tbuckley/cabot-search huggingface dataset:
Major histocompatibility complex class I (MHC 1) expression in clear cell renal cell carcinoma: Correlation with clinical outcome.
Authors: Viraj A. Master, Sarah Holzman, Brian Pollack, Adeboya O. Osunkoya
Journal: Journal of Clinical Oncology (2014)

541 Background: Most patients with clear cell renal cell carcinoma (ccRCC) initially present with localized disease but a fraction subsequently develop metastases. Current predictive models of ccRCC recurrence are imperfect, suggesting a need for additional predictors. Metastatic ccRCC may be modulated by the immune system, suggesting that the immune system plays a role in tumor progression. Major histocompatibility complex class I (MHC I) expression on tumor cells is critical for immune system recognition. Here, we analyzed MHC I expression in ccRCC and its correlation with clinical outcomes. Methods: ccRCC patients who underwent radical nephrectomy with a ≥4 years of follow-up, without T4 disease or metastasis at presentation were included. All slides were re-reviewed by a single Urologic Pathologist and blocks with tumor and adjacent renal parenchyma were selected for each case for immunohistochemical staining for MHC I . Whole slide scanning and automated image analysis was used; representative areas of tumor and normal kidney were selected and averaged with Aperio image analysis software (positive pixel count v. 9). Unpaired t-test and one-way ANOVA were performed in GraphPad Prism. Results: 34 patients were analyzed. Fuhrman nuclear grades (FNG) were: FNG 2 10/34 (29%), FNG 3 20/34 (59%) and FNG 4 4/34 (11%). Although there was no correlation with FNG and MHC1 (ANOVA, p=0.800), patients who were alive at follow up had increased MHCI expression (80.1% average positivity score) than those who died (53% average positivity score; t-test, p&lt;0.0001). Patients living with recurrence had increased MHCI expression (81.3% positivity score) compared to those who succumbed to their disease (53.2% positivity score; t-test, p&lt;0.0001). Conclusions: MHCI expression may be an important prognostic factor in ccRCC for recurrence free survival, and also for prognosis of those patients with recurrence. This is the first study to show that increased MHCI expression is a favorable prognostic indicator in metastatic ccRCC. These results suggest that MHCI expression plays an important role in tumor-host immune system interaction of ccRCC and merits further study.
Assessing bone mineral density as a risk factor for early clinically significant prostate cancer
Authors: R. E. Weiss, S. Marcella
Journal: Journal of Clinical Oncology (2005)

4796 Background: This investigation is a prospective study of bone mineral density (BMD) in men with recently diagnosed clinically significant, but non-advanced prostate cancer (CaP). Three hormonal systems that impact on BMD and that may influence CaP growth are estrogens, vitamin D, and insulin-like growth factors. We hypothesize that if estrogen or vitamin D is more dominant, then denser bones will be associated with protection from CaP. Conversely, if the IGF-1 axis is more dominant, then denser bones will be associated with a greater risk for clinically significant CaP. Methods: Patients with newly diagnosed localized CaP with Gleason scores of 6 or greater had their hip BMD assessed by DEXA scan. Cases were compared against the age-, race-, and weight-standardized reference population to compute Z-scores and against 20 - 40 year-old, race-identical men for T-scores. Cases having surgery for cure are also followed prospectively to investigate the prognostic value of baseline BMD for event-free survival. Preliminary Results: Twelve patients have been enrolled in this ongoing study: 7 whites and 5 blacks with a mean age of 61 years and Gleason scores of six (8), seven (2), and nine (2). DEXA scans have been completed for nine. Z-scores have the following distribution: greater than one (3), minus one to one (6). Similarly, T-scores are: greater than 1.5 (3), between minus one to one (5), and less than one (1). None of our subjects have osteoporosis (T-score <2.5). Conclusions: Although preliminary, this suggests that men with clinically significant CaP have elevated BMD at baseline relative to that of an age-, race-, and weight-standardized population (Z-scores). We continue to increase our sample size and also will follow those men who have surgery for cure to see if BMD is associated with biochemical recurrence. No significant financial relationships to disclose.
HER2 and HER3 expression in hepatic metastases of colorectal cancer: New targets for specific treatment approaches?
Authors: Lena-Christin Conradi, Hanna Styczen, Thilo Sprenger, Hendrik A. Wolff, Peter Middel, Iris Nagelmeier, Josef Rüschoff, Kia Homayounfar, B. Michael Ghadimi, Tim Beissbarth, Torsten Liersch
Journal: Journal of Clinical Oncology (2014)

567 Background: Even though treatment options for coloretal cancer liver metastases have improved with the implementation of multimodal strategies and new agents, progression of distant metastases is still limiting the prognosis of affected patients. In this context we investigated the expression of HER2 and HER3 in patients with metastatic colorectal cancer and primary tumors. Methods: In this study 226 consecutive patients with hepatic metastases of colorectal cancer were included. HER2 and HER3 expression were determined in the tissue from resected metastases and—if available—in primary tumors. Immunohistochemical scoring (IHC 0 to IHC 3) and S-ISH-amplification-detection (for HER2) were used to determine the HER2 and HER3 status. Results: A positive HER2 status was found in 8.4% of all hepatic metastases; an overexpression of HER-3 in 74,8% of all cases. There was a high congruence of the expression pattern of HER2 and HER3 between hepatic metastases and available primary tumors (&gt;90%). Conclusions: HER2 amplification and HER3 overexpression is detectable in a significant proportion of hepatic metastases of colorectal cancer. These results suggest that innovative new targeted treatment agents might be possible opportunities for the specific therapy of patients with HER2/HER3 positive metastatic colorectal cancer and should be further assessed within prospective clinical trials.
Effect of moisturizers on prevention of hand-foot syndrome associated with capecitabine plus oxaliplatin.
Authors: Kazuyoshi Kawakami, Mitsukuni Suenaga, Takashi Yokokawa, Kazuo Sugita, Yutaro Mae, Eri Nakamoto, Hiroshi Imada, Nobuyuki Mizunuma, Toshiharu Yamaguchi, Toshihiro Hama
Journal: Journal of Clinical Oncology (2012)

681 Background: Capecitabine plus oxaliplatin (XELOX) has been established as first-line treatment for patients with metastatic colorectal cancer. Hand-foot syndrome (HFS) is the most common toxicity associated with capecitabine, and the mechanism of which remains to be clarified. Appropriate management of HFS for continuing treatment is needed to ensure improved survival. In this study, we evaluated the efficacy of our candidate moisturizers for HFS, considering its compliance in each patient at a single institute. Methods: Patients who received XELOX for metastatic colorectal cancer at the Japanese Foundation for Cancer Research, Cancer Institute Hospital, between Apr 1 2010 and Apr 30 2011 were included in this study. Pharmacists conducted the skin care for HFS using moisturizers: heparinoid ointment, a mixture of vitamin A oil and white petrolatums (1:1). All HFS events were graded according to NCI–CTC, version 4.0. The relationship between accumulated dose of capecitabine and incidence of HFS events stratified by frequency of daily moisturizers application was analyzed by using the Kaplan-Meier method. P value of &lt;0.05 was considered significant. Results: Moisturizers were applied two or more times a day in 45 patients (Good compliance group) and once a daily in 28 patients (Poor compliance group). In terms of incidence of grade ≥1 HFS, no significant differences were observed between good compliance group and poor compliance group (p = 0.764). Incidence of grade ≥2 HFS was observed slightly higher in the poor compliance group than in the good compliance group, though the differences were not statistically significant (p = 0.286). Conclusions: The onset of capecitabine-associated HFS is independent of frequency of using moisturizers. However, more frequent application of moisturizers appeared to have a possibility to prevent severe HFS. Assessment for compliance with the moisturizers is important as well as patient-compliance-instruction by pharmacist.
Real-world cancer regimen costs for metastatic colorectal cancer patients treated with biologics in first- through second-line.
Authors: Stephen Johnston, Ellen Riehle, Helen Varker, Paul Juneau, Kathleen Wilson, Nicolas Sommer, Sarika Ogale
Journal: Journal of Clinical Oncology (2016)

636 Background: This study examined real-world cancer regimen costs for metastatic colorectal cancer (mCRC) patients treated with biologics in first- (1L) through second-line (2L). Methods: Using a large U.S. commercial/Medicare supplemental insurance claims database, patients with mCRC initiating a 1L bevacizumab (BEV) or cetuximab (CET) containing regimen between 1/1/2008-8/31/2014 and transitioning to a 2L biologic-containing regimen (BEV, CET, panitimumab [PAN], regorafenib [REG], or ziv-aflibercept [ZAF]) were identified. Monthly costs of cancer regimens (biologic/administration, chemotherapy/administration) were measured over a follow-up period beginning at initiation of 1L therapy and ending at the discontinuation of 2L therapy, inpatient death, insurance disenrollment, or 9/30/2014. Results: Among 2,352 patients, mean monthly biologic costs for 1L+2L ranged from $6,738 in the 1LBEV-2LBEV group, to $12,568 in the 1LCET-2LOther group (Table). In contrast, chemotherapy costs ranged from $1,898 in 1LCET-2LOther group to $4,070 in the 1LBEV-2LBEV group. Conclusions: Mean total cancer regimen costs per month for the 1L+2L sequence tended to be lower for patients treated with 1L BEV-containing regimens, compared with 1L CET-containing regimens. The majority of 1L-BEV patients also received BEV in 2L (TML). These agents' real-world comparative costs are an important consideration in treatment decisions. [Table: see text]
Impaired Platelet Function in a P2Y12-Deficient Patient Caused by a Mutation in the Translation Initiation Codon.
Authors: Masamichi Shiraga, Shigeki Miyata, Tsuyoshi Kamae, Hisashi Kato, Teruo Kiyoi, Hirokazu Kashiwagi, Shigenori Honda, Yoshiyuki Kurata, Yoshiaki Tomiyama, Yuzuru Kanakura
Journal: Blood (2004)
Connecting specialty practices with primary care.
Authors: Manasi Tirodkar, Suzanne Morton, Tyler Oberlander, Sarah Hudson Scholle, Michael Barr
Journal: Journal of Clinical Oncology (2016)

47 Background: Public and private payers are beginning to adopt alternative payment structures that call for greater attention to patient-centered care and quality improvement activities (CMMI 2015; MACRA 2015). The National Committee for Quality Assurance (NCQA) developed standards for Patient-Centered Specialty Practice based on American College of Physicians principles. The report describes achievement on the standards among an initial cohort of recognized physicians. Methods: We analyzed practice characteristics and determined how practices performed on each of the 21 elements in the PCSP program by showing the percent of practices scoring less than 50% of points, or 100% of points (i.e. full credit) for each element. Results: One third of the 91 practices recognized in the first year of the program are Oncology/Hematology. Overall, about half of recognized practices have more than 5 clinicians and half are physician-owned (52%). Most specialty practices achieved full credit on having key clinical data in structured fields and using electronic prescribing. More than 75% of practices also achieved full credit for providing culturally and linguistically appropriate services, providing information about specialist visits back to primary care and providing patients/families information about the role of the specialist and coordination of care. Tracking of referrals to secondary specialists was most challenging, with only 6% of practices earning full credit. Only 34% of practices received full credit for coordinating care transitions from hospitals and other facilities; most practices did not even receive half credit. Measuring and improving performance was also challenging for all practices. Compared to other specialties, oncology/hematology practices were less likely to achieve full credit on the following elements: electronic access, measure patient/family experience, patient information, and care planning and support self-care. However, they performed better on documenting clinical data than other specialty practices. Conclusions: Specialty care practices have started to implement the patient-centered care model. Research to identify which components of the model have the greatest impact on outcomes is needed.
Stakeholder-informed “Choosing Wisely” implementation project in regional oncology clinics.
Authors: Karma L. Kreizenbeck, F. Marc Stewart, Constance Lehman, Timothy Carlos, Eric Y. Chen, Barbara Jensen, John W. Rieke, Benjamin E. Greer, Chris Bredeson, Kristie Putnam, Scott David Ramsey
Journal: Journal of Clinical Oncology (2013)

207 Background: ASCO launched the Choosing Wisely campaign to reduce the use of interventions that lack evidence for their use in clinical cancer care. The recommendations have strong support, but lack an implementation plan. The objective of this project is to develop a stakeholder-informed process to improve adherence to ASCO Choosing Wisely within an experimental context. Methods: Participants include Medical Directors from 7 oncology clinics and 1 commercial insurer within the Puget Sound region, and the SEER Puget Sound Cancer Registry. The project consists of 3 phases (1) prioritization, (2) design, (3) implementation and monitoring. For phase 1, Medical Directors were surveyed via e-mail to prioritize the recommendations with the following criteria: importance for improving the value of cancer care; impact of adherence; urgency; and feasibility of implementing an intervention. Participants met via teleconference to discuss survey results, review regional utilization data, and design of interventions. Participants were surveyed again for a final ranking. In phase 2, participants discussed options for interventions and study designs. Results: Initially, the highest ranked recommendations were advanced imaging in staging of local stage prostate cancer, surveillance of local and regional stage breast cancer, and colony stimulating factor (CSF) use for low risk chemotherapy. After discussion, breast cancer surveillance and CSF prescribing ranked the highest. Participants requested utilization and cost-impact data from the health insurer for the top 2 choices. Conclusions: Using a transparent, multi-stakeholder process, it is feasible to implement programs to improve adherence to ASCO Choosing Wisely.
Mean radiation dose to the heart in patients with breast cancer.
Authors: Geraldine Meerbott Jacobson, Sijin Wen, Jianjun Zhang, Hannah Hazard, Jame Abraham
Journal: Journal of Clinical Oncology (2013)

56 Background: Breast irradiation may expose a portion of the heart to radiation. Heart irradiation is associated with late risk of ischemic heart disease, proportional to dose. A recent publication of patients treated with 2-D planning prior to 2001 noted average mean heart dose (MHD) of 6.6 Gy for left breast tumors, 2.9 Gy for right breast. Current treatment planning can minimize the MHD, reducing the risk of late heart injury. Methods: We reviewed treatment plans of 78 patients (86 breasts) treated 1/2012-3/2013 to obtain MHD. Treatment plans were CT-based, field-in-field forward planning with heart blocking. Two treatment regimens were used; hypofractionation (HF) (16 x 2.66 Gy, no boost) or standard (SF) (46.8-50.4 Gy +/- 10 Gy boost). Statistics were obtained for MHD based on right (N = 44) or left breast (N = 42); HF (N = 31) vs SF (N = 55), and total dose. Results: Average (av) MHD for left breast was 1.45 Gy (range 0.19-3.12), for right breast 0.70 Gy (0.12-1.54). For HF patients av MHD left was 1.16 Gy (0.19-1.90), MHD right was 0.48 Gy (0.12-0.91). For SF av MHD left was 1.60 Gy (0.80-3.12), MHD right was 0.84 Gy (0.39-1.54). There was a significant difference in MHD between left and right breasts (p = 0.002) and significant correlation between breast dose and MHD (p = 0.026). Conclusions: MHD from breast RT with current treatment planning is much lower than published reports from 2-D planning. MHD correlates with total breast dose and is greater for the left than right side. Techniques to reduce MHD should be utilized, especially for left-sided breast cancer.
Adjuvant chemotherapy and lymph node irradiation in breast cancer patients with axillary lymph node micrometastases or isolated tumor cells.
Authors: M. Gardner, D. Stevens, S. Zilberman, S. Villette, F. Lerebours, P. Moisson, B. De La Lande, R. Le Scodan, J. Guinebretiere, A. Labib
Journal: Journal of Clinical Oncology (2010)

581 Background: To evaluate the influence of loco-regional radiotherapy and adjuvant chemotherapy on the outcome of breast cancer patients with axillary lymph node micrometastases (MMTS) or isolated tumor cells (ITC). Methods: Between 1995 and 2005, 10,296 breast cancer patients were treated in our institution, 177 of them for unilateral breast cancer with MMTS (147) or ITC (30) by breast-conserving surgery or total mastectomy. The impact of chemotherapy and irradiation on overall survival (OS), disease-free survival (DFS) and metastases-free survival (MFS) were studied. Results: Median follow-up time was 77 months (mean 83.2 months), OS at 5 years 94.1 (89.2- 96.9), DFS 90.1 (84.4–93.9). No improvement in OS, DFS nor MFS were found in patients treated by supraclavicular irradiation (127/177), internal mammary lymph nodes (IMLN) irradiation (103/177) or axillary region irradiation (52/177). The OS, DFS and MFS were similar in patients with (93) or without (84) chemotherapy. Conclusions: Neither loco-regional radiotherapy nor adjuvant chemotherapy influenced the outcome of breast patients with MMTS or ITC. No significant financial relationships to disclose.
Carbonic anhydrase IX (CAIX) as a potential biomarker of efficacy in metastatic clear-cell renal cell carcinoma (mccRCC) in patients (pts) receiving sorafenib: Analysis of a randomized controlled trial (TARGET).
Authors: Angela Q. Qu, SuChun Cheng, Michael B. Atkins, Sabina Signoretti, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2012)

352 Background: No biomarkers have been routinely utilized to provide guidance for treatment in mccRCC. Retrospective data analyses have suggested that CAIX may have a predictive role in pts receiving immunotherapy or vascular endothelial growth factor (VEGF)-targeted therapy (Atkins Clin Cancer Res. 2005, Choueiri BJU Int 2010). We examined the predictive value of CAIX as a biomarker in estimating treatment outcome in pts receiving sorafenib vs. placebo as part of a large randomized trial (RCT). Methods: Paraffin embedded tumor tissue was collected from 133 participants with independently reviewed disease-progression status in the TARGET study (N=903), which randomized pts to receive either sorafenib or placebo following progression on cytokine based therapy. Tumor tissue sections were immunostained for CAIX using the M75 antibody. The percentage of CAIX-positive tumor cells was assessed for each tumor by a single pathologist. The impact of CAIX expression on progression free survival (PFS, primary endpoint), and tumor shrinkage (TS) was analyzed for both sorafenib and placebo treated pts. Results: Overall, 51% of pts were intermediate and 49% low risk per MSKCC criteria. 68% had high CAIX expression (&gt;85% cell staining). Clinical characteristics were similarly distributed between pts with low vs. high CAIX staining, as well as pts with CAIX data vs. not. Median PFS for pts with high CAIX vs. low CAIX was 5.5 months and 5.4 months respectively on the sorafenib arm (p = 0.97), and 1.5 months and 1.7 months on the placebo arm (p = 0.76). Median TS for pts with high CAIX status was −14.9% vs. −12.6% in pts with low CAIX status (p = 0.63) on the sorafenib arm, and +1.3% (high CAIX) vs. +4.8% (low CAIX) in pts on the placebo arm (p=0.60). Conclusions: Despite suggestive retrospective evidence, data from the TARGET study did not find CAIX expression status to be of predictive or prognostic value for treatment with sorafenib in pts with mccRCC following cytokine failure.
Vaccine Properties of a Novel Marker Gene-Free Recombinant Modified Vaccinia Ankara (MVA) Expressing Immunodominant CMV Antigens.
Authors: Don J. Diamond, Zhongde Wang, Corinna La Rosa, Tumul Srivastava, Wendy Zhou, Zhongqi Li, Heang Ly, Tamineh Akbarnejad, Aparna Krishnan, William J. Britt
Journal: Blood (2006)
Relationship between relative dose intensity and mortality in women receiving combination chemotherapy for stage III-IV epithelial ovarian cancer.
Authors: L. J. Havrilesky, R. K. Hanna, M. S. Poniewierski, R. Laskey, A. A. Secord, P. A. Gehrig, M. A. Lopez, A. Shafer, L. Van Le, D. C. Dale, J. Crawford, G. H. Lyman
Journal: Journal of Clinical Oncology (2011)

5084 Background: Although considerable progress has been made in the treatment of advanced ovarian cancer, complications of both disease and treatment limit long term survival. Further research is needed on specific patient- and treatment-related factors that are associated with increased mortality in this population. Methods: A multicenter retrospective study of women with surgical FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy between 1995 and 2008 was conducted. Data were obtained from each institution’s tumor registry and medical records to include the first four cycles of chemotherapy administered. Outcomes included: (1) Chemotherapy relative dose intensity (RDI), defined as actual delivered dose intensity over the course of chemotherapy in comparison with standard ovarian cancer regimens based on literature review; (2) Overall survival. Survival estimates were based on the method of Kaplan and Meier and multivariate analysis was based on the proportion hazards regression method of Cox. Results: Evaluable patients included 327 women with stage III or IV ovarian cancer. With median followup of 26 months (range, 1-170), progression or recurrence was noted in 246 patients (74.3%) and death was recorded in 180 (54.4%). Median time to recurrence or progression was 18 months while median time to death was 48 months. Factors associated with overall survival included disease stage, baseline CA 125 and chemotherapy RDI. In multivariate regression analysis, the following factors were independently associated with overall survival: Noncaucasian race (HR=1.46; P=0.045); Stage IV (HR=1.38; P=0.035); Elevated baseline CA 125 (HR=2.41; P=0.007) and RDI <85% (HR=1.52; P=0.011). Age, type of treatment and comorbidities did not appear to influence overall survival after adjustment for the above prognostic factors. Conclusions: Women who receive reduced relative dose intensity of primary chemotherapy for ovarian cancer have lower survival even after adjustment for race, stage and baseline CA-125. These data suggest that women with ovarian cancer should be treated with target RDI whenever possible.