tbuckley/cabot-search huggingface dataset:
Impact of <i>MGMT</i> promoter methylation in glioblastoma of the elderly.
Authors: M. Weller, B. Hentschel, J. Felsberg, G. Schackert, M. Simon, O. Schnell, M. Westphal, W. Wick, T. Pietsch, M. Loeffler, G. Reifenberger
Journal: Journal of Clinical Oncology (2011)

2001 Background: Methylation of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter identifies a subpopulation of glioblastoma patients with a more favorable course of disease and predicts a major benefit from alkylating agent chemotherapy. Little is known about the prevalence and clinical significance of this molecular biomarker in elderly patients with glioblastoma. Methods: We studied the prognostic and predictive power of MGMT promoter methylation in glioblastoma patients aged 70 years or more who were prospectively enrolled in the German Glioma Network (GGN). MGMT promoter methylation was assessed by methylation-specific PCR (MSP) in all patients and DNA pyrosequencing in a subset of 166 patients. Results: 233 patients (144 male, 89 female, median age 74, range 70.0-86.6) were included. Median progression-free survival (PFS) was 4.8 months (95% CI 4.3-5.3), median overall survival (OS) was 7.7 months (95% CI 6.3-9.0). MGMT promoter methylation was detected by MSP in tumors of 134 patients (57.5%). For the whole cohort, PFS was 5.2 versus 4.7 months (p=0.207), and OS was 8.4 versus 6.4 months (p=0.031), in patients with versus without MGMT promoter methylation. Patients with MGMT promoter-methylated tumors had longer PFS when treated with radiotherapy (RT) plus temozolomide (TMZ) or TMZ alone, compared with patients treated with RT alone (p=0.001). Patients with MGMT promoter- unmethylated tumors had no survival benefit from TMZ whether given at diagnosis together with RT or as a salvage treatment. Patients treated with RT plus TMZ or TMZ alone demonstrated longer OS when pyrosequencing revealed more than 25% MGMT methylated alleles. Conclusions: Despite the overall worse prognosis in the elderly, MGMT promoter methylation is nevertheless more frequent in this population and may be a useful biomarker to stratify elderly glioblastoma patients for treatment with versus without alkylating agent chemotherapy.
Multi-institutional assessment of sphincter preservation for rectal cancer.
Authors: Zaid M. Abdelsattar, Sandra L. Wong, Nancy J. Birkmeyer, Robert K. Cleary, Melissa L. Times, Ryan E. Figg, Nanette Peters, Robert W. Krell, Darrell A. Campbell, Samantha K. Hendren
Journal: Journal of Clinical Oncology (2014)

566 Background: Rates of sphincter preserving surgery (SPS) have been proposed as a quality measure for rectal cancer (RC) surgery. However, administrative and registry-based SPS rates often lack critical patient and tumor characteristics, rendering it unclear if variations in SPS rates are due to unmeasured case-mix differences or selection criteria. The aim of this study was to determine whether hospitals’ SPS rates differ after accounting for clinical characteristics. Methods: As part of a RC quality project, 10 hospitals in the Michigan Surgical Quality Collaborative retrospectively collected RC-specific data from 2007-2012. We assessed for SPS predictors using multivariable regression. Patients were categorized as “definitely SPS eligible” a priori if they did not have any of the following: poor sphincter control, stoma preference, sphincter involvement, tumor &lt;6 cm from the anal verge (an intentionally conservative cutoff) or metastatic disease. We compared hospital performance with and without these clinical data using Spearman’s correlations. Results: In total, 349 patients underwent surgery for RC in 10 hospitals (5/10 high volume and 6/10 major teaching). Of those, 74% had SPS (range by hospital 50%-91%). On multivariable analysis, only pre-op radiation, tumor location, hospital teaching status and hospital ID were independent predictors of SPS, but not age, sex, BMI, AJCC stage, ASA class, or hospital CRC surgery volume. Analyses of the “definitely eligible” patients revealed an overall SPS rate of 88% (65-100%). Hospital SPS rankings using crude versus clinically-adjusted SPS rates proved to be highly correlated (Spearman’s ρ= 0.9). Tumor locations suggest differing selection criteria for SPS in different hospitals (Table). Conclusions: Rates of SPS vary by hospital, even after correcting for clinical characteristics using detailed chart review. These data suggest missed opportunities for SPS, and refute the general hypothesis that hospital variation in SPS rates in previous studies is due to unmeasured case-mix differences. [Table: see text]
A new predictive model based on age, pretreatment LDH, and post-therapy PET-CT in patients with MCL treated with dose-intensive strategies.
Authors: A. R. Mato, T. Feldman, T. Zielonka, S. Goldberg, S. D. Rowley, M. Donato, D. S. D. Siegel, D. H. Vesole, A. Campaiola, K. Facchin, S. Stives, C. Bejot, M. Curtin, M. Miller, H. Agress, D. Panush, P. Lizotte, A. Pecora, P. Bhattacharyya, A. Goy
Journal: Journal of Clinical Oncology (2011)

8051 Background: The use of dose-intensive strategies (R-HyCVAD) and/or high dose therapy with autologous stem cell transplant (HDT/ASCT) in the1st-line setting in MCL has shown improvement in PFS and likely OS over R-CHOP. There is no established prognostic model in the context of dose-intensive therapies. The MIPI has been validated in some studies but not universally. Emerging data suggest predictive value of post-therapy PET in MCL. Methods: Utilizing Cox regression and ROC analyses, we conducted a retrospective study examining risk factors associated with survival (OS and PFS) in MCL: age, ECOG PS, LDH, WBC, beta-2m and post-treatment PET-CT. Our cohort was limited to MCL pts treated with R-HyCVAD (60%) and/or HDT/ASCT (40%). PET-CT images were centrally reviewed by three radiologists blinded to outcome using standardized response criteria (International Harmonization Project in Lymphoma). Results: With a median follow up of 35 months, 93 pts representing 4160 months at risk were identified. In univariate analysis LDH, age ≥ 60 and post therapy PET-CT status were associated with inferior survival. In multivariate analysis LDH (using MIPI cut points) (HR 2.2, p=.008, CI 1.2-4.1), age (HR 5.5, p=.02, CI 1.3-24.1) and post therapy PET-CT status (HR 7.9, p=.009, CI 1.7-37.7) remained independent predictors of OS. Based on these 3 variables a scoring algorithm (Table) was designed leading to a model (AU ROC area 86%, CI 72-94%) able to identify 2 distinct prognostic subgroups (good risk: score 0-2 vs. poor risk: score 3-4) with median PFS (46 vs. 11 months) and OS (median OS not reached vs. 30 months). Conclusions: The value of current prognostic indexes IPI and MIPI in the setting of dose-intensive strategies in MCL is debated and needs validation. Using the clinical variables of these indexes and PET imaging, 3 variables (age, LDH and PET status) were predictive of outcome. Our prognostic model integrates PET status post therapy with baseline clinical parameters and might help identify early on subsets of pts for alternate strategies/maintenance or consolidation to improve outcomes. Points LDH/ULN Age PET-CT status 0 <0.67 <60 years Negative 1 0.67-0.99 ≥ 60 years Positive 2 1.0-1.49 3 ≥ 1.50
Prognostic classifier for stage II gastric cancer based by support vector machine.
Authors: R. Xu, D. Ruan, M. Oiu, Z. Zeng, H. Zhang, H. Luo, Z. Zhu, B. Sun
Journal: Journal of Clinical Oncology (2011)

e14565 Background: Though stage II gastric cancer patients can be cured by surgery, quite a part of them have poor prognosis. Many clinical and molecular features have been reported associated with gastric cancer, determine prognosis and direct clinical decisions. How to select and combine such massive information? Support Vector Machine (SVM), one of machine-learning methods, can solve this problem admirably. Methods: A retrospectively database was established of 154 patients with stage II gastric adenocarcinoma at Cancer Center of Sun Yat-sen University between May 1996 and February 2005. 16 clinical features and 38 molecular indices were investigated, which involved biological characteristics of gastric cancer. Molecular markers were detected by tissue array and immno- histochemical (IHC) staining. Use SVM to screen the clinical-molecular features based on a 103 patients’ training cohort and establish a best survival prediction model. Individual 5-year survival prediction was performed in 51 patients’ validation cohort and the prediction data was compared with the real follow-up data. Results: The SVM model integrates three clinicopathologic features (tumor diameter, preoperative hemoglobin level, adjuvant chemotherapy ) and 24 immunomarkers (Survivin, cmyc, CD44v6, MMP7, CK19, P16, PTEN, TIMP1, CyclinE, MMP2, SMAD4, VEGF, MUC2, Ecadherin, Her2, CK20, P27, APC, CD147, cmet, COX2, CDX2, MGMT, EMA). When analysis was performed with the validation cohort individually, we identified 14 patients with high risk and 37 with low risk according to SVM model. The 1, 3, 5-year survival rates were 85.7%, 21.4% and 14.3% respectively for high-risk patients and 100%, 94.6% and 86.5% for low-risk patients. The SVM model was also strongly associated with overall survival (sensitivity, 94.1%; specificity, 70.6%; positive predictive value, 85.7%; negative predictive value, 86.5%; and overall accuracy, 86.3%). Conclusions: The SVM-based classifier including clinical-molecular information can reliably predict the stage II gastric cancer patients’ prognosis.
Randomized phase II study of S-1/CDDP plus TSU-68 versus S-1/CDDP in patients with advanced gastric cancer.
Authors: Kensei Yamaguchi, Wasaburo Koizumi, Hisashi Hosaka, Yasutaka Takinishi, Norisuke Nakayama, Takuo Hara, Kei Muro, Hideo Baba, Yasutsuna Sasaki, Tomohiro Nishina, Nozomu Fuse, Taito Esaki, Masakazu Takagi, Masahiro Gotoh, Ryuichi Kitamura, Hideki Matsumoto, Tsuneo Sasaki
Journal: Journal of Clinical Oncology (2013)

72^ Background: Gastric cancer (GC) is the second leading cause of cancer death in Japan as well as globally. Effective treatment of GC remains a therapeutic challenge. Although in the AVAGAST trial, bevacizumab was found to offer no survival benefit. Angiogenesis continues to be the standard treatment for GC, and thus, clinical trials on many anti-angiogenic drugs have been conducted. TSU-68 (orantinib) is an oral, angiokinase inhibitor targeting the vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor β, and fibroblast growth factor receptor 1. The present study evaluated the progression-free survival (PFS) and pharmacokinetics (PK) of TSU-68 in combination with Japanese standard S-1 and cisplatin (S-1/CDDP) in patients with advanced GC. Methods: In this open-label, multicenter, randomized, controlled, parallel-group, phase II trial, patients were randomized to Arm A (S-1/CDDP) or Arm B (TSU-68 plus S-1/CDDP). All patients received oral S-1 (40-60 mg/m 2 ) twice daily for 21 days followed by a 14 day rest plus intravenous CDDP (60 mg/m 2 ) on Day 8, repeated every 35 days. In Arm B pts received oral TSU-68 (400 mg/dose) alone, twice daily by addition 35 days. The primary endpoint was PFS. Results: In total, 93 patients were enrolled. For Arm A [male:female ratio], n=47 [35:11]; Arm B, n=45 [30:15]; the respective median age was 63.5 and 62.0 years. The median PFS was 7.0 and 6.8 months in Arms A and B, respectively (HR, 1.23; 95%CI, 0.74 to 2.05; P=0.425); the respective response rates were 56.5% and 62.2%. The most common grade 3/4 toxicities were neutropenia (Arms A and B, 34.8% and 31.1%) and hemoglobin (Arms A and B, 26.1% and 48.9%). There were no differences in other toxicities between the 2 arms, both treatments were tolerated, and no treatment-related deaths were observed. In the PK study, although Arm B had a significantly lower plasma exposure to FT, CDHP, and Oxo compared to Arm A, the exposure to 5-FU was not different between the 2 arms. The exposure to CDDP in Arm B was significantly but slightly lower than that in arm A. Conclusions: Thus,TSU-68 plus S-1/CDDP therapy did not prolong PFS of patients with advanced GC as compared with S-1/CDDP. Clinical trial information: JapicCTI-101327.
Identifying opportunities to improve quality of cancer care: An evaluation of the use of routine surveillance imaging scans in women with early breast cancer (EBC) treated in Ontario, Canada.
Authors: Katherine Enright, Mohammed Ghannam, Lingsong Yun, Nathan Taback, Christopher M. Booth, Maureen E. Trudeau, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2013)

115 Background: Over use of routine surveillance imaging to detect recurrence in women with EBC was recently identified as one of the top five opportunities to improve the quality of cancer care by the American Society of Clinical Oncology. We undertook a population level assessment of the current practice of surveillance imaging in EBC women treated in Ontario Canada. Methods: Incident EBC patients diagnosed 01/07 – 12/09 in Ontario, Canada were identified from the Ontario Cancer Registry. Patient records were linked deterministically to provincial health care databases to provide comprehensive medical follow-up. Basic (chest x-ray, abdominal x-ray and abdominal ultrasound) and advanced (computed tomography [CT] or bone scans) surveillance imaging scans completed during the first and second year of follow-up (starting 6 months after surgery or upon completion of chemotherapy) were identified. Logistic regression models were used to identify covariates associated with advanced surveillance imaging. Results: 16,981 EBC patients were included in the analysis of which 7,907(46.6%) received chemotherapy. In the first year of follow up care, 8,311 (48.9%) had at least 1 basic imaging test, while 4,916 (29.0%) had advanced imaging. This fell to 45.7% (basic) and 25.1% (advanced) in the second year of follow-up. Bone scans were the most common advanced imaging test (14.5%), followed by CT thorax (10.8%). On multivariable analysis age, stage, the use of chemotherapy and comorbidity were associated with increased use of advanced surveillance imaging (Table). Conclusions: Surveillance imaging was common in the first two years of follow-up for EBC patients. While appropriate for symptom driven investigation, the high rate of advanced imaging scans suggests an opportunity for improvement with the Ontario cancer system. [Table: see text]
Impact of the USPSTF D recommendation: Early assessment of referrals for elevated PSA and prostate biopsies in a LUGPA following statement revision.
Authors: Kathleen F. McGinley, Gordon Andrew Brown
Journal: Journal of Clinical Oncology (2013)

e16041 Background: In October 2011, the U.S. Preventative Services Task Force (USPSTF) posted for public comment the draft of their recommendation against PSA-based prostate cancer screening. Extensive media coverage and discussion within the medical community ensued. The USPSTF released their formal statement of a D recommendation in May 2012. While the potential implications of the USPSTF recommendation upon prostate cancer screening will take years to manifest, the early impact of their recommendations upon the market is evaluable. Methods: The electronic medical record of a large urology group practice composed of 32 providers was queried for two variables: the number of referrals for an elevated PSA and the number of individuals who underwent a prostate biopsy. A control period of October 2010-September 2011 was selected and compared to October 2011-September 2012, the twelve month period beginning with release of the USPSTF draft against PSA-based prostate cancer screening. Results: From October 2010 to September 2011, 28,698 patients were evaluated for an elevated PSA by 32 urologists; from October 2011 to September 2012, 25,075 patients were evaluated by the same number of physicians, a difference of 12.6% following release of the USPSTF recommendations. From October 2010 to September 2011, 2465 patients underwent a prostate biopsy; from October 2011 to September 2012, 1989 had a biopsy, a difference of 19.3%. Conclusions: A marked decrease in the number of patients referred to a large urology group practice for evaluation of an elevated PSA, and an even greater decrease in the number of prostate biopsies performed, occurred in the 12 months following release of the USPSTF recommendations against PSA-based prostate cancer screening.
Randomized controlled trial on the skin toxicity of panitumumab in third-line treatment of <i>KRAS</i> wild-type metastatic colorectal cancer: HGCSG1001 (Japanese Skin Toxicity Evaluation Protocol with Panitumumab; J-STEPP).
Authors: Ichiro Iwanaga, Yoshito Komatsu, Satoshi Yuki, Yoshimitsu Kobayashi, Naoya Sakamoto, Minoru Uebayashi, Hiroyuki Okuda, Takaya Kusumi, Susumu Sogabe, Takuto Miyagishima, Miki Tateyama, Yasushi Tsuji, Kazuteru Hatanaka, Michio Nakamura, Jun Konno, Fumiyasu Yamamoto, Kazuhiro Iwai, Manabu Onodera, Koji Oba, Yuh Sakata
Journal: Journal of Clinical Oncology (2014)

541 Background: Panitumumab (Pmab), a fully human monoclonal antibody targeting the EGFR, has been demonstrated the efficacy in patients with KRASwild-type metastatic colorectal cancer (mCRC). Though STEPP study (Lacouture et al, JCO 2010) showed that pre-emptive skin treatment reduced skin toxicities compared with reactive treatment among patients receiving Pmab, the data of Asians has not been reported. We planned a randomized controlled open-label trial to verify the differences between pre-emptive and reactive treatment for skin toxicities in Japanese patients. Methods: Patients receiving Pmab-containing treatments as third line regimen for mCRC were randomly assigned 1:1 to pre-emptive or reactive skin treatment group. In the pre-emptive treatment group, patients received skin moisturizers, sunscreen, topical steroid and minocycline. In the reactive treatment group, patients received only skin moisturizers. The primary endpoint was the cumulative incidence of ≥ grade 2 skin toxicities during the 6-week treatment period. Retrospectively, dermatologist reviewed skin toxicities with photographs in blinded manner. Results: Out of 95 enrolled patients, 47 patients were randomly assigned to pre-emptive group, and 48 to reactive group. The incidence of ≥ grade 2 skin toxicities during the 6-week treatment period (according to investigator’s assessment) was 21.3% and 62.5% (risk ratio [RR] = 0.34, 95% CI 0.19 - 0.62; p&lt;0.001) for the pre-emptive and reactive treatment groups, respectively. A similar trend was observed in central review by dermatologist (18.6% and 50.0%, respectively [RR = 0.37, 95% CI 0.19 - 0.74; p = 0.002]). The concordance rate between them was 75.8%. Median time to first occurrence of ≥ grade 2 skin toxicities was not reached in the pre-emptive group and 3.2 weeks (95% CI 1.9 - 6.1) in reactive group (p &lt; 0.001). Conclusions: The pre-emptive skin treatment could reduce the severity of the skin toxicities during the Pmab treatment. Our data clearly validate that the pre-emptive treatment is also recommended in Japanese patients. Clinical trial information: 000004883.
Comparing three methods for scoring late breast cosmesis in patients treated with lumpectomy and radiation therapy (RT).
Authors: Andrew Thomas Wong, Celina Robertson-Parris, Sonal Sura, Carol White, Manjeet Chadha
Journal: Journal of Clinical Oncology (2014)

128 Background: For intact breast, the Harvard and LENTSOMA criteria are widely used to report late cosmesis. These scales require clinician’s interpretation and thus may be subject to variation between evaluators. Computerized tools exempt from evaluator bias are available to assess cosmesis. The objective of this study was to perform a comparative review of late breast cosmesis using the Harvard, LENTSOMA, and BCCT.core scales (Cardoso JS. et al; doi:10.1016/j.artmed.2007.02.007). Methods: A frontal bilateral breast photograph was used for analysis. Late cosmesis was scored with reference to the baseline breast appearance, ~ 1 year from RT distant from the acute treatment effects. Cosmesis was graded as excellent, good, fair, or poor using the Harvard scale. For LENTSOMA, only atrophy/retraction was assessed from the frontal breast photographs. The BCCT.core software was used as a validated tool for objectively scoring cosmesis and computes a score based on symmetry, color, and scar visibility. All outcomes were assessed by the same investigator (AW). Results: A total of 33 patients had 1-year baseline and follow up photographs. All were treated on a 3-week hypofractionated RT schedule, and none received chemotherapy. One hundred photographs, 1 to 5.7 years from end of RT, were scored. Late cosmesis among patients with good/excellent scores at 1-year remained unchanged by all 3 methods. Among patients graded as fair at 1-year, there was improvement in late comesis detected by Harvard and BCCT.core scoring. Late cosmesis by LENTSOMA criteria remained unchanged from baseline. Conclusions: Our experience suggests easy applicability of BCCT.core for scoring cosmesis in clinical practice. We observed no significant differences in cosmetic score by the methods used. However, these observations were made on a small cohort of patients and evaluation on a larger cohort is needed. The role of objective user-independent grading of cosmesis might be helpful in large comparative studies of clinical outcomes. [Table: see text]
Preoperative intensity modulated radiation therapy for retroperitoneal sarcoma.
Authors: Nancy El Bared, Daniel Taussky, Selma Mehiri, Erika Patocskai, David Donath
Journal: Journal of Clinical Oncology (2013)

322 Background: The use of intensity modulated radiation therapy (IMRT) has allowed for the administration high doses to retroperitoneal sarcomas (RSTS) while limiting toxicity to adjacent organs. The purpose of our study is to assess the outcome and toxicities of patients with RSTS treated with neoadjuvant external beam radiation (EBRT) therapy using IMRT. Methods: This is a retrospective study of 21patients treated with preoperative IMRT for primary or recurrent RSTS between 2005 and 2011. Overall survival (OS) and local recurrence free survival (LRFS) were computed using the Kaplan-Meier method (log-rank test). Acute and chronic toxicities were assessed according to the CTCAE v. 3 criteria. Results: The actuarial 3 and 5-year OS and LRFS was 66% and 51%, 57% and 41% respectively. Factors predictive for LRFS were microscopically negative margins (p=0.022), a median tumor diameter &lt; 15 cm (p=0.007) and a pathology of liposarcoma (p=0.021); however, patients treated for recurrent disease fared worse (p=0.04). As for OS, grade 1 histology was a predictive factor for better outcome (p=0.05). EBRT was generally well tolerated. Acute gastrointestinal grade 1 or 2 toxicity occurred in 33% of patients and one patient had unexplained post-radiation grade 2 fever that resolved after tumor resection. As for chronic toxicities 24% of our patients presented grade 1 gastrointestinal toxicity and one patient presented grade 3 small bowel stenosis not clearly due to radiation toxicity. Conclusions: Despite the location and volume of the tumors treated, preoperative IMRT was very well tolerated in our patients with retroperitoneal sarcoma. Unfortunately local recurrences remain common and dose escalation is to be considered.