tbuckley/cabot-search huggingface dataset:
Correlation between chromosome 17 polysomy and estrogen receptor in HER2-positive breast cancer.
Authors: D. Miura, T. Iwatani, H. Kawabata, K. Ohhashi
Journal: Journal of Clinical Oncology (2010)

e11023 Background: Among HER2 overexpressing breast cancers, chromosome 17 polysomy (C17) may not affect trastuzumab response in several clinical trials. Precise assessment of HER2 is critical in breast cancers and predicts benefit of anti-HER2 therapy. Hormone receptors (HR) and HER2 coexpression in not uncommon in breast cancer, approximately half of HER2 (+) also coexpress HR. Although there are quantitative inverse association between HER2 and both ER and PgR, the biology of triple positive breast cancer and also correlation with C17 are still less known. To analyze the epidemiologic feature of HER2 (+), particularly triple positive in Japanese patients, consecutive operable breast cancer patients during 05-07 treated in single institution were studied. Methods: HER2 status of consecutive 370 patients excluding DCIS and whose specimens were poor quality for study, were analyzed with Pathvysion (FISH). We defined HER2 (+) and C17 as HER2/chromosome 17 ratio > = 2.2 and CEP ratio > = 2.2, respectively. The HR status was evaluated using IHC with the estimated proportion of positive- staining tumor cells according as the Allred score (PS0-5). Results: HER2(+) was found in 19% (71/370) and C17 in 26% (98/370). As regards ER PS2-5 was found in 81% (300/370), particularly PS5 in 68% (251/370). Among 71 HER2(+) cases, PS5 and PS 2-4 were found in 45% (32/71) and 18% (13/71) respectively. Interestingly in HER2(+) cases, there was a trend toward higher FISH ratios with increases in PS score, averages of FISH ratios in PS0-1 (26 cases), PS2-4 (13), and PS5 (32) were 5.9, 6.9, and 7.5 respectively. Although there was no association between the presence of C17 and ER status in HER2(-) cases, ER(+) (PS2-5) was significantly found in higher frequency of 72% (34/47) in HER2(+)C17(-) than 46% (11/24) in HER2(+)C17(+). Conclusions: We found a positive correlation between FISH ratio and proportion of ER positive-staining tumor cells in HER2(+) subset. However, in case of HER2(+), chromosome 17 polysomy drives ER status to negative. No significant financial relationships to disclose.
Is docetaxel-prednisone (DP) feasible in frail elderly (age 75 or older) patients with castration-resistant metastatic prostate cancer (CRMPC)? GERICO10-GETUG P03 trial: A trial from elderly and genitourinary oncology UNICANCER groups.
Authors: Loic Mourey, Emmanuel Sevin, Igor Latorzeff, Nadine Houede, Jérome Meunier, Frank Priou, Gwenaelle Gravis, Elisabeth Carola, Christine Orsini, Thomas Filleron
Journal: Journal of Clinical Oncology (2012)

93 Background: Standard treatment of CRMPC is DP 75 mg/m² every 3 weeks since a symptomatic and overall survival benefit was demonstrated. Little is known about feasibility of DP in unselected elderly patients (day to day practice). Methods: Randomized phase II study evaluating prospectively the feasibility of DP administered every 3 weeks (60 mg / m² C1 then 70 mg / m² for subsequent cycles) or weekly (35mg/m² D1D8 with Day 1 = Day 21) in patients ≥75 years old, evaluated by comprehensive geriatric assessment, belonging to group 2 “vulnerable” or to group 3 “frail” of the classification proposed by the International Society of Geriatric Oncology (SIOG). Feasibility is defined as the possibility for a patient to receive 6 cycles of chemotherapy without fulfilling the criteria for withdrawal from study defined “a priori” by GERICO group: - stop or delay chemotherapy &gt; 2 weeks - necessity to reduce chemotherapy dose &gt; 25% - febrile neutropenia or NCI CTC grade III non-haematological toxicity (except alopecia) - loss of autonomy ( Activity of Daily Living (ADL) decrease≥2 points) →geriatric criterion It is a double randomized phase II based on a Simon’s optimum two stage design for each strata defined according to the SIOG criteria (α = 5%, 1-β = 90 %, p0 = 0.70 and p1 = 0.90). A pharmacokinetic / pharmacodynamic study (method of population pharmacokinetics) and pharmacogenetic study of PXR (pregnane X receptor) CYP3A4 and CYP3A5) are planed. Results: 25 centers participate to the study (23 opened). 10 centers have included 22 patients (16 “vulnerable” and 6 “frail”) from December 2010 until now. Conclusions: The results of this study will support the prescription of chemotherapy and its modalities, in patients aged 75 and over, classified as “vulnerable” or “frail” according to SIOG criteria, after comprehensive geriatric assessment.
Aristolochic acid nephropathy in Taiwan: Harbinger of a global iatrogenic disease.
Authors: A. P. Grollman, C. Chen, M. Moriya, K. Dickman, L. Wu, G. Mihalyne, K. L. Edwards, K. Snappin, Y. Pu
Journal: Journal of Clinical Oncology (2011)

1592 Background: Aristolochic acid (AA), a powerful nephrotoxin and human carcinogen, was shown recently to be the causative agent of endemic (Balkan) nephropathy, a chronic renal disease associated with transitional cell (urothelial) carcinomas of the upper urinary tract (UUC). Following metabolic activation, AA reacts with DNA to form aristolactam-DNA (AL-DNA) adducts. These mutagenic lesions are inefficiently repaired, persisting for years in the renal cortex, where they serve as robust biomarkers of exposure to AA. In Asian countries, exposure to AA occurs through the use of traditional herbal remedies prepared from various species of Aristolochia. Thus, in Taiwan, where one-third of the population has been prescribed herbal remedies containing AA, the incidence of UUC is the highest in the world. This case-control, molecular epidemiology study was designed to test the hypothesis that the high incidence of UUC in Taiwan reflects exposure to AA. Methods: Following nephroureterectomy, DNA was extracted from the renal cortex and tumor tissues of 48 patients with UUC. Nineteen patients with renal cell carcinoma (RCC) and 17 patients with angiomyolipoma (AML) served as controls. AL-DNA adducts were quantified by 32P-postlabelling techniques. Chip-sequencing technology was used to establish the pattern of mutations in the TP53 gene. Results: The TP53 mutational spectrum of patients with UUC revealed a predominance of A:T to T:A transversions located on the non-transcribed strand of DNA, together with several unique mutational hot spots, a pattern previously noted to be a “mutational signature” for exposure to AA. AL-DNA adducts were detected in 30.4%, 36.8% and 31.7% of UUC, RCC and AML cases, respectively, consistent with estimates of exposure of the Taiwanese population to AA. Stage 4 or 5 chronic renal disease was present in 61.5% of patients with UUC. Conclusions: Ingestion of AA contributes significantly to the high incidence of UUC in Taiwan. AA nephropathy, a silent, yet widespread iatrogenic disease, is an international public health problem of significant magnitude.
Phase I study of the combination of alisertib (MLN8237) and gemcitabine in advanced solid tumors.
Authors: Jasmine Huynh, Justin Chen, Edward Jae-Hoon Kim, David R. Gandara, Thomas John Semrad, Jonathan W. Riess, Tianhong Li, Chun-Yi Wu, Chao Zhang, Aiming Yu, Karen Matsukuma, Karen Kelly
Journal: Journal of Clinical Oncology (2020)

3589 Background: Aurora Kinase A (AKA) is a key mitotic regulator overexpressed in multiple solid tumors. This open-label dose escalation and expansion phase I study evaluated the safety and tolerability of alisertib (MLN8237), an oral AKA inhibitor, in combination with gemcitabine. Methods: In dose escalation, patients (pts) &gt; 18y with refractory solid tumors received 28-day cycles of gemcitabine on days 1, 8, 15 and alisertib twice daily on days 1-3, 8-10, and 15-17. Gemcitabine was given at 1000mg/m2. Four dose levels (DL) of alisertib (20-50mg) were given per 3+3 design to investigate dose limiting toxicities (DLT) in cycle 1, to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D). In dose expansion, advanced pancreatic adenocarcinoma pts received the MTD dose twice daily on a modified dosing schedule to allow for pharmacokinetic (PK) evaluation. Anti-tumor activity was assessed by response rate (RECIST 1.1) and progression-free survival (PFS). PK evaluation of plasma gemcitabine and alisertib was performed on all pts enrolled in the dose expansion. PK sampling was performed before treatment, immediately after gemcitabine infusion, and at other pre-specified post-infusion timepoints. Results: Twenty-six pts were treated in total: 21 pts in dose escalation and 5 pts in dose expansion. Overall, median age was 57y [42-82]; 50% male; 62% PS 1 (16 pts); 2 [0-7] median prior therapies. In the dose escalation phase, 9 tumor types were included and NSCLC was most common (7 pts). Maximum administered dose (DL4) achieved 900 mg alisertib per cycle and was tolerated (1 DLT in 6 pts). The dose expansion phase enrolled 5 pts with advanced pancreatic adenocarcinoma; median age 63y [48-82]; 60% male; 60% PS 1 (3 pts); 2 [1-2] median prior therapies. Grade ≥3 TRAEs were observed in 73% of all pts and were predominantly hematologic, including neutropenia (54%), leukopenia (50%), and lymphopenia (31%). Similar TRAEs were seen at DL4; all 14 pts experienced neutropenia with 64% experiencing grade ≥3 neutropenia. Fourteen of 23 evaluable pts (61%) had stable disease and 2 pts (9%) had partial response (PR) as best overall response. Median PFS was 2.9 months (95% CI 2.0-4.2). Analysis of PK data is ongoing and will be reported. Conclusions: Alisertib can be safely administered with gemcitabine. RP2D for alisertib is 50 mg PO BID in combination with full dose gemcitabine. Best response was at least stable disease in a majority of pts with PR observed in 9% of this heavily pretreated group of patients. Most grade ≥3 TRAEs were hematologic. Results of PK studies will also be reported. Clinical trial information: NCT01924260 .
Vinflunine maintenance therapy versus best supportive care after platinum combination in advanced bladder cancer: A phase II, randomized, open label, study (MAJA study, SOGUG 2011-02)—Interim analysis on safety.
Authors: Susana Hernando Polo, Aranzazu Gonzalez del Alba, Begoña Perez-Valderrama, José Carlos Villa Guzman, Miguel Angel Climent, Nuria Lainez, Albert Font, Ignacio Duran, Begoña Mellado, Daniel Castellano, Jesús García-Donas, Juan Antonio Virizuela, Luis Leon, Maria del Mar LLorente, Montserrat Domenech, Rafael Morales, Enrique Gallardo, Javier Puente, Sonia Maciá, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2014)

359 Background: Vinflunine (VFL) is a novel microtubule inhibitor currently approved by EMA as treatment after platinum progression, in metastasic bladder cancer. We evaluated whether maintenance vinflunine delays progression after response to CT. Methods: Multicenter, randomized, open label, proof-of-concept study that is being performed in 21 institutions members of the Spanish Oncology Genitourinary Group (SOGUG). Subjects are randomized to receive (arm A) VFL 320 mg/m 2 (280mg/m 2 for patients with PS=1, age ≥ 75 years, prior pelvic radiotherapy or creatinine clearance Cr &lt;60ml/min) every 21 days plus best supportive care (BSC) vs. (arm B) BSC alone until disease progression. Main inclusion criteria: Subjects ≥18 and&lt; 80 years of age with histological diagnosis of transitional cell carcinoma of the urothelial tract and measurable disease whith radiological response or stabilization after 4 to 6 cy of a cisplatin-containing doublet for metastasic/advanced disease (carboplatin allowed on cy 5-6). Primary objective: progression free survival (PFS). A sample size of 86 patients allocated in a 1:1 ratio is planned. Recruitment started on April 2012. A pharmacogenomic translational study will be conducted. Results: To September 2013, 46 pts have been enrolled, 20 in the VFL+BSC group, 26 in the BSC group. We present the results of the interim analysis including data from first 25 patients who have completed at least 2 cycles. Median age 65.6 years (range 54-77); PS 0/1, 44%/56%; CrCl &lt;60 ml/min 16%; liver metastasis 16%; prior pelvic RT 8%. Primary tumour location: bladder 76%, upper urinary tract 20%, urethra 4%. Pure transitional cells 84%. Metastatic/locoregional disease, 72% / 28%. We analyzed 63 cy in the chemotherapy arm. Most common G3/4 (% cycles) AEs on vinflunine were constipation (12.7%), neutropenia (7.9%), fatigue (4.8%), myalgia (3.2%). One death was reported due to dyspnea, not related to the treatment. No febrile neutropenia was reported at the time of the analysis. Conclusions: Maintenance with vinflunine presented an acceptable security profile leading to trial continuation. Clinical trial information: 2011-001271-39.
Pain incidence and control in hospitalized patients in a medical oncology unit of a general hospital in Italy
Authors: F. Piazza, K. Stocco, G. Vicario, G. Sgarbossa, M. Bortolin, G. Vultaggio, P. Manente
Journal: Journal of Clinical Oncology (2008)

20730 Background: Hospitalized cancer patients suffer from complications or they are terminally-ill and most of them complain of pain. Chronic pain in cancer patients has a multifaceted origin, predominantly caused by the primitive tumor and/or localization to other organs. The physical pain is often associated to psychological pain, in which case suffering involves the entire subject. Variuos psychological phases are usually passed through by the patient: negation, refusal, anger, compromise, depression, acceptance. To optimize the treatment of cancer pain, it is necessary to comprehend all these aspects. Thus, it is important to correctly evaluate the degree of pain. Methods: There are several tools for cancer pain evaluation: VAS (visual analog scale), NRS (numerical rating scale), VDS (verbal descriptor scale). We adopted the VAS scale because of easy and simple administration and wide use. The patient was asked to fill the form at least twice a day (at 8 AM and 8 PM). Low compliant patients (drowsy, critical, not oriented) were excluded. From April 28th 2007 to November 28th 2007, questionnaires were administered to 80 consecutive different cancer patients. In 22 cases they were not completed. 20 patients died. Overall, 72% patients participated to the study. In most cases, patients refused to fill the questionnaire in order to avoid the stress to their disease status. Results: 15% of patients was free of pain, in 10% of them pain was mild, in 30% moderate and in 45% severe. The site of pain was: 40% to the column, 25% legs, 25% abdomen, 20% head. 46% of patients reported stillness and 11% calmness; 31% felt angry and 12% desperate. Conclusions: This survey allowed to observe that in 40% of subjects there was inadequate pain conrol; moreover, 43% of patients reported a significant psychological distress.These results led us to modify the approach to the treatment of suffering (both physical and psychological) of the cancer patient, by associating to the antalgic medical therapy a psycho-therapeutical support. It resulted also important to involve the nursing team in the evaluation of pain intensity, since patients often demonstrated to feel more confortable in telling their suffering to the nurses. No significant financial relationships to disclose.
Adjuvant high-dose dense chemotherapy: Epirubicin-dexrazoxane and paclitaxel with peripheral blood progenitor cell (PBPC) support in high risk stage II-IIIA breast cancer (phase II trial)
Authors: G. L. Frassineti, U. de Giorgi, N. Giovannini, B. Kopf, E. Flamini, O. Carminati, D. Tassinari, L. Cecconetto, L. Mercatali, F. Zumaglini
Journal: Journal of Clinical Oncology (2005)

897 Background: There is evidence to suggest that dose intensity is correlated with clinical efficacy in the treatment of patients (pts) with breast cancer. Methods: Seventy consecutive pts with stage II-IIIA breast cancer and four or more involved lymph nodes received a mobilizing course with epirubicin 150 mg/m2, preceded by dexrazoxane (day 1), and paclitaxel 175 mg/m2 (day 2) plus filgrastim, followed by 3 courses of epirubicin 150 mg/m2 preceded by dexrazoxane (day 1), paclitaxel 400 mg/m2 (day 2) with PBPC support and filgrastim, every 16–19 days. Paclitaxel 400 mg/m2 was given as a 6-hour infusion to the first 25 pts (P6h pts) and as a 24-hour infusion to the next 45 pts (P24h pts) in an attempt to reduce neurotoxicity. Results: No toxic deaths or congestive heart failure occurred. Three pts went off study due to a severe hypersensitivity reaction to paclitaxel (1P6h/2P24h pts) and 8 pts interrupted treatment because of prolonged grade 3 peripheral neurotoxicity (3P6h/5P24h pts). In all cases, neurotoxicity was reversible. Five-year disease-free and overall survival in P6h pts was 46% and 63%, respectively. Results in P24h pts are not available yet. Conclusions: High-dose dense chemotherapy with epirubicin and paclitaxel with PBPC support and filgrastim is a feasible and safe approach in the adjuvant treatment of patients with high risk stage II-IIIA breast cancer. A longer follow-up is needed to define the real toxicity and activity of this regimen. This work was supported by the Italian National Research Council (Project No.31412), and by Istituto Oncologico Romagnolo (Maria Bianca Taroni Scholarship). No significant financial relationships to disclose.
C35: A new prognostic tool and potential target in prostate cancer.
Authors: Deepak Kilari, Jorge Yao, Emelian Scosyrev, Elizabeth E. Evans, Deepak M. Sahasrabudhe
Journal: Journal of Clinical Oncology (2013)

212 Background: Identification and validation of biomarkers can help prognosticate patients and potentially serve as therapeutic targets. C35, a protein encoded by novel gene C17orf37 is located on 17q12 “the hotspot of cancer”. Dasgupta et al. (Oncogene 2009) noted higher expression of C35 in prostate cancer cell lines as compared to minimal expression in normal prostate cells. Furthermore, over expression of C35 enhanced motility and invasion. We hypothesized that C35 expression would correlate with other markers of aggressive clinical behavior and tested this by studying C35 expression in tissue microarrays (TMAs). Methods: TMAs were constructed using tissue samples obtained from normal organs including prostate, primary prostate cancers and prostate cancer from various metastatic sites. The TMAs had triplicates of each specimen which was then stained with rabbit polyclonal anti -C35 antibody. Each sample was scored based on the product of intensity (0-3) and distribution (0-4) of staining, with the maximum score being 12. A blinded review of the final scores and Gleason’s sum were independently conducted by a pathologist. Results: The C35 expression scores were higher in primary prostate cancer compared to benign prostate tissue. The average expression scores increased with increasing Gleason sum. Prostate cancer specimens from the metastatic sites had significantly lower expression scores when compared with the primary prostate cancer specimens. There was minimal to no expression in other normal organs. All these differences were statistically significant (p&lt;0.001). The protein was predominantly cytosolic with membrane localization. Distributions of expression scores according to specimen type are summarized below. Conclusions: C35 expression directly correlates with Gleason sum, a validated prognostic marker. C35 may be a potential target for therapeutic agents. Further studies are needed to determine if increased expression of C35 in normal prostate can predict future development of prostate cancer. [Table: see text]
Assessment of tumor size and tumour response for nasopharyngeal carcinoma (NPC): Implication of different methods of assessment for an Irregular shaped tumor
Authors: B. C. Zee, A. D. King, E. Yuen, B. Ma, S. F. Leung, D. Yeung, M. Kam, A. Chan, A. T. Ahuja
Journal: Journal of Clinical Oncology (2005)

5582 Background: Tumor size is an important outcome for phase II clinical trials. In the past bi-dimensional measurements (BDM) have been commonly used. More recently uni-dimensional measurements (UDM) have been adopted in the response evaluation in solid tumors (RECIST). However, for irregular shaped tumors such as NPC there remains the question as to whether these simple methods reflect the tumor size. The objective of this study is to evaluate the relation of UDM and BDM to total tumor volume (TTV). Methods: Patients undergoing conventional axial magnetic resonance imaging (MRI) of the head and neck for the staging of previously untreated NPC were recruited for this retrospective study. TTV, the summation of areas from cross sectional MRI is used as the reference standard. The UDM was obtained by measuring the maximum diameter of the tumor and BDM was obtained by UDM x (greatest measurement perpendicular to UDM). A general linear model was used to assess if TTV is associated with UDM or BDM. Comparisons of the response criteria RECIST (UDM CR<30%PR<SD<-20%PD), WHO (BDM CR<50%PR<SD<-25%PD) and change in TTV (CR<65%PR<SD<-40%) were made. Kappa statistic and McNemar’s test were performed to assess the degree of agreement and discordance in response. Results: We have 44 patients, of which 28 also had post-treatment measurements. TTV is associated significantly with BDM (p=0.0002) but not with UDM. The change from pre- to post-treatment in TTV is associated significantly with the change in BDM (p<0.0001) but not with the change in UDM. Percent change in TTV is associated significantly with percent change in BDM (p=0.0011) but not with UDM. In terms of response based on TTV, there are 4 CR, 16 PR, 8 SD. However, based on UDM there are 4 CR, 12 PR, 12 SD, kappa of 0.42 (95% CI 0.11 - 0.72). There are 7 PR based on TTV misclassified as SD and 3 SD misclassified as PR (p=0.1714). For BDM (WHO criteria) there are 4 CR, 13 PR, 11 SD, kappa of 0.47 (95% CI 0.16 - 0.77). There are 6 PR based on TTV misclassified as SD, and 3 SD misclassified as PR (p=0.2525). Conclusions: BDM gives a good reflection of the size of NPC, but the association was not significant in UDM. The response using UDM and BDM are comparable. No significant financial relationships to disclose.