tbuckley/cabot-search huggingface dataset:
Association of persistent, unexplained leukocytosis, a paraneoplastic syndrome, with poor prognosis in patients with urothelial carcinoma of the bladder.
Authors: Jason Patrick Izard, John L. Gore, Evan Y. Yu
Journal: Journal of Clinical Oncology (2013)

291 Background: Unexplained leukocytosis, thought to be associated with paraneoplastic GCSF, has been described in several malignancies and is linked to a poor prognosis. We sought to define the disease characteristics and outcomes of those patients presenting with urothelial carcinoma and a persistently elevated WBC. Methods: We queried a prospectively maintained database at the University of Washington. Patients were included if they had a histological diagnosis of urothelial carcinoma of the bladder and a WBC of &gt;20 x 10 3 cells/µl. Patient charts were reviewed and were excluded from analysis if the leukocytosis was not persistent in duration or if an underlying cause for the leukocystosis could be identified. Clinical, histological and laboratory data were then collected from the remaining patient cohort. Results: We identified a total of 44 patients who met the inclusion criteria of having urothelial carcinoma of the bladder with a WBC of &gt;20 x 10 3 cells/µl. Of these patients, 7 (16%) patients with a median age of 61.9 (range 34 - 80) yrs at diagnosis had persistent, unexplained leukocytosis. Mixed histologies were present in 3 patients (extensive squamous differentiation in 2 and sarcomatoid differentiation in 1). At the time of presentation with leukocytosis, 5 of 7 had muscle invasive disease and 3 had evidence of metastatic disease. Leukocytosis was frequently associated with hypercalcemia (n = 5), thrombocytosis (n = 5) and anemia (n = 6). All patients died from their disease with the exception of one who is currently alive with locally advanced and unresectable disease 8 months after presentation. Median time from leukocytosis until death was 55 (range 8 - 139) days. Chemotherapy was able to achieve a WBC response in 2 of 4 patients although neither demonstrated a substantial reduction in tumor volume. Both patients ultimately developed a recurrence of their leukocytosis after chemotherapy and progression of their disease. Conclusions: The presence of leukocytosis conveys a poor prognosis. To our knowledge this represents the largest case series of patients with paraneoplastic leukocytosis secondary to urothelial carcinoma.
Combined treatment of advanced intrahepatic cholangiocarcinoma with transarterial chemoembolisation (TACE) and systemic therapy with gemcitabine and docetaxel
Authors: P. Stuebs, J. Fahlke, P. Habermann, M. Pech, A. Kandulski, K. Schuette, K. Zierau, M. Boessow, H. Lippert
Journal: Journal of Clinical Oncology (2008)

15595 Background: The cholangiocarcinoma has got a poor prognosis. Combining locally ablative procedures with systemic therapy seems to be one way of prolonging lifetime in patients with advanced intrahepatic cholangiocarcinoma. So far standard therapy has not been established. Methods: Prospectively, data of 39 patients was collected from 01/1998 to 10/2006 and analyzed retrospectively. Treatment was either TACE, systemic therapy or a combination of both. With TACE 1–6ml lipiodol and 5–20ml doxorubicin were administered into the vessel supplying the tumor directly. The cycle was repeated every 4 weeks along with a staging CT scan. In progressing disease therapy was changed to a weekly dose of 1000mg/m2 gemcitabine and 35 mg/m2 on days 1, 8 and 15, followed by a break of one week. The cycle was repeated every 4 weeks. A CT scan and physical examination determined disease staging after 3 cycles. Therapy was continued until disease progressed or inacceptable adverse reactions occurred. Altogether 3 groups evolved: 1- 12 patients treated with TACE only (tace), 2- 15 patients with progressive disease treated systemically after initially being treated with TACE (tace+i.v.), 3- 12 patients treated systemically only (i.v.). Results: There were 1 CR - 2.6% (i.v.), 4 PR- 10.3% (2 i.v.) 11 SD- 25.6% (4 i.v., 4 tace+i.v.), 20 PD- 51.3% (7 tace, 8 tace+i.v., 5 i.v.). In 4 patients (10.2%) no staging could be done. Median survival time in tace was 4.16 months, tace+i.v. 20.1 months and 10.93 months in i.v. Median time to tumor progression was 2.1 months in tace, 2.6 months in tace+i.v. and 5.2 months in i.v. Results were obtained with acceptable toxicity and satisfactory quality of life. Conclusions: Combining TACE with systemic chemotherapy in a selected group of patients with progressing cholangiocarcinoma can considerably prolong time of survival with acceptable toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck, Roche, sanofi-aventis
Enhancing the delivery of take-home cancer therapies in Ontario.
Authors: Erin Rae, Amanda Chan, Lyndee Yeung, Scott Gavura, Jessica Arias, Vishal Kukreti, Leonard Kaizer
Journal: Journal of Clinical Oncology (2014)

46 Background: The delivery of systemic cancer therapy has expanded from primarily intravenous (IV) treatment, delivered in cancer centres, to include significant use of take-home cancer therapies (THCT) (e.g., oral medications). An industry pipeline survey suggests half of new cancer drugs are expect to be THCT. While IV treatments administered in hospitals are publicly funded for Ontario residents, public funding of THCT is dependent on age, socioeconomic status, and other factors. The delivery of these therapies may also take place outside the cancer centre. While the lack of universal funding is cited as a significant barrier to access, the growing use of THCT has introduced other system delivery questions. Cancer Care Ontario recently hosted a “Think Tank” to inform public policy recommendations for system change to enhance the delivery of THCT in the province. Methods: The day was highly interactive with health professionals and patient participants, and was structured around a case study of a patient receiving both IV and THCT. Approaches taken with THCT in other Canadian provinces were examined. Participants used a multi-dimensional framework (safety and quality; reimbursement and distribution; data and information) to develop recommendations across pre-defined “checkpoints” in the patient’s treatment journey. Pre-assigned groupings of participants with common professional/patient backgrounds developed recommendations that were subsequently prioritized by reassigned multidisciplinary groups. Results: Over 80 stakeholders developed and prioritized more than 180 recommendations. Major themes included education, technology levers, and drug access model reform. This advice will inform system planning and next steps in defining opportunities for system change. The majority of participants (84%) felt the event broadened their understanding of THCT delivery issues. Conclusions: The strategic design of the “Think Tank” facilitated the development of robust recommendations for improving the delivery and reimbursement of THCT. These recommendations, along with the lessons learned from other provinces, will provide the foundation for potential policy and system changes to enhance the quality of THCT delivery in Ontario.
Incidence of recurrence and prognostic factors of borderline tumors of the ovary.
Authors: N. Ewald-Riegler, O. du Bois, A. Fisseler-Eckhoff, F. Kommoss, P. Harter, A. Traut, R. Hils, A. Du Bois
Journal: Journal of Clinical Oncology (2011)

e15522 Background: Outcome in borderline tumors (BOT) of the ovary is generally favorable; however, some patients experience recurrence, and fatal events occur. There is a need to better characterize prognostic factors to be considered for individualized treatment planning. Methods: Retrospective exploratory analysis of all 158 consecutive patients who underwent surgery for BOT at a tertial referral center for gynecologic oncology between 1997 and 2008. Patient data were retrieved from the prospective clinical tumor registry at the Dr. Horst Schmidt Klinik, Wiesbaden, Germany. All patients’ records are updated annually. Study endpoints were disease-free and overall survival. Statistical analysis was performed with the SPSS statistical package (release 18.0). The Kaplan-Meier method was employed for survival analysis, and individual risk factors were tested for significance with a log-rank test and multivariate Cox regression. Hazard ratios and 95 % confidence intervals were calculated for adverse events. Results: Most patients had early stage disease (FIGO I, 76,6%) and advanced stages FIGO II/III were observed in 23.4%. Serous histology was most frequent (68%), followed by mucinous histology (22%). All patients received surgery as initial treatment without adjuvant systemic therapy. 37 patients (23.4 % of the entire sample or 40.7 % of patients under the age of 50 years) had fertility-sparing surgery. Recurrent disease occurred in 18 patients (11.4 %) and 4 deaths (2.5 %) were observed. Independent risk factors for recurrence were FIGO stages higher than I (HR 37.1; 95 % CI 4.5-155.5), tumor rupture (HR 12.4; 1.5-61.5), incomplete staging (HR 5.9; 1.6-21.3]), and fertility sparing surgery (HR 8.0; 2.0-31.6 [only patients <50 years]). Conclusions: Intraoperative tumor rupture, incomplete staging, and fertility sparing surgery – altogether factors that can be influenced by the surgeon – impose a substantial risk of recurrence in BOT. Therefore, careful counseling and balancing of risk and benefit are mandatory before definitive therapy is applied, especially if fertility-sparing surgery is planned.
Molecular features of BRCA1/2 and PALB2 mutation associated pancreatic cancer (PAC).
Authors: Maeve Aine Lowery, Kirsten Timms, Victor Abkevich, C Neff, Alexander Gutin, Jerry S. Lanchbury, Laura H. Tang, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2014)

206 Background: Several clinical reports have indicated increased sensitivity to DNA damaging agents and PARP inhibitors in patients with PAC arising on a background of known BRCA1/2 or PALB2 germline mutation. While the mechanism of tumorigenesis in these cancer remains unclear, it appears likely that BRCA1/2germline mutations can predispose to PAC via 2 mechanisms, only one of which requires loss of the second allele. Determination as to whether biallelic inactivation of these genes is present in the tumor may have important therapeutic implications in predicting sensitivity to PARP inhibitors and other strategies targeting DNA repair. Methods: Following approval by the IRB and human bio specimen utilization committee at MSKCC, full exon sequencing of coding regions of 28 genes including BRCA1, 2 and PALB2 using exon capture by hybridization and next generation sequencing was performed on DNA extracted from 135 PAC samples. In addition, samples were analyzed for the presence of BRCA1 promotor methylation, KRAS hotspot mutations, and genome wide loss of heterozygosity (LOH) as an exploratory assessment of number and length of LOH as a marker of homologous repair deficiency / genomic instability. All patients underwent surgery for PAC at MSKCC after year 2000. Patients were selected on the basis of survival and included if they suffered a cancer-specific death within 1 year of resection or survived at least 30 months. Results: 7 tumors had mutations in BRCA2, 1 in BRCA1 and 1 in PALB2. Of 4 BRCA2 mutated samples evaluated for LOH at the BRCA2 locus, 2 demonstrated LOH while 2 did not. There was no LOH at PALB2 in the sample where a mutation was identified. Activating KRAS mutations were identified in BRCA2 mutated tumors with and without LOH. Methylation of the BRCA1promotor regions was not identified. Conclusions: The frequency of BRCA1/2 mutation carriers was as anticipated in this population. Biallelic loss of BRCA2 or PALB2 are not required for pancreatic tumorigenesis. The benefit of PARP inhibitors in BRCA1 / 2 mutated PAC may be limited to tumors with LOH of these genes. Inactivation of BRCA1 through promoter methylation is not identified in sporadic PAC.
Implementing quality indicators using health insurance claims data linked to the hospital-based cancer registry.
Authors: Fumiaki Nakamura, Masato Masuda, Norihiro Teramoto, Kazuhiro Mizumoto, Eiji Mekata, Shunichi Higashide, Mikinobu Ohtani, Takahiro Higashi
Journal: Journal of Clinical Oncology (2013)

94 Background: To establish systematic monitoring of cancer care quality, we measured the quality of cancer care in several facilities through chart reviews by tumor registrars. However, this method required both extensive effort of and skills in registrars. To explore less-labor–intensive methods of measuring care quality, we assessed quality measurement using health insurance claims data linked to the Hospital Based Cancer Registry (HBCR). Methods: We previously developed 206 quality indicators (QIs) to assess cancer care processes in collaboration with clinical experts. Ten of these (stomach cancer, 1; colorectal cancer, 1; lung cancer, 2; breast cancer, 3; liver cancer, 1; and supportive care, 2) could be used for analyzing HBCR health insurance claims data. Patients treated at 7 designated cancer hospitals in Japan in 2010 were included. Their characteristics and tumor stages were obtained from HBCR, and processes of care administered to the patients in 2010–2011 were obtained from health insurance claims data. We calculated a score for each QI based on the proportion of patients receiving care among those eligible for QI. Results: Data of 4,785 patients were analyzed (stomach cancer, 1,181; patients with colorectal cancer, 1,077; lung cancer, 1,091; breast cancer, 1,184; and liver cancer, 252). Quality scores of essential laboratory tests were high; 91% patients underwent the HER2 test for invasive breast cancer and 95% underwent the liver function test using indocyanine green clearance before liver cancer surgery. However, indicator scores for adjuvant chemotherapy were relatively lower at only 59% for stomach cancer patients, 57% for colorectal cancer patients, and 56% for lung cancer patients receiving adjuvant chemotherapy. The supportive care scores had even more scope for improvement as only 43% patients received antiemetics for highly emetic chemotherapy and 66% patients received laxatives along with narcotics. Conclusions: These QIs can be implemented for health insurance claims data linked to HBCR and used to identify the potential target area for improvement. In future, such electronic systems will enable rapid cycles of quality measurement and feedback.
Concomitant EGFR mutation and <i>EML4-ALK</i> gene fusion in non-small cell lung cancer.
Authors: J. Yang, X. Zhang, J. Su, H. Chen, H. Tian, Y. Huang, C. Xu, Y. L. Wu
Journal: Journal of Clinical Oncology (2011)

10517 Background: The fusion of the anaplastic lymphoma kinase (ALK) with the echinoderm microtubule-associated protein-like 4 (EML4) and epidermal growth factor receptor (EGFR) mutations are considered mutually exclusive. Advanced non-small cell lung cancer (NSCLC) patients with EML4-ALK did not benefit from EGFR tyrosine kinase inhibitors (TKIs). Methods: Multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) followed by sequencing was performed for EML4-ALK fusion status detection. EGFR and KRAS mutations were determined by direct DNA sequencing. Positive results of EML4-ALK fusion were also confirmed by RACE-coupled PCR sequencing. Results: From April 2010 to January 2011, 412 patients (398 with NSCLC; 14 with SCLC) were tested for mutation status of EGFR, KRAS and EML4-ALK respectively. Frequency of EML4-ALK fusion was 10.6% (42/398) in NSCLC patients. No patients with SCLC were found to have positive EML4-ALK fusion. Frequency of concomitant EGFR and EML4-ALK gene mutations was 1.0% (4/398) in NSCLC patients, and their variants of EML4-ALK gene mutations were Variant 1 (3 patients) and Variant 6 (1 patient); being never smokers, all of them were diagnosed with advanced (3 with stage ‡W and 1 with stage IIIB) adenocarcinoma harbouring wild type KRAS. Two female stage ‡W patients with double gene mutations (1 with L858R and Variant 1; 1 with exon19 deletion and Variant 6) received first-line gefitinib which is one kind of EGFR TKIs and achieved partial response. Conclusions: Though being rare events, NSCLC patients harbouring concomitant EGFR mutation and EML4-ALK gene fusion are sensitive to first-line EGFR TKIs. Whether they could also benefit from ALK inhibition after failure to EGFR TKIs warranted further investigation.
Locally advanced cervical cancer (LACC): Retrospective analysis of outcome of different chemoradiotherapy schedules.
Authors: J. J. Zarba, R. R. Segovia, J. Arcuri, E. Stegmayer, A. P. Medina, L. De Gregorio, R. Audi, G. Chavanne, H. R. Pedruzzi, P. Gonzalez Jazey, S. Holgado
Journal: Journal of Clinical Oncology (2011)

e15581 Background: CCRT is considered the standard of care in LACC since 1999. There is not a clear standard combination and according the last meta-analysis there are no evidence of a difference in the size of the benefit by radiotherapy or chemotherapy dose or scheduling. (J Clin Oncol 26:5802-5812. 2008) In a recently presented phase III study the combination of Cisplatin (P) and Gemcitabine (G) was better in terms of desease free survival (DFS) over weekly P (Dueñas-González A, et al. J Clin Oncol. 2009;27). Methods: The records of all patients (pts) with LACC treated in our service between 2000 and 2004 were reviewed. We consider the different chemotherapy used in association to RT. Overall survival (OS) was the main outcome of our review. Results: We reviewed the records of 330 pts treated from January 2000 to December 2004. Median age: 49 years (21-81). 266 pts (80%) had locally advanced tumors (IIA-IVA). Histology: squamous cell carcinoma 89.6%, adenocarcinoma 2.8%, adeno-squamous 0.9%, carcinosarcoma 0.3%, large cell carcinoma 0.6% and undifferenciate 5.8%. 192/266 pts were treated with Radiochemotherapy, 157 of them with concurrent P and 35 pts with concurrent PG chemotherapy. Median chemotherapy cycles: 6 for both groups. Median of treatment duration (Radiochemotherapy plus Brachytherapy) was 9.6 weeks. 10 weeks for the P group and 7.8 weeks for PG group. With a median follow-up of 26 months, the OS was 32 months with P and 51 months with PG. Conclusions: Although PG is not considered the standard of care for concurrent chemoradiotherapy; in this observational, mono institutional retrospective analysis, there was a clear benefit in median survival in relation to those who received only P. The PG combination should be considered at least as an option for chemoradiation in LACC.
A phase I study of neoadjuvant chemoradiotherapy with S-1/oxaliplatin in patients with gastric cancer.
Authors: D. Lee, J. Lee, D. Lim, S. Kim, S. Park, J. Park, Y. Park, H. Lim, W. Kang
Journal: Journal of Clinical Oncology (2011)

51 Background: To determine the maximum tolerated dose (MTD) of concurrent radiotherapy with S-1 and oxaliplatin, and antitumor activity of the combination treatment in patients with gastric cancer. Methods: This was a phase I, escalating multiple-dose tolerability trial. S-1 and oxaliplatin were administered concurrently with radiotherapy for 4 weeks before surgery. The dose escalation scheme is provided in the table below. S-1 was continuously administered during radiotherapy and oxaliplatin was administered weekly for 4 weeks during radiotherapy. Results: From March 2009 to June 2010, twelve patients were entered at two dose levels. The most common dose-related grade 1 and 2 adverse events were nausea, vomiting, anorexia and abdominal pain. Two of six patients treated at level 1 developed DLT (disabling abdominal pain, stomach perforation). The dose of S-1/oxaliplatin was reduced to 30 mg/m 2 bid and 40 mg/m 2 (Level -1). There one DLT (vomiting and anorexia, grade 3) observed in the expanded cohort of 6 patients at Level -1. Among 12 patients, 1 patient demonstrated pathological CR after neoadjuvant chemoradiation therapy. Conclusions: Neoadjuvant CCRT with S-1/oxaliplatin was well tolerated, at a dose 30 mg/m 2 bid for S-1 and 40 mg/m 2 for oxaliplatin that at which antitumor activity was seen. Phase II study is planned to investigate further the efficacy, tolerability and optimal dose. [Table: see text] No significant financial relationships to disclose.
Nasal-Tip Metastasis on 18F-FDG PET/CT Scan in a Patient With Squamous Lung Carcinoma
Authors: Zhanli Fu, Meng Liu, Jin Zhang, Ziao Li, Qian Li
Journal: Clinical Nuclear Medicine (2017)

A 64-year-old man found a painless soft tissue mass on his nasal tip 3 months ago. The biopsy pathology indicated a metastatic squamous carcinoma. An 18F-FDG PET/CT scan was performed to detect the primary malignancy, and it demonstrated multiple 18F-FDG–avid lesions involving the nasal tip, bilateral lungs, right hilum and mediastinum, and rectum. The nasal-tip mass with high radioactivity was diagnosed as the metastasis from squamous lung carcinoma, which was confirmed by the biopsy of a lung lesion.
Reduction of emergency department utilization via access to outpatient cancer care.
Authors: Kenneth D. Bishop, Mary Anne Fenton, Tara Szymanski, Megan Begnoche
Journal: Journal of Clinical Oncology (2014)

128 Background: Emergency department (ED) utilization for non-emergent medical problems is an inefficient use of medical resources. During calendar year 2013, 224 RIH adult cancer patients presented to the RIH ED. Retrospective review indicated up to 50% of these ED visits were avoidable. Methods: This project was developed for the ASCO Quality Training Program. A multidisciplinary team was assembled to address ED utilization. Retrospective chart review of ED visits included time and reason for visit and primary tumor site. The team selected the Lung Cancer as the target group, developed a cause-and-effect analysis for ED visits, administered a patient survey, and implemented a series of Plan-Do-Study-Act (PDSA) cycles. The team implemented a patient education process of nurse sick-line symptom management and same-day sick visits at RIH CCC as well as developing a single-page patient “sick-line tool” with oncology nurse sick-line contact telephone numbers. A patient navigator introduced the sick-line tool at the first visit and its usage was reinforced at subsequent visits. Results: For RIH CCC lung cancer patients, a standardized symptom-control education process correlated with 30% decrease in ED visits for any presenting complaint (42 visits vs. 60 visits) and 32% decrease in ED visits with presenting complaint of pain (13 visits vs. 19 visits) during January/February 2014 compared to January/February 2013. We did not find significant differences between the proportion of ED visits during Cancer Center business hours, evenings, or weekends. Sick-line calls were found to increase by 53% during January 2014 compared to December 2013 with an additional 35% increase in February 2014. Conclusions: A standardized patient education process resulted in a significant decrease in ED visits, concurrent with an increase in outpatient sick-line utilization. This may reflect an improvement in efficiency of outpatient cancer patient care in a single-institution setting. Given other reports of increased ED utilization by lung cancer patients for similar presenting reasons, these improvements may be generalizable to other institutions.
Phase II multi-institutional study of docetaxel plus aflibercept (AVE0005, NSC# 724770) in patients with recurrent ovarian, primary peritoneal, and fallopian tube cancer.
Authors: R. L. Coleman, L. R. Duska, P. T. Ramirez, S. C. Modesitt, K. M. Schmeler, R. Iyer, M. Garcia, A. Sood
Journal: Journal of Clinical Oncology (2011)

5017
Retrospective Analysis of Post-Transplant Complications in Autologous Hematopoietic Cell Transplantation Patients Receiving Hyperbaric Oxygen Therapy
Authors: Haitham Abdelhakim, Sajjad Akbar Bhatti, Amy Rose Cantilena, Tara L. Lin, Siddhartha Ganguly, Anurag K. Singh, Sunil Abhyankar, Brea Lipe, Joseph McGuirk, Dennis Allin, Leyla Shune, Omar Aljitawi
Journal: Blood (2016)