tbuckley/cabot-search huggingface dataset:
Choosing Wisely in oncology: Screening for a new primary cancer in patients with metastatic disease.
Authors: Simron Singh, Lorraine Lipscombe, Hadas Fischer, Jill Tinmouth, Peter Austin, Kinwah Fung, Matthew C. Cheung
Journal: Journal of Clinical Oncology (2016)

295 Background: The Choosing Wisely Canada (CWC) campaign aims to start conversations about unnecessary treatments and procedures in order to improve quality of care. In particular, the CWC campaign in cancer seeks to reduce interventions that are not supported by evidence and contribute to unnecessary rising costs of cancer care. We sought to document the performance of cancer screening for a new primary cancer in patients with existing metastatic cancer (CWC statement #2). Methods: We used population-based administrative health care databases from Ontario, Canada held at the Institute for Clinical Evaluative Sciences (ICES). The cohort included all adult residents of Ontario of eligible screening age (age 50 or older) diagnosed with incident, stage 4 (metastatic) colorectal cancer (CRC), lung, breast, or prostate cancer between January 1, 2007 and December 31, 2012. We examined screening tests for CRC and breast cancer in the first 1 and 3 years after diagnosis of an unrelated cancer. Given the high mortality rate in this population, screening rates were calculated using the cumulative incidence function which takes into account the competing risk of death or the occurrence of the cancer for which the patient was being screened (prior to being screened). Results: Among the 20,992 patients with stage 4 lung, breast, or prostate cancer, CRC screening within 1 year of cancer diagnosis occurred in 2.8%, 6.1%, and 13.0%, respectively. Within 3 years of diagnosis, screening rates were 3.9%, 11.9%, and 26.9%, respectively. Among the 10,034 women with metastatic CRC or lung cancer, breast cancer screening within 1 year of cancer diagnosis occurred in 8.0% and 8.7% of women, respectively. Within 3 years of diagnosis, screening rates were13.1% and 10.2%, respectively. Screening rates were higher in patients age 50-74 than those ≥75 years. Conclusions: Our findings indicate that up to one quarter of patients with metastatic cancer receive subsequent screening tests for other cancers, which are unnecessary as these patients are unlikely to benefit. Further studies are warranted to examine resource implications, potential patient and societal harms, and the future impact of the CWC campaign on this practice.
Race, inflammation, and prostate cancer: A comparison of African Americans and Caucasians.
Authors: Emma M. Ernst, Elisa M. Ledet, Allison H. Feibus, Jonathan L. Silberstein, Oliver Sartor
Journal: Journal of Clinical Oncology (2016)

246 Background: African-Americans (AA) have the highest rate of prostate cancer (PCa) incidence and mortality. Studies have shown higher rates of chronic prostate inflammation in AAs compared to Caucasians (CA). In order to better understand racial disparity in PCa and chronic inflammation (CI), this study examined the effects of race and CI on clinical parameters among PCa patients. Methods: This retrospective study sample consisted of 61 AA and 52 CA PCa patients who underwent radical prostatectomies (RP) at Tulane Hospital between 2013 and 2015. Clinical data was extracted from biopsy and RP pathology reports. The study examined the relationship between CI, race, percent of positive cores, extra-prostatic extension, PSA, PSA density, urinary PCA3 and TMPRSS2, and prostate size (g). Pearson’s chi-square, Fisher’s exact, and Kruskal-Wallis tests were used to analyze categorical, non-continuous data; ANOVA tests were used to analyze continuous data. Differences between biopsy and surgical/pathologic Gleason scores and clinical/pathological stages were also assessed. Results: 94 patients (52 AAs and 42 CAs) had CI to some degree and 19 did not (9 AAs and 10 CAs). There was no difference in rate of CI between AA and CA patients (P = 0.526). Among all patients sampled, AAs had higher percentages of positive cores (P = 0.005), PCA3 copy levels (P =0.004), and PCA3 scores (P &lt;0.001), lower TMPRSS2 scores (P =0.039), and were more likely to have “high” or “intermediate” NCCN risk strata (P =0.010). Among patients with CI, AAs were more likely than CAs to have extra-prostatic extension (P =0.026) and less likely to have undergone a prior prostate biopsy (P =0.043). Patients without CI were more likely than patients with CI to have positive tumor margins (P =0.035) and SV invasion (P =0.013). There were no significant relationships between race and CI, and changes in either total Gleason score or stage from biopsy to RP. Conclusions: This study showed that AAs and patients without CI had more advanced forms of PCa (possibly due to PSA detection biases). Findings did not reveal any significant link between race and CI. Larger studies are needed to confirm these results and better understand the relationship between race, CI, and PCa.
The impact of systemic chemotherapy on circulating epithelial tumor cells (CETC) in breast cancer
Authors: K. Pachmann, O. Camara, U. Hammer, C. Joerke, S. Krauspe, C. Rabenstein, I. Runnebaum, K. Hoeffken
Journal: Journal of Clinical Oncology (2008)

11001 Background: The number of CETC can be influenced by natural shedding of cells from the tumor, mobilization of tumor cells by diagnostic and therapeutic manipulations (mammography, surgery), apoptosis and cell death. Here we report on the influence of systemic chemotherapy on the number of CETC. Methods: Tumor cells were quantified with an automated microscope (Laser Scanning Cytometer® or Olympus Scan R) from anticoagulated blood drawn before each new therapy cycle and before and after surgery from 70 patients treated with primary systemic chemotherapy. After red blood cells lysis leucocytes were stained with PE-anti-CD45 and tumor cells with FITC-anti-EpCAM and changes registered as % increase or decrease. The same was performed for 150 patients treated with adjuvant therapy and until 3 weeks after the end of chemotherapy. The response of CETC to therapy was correlated to outcome. Results: Almost all breast cancer patients had CETC before therapy, the number of which correlated with tumor size. During primary systemic therapy the variable initial decrease in cell numbers highly correlated with the final tumor size reduction. In spite of a subsequent re-increase in all neoadjuvantly treated patients, the reduction in CETC also predicted for relapse free survival. In response to adjuvant systemic therapy CETC showed three typical groups of response pattern. 1. Reduction in CETC more than tenfold 2. Marginal changes throughout therapy. 3. Increase or initial response and subsequent re-increase more the tenfold in numbers of CETC. During the post-therapy observation interval of 4.5 years, no relapse occurred in the group of patients with good response, whereas most relapsing patients are found in group 3 with an 11 - 16fold hazard ratio. Conclusion: Monitoring CETC will not only provide the earliest and most reliable indicator of successful neoadjuvant treatment and spare patients unnecessary treatment. It also, for the first time, allows monitoring of therapy efficiency in the adjuvant situation which is highly predictive for relapse free survival. This warrants further therapy studies to control what patients may benefit from additional or modified therapy already before metastases appear. No significant financial relationships to disclose.
The clinical significance of SWI/SNF complex in pancreatic cancer.
Authors: Masakatsu Numata, Soichiro Morinaga, Takuo Watanabe, Hiroshi Tamagawa, Naoto Yamamoto, Manabu Shiozawa, Kameda Yoichi, Shinichi Ohkawa, Takashi Oshima, Norio Yukawa, Yasushi Rino, Makoto Akaike, Munetaka Masuda, Yohei Miyagi
Journal: Journal of Clinical Oncology (2013)

149 Background: Chromatin remodeling factors have been the subject of great interest in oncology. However, little is known about their role in pancreatic cancer. The objective of this study is to clarify the clinical significance of SWI/SNF complex, one of the major chromatin remodeling machineries, in patients with pancreatic cancer. Methods: 68 cases with pancreatic cancer who underwent R0, 1 resection were enrolled. Cancer tissues were processed to tissue microarray, then stained immunohistochemically by using antibody of SWI/SNF components; BRM, BRG1, BAF250a, BAF180, and BAF47. The correlation of expression level and clinicopathological outcome including overall survival were analyzed. Results: Expression level of the SWI/SNF components was categorized as low or high according to the median value of Histo score. Statistical analysis revealed that related factors were tumor size, T factor, M factor, lymphatic invasion, and Stage in BRM, histology and Stage in BRG1, tumor size in BAF180, lymphatic invasion in BAF47, respectively. Multivariate Cox propotional hazard analysis showed high-BRM and low-BAF180 expression level were independent predictors of worse survival in patients with pancreatic cancer. The hazard analysis was also examined in the patients treated with adjuvant gemcitabine, indicating that high-BRM, and low-BAF180 were independent prognostic factors for poor survival. Conclusions: These results suggest that the specific cofactors of SWI/SNF chromatin remodeling complex certainly have roles in pancreatic cancer. High-BRM, and low-BAF180 are useful markers for prognosis of pancreatic cancer.
Phase Ib results of c-MET inhibitor ARQ 197 in combination with gemcitabine in a cohort of patients (pts) with advanced breast, ovarian, and uterine tumors.
Authors: L. H. Camacho, S. Pant, M. N. Saleh, G. Abbadessa, J. Kazakin, B. E. Schwartz, J. C. Bendell
Journal: Journal of Clinical Oncology (2011)

3077 Background: ARQ 197 is a non-ATP competitive selective inhibitor of c-MET. In vitro data suggest its synergy with gemcitabine. This study evaluates safety, pharmacokinetics (PK), biomarkers, and preliminary efficacy of the combination treatment in pts with advanced solid tumors. Here we present results of the cohort of pts with metastatic breast, ovarian, and uterine carcinoma. Methods: Multicenter, phase Ib 3+3 dose escalation trial. Oral ARQ 197 administered at doses of 120-360 mg bid across different schedules (continuous vs. continuous with 1 week [wk] break every 2 or 3 wks) in combination with a fixed gemcitabine at 1,000 mg/m2/weekly 3 every 4 wks. Results: As of January 4, 2011, a total of 32 pts with metastatic breast (12), ovarian (14), and uterine (6) carcinoma were enrolled in the study (ECOG 0:1 = 21:11; mean age 61, range 35-77 yrs; with median number of prior systemic therapies = 4 [1–9]). Seven pts had progressed to prior gemcitabine. Adverse events (AEs) considered at least possibly treatment-related were reported in 29 (91%) of these pts. Most commonly observed AEs (>10%) included thrombocytopenia (21; 66%, 4 G 3-4), anemia (21; 66%, 6 G 3-4), neutropenia (20; 63%, 7 G 3-4), fatigue (11; 34%, 3 G 3-4), nausea (9; 31%, 2 G 3-4), vomiting (6; 19%, 1 G 3-4), and leucopenia (4; 13%, 2 G 3-4). Three pts experienced treatment-related serious AEs (pancytopenia, thrombocytopenia, hypotension and interstitial lung disease, grade 3). Post-baseline tumor assessment was done in 27 evaluable pts; of them, 12 remained on study for >10 wks (mean 22; range 10-36), 5 (2 breast, 1 uterine, 2 ovarian) attained partial response (response rate 19%), and 15 demonstrated decline (4-87%) in tumor markers (CA15.3, CA125, CEA). In this study, 2 pts (ovarian and breast) with PR and 2 with SD (breast) had failed prior gemcitabine. Details on efficacy and scheduling will be presented. Conclusions: Orally administered ARQ 197 at the MTD of 360 mg bid in combination with gemcitabine is generally well tolerated and shows encouraging signs of antitumor activity in the presented tumor types.
Multicenter phase II study of FOLFOX or biweekly XELOX and cetuximab as first-line treatment in patients with wild-type KRAS/BRAF metastatic colorectal cancer (mCRC) (FLEET study).
Authors: Ho Min Kim, Hitoshi Soda, Shoichi Hazama, Takao Takahashi, Naoki Nagata, Masahito Kotaka, Emiko Kono, Itsurou Terada, Mutsumi Fukunaga, Koji Oba, Junichi Hasegawa, Junichi Sakamoto, Hideyuki Mishima
Journal: Journal of Clinical Oncology (2013)

463 Background: Cetuximab and chemotherapy as first-line therapy for patients with KRAS wild type prolong survival. However, COIN trial has not demonstrated the survival benefit of FOLFOX or XELOX and cetuximab therapy. Few data are available on its benefit for patients with KRAS and BRAF wild-type. Methods: The aim of this study was to assess the efficacy of first-line FOLFOX or bi-weekly XELOX and bi-weekly cetuximab in KRAS/BRAF wt mCRC. Chemonaive patients received FOLFOX or biweekly XELOX (oxaliplatin 85 mg/ m 2 /day 1 plus capecitabine 2000/m 2 /days 1-7) and biweekly cetuximab 500mg m 2 / day 1 every 2 weeks. Primary endpoint was response rate(RR), other secondary endpoints were PFS, OS, DCR, safety, DI and resection rate. KRAS test (codon12,13) and BRAF test (V600E) by direct sequence were performed in Yamaguchi University. Patients with KRAS/BRAF wt were enrolled in this study. The regimen of FOLFOX or XELOX were selected by investigator’s preference, not randomized. Results: From April 2010 to May 2011, 139 pts were preregistered. KRAS and BRAF were examined from paraffin-embedded sample. 70 (50.3%) pts were KRAS/BRAF wt, and 62 pts were enrolled: The main characteristics of the entered pts were: sex (M/F) 34/28, median age 66 yrs (range 34-83 yrs). Grade 3/4 adverse events were leucopenia 4.8%, neutropenia 25.8%, skin toxity (paronychia/fissure) 9.7%, and acne 9.7%. Two CR (3.2%) and 40 PR (64.5%), 15 SD (24.2%) and 3 PD (4.8%) 2NE were observed, with an overall response rate of 67.7% and a disease control rate (CR+PR+SD) of 91.9%. The RR of FOLFOX or XELOX were 64.9% (24/37) and 72.0% (18/25), DCR were 89.2% and 96% respectively. Conclusions: FLEET was the first multicenter phase II study with prospective KRAS/BRAF analysis as a predictive biomarker for cetuximab in first-line mCRC in Japan. Results of this study indicate that both biweekly combination regimens are feasible, tolerable, and clinically active. Biweekly XELOX+cetuximab study (FLEET2) is ongoing. Clinical trial information: UMIN000003253.
Ribosomal Protein Genes S10 and S26 Are Commonly Mutated in Diamond-Blackfan Anemia.
Authors: Hanna T. Gazda, Mee Rie Sheen, Leana Doherty, Adrianna Vlachos, Valerie Choesmel, Marie-Francoise O'Donohue, Hal E. Schneider, Catherine Clinton, Colin A. Sieff, Peter E. Newburger, Sarah E. Ball, Edyta Niewiadomska, Michal Matysiak, Bertil Glader, Eva Atsidaftos, Jeffrey M. Lipton, Pierre-Emmanuel Gleizes, Alan H. Beggs
Journal: Blood (2009)
A phase II, single arm clinical trial involving an alternative cancer treatment psorinum therapy in patients with unresectable metastatic colorectal carcinoma.
Authors: Aradeep Chatterjee, Amitava Chakraborty, Sudin Bhattacharya, Radhe S. Bhakta, Ashim Kumar Chatterjee, Jaydip Biswas
Journal: Journal of Clinical Oncology (2012)

2581 Background: We prospectively studied the clinical efficacy of an alternative cancer treatment “psorinum therapy” in treating unresectable metastatic colorectal carcinoma (UMCRC). Methods: Our study was phase-II, open level, single arm and single stage. Participants eligibility criteria included (1) histopathology confirmation of the malignancy (2) metastatic and unresectable disease status (3) No prior conventional cancer treatments (4) Karnofsky performance status between 40 – 70%. The primary outcome measures of the study were (1) to assess the radiological tumor response rate (using CT scanning procedure and following the RECIST criteria); (2) to assess how many participants survived at least 1 yr, 2 yrs, 3 yrs, 4 yrs and finally, after 5 yrs of the study. The secondary outcome measure was to assess the side effects of the investigational anti- cancer drug (psorinum) if any. Psorinum (an alcoholic extract of scabies slough and pus cells) was administered orally at a dose of 0.02ml / kg body weight / day as a single dose on an empty stomach for a complete course duration of 2 yrs to all the participants along with allopathic and homeopathic supportive cares. Results: 105 participants included in the final analysis at the end of the study. According to the RECIST criteria, complete response occurred in 12 (11.43%) cases and partial response occurred in 38 (36.19%) cases. 76 (72.38%) of them survived at least 1 yr, 58 (55.24%) survived at least 2 yrs, 51 (48.57%) survived at least 3 yrs, 43 (40.95%) survived at least 4 yrs and 37 (35.24%) of them survived at least 5 yrs. These participants didn’t receive conventional or any other investigational cancer treatments. Conclusions: The results of the study show clinical efficacy of psorinum therapy in treating patients with UMCRC. The investigational drug psorinum is non- toxic. Randomized controlled clinical trial should be conducted for further investigation of this alternative cancer treatment in treating unresectable metastatic colorectal carcinoma to integrate it into the mainstream of oncology treatments.
Metastasectomy or radiofrequency ablation for treatment for colorectal cancer liver metastasis: Comparison of recurrence rates and identification of risk factors for local recurrence.
Authors: Naik Vietti-Violi, Pierre E. Bize, Rafael Duran, Nicolas Demartines, Nermin Halkic, Jean-Francois Knebel, Alban Denys
Journal: Journal of Clinical Oncology (2016)

769 Background: Metastasectomy and radiofrequency ablation (RFA) are currently use for treatment of colorectal cancer (CRC) liver metastasis aiming for total tumor ablation with sparing liver parenchyma. Literature is lacking of studies comparing results and risk of recurrence between both techniques. We aim to compare recurrence rate after RFA and metastasectomy for CRC liver metastasis and to define which lesion is the best candidate for each treatment. Methods: By a lesion-by-lesion analysis, we reviewed 121 metastases treated by metastasectomy (43 patients, median follow up 798 days) and 110 metastases treated by RFA (60 patients, median follow up 590 days). Rate of local recurrence (LR) and hepatic recurrence (HR) were compared. We analyzed patients and primary tumor characteristics, looked for predictive factors for recurrence in metastasis data: size, deepness in liver, distance to hepatic veins, pathological resection margins in case of surgery. Analysis were performed using Chi Square and logistic regression in uni and multivariate analysis. Results: Patients and primary tumor characteristics were similar. Metastasis size was larger in metastasectomy group (18mm, range 2-90mm and 15mm, range 3-55mm; p = 0.03). Lesions were located deeper in the liver parenchyma in RFA group (20mm, range 3-51mm and 26mm, range 6-59mm; p &lt; 0.001). Rate of LR and HR were nearly statistically different in favor of RFA: LR was 19% for metastasectomy group and 10% for RFA group (p = 0.06, delay: 245 and 289 days, p = 0.56), HR were 78% for metastasectomy and 66% for RFA (p = 0.054, delay: 226 and 235 days, p = 0.81). Predictive factors for recurrence in metastasectomy group: R1 status (p = 0.03) and metastasis deepness (p = 0.02). Metastasis deepness and proximity to hepatic veins increased risk for R1 (p = 0.04 and p &lt; 0.001 respectively). We found no predictive factor for recurrence in RFA group. Conclusions: Pending proper selection (small lesions visible under imaging guidance), RFA tends to have a lower recurrence rate than metastasectomy. Lesions localized in depth in the liver parenchyma, close to hepatic veins are at risk of LR after metastasectomy.
Variation in adherence to QOPI core measures based on tumor type.
Authors: Sunil M. Patel, Amit Sarma, Mee-chung Puscilla Ip, Laurie Sturdevant, Leslie Kian, Diane Schaub, Rachel Leigh Theriault, Douglas A. Nelson, Nikesh Ramesh Jasani, Michael Fisch
Journal: Journal of Clinical Oncology (2014)

280 Background: QOPI measures fall into one of three categories: (1) core, (2) disease-specific (breast, colon, lung, non-Hodgkin lymphoma, gynecologic cancers), or (3) domain-specific (symptom control, end-of-life). For each data collection period (DCP), participating sites choose to submit data in at least one disease- or domain-specific module. Charts are identified and abstracted for the selected module(s) based on eligibility criteria. The same charts are also abstracted for core measures. Our group hypothesized that the case mix resulting from choice of module(s) would impact performance for a subset of core measures. Methods: The MD Anderson Regional Care Centers have participated in QOPI over nine DCPs from Fall 2009 to Spring 2014. Unexplained variation was identified in staging documentation (core measure 2) and chemotherapy intent documentation (core measure 10). For each DCP, QOPI chart-level data were reviewed. Adherence for each measure was tabulated and stratified by tumor type. Due to small sample sizes within each DCP, data were pooled and analyzed with descriptive statistics and chi-square testing. Results: Over nine DCPs, stage and chemotherapy intent were documented in 89.1% and 81.3% of charts, respectively. There was a significant association between tumor type and documentation of stage (χ 2 (4) = 30.4, N=727, p &lt;.001) and chemotherapy intent (χ 2 (4) = 157.5, N=534, p &lt;.001). Documentation of stage and chemotherapy intent was highest for breast (100%, 93.6%) and colorectal cancers (92.7%, 92.1%) and lowest for NHL (71.8% 32.8%). Conclusions: Observed variation in documentation of stage and chemotherapy intent was primarily due to tumor type. Reasons for this observation are myriad and likely include factors related to the providers, the practice, the measures, and differing complexity of tumor types. This variation in quality scores by tumor type (driven by module selection) could have significant implications in today’s pay for performance environment. [Table: see text]
Initial results of patients with early-stage prostate cancer on active holistic surveillance.
Authors: Aaron Katz, Andrew S Fontes, Kaitlin E. Kosinski
Journal: Journal of Clinical Oncology (2016)

19 Background: There is currently no consensus on how active surveillance should be utilized in order to optimize the benefit of patients with prostate cancer (PCa) to prevent overtreatment. Our institution’s protocol, known as Active Holistic Surveillance (AHS) integrates MRI screening in the place of serial biopsies. Nutritional supplements and lifestyle changes are also suggested in order to provide a holistic way to reduce progression. We look to compare definitive treatment rates of our cohort on AHS to other publications in the literature. Methods: A retrospective chart review was conducted on 200 patients placed on active surveillance for low and low-intermediate risk PCa under D’Amico criteria from February 2002 to July 2015. Enrollment criteria was defined by clinical stage (T1c), PSA under 20 ng/mL, diagnosis of a Gleason 6 or Gleason 7 with a tumor volume of &gt;50%, and a PSA doubling time of greater than 1 year. The main objective of the study was to evaluate the rate of patients discontinuing AHS to receive definitive therapy and reasons for leaving our AHS protocol. Results: 200 patients (age 44-84 years) have a median follow-up of 40 months (range 4-161). A total of 24 out of 200 patients (12%) moved on to definitive treatment. For patients on AHS before 2010 until 2012, the rates of definitive treatment were 0%. In 2013, 8 patients (4%) received definitive treatment. In 2014, 12 patients (6%) received definitive treatment. In 2015, 4 patients (2%) received definitive treatment to date.The average treatment rate per year is 4%. Reasons for 24 patients discontinuing AHS included biopsy progression (16.67%), MRI progression (29.17%), MRI progression with biopsy confirmation (29.17%), patient preference (20.83%), and 1 patient was deceased due to an unrelated illness (4.17%). Conclusions: Low rates of discontinuation compared to other publications in the literature demonstrate that AHS can be a successful protocol for low-risk and low-intermediate risk PCa patients, and that a holistic approach can be beneficial to active surveillance patients.