tbuckley/cabot-search huggingface dataset:
The role of adjuvant radiotherapy in pathologically node positive prostate cancer.
Authors: Naresh Jegadeesh, Yuan Liu, Chao Zhang, Jim Zhong, Theresa Wicklin Gillespie, Omer Kucuk, Peter John Rossi, Viraj A. Master, Mehrdad Alemozaffar, Ashesh B. Jani
Journal: Journal of Clinical Oncology (2016)

28 Background: The postoperative management of prostate cancer with regional lymph nodal involvement (LNI) is controversial. Prospective evidence to guide the role of radiotherapy (RT) in this setting does not exist. Randomized studies demonstrate an improvement in disease-related outcomes with adjuvant RT in high-risk patients without LNI following prostatectomy (RP). Retrospective evidence supports the selective use of RT with LNI following extended pelvic lymph node dissection. It is unclear if this experience is generalizable to practice in the United States where extended dissection is uncommon. We sought to identify patients with LNI who may derive a survival benefit following adjuvant RT. Methods: The National Cancer Data Base was queried for M0 patients with prostate adenocarcinoma who underwent RP with pathologic LNI. Adjvuant RT was defined as delivered within 6 months following RP. Kaplan-Meier, log-rank test, and multivariable Cox proportional hazards regression were performed with overall survival (OS) as the primary outcome. Propensity score matching (PSM) was employed to further reduce treatment selection bias. Results: 7,902 patients diagnosed between 2003-2011 were eligible for analysis; 1,439 (18.2%) received RT. RT was more frequently employed in patients with lower Charlson-Deyo Comorbidity Score, higher T stage, &lt;5 nodes examined, ≥50% nodal positivity ratio, Gleason 8-10, ≥20 PSA, positive surgical margin, and &lt;65 years of age (all p &lt; 0.05). Five year OS was 87.6% vs. 85% in those receiving RT vs. not (p = 0.075). With androgen deprivation (ADT) (n = 3,265), 5-year OS was 87.2% vs. 82.7% in those receiving RT vs. not (p = 0.004). In multivariable analysis, the use of RT was independently associated with improved OS (HR 0.73, 95% CI 0.59-0.89, p = 0.002). 894 remained in each cohort following PSM. In this analysis, RT remained associated with OS (HR 0.66, 95% CI 0.51-0.85, p = 0.002). Conclusions: Adjuvant RT was associated with improved OS following RP in patients with LNI in this large generalizable retrospective analysis. This effect appears stronger in those receiving ADT. This series is the largest describing adjuvant RT in this population. In the absence of prospective evidence, these results may help guide therapy in this setting.
Compartment-Specific Bioluminescence Imaging Platform for the Open-Ended Identification of Novel Immunomodulatory Agents and High-Throughput Evaluation of Anti-Tumor Immune Function
Authors: Douglas W. McMillin, Jake Delmore, Matthew W. Vanneman, Robert L. Schlossman, John Feather, Nikhil C. Munshi, Jacob P. Laubach, Paul G Richardson, Glenn Dranoff, Kenneth C. Anderson, Constantine S. Mitsiades
Journal: Blood (2010)
Patient (Pt)-reported symptoms of chemotherapy (chemo) and VEGFR/EGFR antibody therapies for the treatment of metastatic colorectal cancer (MCRC) in a U.S. community-based oncology practice network.
Authors: B. A. Feinberg, A. Gilmore, O. Lunacsek, S. Haislip, E. Yu, Y. Yim, J. W. Gilmore
Journal: Journal of Clinical Oncology (2011)

575 Background: Targeted therapies for MCRC have increased treatment (Tx) options in multiple therapy lines. Symptoms associated with MCRC Tx have not been well studied from the Pt perspective. Objective: To characterize symptoms reported by MCRC Pts treated with chemotherapy and/or targeted drugs at a large US oncology network. Methods: Pt reported symptom data were linked to electronic medical records and Pt charts from Georgia Cancer Specialists in Southeast US. MCRC Pts aged ≥18 years with ≥1 administration of chemo or targeted therapy between 1/2007-3/2009 were included. Pt reports captured 13 symptoms, onset, and severity. Due to small sample sizes, no statistical comparisons were conducted. Results: 332 MCRC Pts were included (median age 62 years, 47% male, median weight 74 kg, 48% ECOG PS 0 or 1). Amongst Pts receiving 1L Tx (n=299), 78% received bevacizumab (BV) +/- chemo, 4% cetuximab (CX) +/- chemo, 15% chemo only, and 2% other. 162 Pts received 2L Tx: 49% BV +/- chemo, 17% chemo only, 28% CX +/- chemo, and 6% other. The 5 most common symptoms in 1L Tx for all severity ratings were 36% fatigue, 20% nausea, 17% weight (wt) loss, 15% diarrhea, and 9% constipation. The 5 most common symptoms in all 2L Tx groups were 44% fatigue, 27% nausea, 19% diarrhea, 16% wt loss, and 11% abdomen pain. 2L moderate, severe, or disabling symptoms reported in &gt;10% Pts receiving BV +/- chemo, CX +/- chemo, and chemo only Tx are shown in the table. Conclusions: The most commonly reported symptoms by 1L and 2L MCRC Pts were fatigue, nausea, diarrhea, and weight loss. Overall, a numerically higher % of 2L Pts treated with CX +/- chemo reported moderate, severe, and disabling symptoms than Pts receiving BV +/- chemo and chemo alone. Rash was not observed in the BV +/- chemo group. Further research of MCRC Pt reported symptoms in a larger sample size are warranted. [Table: see text] [Table: see text]
Results of a phase II trial of abiraterone acetate (AA) combined with dutasteride (DUT) for men with metastatic castration resistant prostate cancer (mCRPC).
Authors: Rana R. McKay, Lillian Werner, Katherine A. Zukotynski, Liran Domachevsky, Aymen Elfiky, Mark M, Pomerantz, Glenn J. Bubley, Robert B. Montgomery, Philip W. Kantoff, Mary-Ellen Taplin
Journal: Journal of Clinical Oncology (2014)

126 Background: Although abiraterone acetate (AA), a CYP17 inhibitor, increases survival in men with metastatic castration resistant prostate cancer (mCRPC), tumors eventually progress on therapy. The primary purpose of this study was to identify mechanisms of resistance to AA via analysis of the androgen receptor signaling pathway in serial tumor biopsies of men receiving AA and dutasteride (DUT), a type I and II 5-α reductase inhibitor. In this analysis, we report secondary endpoints including prostate specific antigen (PSA) response, toxicity, and incidence of flare. Methods: We enrolled 40 men with mCRPC. Patients initially received AA (1,000 mg daily) and prednisone (5 mg daily). After two months (mos), DUT (3.5 mg daily) was added. Therapy was continued until radiographic progression. A flare was recorded on bone scan, CT, or both if there were worsening lesions from baseline to 3 mos, decreasing PSA more than 50% from baseline at 3 mos, and stabilization or reduction of lesions at 6 mos. Results: Median follow-up was 13 mos. At the time of analysis, nine men remain on treatment. Twenty five percent and 18% of men received prior therapy with ketoconazole and/or chemotherapy, respectively. The median PSA at baseline was 28.8 ng/mL. After 2 mos of AA, median PSA declined by 54% to 10.9 ng/mL. Median PSA nadir was 6.3 ng/mL, reached at a median of 3.2 mos from baseline. 34 men (85%) experienced some degree of PSA decline. Twenty four men (60%) had a greater than or equal to 50% PSA decline and 12 (30%) had a greater than or equal to 90% PSA decline, reached at a median of 1.4 and 2.4 mos from baseline, respectively. There were 73% grade 1, 23% grade 2, 4% grade 3, and no grade 4 adverse events (AEs).AEs of interest included fatigue (45%), hypertension (38%, n=2 grade 3), hypokalemia (15%, n=0 grade 3), liver function test increases (15%), and edema (2%, n=0 grade 3). Seventeen men had imaging available for analysis, of whom four (23%) had flare on both 3 mos CT and bone scan and four (23%) had flare on only 3 mos CT scan. Conclusions: Given time of median PSA nadir, DUT may enhance efficacy of AA, though this warrants further investigation. Therapy with AA, prednisone (5 mg daily), and DUT is well tolerated with low rates of severe mineralocorticoid toxicity. Flare is seen on imaging in 47% of patients receiving AA. Biopsy data evaluating mechanisms for resistance to AA are not yet available. Clinical trial information: NCT01393730.
Hematologic and transfusion outcomes following implementation of the erythropoiesis-stimulating agent (ESA) National Coverage Determination (NCD) in Medicare cancer patients receiving chemotherapy
Authors: J. Gilmore, B. A. Feinberg, T. Gondesen, J. Jackson, B. K. Bookhart, R. S. McKenzie
Journal: Journal of Clinical Oncology (2008)

6548 Background: The purpose of this study was to determine the impact of Medicare's NCD on clinical outcomes for patients with chemotherapy-induced anemia requiring ESA therapy. Methods: This was a retrospective observational study of an electronic medical record database within a large oncology/hematology practice. Inclusion criteria consisted of Medicare patients receiving ≥2 ESA doses with concurrent chemotherapy and a cancer diagnosis. Patients were excluded if they had a diagnosis of myelodysplastic syndrome (MDS) or prior ESA therapy within 35 days of ESA initiation. Cohorts were defined based on date of initial ESA administration (Pre- NCD cohort: 1/1/2007–4/30/2007; Post-NCD cohort 8/1/2007–11/30/2007) with follow-up until the last ESA dose + 35 days or 7/30/2007 or 11/30/07 for the cohorts, respectively. Due to limited follow-up in the Post-NCD cohort, longitudinal hemoglobin (Hb) levels and transfusions during the initial eight weeks were reported. Results: A total of 285 Medicare patients received ESAs for 8 weeks (Pre-NCD 243, Post-NCD 42). The proportion of women was similar between cohorts (Pre-NCD 56.8% vs Post-NCD 59.5%, p=0.74) while mean age was greater in the Pre-NCD cohort (71.2 ± 9.6 vs 66.0 ± 12.0; p=0.01). Tumor type distribution was similar between cohorts. Hb levels were significantly higher in the Pre-NCD cohort compared to the Post-NCD cohort at each measured timepoint (Mean Hb, g/dL, Pre- vs Post-NCD: Baseline,10.7 vs 9.7; p<0.0001, 4-week Hb, 11.0 vs 10.1; p<0.0001; 8-week Hb, 11.2 vs 10.3; p=0.0016). A greater proportion of patients required transfusion in the Post-NCD cohort (Pre-NCD 9.5% vs Post-NCD 21.4%; p=0.02). Conclusion: This study found lower Hb values and higher transfusion rates in Medicare cancer chemotherapy patients treated following adoption of the NCD for ESA therapies. Limitations include brief follow-up time in the Post-NCD cohort, sample-size, and generalizability to other oncology/hematology sites within the United States. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ortho Biotech Ortho Biotech
A radiation oncology peer review program for community hospitals.
Authors: Laurie Sturdevant, Wendi Martinez, Nikhil Thaker, Anuja Jhingran, Deborah A. Kuban
Journal: Journal of Clinical Oncology (2014)

200 Background: Certified Members within the MD Anderson Cancer Network must perform prospective internal review of radiation oncology cases treated at their institution. Since 2009, several Network sites have been systematically added to a quality oversight program. As part of this process, a sample of the internally peer reviewed cases are assessed by radiation oncology Faculty from MD Anderson Cancer Center (MDACC) who are considered disease site experts. Methods: An electronic tool was used by Network sites to enter clinical treatment information on patients undergoing peer review. This case log was used to select a sample size of not less than 10% of each physician’s case load for an in-depth quarterly evaluation by our Faculty. Quality and appropriateness metrics included review of the technical components of the radiation treatment (RT) plan and multidisciplinary management.. RT was scored as being concordant/non-concordant with MDACC or national guidelines. Non-concordant cases were further reviewed for appropriateness given the individualized case. Feedback was then provided by Faculty to the treating radiation oncologists quarterly, to discuss recommendations and practice pattern modifications. Results: To date, 6 of our 13 Network sites are participating in this peer review process with others being phased in. In 2013, we selected 104 of 719 cases entered into our database by the first four sites. 78% (81) of cases were concordant with guidelines, while 22% (23) were non-concordant. Of the non-concordant cases, 23% were deemed individually appropriate but the remainders (17 of 104) were not appropriate. Concordance in the most frequent disease sites ranged from 80 to 89%. In the less frequent disease sites concordance was lower, ranging from 50 to 73%. Conclusions: The highly technical aspects of radiation treatment, the frequent need to integrate a multidisciplinary approach, and the reality that low volume disease sites will need to be increasingly treated in the community accentuate the need for enhanced oversight and more effective consultation with high volume, expert providers. Our study suggests that an integrated approach to peer review can improve the quality and value of cancer therapy in the community setting.
Efficacy of vemurafenib, a selective BRAF<sup>V600E</sup> inhibitor, in combination with a MEK inhibitor in BRAF<sup>V600E</sup> colorectal cancer models.
Authors: Brian Higgins, Kenneth Daniel Kolinsky, Hong Yang, Min Jung Kim, Jia Kui Li, Zenaida Go, Kathryn Packman, Gideon Bollag, Fei Su
Journal: Journal of Clinical Oncology (2012)

488 Background: BRAF mutations occur in about 10% of colorectal cancer (CRC). Most BRAF mutations involve the V600E amino acid substitution, resulting in constitutive activation of the MAPK signaling pathway. Vemurafenib (RG7204, PLX4032) is a first-in-class, BRAF V600E -specific small molecule inhibitor that dose-dependently inhibits tumor growth in V600E CRC xenografts. However, unlike responses observed in melanoma, single agent vemurafenib in a Phase I extension trial of 20 patients with previously treated metastatic CRC, resulted in only 5% response rate. The goal here was to explore in vitro and in vivo if addition of a MEK inhibitor (MEKi) could increase effects of vemurafenib on anti-proliferation and anti-tumor activity in BRAF V600E CRC cell lines. Methods: Combo of vemurafenib with a MEKi was tested in MTT assay for antiproliferative effect and combination effect was determined by combination index (CI) calculated by the CalcySyn software. Western analysis and Annexin V staining were utilized to evaluate combo effects on pathway inhibition and apoptosis induction. Optimal doses of both vemurafenib and MEKi were tested as single agent and in combination in the Colo205 and LS411N CRC xenograft models in nude mice. Results: Synergistic anti-proliferative effect was observed with the combo of vemurafenib and a MEKi in the V600E positive CRC cell lines tested. More effective pathway inhibition and apoptosis induction were observed with combo than either agent alone. Combination of vemurafenib and a MEKi delivered greater anti-tumor activity and increased life span of animals in the Colo205 and LS411N CRC xenograft models. Conclusions: These in vitro and in vivo data suggest that combined pharmacologic blockade within the RAS/RAF/MEK/ERK pathway is more effective than either agent alone and may be a way to exploit greater antitumor activity CRC patients in clinic.
Webinars as a tool for breast cancer survivorship education.
Authors: Elissa Thorner Bantug, Katherine E. Duffey, Kimberly S. Peairs, Linda A. Lee, Jeffery M. Gould, Mary-Eve Brown, Antonio C. Wolff
Journal: Journal of Clinical Oncology (2013)

109 Background: Survivorship education may facilitate coordination of care between the patient and health care providers, increase adherence to health maintenance recommendations, and improve outcomes. Approximately 80% of Americans regularly use the internet. Interactive seminars (webinars) may offer an efficient tool to reach a diverse audience of cancer survivors, caregivers, and providers. Methods: From September 2012-April 2013, we offered 3 free 1-hour webinars advertised via social media, print flyers, email, newsletters, and advocacy and support groups. Topics included next steps after breast cancer treatment, integrative medicine, and nutrition. Participants registered online or by phone. Format consisted of a 30-minute lecture followed by live Q&amp;A with electronically submitted questions. Demographic data were collected at registration and participants were asked to complete a brief 9-question survey after the webinar. Results: 728 participants registered for at least 1 webinar (median age 56, range 18-81 years; 14% African American). 681 participants were U.S.-based and 47 joined from 21 other countries. Participants self-identified as a cancer survivor (71%), provider (20%), caregiver (8%), or other (2%). Most (79%) had at least a high school education. Among the 184 (25%) who completed the post-webinar survey, 86% reported that information was relevant to situation, 85% said they had the opportunity to ask questions, 94% felt speakers were knowledgeable, and 90% were satisfied with the information quality. Participants ranked one-on-one care followed by webinars as their preferred way to receive survivorship information, above other tools like videos, websites, and handouts. Conclusions: As part of a multidisciplinary approach to breast cancer survivorship care, webinars are a feasible modality to deliver quality health information. Limitations include overall generalizability with a potential selection bias of those who may be more educated than the general population, have access to the internet, and feel comfortable with this technology. Nonetheless, data suggest that this format may allow us to reach a diverse audience that appears receptive and satisfied with survivorship education provided in an electronic format.
Long-term effects of Bacilles Calmette-Guerin perfusion therapy for elderly patients with upper urinary tract urothelial carcinoma in situ.
Authors: Takahiro Yoneyama, Jotaro Mikami, Naoki Fujita, Tendo Sato, Yuta Kojima, Hiromichi Iwamura, Yuki Tobisawa, Tohru Yoneyama, Kazuyuki Mori, Atsushi Imai, Shingo Hatakeyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2016)

404 Background: According to several guidelines, the standard therapy for carcinoma in situ (CIS) of the upper urinary tract is total nephroureterectomy. However, it is difficult to determine a treatment strategy for elderly patients. Bacillus Calmette-Guerin (BCG) therapy has already been established as a treatment for non-muscle invasive bladder cancer. However, although there are several reports indicating the effectiveness of BCG perfusion therapy for the upper urinary tract CIS, it has not been established yet. We conducted a retrospective study to assess the long-term effects of BCG perfusion therapy for the upper urinary tract CIS for elderly patients. Methods: We treated 34 patients with upper urinary tract CIS at our clinic between August 2004 and March 2015. 29 patients (22 men and 7 women) with the age of 65 years or older were enrolled. 11 subjects had the entire urinary tract CIS, 8 had bilateral, 10 had unilateral CIS of the upper urinary tract. The average period of observation was 45.5 months ( 5 to 151 ), and the average subject age was 76.5 years (66 to 90 ). We used a double-J catheter for 22 cases, a transvesical single-J catheter whose curl was positions in an upper calyx for 6 cases, and a straight ureteral catheter inserted for ureterocutaneostomy for 1 case. We used 80 mg of BCG for the first 4 cases, 40 mg for the late 25 cases. The BCG treatment was given once a week for consecutive 6 weeks. Urine cytology was performed to assess the treatment validity. Results: Urine cytology tests became negative in 22 of the 29 subjects (75.9%) who underwent upper urinary tract perfusion therapy. Among these 22 subjects who had negative tests, 6 subjects had a recurrence in their upper urinary tracts. Side effects were observed in 28 subjects (89.7%), and the most common side effect was bladder irritation. Localized renal tuberculosis which was successfully treated with conservative therapy was seen in two cases. Conclusions: BCG perfusion therapy for the upper urinary tract CIS is safe and effective for elderly patients. Results also suggested that this could be one of the effective treatment options. However, we have to be careful for severe side effects.
Association of increased time from chemoradiation (CRT) to esophagectomy (E) with increased surgical complications (Cx) in esophageal cancer (EC).
Authors: Joshua E. Meyer, Alan Thomay, Karen J. Ruth, Talha Shaikh, Andre A. Konski, Steven J. Cohen, Walter Joseph Scott
Journal: Journal of Clinical Oncology (2013)

77 Background: EC is often treated with CRT followed by E. E is typically performed 6 weeks after completion of CRT, but the optimal timing is unknown. Previous work has shown that a longer time interval (TI) between CRT and E resulted in a higher percentage of patients (pts) with pathologic complete response. This study was undertaken to determine whether this improved response comes at the expense of increased surgical Cx. Methods: Complete records were available for 85 pts who underwent CRT and subsequent E at a single academic center from 2001-2011. Surgical Cx were collected. Univariable and multivariable analyses were performed to investigate the association between length of TI from CRT to E and Cx, adjusting for age, gender, and surgery type. Multiple linear regression was performed to examine the association of length of stay (LOS) and estimated blood loss (EBL) with TI, adjusting for covariates. Results: Of 85 patients, 72 were male and the histology was adenocarcinoma in 72. The median age was 61 (range: 36-80), the most common clinical stage was T3N1 and 60% of pts had ECOG performance status of 1 (range 0-2). The median length of CRT (most commonly Cisplatin, 5FU and 50.4 Gy) was 37 days and median TI from initiation of CRT to E was 89 days (range: 64-242). 59 pts (69%) experienced at least 1 complication. The mean TIs for pts with and without Cx were 97 and 87 days (P=0.019). When specific Cx were examined, the mean TI for pulmonary Cx was greater (107 v. 89 days; P=0.018). Patients experiencing anastamotic leaks had shorter mean TIs (83 v. 96 days; P=0.022). Multiple linear regression showed a positive association between LOS and TI (p=0.0027) but none with EBL. On multivariable analysis, increased TI predicted for pulmonary complications (OR 1.05, P=0.0061) and LOS (OR 1.03, P=0.033). Increased TI predicted for decreased risk of anastamotic leak (OR 0.94, P=0.063). Conclusions: In this retrospective data set, we demonstrated an association between longer TI from CRT to E and pulmonary toxicity in EC pts. Longer TI was also associated with increased LOS. In contrast, anastamotic leaks were associated with shorter TIs. These data suggest TI from CRT to E may impact the risk of Cx.