associated with FEC-T, but below clinically relevant threshold. No significant differences between regimens were found post CT. Anxiety was high (24% score >10) at Bs and later decreased (19% C8, 16% 24M). A 3.5-fold increase in depression rates occurred during CT (Bs: 4% score>10; C8: 14%), reducing to near Bs level by 24M (5%). No differences in HADS between regimens at any time. At C1, C8 and 24M, DCs were completed by 458, 410 and 539 pts, respectively. CT toxicities on treatment caused distress and interfered with activities; most were reported more frequently with FEC-T (p<0.001). Rates and differences reduced post CT. Conclusions: Overall CT has a clinically relevant negative impact on QL, whilst greater on treatment impact of FEC-T on QL was observed which resolved during follow-up. However QL assumes greater importance in light of TACT DFS results, showing no overall difference in efficacy between FEC-T and control. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology, sanofi-aventis Pfizer Oncology Pfizer Oncology
Evaluation of side effects in cancer patients during oncological care: A project of the supportive care group of the tumor center Berlin
Authors: P. C. Feyer, U. Steiner, N. Bangemann, S. Kurz, C. Rudolph, C. Schelenz, A. Jagota
Journal: Journal of Clinical Oncology (2009)

e20715 Background: The therapeutic options in tumour treatment protocols include a maximum of tumour cell reduction and at the same time a minimum of side effects in order to secure a good quality of life for the cancer patient. Temporary side effects have been accepted in relation to the benefit risk calculation. A questionnaire for cancer patients was developed to improve the management of side effects of the cancer treatment, to optimize the patient-doctor communication and to register individual problems of the patient. Methods: Cancer patients received a questionnaire with 25 items and were asked for their problems during or after the last tumour specific treatment before having the consultation with the doctor. Gender, age, Karnofsky-index and treatment protocol were additional registered. During September 2007 until December 2007 a total of 272 questionnaires could be collected. The qualitative items have been evaluated with the contigens table method and the parameter free x2 test (Chi-Square-Test). Results: More than 50% of the patients documented additional important points influencing their well being. Nearly all of the evaluated patients had some tumour therapy specific side effects. The most pronounced problem was the physical exhaustion in 71% of the evaluated patients. More than 50% were influenced in their quality of life by more than normal fatigue since the start of their tumour specific therapy. Significant differences could be evaluated in relation to the age, diagnosis and tumour therapy with respect to the symptoms. Conclusions: The questionnaire was be found to be a good method to improve the communication between the patient and the doctor. It was easier to point out individual problems for the patient. The care givers can focus more precisely on important side effects of the tumour specific therapy in order to improve the quality of life of the treated patient. No significant financial relationships to disclose.
Risk assessment in patients with Ph+ chronic myelogenous leukemia at first relapse after allogeneic stem cell transplant: an EBMT retrospective analysis
Authors: Cesare Guglielmi, William Arcese, Jo Hermans, Andrea Bacigalupo, Giuseppe Bandini, Donald Bunjes, Enric Carreras, Agnès Devergie, Francesco Frassoni, John Goldman, Alois Gratwohl, Hans Jochem Kolb, Anna P. Iori, Dietger Niederwieser, H. Grant Prentice, Theo De Witte, Jane Apperley
Journal: Blood (2000)
Epstein–Barr Virus Induces Activation-Induced Cytidine Deaminase Expression in T or NK Cells Leading to Mutagenesis and Development of Lymphoma
Authors: Ayako Arai, Masato Horino, Ken-Ichi Imadome, Kohsuke Imai, Honami Komatsu, Ludan Wang, Go Matsuda, Kasumi Hamazaki, Morito Kurata, Tetsuya Kurosu, Shigeyoshi Fujiwara, Osamu Miura
Journal: Blood (2013)
Ixabepilone and lapatinib for HER2-positive advanced breast cancer: Preclinical rationale and phase I trial
Authors: P. N. Mainwaring, T. Nguyen, G. Price, D. Venter
Journal: Journal of Clinical Oncology (2009)

2582 Trastuzumab with or without taxanes are the cytotoxic therapies of choice for advanced Her-2 positive breast cancer. Ixabepilone and lapatinib have demonstrated clinical efficacy in advanced breast cancer that is resistant to taxanes and trastuzumab. We have compared the therapeutic potential of ixabepilone, lapatinib, paclitaxel and trastuzumab, in vitro, prior to commencing a phase I clinical trial. Three different breast cancer cell lines SK-BR3, BT-474 and MCF-7 (control; non-Her-2 amplified), were seeded 96-well plates, cultured for 24 hours and different concentrations of ixabepilone or paclitaxel and trastuzumab or lapatinib were added. Experiments were performed in triplicate. A MTT viability assay was used to measure the activity of live cells after 0, 3, 24, 48 and 120 hours. The cells and vehicle control wells were averaged and normalized to 100% for comparison to the average value of the 6 replicate wells graphed over time for each cell line, drug concentration and cell density. Student-t test was used to determine the level of significance comparing the 0 hour time point in a pair-wise, pooled variance manner to each other time point. Paclitaxel + trastuzumab significantly reduced proliferation p &lt; 0.001 at 120 hrs; Paclitaxel + lapatinib significantly reduced proliferation p &lt; 0.001 at 120 hrs; Ixabepilone + trastuzumab significantly reduced proliferation p &lt; 0.001 at 120 hrs; Ixabepilone + lapatinib significantly reduced proliferation p &lt; 0.001 at 120 hrs; Dose response curves were clearly evident for all combinations. Of note proliferation was reduced earlier and at lower drug concentrations with lapatinib combinations than with trastuzumab combinations. The drugs whose efficacy was proven in MCF-7 cells were studied in detail on the xCELLigence cell analysis system. These data recapitulated the MTT data and provided in depth detail of the rate of drug action. An international multicentre phase I trial of Ixabepilone with lapatinib ± capecitabine has commenced in patients with Her-2 positive taxane and trastuzumab resistant advanced breast cancer. Toxicity has been as previously described with fatigue, arthralgias, onycholysis and rash occurring. No DLTs have occurred. RECIST responses have been confirmed in 2 of the first 3 patients enrolled. [Table: see text]
Predicting sentinel lymph node status in stage I/II melanoma
Authors: L. Kruper, J. Botbyl, B. Czerniecki, D. Elder, D. Fraker, M. Ming, L. Schuchter, F. Spitz, D. Guerry, P. Gimotty
Journal: Journal of Clinical Oncology (2005)

7501 Background: The histologic status of the sentinel lymph node (SLN) biopsy is one of the most important prognostic factors for recurrence and survival for patients with clinical stage I and II melanoma. SLN biopsy has modest morbidity, is costly, and is negative in the majority of patients. To address the issue of selecting patients at high and low risk for SLN metastasis, we sought prognostic factors that predict SLN involvement by examining characteristics of both the primary tumor and patient. Methods: Our study included a retrospective cohort of 327 patients with primary melanomas greater than 1.0 mm with no clinical evidence of metastatic disease, those commonly offered SLN biopsy, who underwent SLN biopsy between 1995 and June 2003. Logistic regression analyses were used to investigate the association between SLN positivity and Breslow thickness, Clark level, tumor infiltrating lymphocytes (TIL), ulceration, mitotic rate (MR), lesion site, gender, and age. Results: 51 of the 327 patients had at least one positive SLN (15.6%). Only MR, TIL and thickness were found to be independent prognostic factors for SLN positivity. For MR >3, the adjusted odds ratio (OR) was 3.1 (95% Confidence Interval (CI): 1.4–6.7) for absent TIL, the OR was 3.3 (CI: 1.7–6.5) and for thickness >2.0 mm, the OR was 2.6 (CI: 1.2–5.3). The proportion of patients with a positive SLN ranged from 3.8% in those with no risk factor (absent TIL, MR >3, and thickness >2.0 mm) to 48.3% for those with all 3 (see table). Conclusion: By incorporating TIL, MR and thickness into a prognostic model, both patients at high risk and minimal risk for SLN metastasis can be identified. When validated, this model can be used in patient management and trial design to select patients to have and be spared SLN biopsy. No significant financial relationships to disclose.
New therapeutic modalities and survival trends of lung carcinoma
Authors: G. N. Batty, A. Itzhaki, K. Uhm, M. Pereira, T. Herskovic, M. Maroules
Journal: Journal of Clinical Oncology (2008)

7601 Background: Despite the development of new therapeutic modalities for lung carcinoma, the survival rates seem to be unchanged. This study examines the lung specific mortality and treatment strategies among patients diagnosed with lung cancer over fourteen- year period. Methods: We performed a retrospective cohort study of inpatients with lung carcinoma, diagnosed respectively between 1992 and 2006. The patient populations were divided into two subgroups according to the time of diagnosis respectively 1992 - 1995, 1996 - 1999 and 2000–2003. Different treatment strategies, stage at diagnosis and baseline characteristics were reported. Using Chi-square test, different subgroups were compared to lung cancer specific mortality. Results: During 1992 and 2003, 1,156 patients with lung carcinoma were examined (716 male, 439 female, 805 Caucasian and 255 African American, mean age 68 ± 3.7 years). Among which 299, 297, 305 and 255 were respectively diagnosed during (1992 - 1995, 1996 - 1999, 2000–2003 and 2004–2005). They had correspondingly radiation therapy 314 (27.16%), surgery 311 (26.9%), combined radiation with chemotherapy 184 (15.92%), combined surgery with radiation 135 (11.68%) other combination therapies 95 (8.22%) while 117 (10.12%) received no treatment. Morphologies described as 54 (4.67%) NOS, 376 (32.52%) epithelial, 349 (30.2%) squamous, 338 (29.2%) adenocarcinoma. No statistically significant difference was identified between the survival rates of each subgroup within their frame periods respectively 28(9.36%), 32 (10.77%), 37 (8.24%) (Chi-square 1.26, 3 degree of freedom, p = 0.73). Conclusions: No decline in the rate of death from lung cancer was observed in spite of the introduction of new therapeutic modalities. This highlights the importance either of a promising screening and its combination with therapy which may improve the survival. No significant financial relationships to disclose.
Development and validation of a questionnaire for the identification of hereditary breast cancer in primary care
Authors: P. Ashton-Prolla, J. Giacomazzi, A. V. Schmidt, F. L. Roth, E. Aguiar, S. M. Moreira, V. Belo-Reyes, L. Kalakun, M. Caleffi, S. A. Camey
Journal: Journal of Clinical Oncology (2008)

22094 Background: A seven-question instrument to inquire about the family history of breast (BC), ovarian (OC) and colorectal cancer (CRC) was developed to identify patients at-risk for hereditary breast cancer (HBC) syndromes within a large population-based cohort study, the Núcleo Mama Porto Alegre Cohort. The questionnaire was applied to women in primary care units (PCU) from an underserved urban area of Southern Brazil. Patients answering positively to at least one of the questions were referred to genetic cancer risk assessment (GCRA). Methods: The instrument included questions about a FH of BC under age 50, bilateral or male BC, double primary breast and ovarian cancers in the same person, BC or OC in a first degree relative (FDR), two or more relatives with BC, OC and/or CRC. Answers obtained in the PCUs were compared to those obtained to the same questions during cancer risk assessment through Kappa coefficient determination. Another group of patients that responded negatively to the FH questionnaire was submitted to GCRA to confirm the reported FH. The ROC curve was used to verify the cutoff with highest values for the Youden's Index in order to predict genetic risk defined by pedigree analysis consistent with the phenotype of an HBC syndrome. Results: Of the 9234 women included in the study, 1286 (13.9%) answered positively to at least one of the questions; 885 (68.8%) were evaluated by a geneticist. The group without a FH of cancer consisted of 910 participants. The Kappa coefficients for the seven questions were, respectively: 0.872 (BC/OC in FDR), 0.560 (bilateral BC), 0.332 (male BC), 0.084 (BC/OC double primary), 0.790 (BC<50), 0.582 (≥ 2 BC and/or OC) and 0.533 (≥ 2 BC and/or CRC) (p<0.001). The cutoff for the sum of seven questions was one, i.e., one positive answer was sufficient to predict risk for HBC. At this cutoff the Youden's Index, sensibility and specificity are 0.441, 0.876 and 0.565, respectively. Conclusions: A brief and simple questionnaire was developed for the identification of women at-risk for HBC in the primary care setting. A positive answer in a single question of the instrument was associated with a good prediction of the HBC phenotype. No significant financial relationships to disclose.
Comparison of molecular (BluePrint+MammaPrint) and pathological subtypes for breast cancer among the first 800 patients from the EORTC 10041/BIG 3-04 (MINDACT) trial.
Authors: Giuseppe Viale, Leen Slaets, Femke De Snoo, Laura J. van 't Veer, Emiel J. Rutgers, Martine J. Piccart-Gebhart, Jan Bogaerts, Jeroen van den Akker, Kristel Engelen, Leila Russo, Patrizia Dell'Orto, Fatima Cardoso
Journal: Journal of Clinical Oncology (2012)

1022 Background: Biology has become the main driver of breast cancer therapy. Intrinsic biological subtypes by gene expression profiling have been identified. Pathology can be used to define surrogates of these subtypes but these are not always concordant, which may lead to different treatment plans. We investigated the concordance between BluePrint (BP) + MammaPrint (MP) (micro array based) breast cancer subtypes and pathological surrogates (based on ER, PR, HER2, and Ki67). Contrary to the Perou gene set (evolved into PAM50), BluePrint was trained using pathological data. Methods: Using available data (centrally assessed pathology and genomic) from the MINDACT pilot phase (Rutgers et al 2011) 621 tumors were analyzed. Two pathology classifications were used: one with 4 categories and one with 5 categories (Goldhirsch et al 2011). Based on BP 3 subtypes are formed: Luminal, HER2 and Basal. The Luminal subtype is further split into Luminal A (MP low risk) and Luminal B (MP high risk). Results: See table. Conclusions: All pathological Basal cases are BP Basal, apart from 1 BP HER2 case. Of the BP Basal cases, 15 are not pathological Basal: 1 is Luminal A, 11 are Luminal B (of which 8 are IHC ER/PR borderline (≥1% and &lt; 10%)) and 3 are HER2. All pathological Luminal (A &amp; B) that are BP HER2 are HER2- by TargetPrint. 25 of the 26 pathological HER2+ that are BP Luminal A are ER+. Most discordant cases are seen within the Luminal subtype, indicating that Ki67 discriminates Luminal A vs. B differently than MammaPrint does. The observed subtype discrepancies reveal potential important impact for treatment-decision making. MINDACT will provide important information. [Table: see text]
Does zoledronic acid (ZOL) reduce skeletal-related events (SREs) and improve progression-free survival (PFS) in patients (Pts) with multiple myeloma (MM) with or without bone disease? MRC myeloma IX study results.
Authors: K. Boyd, G. Morgan, F. Davies, P. Wu, W. Gregory, S. E. Bell, A. Szubert, N. Navarro Coy, M. Drayson, R. G. Owen, S. Feyler, J. Ashcroft, F. Ross, J. Byrne, H. Roddie, C. Rudin, G. Cook, G. H. Jackson, J. A. Child
Journal: Journal of Clinical Oncology (2011)

8010 Background: Pts with osteolytic lesions from MM receive bisphosphonates (BPs) for reducing the risk of skeletal-related events (SREs). However, guidance has been unclear on whether BPs should be initiated before bone disease (BD) is diagnosed. The MRC Myeloma IX study examined BP effects in MM pts initiating chemotherapy and has already revealed significant OS and PFS benefits for ZOL over clodronate (CLO; Morgan GJ, et al. Lancet. 2010). BD was not a requirement for enrollment. Methods: Newly diagnosed MM pts were randomized to ZOL (4 mg IV q 21-28 days) or CLO (1600 mg/day PO) plus antimyeloma therapy. BPs continued at least until disease progression. All pts received baseline bone evaluations and were defined as having BD if osteolytic lesions or signs of BD were present on axial skeletal surveys. PFS was estimated using Kaplan-Meier methodology, and hazard ratios (HRs) were calculated using stratified Cox models. SREs were analyzed using cumulative incidence functions. Results: Among 1960 evaluable pts, 279 of 981 (28.4%) ZOL- and 261 of 979 (26.7%) CLO-treated pts had no BD. Overall, ZOL improved PFS (HR = 0.88; P = .0179) vs CLO. Among pts with BD, ZOL produced a trend for PFS benefit (20.4 vs 18 mo; HR = 0.90; P = .101) vs CLO. Among pts without BD, there was no significant difference in PFS (18 mo each; HR = 0.99; P = .885) for ZOL vs CLO. During the first year, the risk of a first SRE was 0.29 for CLO and 0.22 for ZOL overall, 0.36 for CLO and 0.29 for ZOL in pts with BD (19% reduction), and 0.12 for CLO and 0.07 for ZOL in pts without BD (42% reduction). Both BPs were generally well tolerated, and renal adverse events were similar between groups. Overall incidence of confirmed osteonecrosis of the jaw (ONJ) was low (ZOL, 3.6%; CLO, 0.3%), and events were generally low-grade. Conclusions: ZOL may increase PFS vs CLO in pts with BD, and significantly reduced SRE risk regardless of baseline BD status in the MRC Myeloma IX study. This supports initiating ZOL in all newly diagnosed MM pts regardless of BD status. The lack of a PFS effect in pts without BD may reflect the unique biology of this group as defined by GEP analysis.