tbuckley/cabot-search huggingface dataset:
Stereotactic body radiation therapy (SBRT) following procedures for benign prostatic hyperplasia (BPH): A report on early toxicity.
Authors: Marie Kate Gurka, Zachary D. Horne, Leonard Chen, Sue Lei, Pranay Krishnan, Keith Kowalczyk, Simeng Suy, Anatoly Dritschilo, John H. Lynch, Sean P. Collins
Journal: Journal of Clinical Oncology (2013)

165 Background: When treating patients with prostate cancer, hypofractionation with SBRT takes advantage of radiobiologically favorable factors as compared to conventional fractionation. However, this may increase the risk of urinary toxicity, especially in patients with prior procedures for BPH. Herein, we report early urinary toxicity following SBRT in patients with a history of procedures for BPH. Methods: Thirty three patients treated with SBRT for localized prostate cancer from February 2009 to October 2011 at Georgetown University Hospital with history of a prior procedure for BPH were included in this retrospective analysis. Treatment was delivered using the CyberKnife with doses of 35 Gy-36.25 Gy in 5 fractions. Toxicities were scored using the CTCAE v.3. Cystoscopy findings were retrospectively reviewed. Patient-reported urinary symptoms were assessed using the American Urological Association Symptom Score (AUA). Results: The median age was 70 years (range, 64 - 84). The median follow-up time was 18.7 months (range 9.2 – 38.9). Grade 2 or 3 urinary toxicity occurred in 9 patients and there were no grade 4 or 5 toxicities. Hematuria occurred in 12 patients. The median time to onset of hematuria from SBRT was 6 months (range 1 – 30). Grade 1 hematuria occurred in 7 patients, grade 2 in 4 patients and 1 patient experienced grade 3. Cystoscopy was performed in 9 of these patients at a median time of 9 months (range 3-27). Eight had hyperemia or evidence of bleeding from the prostatic urethra and 5 of these patients also had evidence of bleeding from the bladder neck/wall. All patients except one, who died from other causes, are still being followed and hematuria has resolved in 9 of the 12 patients. The median baseline AUA symptom score of 7 increased to 11 at 1 month, however decreased to a median score of 6 at 3 months. The median AUA symptom score increased to 9 at 1 year. Conclusions: A history of prior transurethral resection of prostate may predispose patients to increased urinary toxicity and hematuria following prostate SBRT. Stricter urethra/bladder neck dosimetric criteria or alternative fractionation regimens may be required to decrease urinary toxicity in these patients.
Serum levels of vascular endothelial growth factor in patients with gastrointestinal cancers and correlation with malnutrition, immunosuppression involving MDSC, and systemic inflammation.
Authors: Kenji Gonda, Masahiko Shibata, Satoshi Suzuki, Izumi Nakamura, Kensuke Kumamoto, Tatsuo Shimura, Seiichi Takenoshita
Journal: Journal of Clinical Oncology (2014)

514 Background: Vascular endothelial growth factor (VEGF) reportedly plays an important role in the progression of malignant neoplasms, and have been reported to induce myeloid-derived suppressor cells (MDSC) that appears in cancer and inflammation. Methods: Blood samples were collected from 57 patients, including 8 with esophageal cancer, 20 with gastric cancer, 29 with colorectal cancer, and from 18 healthy volunteers. We measured serum concentrations of VEGF and analyzed correlations with nutritional damage, immune suppression and systemic inflammation. As markers of immune function, IL-12 production of PBMC and MDSC (CD 11b + , CD14 - , CD33 + ) were measured. Serum concentrations of albumin and rapid turnover protein were measured as a marker of nutritional status. Results: A significant increase in serum levels was seen in patients with esophageal, gastric, and colorectal cancers compared to healthy volunteers. Levels of VEGF were inversely correlated with serum concentrations of albumin, prealbumin and retinol-binding protein. Serum concentrations of VEGF were inversely correlated with the production of interleukin (IL)-12 and correlated with MDSC. VEGF levels also correlated with neutrophil count and neutrophil/lymphocyte count, and correlated inversely with lymphocyte count. Serum VEGF levels were then divided about a cutoff of 500 pg/ml, with levels of prealbumin and retinol-binding protein significantly decreased in patients with higher VEGF levels. Stimulation index and IL-12 production were significantly decreased in the group with higher VEGF levels, and MDSC counts tended to be higher in this group. Conclusions: These results demonstrated that increased production of VEGF correlated with systemic inflammation, nutritional impairment and inhibition of cell-mediated immunity involving MDSCs. An inactivation of dendritic cells may be occurring by the activation of MDSC. Anti-VEGF therapy may be of importance in treating digestive system cancers.
Safety and efficacy of regorafenib in Japanese patients with metastatic colorectal cancer (mCRC) in clinical practice: Interim result from postmarketing surveillance (PMS).
Authors: Yoshito Komatsu, Kei Muro, Kensei Yamaguchi, Hiroyuki Uetake, Taroh Satoh, Takayuki Yoshino, Toshirou Nishida, Naoya Yamazaki, Hajime Takigawa, Yoko Hamada, Masayuki Chosa, Toshiyuki Sunaya, Yuka Yamamoto, Yuichiro Ito, Toshiaki Watanabe, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2016)

680 Background: The oral multikinase inhibitor regorafenib (REG) was approved for unresectable mCRC in Japan in 2013 based on results of the global CORRECT phase 3 trial of 760 patients (pts), which included 100 Japanese pts. A Japanese PMS (NCT01843400) has been conducted since approval, to assess the safety and efficacy of REG for the treatment of mCRC in clinical practice. Methods: Pre-registration was applied in the PMS. Adverse events (AEs), laboratory tests, drug exposure and anti-tumor effects were prospectively monitored for 6 months after initiating REG. One-year survival data was also collected. The target enrollment was 1,250 Japanese pts. Results: A total 1,307 pts were enrolled in the PMS from March 2013 to May 2015. At the interim analysis as of June 2014, 545 pts were evaluable for safety and efficacy: male 59%; age ≥ 65 yrs 48%; Eastern Cooperative Oncology Group Performance Status 0/1/2 40%/51%/9%; KRAS status wild-type/mutant 50%/47%; treatment line of REG 3 rd /4 th / ≥ 5 th line 33.8%/37.6%/27.7%; initial dose of REG 160 mg/120mg 76%/17%. Drug related AEs were reported in 483 patients (89%). The most common events were hand foot skin reaction [(HFSR) 57%], liver dysfunction [31.8% (including hepatic laboratory abnormalities (15%)], hypertension (28%), platelets count decreased (16%) and fatigue (15%). The incidence of major AEs of any grade typically peaked the first 2 months after starting REG and was relatively stable afterwards. Median time to treatment failure was 2.3 months [range 2.1– 2.4]; median overall survival (OS) was 6.9 months [range 6.0– 7.7]. Exploratory analysis suggested that pts who experienced HFSR had a significantly longer OS than pts who did not (hazard ratio 0.351; 95% confidential interval0.253– 0.488; p &lt; 0.0001). Conclusions: Interim results suggested that the safety and efficacy profile of REG in Japanese pts in clinical practice was consistent with those of Japanese pts in the CORRECT trial. Follow-up and data collection are ongoing. Updated data will be presented. Clinical trial information: NCT01843400.
Does a quality-of-care problem exist? Cancer Care Ontario practice pattern data and the recommendations of two lung cancer practice guidelines.
Authors: Melissa C. Brouwers, Julie Makarski
Journal: Journal of Clinical Oncology (2012)

190 Background: Practice-pattern data, evidence-based knowledge and transfer, and performance management strategies define Cancer Care Ontario’s quality improvement strategy. Knowledge products, such as practice guidelines, are intended to provide recommendations for practice, based on best available evidence, to improve quality of care and reduce variation in practice. Review of 2010-2011 Cancer System Quality Index (CSQI) data revealed complex practice patterns in treatment of non-small cell lung cancer patients with stages II and IIIa resected and stages IIIa and IIIb non-resected disease in Ontario. A multi-method study was initiated to understand the patterns, to identify if a quality of care problem exists and to propose improvements moving forward. Methods: Surgeons, medical oncologists and radiation oncologists from Ontario were invited to participate in a survey consisting of 6 areas of inquiry. A grounded theory approach was used to guide key informant interviews of purposively sampled clinicians and administrators. A more in-depth analysis of the CSQI data was planned. Results: Clinicians responding to survey provided positive assessments of PG recommendations and evidentiary base; perceptions of practice patterns were less problematic than hypothesized; estimates of benchmarks were highly variable; and assessments of barriers to recommendation implementation included slow referral process, lack of organization support and patients seen in practice not reflected in the evidence. From the interviews, 5 themes emerged: unique patient, unique physician, family, clinical team, and clinical evidence. Further analysis of CSQI data was not possible given limitations related to data collection. Conclusions: A perceived quality of care problem initiated this study. Concerns centred on significant proportion of patients receiving no treatment; modest percentage of patients receiving treatment that aligned with PG recommendations; and regional variation within each of the clinical care options. Our data show that defining a quality of care problem is significantly more complex than consideration of practice patterns alone.
The effect of trastuzumab therapy on clinical benefit from fulvestrant treatment for metastatic estrogen receptor-positive breast cancer patients.
Authors: Mahmoud Charif, Elyse E. Lower, Diane Kennedy, Harriet Kumar, Shugufta Khan, Neetu Radhakrishnan, Xiaoting Zhang
Journal: Journal of Clinical Oncology (2014)

155 Background: Overexpression of HER2/neu is associated with tamoxifen resistance in breast cancer (Osborne CK et al. J Natl Canc Inst 2003; 95:353-361). However pts may present with both estrogen receptor (ER) and HER2/neu + tumors. The benefit of adding fulvestrant to trastuzumab is unclear. The objective of the study was to determine the effect of trastuzumab on fulvestrant therapy. Methods: This was an IRB approved record review of patients (pts) from three medical oncologists with biopsy-proven ER+ metastatic breast cancer treated with fulvestrant who also had their primary tumor tested for HER2/neu. Demographic data collected included age at diagnosis, type and stage of cancer, original and metastatic ER, progesterone receptor (PR), and HER-2/neu biomarkers, and site(s) of metastasis, and primary local and systemic treatment. All pts with HER-2/neu + primary tumors received trastuzumab. The duration of fulvestrant therapy was calculated. Time to clinical disease progression on fulvestrant was measured as a surrogate for duration of clinical benefit. Results: Eighty-five metastatic ER+ fulvestrant treated breast cancer pts with known primary tumor HER2/neu status were identified and the duration of therapy calculated. All eleven (13%) pts with documented HER2/neu + primary tumors received trastuzumab. The duration of therapy for HER2/neu + pts (772 (51-1911) days (median (range)) was longer than HER2/neu negative pts (360 (60-2,739) days, p=0.059). The median duration of fulvestrant therapy was 425 days. Pts with HER2/neu + tumors were more likely to be treated beyond the median fulvestrant therapy with an odds ratio of 6.2 (1.26 to 30.92 95% confidence interval, p=0.0249). Conclusions: Trastuzumab plus fulvestrant therapy was associated with a more prolonged clinical response than fulvestrant alone in pts with metastatic breast cancer. This synergism may be due to the effect of trastuzumab inhibiting the activation of transcriptional coactivator MED1, a recently discovered key crosstalk point between HER2/neu and ER signaling pathways in mediating endocrine resistance (Cancer Res 2012;72(21):5625;PLoS One 2013; 8:e70641).
Genetic Profile of Acute Erythroid Leukemia
Authors: June Takeda, Kenichi Chiba, Yuichi Shiraishi, Tetsuichi Yoshizato, Yusuke Shiozawa, Yasunobu Nagata, Akira Hangaishi, Ken Ishiyama, Keisuke Kataoka, Masashi Sanada, Hiroko Tanaka, Kensuke Usuki, Shuichi Miyawaki, Satoru Miyano, Arnold Ganser, Seishi Ogawa, Michael Heuser, Felicitas Thol, Kenichi Yoshida
Journal: Blood (2016)
Readmissions following umbilical cord blood stem cell transplantation.
Authors: Jennifer Crombie, Laura Michelle Spring, Shuli Li, Robert Soiffer, Joseph Harry Antin, Edwin Alyea, Brett Glotzbecker
Journal: Journal of Clinical Oncology (2014)

272 Background: Readmission within 30 days of discharge has been perceived by the Centers for Medicare and Medicaid Services to be an indicator of poor healthcare quality, however it is unclear how accurately this applies to oncology patients. Patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) have high rates of readmission, but the incidence following umbilical cord blood transplantation (UCBT) is poorly described. The goal of this study was to identify the incidence, reasons, and risk factors for readmission following UCBT. Methods: A retrospective review of patients receiving an UCBT at Dana-Farber/Brigham and Women’s Hospital between January 1, 2004 and December 31, 2013 was performed. The 30-day and the day +100, a traditional assessment point in transplantation, readmission rates were examined. Reasons for readmission, as well as sociodemographic and disease and stem cell transplant related variables were evaluated. Predictors of readmission were identified using multivariate regression analysis. Results: 33.6% (42/125) of patients were readmitted within 30 days of discharge. Of patients who survived until day +100, 46.7% (57/122) were readmitted within 100 days of UCBT. The most common cause for readmission was infection (38.3%), followed by fever without a source (14.8%) and graft vs. host disease (GVHD) (8.6%) (Table). A multivariate logistic regression model of the probability of being readmitted within 30 days and by day +100 suggested that infection during transplant admission was a significant risk factor for readmission (OR: 5.1, p=0.003 and OR: 2.9, p=0.014, respectively). Conclusions: There is a high rate of readmission within 30 days and by day +100 following UCBT. The most common causes of readmission were infection and fever without a source. Infection during the transplant admission predicted a higher risk of readmission, suggesting a possible group to target for interventions aimed at reducing readmissions and improving quality of care. [Table: see text]
Upfront Imatinib with Selective Early Switching to Nilotinib Leads to Excellent Achievement of Deep Molecular Response in Chronic Phase CML: 5 Year (Final) Analysis of the TIDEL-II Study
Authors: David T. Yeung, Michael Philip Osborn, Deborah L White, Susan Branford, Tracey Gerber, Belinda Butcher, Samar Issa, Devendra K Hiwase, Mark S Hertzberg, David Gottlieb, Anthony P Schwarer, Robin Filshie, Christopher Arthur, Yiu-Lam Kwan, Cecily Forsyth, John Taper, David M. Ross, Constantine S. Tam, Anthony K. Mills, Andrew Grigg, Timothy P. Hughes
Journal: Blood (2016)
Therapy response of Chinese herbal medicine in primary liver cancer.
Authors: Yongling Gong
Journal: Journal of Clinical Oncology (2015)

488 Background: Aiming at starting the ball rolling and contributing humble effort to promote Chinese traditional medicine, we report successful cases of Chinese herbal decoction for primary liver cancer. Methods: Conventional therapy of surgical resection and artery catheterization chemotherapy was applied in cases reported. In the meantime, we administered Chinese medicine (Gan Decoction, mixed with a variety of effective herbal components) to help them to recover from poor condition. Results: After taking the Chinese herbal decoction for months, the tumour marker (AFP, CA19-9) level dramatically decreased to the normal range. Most residual intrahepatic metastatic sites reduced according to ultrasonography/CT imaging, and the patient felt free from the complaint of abdominal discomfort. The quality of life has been greatly improved, we managed to have prolonged the PFS (Progression-Free-Survival) and TTP (Time-to-Progression) from the onset to date. Conclusions: Chinese medicine considers human body as a dynamic platform in which all organs are correlative and bind each other. Each case showed distinguished liver cancer progression and heterogeneity with individual therapy response. Our report suggested that Chinese herbs might be an additional choice with its better benefits and tolerability in the treatment of primary liver cancer.
Central nervous system relapse in pediatric acute lymphoblastic leukemia: Should we be making the diagnosis sooner?
Authors: A. E. Aguilar, A. K. Agrawal, J. H. Feusner
Journal: Journal of Clinical Oncology (2011)

9567 Background: Central nervous system (CNS) disease in acute lymphoblastic leukemia (ALL) is based solely on consensus guidelines, which define involvement as the presence of at least 5 white blood cells (WBC) per μL in the cerebrospinal fluid (CSF) with lymphoblasts (CNS3) (Med Pediatr Oncol:1986;14). Relapsed disease utilizes the same definition unless there are immunohistochemical or flow cytometric markers prior to the advent of CNS3 disease. We have observed patients with multiple consecutive abnormal CSF cytology exams prior to meeting the standard definition of CNS relapse and wonder if this may be a sufficient criterion for relapsed disease. Methods: We reviewed all CSF cytology reports for ALL patients treated at our institution from 2003 through 2010. We then reviewed all cytology slides from patients with CNS relapse, comparing the pre-relapse slides to those from the relapse specimen, applying the method of Goldsby et al. (Med Pediatr Oncol:1997;29). Results: 239 patients had 3425 CSF cytology exams. Ten patients had CNS relapse, 9 of which had morphologic evidence of early CSF leukemic involvement, ranging from 7 to 28 weeks (median 13, mean 15 weeks), before meeting the standard definition for relapse. Consecutive CSF analysis with suspicious cells (WBC < 5/μL) outside induction was highly significant for the presence of relapsed CNS disease: 6 of the 10 patients with eventual CNS3 relapse had this finding, as compared to 3 of 225 patients (0.3% of all CSF examined) without CNS disease (p<0.0001 by Fisher’s Exact test; excluding 4 patients, 2 treated for CNS disease before CNS3, 2 with abnormal CSF with peripheral blasts at or after bone marrow relapse). Conclusions: Patients with CNS relapse may wait months with cells suspected of being leukemic prior to developing CNS3 disease. In our analysis, consecutive abnormal CSF exams without pleiocytosis was highly significant for relapse. With careful morphologic analysis, we suggest the diagnosis of CNS relapse can be confidently established earlier than is currently done. Continuing a failing treatment regimen in these cases increases parental and patient anxiety and could potentiate resistant disease and worse outcomes.
Factors associated with quality of life in a cohort of patients with palliative advanced cancer from a developing country: Relevance of perception of cancer curability.
Authors: Pedro Emilio Perez-Cruz, Paola Langer, Cecilia Carrasco Escarate, Pilar Bonati, Bogomila Batic, Laura Tupper Satt, Marcela Gonzalez Otaiza
Journal: Journal of Clinical Oncology (2016)

93 Background: Improving quality of life (QOL) is a key goal in palliative care for patients with advanced cancer. Most studies about QOL in palliative care patients have been performed in the developed world. However, little is known about the factors that influence patients QOL in developing countries. The aim of this study is to describe factors associated with QOL in a cohort of patients with advanced cancer who were enrolled in the outpatient clinic public hospital in Santiago, Chile. Methods: Patients with advanced cancer admitted to the National Program of Palliative Care at a public Hospital in Santiago, Chile were prospectively enrolled in a study to assess QOL longitudinally. QOL was assessed with the EORTC-QLQ-PAL 15 questionnaire. Demographics, symptom intensity, depression and anxiety were assessed. Descriptive statistics and regression analysis were performed. Information about cancer curability and perception of personal health were also included. Results: In this preliminary report, the first 37 patients were included. Baseline characteristics were: mean patient age was 64, 21 (57%) females, 14 (38%) had GI cancer, 7 (19%) lung cancer, 4 (11%) breast cancer and 12 (22%) other. Mean (SD) QOL was 63 (34) in a 0 to 100 scale. QOL was not associated with age, gender, functionality, depression, anxiety, spiritual pain or financial distress. QOL was negatively associated with total symptom burden (coef -.53, p = .48), and positively associated with believing that cancer was curable (coef 33.3, p = .003). In a multivariate analysis, QOL was independently associated with both lower overall symptom burden (coef -.55, p = .38) and believing that cancer was curable (coef 28.6, p = .009). Conclusions: In palliative care patients with advanced cancer from a developing country, QOL was associated with lower overall symptom burden and with believing that cancer was curable. Further studies are needed to explore whether clarifying prognostic information about cancer curability in developing countries may impact patients’ QOL.
Barriers to palliative care in outpatient oncology practice.
Authors: Joshua Murray Wilfong, Maria Silveira
Journal: Journal of Clinical Oncology (2014)

45 Background: In 2009 ASCO released a policy statement recommending integration of palliative care as part of comprehensive cancer care. The various needs of cancer patients and the complex organization of health care makes this integration challenging. With this idea in mind, we conducted focus groups with oncologists and oncology nurses to identify the barriers to providing palliative care within oncology. Methods: We conducted 11 focus groups with oncologists and their nursing staff at 5 sites throughout Southeast Michigan to explore their care of patients with incurable and advanced cancer. Physicians and nurses were interviewed separately. Interviews were taped, transcribed, and analyzed using cross-case comparison. Transcripts were reviewed by multiple readers to: 1) develop a coding scheme, 2) identify themes, and 3) design an interpretive model. Results: Oncologists and their nursing staff acknowledge the importance of providing high quality palliative care to their patients. Multiple barriers that affect their abilities to provide the quality of palliative care that they desire for their patients were discussed. These issues include 1) Time limitations for discussion of symptoms and advance care plans during office visits; 2) Limited access to secondary supports (e.g. palliative care physicians, social workers, and psychiatrists) available and difficulty coordinating a timely referral; 3) Limited availability of effective case management and telephone care for coordinated patient communication between visits. Conclusions: Oncologists and their nursing staff value and acknowledge the importance of providing their patients with high-quality palliative care but multiple limitations in the organization of oncology care prevent them from doing so. Allowing longer visits, access to secondary supports, and effective case management may improve the quality of palliative care offered within outpatient oncology.