tbuckley/cabot-search huggingface dataset:
Bevacizumab, temozolomide, and radiation therapy followed by bevacizumab, temozolomide, and oral topotecan for newly-diagnosed glioblastoma multiforme (GBM).
Authors: J. J. Vredenburgh, A. Desjardins, D. A. Reardon, K. Peters, J. Kirkpatrick, A. D. Coan, L. Bailey, D. Janney, C. Lu, H. S. Friedman
Journal: Journal of Clinical Oncology (2011)

2098 Background: The prognosis for newly-diagnosed GBM remains poor. Adding temozolomide to radiation therapy improved the median event-free survival (EFS) to 6.9 months and median overall survival to 14.6 months. The five year survival remains < 10%. GBM’s have abundant neo-vascularization and the highest level of vascular endothelial growth factor (VEGF). Bevacizumab is an antibody to VEGF and is the most active agent for recurrent GBM. Hypoxia inducing factor-1 α (HIF-1 α) is an important regulator of VEGF, and topotecan may inhibit HIF-1 α. We performed a phase II trial in newly diagnosed GBM patients, adding bevacizumab and topotecan to standard therapy. Methods: Eighty newly diagnosed GBM patients were enrolled after their craniotomy between December 2009 and December 2010. Patients received standard radiation therapy and temozolomide at 75 mg/m2/d beginning between 2-6 weeks post-craniotomy. Bevacizumab, 10 mg/kg every 14 days was added a minimum of 4 weeks post-op. Two weeks after radiation therapy was completed, 12 monthly cycles of temozolomide at 150-200 mg/m2/d days 1-5, oral topotecan at 1.5 mg/m2/day days 2-6 for patients not on an enzyme inducing anti-epileptic drug (EIAED) and 2.0 mg/m2/day days 2-6 for patients on an EIAED bevacizumab at 10 mg/kg on days 1 and 15. Results: Adding bevacizumab and topotecan to standard therapy resulted in a 6-month EFS of 90%. The median overall survival has not been reached, but 96% of the patients are alive at 8 months. The regimen was tolerable, 96% completed radiation therapy. Eight patients came off due to toxicity, there were 2 CNS hemorrhages, 2 grade 4 thrombocytopenias, 1 pulmonary embolus, 1 colon perforation, 1 craniotomy bone flap infection, and 1 CMV pneumonitis. There were 2 toxic deaths, 1 from CMV pneumonits and 1 from CNS hemorrhage. There are 10 progressions. A comprehensive analysis of tumor biomarkers is underway. Conclusions: Adding bevacizumab to temozolomide and radiation followed by temozolomide, bevacizumab and oral topotecan is tolerable. The 6-month EFS is encouraging. Randomized phase III trials of the addition of bevacizumab to the treatments of newly diagnosed GBM patients are essential.
Change in neutrophil to lymphocyte ratio as a prognostic and predictive marker in response to targeted therapy for metastatic renal cell carcinoma.
Authors: Nimira S. Alimohamed, Arnoud J. Templeton, Jennifer J. Knox, Xun Lin, Ronit Simantov, Wanling Xie, Nicola Jane Lawrence, Reuben James Broom, Andre Poisl Fay, Brian I. Rini, Georg A. Bjarnason, Martin Smoragiewicz, Christian K. Kollmannsberger, Ravindran Kanesvaran, Connor Wells, Eitan Amir, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2015)

404 Background: The neutrophil to lymphocyte ratio (NLR) is a marker of inflammation. We evaluated whether NLR is independently prognostic when adjusted for the International mRCC Database Consortium (IMDC) model and evaluated change in NLR ("NLR conversion") as a predictive marker of response to targeted therapy. Methods: A total of 5,227 metastatic renal cell carcinoma (mRCC) patients treated with targeted therapy were included; 1,199 patients in the training cohort from the IMDC and 4028 patients as the validation cohort from pooled prospective randomized controlled trials involving targeted therapy. NLR was examined at initiation of first-line targeted therapy and at 6 weeks after. The prognostic role of NLR and NLR conversion on overall survival (OS) and progression free survival (PFS) was assessed using Cox regression models adjusting for IMDC prognostic score. Results: Median baseline NLR was 3.4 and 2.9 in the training and validation cohorts, respectively. NLR &gt;3.0 at baseline was independently associated with OS and PFS in both the training and validation cohorts (Table). A decrease in NLR by week 6 was associated with longer OS (21.1 vs. 9.7 months; HR 0.57, p&lt;0.001), PFS (8.8 vs. 4.6 months; HR 0.54, p&lt;0.001), and higher objective response rates (35% vs. 13%, p&lt;0.001) compared to patients without a decrease. A rise in NLR showed opposite effects for all three endpoints. These findings were also confirmed in the validation set. Conclusions: NLR is an independent prognostic factor after controlling for IMDC criteria. NLR conversion can be an early biomarker of benefit to targeted therapy. [Table: see text]
Recurrence of hepatocellular carcinoma after liver transplantation: Comparison between superselective and non-superselective chemoembolization.
Authors: Andrew Smith, Michael Heckman, Daniel Serie, Denise M Harnois, Justin H. Nguyen, Ricardo Paz-Fumagalli
Journal: Journal of Clinical Oncology (2013)

238 Background: To compare post-transplant recurrence rates of hepatocellular carcinoma (HCC) and differences in percent tumor necrosis in patients with pre-operative superselective chemoembolization (CE) vs. non-superselective CE. Methods: Retrospective review of 147 patients with liver transplant (LT) for HCC treated with pre-operative CE. Those transplanted less than 24 hours after CE and those who had other concomitant treatments were excluded. The angiographic studies and written reports were reviewed to categorize patients into superselective and non-superselective groups. CE was done with an emulsion of lipiodol, cisplatin, doxorubicin, mitomycin C, and contrast, with or without embolization particles. Superselective CE was defined as treatment directly into the vessel(s) feeding the tumor. Treatment from more proximal vessels was considered non-superselective. Data gathered included age, gender, date of CE, date of LT, tumor size and number, tumor stage, MELD score, Child-Pugh class, alpha fetoprotein, percent tumor necrosis at explant, date of recurrence, date and cause of death, and date of last follow-up. Patient and disease characteristics and percent tumor necrosis were analyzed with a Wilcoxon rank sum test or Fisher’s exact test. The Kaplan-Meier method was used to estimate the cumulative incidences of death due to recurrent disease after LT. Results: 99 patients were included, 53 had superselective CE and 46 non-superselective. HCC recurrence rates at 1, 3, 5, and 8 years were all significantly less for superselective CE compared to non-superselective CE (p = 0.039 single, p = 0.011 multivariable). Using multivariable analysis, superselective CE had a lower risk of death due to recurrent HCC at 1, 3, 5, and 8 years (p = 0.046). There was a trend toward more percent tumor necrosis after superselective CE, but it did not reach significance (p = 0.057). Conclusions: This study provides evidence that HCC recurrence after LT and death due to recurrent HCC is lower after pre-LT superselective CE versus non-superselective CE. The strong trend for greater percent tumor necrosis with superselective CE may explain the differences in recurrence rate.
Improving the safe delivery of systemic treatment by assessing concordance with labeling guidelines.
Authors: Kathy Vu, Vicky Simanovski, Leonard Kaizer, Esther Green, Sherrie Hertz, Erin Rae, Monika K. Krzyzanowska, Noor Ahmad
Journal: Journal of Clinical Oncology (2014)

257 Background: Improper labeling of medication may lead to errors. In 2009, Cancer Care Ontario published Key Components of Chemotherapy Labeling, with recommendations for the necessary components and formatting of intravenous chemotherapy labels. A jurisdiction-wide evaluation for concordance occurred in 2011. Results were shared, improvement efforts were supported through a provincial quality network, and a re-evaluation was conducted in the fall of 2013. Methods: Three defined chemotherapy labels were evaluated at baseline and after improvement strategies were implemented at each of Ontario’s 77 hospitals providing systemic treatment. Labels were reviewed centrally and awarded points for concordance for each of 15 guideline-specified criteria. Results: The provincial average overall score for concordance increased from 59% to 80% (p&lt;0.001). Improvement was seen for 12 of the 15 criteria evaluated and for 64 of the 77 facilities. The greatest increase in overall score by a facility was 53.4%. The greatest overall improvement in score for an individual component was 67% (TALLman lettering). The scores of 2 components were unchanged, as 100% concordance was achieved on both the baseline and re-evaluation. Conclusions: Improvement in concordance to chemotherapy labeling guidelines was observed following the implementation of a measurement strategy and improvement plans. This approach is one component of a larger strategy to promote a culture of safety in chemotherapy delivery in Ontario. [Table: see text]
Influence of primary systemic therapy on minimal residual disease in primary breast cancer.
Authors: B. Aktas, H. Neubauer, O. Hoffmann, S. Becker, S. Kümmel, D. Wallwiener, R. Kimmig, E. Solomayer, S. Kasimir-Bauer, T. N. Fehm
Journal: Journal of Clinical Oncology (2010)

647 Background: The aim of primary systemic therapy is to minimize size of the primary tumor and to eradicate minimal residual disease (MRD). Evaluation of therapy response is routinely performed by palpation and radiologic imaging of the breast. However, the effect of PST on minimal residual disease is not assessed. One of the surrogate markers for MRD are disseminated tumor cells (DTC) in the bone marrow (BM). Therefore, we investigated in 368 primary breast cancer patients the incidence of DTC after completion of PST. Methods: Bone marrow aspirations were performed in 336 patients after primary chemotherapy between 2002 and 2008 at the Dept. Gyn/OB of Tuebingen and Essen, Germany. DTC were determined according to the recommendations of the working group tumor cell dissemination of the german senology (Fehm et al., Cancer 2006). Results: The incidence of disseminated tumor cells in breast cancer patients was 35% (119 of 336 pts) after completion of primary systemic therapy. No association between BM positivity and clinicopathological factors including ER, PR, HER2, grading and pathological nodal status could be found except for pathological tumor size. The pathological therapy response was not reflected by the presence of disseminated tumor cells in the bone marrow of breast cancer patients (p = 0.9). The BM positivity rate in patients with complete remission was 33% (17 of 51) compared to 36% (93 of 256) in those patients with partial remission. In patients with stable or progressive disease 9 of 29 patients were DTC positive. Conclusions: PST is not able to completely eradicate DTC which is a surrogate marker for minimal residual disease - the precursor for metastatic disease. To improve the efficacy of primary systemic therapy, not only the primary tumor but also minimal residual disease should betargeted. No significant financial relationships to disclose.
Final result of phase II study of amrubicin (AMR) combined with carboplatin (CBDCA) for elderly patients with small cell lung cancer (SCLC)
Authors: O. Ishimoto, A. Inoue, S. Sugawara, M. Harada, K. Usui, T. Suzuki, H. Yokouchi, M. Maemondo, T. Nukiwa
Journal: Journal of Clinical Oncology (2009)

8054 Background: AMR, a new anthracycline agent, is active for SCLC. We had previously reported a phase I study of AMR combined with CBDCA for elderly patients with SCLC (J Thorac Oncol 1:551, 2006). The objective of this study is to evaluate the efficacy and the safety of this combination for elderly patients with SCLC. Methods: Chemotherapy naïve elderly patients (70 years or older) with SCLC received AMR (35 mg/m 2 , day1–3) and CBDCA (AUC 4.0, day1) every 3 weeks. The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival and toxicity profile. Assuming that ORR of 60% in eligible pts would indicate potential usefulness while ORR of 40% would be the lower limit of interest, with alpha = 0.10 and beta = 0.20, the estimated accrual was 30 patients. Results: From January 2005 to November 2007, 36 pts were enrolled from 11 institutions. Patient characteristics were: Male/Female 27/9; median age 76 (range 70–83); Performance status 0/1 17/19. The median numbers of treatment cycles were 4 (range 2–7). The objective responses were CR 1, PR 31, SD 2, PD 2, and the ORR was 89%. Median PFS was 5.8 months and median survival time was 18.6 months. Grade 3–4 neutropenia was observed in all the patients and 5 patients (14%) suffered from grade 3–4 febrile neutropenia. Other toxicities were moderate and no treatment related death was observed. Conclusions: AMR combined with CBDCA is quite effective for SCLC with acceptable toxicities even for the elderly population. Further evaluation of this regimen is warranted. No significant financial relationships to disclose.
Screening for cancer-related fatigue (CRF) in a thoracic oncology clinic is feasible
Authors: P. Fidias, W. Pirl, J. Temel, B. Cashavelly, T. J. Lynch
Journal: Journal of Clinical Oncology (2005)

8208 Background: Fatigue is the most frequently reported symptom by cancer patients. Due to the high prevalence of CRF, the NCCN recommends routine screening for fatigue in clinical practice. The goal of this study was to assess the feasibility of instituting a routine screening program for fatigue in a comprehensive cancer center. Methods: We performed a pilot study to assess the feasibility of a screening program for CRF in a thoracic oncology clinic. A physician and a nurse manager instructed medical assistants about CRF and the NCCN guidelines for fatigue in a one-hour training session. As part of the vital signs, the medical assistants screened for fatigue with a one-item scale, adapted from the Brief Fatigue Inventory: “How would you rate your fatigue now on a scale of 0–10, with ‘0’ being ‘no fatigue’ and ‘10’ being ‘the worst possible fatigue?’” Patients were shown a pocket-sized visual analogue of the 0–10 fatigue scale. The fatigue score was recorded with the vital signs and entered into the medical record. Vital signs for all patients were reviewed over the three-month period to assess the rate of screening for fatigue. Results: Between June 2004 and August 2004, 600 patients participated in 1,418 visits to the thoracic oncology clinic. The number of visits per patient ranged from one to thirteen with a median of two. A fatigue score was documented in the medical record in 96.6% of the visits. The mean level of fatigue for the first encounter of each patient was 3.4 (sd=3.2). 36.1% reported no fatigue (score=0), 15.2% reported mild fatigue (scores of 1–3), 27.0% reported moderate fatigue (scores of 4–6), and 21% reported severe fatigue (scores of 7–10). Conclusions: This study demonstrates the feasibility of a screening program for CRF in an ambulatory oncology clinic. Based on our pilot data, we have instituted a routine screening program for CRF throughout our cancer center. This screening program will identify patients who might benefit from an intervention for CRF. Based on our patient screening, we are referring patients to our newly formed CRF clinic and our active clinical trials program for CRF. No significant financial relationships to disclose.
Breast density and the risk for positive lumpectomy margins.
Authors: Freya Ruth Schnabel, Tanir Allweis
Journal: Journal of Clinical Oncology (2015)

50 Background: Current methods for intraoperative assessment of lumpectomy margins are limited, and a meaningful proportion of patients require re-excision to achieve acceptable margins. There is little available information regarding the relationship of mammographic breast density (BD) and positive margin rate. Methods: The MarginProbe device uses radiofrequency spectroscopy to evaluate the margins of lumpectomy specimens. The current study utilized data from the MarginProbe Pivotal Trial (Dune Medical Devices, Israel, NCT00749931). This randomized clinical trial compared adjunctive intraoperative use of the MarginProbe device with surgeons’ standard approach to lumpectomy surgery. For the current analysis, data was compiled from the period prior to patient randomization and device use. Variables of interest included BD, patient and tumor characteristics, and the margin status of the main lumpectomy specimen (prior to device use in the device arm). For the purpose of this analysis, a positive margin was considered tumor on ink. Statistical analysis was performed with univariate and multivariate analysis, and linear/logistic regression. Results: A total of 664 patients were enrolled in the trial. 450 patients had preoperative breast density information available, and formed the basis for this analysis. As expected, higher BD was associated with younger age, lower BMI and smaller breast and specimen volume. Increased BD was also associated with increased use of preoperative MRI imaging (odds ratio 2.2, p&lt;0.0001). Higher BD was also associated with a significant increase in main lumpectomy specimen positive margin rate (Table). The odds ratio was 1.46 per change in density category (p=0.011). BD remained significantly associated with positive margins after controlling for age, BMI and breast volume. Conclusions: Higher BD is an independent risk factor for positive margins in main lumpectomy specimens, suggesting that adjunctive methods for intraoperative margin assessment may be particularly helpful in these patients. [Table: see text]
Alkaline phosphatase (ALP) normalization and overall survival in patients with bone metastases from castration-resistant prostate cancer (CRPC) treated with radium-223.
Authors: C. Parker, C. G. O'Bryan-Tear, B. Bolstad, A. Lokna, S. Nilsson
Journal: Journal of Clinical Oncology (2011)

49 Background: Radium-223 (Alpharadin) is a first-in-class alpha-pharmaceutical. It targets bone metastases with high-energy alpha-radiation of extremely short range that spares bone marrow. Radium-223 has a profound effect on serum markers of bone metabolism, including ALP, in patients with bone metastases from CRPC. In an exploratory analysis, we studied whether this effect is associated with a meaningful clinical benefit. Methods: Patients with CRPC and bone metastases were treated in 2 randomized phase II studies. BC1-02 was a placebo-controlled study of radium-223 (50 kBq/kg) every 4 weeks for 12 weeks. BC1-04 evaluated radium-223 (25, 50, or 80 kBq/kg) every 6 weeks for 12 weeks. Baseline total ALP values &gt; 128 U/L were considered elevated; those decreasing to below 128 U/L during treatment with radium-223 were defined as normalized, and those remaining above that value as non-normalized. Results: In BC1-02, ALP normalization was seen in 12/26 (46%) patients treated with radium-223. Median survivals of those with and without ALP normalization were 102 weeks and 42 weeks, respectively (log-rank P &lt; 0.001). In BC1-04, ALP normalization was seen in 25/75 (33%) cases: 5/29 (17%) in the 25 kBq/kg group, 10/25 (40%) with 50 kBq/kg, and 10/21 (48%) with 80 kBq/kg, indicating a dose-response relationship. Median survivals for the 25 patients with, and the 50 patients without, ALP normalization were 102 weeks and 58 weeks, respectively (log-rank P = 0.0086). Conclusions: Inpatients with metastatic CRPC and bone metastases treated with radium-223, ALP normalization was associated with significantly better overall survival. These data support the rationale for the ongoing ALSYMPCA phase III trial of radium-223. [Table: see text]
Phase I trial of proteasome inhibition with bortezomib (BOR) with concurrent chemoradiation (chemoXRT) for stage III non-small cell lung cancer (NSCLC)
Authors: M. Suntharalingam, M. J. Edelman, K. Kwong, R. Smith, M. Bedor
Journal: Journal of Clinical Oncology (2005)

7300 Background: Concurrent chemoXRT has been demonstrated to improve outcome in stage III NSCLC. However, both local and systemic failure remain problematic. BOR has been demonstrated to be a potent radiosenstizer in vitro. We have undertaken a Phase I trial of BOR in addition to chemoXRT in this setting. Methods: Patients (pts) with stage IIIa or selected IIIb (T4N2 or TxN3) NSCLC with PS 0–1, normal organ function are eligible. ChemoXRT consisted of carboplatin (AUC =2), paclitaxel (50 mg/m2), both q week x6 + 61 Gy (180 cGy/day Mon-Fri). BOR is administered at the following dose levels: .3, .5, .7 and 1.3 mg/m2 twice a week on weeks 1,2,4,5, in cohorts of at least 3 pts. Cohorts are to be expanded to six pts if drug related grade 3 non-hematologic toxicity is encountered. Pts with mediastinal clearance undergo resection. All pts receive consolidation with 2 cycles of carboplatin (AUC =6), paclitaxel (225mg/m2) d1 q21 d x 2. Results: 6 pts (3M/3F, median age 55; 5 IIIA/1 IIIB) have been enrolled, 3 at .3 and 3 at .5 mg/m2 of BOR. 5 pts are evaluable for toxicity, 1 too early. No unexpected drug related toxicity have been encountered. The primary toxicities have been grade 2 esophagitis and grade 3 neutropenia without infection. All pts on the initial cohort demonstrated mediastinal clearance and 2 have undergone surgical resection of tumor without complication. Conclusions: BOR with concurrent chemoXRT is tolerable. Dose escalation continues. This is the first report utilizing BOR with thoracic radiotherapy. Supported in part by Millennium Pharmaceuticals Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millenium Millenium
Association of radiation therapy with overall survival in patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum.
Authors: David Mitchell Marcus, Dana Nickleach, Bassel F. El-Rayes, Jerome Carl Landry
Journal: Journal of Clinical Oncology (2014)

528 Background: The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiation followed by surgery, but many physicians question the benefit of multimodality therapy in patients with stage T3N0M0 disease. We aimed to determine the impact of radiation therapy (RT) on overall survival (OS) in this group of patients. Methods: We used the Surveillance, Epidemiology, and End Results database to identify patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum from 2004 to 2010. The Kaplan-Meier method was used to compare OS for patients receiving RT vs. no RT, along with for pre-op vs. post-op RT among patients that received RT. Multivariable analysis (MVA) using a Cox proportional hazards model was performed to assess the association of RT with OS after adjusting for patient age, gender, race, tumor grade, carcinoembryonic antigen, type of surgery, and circumferential margin status. The analysis was repeated separately on patients that underwent total colectomy (TC) vs. sphincter-sparing surgery. Results: The cohort included 8,679 patients, including 4,705 who received RT and 3,974 who did not. Median age was 66 years. Five year OS was 76.5% in patients who received RT, compared to 60.0% in patients who did not receive RT (p &lt;0.001). Five year OS was 76.9% for patients receiving pre-op RT vs. 75.7% in patients receiving post-op RT (p = 0.247). In patients undergoing TC, five year OS was 74.7% for patients receiving RT, compared to 47.5% in patients not receiving RT (p &lt;0.001). In patients undergoing sphincter-sparing surgery, five year OS was 77.7% in patients receiving RT, compared to 62.9% in patients not receiving RT (p &lt;0.001). Use of RT was significantly associated with OS on MVA, both in the entire cohort (HR 0.70 [95% CI 0.60-0.81]; p&lt;0.001) and in subsets of patients undergoing TC (HR 0.55 [95% CI 0.38-0.79]; p=0.001) and sphincter-sparing surgery (HR 0.70 [95% CI 0.59-0.84]; p&lt;0.001). Conclusions: The use of RT is associated with superior OS in patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum. This benefit is demonstrated in both the pre-op and post-op settings and applies to patients undergoing both TC and sphincter-sparing surgery.