tbuckley/cabot-search huggingface dataset:
Automated tumor detection on bone scans for treatment response assessment.
Authors: M. S. Brown, G. H. Chu, H. J. Kim, M. Auerbach, C. Poon, A. Vidovic, B. Ramakrishna, D. W. Gjertson, M. J. Morris, S. M. Larson, H. I. Scher, J. G. Goldin
Journal: Journal of Clinical Oncology (2011)

e15169 Background: Treatments that target pathways that contribute to prostate cancer such as MET and VEGF kinases show promise in reducing tumor burden on bone scans. The Prostate Cancer Working Group 2 recommends that in clinical trials, progression be defined as visual evidence of two or more new lesions on a bone scan. No criteria are provided for response, and lesions may shrink without changing in number, or may break into smaller components, thus appearing to increase the burden by simple count. We propose that early treatment response be assessed as a reduction in overall tumor area and/or intensity. A key foundation step for accurate and reproducible computation of these measures is automated detection of tumor pixels on bone scans. Methods: From an anonymized image database, original DICOM format scans were selected from 20 subjects with confirmed prostate cancer who had undergone standard of care whole body scintigraphy, 2 - 4 hours post injection of 20 - 25 mCi of Tc MDP. An automated computer-aided detection (CAD) system was used to analyze images. The system performs intensity normalization to a standard bone scan atlas to account for differences in radiotracer dosing levels and scan timing and improve reproducibility. Region-specific intensity thresholding and connected-component filtering are then used to automatically identify bone lesions. The system performance was evaluated against manual tumor contouring by two expert imagers experienced in the interpretation of bone scans. Accuracy was assessed using the expert markings as true positive pixels and other bone pixels as true negatives. Results: The CAD system showed median (IQR) sensitivity of 94.1% (88.2, 97.0), specificity of 89.2% (85.3, 94.6), and accuracy of 89.4% (86.2 94.5) for tumor pixels on bone scans. False positives were primarily due to degenerative joint disease, which can be removed manually or automatically with further algorithm development. Conclusions: An automated CAD system can detect tumor pixels on bone scans with high accuracy, and facilitate quantitative assessment of tumor burden with the advantages of objectivity and consistency over manual approaches. This work lays the foundation for development of a bone scan biomarker for response assessment.
Preclinical evidence that chemotherapy for prostate cancer should be given at the same time as androgen withdrawal
Authors: B. J. Eigl, J. Baybik, S. Ettinger, K. N. Chi, C. Nelson, M. E. Gleave
Journal: Journal of Clinical Oncology (2005)

4617 Background: Androgen ablation is the mainstay of systemic therapy for prostate cancer, with cytotoxic chemotherapy reserved for hormone refractory disease. Earlier use of chemotherapy at the time of androgen dependence when there are potentially fewer multi-resistant clones, may yield greater benefit. This study addresses the ideal timing of systemic treatments in the androgen-dependent Shionogi tumour model. The hypothesis that stress-induced changes in gene expression after chemotherapy can induce a hormone independent phenotype was further explored in the LNCaP setting. Methods: Three groups of ten mice bearing Shionogi xenografts were treated with: 1) initial castration and delayed paclitaxel, 2) initial paclitaxel and delayed castration, or 3) combined therapy. Endpoints were time to tumour progression and time to sacrifice. The additive effects of combined therapy were also assessed through in vitro proliferation studies on LNCaP cells. Spotted microarray and RT-PCR analyses were carried out on mRNA from LNCaP cells exposed to paclitaxel to identify gene expression changes over time. Results: Mice receiving combined therapy demonstrated a significant improvement in time to progression (median 65 vs. 38 days, p=0.004) and time to sacrifice (median 83 vs. 66 days, p<0.014) versus sequential therapy. A marked lack of response to castration in the mice treated with paclitaxel first was observed. Similar effects were seen in vitro. Microarray studies identified increases in several genes known to play a role in androgen independence in response to paclitaxel exposure. Quantitative RT-PCR demonstrated an increase of expression of clusterin, bcl-2, bcl-xL and Hsp27 of between 30% and 60% after 48 hours of paclitaxel exposure. Conclusions: In laboratory models of prostate cancer, the combination of androgen deprivation and paclitaxel is more effective than sequential treatment. Molecular studies confirm that chemotherapy can induce alterations in gene expression associated with androgen independent proliferation. These findings provide pre-clinical proof-of-principle for ongoing clinical trials addressing the role and timing of systemic therapies in prostate cancer. No significant financial relationships to disclose.
Pain, opioids, and polysomnographic measures of nocturnal and daytime sleep in patients with advanced cancer
Authors: K. P. Parker, D. L. Bliwise, S. Jain, J. A. Dalton, C. Vena
Journal: Journal of Clinical Oncology (2005)

8020 Background: Explore relationships among pain, opioids, and sleep in patients with advanced cancer. Methods: The sample included 52 subjects (solid tumor, Stages III and IV). The mean age was 55.7 (± 8.8); 32 were male. All were taking opioids. Subjects underwent ambulatory polysomnography for 48 hours in their homes. Sleep parameters obtained included total sleep time (min), sleep efficiency (%), sleep latency (min), latency to the onset of rapid-eye-movement (REM) sleep (min), and the percentages (%) of Stages 1 through 4 non-rapid-eye-movement (NREM) and REM sleep. All kept a diary of the opioid medications taken during the study, data that were converted into morphine equivalents and a mean hourly morphine equivalent dose (HMED; .10 ± .13). Subjects also completed the Brief Pain Inventory. Descriptive and correlational parametric procedures were used for analyses. Results: Subjects had an average of 396.2 ± 99.0 min of nocturnal sleep (range 160 to 579). The sleep latency was relatively long (30.0 ± 48.2 min) and sleep efficiency was low (76.8 ± 12.5%). A majority of sleep was light NREM Stages 1 and 2. An absence of NREM Stages 3 and 4 was noted in most subjects. REM sleep was reduced (14.4 ± 8.5%) and the REM latency was prolonged (149.1 ± 105.1 min). During the day, subjects slept an average of 96.7 ± 112.1 min (range 0 to 552.5) that included NREM Stages 1 and 2 and REM. Neither pain variables nor HMED were correlated with nocturnal or daytime total sleep time. HMED was positively associated with nocturnal REM latency (r = .26, p = .042) and negatively associated (weakly) with total nocturnal REM % (-.20, p = .09). Nocturnal Stage 1% was positively associated with HMED (r = .44, p = .001) and pain intensity (r = .36, p = .006). No association between HMED or pain variables and daytime sleep were observed. Conclusions: Poor nocturnal sleep and significant daytime sleep characterized the group. The absence of deep NREM sleep and the REM sleep changes noted may reflect the effects of opioids on sleep architecture. Both pain and opioids appear to lighten nocturnal sleep. Further studies of the effects of pain/opioids on sleep and wakefulness are needed to develop treatment regimens that maximize pain relief and minimize sleep disruption. No significant financial relationships to disclose.
Pilot study to evaluate the effect of erlotinib (E) administered before surgery in operable patients with squamous cell carcinoma of the head and neck (SCCHN).
Authors: M. Porosnicu, J. D. Waltonen, C. Sullivan, L. McWilliams, G. L. Kucera, A. Thomas, R. Plasser, J. D. Browne
Journal: Journal of Clinical Oncology (2011)

5568 Background: Strategies for early detection of cellular response to EGFR inhibitors are critical to personalizing therapy for SCCHN. The glycolytic enzymes responsible for uptake of the positron emission tomography (PET) tracer [18F] 2- fluoro-2-deoxy-d-glucose (FDG) are regulated by intermediates of the EGFR pathway such as AKT, mTOR and MAPK. It was hypothesized that the inhibition of these EGFR pathway markers could be read by the 18[F]-FDG uptake by tumor. It is also possible that the EGFR pathway is aberrantly activated in some cancers and that glycolysis and downstream effects are not always linked. Previous in vitro and in vivo studies showed that 18[F]-FDG uptake changes very early in SCCHN tumor models responsive to EGFR inhibition. We developed a pilot clinical protocol to investigate this further in patients with SCCHN. Methods: Patients with operable SCCHN with a window of at least 15 days between the time of initial biopsy and established surgery will receive E 150 mg/day or 300 mg/day if the patient is actively smoking. Smokers metabolize E rapidly with an MTD that is twice that of non-smokers. Patients must have additional biopsy tissue for laboratory research studies. 18[F]-FDG PET scan and neck CT with contrast are performed before treatment, 4-6 days through treatment and at the end of E administration. Results: 11 patients have been treated to date with an average of 18.6 days of treatment. Of the 10 evaluable patients, 7 showed partial response (PR) and 3 patients showed stable disease (SD). 8 patients received E 300 mg. No grade 3 or 4 toxicities. Early (4-6 days)18[F]-FDG PET scans showed a decrease in SUV max to 93.25% +/- 18% in patients with SD and to 51% +/- 22% in patients with PR (defined as at least 20% reduction in maximum diameter). This pilot trial will continue to enroll patients to address the primary laboratory research correlative aim. Pre-and post-treatment tumor tissue is available in all patients. Conclusions: Short course treatment with E in a dose adjusted per smoking status is very active in previously untreated patients with SCCHN. Early changes in the 18[F]-FDG PET scan uptake can be used as a marker predictive of response to EGFR inhibition.
Cost, value, and policy in quality: Evolving relationship of payers and providers.
Authors: Diane Denny, Caitlin Keenan
Journal: Journal of Clinical Oncology (2014)

44 Background: Cancer Treatment Centers of America (CTCA), a network of five hospitals, has multiple pay for performance contracts. Some apply to all hospitals, while others are unique to individual facilities. While many metrics are managed by site, some metrics are collected and measured centrally by corporate. Varying levels of oversight were required from site quality teams, executive teams and externally-facing corporate departments. In order to coordinate these efforts, CTCA implemented a real-time tracking system for monitoring pay for performance metrics. Methods: CTCA’s corporate Quality department designed a central repository for monitoring metrics that is populated monthly using customized workbooks submitted from each site. The central repository compiles monthly data and displays it in several formats broken down by timeframe, site and contract. The repository incorporates features allowing easy sharing and data accuracy. An accompanying process for collecting data was created to ensure timely, efficient updates to the repository. Results: The monthly monitoring process was implemented in January 2014 and continues to operate successfully. For one enterprise-wide contract cycle closing on April 31, CTCA met requirements and outperformed the contract-specified goal for each by an average of 19.8%. Pre-implementation, metrics were monitored quarterly. Although two metrics showed a small (&lt;2.5%) decrease in average performance, given the intensified focus, the remaining metrics showed an average 7.95% improvement in performance during the second six months with monthly monitoring. Metrics associated with the remaining contracts are on track to meet or exceed specified performance standards. Conclusions: The new tool and monthly reporting process successfully monitored pay for performance metrics at CTCA. Most importantly, the system allowed for close to real-time assessment and therefore promoted ongoing intervention if warranted. The repository created a single source of data sharing and visibility for these important elements of performance. As CTCA continues to participate in pay for performance activities, this method will be adapted to accommodate more contracts and metrics.
Impact of body composition on pharmacokinetics of doxorubicin in pediatric patients: A Glaser Pediatric Research Network study
Authors: S. L. Berg, L. Bomgaars, C. Twist, K. Matthay, T. Moore, D. Wypij
Journal: Journal of Clinical Oncology (2005)

8519 Background Body composition affects various physiologic processes involved in the distribution, metabolism, and elimination of drugs. Therefore body composition might be related to important pharmacokinetic (PK) parameters like clearance or half-life. These relationships have never been systematically studied for doxorubicin (dox) and its metabolite doxorubicinol (doxol). In addition, the PK behavior of dox and doxol have not been thoroughly described in children. In this study we evaluated the relationship between body composition and doxorubicin PK in children. Methods Eligible subjects were ≥ 1 and ≤ 21 years old; weighed ≥ 12 kg; received dox administered as an infusion of any duration < 24 hours, on either a 1-day or 2-day schedule; had ALT/AST ≤ 3 times the upper limit of normal and bilirubin ≤ upper limit of normal tested within 14 days prior to dox; and provided informed consent/assent. Blood samples were drawn prior to dox administration, at the midpoint of the infusion and at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours after the infusion for 1-day schedules, or at 0, 0.5, 1, 2, 4, and 6, hours after the day 1 infusion and immediately prior to the day 2 infusion, then at 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 hours after the day 2 infusion for 2-day schedules. Body composition was determined using dual-energy x-ray absorptiometry (DXA). Body mass index (BMI) was calculated from height and weight. Dox and doxol concentrations were analyzed by reverse-phase high-pressure liquid chromatography with fluorescence detection. Dox plasma PK were analyzed with maximum likelihood estimation as implemented in ADAPT II. Results Data are available for 16 subjects (12 male; 8 Hispanic, 6 Caucasian, 2 Asian). The median age is 15 years (range 3–21). The median % body fat by DXA is 22 % (range 16–36). The median BMI is 20 (range 14–30). The median dox clearance is 382 ml/m2/min (range 141–768). The median terminal half-life is 30.6 hr (range 18.1–146.6). Dox clearance decreases with increasing BMI (r=-0.56, P=0.02) and tends to decrease with increasing % body fat (r=-0.43, P=0.10). Conclusions Potential relationships between increasing BMI, decreasing dox clearance, and dox toxicity should be explored. No significant financial relationships to disclose.
Impact of comorbidities using Adult Comorbidity Evaluation-27 (ACE-27) score on survival in stage II colon cancer: Age, TNM staging, and pathological high risk-disease.
Authors: Manik A. Amin, Andrea Wang-Gillam, Benjamin R. Tan, Rama Suresh, Joel Picus, Preet Paul Singh, Kian-Huat Lim, Ashiq Masood, Albert C. Lockhart
Journal: Journal of Clinical Oncology (2016)

659 Background: Impact of comorbidities is identified in stage III colon cancer patients (CCPs) receiving adjuvant chemotherapy (Wildes et al, PMID 21113435) but is not well defined in predicting overall survival (OS) in stage II CCPs undergoing either adjuvant treatment or observation depending upon high-risk disease. The goal of this study was to identify impact of comorbidities on OS in this potentially curable disease using ACE-27 score, which uses 27 different patient comorbid conditions has been developed and validated by Piccirrillo et al at Barnes Jewish Hospital (BJH) (PMID: 24933715). Methods: We identified stage II CCPs treated at BJH, Siteman cancer center from January 1, 1996 to October 31 st , 2013 from BJH oncology data cancer registry. The primary outcome was OS, defined as the time from date of surgery to death from any cause, censored at the time of last follow-up. Patient comorbidities at diagnosis were recorded using ACE-27 score, assigning a comorbidity score of none, mild, moderate and severe to the patients. Survival analysis was done using Cox proportional hazard modelling using STATA/SE 11.2 software. Pathological high risk features such as T4 lesions, &lt; 12 LN, perineural, lymphovascular invasion, positive margins &amp; perforation/obstruction were identified. Results: Out of 579 stage II CCPs, 48% male and 51% were females. High risk features were identified in 45% of patients. ACE-27 comorbidity score of none (n = 146), mild (n = 229), moderate (n = 132) and severe (n = 72) was calculated. 497 patients had T3N0M0 and 82 had T4N0M0 staging. Cox regression hazard model using histological prognostic factors, age at surgery, sex, race, prior cancer history and TNM staging showed that ACE-27 score of moderate and severe were independent predictors of OS with a hazard ratio of 1.6 (95% CI 1.0-2.4), P = 0.036 and 2.5 (95% CI 1.5-4.0), P = 0.00 respectively. Conclusions: Highest commodity burden using ACE-27 comorbidity score was associated with poor OS in stage II CCPs and was independent of other prognostic risk factors including high-risk features. Treatment related mortality will be calculated in patients with high risk disease.
Rapamycin Can Reduce Apoptosis of CD4+CD25+ Regulatory T Cells from Mouse Model of Severe Aplastic Anemia
Authors: Zenghua Lin, Hong Liu, Li Zhu, Xuli Wang, Yu Qian, Xi Yang, Xin Cao, Yifeng Cai, Yaping Zhang, Guoqi Song, Juan Qian
Journal: Blood (2014)
Endoscopic single port skin-sparing total mastectomy with periareolar incision: Early results.
Authors: Koji Yamashita
Journal: Journal of Clinical Oncology (2013)

77 Background: Early-stage breast cancer, such as DCIS, may force to complete removal of the mammary gland because of its wide spread in the breast. For such cases, skin-sparing mastectomy (SSM) should be recommended. However, the conventional oncoplastic surgery leaves some ugly scars on the breast due to large skin incisions. By applying the endoscopic video-assisted breast surgery (VABS), we can provide more aesthetic surgery with single periareolar port approach, leaving only a small and inconspicuous scar on the breast. Methods: VABS of SSM consists of periareolar skin incision, dissection of whole mammary gland, sentinel node (SN) biopsy, and axillary node (AN) dissection. After SSM, the breast reconstruction was performed by the delayed or simultaneous method. We use the implant for simultaneous reconstruction. SN biopsy was performed endoscopically with only 1 cm incision in the axilla which was marked with 3D-CT lymphography prior to surgery. For SSM, we made a skin incision of 2.5 - 3.5 cm incision at the foot-side edge of the areola, to preserve blood flow around the areola. We cut across the gland near the nipple and quickly checked the transected stump by fast frozen section. Subcutaneous detachment was applied to the entire gland. Back of the gland was peeled just above the pectoralis major muscle fascia. The liberated gland was removed through the port with a plastic bag. Results: We performed VABS on 300 patients since 2001, and SSM on 30 patients. Tumor size is 1.6 cm on average. Age is 57.2 years. 23 nipples were preserved. 17 cases were DCIS. 4 were invasive lobular carcinoma. 9 were invasive ductal carcinoma. 2 cases had SN metastasis. One case had AN metastasis. Between VABS and the conventional surgery, there was no difference in the amount of blood loss and operation time. Postoperative aesthetics was particularly good after simultaneous reconstruction. They had less sensory disturbance and high satisfaction. After 38 months, there have been no distant metastases, no postoperative deaths, and one local recurrence). Conclusions: VABS SSM with periareolar skin incision approach makes better aesthetic results.
Cetuximab-related infusion reaction rate in cancer patients differs by race.
Authors: E. N. Kiwan, E. Siegel, L. F. Hutchins, A. Maddox, R. Govindarajan, A. M. Safar, I. Makhoul
Journal: Journal of Clinical Oncology (2011)

e14075 Background: Cetuximab, an anti-EGFR IgG1 chimeric monoclonal antibody, is approved in colorectal (CRC) and head and neck (H&N) cancers and is being used in other solid tumors. Severe infusion reactions (IR) are noted in <3% of pts who received the drug in the U.S. The incidence of IR in Arkansas has been consistently higher than the rest of the country and tended to cluster in certain groups. Methods: Details on all cancer patients treated with ANY dose of cetuximab between 1/2004 and 10/2010 at UAMS hospital were included in our retrospective data base review. The data collected included age, sex, race, personal history of allergy, premedications used, cancer type, and associated treatments. Severe IR was defined as anaphylactic shock, syncope, severe hypotension, respiratory distress, desaturation (<92% on room air), generalized and facial edema and severe hives/rash. Results: A total of 166 Pts were identified and included in our study. 69 pts with CRC, 67 Pts with H&N cancer, and 30 Pts with each of the following cancers: gastroesophageal CA (10), NSCLC (7), squamous cell carcinoma (SCC) of the anus (5), SCC of the cervix (5), and carcinoma of liver, unknown primary, and mesothelioma (1 each). The incidence of IR was 16% (26/166); of them 4 Pts or 2.5% (4/166) had severe anaphylactic shock but no death was reported. Median age of Cetuximab exposure was 61 for pts with FIR vs. 55 for pts without (P=0.07). No difference of IR rates by gender 20% (20/102) in males vs. 9% (6/64) in females (P=0.08). In contrast, IR rates by race were 20% (25/133) among Caucasians vs. 3% (1/33) among African-Americans (P=0.02). The premedications used, personal history of allergy, and cancer type did not seem to play a role. Conclusions: The incidence of severe or life threatening IR to cetuximab is at least five fold higher in Arkansas than in the rest of the country. In our population, white race is significantly associated with this reaction. Difference by age and gender was not statistically significant. Our finding is hypothesis generating and might suggest racial genetic differences or polymorphisms that interfere with the processing of certain ubiquitous antigens.