tbuckley/cabot-search huggingface dataset:
Compliance with evidence-based guidelines for radiation of vertebral metastases.
Authors: Heather A Curry, Arlene A. Forastiere, Reshma Jagsi, M. Lou Palladino
Journal: Journal of Clinical Oncology (2013)

36 Background: Evidence based guidelines pertaining to the management of bony metastases have been published. However, up to 30% of oncology treatments deviate from evidence based standards and widespread variations in clinical practice continue to exist. To explore patterns of care in the treatment of vertebral metastases in a group of working age, insured patients, we assessed treatment plans submitted for preauthorization through eviti Connect. Methods: Eviti Connect is a web-based application that enables oncology providers to obtain automated precertification for patients. The platform evaluates treatment plans for consistency with EBM and compliance with payer policies and plan language. All requests for radiation treatment submitted during a two year period from 6/1/11-5/31/13 were reviewed. Peer to peer discussions were conducted in cases that deviated from EBM. Results: A total of 229 cases for the treatment of vertebral metastases were submitted. 46/229 plans (19.8%) did not meet EBM standards. Some cases displayed more than one deviation. Reasons for non-compliance included atypical treatment schedules (8.69%), SRS/SBRT (36.9%), IMRT (32.6%), and IGRT (58.7%). In 26/46 cases (56.5%) the treating physician provided a medical rationale for the deviation. In 9 cases the physician altered the plan to be compliant; in 5 cases the physician did not agree to a change. The most common dose fractionation schedules were 30 Gy/10 fractions (48.9%) and 37.5 Gy/15 fractions (20.5%). 17 cases were treated using 20 Gy/5 fractions and only 2 cases were treated using 8 Gy X 1. Conclusions: Radiation of vertebral metastases was prescribed in accordance with EBM in the majority of cases. The main reasons for deviation were patient-specific issues that justified the medical necessity of the variance. Case review and peer to peer discussion contributed to understanding the rationale for treatment deviation from guidelines and allowed providers to bring plans into compliance with EBM. Overall only 5% of plans were non-evidence based or lacked a medical justification for deviation. Consistent with patterns of care across the US, within this group of patients, single fraction and hypofractionated radiation regimens were underutilized.
Association of metastasis-free survival (MFS) with overall survival (OS) in men with PSA-recurrent prostate cancer treated with deferred androgen-deprivation therapy.
Authors: Michael Thomas Schweizer, Xian C. Zhou, Hao Wang, Ting Yang, Farah Shaukat, Mario A. Eisenberger, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2013)

109 Background: To support the hypothesis that metastases are a significant clinical event, we aimed to explore the association between MFS with OS in men with biochemically-recurrent prostate cancer. Methods: This is a retrospective analysis of 450 men treated at a single institution between July 1981 and July 2010 with biochemical recurrence following prostatectomy, of which 140 (31%) developed subsequent metastases. In all patients, androgen deprivation therapy was deferred until after the development of radiographic metastases. Univariate and multivariable Cox regression models were developed to investigate factors influencing OS. Results: The median time from biochemical recurrence to metastasis (i.e. MFS) was 10.2 y (95% CI, 7.6–14.0 y), and the median time from first metastasis to death (i.e. OS) was 6.6 y (95% CI, 5.8–8.4 y). Using multivariable Cox regressions, we identified 4 variables that were independently prognostic for OS (Table): MFS (≤3 vs &gt;3 y; P=0.009), number of metastases (≤3 vs ≥4; P=0.001), painful metastases (present vs absent; P&lt;0.001), and ECOG performance status (0 vs ≥1; P=0.001). The concordance index reflecting the association between MFS and OS was 0.67. Conclusions: After adjusting for other prognostic variables, MFS was independently associated with OS in men with biochemically-recurrent prostate cancer. While this observation requires prospective validation, it suggests that MFS may be a reasonable endpoint in future clinical trials. [Table: see text]
Quantifying the potential of C-11 acetate PET scanning in avanced prostate cancer patients.
Authors: Thomas A. Gardner, Jack Thygesen, John Cox, Steven M Westphal, Mark A Green, Mark Tann, James W. Fletcher
Journal: Journal of Clinical Oncology (2016)

300 Background: Detection of advanced prostate cancer has historically relied on radionuclide bone scanning and cross-sectional imaging with varying degrees of sensitivity and specificity based on the clinical scenario. In the current era, use of NaF and Choline based whole body scans have led to increased detection, but access to these scan can be limited and expense can be prohibitive. Similar to choline based scanning, acetate is metabolically active in cancer, including prostate. Methods: Fifty-six men previously diagnosed with prostate cancer with PSA recurrences after some failed primary treatment, have undergone whole body C-11 Acetate PET scans at Indiana University since June of 2013. Patient demographics, prior treatments, PSA values, prior imaging, post-scan therapies, and therapeutic outcomes have been recorded prospectively and updated as follow-up information becomes available. Results: Analysis of these initial 56 men demonstrated 31/56 men had a C-11 Acetate PET scan that lead to further definitive loco-regional treatments, including salvage radiation therapy ( 12), salvage regional lymph node dissection (11) and salvage cryo-ablation (8), while 9/56 men had initiation of hormonal ablation, secondary to detection of systemic disease. The remainder of these men had negative scans and are currently under continued active surveillance without evidence of disease progression requiring either loco-regional or systemic therapy. Closer analysis of the 31 men who received loco-regional treatments revealed 10 men who benefited with clear PSA declines, 4 men who failed to demonstrate a benefit from the definitive loco-regional therapy and 17 of men are too early to determine at the time of analysis. Careful pathological analysis of the regional lymph dissections revealed the limit of detection of the C-11 Acetate PET scan of greater than or equal to 3mm. Correlations of SUV readings of detected prostate cancer lesions with PSA kinetics, suggest importance of both PSA doubling time and absolute PSA value cutoffs. Conclusions: The C-11 Acetate PET scan is a useful adjunct to current imagining techniques and provides additional clinical information to guide clinicians caring for prostate cancer patients.
Efficacy of continuing zoledronic acid beyond 24 months in metastatic prostate cancer.
Authors: A. Ferreira, M. C. Mauricio, L. F. Azevedo, A. Teixeira-Pinto, N. Sousa
Journal: Journal of Clinical Oncology (2011)

e15037 Background: Zoledronic acid (ZA) is effective in preventing skeletal related events (SRE) in prostate cancer patients with bone metastasis (mPC). However its efficacy beyond 24 months is uncertain. We aimed to assess the comparative effectiveness ZA discontinuation at 24 months vs its maintenance. Methods: A retrospective cohort of mPC, in a Portuguese cancer centre, included mPC treated with ZA between 2002 and 2009. Three months of ZA were required for efficacy analysis. Time to first SRE was the efficacy outcome. Pathologic bone fracture; spinal cord compression; skeletal surgery; palliative bone radiotherapy or malignant hypercalcemia diagnosed after >3 months of ZA were considered SRE. ZA efficacy in mPC treated <24 months (group A) vs >24months (group B) was compared with a cumulative incidence function (CIF) considering death a competing risk. Impact of potential confounders was assessed with a Cox proportional hazards model. Sample size of 400 patients was computed to identify a 48% reduction in the risk of SRE for mPC treated for >24months with 80% power. Results: A total of 212 mPC were included in the efficacy analysis, 23% treated for >24 months. Overall 68% had mPC at diagnosis and 44% were castration resistant at ZA initiation. The overall SRE rate was 15% and 58% of the patients died. CIF for group A and B were similar with an estimated hazard ratio of 0.93 (95CI 0.59; 2.01) which was unchanged after adjusting for age, AJCC stage, castration resistance status at ZA initiation, palliative chemotherapy and palliative radiotherapy before ZA initiation. Conclusions: It would be clinically important to clearly demonstrate the benefit of ZA beyond 24 months, as discontinuation may be an issue. From our results, no clear evidence exists of such a benefit. However the retrospective design, low SRE rate and smaller than anticipated sample size are limitations to be considered.
Treatment of patients with advanced neurofibromatosis type 2 (NF2) with novel molecularly targeted therapies.
Authors: V. Subbiah, J. M. Slopis, D. S. Hong, L. S. Angelo, I. E. McCutcheon, R. Kurzrock
Journal: Journal of Clinical Oncology (2011)

2100 Background: There are minimal treatment options for advanced inoperable neurofibromatosis type 2(NF2), a rare and debilitating disorder presenting with multiple vestibular schwannomas, meningiomas, and ependymomas. Since NF2 patients harbor an aberration in a single gene (merlin), whose protein product impacts multiple signals, including PI3-kinase/Akt, Raf/MEK/ERK and mTOR, it is conceivable that one of the many agents targeting these pathways that have already shown antitumor activity in malignancies, will also cause regression of NF2-related tumors. Because of its extreme rarity, large clinical trials are challenging; we therefore enrolled patients in a variety of rationally targeted trials and sought response signals. Methods: We reviewed the records of consecutive NF2 patients referred to the Clinical Center for Targeted Therapy (Phase I Clinical Trials Program clinic) who were treated on ≥1 trial starting in January 2007. Patients were evaluated every 6-8 weeks for response using RECIST criteria and CT / MRI. Results: Six patients (men: N = 3) were enrolled on an early clinical trial. Median age at diagnosis was 26 (range 8-47). Two pts were treated with a RAS inhibitor (salirasib), and both achieved stable disease (SD) for 10 and 48+ months. One patient had SD on a MEK inhibitor for 7 months and was subsequently enrolled on several target agent-based studies including multi-kinase+HDAC, EGFR + HDAC, or EGFR inhibitor alone and has ongoing SD with a VEGF antibody (bevcizumab) for 22+ months. Two patients treated with combined bevacizumab and mTOR inhibitor show SD for 4+ and 5+ months, with the latter individual demonstrating, so far, a 9% decrease in tumor size on scans, improvement in neurologic symptoms and almost complete flattening of subcutaneous lesions. Conclusions: Referral of NF2 patients to a clinical trials center for targeted therapy demonstrates an acceptable safety profile, preliminary evidence of activity, and is pragmatic in this rare disease setting. Further evaluation of several of these therapies is warranted.
Incidence and risk of infections in renal cell cancer (RCC) and non-RCC patients treated with everolimus and temsirolimus: A meta-analysis of randomized control trials.
Authors: Marina Kaymakcalan, Youjin Je, Guru Sonpavde, Matt D. Galsky, Paul Linh Nguyen, Fabio Schutz, Daniel Yick Chin Heng, Christopher J. Richards, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2013)

353 Background: Everolimus and temsirolimus are mammalian target of rapamycin (mTOR) inhibitors used in a variety of malignancies including renal cell carcinoma (RCC). These targeted agents have been associated with a unique set of adverse events including infections. We performed an up-to-date meta-analysis of published clinical trials to further characterize the risk of infections in cancer patients treated with mTOR inhibitors. Methods: Pubmed and oncology conference proceedings were searched for studies from January 1966 to June 2012. Eligible studies were limited to phase II and III randomized controlled trials (RCTs) of everolimus or temsirolimus that reported on patients with cancer of any tumor type including RCC and with adequate safety profiles. Summary incidence, RR, and 95% CIs were calculated using random- or fixed-effects models based on the heterogeneity of the included studies. Results: A total of 2,990 patients from 8 RCTs were included. The incidence of all-grade infections due to mTOR inhibitor treatment was 35.7% (95% CI, 28.8-43.3) and that of high-grade infections was 4.2% (95% CI, 2.1-8.4). The relative risk of all-grade infection due to mTOR inhibitors was 1.95 (95% CI, 1.67-2.29, p&lt;.001) and that of high-grade infection was 1.91 (95% CI, 1.09-3.35, p=.024). Subgroup analysis found no difference in the incidence or risks of infections between everolimus and temsirolimus or between different tumor types (RCC vs. non RCC). Infections included respiratory tract (38.0%), urinary tract (17.1%), skin/soft tissue (3.6%), others (2.6%), and infection/not specified (38.7%). No evidence of publication bias was observed. Conclusions: Treatment with mTOR inhibitors, everolimus and temsirolimus, is associated with a significant increase in risk of infection in RCC and non-RCC patients.
Osteopontin as a potential molecular target for ovarian clear cell carcinoma therapy.
Authors: M. Matsuura, T. Suzuki, Y. Tabuchi, S. Habata, E. Tanigaki, M. Suzuki, R. Tanaka, M. Iwasaki, O. Hayakawa, E. Ito, Y. Ebina, T. Saito
Journal: Journal of Clinical Oncology (2011)

e15550
Comparison of combination vs. single-agent chemotherapeutic responses in primary cultures of human breast cancer cells
Authors: A. Wells, P. Kornblith, M. Connell, R. L. Ochs, D. Burholt
Journal: Journal of Clinical Oncology (2005)

831 Background: A preliminary study was conducted of the utility of the ChemoFx assay, an ex vivo chemoresponse assay, in predicting the relative effectiveness of combinations of drugs compared to the corresponding single agents in patients with breast cancer. Methods: In this retrospective study, 146 breast carcinomas were tested commercially with the ChemoFx Assay. Dose response curves were generated for each drug or combination evaluated, and a numerical score of 0–5 was assigned based on the percent cell-kill observed at each concentration of drug or combination tested. A positive response rate was defined as a score of 3 or higher. Results: One hundred out of 146 (68%) of the tumors responded to single agent Cyclophosphamide, 45 out of 91(49%) to single agent Doxorubicin, and 16 out of 20 (80%) responded for those tumors tested in combination. In 7 of 18 cases that were tested with Cyclophosphamide and Doxorubicin both as single agents and in combination, Cyclophosphamide alone was as effective ex vivo as the combination, and in 2 cases, Doxorubicin was as effective as the combination. Conclusions: The findings of this ex vivo assessment of drug response are consistent with the expected population response rate, with the majority of breast cancers tested responding to the combination of cyclophosphamide and doxorubicin. These findings suggest the assay may be clinically useful in selecting the most effective chemotherapy regimen for individual patients. A prospective evaluation of assay and clinical response is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Precision Therapeutics Precision Therapeutics Precision Therapeutics
Health-related quality of life (HRQOL) of patients 3 years after radiation therapy (RT) for early head and neck cancer (HNC).
Authors: I. Bairati, F. Meyer
Journal: Journal of Clinical Oncology (2011)

9077 Background: Cancer survivors typically experience progressive improvements in HRQOL following initial impairments associated with diagnosis and treatments. As previous studies often focused on cancer-free survivors (CFS), little information is available for non-CFS. We report a comparison of HRQOL of HNC survivors either living with cancer or cancer-free 3 years after RT. Methods: We conducted a randomized trial among 540 patients treated with RT for stage I or II HNC to test whether vitamin E supplementation improved outcomes. We assessed prospectively HRQOL with two validated instruments, the EORTC QLQ-C30 and the Head and Neck Radiotherapy Questionnaire (HNRQ), prior treatment and 3 years after RT. Three years after RT, 416 patients provided HRQOL data. Among them, 85 were non-CFS because they had been diagnosed with a relapse or a second primary cancer (SPC). We used t-tests to compare HRQOL dimensions at baseline and at 3 years between non-CFS and CFS. We also compared their HRQOL changes from baseline to 3 years. Results: At baseline, the HRQOL of future non-CFS and CFS was similar except that future non-CFS experienced more HNRQ throat symptoms (p=0.04). At 3 years, the HRQOL of non-CFS and CFS was also similar except that non-CFS had poorer QLQ-C30 global health status than CFS (p=0.01). Most changes from baseline to 3 years after RT were similar for non-CFS and CFS. There were improvements for emotional and social functioning, sleep and financial difficulties of the QLQ-C30, throat symptoms and psychosocial domain of the HNRQ, while both non-CFS and CFS had increased HNRQ oral cavity and skin symptoms. Few HRQOL changes from baseline to 3 years differed significantly between non-CFS and CFS. Non-CFS experienced a worsening in 4 HRQOL dimensions while CFS showed improvements in these 4 dimensions: global health status (p=0.01), pain (p=0.01) and appetite (p=0.02) of the QLQ-C30 and HNRQ energy (p=0.03). Conclusions: Most changes in HRQOL over the 3 years after RT are similar for CFS and non-CFS. However, patients living with cancer after HNC relapse or SPC experienced increased pain and decreased appetite, global health status and energy while CFS showed improvement in these 4 dimensions.
Serum interleukin-6, cardiovascular disease, and mortality in chronic lymphocytic leukemia.
Authors: D. E. Dawe, J. Yoon, S. Gibson, J. B. Johnston
Journal: Journal of Clinical Oncology (2010)

6581 Background: Interleukin-6 (IL-6) plays an integral role in the process of aging and autoimmunity and contributes to the increased incidence of cardiovascular disease. IL-6 levels may be elevated in chronic lymphocytic leukemia (CLL) but whether these patients also have an increased incidence of cardiovascular disease leading to mortality is unknown. Methods: 193 patients (107 males, 86 females; ages, 37-92 yr (median, 67.6 yr) with CLL attending CancerCare Manitoba between 1/1/04 and 30/12/08 were evaluated. There were an equal number of patients aged < 65 yrs and ≥ 65 yrs. Serum IL-6 levels were determined by an ELISA assay. Cardiovascular disease was defined as any symptom referable to the cardiac, neurovascular or peripheral vascular system and/or vascular procedures. Results: Plasma IL-6 levels ranged from < 0.01 to 93.1 pg/mL (median, 1.43 pg/mL). The median plasma IL-6 level in 37 age- and sex-matched controls was 0.83 pg/mL (range, 0.06-8.11 pg/mL). Using a cut-off of 3 pg/mL to define an elevated IL-6 level, high IL-6 levels occurred in 23% of patients and levels correlated with Rai stage, β2-microglobulin and age. The median number of traditional cardiac risk factors did not differ between patients with high and low IL-6 (1.66 ± 1.1 vs. 1.52 ± 1.1, respectively). Patients with cardiovascular disease had increased IL-6 (p < 0.05) and there was a trend to a higher incidence of cardiovascular disease in patients with high IL-6 (36.4% vs. 22.8%, p = 0.07). In addition, patients with high IL-6 had considerably increased mortality as 31.8% of patients with high IL-6 died versus 12.8% for patients with low IL-6 (p = 0.003). This mortality difference was amplified in those ≥ 65 years old (42.8% vs. 10.4%, p = 0.0003). The major causes of death were progressive CLL, second malignancies, and infections. Conclusions: Thus, high levels of IL-6 in CLL are associated with a significantly increased risk of mortality and this is most evident in those ≥65 years old. Although cardiovascular disease is not the primary cause of death, it is associated with high levels of IL-6 and may contribute to progression of CLL. No significant financial relationships to disclose.
Predictors of disease control in patients treated with platinum-based chemotherapies for metastatic squamous-cell esophageal cancer: First results of the e-DIS trial.
Authors: Antoine Adenis, Jaafar Bennouna, Marie-Pierre Galais, Emmanuelle Tresch, Eric Francois, Pierre-Luc Etienne, Meher Ben Abdelghani, Pierre Michel, Jean-François Seitz, Thierry Conroy, Francois Ghiringhelli, Laurent Bedenne, Emmanuelle Samalin, Guillaume Piessen, Sandrine Hiret, Charlotte Peugniez, Helene Herin, Stephanie Clisant, Andrew Kramar, Christophe Mariette
Journal: Journal of Clinical Oncology (2014)

95 Background: There is little evidence that chemotherapy (CT) impacts on outcome of patients with MSEC. We designed an ongoing randomized phase 2 trial to detect a progression-free survival benefit of CT continuation over CT discontinuation in disease-controlled and ECOG≤2 patients at 6 weeks after an initial CT treatment. The aim of the present study was to identify predictors of disease control at 6 weeks (DC 6wkx ) in MSEC patients receiving platinum-based CTs as first-line treatment for metastatic disease. Methods: Among 68/70 evaluable patients included between 1/2011 and 7/2013 who received at least 1 CT cycle, 58 were evaluable for disease assessment at 6 weeks. Ten patients were not evaluable (early death: 4, patient’s decision: 2, concomitant disease 1, early progressive disease 1, other reasons: 2). Baseline demographic, clinical, biological, and tumor characteristics were tested for prediction of DC 6wkx . Significant variables for DC 6wkx were identified with the chi-squared test and logistic regression. Results: Baseline patients characteristics were as follows: median age: 61.5yo; male: 57/68; ECOG 0/1/2: 13/42/13; metachronous/synchronous MSEC: 38/30; number of metastatic sites 1/2/&gt;2: 35/20/13; metastatic location: lung 36, liver 23, bone 11, nodes 37, other 11; prior exposure to CT: 37/68; time from previous CT exposure: ≤ 6m 6/37, 6-12m 14/37, &gt; 12m 17/37; gr&gt;2 dysphagia (Atkinson) 19/67; BMI&lt;18.5kg/m²: 13/68. Current CTs were FU-CDDPq3w 2/68, LV5FU2-CDDPq2w 15/68, FOLFOX 51/68, and patients received the following number of cycles 1/2/&gt;2: 5/7/54. DC 6wkx rate was 65.7%, with 16/68 PR (23.5%) and 28/68 SD (42.2%). Albumin (p&lt;0.01), BMI (p&lt;0.02), bone metastases (p&lt;0.005), gender (p&lt;0.047) and ECOG status (p&lt;0.05) were predictive of DC 6wkx . Normal or overweight BMI, grade 0 albumin, and no bone metastases, were predictive of DC 6wkx in multivariate analysis. Conclusions: DC at 6 wks was 65.7% in MSEC receiving platinum-based CTs as first line treatment for metastatic disease. Normal or overweight BMI, normal albumin, and the absence of bone metastasis were significant predictors of DC 6wkx in this prospective phase 2 trial. Clinical trial information: NCT01248299.