tbuckley/cabot-search huggingface dataset:
Quantification and molecular profiling of circulating tumor cells (CTCs) in urothelial cancer (UC) before and during systemic treatment: Implications across the clinical stages.
Authors: Andrea Necchi, Emanuela Fina, Patrizia Giannatempo, Maurizio Colecchia, Chiara Iacona, Elena Farè, Daniele Raggi, Nicola Nicolai, Roberto Salvioni, Alessandro M. Gianni, Luigi Mariani, Maria Grazia Daidone, Vera Cappelletti
Journal: Journal of Clinical Oncology (2014)

319 Background: CTCs from patients (pts) at different clinical stages were analyzed by a never explored experimental approach based on a combination of two techniques. Provision of this information may contribute to optimize tailored therapies. Methods: 3 cohorts were analyzed: pts with muscle-invasive bladder cancer receiving neoadjuvant (NA) sorafenib + chemotherapy (CT) (NCT01222676), and metastatic (M1) pts receiving 1st-line MVAC, and 2nd-line (M2) anti-TGFβ receptor ALK1 PF-03446962 (NCT01620970). 5 ml of whole blood were filtered by ScreenCell Cyto devices and CTC status was assessed with centralized scoring by referral pathologists. Additional 5 ml of whole blood were processed by immunomagnetic beads (AdnaTestSelect kit) and the expression level of a panel of markers (including EPCAM and MUC1) was studied using RT-multiplex PCR. The objective was the association with clinical response/relapse. Results: From 07/2012 to 08/2013, 48 pts (17 NA, 17 M1, and 14 M2) were enrolled. Rates of baseline CTC+ were: 91, 77, 75% (ScreenCell), and 36, 41, 69% with AdnaTest, respectively. NA setting: from baseline to post-CT, all pts had a stepwise reduction of CTC count/5 ml blood by ScreenCell (median baseline of 15 [0-40] to 0 [0-3]). Increase in circulating EPCAM±MUC1 levels by CTC was seen in accordance with the 3 disease progressions (PD). M1 setting: Pts who relapsed had a median of 25 CTC/5 ml (IQR: 12-47) at the end of CT, while all the others had levels &lt;10. EPCAM profile was concordant in all cases (median 1.10 vs 0.42 ng/µl). Despite classified as partial/complete responders by RECIST criteria, 5/7 cases with &gt;6 month follow-up displayed an increase in EPCAM levels and CTC number which anticipated a relapse. M2 setting: increase in CTC signals from baseline to +2 months was observed in 8/9 evaluable cases by AdnaTest and 4/5 evaluable cases by ScreenCell, in accordance with PD. Conclusions: This combined technique showed a promising ability to anticipate the detection of clinical relapse, although it still needs a larger sample size. Refining molecular characterization will help designing informed clinical trials.
Updated analysis: Observational cohort study of first-line bevacizumab combined with chemotherapy in metastatic colorectal cancer (HGCSG0802)—Sub-group analysis by <i>KRAS </i>Exon2 status.
Authors: Michio Nakamura, Satoshi Yuki, Kentaro Sawada, Ayane Oba, Atsushi Sato, Takashi Kato, Takashi Meguro, Nobuyuki Ehira, Miki Tateyama, Kazuteru Hatanaka, Kazunori Eto, Hiroyuki Okuda, Yoshimitsu Kobayashi, Osamu Muto, Masakazu Abe, Kanji Kato, Mineo Kudo, Kencho Miyashita, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2016)

522 Background: A few reports have shown the efficacy of bevacizumab (BV) independent of the KRAS Exon2 mutational status (KRAS). We performed a sub-group analysis by KRAS from the HGCSG0802 observational cohort study that investigated 115 patients (pts) treated with 1st line BV for metastatic colorectal cancer (mCRC). Methods: The objective of HGCSG0802 was to evaluate progression-free survival (PFS), overall survival (OS), response rate (RR), and safety. The key eligibility criteria were with evaluable lesions, older than 20 years, ECOG PS 0-2. In this analysis, pts characteristics, RR and safety were compared using Fisher’s exact test. Univariate and multivariate analysis for PFS and OS were performed using patient characteristics. Survival analyses were performed with Kaplan-Meier method and Cox proportional hazards model. Results: Of 108 pts (the full analysis set), 99 pts were evaluable for KRAS. Sixty-two pts (62.6%) had KRAS wild-type (wt) and 37 pts (37.4%) had mutation (mt). The pts characteristics between those with wt and with mt were generally balanced except for PS 0 (91.9% in wt, 75.7% in mt; p = 0.036) and lung metastasis (33.9% in wt, 62.2% in mt; p = 0.007). RR was 70.0% in wt versus 65.7% in mt. Adverse events related to BV were almost balanced except for bleeding (any grade) (30.6% in wt, 13.5% in mt; p = 0.088). The median PFS and OS was 9.9 and 26.8 months in wt versus 7.9 and 17.5 months in mt (PFS ; HR 1.519, p = 0.064 and OS ; HR 1.944, p = 0.005). In Cox multivariate analysis, KRAS mt showed significantly shorter PFS and OS (PFS ; HR 1.637, p = 0.045 and OS ; HR 2.132, p = 0.005). Conclusions: In this cohort, depending on the KRAS Exon2 mutational status, severe adverse events were no significant difference. The multivariate analysis showed that PFS and OS were significantly longer in the KRAS Exon2 wild-type patients. So, KRAS Exon2 mutational status can be a predictive and prognostic marker in bevacizumab combined 1st line chemotherapy. Clinical trial information: UMIN000018935.
Postoperative treatment with fermented mistletoe (Viscum album L.) extract stratified by therapy regimen in patients with primary non-metastatic colorectal carcinoma
Authors: M. R. Schlaeppi, H. Matthes, W. E. Friedel, P. R. Bock
Journal: Journal of Clinical Oncology (2008)

20536 Background: The therapy with fermented mistletoe extract Iscador (ISC) is a frequently used supportive treatment in colorectal carcinoma patients in Germany and Switzerland to improve quality of life (QoL) and reduce conventional therapy (CONTH)-related adverse drug reactions (ADR). Methods: In a multicenter comparative observational cohort study the efficacy and safety of ISC in supportive care of patients with colorectal carcinoma in comparison with parallel control groups were evaluated. The patients received either CONTH, CONTH with ISC, ISC only or no therapy. Unselected standardized pseudonymized data from medical records that met the eligibility criteria were followed up until the last visit or death. The pre-specified endpoints were ADR, QoL and disease-free survival (DFS). All endpoints were adjusted to confounders. Results: 804 (429 ISC and 375 control) eligible patients from 26 centers were evaluated with a median follow up of 58 vs 51 months and a median ISC therapy duration of 52 months. Significant fewer ISC than control patients developed ADR by CONTH (p<0.001). Patients with supportive ISC showed a better QoL. Results of DFS-analysis (HR=hazard ratio): see Table 1 Severe ISC-related ADR or tumor enhancement were not observed. Conclusions: These results show reliable safety and clinically relevant, independent beneficial effect of supportive ISC treatment in reduction of ADR by CONTH, better QoL, and suggest a prolongation of DFS. Prospective trials are planned to confirm these data. Table 1. DFS analysis. No therapy = control (reference) No therapy ISC CONTH CONTH+ISC Patients% 22.5 24.9 24.5 28.1 HR 1 0.54 0.18 0.13 p value 1 0.005 <0.001 <0.001 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Society for Cancer Research, Switzerland
Current management of chemotherapy-induced anemia with darbepoetin alfa: The APRIORI study.
Authors: N. Bittner, A. Cipkova, H. Móciková, E. Wojciechowska-Lampka, M. Balázs, J. Ocvirk
Journal: Journal of Clinical Oncology (2011)

e19723 Background: Darbepoetin alfa (DA, Aranesp) is an erythropoesis-stimulating agent (ESA) used to treat chemotherapy (CT)-induced anemia (CIA). In 2008, EORTC guidelines were changed to recommend ESA treatment at hemoglobin (Hb) values of 9-11 g/dL, and discontinued if Hb values were >13 g/dL. In February 2008 the SmPC for DA was revised to recommend treatment initiation at Hb ≤10 g/dL and to maintain Hb in the 10-12 g/dL range. APRIORI is a prospective, noninterventional, observational study collecting data from patients with CIA receiving DA and chemotherapy in Central and Eastern Europe (CEE). The aims were to assess Hb values and transfusion rates (%RBCT) in CIA patients receiving DA, and to evaluate adherence to DA label guidance before (BLC) and after (ALC) the 2008 label change. Methods: This interim analysis includes data from patients with solid and non-myeloid hematologic malignancies from CEE (Czech Republic, Hungary, Poland, Slovakia, Slovenia, and Russia) between 09/2006 and 02/2008 (BLC) and between 03/2008 and 08/2010 (ALC). CT included alkylating agents, anthracyclines, tyrosine kinase inhibitors, taxanes, and targeted therapies. Data collected at enrolment and up to the first follow-up visit after CT completion. The End of Treatment Period endpoint (EOTP) was calculated from week 5 of DA treatment. Results: Out of 5,086 patients enrolled, DA was initiated in 86.3% at Hb <10 g/dL (mean age 59.6 ± 12.7 years, 45% male). In most patients Hb increased at EOTP (see ΔHb in table); 73% of patients had Hb ≥ 10 g/dL, and 51% had Hb 1012 g/dL at EOTP. One serious (pulmonary embolism) and 8 nonserious adverse drug reactions were reported. Conclusions: Based on these data, patients are being treated in accordance with the current SmPC for darbepoetin alfa. Interval/tumor type Hb at enrollment mean (SD) Hb at EOTP mean (SD) ΔHb mean (SD) % RBCT BLC Breast (N= 175) 9.8 (1.1) 11.3 (1.5) 1.5 (1.6) 2.3 Lung (N= 240) 9.1 (0.9) 10.4 (1.4) 1.3 (1.3) 6.7 Other tumors (N= 1,186) 9.2 (1.0) 10.9 (1.7) 1.7 (1.7) 7.3 ALC Breast (N= 327) 9.5 (0.8) 11.2 (1.3) 1.7 (1.4) 2.4 Lung (N= 614) 9.2 (0.8) 10.5 (1.4) 1.3 (1.4) 7.8 Other tumors (N= 2,544) 9.2 (0.8) 10.9 (1.5) 1.7 (1.5) 4.2
Phase II trial of oral vinorelbine for treatment of metastatic breast cancer in women 65 years and older: N003A
Authors: M. Baweja, V. Suman, T. R. Fitch, J. A. Mailliard, A. Bernath, K. M. Rowland, S. R. Alberts, J. S. Kaur, E. A. Perez
Journal: Journal of Clinical Oncology (2005)

740 Background: Intravenous vinorelbine is a semi synthetic vinca alkaloid with known antitumor activity in breast cancer. The aim of this NCCTG phase II trial was to assess the efficacy and safety of oral vinorelbine in patients 65 years and older with metastatic breast cancer, as first or second line chemotherapy. Methods: Women 65 years and older with stage IV breast cancer, who had received at most one prior chemotherapy regimen for metastatic disease were enrolled in this one stage phase II study from January 2002 to February 2003. Prior adjuvant therapy was permitted. Oral vinorelbine gel capsules were administered at 60 mg/ m2 for 4 doses on days 1, 8, 15 and 22 of a 28 day cycle. Dose was increased to 70 mg/ m2 if at most one episode of grade 3 and no grade 4 myelosuppression occurred. Results: Twenty five eligible patients were enrolled. Characteristics: median age 73 (65–84); PS: 0 (40%), 1 (48%), 2 (12%); ER positive: 68%; prior adjuvant therapy: hormonal (36%), chemotherapy (36%), both (16%). Prior first line therapy: chemotherapy (32%); hormonal therapy (44%). Eleven (44%) had 3 or more metastatic sites, 18 (72%) had dominant visceral metastases. Twenty five patients were evaluable for response, all are off study treatment. Median cycles administered: 4 (1–20). For cycle 2, 11 patients were able to initiate the higher dose, 5 required 25% dose reduction. The overall response rate was 4% (90% CI: 0.1–20.4%); one patient achieved a partial response for 17.4 months. One patient (4%) maintained stable disease for more than 6 months while on treatment and progressed at 11.5 months. Median time to progression was 4.8 months (95% CI: 2.0–5.5 months) and the Kaplan-Meier estimated one-year survival was 48% (95% CI: 30–74.5%). Toxicity data were available for 24 patients. Grade 3 toxicities included neutropenia (13%), fatigue (13%), dizziness (8%) and leucopenia (8%). Others included grade 2 neuro-motor toxicity (13%) and neuro-sensory toxicity (8%). Conclusion: Oral vinorelbine was well tolerated but provided minimal anti-tumor activity at this dose in this population with metastatic breast cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi Aventis, Bristol-Myers Squibb, Eli Lilly, Genentech, Pfizer
Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma.
Authors: Eugene K. Cha, Shahrokh F. Shariat, Matthias Kormaksson, Giacomo Novara, Michael Rink, Yair Lotan, Douglas Scherr, Jay D. Raman, Wassim Kassouf, Richard Zigeuner, Karim Bensalah, Alon Z. Weizer, Christian Bolenz, Marco Roscigno, Theresa M. Koppie, Hans-Martin Fristche, Vincenzo Ficarra, Cord Langner, Christopher G. Wood, Vitaly Margulis
Journal: Journal of Clinical Oncology (2012)

267 Background: Novel prognostic factors for patients after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) have recently been described. We tested the prognostic value of pathologic characteristics and developed models to predict the individual probabilities of recurrence-free survival (RFS) and cancer-specific survival (CSS) after RNU. Methods: Our study included 2,244 patients treated with RNU without neoadjuvant or adjuvant therapy at 23 international institutions. Tumor characteristics included T classification, grade, lymph node status, lymphovascular invasion, tumor architecture, location, and concomitant CIS. The cohort was split for development (12 centers, n=1273) and external validation (11 centers, n=971). Results: At a median follow-up of 45 months, 501 patients (22.3%) experienced disease recurrence and 418 patients (18.6%) died of UTUC. On multivariable analysis, T classification (p-for-trend &lt;0.001), lymph node metastasis (HR:1.98, p=0.002), lymphovascular invasion (HR:1.66, p&lt;0.001), sessile tumor architecture (HR:1.76, p&lt;0.001), and concomitant CIS (HR:1.33, p=0.035) were associated with disease recurrence. Similarly, T classification (p-for-trend &lt;0.001), lymph node metastasis (HR:2.23, p=0.001), lymphovascular invasion (HR:1.81, p&lt;0.001), and sessile tumor architecture (HR:1.72, p=0.001) were independently associated with cancer-specific mortality. Our models achieved 76.8% and 81.5% accuracy for predicting RFS and CSS, respectively. In contrast to these well-calibrated models, stratification based upon AJCC stage grouping resulted in a large degree of heterogeneity and did not improve discrimination. Conclusions: Using standard pathologic features, we developed highly accurate prognostic models for the prediction of RFS and CSS after RNU for UTUC. These models offer improvements in calibration over AJCC stage grouping and can be utilized for individualized patient counseling, follow-up scheduling, risk stratification for adjuvant therapies, and inclusion criteria for clinical trials.
Germline Genetic Predisposition to Hematologic Malignancy
Authors: Elissa Furutani, Akiko Shimamura
Journal: Journal of Clinical Oncology (2017)

Development of hematologic malignancies is driven by mutations that may be somatic or germline. Availability of next-generation DNA sequencing technologies has facilitated the development of individualized diagnostic evaluations and tailored treatment strategies. Until now, such personalized medical approaches have largely centered on prognostic stratification and treatment strategies informed by acquired somatic mutations. The role of germline mutations in children and adults with hematologic malignancies was previously underappreciated. Diagnosis of an inherited predisposition to hematologic malignancy informs choice of therapy, risk of treatment-related complications, donor selection for hematopoietic stem cell transplantation, evaluation of comorbidities, and surveillance strategies to improve clinical outcomes. The recognition that patients with inherited hematologic malignancy syndromes may present without classic clinical stigmata or suspicious family history has led to increased reliance on genetic testing, which, in turn, has raised new diagnostic challenges. Genomic testing is a rapidly evolving field with an increasing number of choices for testing for the practicing clinician to navigate. This review will discuss general approaches to diagnosis and management of patients with germline predisposition to hematology malignancies and will consider applications and limitations of genomic testing in clinical practice.
Concurrent Somatic Mutations in Exon 14 of Janus KINASE2 (JAK2) and Exon 10 of Myeloprolifeative Leukemia Virus Oncogene (MPL) in Myeloproliferative Neoplasms (MPN) and Myelodysplastic Syndromes (MDS)/MPN
Authors: Krishna Gundabolu, Catalina C Amador, Allison M Cushman-Vokoun, Vijaya R. Bhatt, Lori J. Maness, Timothy C. Greiner
Journal: Blood (2015)
Stereotactic radiosurgery for early-stage breast cancer: A new paradigm.
Authors: C. X. Yu, W. Regine, M. Zheng, J. Zhang, S. J. Feigenberg
Journal: Journal of Clinical Oncology (2011)

120 Background: Stereotactic radiosurgery (SRS) has not been widely used for breast cancer partly due to: 1) the lack of a suitable immobilization device; and 2) the lack of a delivery system that can concentrate a high radiation dose noninvasively. We have developed a SRS system that effectively addresses these obstacles and demonstrated the dosimetric feasibility of simultaneously ablating the intact tumor and sterilizing the tumor bed. Methods: A breast immobilization device consists of a solid outer cup with embedded stereotactic frame and a porous inner cup; the two cups join at the chest wall side by a soft goggle-like lip for comfort. A negative pressure is applied to the space between the two cups to immobilize the breast tissues. 15 patients with surgical clips in their breast underwent a geometric reproducibility trial, in which the patients received two CT scans spaced 10-60 minutes while wearing the cup. A SRS delivery system uses 36 Co-60 sources that rotate around a focal point to produce 36 non-coplanar arcs. The breast cup is locked on the treatment couch with the patient in prone position. The couch moves dynamically during treatment, allowing the focal spots to “paint” the desired 3D dose distribution. Results: The reproducibility of the 42 available clips was 1.83 mm ± 1.08 mm (2 std) and patients reported good comfort. 8 treatment plans simultaneously delivering an ablative dose of 18Gy to an intact tumor plus a 3mm margin (CTV1) and 10Gy to the tumor bed (CTV2 = CTV1+1cm) have been developed and verified with measurements. The dose-volume histograms showed very uniform dose coverage with 98% of CTV1 receiving 18Gy and 100% of tumor bed receiving 10Gy. On average, only 21% of the normal breast receives greater than 5Gy, safe to deliver 3 fractions of such doses. Conclusions: A breast-specific SRS system has been developed. Dosimetric studies illustrated the feasibility of managing early-stage breast cancer with SRS. Clinical studies that will identify patients in whom current forms of surgery and postoperative radiation may be eliminated are planned, allowing completion of local therapies noninvasively within a few days rather than months.
Association between Ki-67 and histologic grading in Nigerian patients with breast cancer.
Authors: C. A. Adebamowo, A. O. Famooto, E. E. Akang, T. O. Ogundiran, S. N. Akarolo-Anthony, D. C. Allred
Journal: Journal of Clinical Oncology (2011)

e11030 Background: Ki-67 is a nuclear protein expressed during all active phases of the cell cycle and is an excellent marker for determining the growth fraction of tumor cell populations. There is a paucity of African studies correlating Ki67 with pathological parameters of breast cancer. The aim of this study was to correlate Ki-67 index with histological grade of breast carcinoma. Methods: This is a prospective analysis of 101 breast cancer cases from the surgical oncology unit of the University College Hospital Ibadan over a twelve months period from March 2008 to February 2009. Breast carcinomas were graded using the Scarff-Bloom-Richardson (SBR) and Van Nuys (VN) methods. Ki-67 immunohistochemical assay was performed using a novel technique and correlated with conventional Scarff-Bloom-Richardson (SBR) and Van Nuys (VN) grading parameters. Results: Ki67 expression ranged from 0-95% with a mean of 36 ± 24%. There was significant correlation between Ki67 expression and SBR mitotic score (p = 0.03) and a weak non significant correlation with composite SBR grade (p = 0.06). There was also a significant correlation between Ki67 expression and VN nuclear score (p = 0.05) and presence of extensive tumor necrosis (p = 0.03. Conclusions: The present study has displayed the feasibility of accurate and reproducible assessment of Ki67 immunohistochemical staining in breast cancer tissue using a novel technique. It is recommended that further studies should be performed in order to investigate the role of Ki67 and other prognostic markers in determining clinical outcome in patients with breast cancer in this environment.
Effect of six months neoadjuvant imatinib on resectability potential of gastric stromal tumors in Egyptian patients.
Authors: G. M. Saied, A. M. Kensarah
Journal: Journal of Clinical Oncology (2011)

151 Background: Though recurrence is high, local excision is the preferred approach for dealing with gastric stromal tumors. Achieving negative margins is mandatory, sometimes requiring subtotal gastrectomy. Adjuvant imatinib is essential for advanced cases and prolonging survival; however, there is not enough data to recommend its use before surgery to increase resectability. The current study aims at investigating this concept in Egyptian patients. Methods: The study included 16 patients (13 males, 3 females, mean age 60 years) presenting with gastrointestinal stromal tumors (GISTs) who were candidates for emergency (n = 3) or elective (n = 13) surgery. Investigations included endoscopy (+ biopsy), sonography, and computed tomography (CT). Patients were enrolled in two groups: A (n = 6: projected to planned surgery) and B (n = 7: harboring c-kit+ tumors). Each B patient received imatinib (400 mg/day) for 6 months before surgery. Clinical and radiological evaluation was at day 100. The Chi-square test was used to check size changes, and p = &lt;0.02535 was considered significant. Results: All patients had abdominal discomfort, while 62.5% had epigastric pain, and 12.5% had hematemesis. Tumor sizes ranged from 8.4 to 20 cm; 2/3 were located in the upper stomach. Five patients (31.3%) harbored lesions with low risk malignancy, eight (50%) with moderate risk and three (18.8%) with high risk. Wedge gastrectomy was the most common operation performed (81.25%) while partial gastrectomy was carried out in the rest, reporting no recurrence for 6 months. Not determined in group A patients, c-kit status was strongly positive in all members of group B; in two of them treatment was suspended due to poor response. Conclusions: Imatinib has an acceptable safety profile and can be considered as a neoadjuvant therapy in GISTs. Until clear guidelines have been developed, we report that a 6-month intake may noticeably increase their resectability potential and improve prognosis. No significant financial relationships to disclose.