bluuebunny/crossref_metadata_2025_split huggingface dataset:
3-D MRI guided breast conserving surgery
Authors: Hisamatsu K. 
Published: March 2020

610 Background: In breast cancer patients, accurate diagnosis of ductal spreading is of great importanace for deciding sugical procedure. The role of imaging diagnosis using 3D-MRI in deciding of ductal spreading was assessed histologically and efficacy of 3D-MRI guided surgery was evaluated. Methods: Preoperative 3D-MRI was underwent 374 cases of breast cancer patients. Images were obtained 371 cases (99%). These patients could be divided into four groups according to 3D-MRI images: pattern 1) localized type, 2) widely enhanced type A (enhanced area: less than Quadrant) and 3) widely enhanced type B (enhanced area: more than Quadrant) and 4) multifocal type. Diagnosis of ductal spreading was confirmed histologically and relation between 3D-MRI patterns and ductal spreading were assessed retrospectively. Local failure of 3D-MRI guided surgery was assessed by 3D-MRI image patterns Results: The rate of histological confirmed ductal spreading were seen in 59% (125/212cases), 86% (49/57 cases) and 83% (19/23cases) of patients with 3D-MRI pattern 1), 2), and 3), respectively. From April 2005, resected specimen was serially step cut and total specimens were evaluated. Tumor diameter from nipple side to lateral margin were measured by MRI and resected specimens, tumor size was correlated between MRI and resected specimens, significantly (n=80, r=0.790887, P < 0.001). Whole breast examination revealed that only 4 cases were multifocal cancer in 17 cases of multifocal image in 3D-MRI. Patient selection for breast conserving surgery was based by 3D-MRI images. The proportion of breast-conserved surgery were obtained 96% (203/212 cases), 86% (49/57 cases), 26% (6/23cases) and 89% (68/76 cases) of patients with 3D-MRI pattern 1), 2), 3), and 4), respectively. Local failures were seen 2cases in pattern 1), one case in 3) and one case in 4) (2–77 months, median follow up 39 months). Conclusions: These results suggest that MRI will be the useful breast imaging tool in diagnosing ductal spreading and tumor size in breast cancer patients. Safety breast conserving surgery was achieved by MRI guided surgery. No significant financial relationships to disclose.
Therapeutic radiation for breast cancer in BRCA mutation carriers and contralateral breast cancer (CBC) risk
Authors: Moore H. C. , Wesolowski R. , Choueiri T. K. , Rybicki L. , Shealy A. G. , Casey G. , Weng D. 
Published: March 2020

611 Background: BRCA mutation carriers diagnosed with breast cancer are at high risk for contralateral second primary breast cancers. Mutations in BRCA1 and BRCA2 lead to defects in DNA repair. Radiation treatment for breast cancer is felt to increase risk of CBC, but the interaction between BRCA status and local radiation therapy with respect to their effects on CBC is unclear. Methods: Through an IRB approved database registry at the Cleveland Clinic, breast cancer patients tested for BRCA1 and BRCA2 mutations were identified and evaluated for CBC events and radiation treatment history. Patients with inadequate clinical follow-up, those with bilateral synchronous breast cancer and those undergoing bilateral mastectomy within one year of the original breast cancer diagnosis were excluded from the analysis. Chi-square test was used to compare CBC rates with or without prior radiation separately in patients testing positive and those testing negative for BRCA mutations. Results: Of 115 identified breast cancer patients tested for BRCA mutations, 57 met the inclusion criteria. Twenty-one carried BRCA1 or BRCA2 mutations and 36 tested negative for these mutations. Median follow-up for the two groups was 69.5 months (92 months in BRCA positive group and 51.5 months in BRCA negative group). Median age at diagnosis was 45 years (41 years in BRCA positive group and 48.5 in BRCA negative group). Among the 21 carriers, 9 patients (43%) developed CBC while only 3 of 36 patients (8%) testing negative for BRCA mutations developed CBC. Thirteen of 21 mutation carriers (62%) had received radiation treatment for the original cancer: CBC occurred in 3 of 13 (23%) radiated patients and 6 of 8 (75%) patients who had not received radiation (p= 0.02). Among 36 patients with negative BRCA testing, 30 (83%) had received radiation: CBC occurred in 3 of 30 (10%) mutation negative patients who had received prior radiation and in 0 of the 6 patients who had not received radiation (p = 0.42). Conclusions: CBC incidence was higher among BRCA mutation carriers than a control group suspected of having hereditary breast cancer but testing negative for these mutations. The use of radiation in the presence of a BRCA mutation, however, does not appear to further increase the risk for CBC. No significant financial relationships to disclose.
Impact of poor prognostic features on the surgical treatment of breast cancer in an intergroup adjuvant chemotherapic trial
Authors: Pockaj B. A. , Dueck A. , Tenner K. , Perez E. 
Published: March 2020

612 Background: The adoption of new breast surgical techniques has been rapid for early stage breast cancer. The utilization of these techniques in patients with high risk operable breast cancer has not been thoroughly investigated. Methods: Retrospective surgical data was summarized for patients entered into N9831 “Phase III Trial of Doxorubicin and Cyclophosphamide Followed by Weekly Paclitaxel With or Without Trastuzumab as Adjuvant Treatment for Women With HER-2 Over-expressing or Amplified Node Positive or High-Risk Node Negative Breast Cancer.” Results: 3,505 patients were entered into N9831 from 2000–2005 following primary surgery for breast cancer. The median age was 50 and 43% were premenopausal. 93% of patients underwent a diagnostic biopsy prior to their definitive surgical procedure. Whether HER2-neu status was available at time of definitive surgery is unknown. 61% underwent a mastectomy whereas 39% underwent breast conserving surgery (BCS). The rate of BCS was relative stable over the course of the trial. Patients with T1 tumors had a higher rate of BCS (49%) compared to T2 tumors (37%) and T3 tumors (6%). Sentinel lymph node (SLN) biopsy was performed in 54% of the cases. The rate of SLN biopsy increased from 40% in 2000 to 66% in 2005. Patients who underwent mastectomy had a lower rate of SLN biopsy than patients who underwent BCS (44% versus 71%, respectively). Tumor size was also associated with the rate of SLN biopsy: T1 (60%), T2 (53%), and T3 (36%). Data on local and regional recurrences are still maturing. Conclusions: Surprisingly, low numbers of patients on this trial underwent BCS whereas the adoption of the SLN biopsy procedure among the same group of surgeons was relatively high. The relatively low rate of BCS in this study population needs further investigation to determine what surgeon and patient factors impacted the surgical decision. No significant financial relationships to disclose.
Perception of African American men of their likelihood of a cancer diagnosis at the time of prostate biopsy
Authors: Dale W. , Hemmerich J. , Ahmad F. , Meltzer D. 
Published: March 2020

6503 Background: Men are supposed to have an “informed discussion” before undergoing PCa screening. African Americans (AA) are diagnosed at later stages of prostate cancer (PCa) than their white counterparts. We studied racial differences in self-prediction compared with actual likelihood of positive biopsy. Method: Face-to-face surveys with patients (n = 172), referred after screening positive for possible PCa, were conducted in urology clinics at the time of biopsy. The surveys include socio-demographics, general anxiety (Hospital Anxiety and Depression Scale), disease-specific anxiety (Memorial Anxiety Scale for Prostate Cancer), and self-estimated likelihood of a positive biopsy. Medical records were reviewed for biopsy results. Results: Average age was 63±7.9, AA comprised 39% of the sample, and 56% had at least a college degree. The overall rate of positive biopsy was 55%, with AA being much more likely to have a positive biopsy (70% vs. 44%; p< 0.05). Despite being referred for biopsy for concern about PCa, 37% of the men indicated that they had a 0% likelihood of having prostate cancer (i.e. that it was impossible), and AA were more likely than whites to say this (58% vs. 24%; p < 0.01). In a logistic regression with important covariates, patients’ ratings of their likelihood of PCa diagnosis were not predictive of a positive biopsy, while older age, higher PSA score, and lower self-rated health were. Generalized anxiety was not correlated with estimated likelihood of having PCa, but cancer-specific anxiety was correlated (p = 0.02). Neither was correlated with likelihood of having PCa. Conclusion: AA are more likely to have PCa at biopsy than whites. Both groups dramatically underestimate their statistical likelihood of having PCa at the time of biopsy. More concerning, AA estimates are lower, yet their likelihood is higher. No significant financial relationships to disclose.
Standard therapy deviations in the practice of clinical oncology
Authors: Rivarola E. G. , Gil Deza E. , Negro A. , Morgenfeld E. , Juarez D. , García Gerardi C. , Santillán D. , Gercovich F. G. 
Published: March 2020

6504 Background: “Errors can be prevented by designing systems that make it hard for people to do the wrong thing and easy for people to do the right thing” (To Err is Human: Building a Safer Health System - report from the Institute of Medicine- USA). The current paper was designed to evaluate, prospectively, the different types of prescription deviation from standards as well as the way they are worked out in the daily practice. Methods: Between October 2004 and December 2006, the Tx of 6611 patients ( pt) were progressively entered into a database and compared with the national and international Tx recommendations (Evidence Based Oncology). The deviations between actual and recommended Tx were classified in two groups: Type I, or deviation from “Gold standard” (Off label prescription, experimental treatments or application of translational research with no evidence of better results regarding survival and/or quality of life over a standard Tx) and Type II, or medical errors with high malpractice risk (misdiagnosis, or drug prescription error in dosage, administration or schedule). The deviation was then pointed out to the attending physician, and their response was catalogued as: “A” (Immediate Correction), ‘B‘ (Administrative appeal to determine the treatment) or “C” (Court appeal to determine the treatment). Results: Eight hundred and sixty two errors were identified in the 6611 pt (13%). Six hundred and forty four (74,7%) were Type I and 218 (25,3%) were Type II.. The physicians were more reluctant to recognize Type I than Type II deviations. The response to the deviations were the following: Type I, response A= 454 cases (71%), Type I, response B 184 cases (28%), Type I, response C: 6 cases (1%). Type II response A: 196 cases (90%), Type II response B: 22 cases (10%). Type II response C: 0. Conclusions: 1) The implementation of a treatment-supervision system is the first step towards providing safer health care in oncology. 2) The 644 Type I prescriptions deviation appear to increase in relation to diffusion of innovations, and their modification is more conflictive. However, 71% are corrected immediately. 3) The 218 Type II prescriptions deviation appear to be related with medical expertise, and their resolution is simpler (90 % with immediate correction). An exhaustive taxonomy of deviations will be presented. No significant financial relationships to disclose.
Trends in the quality of external beam radiotherapy for elderly men with localized prostate cancer
Authors: Bekelman J. E. , Zelefsky M. J. , Jang T. L. , Basch E. M. , Schrag D. 
Published: March 2020

6507 Background: External beam radiotherapy (EBRT) is a commonly used for treatment of clinically localized prostate cancer. Yet, secular trends in the delivery of this highly technical therapy have received little attention. Methods: Using data from the linked Surveillance, Epidemiology, and End Results (SEER) Medicare program, we evaluated trends in five EBRT quality measures among 23,018 patients age 65 or older diagnosed from 1994 to 2002 with clinically localized prostate cancer and treated with primary EBRT. Using tumor registry data from SEER and Medicare claims, we excluded 6,956 patients who received brachytherapy and 7,009 patients who received combination EBRT and brachytherapy. We identified treating radiation oncologists via unique physician identification numbers reported on claims and obtained board certifications from the AMA Masterfile. We assessed the five EBRT quality measures proposed by a RAND expert panel that were amenable to analysis using SEER-Medicare data: 1) use of conformal radiotherapy treatment planning; 2) use of high-energy (=10MV) photons; 3) use of custom immobilization; 4) radiation oncologist board certification; and 5) completion of two follow-up visits with a radiation oncologist in the year following therapy. Results: As shown in the table , conformal radiotherapy increased over the study period. Approximately one-third of patients received consistent follow-up from a radiation oncologist in the year following therapy. Notably, however, claims data revealed that 80% of patients completed at least two follow-up visits with either urologists or radiation oncologists. Conclusions: Conformal radiotherapy is now routine for elderly men with localized prostate cancer. Observed practice patterns deviate from the RAND metric for patient follow-up, suggesting that this measure merits clarification. Future research should examine whether variation in receipt of these quality measures affects important clinical outcomes. No significant financial relationships to disclose. [Table: see text]
Questionable value of attribution when interpreting adverse event data: A joint evaluation by North Central Cancer Treatment Group (NCCTG) and American College of Surgeons Oncology Group (ACOSOG)
Authors: Hillman S. L. , Sargent D. J. , Bot B. M. , DeMatteo R. P. , Perez E. A. , Ballman K. V. , Mandrekar S. J. 
Published: March 2020

6511 Background: In March 1998, the Common Toxicity Criteria (CTC) version 2.0 introduced the collection of attribution of adverse events (AE) to study drug. Collection of attribution adds time and cost to the clinical trial process, and reporting in the literature has varied. At ASCO 2006 results were presented from NCCTG trial 97–24–51 that showed ∼ 50% of events on the placebo arm were reported as attributed to study drug and 25% of the time the same event was not consistently attributed. We sought to validate these results in a second placebo controlled trial. Methods: Patients on the placebo arm of the phase III ACOSOG trial Z9001 (imatinib mesylate vs. placebo after resection of primary gastrointestinal stromal tumors) were evaluated since the reported AEs could not be due to study drug. Attribution was collected per CTCv3.0 as not related, unlikely, possibly, probably, or definitely related, and categorized as “unrelated” (not related or unlikely) and “related” (possible, probable, or definite). Patterns were evaluated using generalized estimating equations adjusting for multiple events per patient. Results: 202 patients and 2871 AEs were included. 52% of AEs were reported as “related”. Known imatinib AEs were more likely to be reported as “related”. The reported rate of AE relatedness varied by AE type. No patterns were observed by gender, age, PS, severity or visit of AE. When the same event was reported on the same patient on multiple visits, the attribution category changed at least once 33% of the time with 19% changing from “related” to “unrelated” or vice versa. Conclusion: 52% of events on the placebo arm of Z9001 were reported as attributed to study drug and 19% of the time the same event was not consistently attributed. These data provide further evidence that attribution is difficult to determine, unreliable, and of questionable value in interpreting randomized clinical trials. No significant financial relationships to disclose. [Table: see text]
Statistical power of negative randomized clinical trials (RCTs) presented at the American Society of Clinical Oncology (ASCO) Annual Meetings
Authors: Bedard P. , Krzyzanowska M. K. , Pintilie M. , Tannock I. F. 
Published: March 2020

6516 Background: Underpowered randomized clinical trials (RCTs) may expose participants to risks and burdens of research without scientific merit. We investigated the prevalence of underpowered RCTs presented at ASCO annual meetings. Methods: We surveyed all two-arm parallel phase III RCTs presented at the ASCO annual meeting from 1995–2003 where differences for the primary endpoint were non-statistically significant. Post hoc calculations were performed using a power of 80% and a=0.05 (two-sided) to determine the sample size required to detect a small, medium, and large effect size between the two groups. For studies reporting a proportion or time to event as a primary endpoint, effect size was expressed as an odds ratio (OR) or hazard ratio (HR) respectively, with a small effect size defined as OR/HR=1.3, medium effect size OR/HR=1.5, and large effect OR/HR=2.0. Logistic regression was used to identify factors associated with lack of statistical power. Results: Of 423 negative RCTs for which post hoc sample size calculations could be performed, 45 (10.6%), 138 (32.6%), and 333 (78.7%) had adequate sample size to detect small, medium, and large effect sizes respectively. Only 35 negative RCTs (7.1%) reported a reason for inadequate sample size. In a multivariable model, studies presented at plenary or oral sessions (p<0.0001) and multicenter studies supported by a co-operative group were more likely to have adequate sample size (p<0.0001). Conclusion: Two-thirds of negative RCTs presented at the ASCO annual meeting do not have an adequate sample to detect a medium-sized treatment effect. Most underpowered negative RCTs do not report a sample size calculation or reasons for inadequate patient accrual. No significant financial relationships to disclose.
Myths in the assessment of progression: How frequently should we assess patients in clinical trials?
Authors: Stone A. M. , Fernandes N. , Morris C. 
Published: March 2020

6521 Background: It is often believed that within a clinical trial a patient’s progression status should be assessed as frequently as practically possible if the primary objective is to compare progression-free survival (PFS). However, the statistical analysis of PFS data compares rates of progression rather than a specific percentile such as a median, and results in an estimate of the hazard ratio (HR)—the ratio of event rates. Methods: We provide results of simulations assessing the power and bias of an analysis of PFS in controlled trials according to visit frequency, rate of progression and analysis method. The simulations assume a true HR of 0.8 and that data are analyzed after 630 patients have an event to provide a nominal power of 80%. All simulations assume patients are assessed according a symmetric visit schedule as otherwise, if data are analyzed asymmetrically, bias will follow (Proc Am Assoc Cancer Res 2002; abst 975). Results: If patients are assessed at a time interval equal to the median divided by two, there is a negligible (=2%) loss of power for the analysis of PFS data. Data presented in the table show that in a disease with a comparator median of 4 and 8 months when 1,000 patients are randomized, there is little increase in power if patients are assessed more often than every 2 and 4 months, respectively, using a standard log- rank test. The simulations presented assume there is some variability (SD=1 week) of the actual assessment date around the protocolled date. If PFS data are analyzed by moving PFS times to the scheduled assessment time, alternative methods of analysis (grouped survival techniques) preserve power and avoid bias by appropriately handling the excessively tied PFS times. Conclusions: Within the context of a clinical trial, a fully powered analysis of PFS is possible if patients are assessed at a frequency which is one-half of the median of the disease under study, and therefore patients need not be assessed more frequently unless clinical practice outside of a clinical trial would dictate otherwise. [Table: see text] [Table: see text]
Inter-observer variability in chemotherapy trials for pancreatic cancer
Authors: Baumann B. C. , Ford R. , Dasse K. , Zhou K. 
Published: March 2020

6522 Background: No studies have examined differences in imaging assessment of drug response for unresectable pancreatic cancer between investigators and independent central review panels. This study reports such discrepancies. Methods: 133 patients in two multi-center, randomized Phase II drug trials had their response assessed by measurement of tumor size or new lesions on serial CT scans. Protocols specified techniques for tumor measurement and defined responses as complete (CR) or partial responses (PR), stable (SD) or progressive disease (PD). Objective responses were confirmed by repeat imaging evaluations after an interval > 4 weeks. Cases of PR or SD withdrawn from the study <8 weeks after enrollment were scored as non-evaluable (NE). The same images were then blindly reviewed by protocol trained radiologists at an Independent Core Lab. Cases of discordance in the interpretation of best response between investigators and reviewers were then blindly re-reviewed by an independent adjudicator. Results: In 50/133 cases (38%), there was sufficient discrepancy between investigators and reviewers to result in a change in overall response. In 10 cases (8%), investigators reported responses inconsistent with protocol standards for their tumor measurements. In 40 cases (30%), reviewers disagreed with the radiological findings of the investigators. In 47 of the 50 cases, the films were available for a second review by the adjudicator who confirmed the reviewers’ assessment of response in 39/47 (83%) of cases. Discrepancies in assessment of response were not randomly distributed. Investigators reported significantly more confirmed objective responses (CR + PR) than reviewers even after investigators’ response coding errors were corrected. As shown in Table 1 , investigators reported favorable responses in 21/133 (16%) cases compared with 6/133 (5%) responses noted by reviewers (p=0.01). Conclusions: The results support the use of independent review of trial data when the endpoint of the trial (response rate) is based on imaging data. [Table: see text]