tbuckley/cabot-search huggingface dataset:
Impact of early prostate cancer diagnosis in the United States.
Authors: Y. Zhang, B. K. Hollenbeck, J. E. Montie, J. T. Wei
Journal: Journal of Clinical Oncology (2011)

6078 Background: The widespread use of PSA testing has resulted in a heated debate regarding the benefits of early diagnosis of prostate cancer (PCA). In this context, we estimated the effect of PCA early detection on the change of health status among Medicare beneficiaries. Methods: We applied a health state transition model on SEER-Medicare 1992-2006 to assess the impact of early diagnosis (measured by both time since diagnosis and disease severity at diagnosis) on disease progression and all-cause mortality adjusting for age, tumor stage and grade. We constructed combinational health states based on an individual’s current health state, health state at diagnosis (no PCA, localized PCA, advanced PCA, and death) and duration since diagnosis. Next, we recovered age-specific probabilities of all the possible health state transitions by the combinational states to assess the effect of early diagnosis on health state transition. The key assumption of this approach is that the variation of patient use of diagnostic tests (affected by regional variation) is uncorrelated with latent health state after adjusting for age, tumor stage and grade. Results: Among men with advanced PCA, all-cause mortality for those diagnosed 5 or more years ago is 46% lower than that for those diagnosed less than 2 years ago (p-value < 0.01) . Among men with localized PCA, the probability of progression to advanced PCA for those diagnosed 1 or more years ago is 85% lower than those diagnosed just in the past year (p-value < 0.01). The table illustrates these findings for a typical 70-year-old American male. Conclusions: This study provides empiric evidence for an early PCA diagnosis benefit on stage progression and all-cause mortality in the United States. Early PCA detection and health state transition probabilities for 70-year-old men. Health state at the beginning of year Health state at the end of year Duration since diagnosis (year) Probability P value Localized PCA Advanced PCA <1 0.024 <0.01 ≥1 0.007 Advanced PCA Death <2 0.223 <0.01 ≥2 and <5 0.143 ≥5 0.123
Unanticipated hospital admissions (UHA) in patients undergoing palliative radiotherapy (RT) with or without concurrent chemotherapy.
Authors: Mark Raymond Waddle, Rebecca L. Green, Fan Ye, Nabeel H. Arastu, Frances A. Collichio, Jayne Camporeale, Lawrence Bruce Marks, Ronald C. Chen
Journal: Journal of Clinical Oncology (2014)

e20661 Background: Patients with metastatic/incurable cancer often receive RT for palliation of symptoms, with the primary goal of improving quality of life. Unplanned hospital admissions during or soon after treatment may conflict with this goal, can be costly, and may reflect RT-associated morbidity or sub-optimal care. The goal of this retrospective study was to evaluate the rate, reasons for, and predictors of unplanned admission. Methods: The records of all 427 patients receiving palliative RT in 2010 were reviewed. Primary outcome was an UHA within 90 days of starting RT. Multivariable logistic regression was used to examine patient and treatment factors associated with admissions. Results: 30% of patients experienced an UHA. This was especially likely in patients receiving RT for bone metastases (34%), concurrent chemotherapy (41%), and those who were unmarried (38%). The most common causes for admission were neurologic, respiratory, pain, gastrointestinal symptoms, and fever/infection. 41% of admitted patients were seen in clinic in the two weeks before UHA, and 56% of those patients reported a related complaint during this clinic visit. Multivariate analysis showed being married (OR 0.48, p=0.001) and no concurrent chemotherapy (OR 0.55, p=0.04) were associated with lower odds for unplanned admission. Conclusions: A high proportion of patients receiving palliative RT experienced an unplanned admission. Some admissions may be preventable as patients were seen in clinic with a similar complaint before admission. For patients receiving palliative treatment, unplanned admissions may be an important quality of care indicator. Studies are needed to examine if proactive supportive care can reduce these unplanned admission rates. Multivariate logistic regression for UHA. OR (95% CI) P-Value Marital Status (REF=Unmarried) Married 0.48 (0.31, 0.75) 0.001 Concurrent Chemo (REF=Chemo) No Chemo 0.55 (0.31, 0.98) 0.04 Gender (REF=Male) Female 0.75 (0.48, 1.18) 0.22 Race (REF=White) Black 0.95 (0.56, 1.61) 0.85 Other 1.59 (0.71, 3.57) 0.26 Treatment Site (REF=Lung) Bone 1.83 (0.76, 4.39) 0.18 Brain 1.68 (0.69, 4.10) 0.26 GU/GYN 1.37 (0.43, 4.35) 0.59 Other 1.11 (0.42, 2.92) 0.83
Effect of short course radiation followed by four cycles of FOLFOX as preoperative therapy for rectal cancer on rate of PCR: A phase II trial.
Authors: Robert J. Myerson, Parag J. Parikh, Steven R. Hunt, Benjamin Tan
Journal: Journal of Clinical Oncology (2013)

471 Background: Preoperative radiotherapy (RT) with 5FU chemotherapy (CT) is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents have resulted in increased morbidity with little benefit. We evaluate a template that seeks to (1) include the benefits of preoperative RT on local response/control, (2) provide preoperative multi-drug CT, (3) avoid the morbidity of concurrent RT and multi-drug CT. Methods: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for surgery, provided the response was sufficient. Preoperative treatment was 5 fractions RT (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of mFOLFOX6. Postoperative CT was at the discretion of the medical oncologist. The principal objectives were to achieve T stage down staging (ypT &lt; cT) and acute grade 3+ gastrointestinal (GI) morbidity equal or better than historic controls. Results: 80 patients were enrolled from 11/2009 through 4/2012. All have had sufficient time for principal endpoint analysis. Four are inevaluable for response: 1 patient withdrew consent after completing RT and never received CT and 3 did not undergo surgery (new comorbidity in 2 cases, progression of distant metastatic disease in 1 case). Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). The 76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, 8 cM1. Sphincter preserving surgery was performed on 49 (64%) cases. At surgery 53 (70%) had ypT0-2 residual disease including 21 (28%) ypT0; 24 (32%) were ypN+. For M0 evaluable cases 2 year NED survival is 91+/-6% with no local failures. Cases were sub-analyzed by whether disease met requirements for the recently activated ACOSOG preoperative FOLFOX vs. 5FU-RT trial. Thirty eight cases met ACOSOG eligibility and achieved 16 ypT0 (42%) and 33 ypT0-2 (87%). Conclusions: This regimen achieved high response and low morbidity rates that compare favorably with conventionally fractionated RT and concurrent CT. The ongoing RAPIDO trial compares a similar regimen to conventional chemoradiation in poor risk locally advanced rectal cancer patients.
Survival of 1,181 patients in a phase I clinic: The University of Texas M. D. Anderson Cancer Center experience.
Authors: B. Stephen, J. J. Wheler, A. M. Tsimberidou, S. Wen, A. Naing, D. S. Hong, G. S. Falchook, S. A. Piha-Paul, S. Fu, F. Janku, S. L. Moulder, R. Kurzrock
Journal: Journal of Clinical Oncology (2011)

2528 Background: In order to determine if the Royal Marsden Hospital (RMH) prognostic system for phase I patients can be validated in a large group of patients seen in a different center, and if other prognostic variables are also relevant, we present an analysis of 1,181 patients treated in the MDACC Phase I Clinic. Methods: Medical records of 1,181 consecutive patients who were treated on at least one trial in the Phase I clinic at M. D. Anderson Cancer Center starting on January 1, 2006 were reviewed. Results: The median patient age was 58 years (range, 3-89 years). 594 patients (50%) were women. The median number of prior therapies was 4 (range, 0 to 17). The median survival was 10 months (95% confidence interval, 9.1 to 10.9 months). In univariate analysis, the factors that predicted shorter survival were ECOG performance status ≥1 (p<0.0001), tumor type (p<0.0001), history of liver metastases (p<0.0001), history of thromboembolism (p=0.0005), increased platelet levels (>440 K/UL) (p<0.0001), low albumin levels (<3.5 g/dL) (p<0.0001), increasing number of prior therapies (p<0.0001), prior radiation (p=0.028), Phase I study that included a chemotherapeutic agent (p=0.003), >2 metastatic sites (p<0.0001), LDH levels above normal (>618 IU/L) (p<0.0001), and RMH score >1 (RMH variables being albumin < 3.5 g/dL, LDH > normal, and >2 sites of metastases) (p<0.0001). Independent factors that predicted shorter survival in a multivariate Cox model fitted with stratification by tumor classification included: RMH score >1 (relative risk (RR) = 1.92, p<0.0001); ECOG performance status ≥1 (RR 1.32, p<0.001); elevated platelet levels (>440 K/UL) (RR1.44, p<0.001) and ≥3 prior therapies (RR1.32, p=0.001). Conclusions: Patients who were referred to the Phase I clinic had a median survival of 10 months. The RMH scoring system was validated in a large group of patients at MDACC. In addition, 3 additional variables (ECOG performance status ≥1, elevated platelet levels and ≥3 prior therapies) provided independent prognostic information.
Role of personal history in the development of recurrent venous thromboembolism during cancer chemotherapy.
Authors: W. B. Webb, Z. Li, J. Mao, S. Gautam, S. Singh, N. M. Kuderer
Journal: Journal of Clinical Oncology (2011)

e19677 Background: The role of prior venous thromboembolism (pVTE) as a risk factor for VTE recurrence (rVTE) during cancer chemotherapy has not been defined. We retrospectively studied the association between pVTE and rVTE within the 183 days after chemotherapy initiation in a community oncology population. Methods: All adult patients who started chemotherapy at a 29 center community oncology practice from 2007 to 2009 were included. Several variables for each patient were determined, including primary cancer site, age, sex, body mass index (BMI), and pVTE. In addition, pre-chemotherapy lab values were determined including hemoglobin (Hgb), white blood cell (WBC) and platelet (Plt) counts. pVTE and rVTE were identified by review of diagnostic codes (ICD9), hospitalizations and administration of treatment dose anticoagulation. Logistic regression was used to evaluate the relationship between pVTE and rVTE at three levels of adjustment: none, cancer site, and CaseMix (site, age, sex, BMI and CBC labs). Sub-analysis was performed for solid and hematological malignancies (leukemia, lymphoma and myeloma). Patients with missing CBC values were excluded from the CaseMix analysis. Results: 19.3% (35/181) of patients with pVTE developed rVTE, compared with 8.3% (460/5522) of the patients without pVTE. This trend was significant and was also observed in solid and hematologic tumor groups independently. These analyses and the relative risk (RR) are shown in the table. 9.5% (92/973) and 10.3% (485/4,730) of patients were excluded due to missing baseline CBC for hematological malignancy and solid tumor patients, respectively. Conclusions: pVTE is strongly associated with rVTE among cancer chemotherapy patients in the community setting, and its predictive role persists with adjustment for pre-chemotherapy CBC values, cancer site, age, VTE history and BMI. All patients Solid tumors Hematologic No rVTE rVTE No rVTE rVTE No rVTE rVTE No pVTE 5522 460 (8.3%) 4585 404 (8.8%) 937 56 (6.0%) pVTE 181 35 (19.3%) 145 26 (17.9%) 36 9 (25.0%) Adj level RR* P value RR* P Value RR* P value None 2.64 <0.001 2.62 <0.001 5.24 <0.001 Site 1.95 0.003 1.95 0.003 5.18 <0.001 CaseMix 1.86 0.007 1.86 0.007 4.88 <0.001
Vascular hemodynamic profiles of vestibular schwannomas and glioblastoma using MRI.
Authors: S. R. Plotkin, D. Jennings, K. Mouridsen, K. E. Emblem, A. G. Sorensen
Journal: Journal of Clinical Oncology (2011)

2047 Background: Bilateral vestibular schwannomas (VS) are the hallmark of neurofibromatosis 2 (NF2), a tumor suppressor syndrome that affects the central nervous system. These benign tumors cause progressive hearing loss and brainstem compression. Current options, including surgery and radiotherapy, can cause hearing loss, facial weakness and dysphagia. Treatment with anti-VEGF antibody improves hearing and reduces tumor volume in the majority of patients. Our aim was to evaluate the angiogenic phenotype of VS compared to glioblastoma (GBM), a malignant tumor that is dependent on new blood vessel formation. Methods: Eleven patients with NF2 and eight patients with GBM were scanned on a 3 Tesla imaging spectrometer. Estimates of Ktrans (a measure of vascular permeability) were derived from dynamic contrast enhanced MRI, apparent diffusion coefficient (ADC, a measure of tissue water content) estimates were derived from diffusion imaging, and relative cerebral blood volume (rCBV, a measure of blood volume) estimates were derived from dynamic susceptibility MRI. The mean values for each parameter were compared for VS and GBM by a Student’s t-test. Results: The mean tumor volume for VS was 11.2 ml (range, 1.4 to 29.1 ml) and for GBM was 24.8 ml (range, 4.5 to 56.3 ml). The mean ADC value was significantly greater in VS than in GBM (1.406 x 10-3 mm2/sec vs. 1.014 x 10-3 mm2/sec; P=0.0001). The mean Ktrans estimate was higher in VS than in GBM (0.068 hour-1 vs. 0.021 hour-1), although this did not reach statistical significance (P=0.106). The mean rCBV value was similar between VS and GBM (2.294 vs. 1.934, P=0.269). Conclusions: Our results suggest that VS have strikingly abnormal vasculature, with features similar to that of GBM. The tumor vasculature is highly permeable and the tumors show increased diffusion of water molecules (eg., radiologic marker of tissue edema). Our preliminary data suggest that histologically benign tumors may have abnormal vessels and that these vessels may contribute to increased tissue edema. Anti-VEGF therapy is a rational approach to treatment of progressive VS through an anti-edema effect. Novel VEGF inhibitors may improve outcomes for this tumor.
Fractures in association with breast and endometrial cancer survival in the Women’s Health Initiative.
Authors: Polly A. Newcomb, Scott V. Adams, Michael N Passarelli, Dorothy Lane, Wenjun Li, Rowan T. Chlebowski, Carolyn Crandall, Lesley Tinker
Journal: Journal of Clinical Oncology (2016)

148 Background: Postmenopausal fracture rates appear to be an integrated marker of usual estrogen levels and have been associated with decreased risk of breast and endometrial cancer. The association between fractures and cancer mortality has been difficult to assess, as fractures are a consequence of both the pathological process and the treatment of cancer. Due to the reduced proliferative effects of the hormonal milieu, pre-diagnosis fractures may be a hallmark of decreased cancer mortality. Methods: We evaluated a cohort of breast (N = 6,458) and endometrial (N = 1,138) cancer cases who were diagnosed with cancer during the Women’s Health Initiative (WHI; 1992-2010). Fracture history was assessed by combining baseline reports of fractures prior to WHI and after age 50; with fractures ascertained during WHI follow-up, but prior to cancer diagnosis. We used Cox proportional hazards models based on time since cancer diagnosis to estimate hazard ratios (HR) with 95% confidence intervals for overall and cancer-specific mortality, comparing women with prior fractures to those without fractures. Clinical factors, including bisphosphonate and hormone use, were in the model. Results: Among breast cancer cases, during the average 6.2 years of follow-up, 1,464 had a prior fracture and 905 deaths occurred (415 due to breast cancer). Among endometrial cancer cases, during follow-up, 267 had a prior fracture and 192 deaths occurred (83 due to endometrial cancer). Any pre-diagnosis fracture was associated with increased all-cause mortality (breast HR: 1.39 (1.20, 1.62); endometrial HR: 1.41 (1.02, 1.95)). Among breast cancer cases, the strongest association was with hip fracture (HR: 2.76 (1.80, 4.25)). Associations with cancer-specific mortality were similar in direction and magnitude, but did not reach statistical significance. Conclusions: A history of pre-diagnostic fractures was associated with increased overall but not cancer-specific mortality. Fracture history may be indicative of frailty or other co-morbidities. Breast and endometrial cancer cases with a fracture history may benefit from concurrent supportive care to mediate risk of death due to co-morbid health conditions.
Adjuvant treatment and outcomes in patients with stage III colon cancer (CC) who do not fit clinical trial eligibility criteria (CTEC).
Authors: Khodadad Rasool Javaheri, Hagen F. Kennecke, Daniel John Renouf, Howard John Lim, Tina Hsu, Caroline Speers, Ozge Goktepe, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2013)

486 Background: Trials have strict inclusion and exclusion criteria to maintain internal validity. However, study findings are often applied to pts in clinical practice who do not satisfy all of the CTEC. Whether these pts benefit from treatment is unclear. Our objectives were 1) to characterize cancer-specific (CSS) and overall survival (OS) in a population-based cohort of trial-eligible (TE) and trial-ineligible (TI) pts receiving adjuvant chemotherapy (CT) and 2) to compare their outcomes with those not treated with CT. Methods: Pts diagnosed with stage III CC between 2006 and 2008, referred to 1 of 5 regional cancer centers in British Columbia, and evaluated for possible adjuvant CT within 12 weeks of curative surgery were reviewed. Pts were defined as TE if aged 18 to 79 years, ECOG 0 to 1, CEA &lt;10 ng/ml, had not received prior CT or radiation, and had adequate blood counts, cardiac, liver, and kidney function. All other pts were considered TI. Using Kaplan-Meier and Cox regression analyses, we compared outcomes between TE and TI pts who received CT vs. those who did not. Results: A total of 821 pts were identified: median age was 68 years, 52% were men, 85% were ECOG 0 to1, and 71% received adjuvant CT. Among pts treated with CT, 405 (70%) were TE and 177 (30%) were TI. Compared to TI pts, those who were TE were younger (p&lt;0.01) and more likely to receive FOLFOX than capecitabine (65 vs. 46%, p&lt;0.01). CSS and OS were significantly different among pts who were TE, TI, and those who did not receive CT (p&lt;0.01) (Table). In multivariate analyses that adjusted for confounders, both TI pts and those not treated with CT had worse prognoses than TE pts (HR for CC deaths 1.32, 95%CI 0.86-2.02 and 2.77, 95%CI 1.92-3.99, respectively, p trend &lt;0.01; HR for all deaths 1.24, 95%CI 0.85-1.80 and 2.95, 95%CI 2.17-4.00, respectively, p trend &lt;0.01). Conclusions: A considerable number of stage III CC pts who did not fit CTEC were treated with adjuvant CT. While outcomes in the TI group were worse than those in the TE group, CSS and OS were still better than the subset that did not receive any CT. [Table: see text]
Local effects of tamoxifen versus aromatase inhibitors (AI) on breast tissue: A longitudinal dynamic contrast enhanced (DCE) breast MRI cohort study.
Authors: C. K. Kuhl, S. Schrading, W. Kuhn, H. H. Schild
Journal: Journal of Clinical Oncology (2010)

663 Background: Contrast enhancement of fibroglandular tissue in DCE breast MRI correlates closely with the level of hormonal stimulation. Accordingly, enhancement in DCE MRI could serve as biomarker for the local effects of systemic anti-hormonal therapy. We investigated the use of DCE MRI to delineate the local effects of two different types of anti- hormonal therapy (TAM vs. AI). Methods: Intraindividual longitudinal study on 40 women (mean age: 56) diagnosed with early-stage ER-positive breast cancer who underwent DCE MRI three times: (1) at the time of diagnosis, i.e. before treatment, (2) under TAM medication (after > 3 months of treatment), and (3) after switching to an AI for at least 3 months. Results: In 40/40 women (100%), enhancement rates of breast tissue and prevalence of benign focal enhancement were highest before treatment, and were significantly reduced after taking TAM. After switch to AI, background enhancement reappeared, although not back to baseline, in 34/40 women (85%). In the remaining 6/40 (15%), enhancement remained suppressed under AI (no change vs. under TAM). Mean enhancement before treatment was 50.3% vs. 4.3% under TAM, and 17.4% under AI (p > 0.0025). Enhancement before treatment was moderate or strong (grade 3 or 4) in 32/40 (80%). Under TAM, it was absent or minimal (grade 1 or 2) in 35/40 (88%). After switch to AI, it was grade 2 or 3 in (34/40, 85%) (p > 0.0035). Prevalence of benign focal enhancement in the MRI studies under AI (16/40; 40%) was significantly higher compared to the the same women's studies under TAM (4/40; 10%) (p > 0.0047) and was only slightly lower than before treatment. Conclusions: DCE breast MRI is a sensitive tool to monitor and quantify the local effects of systemic antihormonal therapy. There appears to be a fundamental difference between the local effects achieved by TAM vs. AI. Our findings indicate that either TAM leads to a more complete suppression of local hormonal stimulation than AI, or the local effects of TAM are not only caused by hormonal deprivation, but by additional (e.g. antiangiogenic) effects. Due to the high sensitivity for TAM induced effects, DCE breast MRI may help identify TAM nonresponders/low metabolizers. No significant financial relationships to disclose.
Biologic consequences of androgen receptor (AR) activity in MDV3100-resistant LNCaP cells and dependence on AR full length.
Authors: Yoshiaki Yamamoto, Yohann Loriot, Eliana Beraldi, Tianyuan Zhou, Youngsoo Kim, Brett P. Monia, A. Robert MacLeod, Ladan Fazli, Amina Zoubeidi, Martin Edwin Gleave
Journal: Journal of Clinical Oncology (2014)

74 Background: While recent reports link androgen receptor (AR) variants (AR-Vs) to castration resistant prostate cancer (CRPC), the biological significance of AR-Vs in AR-regulated cell survival and proliferation, independent of AR full length (AR-FL), remains controversial. To define the functional role of AR-FL and AR-Vs in MDV3100-resistant (MDV-R), we designed antisense oligonucleotide (ASO) targeting exon 1 and exon 8 in AR to knockdown AR-FL alone or in combination with AR-Vs and examined these effects in MDV-R LNCaP-derived cells in vitro and in vivo. Methods: We generated by selection MDV-R LNCaP-derived sub-lines that uniformly expressed high levels of both AR-FL and AR-V7 compared to CRPC LNCaP xenografts. Cell growth rates, protein and gene expression were analyzed using crystal violet assay, western blotting and real-time PCR, respectively. Exon 1 and 8 AR-ASO were evaluated in MDV-R49F CRPC LNCaP xenografts. Results: AR-V7 was transiently transfected in MDV-R49F cells and differential knockdown of AR-V7 and/or AR-FL by exon 1 versus exon 8 AR-ASO was used to evaluate relative biologic contributions of AR-FL versus AR-V7 in MDV-R LNCaP AR-V7 overexpressing cells. Exon 1 and 8 AR-ASO treatment in these cells similarly decreased prostate-specific antigen (PSA) expression and induced apoptosis as measured by caspase-3 and PARP cleavage and cell growth inhibition. To further define the functional role of AR-Vs in MDV-R LNCaP cells, we used a CE3 siRNA that specifically silenced AR-V7, but not AR-FL in MDV-R LNCaP cells. AR-V7 knockdown did not decrease PSA levels, did not induce apoptosis, and did not inhibit cell growth. In MDV-R LNCaP cells, exon 1 and 8 ASO similarly suppressed cell growth and AR-regulated gene expression in vitro and in vivo. Conclusions: These results indicate that the AR remains an important driver of MDV3100 resistance and, the biologic consequences mainly driven by AR-FL in MDV-R LNCaP models.