tbuckley/cabot-search huggingface dataset:
Predictors of second- and third-line chemotherapy receipt in stage IV colon cancer Medicare beneficiaries.
Authors: Emily S Reese, Ebere Onukwugha, Nader Hanna, Brian S. Seal, C. Daniel Mullins
Journal: Journal of Clinical Oncology (2013)

588 Background: The prognosis for elderly patients with metastatic colon cancer (mCC) is poor with 5-year survival rate of 6 %. There is limited evidence to explain why some elderly mCC patients progress through multiple lines of treatment and others with similar clinical characteristics do not. This study examines the predictors of second- and third-line chemotherapy receipts in Medicare beneficiaries with mCC who initiate treatment. Methods: Using the SEER-Medicare dataset, elderly beneficiaries diagnosed with mCC from 2003-2007, were followed until death or censoring in 2009. Treatment lines were classified in combinations of chemotherapy and biologics. Logistic regression was used to predict receipt of treatment and subsequent treatment. Results: Among 3,266 beneficiaries diagnosed with mCC and initiated therapy, 1,440 progressed to 2nd line treatment and 274 progressed to 3rd line treatment. The strongest predictors of progressing to 2nd line treatment was surgery of the primary tumor site (OR: 2.42, 95% CI: 2.17-2.70) and regional/distal sites (OR: 1.32, 95% CI: 1.14-1.53) and marital status (OR: 1.64, 95% CI: 1.47-1.83). Older beneficiaries (80-84 years (OR: 0.31, 95% CI: 0.26-0.37) and &gt; 85 years (OR: 0.10, 95%CI: 0.08-0.12)) and those with poor performance status indicators (walk aid (OR: 0.46, 95% CI: 0.26-0.82), wheelchair use (OR: 0.43, 95% CI: 0.29-0.64), and use of oxygen (OR: 0.54, 95% CI: 0.41-0.69)) were less likely to proceed to 2nd line treatment. Older age was the biggest predictor of not proceeding to third-line treatment (80-84 years (OR: 0.42, 95% CI: 0.28-0.61) &amp; &gt; 85 years (OR: 0.10, 95%CI: 0.05-0.19)). No variables were statistically significant in predicting receipt of third-line chemotherapy. Conclusions: Surgery of the primary tumor site and of regional/distal sites were the most significant clinical variables predicting whether or not elderly patients proceed to second-line chemotherapy. Sociodemographic variables also predicted receipt of second-line chemotherapy.
Predictors of primary and distant site surgery in patients with stage IV colorectal cancer.
Authors: Lori Uyeno, Rebecca A. Nelson, Gagandeep Singh, Julio Garcia-Aguilar, Joseph Kim
Journal: Journal of Clinical Oncology (2012)

499 Background: Operative management of primary tumor and distant metastases in stage IV colorectal cancer is highly variable and removal of asymptomatic primary tumors in the setting of distant disease remains controversial. The purpose of our study was to describe the patterns of surgery in stage IV colorectal cancer patients in a US population-based cohort and explore patient and tumor characteristics associated with treatment selection and survival. Methods: Stage IV colorectal cancer patients in Los Angeles County from 2000 to 2006 were identified using the LA County Cancer Surveillance Program registry. The cohort included 2,956 patients (2,211 stage IV colon and 745 stage IV rectal cancers). Cox proportional hazard models were used to estimate survival. Treatment was categorized as primary surgery, distant site surgery, or chemotherapy only. Multivariate logistic regression was used to identify patient and tumor variables associated with treatment. Results: Greater than 65% of the stage IV colorectal cohort had primary tumor surgery of which 51% had chemotherapy. Only 4.5% had surgery to remove distant disease. Patients who had chemotherapy only and no surgery was 15%. Median survival of primary surgery, distant surgery, or chemo only was 14, 21, and 11 months. Multivariate Cox regression revealed that primary surgery and distant surgery had a decreased risk of death compared to no surgery (HR= 0.4 p&lt;.0001, HR=0.7 p&lt;.004). Multivariate logistic regression was used to identify predictors associated with treatment selection. Patients &gt;65 years (p&lt;.003); low socioeconomic status (p&lt;0.05); and rectal tumors (p&lt;.0001) were less likely to have surgery of the primary tumor. Female gender (p&lt;.0001) and primary tumor surgery (p&lt;.0001) were predictors for distant site surgery whereas age&gt;65 years (p&lt;.0001) had a negative association. Conclusions: Our population-based study of stage IV colorectal cancer patients suggests that the majority of stage IV patients with distant disease have surgery, but less than 5% have surgery for distant disease. Although survival of stage IV colorectal patients is improved with surgery, increasing age, low socioeconomic status, and rectal tumors are negative predictors for undergoing surgery.
The preclinical anti-angiogenic and pro-apoptotic activity of lenalidomide in urothelial carcinoma (UC).
Authors: Weiguo Jian, Jonathan M. Levitt, Keith S. Chan, Seth P. Lerner, Guru Sonpavde
Journal: Journal of Clinical Oncology (2013)

294 Background: Lenalidomide (Len) is an immunomodulatory drug (IMiD) approved for hematologic conditions and demonstrates immune modulation, anti-angiogenic activity and direct anti-tumor cytotoxicity. A rationale can be made to evaluate the preclinical activity of Len in UC. Methods: The in vitro anti-tumor activity of Len was evaluated in 4 human (5637, TCC-SUP, RT4, RT112) and 1 murine (MB49) cell line. Anti-proliferative activity activity (MTT assay), apoptosis (Annexin-FITC immunohistochemistry [IHC], flow cytometry) and cell viability by colony forming assay were measured. In vivo activity of daily oral Len 10 mg/kg or placebo orally for 5 days a week for up to 4 weeks was examined in syngeneic immunocompetent C57BL/6 mice bearing subcutaneous (SC) MB49-Luc25 tumors and RT4 subcutaneous xenografts. Tumors underwent immunohistochemistry (IHC) for microvessel density (CD31), apoptosis (cleaved caspase [cc]-3) and CD3+/CD20+ lymphocyte infiltration. Cereblon, a molecular target of Len was analyzed by IHC. Results: In vitro cultures for 3 days with daily repletion of Len showed significant pro-apoptotic activity (flow cytometry) at low micromolar concentrations attainable in human subjects (2.2 µM) against RT4 cells, a superficially invasive human UC cell line. Long-term cultures of RT4 cells for 2 weeks with daily repletion of Len significantly reduced cell viability and colony forming ability. Cereblon expression was numerically lower in sensitive RT4 cells compared to resistant 5637 cells (p=NS). In the immunocompetent model in vivo, Len did not decrease tumor size, or increase cc-3 and CD3+/CD20+ lymphocytes, but post-Len tumors exhibited decreased CD31 (p&lt;0.05). In RT4 xenografts, Len significantly decreased the size of tumors and CD31, and increased cc-3 (all p&lt;0.05). Cereblon expression increased in Len treated RT4 xenografts (p=0.024). Conclusions: Lenalidomide demonstrated selective preclinical activity against superficially invasive low grade human UC cells attributable to direct tumor cell apoptosis and anti-angiogenic activity. Clinical evaluation in patients with low grade or non-invasive UC and further study of cereblon as a predictive biomarker may be warranted.
Predictors of gastrointestinal toxicity during pelvic radiotherapy.
Authors: T. Jonathan Yang, Jung Hun Oh, Christina Son, Aditya Apte, Joseph O. Deasy, Abraham Jing-Ching Wu, Karyn A. Goodman
Journal: Journal of Clinical Oncology (2013)

472 Background: To identify clinical and dosimetric factors associated with acute gastrointestinal (GI) toxicities due to pelvic radiotherapy (PRT) in patients with rectal cancer. Methods: We analyzed 177 consecutive rectal cancer patients treated between 2007-2010. Clinical information including age, gender, stage, chemotherapy, and weekly proctitis and diarrhea grade (CTCAE 3.0) during PRT were obtained. The bowel, rectum, and anal canal were contoured on CT treatment planning images. Doses to GI structures were calculated using the original treatment plan, and dose-volume parameters were extracted for modeling using CERR software. Logistic regression models were used to test the association between GI toxicity grade and predictors. Results: The mean age was 59; 76 (43%) patients were women; 166 (94%) received concurrent 5-FU based chemotherapy. Over half (56%) were treated with intensity modulated radiotherapy (IMRT), 44% were treated with 3D conformal RT (3DCRT). Grade 2+ proctitis and diarrhea were seen in 57 (32%) and 44 (25%) patients, respectively. On univariate analysis, age inversely predicts for Grade 2+ proctitis (Rs=-0.22, p=0.009). 3DCRT (Rs=0.27, p=0.001) and female gender (Rs=0.28, p=0.0008) predict for Grade 2+ diarrhea. On multivariate analysis, the normal tissue complication model including volume of anal canal receiving &gt;15Gy, anal canal minimal dose, and age was most predictive of Grade 2+ proctitis (AUC=0.67, Rs=0.25, p&lt;0.001). The model including bowel volume receiving 45Gy, female gender, and use of 3DCRT was highly predictive of Grade 2+ diarrhea (AUC=0.76, Rs=0.35, p&lt;0.001). Patients treated with IMRT had significantly less bowel volume receiving ≥ 45Gy compared to 3DCRT (V45Gy=10.9% vs. 21.7%, p&lt;0.0001). Conclusions: In this analysis of a large cohort of patients receiving PRT for rectal cancer, we identified clinical and dosimetric predictors of acute GI toxicity. Younger patients and women have higher rates of acute Grade 2+ proctitis and diarrhea, respectively. IMRT resulted in a 50% relative reduction in bowel volume receiving 45Gy and a lower risk for clinically significant diarrhea. Dose-volume constraints using these parameters should be considered, particularly in higher risk patients.
Effect of shear stress on structure and function of polyplex micelles from poly(ethylene glycol)-poly(l-lysine) block copolymers as systemic gene delivery carrier
Authors: Kaori M. Takeda, Yuichi Yamasaki, Anjaneyulu Dirisala, Sorato Ikeda, Theofilus A. Tockary, Kazuko Toh, Kensuke Osada, Kazunori Kataoka
Journal: Biomaterials (2017)
Blinded independent central response assessment using RECIST, mRECIST, and CHOI criteria in patients treated with sorafenib for advanced hepatocellular carcinoma (HCC).
Authors: Mohamed Bouattour, Johanna Wassermann, Onorina Bruno, Chantal Dreyer, Beatrice Larroque, Laurent Castera, Valérie Vilgrain, Jacques Belghiti, Eric Raymond, Sandrine J. Faivre
Journal: Journal of Clinical Oncology (2012)

172 Background: Despite survival benefit in patients with advanced HCC, sorafenib has been infrequently associated with changes in tumors dimensions, challenging standard RECIST criteria. Experts have suggested new response criteria based on changes in tumor vascularization and density (mRECIST and Choi). Aim is to evaluate response in patients treated with sorafenib using three different methods and their correlation with overall survival (OS) Methods: Radiological evaluations were performed from consecutive patients treated with sorafenib from January 2007 to February 2009. Patients were considered evaluable if CT scans were performed within 6 weeks before sorafenib and in the three months following treatment initiation at the first evaluation. A radiologist blinded for clinical data performed tumor evaluations according to RECIST, mRECIST, and Choi criteria. Best response was correlated with OS Results: Among 82 patients, 60 were evaluable (median age 63, male/female 52/8). The majority of patients were Child A (80%). Tumor staging showed BCLC stage B and C in 33% and 67%, respectively. The median duration of treatment with sorafenib was 6.6 months (range 1.2-16.5). Tumor evaluations by CT scan were performed in a median of 2.1 months (range 1.5-3.2). For the entire cohort, median OS was 9.9 months, and survival rates at 6, 12, and 24 months were 69%, 39% and 22%, respectively. The table summarizes the best responses measured using RECIST, mRECIST, and Choi criteria. Conclusions: Better OS was observed in patients with complete/partial response than in patients with stable disease and progression, regardless the type of radiological criteria. However, mRECIST and Choi criteria identified more adequately than RECIST subgroups of patients with complete/partial response who also experienced longer survival [Table: see text]
Effect of genetic variants in <i>CYP2C8</i>, <i>CYP3A4</i>, <i>CYP3A5</i>, and <i>ABCB1</i> on paclitaxel pharmacokinetics
Authors: A. Sparreboom, S. Marsh, A. Henningsson, M. O. Karlsson, A. Garsa, W. J. Loos, J. Verweij, H. L. McLeod
Journal: Journal of Clinical Oncology (2005)

2019
Long Term Results of High-Dose Melphalan and Autologous Stem Cell Transplantation in Non-Amyloid Monoclonal Immunoglobulin Deposition Disorders.
Authors: Saulius Girnius, David C. Seldin, Karen Quillen, Kathleen T. Finn, Nancy T. Andrea, John Mark Sloan, Vaishali Sanchorawala
Journal: Blood (2009)
The role of HPV genotypes and persistence in follow-up of cervical intraepithelial neoplasia after treatment.
Authors: Y. Huang, L. Wu, J. Zuo, N. Li, J. An, J. Hu, M. Huang
Journal: Journal of Clinical Oncology (2011)

1561 Background: HPV testing is considered as an acceptable strategy for surveillance after treatment of cervical intraepithelial neoplasia (CIN). The role of high risk HPV (HR-HPV) genotypes and persistent infection in follow-up remains unclear. Methods: A prospective observational study was conducted on 249 patients with CIN (CIN1=11, CIN2=34, CIN3==204) after conization. Besides traditional follow-up with cytology and colposcopy, HPV genotyping test identifying 13 HR-HPVs (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) was performed every 6 months after treatment. Endpoint of this study was a histological confirmed CIN during follow-up. Results: 17 recurrences occurred during a median follow-up of 28 months. HR-HPV positive rate decreased over time (29.3% (73/249) for 6 months, 20.1% (50/249) for 12 months, and 15.3% (38/249) after 12 months, respectively). HR-HPV positive results predicted 88.2% (15/17) of recurrences. The most common HR-HPV genotypes appeared post-treatment were HPV 16 (19.3%), HPV 58 (12.0%), HPV 52 (8.0%), HPV18 (4.4%) and HPV33(4.0%). HPV 16, HPV 58 and HPV52 remained as the top three most frequent genotypes in type specific persistent infection. There was no correlation between recurrence and individual HR-HPV infections such as HPV 16, HPV 52 or HPV58 (P>0.05). Recurrent disease was more likely to occur in patients with multiple HR-HPV infection than with single infection (11/27 vs. 4/72, P<0.001). Persistent HR-HPV infection had a higher risk of recurrence than transient infection as compared to negative (hazard ratio [95%CI]: 28.8 [6.35-103.96] for persistence, 1.40 [0.12-14.35] for transition, P<0.0001). Type specific HPV infection had an elevated risk of recurrence (hazard ratio [95%CI]: 40.86 [9.01-185.36]). Conclusions: HPV genotyping test is useful in follow-up. Multiple HR-HPV infection and persistent especially type specific persistent HR-HPV infection indicates a higher risk of recurrence, unlike appearance of the most common HR-HPV genotypes (HPV16, 58, 52) post-treatment.
Professional practice gaps and barriers to optimal care of renal cell carcinoma (RCC) among oncologists in the United States.
Authors: Brian I. Rini, Andrew Bowser, Patrice Lazure, Luba Goldin, Sophie Peloquin, Sean Hayes, Jim A. Mortimer, Eric D Peterson, Thomas E. Hutson
Journal: Journal of Clinical Oncology (2014)

404 Background: New therapies for advanced RCC have improved patient outcomes while increasing the complexity of care. We sought to quantify practice gaps and barriers to optimal care among oncologists treating patients with RCC at academic and/or community centers in the United States. Methods: In total, 248 oncologists were recruited for a 2-phase (qualitative/quantitative) study. Eligible participants who had fully completed either one of the 2 phases were included in the analyses (n = 169). In the first phase, participants (n = 27) completed a brief online case-based survey and a 45-minute telephone interview on the attitudinal, contextual, and behavioral factors that influenced diagnosis and treatment. Selected interviews were transcribed and analyzed through thematic analysis. In the second phase, participants (n = 142) completed an online survey including case vignettes. Respondents’ answers were compared with optimal answers based on National Comprehensive Cancer Network kidney cancer guidelines (version 1.2013) and evidence-based opinions of 2 RCC experts. Results: Forty-six percent of participants correctly identified all predictors of short survival/poor risk in RCC. Regarding treatment options for a poor-risk patient, 37.5% chose temsirolimus and 11% sunitinib, both felt to be reasonable options. In a scenario focused on dose and treatment modification in a patient with treatment-related hypertension, 34% selected a nonoptimal management option. In a scenario focused on the importance of recognizing clinical symptoms as a component of treatment decision making, 40% of respondents were in agreement with expert- and evidence-supported treatment approach. Detailed results of this analysis will be presented. Conclusions: This study revealed clinically relevant practice performance gaps that affect delivery of care and patient health outcomes. Not recognizing predictors of poor risk or the importance of evaluating clinical symptoms can result in missed opportunities to change treatment strategy, leading to suboptimal outcomes. These results will support design of educational programs and performance improvement interventions.
Engaging new media to drive advance care planning.
Authors: Mary Frances Mulcahy, Daniel M. Gaitan, Randi Belisomo
Journal: Journal of Clinical Oncology (2013)

153 Background: Though Congress enacted the Patient Self-Determination Act in 1991, only 18-36% of Americans have completed an advance directive. Less than half of severely ill patients had an advance directive in their medical record, only one in three with a chronic illness completed an advance directive, and studies suggest that two-thirds of physicians whose patients had advance directives were unaware of the existence of the documents. The Act required healthcare facilities to provide written information on rights to make treatment decisions and to make information available to patients who did not have an advance directive. There was a mandate directing HHS to conduct an awareness campaign about advance directives. The low acceptance of the directives demonstrates a failure to educate patients about their rights. Hypothesis: A patient-centered approach to end of life issues will generate better communication and result in greater acceptance of advance directives- achieving the goals of the Patient Self-Determination Act. Methods: A survey of 196 people showed that 67.7% felt that end of life issues were not covered enough in the media. We created a Newswire using WordPress and posted an average of three news stories weekly on topics pertaining to end of life. Posts were generated from existing media coverage and original reporting. The topics included culture, society, politics, healthcare, caregiving, law, advance care planning, hospice, and palliative care services. We tracked the number of views, the most viewed reports, monthly traffic and referral sources. We established Facebook, Twitter, and Pinterest accounts. We tracked followers, likes, re-tweets, pins, and shares. Results: From 8/2012 through 2/2013, the number of views increased from 566 to 2,452 with a peak of 3,809 in 11/2012. The most viewed day was 11/7/2012, the day following Election Day. The most viewed reports to date have been “Caregiver Discrimination Against LGBT Seniors,” “Psychedelic Drugs at the End of Life,” and “POLST Moving Forward in Illinois.” The referral sources in descending order are Facebook, Twitter, and Yahoo. Conclusions: We demonstrated that there is an interest in patient-centered topics pertaining to the end of life and that social media drives interest, education and conversation.
Phase II study of low-dose paclitaxel and cisplatin as second-line therapy in 5-fluorouracil and platinum pretreated gastric cancer
Authors: K. W. Lee, D. Y. Oh, J. H. Kim, D. W. Kim, S. A. Im, T. Y. Kim, S. S. Yoon, D. S. Heo, Y. J. Bang, N. K. Kim
Journal: Journal of Clinical Oncology (2005)

4194 Background: Paclitaxel has shown promising activity as a single agent in gastric cancer and has synergism with cisplatin in human gastric cancer cell lines. This study was performed to evaluate the efficacy and toxicity of an outpatient regimen composed of low-dose paclitaxel and cisplatin in patients with metastatic or relapsed gastric cancer who had progressed disease during or after treatment with 5-fluorouracil (5-FU) and platinum compounds. Methods: Patients with documented progression on or within 6 months of 5-FU and platinum-based chemotherapy were enrolled. As second-line treatment, paclitaxel 145 mg/m2 was administered intravenously over 3 hours, followed by cisplatin 60 mg/m2 on day 1 every 3 weeks in the outpatient setting. Results: Between October 2002 and June 2004, 28 patients (25 male and 3 female) were enrolled. As first-line treatment, 24 patients received 5-FU/cisplatin and 4 patients received 5-FU/oxaliplatin/leucovorin. Median age was 62.5 years. Of these patients, 8 (29%) had partial responses. Six (21%) had stable disease and 12 (43%) had progressive disease. Two patients (7%) were not evaluable because of early drop-out from this study due to treatment-related toxicities. With the median follow-up duration of 10.5 months, the median time to progression (TTP) in all patients was 2.9 months (95% confidence interval [CI]: 1.9∼3.9 months) and the TTP in responders was 4.3 months (95% CI: 3.1∼5.5 months). The median overall survival was 9.1 months (95% CI: 7.0∼11.2 months). The most common hematologic toxicity was grade 1∼2 anemia (43%). Grade 3 leucopenia developed in 7% and no other grade 3∼4 hematologic toxicity or neutropenic sepsis were observed. The most common non-hematologic toxicities were peripheral neuropathy (32%) and emesis (25%). One case (4%) of grade 4 emesis and 2 cases (7%) of grade 3 peripheral neuropathy were developed; 2 (7%) patients were dropped out from this study due to toxicities. No other grade 3∼4 non-hematological toxicities were observed. Conclusions: As second-line treatment, low-dose paclitaxel and cisplatin chemotherapy in the outpatient setting was active and had acceptable toxicities. No significant financial relationships to disclose.