tbuckley/cabot-search huggingface dataset:
Cetuximab-induced skin rash: A molecular map relating polymorphisms, cell-adhesion, and autoimmunity.
Authors: Sebastian Schaaf, Matthias Froelich, Thomas Kirchner, Volker Heinemann, Andreas Jung, Sebastian Stintzing, Ulrich Robert Mansmann
Journal: Journal of Clinical Oncology (2015)

570 Background: Colorectal cancer (CRC) treatment with the EGFR-inhibitory antibody Cetuximab (CTX) is known to cause skin rashes (SR) of varying degree in most patients. Severity of SR is positively associated with tumor response. The underlying molecular mechanism linking both effects is still unknown. Detangling its genetic background would allow a simultaneous understanding of SR and response. Stratification of patients based on the related polymorphisms (PMs) is of clinical relevance. Methods: A systematic literature review was performed to develop a molecular map which incorporates specific pathways related to cancer, CTX specific mechanisms of action, skin rash, and autoimmunity. Exome data was generated from blood samples of 23 KRAS wild type patients taken prior to CTX treatment. Under CTX, eleven of the 23 patients showed SR of grades 3-4, twelve reacted with a grade 1 SR. Differential somatic PMs were analyzed between both groups. A gene set enrichment analysis for the imbalanced PMs was performed against gene sets of our molecular map. Imbalance was stated if at least seven patients more in the one group compared to the other carried this specific PM. Results: A total of 591 genes containing imbalanced PMs were found. Bioinformatic validation focused on the following findings of potential clinical interest: (1) PMs in genes specifically related to cell adhesion (CDH1, LAMC1, FBN2, NCAM1) or its regulation (WNT9B), (2) to autoimmunity (CXCL16, ADAM12, OS9, DOCK2), (3) in the central regulator TP53, (4) in genes playing a role in immunity and cell adhesion (DOCK2 and THBS2). PMs in the mentioned genes enabled to discriminate patients with and without severe skin rash. Validation of these findings is needed based on new independent CTX treated patients. Conclusions: Our findings suggest that genomic predisposition may exist which interact with CTX treatment by inducing alteration of cell adhesion. Altering adhesion between tumor cells makes them more accessible to the EGFR-inhibitory effect of CTX. Altering cell adhesion between epithelial cells introduces the acne like phenotypes of skin rash, presumably via the mechanism of epithelial activation. This will be the starting point for further research.
Treatment, mortality, and health care costs in a U.S. cohort of indolent non-Hodgkin lymphoma patients with relapsed or refractory disease.
Authors: Nicole Meyer, Xue Song, Stephanie A. Gregory, Scott David Ramsey
Journal: Journal of Clinical Oncology (2014)

35 Background: Indolent non-Hodgkin lymphomas (iNHL) have relapsing courses after initial therapy. For those who relapse, the response duration to subsequent lines of therapy shortens with time, eventually becoming refractory. Using a large national claims database, this study examined the treatment, mortality and healthcare costs of iNHL patients who relapse after initial therapy. Methods: Patients newly diagnosed with iNHL (i.e., follicular lymphoma, small lymphocytic lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma) during 2004-2013 were identified from the Truven Health MarketScan Commercial and Medicare claims databases. Relapsed or refractory disease (R/R) was defined as those patients relapsing/not responding within 6 months on any combination of alkylating agents (AA) and rituximab (R) as evidenced by having claims indicating a change in treatment. Patients were followed from the start of the new treatment (index date) until death or end of data. Healthcare costs were adjusted to 2013 dollars. Results: Among a total of 254,067 iNHL patients, 1,483 (1.4%) met study criteria for R/R. The average age was 63 (SD 13) and 61% were male. Common comorbidities were: lipometabolic disorders (44%), hypertension (40%), diabetes mellitus (17%), chronic pulmonary disease (15%), cerebrovascular disease (7%) and renal disease (6%). The most common first line regimens were rituximab, cyclophosphamide, doxorubicin and vincristine ± prednisone/ dexamethasone (22%). The mean duration of first-line and second-line therapy was 230 (SD 401) and 369 (SD 544) days, respectively. Among the 45% patients with mortality information, the median survival time from R/R was 5.3 months (mean 16.4, SD 17.7). During the follow up period from the initial date of R/R, the mean annual total medical cost was $170,179 (SD $250,376): 62% outpatient, 34% inpatient and 4% outpatient pharmacy. Conclusions: Patients with R/R iNHL represented a relatively small fraction of all iNHL patients, but had high mortality rate and incurred substantial medical cost.
The impact of subsequent metastasis on medical costs in Medicare patients with prostate cancer.
Authors: Tracy Li, Neal D. Shore, Maneesha Mehra, Mary Beth Todd, Ryan Saadi, Gaetan Leblay, Robert Griffiths
Journal: Journal of Clinical Oncology (2016)

81 Background: The objective of this study was to estimate the direct medical costs of secondary metastases in prostate cancer (PC) patients initially diagnosed with locoregional disease. Methods: We used data from the United States Surveillance, Epidemiology, and End Results (SEER) cancer registry linked to Medicare claims to identify a cohort of PC patients initially diagnosed with locoregional disease between 2000 and 2011, who were age ≥ 66 at diagnosis, and who first had a diagnosis of metastasis (index date) ≥ 4 months after PC diagnosis (cases). We matched each case to up to four controls (patients without metastasis) on baseline patient characteristics to assess the incremental impact of developing metastasis. A “match date” corresponding to the index date of the case was constructed for each control. Cases and controls were followed from up to 12 months before and up to 12 months after metastasis. Medicare claims were used to calculate the average total cost per month in the cases and controls. Monthly costs also were stratified according to place and type of service, e.g. inpatient, outpatient, and by whether costs pertained to cancer services, i.e. chemotherapy or androgen deprivation therapy (ADT), other services with an ICD-9 code for cancer, or other care. Results: The cohort consisted of 10,370 cases and 39,200 controls, with a mean age at baseline of 79 years in both groups. The median time to subsequent metastasis (cases) was 37 months and 85% had bone metastasis. In the control group, total costs remained stable throughout the observation period, averaging $1,354/month before and $1,173 12/month after matched index date. In the cases, costs were similar to the controls from -12 to -6 months before the index date. Thereafter, medical costs rose sharply to $11,982 in the month of diagnosis of metastasis (index date), and then declined but stayed &gt; $2,000/month higher than the control for the remainder of the observation period. Expenses from inpatient, physician services, outpatient, and skilled nursing facility accounted for the largest proportions of total costs. Conclusions: Developing metastasis in Medicare PC patients results in substantial additional costs to the healthcare system.
Patient informational needs about breast reconstruction post-mastectomy.
Authors: Ivy A. Ahmed, Allison Harvey, Erica Weiss, Marni Amsellem
Journal: Journal of Clinical Oncology (2012)

88 Background: For many women, receiving a breast cancer diagnosis is further complicated by decisions they will face about breast reconstruction post-mastectomy. While women are typically provided with some information about reconstruction options, little is known about the perceived value of this information and how it might ultimately affect their decision about reconstruction. The Cancer Support Community investigated these questions in a national sample of women with breast cancer to better understand their information-seeking experiences, knowledge, and decision-making about reconstruction. Methods: In 2011, 439 participants attending Frankly Speaking about Cancer: Spotlight on Breast Reconstruction, a national educational workshop, completed a post-workshop survey (56.4% response rate). 76.2% of respondents were women diagnosed with breast cancer, who reported their decisions about reconstruction as well as their experience receiving information about reconstruction. Results: Respondents were Caucasian (74.8%), black (11.4%), and Hispanic (10.1%), and the mean age was 48.9. Nearly half (42%) of respondents reported low levels of knowledge about breast reconstruction prior to the workshop. Of those eligible for breast reconstruction, 18.2% reported they had decided against reconstruction, 40.7% were considering their options, and 41.1% planned to undergo or had undergone reconstructive procedures. Women reported they would have liked to have had more information prior to reconstruction about a variety of topics, including more information about the procedure (43.6%), how they would look (31.1%) and feel (29.7%) after reconstruction, and information about their future breast health (31.8%). No differences were found in unmet informational needs based on their reconstruction decisional status with one exception: those who decided against reconstruction were more likely to endorse that they would have wanted more information about when to make their decision about reconstruction than the other two groups (chi square=24.6, p &lt;.01). Conclusions: Findings suggest women facing breast reconstruction often are not equipped with comprehensive information about procedures, options, outcomes, and recovery.
The importance of combined hematologic and CT diagnosis for monitoring response in patients with multiple myeloma treated with Bortezomib based therapy
Authors: M. Horger, K. C. Weisel, H. Brodoefel, B. Denecke, C. D. Claussen, L. Kanz
Journal: Journal of Clinical Oncology (2008)

8597 Background: To assess the potential role of radiological monitoring (conventional CT) of lytic bone lesions for diagnosis of progressive (PD) or relapsing (R) multiple myeloma (MM) in comparison with laboratory-based diagnosis, soft-tissue based CT-diagnosis and combined hematologic-radiological diagnosis. Materials and Methods: Between 3/03 and 12/07, 201 patients with MM underwent nonenhanced whole-body low-dose multidetector-CT (WBLD-MDCT) survey parallel to hematological follow up (582 investigations). CT-scans were performed using a standardized low-dose protocol assessing number and size of lytic bone lesions (bone window setting, bW) similar to conventional X-ray diagnosis. In addition, number, size and density of medullary and extra-medullary lesions (soft-tissue window setting, s-tW) were analyzed. Progressive or relapsing myeloma was defined by progression of lytic bone lesions, medullary and extra-medullary tumor infiltration and/or of established basic hematologic parameters. Results: 210/582 investigations showed PD or R. 50/210 (24%) yielded the correct diagnosis by all three methods, 50/210 (24%) were diagnosed correctly by WBLD-MDCT (bW), 133/210 (63%) by laboratory-based testing and 195/210 (93%) by WBLD-MDCT (s-tW) as well as by the combination of the latter two. 8/26 assessments of R were biomarker negative. Only 1 of these examinations proved positive on WBLD-MDCT (bW) while the other 7 were correctly diagnosed by WBLD-MDCT (s-tW) due to progress of medullary infiltration and/or extra-medullary manifestation. Of the biomarker-negative assessments of PD (84/210), only 24 (24/84) showed progress of osteolysis on WBLD-MDCT (bW) while all were correctly assessed by WBLD-MDCT (s-tW). Discussion: This retrospective analysis indicates that monitoring of lytic bone lesions in patients with MM is inaccurate for assessment of progression or relapse of multiple myeloma. Due to the effects of specific chemotherapy and accompanying bisphosphonates therapy, progression of lytic bone lesions seems to occur much later in the course of the disease showing slower growth kinetics compared with medullary and extra-medullary myeloma manifestations. No significant financial relationships to disclose.
Community-based dental evaluation program for hematopoietic cell transplantation.
Authors: Jennifer L. Frustino, Nathaniel S. Treister, Stephen T. Sonis, Sook-Bin Woo
Journal: Journal of Clinical Oncology (2013)

143 Background: Conditioning regimens for hematopoietic cell transplantation (HCT) may result in profound neutropenia placing patients at risk for infection. Since the mouth is a common site of origin for infection and bacteremia, elimination of pre-existing oral and dental disease prior to HCT favorably impacts infection risk and attendant morbidities. While pre-HCT dental screening is highly desirable, the logistics of assuring that all HCT patients are comprehensively evaluated and appropriately managed is challenging. Dana-Farber/Brigham and Women’s Cancer Center (DFBWCC) implemented a community-based dental evaluation program (CBDEP) for all patients scheduled to undergo HCT which has proved to be effective, cost-efficient and patient-friendly. The objective of this presentation is to describe that program. Methods: We describe the CBDEP and evaluate volume trends and clinical and cost outcomes. As part of the HCT work-up, the patient is provided with education materials, evaluation guidelines and forms to be completed by the community dentist (CD). The patient is responsible for making a timely appointment with the CD who obtains a full series of radiographs and completes a comprehensive examination and treatment plan. The completed documents and radiographs are returned to DFBWCC and reviewed by the oral medicine specialist. The CD is contacted immediately with any discordance in the plan. A letter confirming the final treatment plan is sent to the CD and entered into the electronic medical record. Upon admission for HCT, the patient is evaluated bedside to ensure all work is completed and there are no new symptoms. Results: From 2009-2012 an average of 523 patients per year participated in the CBDEP, with an increasing trend due to growing HCT volume with 440 patients evaluated in 2009 and 563 in 2012. Once returned, evaluations were reviewed within 1-10 days. The average cost for examination, radiographs, scaling and prophylaxis was $255. The average cost rose to $453 if additional treatment was required. Conclusions: The CBDEP provides an efficient and effective model for clearance prior to HCT. This directly involves the patient and the CD, is inexpensive and easy to implement, and may reduce complications during HCT.
Multidisciplinary clinic evaluation changes prostate cancer stage and risk stratification.
Authors: Debasish Sundi, Jason Cohen, Alexander Cole, Brian Neuman, Jack Cooper, Farzana Faisal, Marian Raben, Danny Y. Song, Charles G. Drake, George J. Netto, Katarzyna Macura, Theodore L. DeWeese, Alan Wayne Partin, Ashley E. Ross, Edward M. Schaeffer
Journal: Journal of Clinical Oncology (2014)

91 Background: The use of multidisciplinary clinics (MDCs) for outpatient cancer evaluation is increasing. Data on whether MDCs improve prostate cancer (PCa) care are limited. We studied the frequency of changes in PCa grade and stage upon MDC evaluation. Methods: Between May 2008 and December 2012, 887 consecutive patients underwent consultation for newly diagnosed prostate cancer at the Johns Hopkins Hospital (JHH) MDC, which features real-time collaboration among urologists, radiation oncologists, and medical oncologists. Retrospective chart review identified presenting tumor characteristics, based on outside assessment (medical records sent upon referral to MDC), as compared with disease stage and grade as determined at MDC evaluation. All outside biopsy slides were reviewed by JHH pathologists, and all outside imaging (CT, MRI, bone scan) was reviewed by JHH radiologists. Results: The three most chosen treatments after MDC evaluation were external beam radiotherapy +/- androgen deprivation (39.3%), radical prostatectomy (32.0%) and active surveillance/expectant management (12.9%). Using the NCCN guidelines as a benchmark, many men were found to have undergone non-indicated imaging (bone scan 23.9%, CT/MRI 47.4%). Overall, 186/647 (28.7%) had a change in their NCCN risk classification or N or M stage. For example, 2.9% of men were down-classified as very-low-risk, rendering them eligible for active surveillance. 5.7% of men thought to have localized cancer were up-classified as metastatic, thus prompting systemic management approaches. Conclusions: Comprehensive evaluation of prostate cancer patients in a MDC is associated with critical changes in presenting disease classification from baseline in over one in four men. While questions about the long term costs and benefits of MDCs remain, these results lend credence to the growing belief that MDCs may dramatically impact management for a large number of men with prostate cancer. [Table: see text]
An integrated cross-species approach for the discovery of serum-based diagnostic biomarkers of PDAC using a genetically engineered murine model (GEMM).
Authors: Ferdinandos Skoulidis, Ralph Schiess, Ruedi Aebersold, Ashok R. Venkitaraman
Journal: Journal of Clinical Oncology (2012)

218 Background: The development of sensitive and specific biomarkers for the early diagnosis of human pancreatic ductal adenocarcinoma (PDAC) represents a major unmet clinical need. GEMMs that faithfully recapitulate the clinical, histological and molecular features of PDAC and capture its genomic complexity (including that triggered by a truncating germline Brca2 mutation) coupled with state of the art proteomic technologies can overcome some of the challenges associated with the analysis of a heterogeneous human disease. We have conducted a large scale screen for differentially expressed glycoproteins in pancreatic tissue and serum from mice with PDAC, pancreatic intra-epithelial neoplasia (PanIN) and matched healthy controls, using the well validated KPCB model of PDAC. Methods: Tryptic digests of protein extracts from snap frozen PDAC, pre-malignant and normal pancreata were subjected to solid-phase extraction of N-glycopeptides and the samples were analysed on a LTQ Orbitrap XL mass spectrometer. LC-MS feature maps were compared employing SuperHirn software and used for the label-free quantification of corresponding proteins. Primary mPDAC cell lines and their supernatants were also analysed. Selected candidate proteins were then quantified in mouse serum by SRM-based targeted proteomics. Results: 146 glycoproteins were identified as overexpressed by &gt;2 fold (p&lt;0.05, Student’s t test) in PDAC compared to normal pancreas and 60 were prioritised for targeted identification in mouse serum. 12 proteins were significantly upregulated (p&lt;0.01, Mann-Whitney U test ) in the serum of tumour-bearing mice with PDAC compared to controls. Conclusions: Using a state of the art GEMM of PDAC, we have successfully applied a two-stage strategy for the tissue-based identification followed by quantification in murine serum of a panel of glycoproteins that are consistently over-expressed during mPDAC development. Validation in serum collections from patients with PDAC, chronic pancreatitis and healthy controls is underway and updated results will be presented at the conference.
The effect of tobacco exposure in renal cell carcinoma (RCC) overall and cancer-specific survival.
Authors: N. Kroeger, T. Klatte, F. D. Birkhaeuser, E. N. Rampersaud, D. B. Seligson, N. Zomorodian, F. F. Kabbinavar, A. S. Belldegrun, A. J. Pantuck
Journal: Journal of Clinical Oncology (2011)

4578 Background: Tobacco use is a leading cause of premature death in the United States, yet few studies have investigated the effect of tobacco exposure on RCC outcomes. We retrospectively studied the impact of smoking history on clinicopathological factors, survival outcomes, and p53 expression status in a large cohort of RCC patients. Methods: 802 patients with ccRCC treated at UCLA formed the study cohort. Patients were divided into two groups, never smokers (457 patients) and patients with a positive tobacco exposure history (345 patients). The Kaplan Meier method and log rank test were used to evaluate survival outcomes. Cox models were constructed to evaluate independent risk factors. Immunohistochemistry (IHC) differences in p53 expression were correlated with smoking status. Results: Patients who were current smokers presented more commonly with pulmonary (p< 0.0001) and cardiac medical co-morbidities (p=0.014), and with a worse performance status (p=0.031) than non-smokers. Smoking was significantly associated with tumor multifocality (p=0.022), higher pT stages (p=0.037), increased risk of lymph node metastases (p=0.031) especially bulky N2 disease (p=0.009), presence of distant metastases (p<0.0001), especially lung metastases (p<0.0001). Both overall survival (OS 62.37 months vs. 43.64 months (p= 0.001) and cancer specific survival (CSS 87.43 months vs. 56.57 months (p=0.005) were significantly worse in the group of patients with a smoking history. In multivariate Cox models the number of pack years was retained as an independent predictor of CSS and OS in non-metastatic patients. Mutated p53 was detected in 70.8% of current and 53.0% of non-smokers, respectively (p=0.017), and mean expression was significantly higher in current versus non-smokers (p=0.012). Conclusions: In RCC patients, a history of smoking was associated with worse pathologic features and survival outcomes, and with increased risk of having mutated p53. Further investigation of the genetic and molecular mechanisms associated with decreased CSS in RCC patients with a smoking history are indicated.
Characterizing terminal oncology ICU hospitalizations.
Authors: Robert Michael Daly, Andrew Hantel, Blase N. Polite
Journal: Journal of Clinical Oncology (2015)

167 Background: Twenty-five percent of Medicare cancer beneficiaries use the ICU in the last month of life, and 8% of cancer patients expire there. Cancer patients who die in the ICU have worse quality of life compared with those who die at home. Terminal ICU hospitalizations also come at high financial cost, accounting for 80.2% of all terminal hospitalization costs. Our hypothesis is that a significant number of oncology patients suffer avoidable terminal ICU hospitalizations. By better characterizing these hospitalizations, we will provide the knowledge backbone for future interventions. Methods: Using data from the University of Chicago (UC) cancer registry, we identified patients who died in UC adult ICU’s in FY2013. Of the 1,388 oncology deaths, 115 were in the ICU. Of those, 73 were established patients having had at least one visit with a UC oncologist. We performed a chart abstraction to identify patient, clinical, and hospitalization characteristics. Results: The average age of this patient population was 64 years and 71% were men. Solid and hematologic malignancies comprised 71% and 29%, respectively. Of the solid malignancy patients, 54% had metastatic disease. The average duration of the patient-oncologist relationship was 693 days, and 77% had their last oncology appointment within 2 months of index hospitalization. The ECOG performance status was ≥ 2 prior to admission in 51% of patients. These patients had an average of 3 hospitalizations and 15 outpatient visits in the year prior to death. Eighty-one percent did not have advance directives and 86% did not have an outpatient palliative care consult. The average duration in the ICU was 8 days, during which 95% did not have an inpatient palliative care consult, 79% were intubated, and 38% had resuscitation attempted. Conclusions: Most cancer patients who died in the ICU had an advanced stage malignancy and/or poor clinical status prior to admission. In addition, a significant number received intubation and resuscitation. Despite evidence of adequate interaction with the healthcare system, most patients had not had a palliative care consult or advance directives. This study will allow for further exploration of the avoidability of terminal oncology ICU hospitalizations to inform future interventions.