tbuckley/cabot-search huggingface dataset:
Detection of estrogen receptor α and β in a relevant model of human invasive urinary bladder cancer.
Authors: S. K. McMillan, D. Dhawan, L. Cheng, N. M. Hahn, D. W. Knapp
Journal: Journal of Clinical Oncology (2011)

e15160 Background: Each year in the US, >14,000 people die from invasive urinary bladder cancer (transitional cell carcinoma, InvTCC). Defining effective means to prevent InvTCC development and growth is crucial. Estrogen receptors (ERs) are present in InvTCC, but their role in InvTCC progression and potential value as targets for intervention are not clearly defined. Naturally occurring canine InvTCC closely mimics human InvTCC in molecular features and biological behavior. Gender and neuter status affect InvTCC risk in dogs. Canine InvTCC may offer a relevant in vivo system to study the role of ERs. ERα and β expression in canine InvTCC, with comparison to human InvTCC, were studied as an initial step to determine the role of ERs in InvTCC. Methods: ERα and β expression were determined by immunohistochemistry in canine and human InvTCC samples and normal bladder tissues. The majority of tissues were obtained from patients that had received previous treatment. Antibodies for ERα (SC-7207) and ERβ (SC-8974) were obtained from Santa Cruz Biotechnology, Santa Cruz, CA. The percentages of immunoreactive tumor cells and staining intensity in 10 HPFs were recorded by 2 independent reviewers. Tissues with immunoreactivity in greater than 10% of tumor cells were considered positive for ER expression. Results: Results of immunohistochemistry are outlined in the table. Paired tissues from primary and metastatic InvTCC in 17 dogs were evaluated. The ER expression between sites correlated in 17 of 17 cases for ERα, and in 12 of 17 cases for ERβ. ERα and β expression was similar between tissues from males and females analyzed to date. Conclusions: ERα and β were expressed in canine InvTCC, similar to that in human InvTCC. Canine InvTCC offers a relevant system to define the role of ERs in InvTCC development and progression. ERα immunostaining ERβ immunostaining Canine InvTCC 34/39 (87%) 29/39 (74%) Human InvTCC 7/15 (47%) 11/15 (73%) Canine lung metastases 12/14 (86%) 8/14 (57%) Canine lymph node metastases 9/11 (82%) 9/11 (82%) Canine normal bladder 7/7 (100%) 4/6 (67%) Human normal bladder 12/14 (86%) 9/14 (64%)
Tesetaxel, a novel oral taxane, as second-line therapy for advanced gastroesophageal cancer: Activity in a dose-ranging study.
Authors: Jaffer A. Ajani, Weijing Sun, Sun Young Rha, Jackie S. Baker, Mary Frances Mulcahy
Journal: Journal of Clinical Oncology (2012)

47 Background: Standard taxanes require extended IV infusion and are associated with potentially severe hypersensitivity and cumulative neuropathy. Tesetaxel is a structurally novel orally active taxane with potent and superior antitumor activity relative to standard taxanes in human tumor xenografts that overexpress P-glycoprotein. Tesetaxel is not associated with hypersensitivity, thus eliminating the need for both premedication and extended medical/nursing observation. A prior study showed an overall major response rate (ORR) of 20% as 2nd-line therapy in pts with advanced gastric cancer. Since pharmacokinetic and safety data suggested that flat dosing of tesetaxel might be feasible, we evaluated both flat and weight-based dosing in a new dose-ranging study. Methods: Eligibility: adenocarcinoma (stomach or GE junction); treatment with 1 fluoropyrimidine/platinum analog regimen; ECOG PS 0-1; and adequate organ function. Tesetaxel was administered Q3 weeks at flat starting doses (40 mg and 50 mg) in Cohorts 1 and 2, respectively. When flat dosing proved impractical, a weight-based dose was used for Cohort 3 (27 mg/m 2 with escalation to 35 mg mg/m 2 pending tolerability). ORR was the primary endpoint. Results: To date, 36 pts (29 men, 7 women; median age, 58 years [range: 25-81]) have been enrolled in this ongoing study, with results as shown below. Median survival is 7.8 and 7.5 months in Cohorts 1 and 2, respectively, and is too early to estimate in Cohort 3. Uncomplicated neutropenia was the most common ≥ 3 event (13%). Conclusions: Extreme body weight differences resulted in marked underdosing and precluded flat dosing. Our data confirm that tesetaxel is active against gastroesophageal cancers in the 2nd-line setting using the weight-based Q3 week regimen. [Table: see text]
Complicated postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in advanced testicular germ cell tumours: Is it worth the efforts?
Authors: Axel Heidenreich, Daniel Porres, David J. K. P. Pfister
Journal: Journal of Clinical Oncology (2015)

382 Background: PC-RPLND is performed in patients with residual masses following chemotherapy for advanced testicular cancer. Complicated PC-RPLND is defined by redo, salvage or desperation procedures including the necessity to resect major adjacent vascular, skeletal or intestinal structures. We report on our single centre experience of complicated (group A) versus uncomplicated PC-RPLND (group B). Methods: A total of 138 patients underwent PC-RPLND and 24 (14.8%) patients underwent complicated RPLND: resection of major retroperitoneal vessels n=15 (9.3%), skeletal and pancreaticoduodenal structures in 5 (3.1%) and 4 (2.5%) patients, respectively. We performed a retrospective analysis of treatment-associated complications (Clavien-Dindo classification). Progression-free, cancer-specific and overall survival was calculated. Results: There were significant differences between group A and B concerning tumour diameter (5.9 vs 18.6cm, p = 0.03), intermediate/poor IGCCCG risk (39.9% vs 83.4%, p=0.02), seminomatous primary (7.9% vs 20.8%, p=0.03). Pathohistology of the residual masses was significantly different between group A and B: vital cancer was identified in 6 (4.3%) and 8/24 (33.3%, p=0.02) pts, resp., whereas teratoma was identified in 37 (26.8%) and 14/24 (58.3%, p=0.01), resp. In addition 3 pts in group B demonstrated malignant somatic transformation. After a median follow-up of 32 months for group B, 3 patients with MTS experienced recurrences, 1 patient died of the disease. The remainder survived event-free. In group A, median follow-up was 37 months and DOD was observed in 2 pts, 8 pts (5.8%) experienced recurrences. Frequency of complications grade I-IIIb did not differ significantly between group A and B with vascular or skeletal surgery (6.2 vs 13.3%), however, it increased significantly to 65% in pancreatic surgery (p &lt; 0.001). Conclusions: Few patients with advanced NS need complex surgery in an interdisciplinary setting with good functional and oncological outcome. Despite an increased risk of short-term complications complicated PC-RPLND results in long-term survival &gt; 90% and it is justified if performed at specialized centres.
Efficacy of single-agent pemetrexed in platinum refractory metastatic urothelial cancer (mUC).
Authors: David J. Benjamin, Richard M. Bambury, Joshua Chaim, Emily C. Zabor, Irina Ostrovnaya, Ilana Rebecca Garcia-Grossman, Gopa Iyer, Dean F. Bajorin, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2014)

322 Background: No standard therapy exists for platinum refractory mUC. Single agent pemetrexed (Pmt) had objective response rates (ORR) of 8% and 28% in two phase II studies (enrolling 13 and 47 patients) and is commonly used in this setting. To address the difference in reported ORRs, we performed a retrospective analysis of Pmt use at MSKCC to evaluate objective response in a larger cohort of patients. A secondary aim was to explore whether neutrophil-lymphocyte ratio (NLR) added prognostic value beyond known factors (time from prior chemotherapy (TFPC), ECOG performance status (PS), liver metastases, and hemoglobin) in the UC salvage setting. Methods: Patients who received Pmt for platinum refractory mUC between 2008 and 2013 were identified. Baseline demographics, clinical characteristics, prior therapies, Pmt dose, and number of cycles were recorded. ORR was determined according to RECIST 1.1. Kaplan-Meier method and Cox regression were used to analyze associations with overall survival (OS). Results: 135 patients were identified with median age 66 (range 45-88), male 76%, ECOG 0 in 14% / 1 in 54% / ≥2 in 32%. Pmt was administered as 2nd-line chemotherapy in 56% / 3rd line in 30% / ≥4th line in 14%. ORR was 7% with median duration of response 10.2 months. There was no significant difference in ORR by line of therapy or PS. Median progression free survival was 2.4 months and median OS was 6.6 months. In this dataset, TFPC was not prognostic, while liver metastases, PS, and hemoglobin were prognostic. Higher NLR was significantly associated with worse OS independent of other known factors. Conclusions: In the largest reported series to date, Pmt had an ORR of 7% in metastatic UC regardless of line of therapy or ECOG performance status. This limited activity highlights the urgent need to develop novel therapeutic strategies. NLR was identified as an independent prognostic factor in this setting. [Table: see text]
Assessing cancer clinic visit time as a marker of quality care.
Authors: Lauren M. Hamel, Susan Eggly, Louis Penner, Robert Chapman, Jennifer Vichich, Rifky Tkatch, Terrance Lynn Albrecht
Journal: Journal of Clinical Oncology (2013)

95 Background: The uses of patient time and clinic space in outpatient cancer clinics can be indicators of efficiency and quality of cancer care. Inefficient use of these can have deleterious effects on clinic flow, patient satisfaction, physician/staff morale, and treatment adherence. We tested a unique method of assessing patient time and clinic space in cancer clinics as a measure of cancer care quality. Methods: We video recorded patient occupancy in exam rooms in two outpatient cancer clinics (n = 53) using an IRB-approved, custom-designed unobtrusive recording system (Albrecht et al. 2005) and analyzed use of time. Coders assessed: Patient Occupancy Time (total time in the exam room; POT); Patient Wait Time (time spent in the exam room prior to seeing the oncologist; PWT); and Physician-Patient Interaction Time (PPIT). POT was compared with Scheduled Occupancy Time (from clinic records; SOT) to obtain measures of Discrepancy in Occupancy Time (difference in scheduled exam room time and actual time the patient spent in the exam room; DiOT). Results: Mean POT across both clinics was 82.0 minutes (SD = 36.2), mean PWT was 24.8 minutes (SD = 26.0), and mean PPIT was 31.4 (SD = 14.9) minutes. SOT was only available for Clinic A in which case mean DiOT was 42.6 minutes with a range of 3.5 to 146.5 minutes. Only three cases used the room for less time than originally scheduled. SOT was unrelated to POT, PWT, and PPIT. DiOT was unrelated to PPIT. Conclusions: This method of objectively measuring cancer clinic time can help inform interventions to improve clinic efficiency. We found wait times were lengthy, suggesting an inefficient use of time and space. Importantly, there was no consistent relationship between scheduled and actual time spent in the exam room, reflecting an inefficient use of resources and potential inaccuracy in using scheduled time as a valid measure of quality. [Table: see text]
Concomitant radio-chemotherapy plus adjuvant chemotherapy in the post-operative treatment of glioblastoma multiforme
Authors: M. Valeriani, P. Bonfili, A. Ferretti, P. Franzese, V. Tombolini
Journal: Journal of Clinical Oncology (2005)

1579 Background: The results in patients with Glioblastoma Multiforma (GM) are poor. With the aim to improve the outcome we started to use temozolomide concomitant and adjuvant to post-operative radiotherapy. Methods: From March 2001 to March 2004, 25 patients with histologically proven GM were treated. Median age was 63 years (range 31–75 years). All patients underwent neurosurgical intervention that was: biopsy in 4 patients (16%), partial resection in 8 (32%) and total resection in 13 (52%). Four-six weeks after surgery patients received adjuvant radio-chemotherapy. Radiotherapy (RT) was delivered at 2 Gy per fraction, for a total of 60–66 Gy (median 66 Gy). All patients received temozolomide 75 mg/m2/daily during the irradiation time and 200 mg/m2 daily per 5 consecutive days, every 28 days starting four weeks after the end of radiotherapy for two-nine cycles (median 6 cycles). Results: Median follow-up was 14 months (range 6–26 months). Median actuarial overall survival (OS) was 17 months (95% C.I. = 13–21), 1 and 2-year OS were, respectively, 74,1% and 20,6%. Univariate analysis (Kaplan- Meier method) point out no statistical difference for extension of surgery (p > 0,05), total dose of RT (p = 0,4965) and age (≥ or <70 years) (p = 0,1447). Instead, for Performance Status (PS) (< or ≥70) (p = 0,0041) and number of adjuvant cycles (NAC) of temozolomide (> or ≤3) (p = 0,0093) statistical difference was noticed. Multivariate analysis (cox model) evidenced statistical difference for PS (p = 0,04) and for NAC (p = 0,018). No statistical difference was recorded for extension of surgery (p >0,18). Temozolomide was interrupted in the last week of combined treatment in 1 patient (4%) because grade III thrombocytopenia; other 2 (8%) presented grade I-II thrombocytopenia. Six patients (24%) presented grade I-II neutropenia. Conclusions: In our study, extension of surgery not influence OS. Patients not submitted to debulking surgery seems to have the major advantage. The PS remain the most important prognostic factor. Also NAC of temozolomide seems important but this data necessitate to further randomised investigation to avoid selection bias. The tolerance of combined regimen is very good. No significant financial relationships to disclose.
Integrating outpatient palliative care into a metastatic breast oncology clinic.
Authors: Rebecca Small, Jeffrey Belkora, Alexander Jow, Michael W. Rabow, Melanie Catherine Majure, Michelle E. Melisko, Amy Jo Chien, Hope S. Rugo
Journal: Journal of Clinical Oncology (2015)

154 Background: The Advanced Breast Cancer (ABC) program at UCSF aims to improve metastatic breast cancer outcomes through early integration of palliative and oncologic care. Oncologists now routinely refer stage 4 patients to a palliative care physician and social worker. Thus this initiative translates ASCO policy recommendations into clinical practice. We report early results from our development, implementation, and evaluation of this novel program. Methods: To evaluate ABC, we used the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation and Maintenance), and Rogers’ Diffusion of Innovations theory. Results: Reach: From 10/2014 to 6/2015, 43 women participated out of 64 invited. Decliners’ main reason for refusal was to avoid additional appointments. Effectiveness: 36 patients reported improvements in 13 of 15 quality criteria, including care coordination, emotional support, and propensity to recommend the program. 34 patients responded to ESAS, QUAL-E and Steinhauser Spiritualty Screen questionnaires, with improvement in 10 out of 14 outcomes at 1-2 month follow-up. Improvements included reduction of anxiety, improved quality of life, and decreased nausea. Adoption: Early integration of palliative care is complex and requires additional coordination among busy clinicians. To address this, we embedded a palliative care physician in the oncology clinic two half-days per week; relied on an oncology fellow to facilitate ongoing cross-disciplinary collaboration; and leveraged the program coordinator’s capacity for following up on both project and patient issues. We also instituted a monthly team meeting to review patient cases. Implementation: Overall, our program design succeeded. Challenges included how to best communicate about patient prognosis and reason for referral. We also struggled to determine what patient eligibility criteria should trigger a referral. Maintenance: The program is currently sustained by grants and intramural cancer center funding. We are seeking continued investment. Conclusions: The ABC program demonstrates that early integration of palliative and oncologic care is feasible and associated with the psychosocial benefits previously found in efficacy studies.
Cancer incidence in Kyrgyzstan
Authors: E. K. Makimbetov
Journal: Journal of Clinical Oncology (2005)

9699 Background: To study age, sex, geographic, site specific and ethnic cancer incidence in Kyrgyzstan. Methods: Calculated the incidence of cancer between 1997 and 1999 in all population. Estimated population relative risk for main tumours in urban and rural areas. Detailed population figures from census are available from National Center of Statistics. The population figures and cancer incidence rates were provided in for each age, ethnic and sex groups. Counted crude, age-standardised rates (ASR) per 100 000. Results: There were 4896 males and 5034 females registered with new diagnoses of cancer. Male-female proportion - 1,03. Histologically verified cases 80,5%. ASR annual incidence was in males 201.2 and females 137.9 (total 169.55)The most frequent diagnostic groups in males were tumours of the stomach (44.65), lung (41.0), skin (27.8), oesophagus (11.65), haemoblastoses (8.6), bladder (6.6) colon (5.9), and prostate (5.9); in females - skin (23.5), breast (19.1), stomach (16.2), cervical cancer (15.5), ovary (6.7), lung (5.9), corpus uteri (5.5), oesophagus (5.4), blood and lymph (5.2). Cancer incidence was significantly higher in urban (255.5-male, 161.9-female) than rural (161.8-male, 118.5-female) regions. However, in some tumours (oesophagus, stomach in males and cervical cancer in females) incidence rate was slightly higher in rural areas. Incidence was significantly higher in the Slavic ethnic groups (Russians, with an ASR of 263.8 cases per 100 000, Ukrainians 239.8, Byelorussians 185.0) compared with 65.7 for Kyrgyzs, 52.5 for Uzbeks and 61.5 for Kazakhs people. Excess relative risk (RR) was higher among Russians in tumours of skin (6,6), endometrial cancer (2,5), breast cancer (2,2), and lung cancer (1,7). However, oesophagus, cervix of uteri, stomach cancer incidence in native ethnic people was significantly higher than Russians and other Slavic groups. Cancer incidence in the mountain areas was differing. High incidence registered in low altitude (650 - 1500 m. above level sea), with ASR 205.9, middle altitude (1500 - 2500 m.), with ASR 118.7, than high altitude (2500 - 3500 m.) regions, with ASR 60.8. Conclusions: Cancer incidence in Kyrgyzstan is low and similar to those reported from some Asian developing countries. No significant financial relationships to disclose.
Phase II single arm trial of aflibercept in patients with recurrent temozolomide-resistant glioblastoma: NABTC 0601
Authors: J. F. De Groot, P. Y. Wen, K. Lamborn, S. Chang, T. F. Cloughesy, A. P. Chen, L. M. DeAngelis, M. P. Mehta, M. R. Gilbert, W. K. Yung, M. D. Prados
Journal: Journal of Clinical Oncology (2008)

2020 Background: Anti-vascular endothelial growth factor (VEGF) therapy is a promising treatment approach for patients with recurrent glioblastoma. Aflibercept (VEGF Trap) is a recombinantly-produced fusion protein which scavenges both VEGF and placental growth factor (PlGF) removing important ligands for the VEGF family receptors expressed on tumor endothelium. Methods: We report the results of a phase II trial of aflibercept monotherapy for patients with temozolomide-resistant recurrent glioblastoma and anaplastic glioma at first relapse. Patients received 4 mg/kg aflibercept IV every 2 weeks. The primary endpoint was 6-month progression free survival (PFS) and secondary endpoints include radiographic response rate (RR), PFS, overall survival and toxicity. Response was assessed using Macdonald's criteria. At this time, we provide preliminary response and toxicity data but complete information will be available at the time of presentation. Results: A total of 48 patients have been enrolled; 32 patients with glioblastoma and 16 patients with anaplastic glioma (median age 54; median KPS 90%). Investigator assessment of RR demonstrated a 50% response rate for the anaplastic glioma cohort (4 SD, 5 PR, 2 CR of 14 evaluable patients) and a 30% response rate for patients with glioblastoma (14 SD, 8 PR of 27 evaluable patients). The primary endpoint assessment of 6-month PFS will be presented. The main treatment-related NCI CTC grade 3 adverse events (18 total) included fatigue, hypertension, hand-foot syndrome, lymphopenia, thrombosis and proteinuria. One CNS ischemia and one systemic hemorrhage grade 4 toxicities were reported. A total of 12 patients (25%) discontinued therapy due to toxicity, on average less than 2 months into treatment. In conjunction with a decrease in permeability on DCE-MRI, aflibercept therapy induced a rapid and prolonged decrease in free levels of VEGF and PlGF confirming sequestration of target growth factors. Analysis of growth factors mediating angiogenic escape is ongoing. Conclusions: Aflibercept was moderately well tolerated and has evidence of single agent activity in patients with recurrent glioblastoma and anaplastic glioma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis, Schering-Plough, Semafore Johnson and Johnson, Pfizer Genentech, Novartis, Schering-Plough Genentech, Novartis, Regeneron
Primary care provider (PCP) views on survivorship care plans (SCPs) generated by an electronic health record (EHR).
Authors: Amye Tevaarwerk, SarahMaria Hill Donohue, Kevin A Buhr, David Hahn, Wenjun Sun, Abigail Terhaar, Douglas Wiegmann, Mary E Sesto
Journal: Journal of Clinical Oncology (2014)

168 Background: SCPs may address inadequate provider-to-provider communication but PCP views regarding EHR-generated SCPs have not been assessed. A multiple choice survey was used to evaluate an EHR-generated SCP for appropriate content, length, perceived accuracy, need for updates and preferred method of delivery (the Clinican survEy of Care Plan [ChECkuP]). Methods: PCPs were recruited from the Wisconsin Research and Education Network (WREN), a cohort of family practitioners working in urban and rural Wisconsin. WREN practitioners were e-mailed and invited to participate if they currently saw patients with a breast cancer history. PCPs were provided a sample 10-page EHR-generated SCP and completed the ChECkuP at one time point. Results: 36 PCPs participated in Summer 2014. Most PCPs reported the sample EHR-generated SCP as accurate (75%), easy to use (58%) and useful in coordinating care (75%). Few felt using SCPs would disrupt their clinic workflow (11%) or that SCP use would take too much time (14%). Most (75%) preferred receiving SCPs via EHR, vs paper (36%), having the patient provide (19%) or viewing the SCP on an external website (6%). Most deemed consistent provision (69%) and standard location (78%) important. With regards to timing, 42% reported desiring an SCP immediately after completion of primary treatment. However, PCPs requested some changes: 33% requested a shorter SCP (ideally 1-3 pages) and 53% advocated for SCPs specifically written for PCPs rather than producing one document for both PCP and survivor. Also, most (53%) felt that SCPs should be updated based on information changes rather than on a regular schedule, including changes to screening guidelines (100%), late or long term side effects (89%) and followup recommendations (95%). Conclusions: PCPs regarded EHR-generated SCPs as useful in coordinating care between oncologists and primary care. PCPs desired a standardized SCP accessible within the EHR. EHR-generated SCP content, length and layout will be revised based on the feedback provided. Clinical trial information: OS12122.