tbuckley/cabot-search huggingface dataset:
Modern patterns of care in testicular seminoma: Results from the National Cancer database.
Authors: Phillip John Gray, Chun Chieh Lin, Jonathan J. Paly, Ahmedin Jemal, Jason Alexander Efstathiou
Journal: Journal of Clinical Oncology (2014)

368 Background: The management of testicular seminoma (TS) is evolving with guidelines supporting differential use of chemotherapy (CT) and radiotherapy (RT) depending on stage and presentation. We examined modern practice patterns in TS using the National Cancer Data Base. Methods: Data on 41,745 patients with TS treated between 1998 and 2010 were analyzed. Patients were grouped by stage based on National Comprehensive Cancer Network treatment guidelines. Multivariate generalized estimating equation models were used to assess factors associated with treatment paradigms. Results: Rates of surveillance after orchiectomy for those with stage IA/B TS increased from 21.4% during 1998-2001 to 40.4% from 2006-2010. Despite this, RT remained the most common adjuvant therapy (47.9% in 2006-2010). Use of adjuvant CT increased from 1.7% to 10.6% during this time. Patients with stage IS TS most commonly received RT; however, in 2006-2010, 32.4% of patients received surveillance and 15.6% received CT. Receipt of surveillance for those with stage IIA/B TS remained flat at ~12% while the use of CT rose (34.4% in 2006-2010 vs. 22.5% in 1998-2001). For patients with stage IA/B TS, Medicare or uninsured patients were more likely to receive surveillance vs. CT/RT (OR 1.54, p&lt;0.0001 and OR 1.26, p&lt;0.0001 respectively). Adjuvant CT/RT was more common at high volume centers (OR 0.63 vs. low volume, p&lt;0.0001) and in patients with larger tumors (OR 0.80 for tumors ≥ 4 cm, p&lt;0.0001). Among patients with stage IA/B TS who received adjuvant RT/CT, Medicaid or uninsured patients (OR 0.55, p&lt;0.0001 and OR 0.68, p&lt;0.0001 respectively) and those treated at NCI network cancer centers (OR 0.40 vs. community centers, p&lt;0.0001) were less likely to receive RT vs. CT. For stage IIA/B TS patients, facility type was the strongest predictor for the receipt of RT vs. CT (OR 0.54 at NCI network centers, p&lt;0.0001). Conclusions: Management of TS appears at least partially driven by economic concerns and facility type, especially in regards to selection of stage I patients for surveillance, the preferred management for this group. Many patients with stage IS are not managed according to published guidelines. Action is needed to ensure all patients with TS receive guideline supported care.
OSNA for detection of sentinel lymph node metastasis.
Authors: Masahiko Suzuki
Journal: Journal of Clinical Oncology (2013)

74 Background: SLN (sentinel lymph node) biopsy is a common procedure in surgical treatment of clinically node-negative breast cancer. OSNA (One-step nucleic acid amplification) is a semi-automated examination using molecular biological technique, and OSNA allows straightforward diagnosis of SLN metastasis without a pathologist by quantitative evaluation of CK19 m-RNA. The objective of this study was to confirm the reliability of OSNA for detection of sentinel Lymph node metastasis, and OSNA is also useful even in neoadjuvant chemotherapy (NAC) patients. Methods: Surgically obtained 159 SLNs from 106 breast cancer patients were evaluated and compared. The SLNs were sectioned into three pieces along the major axis. The central piece was sent to pathologists in an outside laboratory for postoperative histological investigation to diagnose metastasis. The other two pieces were examined with the OSNA to detecting metastasis during an operation. The OSNA analysis and the histological investigation were compared. Then, the patients were divided into two groups, one group was the patients with NAC (22 SLNs from 13 patients), and another group was the patients without NAC (137 SLNs from 93 patients). It was examined whether those concordance rates were similar. Results: 151 SLNs were same diagnosis using both methods. 4 SLNs were negative on OSNA but positive on histology, and these 4 SLNs contained only micrometastasis lesion. Other 4 SLNs were positive on OSNA but negative on histology. The concordance rate was 95.0%. In the patients with NAC, 20 SLNs were same diagnosis. Two SLNs were negative on OSNA but positive on histology, and these 2 SLNs were micrometastasis. The concordance rate was 90.9%. In the patients without NAC, 131 SLNs were same diagnosis. 2 SLNs were positive on OSNA but negative on history, and these 2 SLNs were micrometastasis. 4 SLNs were positive on OSNA but negative on history. The concordance rate was 95.6%. Conclusions: The concordance rate in patients with NAC was as high level as the rate in patients without NAC. The false negative SLNs were all micrometastasis. These results suggest that OSNA is very useful for detecting SLN metastasis and it is clinically acceptable in NAC patients.
A phase I/II trial of the oral mTOR-inhibitor everolimus (E) and imatinib mesylate (IM) in patients (pts) with gastrointestinal stromal tumor (GIST) refractory to IM: Study update
Authors: A. van Oosterom, P. Reichardt, J.-Y. Blay, H. Dumez, J. Fletcher, M. Debiec-Rychter, N. Shand, S. Drimitrijevic, A. Yap, G. Demetri
Journal: Journal of Clinical Oncology (2005)

9033 Background: Primary resistance to IM in advanced GIST pts is rare but after durable benefit, most pts eventually develop secondary resistance. Molecular pathways of resistance may activate alternate oncogenic signaling mechanisms, including AKT/mTOR pathway. Synergism in-vitro between IM and E has been shown in human GIST cell lines resistant to IM, serving as the basis for this targeted phase I/II trial which previously reported a 3-fold increase in exposure of E when dosed concurrently with IM due to a PK interaction. PET imaging noted increased tumoral FDG uptake with interruption of IM, with subsequent reduced FDG uptake when combined dosing with IM and E. Methods: GIST pts refractory to IM were treated with continuous dose of IM (600 mg/day) in combination with E dosed either weekly (20 mg) or daily (2.5, 5 mg). Serial assessments include FDG-PET and CT. Tumor biopsies were performed before and on drug therapy to evaluate proteomic and genetic biomarkers of clinical benefit. Results: 31 pts were treated in different E dosing cohorts: 13 (20 mg/week), 13 (2.5 mg/day) and 5 (5 mg/day). Grade 3–4 DLTs occurred in 3 pts at 5 mg/day E with IM: stomatitis and thrombocytopenia (1), gastritis (1) and hemorrhagic gastritis (1). Thus the 2.5 mg/day E cohort was expanded to include 13 pts. The most frequent suspected AEs were CTC grade 1–2 fatigue, diarrhea, vomiting, nausea, anemia, edema, headache and rash. The median duration of treatment was 14 weeks (range 3–60). 17 pts withdrew due to PD, 9 due to AE, 2 withdrew consent and 3 are ongoing. Stable disease (SD) was observed in 8 pts for more than 4 months (1 pt at 20 mg/week, 5 pts at 2.5 mg/day and 2 pts at 5 mg/day E). 2 of the ongoing pts (at 2.5 mg/day E) have improved to partial response (PR). Molecular analyses are ongoing to identify responding pts prospectively. Conclusions: The dose of E was identified as 2.5 mg/day in combination with IM (600 mg/day). Prolonged SD and 2 episodes of PR suggest potential benefit in a subset of pts. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharma AG Novartis, Pfizer Novartis Pharma AG Novartis Novartis Novartis
Regional initiative to use data transparency to improve cancer care.
Authors: Karma L. Kreizenbeck, Catherine R. Fedorenko, Teah Hoopes, Gary H. Lyman, Thomas David Brown, Eric Y. Chen, Ted Conklin, John M. Corman, Matt Lonergan, Daniel Lessler, Renato Martins, Csaba Mera, John Whitelaw Rieke, Elie P. Saikaly, Julie C. Smith, F. Marc Stewart, Richard Whitten, Scott David Ramsey
Journal: Journal of Clinical Oncology (2016)

39 Background: In the context of many initiatives aimed at measuring quality and value in cancer care, the Hutchinson Institute for Cancer Outcomes Research (HICOR) has adopted a multi-stakeholder approach to characterize oncology care, prioritize areas for improvement, design programs, and evaluate outcomes. Beginning in 2014, HICOR initiated a process to move towards data transparency in the reporting of regional quality and value metrics. Methods: The HICOR team constructed clinic-level adherence reports for community-prioritized metrics and the 2012 ASCO Choosing Wisely recommendations using a registry-claims linked database. In the fall of 2014, a national external advisory board reviewed methodology for measuring adherence. De-identified regional results were presented at a provider meeting in late 2014 to elicit provider feedback on methodology and on strategies for reporting clinic-identified adherence. Clinics were privately given their own adherence data. In 2015, revised de-identified regional reports were presented at a Value in Cancer Care Summit poster session and made available through HICOR IQ, a regional oncology informatics platform, for further discussion. Results: Results show that no clinic was also the best or worst performing clinic. The table shows the performance by clinic for the 5 Choosing Wisely recommendations. There is now increased demand by clinics to view their own adherence benchmarked with the region as a next step in moving towards full data transparency. Additionally, there is support from provider members in the community to re-identify clinics in order to compare results against their peers. Conclusions: Using an iterative, transparent, multi-stakeholder process, it is feasible build regional consensus towards releasing clinic-level adherence to quality and value metrics. By consulting trusted experts in the field and allowing multiple opportunities to provide feedback, providers are requesting even more transparency in order use the oncology measures to improve care in their practice and the region. [Table: see text]
The molecular relationship among concurrent prostate cancer foci.
Authors: David James VanderWeele, Jerome B. Taxy, Walter Michael Stadler, Kevin P. White
Journal: Journal of Clinical Oncology (2013)

43 Background: Prostate cancer management is influenced by how one views prostate cancer progression and how one calculates the risk of prostate cancer metastases and death. Currently this is based largely on histologic appearance, or Gleason score. Cancers with a Gleason score of 6 exhibit indolent behavior and are often considered low risk. NCCN guidelines endorse surveillance for many of these tumors. Malignancies with a Gleason score of 8-10 exhibit aggressive behavior and are considered high risk. Methods: Prostate cancer is usually multifocal, and these concurrent foci are often histologically distinct. In this study the molecular relationship between a Gleason 6 focus and a concurrent Gleason 8 or higher focus was determined for four subjects. In two subjects a lymph node metastasis was also examined. Laser capture microdissection was used to isolate these multiple matched foci, and somatic mutations were identified using exome sequencing. Results: We obtained an average of 40-fold median coverage of the exome, with an average high confidence mutation rate of 0.64/Mb, excluding nonsynonymous mutations. Seventy of 80 (0.875) high confidence somatic mutations in low grade disease were private to the low grade foci. For the cases for which a metastatic focus was available, 17 of 79 (0.215) high confidence somatic mutations in the high grade focus were private. Eight of the 79 (0.101) were shared with low grade foci, and 62 (0.785) were shared with metastatic foci. Conclusions: The pattern of shared versus private mutations was consistent with early divergence between Gleason 6 and Gleason 8 or 9 disease, and late divergence between Gleason 8 disease and lymph node metastases. These data support a model of parallel evolution of lower and higher Gleason score disease, rather than progression from Gleason 6 to higher Gleason scores.
Association of germline variation with androgen ablation (AA) failure in advanced hormone-sensitive prostate cancer (HSPC).
Authors: Samith Thomas Kochuparambil, Ben Yiming Zhang, Shaun M. Riska, Douglas W. Mahoney, Shannon McDonnell, Adam M Lee, Fernando Quevedo, Brian Addis Costello, Henry Clement Pitot, Ricardo Ribeiro, Rui Medeiros, Catia Monteiro, Augusto Nogueira, Joaquina Mauricio, Avelino Manuel Fraga, Fernando Eduardo Calais Da Silva, James Robert Cerhan, Manish Kohli
Journal: Journal of Clinical Oncology (2015)

209 Background: Predictive markers of response to AA are not known. In a prior study, we found that 8 single nucleotide polymorphisms (SNPs) from 4 candidate hormone-related genes (JAK2, TRMT11, NKX3-1 and HSD17B12) were associated with response to AA in HSPC in a North American cohort of 519 subjects. We attempt to replicate these findings in a cohort of Portuguese patients. Methods: The Portuguese cohort consisted of 308 HSPC patients, and the primary endpoint was time to AA failure, defined as time from initiating continuous AA to two serial PSA increases over the nadir, initiation of chemotherapy for progressive disease, or clinical or imaging based progression, whichever came first. For each SNP, we calculated hazard ratios (HRs) and 95% confidence intervals (CI) for time to AA failure using a recessive model with adjustment for Gleason score (GS). Results: The median age of the Portuguese cohort was 69 years (range 43, 85). The GS distribution was 35% subjects with GS≥8; 35% with GS=7 and 30% with GS&lt;7. Median time to AA failure for the cohort was 1.8 years (IQ range: 0.3, 3.6). Association of each SNP with time to AA failure is shown in the Table. None of the SNPs replicated. However, there was a suggestive inverse association for rs10503733 (NKX3.1) with time to AA failure (P=0.07). Conclusions: While we were not able to replicate our initial findings, there was an unexpected association with rs10503733 (NKX3.1 gene) that may warrant additional clinical validation. [Table: see text]
The use of bioimpedance spectroscopy to monitor response to treatment interventions with breast cancer-related lymphedema.
Authors: Chirag Shah, Frank Vicini, Peter D. Beitsch, Beth Anglin, Alison Lisa Laidley, Sheila H. Ridner, Maureen Lyden
Journal: Journal of Clinical Oncology (2013)

138 Background: Currently, limited tools are available to assess response to therapy in patients with breast cancer related lymphedema (BCRL). The purpose of this study was to perform an exploratory analysis to determine if, in clinical settings, bioimpedance spectroscopy (BIS) can detect changes in extracellular fluid volume in response to treatment of BCRL. Methods: Three centers that had experience with BIS (L-Dex U400, ImpediMed Limited, Brisbane, Australia) provided retrospective data on 50 patients with breast cancer who were evaluated with BIS at baseline and following loco-regional procedures. Patients had a pre-surgical L-Dex measurement as well as at least 2 post-surgical measurements (before and after BCRL intervention). Decisions regarding intervention were made by physicians with no L-Dex score cut-off utilized. An analysis was performed comparing changes in L-Dex scores for those patients undergoing treatment for BCRL (n=13) versus those not undergoing intervention (n=37). A second analysis was also performed on all patients with elevated L-Dex scores compared to baseline prior to intervention (n=32). Results: The mean age was 54 years old. Fifty four percent of patients underwent SLN biopsy with a mean of 7.9 nodes removed. The mean change in L-Dex score from baseline (pre-treatment) to the first post-surgical L-Dex score measurement was 3.3 +/- 6.8. When comparing the cohort treated for BCRL to those not treated, L-Dex scores were significantly reduced (-4.3 v. 0.1, p=0.005) following intervention. For the subset of patients with elevated L-Dex scores post-surgery, the change in L-Dex score following BCRL intervention was significantly reduced (-5.8 v. 0.1, p=0.001) compared with those observed. Conclusions: These results confirm that BIS can detect increases in L-Dex scores following breast surgery and can also detect reductions in L-Dex scores following intervention for early onset lymphedema. These results demonstrate that BIS has significant clinical utility as it can be used to monitor patients with early BCRL who undergo intervention and to follow these patients (through serial measurements) to document their short and long-term response to these treatments.
Management and outcomes of patients with renal medullary carcinoma (RMC): A multicenter retrospective study of 39 patients.
Authors: Amishi Yogesh Shah, Jose A. Karam, Priya Rao, Eric Jonasch, Kimryn Rathmell, Surena F. Matin, Ulka N. Vaishampayan, Daniel Heng, Elizabeth R. Plimack, Elizabeth A. Guancial, Chunkit Fung, Stefanie Rose Lowas, Zita D. Lim, Christopher G. Wood, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2015)

438 Background: RMC is a rare and aggressive neoplasm that afflicts primarily young black patients with sickle cell trait. Our primary objective is to report the outcomes of RMC patients through a collaborative initiative. Methods: After IRB approval, we retrospectively reviewed records of RMC patients treated from 2000-2013 at 7 academic institutions. Overall survival (OS) was calculated from RMC diagnosis to date of death. Descriptive statistics were used. Results: A total of 39 patients were included. Median age was 27.8 years and 29 (74%) were males. 38 (97%) had sickle cell trait. Median renal tumor size at presentation was 5.8 cm (range 3.4-11.4 cm). 3 patients presented with stage I disease, 13 with stage III disease, and 23 with stage IV disease. 22 patients had ECOG PS 0-1 and 17 had ECOG PS 2-3. The most common metastatic sites at diagnosis were lymph nodes in 27 and lung in 13. 26 patients (66.7%) had a nephrectomy. Pathologic stage was pT1-2 in 6 and pT3-4 in 20. 23 of these patients (88.5%) had positive lymph nodes at RPLND. 7 patients received preoperative systemic therapy. Median duration of pre-op therapy was 16 weeks (range 12-27 weeks). 1 patient had CR, 3 had PR and 3 had SD as best response to pre-op therapy. All patients received at least 1 line of systemic therapy. Median OS was 12.2 months. One patient had clinical CR with preoperative chemotherapy, near path CR on nephrectomy, and is currently NED at 27.4 mos. 5 patients are alive to date, though no patients have survived past 37 months. Conclusions: Patients withRMC have a grave prognosis. Nephrectomy (upfront or delayed) was associated with improved OS, even in patients with poor PS, though poor PS patients should be considered for upfront chemo. More effective therapies are desperately needed to improve patient outcomes. [Table: see text]
Retrospective Analysis of 56 Cases of Transformed Waldenström Macroglobulinemia. a Study on Behalf of the French Innovative Leukemia Organization (FILO)
Authors: Eric Durot, Cecile Tomowiak, Anne-Sophie Michallet, Jehan Dupuis, Stephane Lepretre, Elise Toussaint, Sophie Godet, Fatiha Merabet, Eric W Van Den Neste, Sarah Ivanoff, Jean-Marc Zini, Caroline Régny, Aurore Perrot, Lukshe Kanagaratnam, Pierre Morel, Veronique Leblond, Alain Delmer
Journal: Blood (2016)
Incidence of patient-reported urinary incontinence after stereotactic body radiation therapy for clinically localized prostate cancer.
Authors: Leonard N. Chen, Jennifer Ai-Lian Woo, Aditi Bhagat, Rudy A. Moures, Joy S. Kim, Thomas M. Yung, Brian Timothy Collins, Simeng Suy, John H. Lynch, Anatoly Dritschilo, Sean P. Collins
Journal: Journal of Clinical Oncology (2014)

254 Background: Urinary incontinence (UI) following prostate radiotherapy is a rare toxicity that adversely affects a patient’s quality of life. The potential for hypofractionated radiotherapy to increase the risk of UI was investigated. This study sought to evaluate the incidence and severity of UI following stereotactic body radiation therapy (SBRT) for prostate cancer. Methods: Between February 2008 and August 2011, 216 men with clinically localized prostate cancer were treated definitively with SBRT at Georgetown University Hospital. Patients were treated to 35 to 36.25Gy in five fractions delivered with the CyberKnife (Accuray). UI was defined as self-reported involuntary urine loss and was assessed via the UI domain of the Expanded Prostate Index Composite (EPIC)-26 at baseline and at months 1, 3, 6, 9, 12, 18, and 24. EPIC scores range from 0 to 100 with lower values representing worsening incontinence. The minimally important difference (MID) was defined as a change of one-half standard deviation from the baseline. Results: The median age was 66 with a median prostate volume of 38 cc. The median follow-up was 3.2 years. Baseline UI was common with 22.0%, 26.2%, and 3.3% of patients reporting leaking, dribbling and pad usage, respectively. At two year post treatment, 31.1%, 34.7%, and 7.1% of patients reported some degree of incontinence based on leaking, dribbling and pad usage, respectively. Average EPIC UI domain scores showed a slow decline over the first two years following treatment. At two year post treatment, the median decreased from a baseline of 92.1 to 88.0. This change was statistically (p &lt; 0.001) but not clinically significant (MID=6.7). The proportion of men feeling that their UI was a moderate to big problem increased from 1% at baseline to 6% at two years post treatment. Conclusions: SBRT for clinically localized prostate cancer was well tolerated with UI rates comparable to conventionally fractionated radiotherapy and brachytherapy. Greater than 90% of men who were pad-free prior to treatment remained pad-free two years following treatment. Less than 10% of men felt posttreatment UI was a moderate to big problem.
ATP Dependent Interferon Responsive (ADIR) Gene Encodes an Activation Induced Minor Histocompatibility Antigen Recognized on Multiple Myeloma by CD8+ T Cells.
Authors: Cornelis A. Van Bergen, Michel G. Kester, Inge Jedema, Mirjam H. Heemskerk, Simone A. Van Luxemburg, Freke M. Kloosterboer, Erik W. Marijt, Arnoud H. De Ru, Martyn R. Schaafsma, Roelof Willemze, Peter A. Van Veelen, J.H. Frederik Falkenburg
Journal: Blood (2006)