tbuckley/cabot-search huggingface dataset:
Prediction of relapse in stage I nonseminomatous germ cell tumors (NSGCT) by CXCL12: Results from the MRC TE08 and TE22 clinical trials.
Authors: Duncan Charles Gilbert, Khin Thway, Ian Chandler, Reem Al-Saadi, Rhian Gabe, Sally P. Stenning, Janet Shipley, Robert Anthony Huddart
Journal: Journal of Clinical Oncology (2013)

319 Background: Stage I NSGCT harbor occult metastatic disease in up to 50% of patients and undergo surveillance with chemotherapy at relapse or adjuvant treatment with excellent survival but concern around subsequent toxicity. Better prediction of relapse would minimize exposure to unnecessary treatments. Previous data suggested CXCL12 aided assessment of relapse risk (Gilbert DC, et al. J Pathol. 2009 Jan;217:94-102). MRC TE08 (Rustin GJ, et al. J Clin Oncol. 2007 Apr 10;25:1310-1315) and TE22 (Huddart RA, et al. J Clin Oncol. 2007 Jul 20;25:3090-3095) were clinical trials incorporating surveillance in stage I NSGCT. Methods: Tumor samples from patients enrolled in TE08 and TE22 were obtained with ethical approval and subjected to immunohistochemical staining for CXCL12. These were scored and CXCL12 analysed as a prognostic factor for relapse independently of vascular invasion (VI - the only currently validated marker). Results: Samples were obtained from 182/466 eligible patients. The 2-year relapse-free rate (RFR) was 76.4%. In CXCL12 moderate/strong cases this was 80.1% (95% CI 73.4-86.8). In CXCL12 absent/weak cases (&lt;1% cells staining moderately or strongly) this was 64.9% (49.6-80.2); hazard ratio 0.54 (95% CI 0.28-1.04). CXCL12 intensity was independently prognostic, p=0.006 (logrank test stratified by VI). Absent/weak CXCL12 expression was significantly associated with embryonal histology (p=0.001). In multivariate analysis including clinical and pathological features, only CXCL12 (HR 0.43, 95%CI 0.22-0.83) and VI (HR 4.77, 95%CI 2.49-9.13) were predictive of relapse. Conclusions: CXCL12 intensity is prognostic for relapse independently of VI. This additional prognostic information can identify groups at very low and very high risk of relapse with potential clinical utility. Acknowledgements: Supported by MRC Biomarkers Grant G0801477 and the NCRI Testis Cancer Clinical Studies Group. [Table: see text]
Activity of XL647 in clinically selected NSCLC patients (pts) enriched for the presence of EGFR mutations: Results from Phase 2
Authors: N. A. Rizvi, M. G. Kris, V. A. Miller, L. M. Krug, S. Bekele, A. Dowlati, K. M. Rowland, R. Salgia, N. Aggarwal, S. M. Gadgeel
Journal: Journal of Clinical Oncology (2008)

8053 Background: XL647 is a small molecule inhibitor of EGFR, HER2, and VEGFR2. Oral administration of XL647 results in dose-dependent, sustained inhibition of these target enzymes in preclinical studies. Increasing evidence of a close relationship between EGFR- and VEGFR2-mediated signaling pathways suggests that simultaneous inhibition of these pathways may provide improved efficacy. Methods: XL647 is administered orally as a single dose of 350 mg on Days 1–5 of each 14 day cycle (intermittent cohort). A second cohort will receive 300 mg daily. The primary endpoint is tumor response by RECIST. Pts with previously untreated advanced NSCLC (Stage IIIB or Stage IV) with adenocarcinoma histology that meet at least one of the following demographic criteria: Asian, female, minimal (<15 pack-yrs) or no smoking history are eligible. The mutational status of EGFR and KRAS in tumor tissue is being analyzed when archived material is available. Results: Enrollment into the intermittent cohort is complete with 41 pts (median age 67 yrs, range 45–87; 30F/11M). A 28% partial response (PR) rate (10/36 evaluable pts) was observed. 7/10 patients with a PR had an EGFR mutation detected in tumor tissue (6 pts with exon 19 deletions and 1 pt with L858R mutation). 3/10 patients with PR did not have detectable EGFR mutations. One pt with EGFR L858R had modest tumor shrinkage (SD). Stable disease for ≥ 3 months was observed in a total of 36% of patients. Common adverse events reported to date are Grade 1/ 2 diarrhea, fatigue, rash, nausea and clinically asymptomatic QTc prolongation. Conclusions: This study supports a clinical selection strategy to enrich a NSCLC population for EGFR mutations. XL647 has anti- tumor activity in selected NSCLC pts, demonstrating a 28% PR rate and 36% SD for ≥ 3 months, for an overall clinical benefit rate of 64%. All 8 pts with EGFR activating mutations experienced tumor shrinkage (7 with PRs and 1 SD). Three pts without an EGFR mutation experienced a PR. XL647 is well-tolerated in this patient population. Data from the daily dosing cohort will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Exelixis Exelixis
Challenges with genomic testing in pancreaticobiliary cancers: Results of a prospective cohort study.
Authors: Davendra Sohal, Brian I. Rini, Bassam N. Estfan, Dale Randall Shepard, Michael J. McNamara, Robert Dreicer, Brian James Bolwell, Alok A. Khorana
Journal: Journal of Clinical Oncology (2015)

314 Background: Therapeutic options for advanced pancreaticobiliary (PB) malignancies may be improved by genomics-driven therapies. We conducted a prospective cohort study of outpatient genomic testing to identify prevalence of actionable alterations and therapeutic impact of such testing in PB cancers. Methods: Eligibility requirements included confirmed pathologic diagnosis of select solid tumor malignancies without a known curative option, age ≥ 18 years, and an ECOG performance status of 0-2. Data for the PB cancer subgroup are presented here. Tumor samples were sequenced for up to 315 candidate genes in collaboration with Foundation Medicine, Inc. (Cambridge, MA). Results were discussed at the Cleveland Clinic Genomics Tumor Board that made therapeutic recommendations to treating physicians. Results: From Aug 2013 to Aug 2014, samples from 228 patients were analyzed; 24 (11%) had PB cancers. For the latter subgroup, median age was 60 years; 14 (58%) were male; 20 (83%) were white. Twelve (50%) tumors were pancreatic, 11 (46%) from biliary tract/gallbladder, and 1 (4%) periampullary. Median time from consent to result was 24 (range, 3-84) days. Eight (33%) samples had inadequate tissue compared with 6/174 (3%) non-PB samples (p&lt;0.001). Among patients with adequate tissue (n=16), a median of 3 (1-7) mutations were detected per sample; TP53 (50%), CDKN2A/p16 (44%) and KRAS (38%) were most common. A targeted therapy was recommended in 7 (44%) patients. Of these, 78% of recommendations were for specific clinical trials. To date, no patient with PB cancer has received a targeted therapy, compared with 6/45 (13%) patients with colorectal cancer (p=0.18). The most common reason for non-receipt of recommended targeted therapy was non-availability of clinical trials. Conclusions: Compared with other common solid tumors, genomic profiling in pancreaticobiliary cancers is challenged by paucity of diagnostic tissue collected during routine clinical care. Targeted therapy options (on-study or off-label) are few at this time. Precision oncology in pancreaticobiliary cancers will remain under-utilized until access to clinical trials is enhanced.
Treatment of patients with relapsed/refractory CLL using a combination of fludarabine, cyclophosphamide and alemtuzumab: First safety analysis of the CLL2L trial of the German CLL Study Group
Authors: T. Elter, R. James, C. M. Wendtner, S. Stilgenbauer, D. Winkler, M. Ritgen, M. Hallek, A. Engert
Journal: Journal of Clinical Oncology (2008)

7053 Background: Purine nucleoside combination therapy has become the standard treatment approach in B-CLL. In order to enhance efficacy, various combinations with monoclonal antibodies are under investigation. As alemtuzumab has proven to be the most effective antibody in CLL treatment, we developed a multicenter phase II trial combining fludarabine, cyclophosphamide and alemtuzumab in a 4-weekly schedule. Methods: Fludarabine 25mg/m2 iv, cyclophosphamide 200mg/m2 iv and alemtuzumab 30 mg sc were given on days 1 - 3 and repeated on day 29 for up to six cycles. A 2-day escalation of alemtuzumab was administered prior to the first cycle. Minimal residual disease (MRD) was measured by 4-color flow cytometry. Antiinfective prophylaxis consisted of TMP-SMZ DS twice daily 3d/wk and valacyclovir during and at least two months after completion of treatment. CMV antigen in blood was tested in 14-days intervals. Results: A total of 39 patients of a planned sample size of 61 patients were included in this phase-II study so far, of which 20 patients are evaluable for response and safety analysis. Median age is 64 (range 48–78) years with a medium number of 1 prior regimen; 14/20 patients completed at least four cycles with a median number of 4.5cycles. Pretreatment consisted of fludarabine (8/20), fludarabine and cyclophosphamide (12/20) or rituximab combination (1/20). Thrombocytopenia and neutropenia were the most serious side effects and detailed data will be presented. 2 CMV-reactivations, 1 Herpes-zoster-reactivation and 12 fever of unknown origin have been reported. The overall response rate was 70% with 5 CR (25%), 9 PR (45%), 2 SD and 2 PD. All complete responders became MRD negative in peripheral blood or bone marrow; response was independent of FISH status. A correlation of response with prior treatment was observed, with 88% ORR for fludarabine pre-treatment versus only 65% for those patients pretreated with fludarabine and cyclophosphamide. Conclusions: The concomitant application of fludarabine, cyclophosphamide and alemtuzumab appears as a safe and effective approach for patients with relapsed CLL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Schering AG, Schering AG Schering AG
Preliminary in vitro study of MUC1-ETR/pDC316 vector-mediated specific MR imaging of pancreatic cancer.
Authors: W. Ma, D. Xie, D. Chen, Q. Yang, Z. Jiang, Y. Zhang, S. Zhou
Journal: Journal of Clinical Oncology (2011)

e14517 Background: Meta-analysis indicates the aberrant expression of mucin 1 (MUC1) could be a relatively specific early event of pancreatic oncogenesis (2008 ASCO, Abst 15680). Probing the aberrant expression of muc1 by transferring receptor (TfR) mediated molecular imaging may provide a new choice for early specific detection of pancreatic cancer. Methods: A eukaryotic expression vector MUC1-ETR/pDC316 containing a tissue-specific muc1 promoter and the engineered transferrin receptor gene sequence (ETR), and a positive controlled plasmid MCMV-ETR/pDC316 had been constructed. MUC1-ETR/pDC316 plasmid was transfected into muc1 gene positive pancreatic cancer cell lines Panc-1, Capan-2 and muc1gene negative cell line MDA-MB-231. The same cell lines transfected with PBS, MCMV-ETR/pDC316 plasmid and blank pDC316 plasmid were served as negative group, positive group and blank group. Real-time PCR, western blot, AAS, FLM, MR, MTT, scratch method and transwell were performed on cells to detect TfR expression and effect after transfection. Results: The ectogenous gene TfR were identified from both nucleic acid and protein levels in muc1 positive pancreatic cancer cell lines after transfection of MUC1-ETR/pDC316 plasmid, the over-expression TfR on cell surface had the normal iron-uptake function. The growth after transfection MUC1-ETR/pDC316 into Panc-1cell was significantly suppressed, displaying the amount of G0/G1cells increased and the amount of S phase cells decreased significantly. The ability of migration was significantly suppressed compared with negative group (P<0.05). A trend of declination in T2 value after transfection of MUC1-ETR/pDC316 plasmid was observed in muc1 positive cell compare with untreated group. Conclusions: Over-expressed TfR can specifically express in muc1 positive pancreatic cancer cell lines after transfection of MUC1-ETR/pDC316 plasmid, and it has the normal iron-uptake function. Transfection of MUC1-ETR/pDC316 plasmid would not increase malignant degree of Panc-1 cells. In vitro MR imaging requests further study.
A new survivorship model for adolescents and young adults (AYA).
Authors: Erin Marie Barthel, Sabrina Karim, Elizabeth Kiernan, Katherine Spencer, Rachel Murphy-Banks, Rebecca Burns, Mingqian Lin, Nadine Linendoll, Tully Saunders, Susan K. Parsons
Journal: Journal of Clinical Oncology (2016)

43 Background: The AYA population is a growing group of cancer survivors, currently exceeding 600,000 in the US, with 70,000 new diagnoses each year. These survivors experience deficits in general health, mental health, and functional status. Unfortunately, many are lost to follow-up after the completion of active therapy. They lack clarity about where to go for care and why such care is needed. To further complicate this, many have not established a primary care provider (PCP). Methods: We present a model of survivorship care tailored to the AYA population. Our clinic has dedicated physical space and is staffed by pediatric- and adult-trained oncologists. Survivors are paired with age-matched peer navigators to guide them through the logistics of follow-up care and assist with age- related transitions in education, housing, and insurance. Additionally, we have established a new model of survivorship care, introduced immediately at the end of active therapy, utilizing a staged curriculum, survivorship care plans, and point-of-care health-related quality of life assessment. Results: Fifty-five unique patients seen in 182 visits provided data for this report. The median age was 26 years (range 18-40). Twenty-nine (53%) of the patients were female. The majority of patients (58%) had been treated for a hematologic malignancy. One third of patients had completed college (31%). Most were employed (71%), but a majority still lived with their parents (64%). The majority of patients had more than one late effect (62%). Twenty-three (43%) reported mental health symptoms, including anxiety, mood swings, or sleep problems. Conclusions: A survivorship clinic with tailored programs for AYAs is feasible and necessary. In our sample, many AYA survivors have late effects and almost half reported psychosocial distress. Clinicians need to monitor this age group closely to ensure that patients are not lost to follow-up as they transition from active treatment to survivorship care and from pediatric to adult-based care. Our clinic provides an integrated medical home for the AYA survivor that continues to care for them when active treatment comes to completion and provides ongoing care coordination with PCPs and subspecialists to co-manage their complex health issues.
Prognostic value of expression of RANK and c-Src in patients with breast cancer with bone metastasis.
Authors: X. Qu, L. Zhang, Y. Teng, Y. Zhang, J. Liu, L. Xu, J. Qu, K. Hou, X. Yang, Y. Liu
Journal: Journal of Clinical Oncology (2011)

e21024 Background: Receptor activator for nuclear factor kappa B ligand/receptor activator for nuclear factor kappa B (RANKL/RANK) pathway is critical for RANK-expressing cancer cells to home to bones, and c-Src is critical for cancer progression. However, there are no data currently available about the effect of RANK/c-Src on breast cancer patient prognosis. This study was aimed to evaluate the effect of RANK and c-Src on prognosis in metastatic breast cancer patients. Methods: RANK and c-Src expression were evaluated by immunohistochemical staining in primary breast cancer tissues of 102 patients with distant metastasis. The median follow-up period was 40 (range 7-143) months. The relationship between RANK and/or c-Src expression and clinical outcome were explored. The log-rank test and the Kaplan-Meier method were used for the patient survival analysis. Multivariate analysis was performed according to the Cox proportional hazards model. Results: The RANK and c-Src positive expression rates were 47.1% and 54.9%, respectively, in breast cancer tissues. All patients developed distant metastases, in which 62 patients developed bone metastases. Patients with RANK positive expression showed significantly poorer progression-free survival (p=0.023) and disease-specific survival (p=0.001). Similarly, patients with c-Src positive expression also showed significantly poorer progression-free survival (p=0.044) and disease-specific survival (p=0.017). Subgroup analysis demonstrated that the signiﬁcant difference in prognosis completely related to the occurrence of bone metastasis. Furthermore, RANK and c-Src co-expression correlated to poorer bone metastasis-free rate (p=0.007) and disease-specific survival rate (p=0.002) in bone metastasis patients. Multivariate analysis demonstrated that co-expression of RANK and c-Src was an independent predictor of bone metastasis-free survival (RR=2.281; 95%CI: 1.105-4.710; p=0.026) and disease-specific survival (RR=4.434; 95%CI: 1.697-11.586; p=0.002). Conclusions: Co-expression of RANK and c-Src might be an independent predictor of poor prognosis in breast cancer patients with bone metastasis.
The dosimetric impact of supraclavicular nodal irradiation on the thyroid in patients receiving radiotherapy for breast cancer.
Authors: Kim Ann Ung, Brigid Moran, Maria Portillo, Tomas Kron, Brooke Sawyer, Alan Herschtal, Boon H Chua
Journal: Journal of Clinical Oncology (2012)

198 Background: The thyroid is not routinely considered an organ at risk in supraclavicular (SC) nodal radiotherapy (RT) for breast cancer. We aim to compare the dosimetric impact of two RT planning techniques on the thyroid: (1) conventional single anterior field to encompass the SC nodal volume defined using clinical and radiological landmarks; and (2) 3-dimensional (3D)-conformal planning to encompass the SC nodal volume contoured on planning computed tomography (CT) scans. Methods: The thyroid and SC nodal volumes were contoured on the planning CT datasets of 20 patients who had RT to the breast/chest wall and SC nodes to a dose of 50 Gy in 2-Gy daily fractions. Comparison of the following dosimetric parameters between the techniques was performed: mean and maximum thyroid dose; V5, V30, and V50 (percentage of thyroid receiving ≥5, ≥30, and ≥50 Gy respectively); percentage of SC nodal volume receiving 95-107% of the prescribed dose (homogeneity index, HI); and maximum spinal cord dose. Anatomical characteristics that influenced the dose distribution were investigated. Results: The 3D-conformal planning technique significantly increased all dosimetric parameters for the thyroid (p&lt;0.001) (Table). It improved the mean HI of the SC nodal volume (16% vs. 93.2%; p&lt;0.001) but resulted in a higher spinal cord dose (mean maximum dose 6.1 Gy vs. 30 Gy). The thyroid volume and depth of SC nodes did not influence the differences in the thyroid doses between the two techniques. The depth of SC nodes was significantly associated with the difference seen in the HI of SC nodal volumes between the techniques (p=0.004). Conclusions: The 3D-conformal planning technique improved the dosimetric coverage of the SC nodal volume but increased radiation doses to the thyroid compared to the single field technique. The longer term clinical consequences of radiation to thyroid should be considered in SC nodal irradiation for patients with breast cancer. [Table: see text]
Lenalidomide plus low-dose dexamethasone compared with thalidomide plus low-dose dexamethasone in the treatment of newly diagnosed multiple myeloma: Results of an ongoing prospective randomized phase III trial.
Authors: A. Mookerjee, A. Sharma, R. Gupta, L. Kumar
Journal: Journal of Clinical Oncology (2011)

e18572 Background: Both Thalidomide and Lenalidomide are approved for first line treatment of multiple myeloma (MM). We compared the efficacy and safety and assessed quality of life (QOL) of the two agents in combination with dexamethasone. Methods: Between March 2009 and December 2010, 39 newly diagnosed MM patients (median age 52 years, range, 20 to 70 years, M: F=16:7. ISS stage: I-14, II-14, III-11. Durie-Salmon stage: IIA-2, IIIA-30 and IIIB-7. Patients received Lenalidomide, 25 mg/d, d 1-21 every 28 d or Thalidomide 100-200 mg/d along with dexamethasone (dex) 20 mg PO d 1-4 and d 9-12 every 28 d in both arms. The study was approved by Institution Ethics Committee and written informed consent was obtained. Response was assessed according to the IMWG criteria after 4 cycles. QOL was assessed by EORTC QOL questionnaire C30. Responders (CR or VGPR) received maintenance dex 20 mg PO from day 1-4 every month until progression. All patients received inj zoledronic acid 4 mg IV every month for 6-9 months. Eligible patients were offered ASCT. Median follow-up is 9.5 months (range 1-21). Analysis was by intention to treat. Results: 23 patients (Len-dex, n=12 and Thal-dex, n=11) have completed at least 4 cycles of therapy. 16 patients responded; VGPR-7, PR-9, 2-stable disease. Two patients died of progressive disease (1 in each group). Response was similar in both arms. 6 patients have proceeded to ASCT. In Len-dex arm, the major toxicities were grade III-IV neutropenia-2, thrombocytopenia-1 and anemia in 1 pt. Other toxicities were: fatigue-4, URTI- 3, constipation-2, dizziness-2, autoimmune thrombocytopenia-1 and rest tremors in 1 patient. In Thal-dex arm, toxicities were sensory neuropathy-5 (all grade I), constipation-4 (grade I-3, grade III-1), skin infection-2, fatigue-1 and coarse tremors in 1 patient. QOL analysis showed improvement in physical functioning among patients of Len-dex arm (p<0.008). Conclusions: For newly diagnosed myeloma patients, induction treatment with Lenalidomide-dexamethasone is associated with better toxicity profile and improved QOL compared to thalidomide-dexamethasone.
Using a web analytic tool to evaluate Pathways program engagement in 36 Michigan oncology practices.
Authors: Amy Hatfield Seung, Rachel Justus, Justin Frank Antoni Klamerus, Douglas W. Blayney
Journal: Journal of Clinical Oncology (2016)

198 Background: Evidence-based, cancer treatment pathways reduce unnecessary variation in care, reduce waste, and improve value. Financial incentives and sharing adherence rates may motivate oncologists to change treatment patterns. The Michigan Pathways Program (Pathways) is a statewide quality improvement program sponsored by BlueCross BlueShield of Michigan and supported on the Caret web-based registry. Pathways measures and incentivizes adherence to local treatment pathways (JOP 8e32s, 2012; ASCO 2015 Ann Mtg, abst 6584). Caret reports allow participants to review adherence rates. Using Google Analytics (GA), we measured access by participants of adherence reports and attempted to correlate this measure of engagement with adherence. Methods: Caret provides decision support for regimen selection within the Pathways. BCBSM medical claims are uploaded to ensure completeness of data. Caret generates reports allowing participants to review site-specific adherence data and compare with de-identified aggregate data from all participants. GA gathers data about page tags being accessed at a location by users, which were assumed to correlate to Pathways practices. Unique page views for web-based adherence reports were assessed for each location and compared to adherence rates. Results: 36 practices were included from 34 unique locations. 34.4% of practices are accessing adherence reports. For users the mean treatment adherence was 82.7% compared to 79.3% for non-users. Conclusions: Web analytics offers a novel method for gauging practice engagement in our program. This initial assessment will help to target education sessions based on location in addition to identifying potential best practices. At this time conclusions cannot be made to correlate application engagement to adherence rates. We predict an increased need for web analytics to measure the use of resources utilized by practices. [Table: see text]