tbuckley/cabot-search huggingface dataset:
CyberKnife stereotactic body radiation therapy for palliation and local control in patients with advanced pancreatic cancer: A retrospective review.
Authors: R. Shirazi, P. M. Goldfarb, D. B. Fuller, H. Sanati
Journal: Journal of Clinical Oncology (2011)

e14506 Background: Stereotactic body radiation therapy (SBRT) offers a non-invasive, and short-in-duration option for patients with advanced pancreatic adenocarinoma for palliation or local control. Methods: Gold fiducial seed markers (1-4) were placed in, or around, the tumor in the pancreas to guide tracking of the tumor. Triple phase contrast CT images, and as necessary PET/CT, or MRI images were obtained for treatment planning. Treatment planning was performed using the MultiPlan treatment planning (Accuray Incorporated, Sunnyvale, CA). Treatment was performed using the CyberKnife with Synchrony motion tracking. A 3-5 mm margin was added to gross disease to specify the planning target volume (PTV). Results: Between July 2007 and January 2010, 26 pancreatic cancer patients were treated for 27 tumors with SBRT at CyberKnife Centers of San Diego. 12 patients were locally advanced, 12 patients had metastatic disease, 1 patient had recurrence following surgery, and 1 patient refused surgery. 9 patients had prior external radiation therapy (45-50.4 Gy) with concurrent chemotherapy. Twelve patients had received prior chemotherapy alone. The median lesion volume was 46.7 cc (10.1-263.8 cc). Typical prescribed doses was 35 Gy in 5 fractions. All patients tolerated treatments well with no grade 3 or 4 toxicities. Five grade 2 acute toxicities and two grade 2 late toxicities were observed. Fourteen of the patients presented with pain; of these 12 (86%) had substantial pain relief from SBRT, 1 (7%) minor and 1 (7%) had no pain relief. For the 18 patients with a minimum of 3 months follow-up (3-24 months), 14 (78%) were locally controlled, 3 had local failures and 1 had unknown local control. Median overall survival from time of diagnosis was 10.9 months (range, 3-31 months). The median overall survival length from time of SBRT was 5.4 months (range, 1-24 months). Kaplan-Meier estimated overall survival from time of diagnosis was 96%, 88%, 42% and 12% at 3, 6, 12 and 24 months, respectively. Conclusions: In this group of heavily pre-treated patients with advanced pancreatic cancer, CyberKnife SBRT was well tolerated and offered a quick palliation with good local control.
[<sup>18</sup>F]NaF PET/CT imaging biomarkers of progression-free survival in metastatic prostate cancer.
Authors: Stephanie Harmon, Tim Perk, Jens C. Eickhoff, Mary Jane Staab, Peter L. Choyke, William L. Dahut, Andrea B. Apolo, John Humm, Steven M. Larson, Michael J. Morris, Scott Perlman, Glenn Liu, Robert Jeraj
Journal: Journal of Clinical Oncology (2016)

277 Background: 18 F-Sodium Fluoride (NaF) PET/CT has been shown to be superior to 99m Tc-MDP SPECT in detection of bone metastases and shows great promise to reliably measure functional changes in bone. This study assesses the relationship of Progression Free Survival (PFS) with NaF PET/CT measures in patients with metastatic Castration-Resistant Prostate Cancer (CRPC). Methods: 55 CRPC patients had NaF PET/CT scans performed at baseline, which was repeated at week 9 if receiving taxane-based therapy (N = 16) or week 12 if receiving androgen-signaling pathway (AR) inhibitors (N = 39). Bone lesions were identified using a novel technique allowing for extraction and tracking of PET metrics from individual lesions at every timepoint. Cox proportional hazard regression analyses were conducted to evaluate associations between imaging metrics and PFS. Results: Median PFS was 8.3 months (range 1.0-30.3+). The strongest predictor of PFS in univariate analysis was total functional burden (SUV total ) (P &lt; 0.0001) during treatment for all patients. Predictors of PFS differed between both treatment cohorts of patients (Table 1), including number of lesions, fraction of skeletal involvement, and average lesion activity (SUV mean ). Maximum PSA benefit (percent decrease) during the first 12 weeks of therapy was highly predictive of PFS in the AR-directed cohort of patients (HR = 1.012 , P = 0.0005), as was change in the number of lesions (HR = 1.01, P = 0.03). Conclusions: There is indication thattotal functional burden of disease during treatment with taxane or AR-directed therapy is a strong predictor of PFS. In addition, change in number of lesions was predictive of treatment efficacy. This supports ongoing development of NaF PET/CT based imaging biomarkers in mCRPC. Clinical trial information: NCT01516866. [Table: see text]
Value of help from someone who's been there.
Authors: Debbie McCally Schultz, Susan Penn French
Journal: Journal of Clinical Oncology (2015)

241 Background: Cancer patients want to speak with someone who has their diagnosis, treatment or experience; but speaking with someone before an ostomy surgery, pelvic extenteration or the Whipple procedure, etc. can be particularly helpful due to the increased anxiety related to these and other serious procedures. A custom peer mentoring program by the cancer center for diagnosis or serious treatment purposes is optimal. Clinicians and patients want the service and attest to the importance of a one-on-one support connection. Methods: Steps were taken to partner with clinicians feeling peer support would be important to their patient. They want to make the best connection possible in a timely manner. Clinicians worked with the psychosocial program offering support to customize the connection so it would match the patient’s next treatment step. Peer mentors were recruited and trained to deliver a motivational interview style of approach in speaking with others who have the same cancer treatment experience. Mentors share resiliency tips they have developed or have found helpful. Results: MD Anderson Cancer Center’s Volunteer Services department offers a One-on-One support program of trained survivor volunteers available to support other survivors. The program has become a valued psychosocial offering by the MD Anderson. The clinicians and Volunteer Services staff team together to create a specific type of peer mentoring for a serious treatment or procedure or diagnosis. The volunteer staff department administers the One-on-One support program by recruiting, training and making available the connections when requested by clinician or patient. Currently, there are 1912 active survivor volunteers in the One-on-One support database. 2370 connections were made in FY14 and 1596 connections to date in FY15. Conclusions: Patients get support from survivors who have had the same experience at a time when their anxiety may be highest. Survivors who have lived through the same serious treatment and are hopeful and resilient after the procedures make the patient feel less isolated, frightened and supported by others. Caregivers, who often have more anxiety than the patient, welcome the support for their loved one.
Genomic insights into divergence and dual domestication of cultivated allotetraploid cottons
Authors: Lei Fang, Hao Gong, Yan Hu, Chunxiao Liu, Baoliang Zhou, Tao Huang, Yangkun Wang, Shuqi Chen, David D. Fang, Xiongming Du, Hong Chen, Jiedan Chen, Sen Wang, Qiong Wang, Qun Wan, Bingliang Liu, Mengqiao Pan, Lijing Chang, Huaitong Wu, Gaofu Mei, Dan Xiang, Xinghe Li, Caiping Cai, Xiefei Zhu, Z. Jeffrey Chen, Bin Han, Xiaoya Chen, Wangzhen Guo, Tianzhen Zhang, Xuehui Huang
Journal: Genome biology (2017)

Cotton has been cultivated and used to make fabrics for at least 7000 years. Two allotetraploid species of great commercial importance, Gossypium hirsutum and Gossypium barbadense, were domesticated after polyploidization and are cultivated worldwide. Although the overall genetic diversity between these two cultivated species has been studied with limited accessions, their population structure and genetic variations remain largely unknown. We resequence the genomes of 147 cotton accessions, including diverse wild relatives, landraces, and modern cultivars, and construct a comprehensive variation map to provide genomic insights into the divergence and dual domestication of these two important cultivated tetraploid cotton species. Phylogenetic analysis shows two divergent groups for G. hirsutum and G. barbadense, suggesting a dual domestication processes in tetraploid cottons. In spite of the strong genetic divergence, a small number of interspecific reciprocal introgression events are found between these species and the introgression pattern is significantly biased towards the gene flow from G. hirsutum into G. barbadense. We identify selective sweeps, some of which are associated with relatively highly expressed genes for fiber development and seed germination. We report a comprehensive analysis of the evolution and domestication history of allotetraploid cottons based on the whole genomic variation between G. hirsutum and G. barbadense and between wild accessions and modern cultivars. These results provide genomic bases for improving cotton production and for further evolution analysis of polyploid crops.
A single-arm phase II trial evaluating docetaxel, vinorelbine, and GM-CSF in stage IV melanoma.
Authors: J. P. Fruehauf, Z. Eroglu, K. M. Kong, J. G. Jakowatz, W. L. Akerley, W. E. Samlowski
Journal: Journal of Clinical Oncology (2011)

8546 Background: Metastatic melanoma patients have a poor prognosis. Currently only immunotherapy has offered a limited survival benefit. More effective and less toxic treatments are needed. Docetaxel (Taxotere) has clinical activity in melanoma and may be more active when combined with vinorelbine (Navelbine). Granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown activity as an adjuvant melanoma therapy (E4697). We therefore carried out a Phase II study of these three agents in patients with stage IV melanoma. Methods: Patients had documented stage IV melanoma and may have had prior immuno- or chemotherapy. Previously treated and controlled brain metastases were allowed. The DVS regimen: Docetaxel (40 mg/m2 IV), Vinorelbine (30 mg/m2 IV) were administered every 14 days, followed by GM-CSF (sargramostim, 250 mg/m2 SC on days 2 to 12). The primary endpoint of the study was one year overall survival (OS) rate. Secondary objectives were median overall survival, response rate (per RECIST criteria) and the toxicity profiles. Results: Fifty-two patients were enrolled. 80% had M1c stage disease. Brain metastases were present in 21%. Fifty-two percent of patients had received prior chemotherapy, including 35% who had received prior biochemotherapy. Toxicity of the DVS regimen was manageable. Grade III/IV toxicities included neutropenia (31%), anemia (14%), febrile neutropenia (11.5%), and thrombocytopenia (9%). DVS chemotherapy demonstrated clinical activity, with a partial response of 15%, and disease stabilization in another 37%. Six-month progression free survival was 37%, and median overall survival was 11.4 months. Comparison to historical controls was made from a model by Korn et al (J Clin Oncol 2008; 26:527-34) that determines predicted one year OS rates for metastatic melanoma patients in single-arm phase II trials. While a historical one year OS of 24.3% was calculated, the actual one year OS rate for the patients in this trial was 48.1% (p = 0.01). Conclusions: The DVS regimen was active in patients with advanced, previously treated melanoma, with manageable toxicity. The favorable one-year overall survival and median survival rates suggest that further evaluation of the DVS regimen is warranted.
Partial Efficacy of Bortezomib on Acute Myeloid Leukemia (AML) Cells in a Patient with Concomitant Multiple Myeloma and AML.
Authors: Bertrand Joly, Patrick Quillet, Celia Salanoubat, Selwa Bouledroua, Charlotte Petitdidier, Alain Devidas
Journal: Blood (2007)
Randomized, phase II study comparing cisplatin and high-dose 5-fluorouracil/leucovorin with paclitaxel and high-dose 5-fluorouracil/leucovorin in patients with advanced gastric cancer and adenocarcinomas of the gastroesophageal junction
Authors: M. E. Tesselaar, S. Luelmo, M. Polee, A. van Bochove, J. Ouwerkerk, H. Pruijt, H. Sleeboom
Journal: Journal of Clinical Oncology (2008)

4567 Background: This randomized phase II trial compared the response rate (RR) of high-dose 5-fluorouracil (5FU) plus leucovorin (LV) and cisplatin (CDDP) with 5FU plus LV and paclitaxel in previously untreated, metastatic gastroesophageal adenocarcinoma. Methods: Patients (pts) with measurable histologically confirmed adenocarcinoma were randomized into 2 groups. Arm A (n=49): weekly 5FU (2.0 g/m2 d 1,8,15,22,29,36) plus LV (500 mg/m2) and biweekly CDDP (50 mg/m2 day 1,15,29) with cycles repeated every 7 weeks. Arm B (n=47): weekly 5FU (2.0 g/m2 d1,8,15) plus LV (500 mg/m2) and weekly paclitaxel (80 mg/m2 d1,8,15) with cycles repeated every 4 weeks. Treatment was continued until disease progression or up to 24 weeks of treatment. The primary endpoint was response rate. Results: Results for responses are presented for the first 55 pts and for toxicity for 94 pts. The best overall response rate (ORR) was 46% (95% CI, 27% to 66%) for treatment arm A and 44 % (95% CI, 26% to 65%) for treatment arm B. This included 2 (6% of group A) vs. 2 (6%) complete responses, and 11 (33% of group A) vs. 10 (30%) partial responses. Ten pts in group A (30%) vs. 10 pts (30%) in group B had stable disease and 5 pts (15%) vs. 5 (15%) in respectively group A and B progressed while on treatment. The median time to progression (TTP) was 3.9 months (mo) (range 0.3–18.5) for treatment arm A vs. 4.2 mo (range 0.1–16.4) for treatment arm B. The median overall survival time (OS) was 4.9 mo (range 1.0–19.1) for treatment arm A vs. 5.4 mo (range 0.7–26.2) for treatment arm B. Hematological toxicity was common, although WHO grade 3–4 toxicity only occurred in 2 patients in group A. Neutropenic fever occurred in 3 resp 4 pts of whom 1 pt died (group A). Nonhematologic adverse reactions were usually mild to moderate; WHO grade 3–4 toxicities included emesis in 5 pts, fatigue in 7 pts, stomatitis in 2 pts, with a majority of pts in group A, diarrhea in 6 pts, with a majority in group B and thromboembolism in 3 pts (all from group A). Conclusions: These results suggest that both treatment arms have comparable overall response rates, TTP and OS. Paclitaxel however had a slightly better toxicity profile. No significant financial relationships to disclose.
Inappropriate utilization of radiographic imaging in men with newly diagnosed prostate cancer.
Authors: S. M. Prasad, X. Gu, S. R. Lipsitz, P. L. Nguyen, J. C. Hu
Journal: Journal of Clinical Oncology (2011)

120 Background: The use of radiographic imaging (bone scan, computerized tomography and magnetic resonance imaging) following diagnosis of prostate cancer is recommended only in the setting of high-risk pathologic features. This study sought to characterize utilization patterns of imaging in men with newly diagnosed prostate cancer. Methods: We identified 30,183 men diagnosed with prostate cancer from 2004-2005 using Surveillance, Epidemiology and End Results-Medicare linked data to characterize the determinants of radiographic staging following prostate cancer diagnosis. Results: 36% of men with low risk and 49% of those with intermediate risk prostate cancer underwent unnecessary imaging for staging, while only 61% of men at high risk received any imaging test prior to treatment. Use of imaging was more common in men who were older than 75 (OR 1.25, CI 1.17–1.33) black (OR 1.11, CI 1.01–1.21), wealthier (OR 1.19, CI 1.08–1.32 for median income &gt;$60,000 vs &lt;$35,000), living in rural regions (OR 1.22, CI 1.11–1.34) and who underwent radiation therapies ( Table ). It was less common in men who were educated (OR 0.84, CI 0.76–0.92 between highest and lowest education levels) and chose active surveillance. There was no association between use of imaging and either marital status or Charlson score. Conclusions: There is widespread overutilization of staging in low and intermediate risk patients, while a worrisome number of men at high risk undergo treatment without appropriate diagnostic imaging. Physicians may be prescribing costly and unnecessary tests with associated harmful radiation in over a third of patients while forgoing the recommended metastatic workup in almost 40% of high-risk patients prior to treatment. [Table: see text] No significant financial relationships to disclose.
Lymphopenia as an independent predictor of worse survival in papillary renal cell carcinoma.
Authors: Reza Mehrazin, Robert G. Uzzo, Alexander Kutikov, Jeffrey J. Tomaszewski, Serge Ginzburg, Karen J. Ruth, Essel Al-Saleem, David Y. T. Chen, Rosalia Viterbo, Richard E. Greenberg, Marc C. Smaldone, Tahseen I. Al-Saleem
Journal: Journal of Clinical Oncology (2014)

397 Background: Lymphopenia signifies inflammatory response and is an index of poor systemic immunity which can be associated with poor survival outcomes. The aim of this study was to evaluate the prognostic relevance of preoperative absolute lymphocyte count (ALC) in patients with papillary renal cell carcinoma (RCC). Methods: We retrospectively analyzed our institutional, prospectively maintained, renal cancer database and identified patients with pathologic diagnosis of papillary RCC after partial or radical nephrectomy. Patients with preoperative ALC value within 3 months prior to surgery were eligible for the study. ALC of 1,300 cells/µl was used as the cutoff value (our lowest laboratory reference value). We evaluated the correlation between ALC and age, gender, Charlson comorbidity index (CCI), pathologic T stage, nuclear grade, and overall TNM stage. Differences in overall survival (OS) by ALC status were assessed using the log−rank test. Cox proportional hazards modeling was used for multivariable analyses. Results: We identified 314 out of 2,732 patients with a pathologic diagnosis of papillary RCC after partial or radical nephrectomy from 1997 to 2013. Those undergoing multiple surgical procedures (multifocal or bilateral disease) or missing preoperative ALC were excluded from the study. A total 205 patients met inclusion criteria with a median follow up of 37.3 months. As a continuous variable, low absolute lymphocyte count was associated with higher pT stage (p=0.038), TNM stage (p=0.029) and older age (p=0.022). Lymphopenia below 1,300 cells/µl was also associated with pT stage (p=0.008) and TNM stage (p=0.018). On multivariable analysis, independent of stage, older age,and CCI, lymphopenia was associated with inferior overall survival (HR 2.1 [CI 1.1−4.03], p=0.037). Conclusions: In our series of patients with papillary renal cell carcinoma, lymphopenia was associated with lower overall survival independent of stage, age,and charlson comorbidity index. ALC significantly increases the accuracy of already established prognostic factors and can be helpful for patient counseling and design of clinical trials.
Effects of radium-223 dichloride (Ra-223) on risk for hospitalization and health care resource use in the phase 3 ALSYMPCA trial.
Authors: Paul Cislo, Jonathan Reuning-Scherer
Journal: Journal of Clinical Oncology (2014)

21 Background: Ra-223 is a first-in-class alpha-emitter approved for treatment (tx) of patients (pts) with castration-resistant prostate cancer and symptomatic bone metastases. In ALSYMPCA, Ra-223 significantly improved overall survival by 3.6 months vs placebo (pbo) (HR = 0.70; 95% CI, 0.58-0.83; P &lt; 0.001) and was well tolerated. To understand whether the tx benefit corresponds to differences in utilization, hospitalization and other types of health care resource use were evaluated. Methods: Data on hospitalization, nursing home visits, home health care and adult day care services use, and physician visits were captured for each pt. Tx groups were compared, based on percentage needing each type of health care resource, using Fisher’s exact test. To account for differences in each pt resource use in ALSYMPCA, the number of encounters (eg, office visits) and duration of encounters (eg, days hospitalized) were divided by observation time. The mean number and duration of encounters were compared using analysis of variance. To compare tx groups based on the rate of use per year, incidence rates and ratios were calculated using a generalized estimating equation (GEE) regression model. Results: The mean follow-up time in months for Ra-223 vs pbo was 10.0 vs 8.6. The incidence rate for Ra-223 vs pbo was 1.1 vs 1.4 (incidence rate ratio = 0.77; 95% CI, 0.62-0.95; P = 0.013). The mean number of hospitalizations and hospitalization days per year for Ra-223 vs pbo were 1.3 vs 1.7 (P = 0.020) and 8.1 vs 14.6 (P &lt; 0.001), respectively. The percentage of pts that required hospitalization was nominally lower for Ra-223 vs pbo (42.3% vs 49.0%, P = 0.062). Among pts who experienced at least one hospitalization, the mean number of hospitalization days per year for Ra-223 vs pbo pts was 19.4 vs 30.4 (P &lt; 0.001). No significant differences were found between tx groups in terms of visits or durations of time in nursing homes per year, amount of adult day care and home health care services utilized per year, and number of physician visits per year. Conclusions: Compared with pbo, Ra-223 tx resulted in a 23% reduction in incidence of hospitalizations per year and about 6.5 fewer hospitalization days per pt per year. Clinical trial information: NCT00699751.
Developing pathways for cancer rehabilitation in tertiary oncology centers: Initial observations at the McGill University Health Centre.
Authors: Sabrina Cesare, Irina Uscatescu, Jonathan di Tomasso, Lorella Ciutto, Kevin Yu-Chueh, Henry Olders, Nathalie Aubin, Mary Lou Kelly, Marta Jelowicki, Rabiaa Laroui, Rosemary O'Grady, Manuel Borod, Robert Kilgour, Antonio Angelo Luciano Vigano
Journal: Journal of Clinical Oncology (2014)

17 Background: No definitive rehabilitation pathways exist for cancer patients. To address this gap, the Cancer Rehabilitation interdisciplinary team at the McGill University Health Centre has developed three program paths (e.g., Restorative, Supportive, and Cachexia) to meet the various specialized and personalized needs of cancer patients. Methods: A consecutive cohort of patients referred to the Cancer Rehabilitation Clinic between January 1 st and June 30 th , 2014 was considered. We examined the following baseline characteristics: handgrip strength (HGS), the abridged Patient Generated-Subjective Global Assessment (aPG-SGA) and Edmonton Symptom Assessment System (ESAS) self-reported questionnaires. Results: Of the 54 patients evaluated (57.4% male), 20 (mean age: 47.4 yrs), 8 (59.9 yrs) and 26 (64.6 yrs) were assigned to the restorative, supportive and cachexia streams, respectively. The most common cancer diagnoses were gastrointestinal (15%), gynecological (13%), breast (12%) and lung (12%). Table 1 contains baseline aPG-SGA, ESAS and HGS scores. Conclusions: Our preliminary data confirm clinically significant differences in muscle strength across the 3 streams for both males and females, as well as significant differences in nutritional, appetite and well-being scores between the patients in the restorative and cachexia pathways. Our data confirm the need of personalized and targeted interventions to achieve or maintain optimal performance and quality of life in cancer survivors with different disease and treatment characteristics. [Table: see text]