bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review of postmarketing surveillance of molecular targeted anticancer agents in Japan
Authors: Miura Y. , Kami M. , Morita T. , Tsubokura M. , Takei N. , Murashige N. , Hori A. , Komatsu T. 
Published: August 2020

6598 Background: Since the safety profile of molecular targeted anticancer agents is different from that of conventional anticancer agents, the safety information is limited. Although postmarketing surveillance (PMS) on safety is important, the appropriate methods of PMS have not been established. Methods: We investigated PMS methods, patients’ performance status (PS), and safety of the eight molecular targeted anticancer agents (imatinib, rituximab, trastuzumab, gefitinib, gemtuzumab ozogamicin [GO], bortezomib, bevacizumab, erlotinib) approved in Japan. We excluded sunitinib and sorafenib as the PMS of these agents were ongoing. Results: Besides PMS of gefitinib, seven PMS enrolled all the patients that received the study agents. The inclusive type of PMS was required at approval of the latest four agents, GO, bortezomib, bevacizumab, and erlotinib. The total number of enrolled patients was 8,776. Seven PMS of imatinib, rituximab, trastuzumab, GO, bortezomib, bevacizumab, and erlotinib enrolled 309, 2,575, 1,142, 316, 666, 2,698, and 1,070 patients, respectively. Data on the frequencies of patients with PS 3–4 were available in five of seven PMS, which were 7%, 7%, 20%, 3%, and 0.1% in PMS of rituximab, trastuzumab, GO, bortezomib, bevacizumab, respectively. Frequencies of severe adverse events were described in four of seven PMS, which were 3–6%, 0.3–4%, 0–45, and 0–2% in PMS of imatinib, rituximab, bortezomib, and bevacizumab, respectively. Interstitial lung disease related to Bevacizumab was unknown in premarketing studies and was observed in 0.4% in PMS. Drug related mortality rates were described in four of seven PMS, which were 1%, 8%, 3%, and 2% in PMS of rituximab, GO, bortezomib, and bevacizumab, respectively. Conclusions: Although PS varied among PMS of different molecular targeted anticancer agents, patients with poor PS were not included in most PMS. Disclosure of PMS results was insufficient. Further investigation on appropriate methods of PMS and its disclosure is warranted. No significant financial relationships to disclose.
Clinical utility of routine proteinuria evaluation in the treatment decisions of patients receiving bevacizumab for metastatic solid tumors: A retrospective study
Authors: Yeh J. , Frieze D. , Martins R. , Carr L. 
Published: August 2020

6599 Background: Bevacizumab is an anti-VEGF monoclonal antibody approved for use in metastatic breast, colorectal, and non-small cell lung cancer patients. In the pivotal Phase III clinical trials, Grade 3/4 proteinuria occurred in <5% of patients. The manufacturer recommends monitoring for the development of proteinuria but does not provide specific recommendations, except to discontinue treatment if the patient develops nephrotic syndrome. This retrospective analysis describes the incidence, severity, and cost of routine proteinuria monitoring in patients with metastatic solid tumors. Methods: A retrospective chart review was performed in our institution from June 1, 2005 to November 30, 2007. Patients treated with bevacizumab and seen in the breast, lung, and gastrointestinal cancer clinics were included. The primary endpoints are the incidence and severity of elevated proteinuria and the frequency of changes in bevacizumab due to elevated proteinuria. The secondary endpoints include analysis of the cost of routine proteinuria monitoring and to describe the correlation of proteinuria with bevacizumab-induced hypertension and other patient co-morbidities. Results: 243 patients were included in the analysis. Only 1.2% (3 of 243) of patients developed Grade 3/4 proteinuria. One of these patients had prior chronic renal insufficiency, while the other two patients had hepatitis and hepatocellular carcinoma. Seven patients developed Grade 3/4 bevacizumab-induced hypertension, however this did not correspond with the development of proteinuria. Over $130,000 was charged to patients for monitoring of proteinuria. Conclusions: These results demonstrate that clinically significant proteinuria is rare and routine proteinuria monitoring is associated with high cost. [Table: see text] No significant financial relationships to disclose.
Tumor registry versus physician medical record review: A head-to-head comparison of malignant pancreatic neuroendocrine tumor (mPNET) cases
Authors: Manasanch E. E. , McDade T. P. , Bodnari A. , McKinney J. , Sullivan M. E. , Whalen G. F. , Piperdi B. , Rosmarin A. G. , Tseng J. F. 
Published: August 2020

6600 Background: Researchers have underutilized single-institution tumor registry (TR) data, instead using researcher medical record review and/or personal, departmental or institutional databases to identify patients with particular malignancies. However, TR data is becoming increasingly prominent on a national level through broader use of the National Cancer Database (NCDB). We selected mPNETs as example to compare the accuracy of TR identification of these tumors with physician medical record review (MD Review). Methods: For MD Review, the health information services department of a single academic medical center was queried for all patients with pancreatic ICD9 codes (157.0–157.9; 211.6–211.7) January 2000-August 2008. A single physician reviewer analyzed computerized and paper medical records and identified mPNET cases. For TR data, mPNET patients were identified using the TR database with assistance of TR staff by two separate strategies. From January 2000-December 2006, patients were identified by using diagnosis codes from manual review of admission, discharge, clinic and pathology reports. From January 2007-August 2008 the TR used an automated case finding program (CAL by C/NET, California, USA) that downloaded cases with terms and codes related to malignancy. All MD Review- and TR-identified mPNET cases were reviewed by a second investigator blinded to identification strategy to assure consistency of mPNET definitions. Results: Using MD Review, 1194 pts with pancreatic ICD9 codes were identified. After MD Review, 42 mPNET patients were identified and confirmed. In comparison, TR identified 17 patients, of whom 5 were not identified by MD Review. Of the 47 patients identified by either strategy, TR identified 17/47 (32.6%) patients, whereas MD Review identified 42/47 (89.4%). TR identification rate in time periods 1 and 2 were 30% and 40%, respectively. Conclusions: Analysis of an academic tumor registry demonstrates that a substantial proportion of mPNET cases are missed when compared to ICD-9 identification and physician medical record review. Since MD review is imperfect, the TR may be even less effective at identifying PNETs than our data suggest. This may be applicable to other tumor registries and TR-based national studies. No significant financial relationships to disclose.
Analysis of the rate of non-target disease progression in patients with stable or responding target disease by the Response Evaluation Criteria in Solid Tumors (RECIST)
Authors: Borradaile K. , Ford R. 
Published: August 2020

6603 Background: RECIST suggests progression of non-target disease is rare in patients with stable or responding target disease. We reviewed outcomes by RECIST to determine the rate of non-target (NT) progressive disease (PD). Methods: Outcomes of RECIST-based blinded independent central review (BICR) of 962 breast and colon cancer patients were used to identify 514 patients that had a progression event in order to determine the incidence of NT-PD. The radiographs of the 55 patients that had NT-PD were further reviewed by the authors (KB, RF) to confirm the NT-PD was “unequivocal.” To be considered unequivocal, there had to be a definite, substantial increase in the size of one or more metastatic NT lesions that was clearly not related to differences in imaging technique. To confirm the subjective nature of the “unequivocal progression,” the lesion(s) upon which PD was assessed was measured and a 20% increase in the lesion(s) since nadir was required. Results: Of the patients with PD, 11% (55/514) progressed only on worsening of NT disease. In 82% (45/55) of cases where the NT-PD was unequivocal, either the target disease was increasing but had not met the quantitative requirement for progression or the increase in NT disease would have resulted in target progression had the NT site(s) of disease been included with the baseline target lesions. Of the remaining 18% (10/55) where the two criteria described above did not apply, and an additional evaluation was performed, the next evaluation confirmed PD. Conclusions: Progression on the basis of NT disease can be reliably assessed if the target disease has started to increase from the nadir or if the increase in NT disease is significant enough to have resulted in target disease progression if classified as such. If one of the above criteria is not met, it is recommended that treatment continue until progression can be confirmed at the next evaluation. No significant financial relationships to disclose.
Association of adolescent and young adult cancer treatment trial activity with a national mortality reduction benefit in the United States
Authors: Bleyer A. , Friedman S. , Finnegan S. , Montello M. , Budd T. , Anderson B. , Trimble E. L. 
Published: August 2020

6605 Background: Adolescent and young adult (AYA) cancer patients in the U.S. have had less mortality and survival improvement than have children or older adults with cancer. Because <3% of 20–35 year-olds are entered onto national cancer treatment trials (NCTT), in contrast to ∼50% of children, initiatives were undertaken during the past 6 years to increase NCTT AYA participation. Methods: NCTT accrual data were obtained from the Cancer Treatment Evaluation Program, NCI. Survival, mortality, and incidence data were obtained from the NCI Surveillance, Epidemiology, and End Results (SEER) program. Results: In comparison of 2002–2006 with 1996–2001, the average annual NCCT accruals of patients 15–39 years of age increased from 1,032 to 1,792, the estimated proportion of patients in this age group on NCTT increased from an average of 4.2% to 6.5%, and the proportion of all NCCT accruals (of all ages) that were in the 15–39 year age group increased from an average of 5.2% to 8.2%. Of the 11 national NCTT groups, the pediatric group (Children's Oncology Group [COG]) had the largest AYA accrual number and increase, enrolling more than twice the number of 15–39 year-olds than any other cooperative group and 1/3 of all of them. Among 15–29 year-olds nearly all of the increased accrual occurred in patients with leukemia or lymphoma, in whom the ratio of the national death rate to SEER incidence fell below the projected linear regression for this ratio in each year during 2002–2005. Conclusions: In the U.S., COG is now contributing more AYA patients to NCTT than any adult cooperative group, suggesting that the adult-treating groups and cancer centers have increased capability to increase AYA accrual and should complement the pediatric effort. That the disease group that accounted for nearly all of the increase also had a concomitant reduction in deaths relative to incidence may be cause and effect. These favorable trends should encourage implementation of the clinical trial recommendations of the NCI Program Review Group in AYA Oncology ( http://planning.cancer.gov/disease/AYAO_PRG_Report_2006_FINAL.pdf ) that are being implemented in part by the LIVESTRONG Young Adult Alliance (Closing the Gap: A Strategic Plan). [Table: see text]
Locally advanced prostate cancer: A population-based study of treatment patterns and predictors
Authors: Lowrance W. , Eastham J. , Jacks L. , Yee D. , Scardino P. , Elkin E. 
Published: August 2020

6606 Background: Treatment of locally advanced prostate cancer (LA PCa) is controversial, but recent trial results demonstrate superior outcomes for combination therapy compared to monotherapy. We aimed to identify treatment patterns, predictors, and trends in a population-based cohort of men with LA PCa. Methods: From Surveillance, Epidemiology and End Results (SEER) cancer registry records linked with Medicare claims, we identified men age 65 and older diagnosed with clinical stage T3 and T4 nonmetastatic PCa from1995 through 2002. Using Medicare claims, we classified treatments (radical prostatectomy (RP), radiation therapy (RT), or androgen deprivation (AD)) received within 6 and 24 months of PCa diagnosis. We assessed trends over time and used multivariable logistic regression to assess sociodemographic and clinical predictors of treatment. Results: The Table shows the distribution of treatments given within 6 months following diagnosis among 3,412 men with LA PCa. Approximately one third of patients were treated with a combination of RT and AD (31%), 46% received monotherapy, and 17% received no active treatment. Between 1995 and 2002, the most notable change was an increase in use of the combination of RT and AD as primary therapy. The percent of patients who received RT and AD rose from 16% in 1995 to 39% in 2002. Significant predictors of receiving combination therapy over the study period were age, race, urban residence, marital status, clinical stage, year of diagnosis, and Charlson comorbidity score. All results were similar when we examined treatments received within 24 months of diagnosis. Conclusions: Patterns of treatment for locally advanced prostate cancer shifted during the study period, with the combination of RT and AD becoming the most common treatment modality. This movement toward combination therapy for LA PCA is encouraging, given recent evidence of the superiority of such therapy in these patients. Future efforts should focus on further increasing the use of multimodality therapy in LA PCa. [Table: see text] No significant financial relationships to disclose.
Does quality of treatment-related harms reporting affect conclusions about superiority of treatment?
Authors: Mhaskar R. S. , Kumar A. , Soares H. , Schell M. , Djulbegovic B. 
Published: August 2020

6607 Background: It is often not known if harms were considered in the overall benefit-risk evaluation in deciding about the superiority of treatments. Here we present a study examining the relationship between researchers’ conclusions about the superiority of treatment with quality of treatment-related harms reporting. Methods: We reviewed all consecutive phase III randomized clinical trials (RCTs) conducted by Southwest Oncology Group from 1960 to 2003 (117 RCTs involving 139 comparisons enrolling 58,908 patients). We extracted data on primary outcomes [overall survival (OS), event free survival (EFS)], and treatment-related mortality (TRM). We classified the quality of reporting as good, intermediate or poor. Association of superiority of treatment and harms reporting was evaluated using chi-square test and meta-analytic techniques. Results: 76% of studies (106/139) reported TRM. Of these, the quality of reporting of harms was considered as “good” in 36% (38/106) of studies, “intermediate” in 55% (58/106), and “poor” in 9% (10/106). Investigators judged experimental treatments to be superior in 34% of trials (48/139) while standard treatment was superior in 66% (91/139). TRM data was reported in 75% (36/48) of results favoring experimental treatments and 78% (70/91) of results favoring standard treatments. There was no association between superiority of a treatment and TRM reporting (p = 0.80) or quality of harms reporting (p = 0.83). The pooled hazard ratio (HR) for OS in RCTs reporting TRM was 0.94 (95% CI: 0.90, 0.99) and for RCTs not reporting TRM was 0.99 (95% CI: 0.89, 1.09) (test of heterogeneity p = 0.06). The pooled HR for EFS among RCTs reporting TRM was 0.88 (95% CI: 0.83, 0.94) and for RCTs not reporting TRM it was 1.01 (95% CI: 0.79, 1.29) (test of heterogeneity p = 0.07). Additionally, the pooled HR for OS and EFS did not show any bias in reporting of harms according to harms reporting quality. Conclusions: Investigators’ conclusion regarding the superiority of experimental or standard treatment does not appear to be associated with outcome reporting bias for harms. Investigators judge both harms and benefits when they draw conclusions about treatment superiority. No significant financial relationships to disclose.
Presentation of breast cancer in young women
Authors: Ruddy K. J. , Gelber S. , Tamimi R. , Schapira L. , Come S. , Kereakoglow S. , Lin N. U. , Winer E. P. , Partridge A. H. 
Published: August 2020

6608 Background: Current guidelines for early detection of breast cancer do not adequately address diagnosis in young women. Furthermore, a lower suspicion for malignancy in this population may cause diagnostic delays. It is unknown how much the lack of routine screening and potential diagnostic delays contribute to the poorer outcomes of younger women. Methods: We surveyed women age <40 with recently diagnosed breast cancer in a prospective multicenter cohort study started in late 2006. We evaluated initial sign/symptom of cancer, time to first seeking medical attention, time from seeking medical attention to diagnosis, and patient factors associated with delays of >30 days in either timeframe. Chi square and Fisher's Exact tests were used to compare those with and without delays. Results: The first 222 women enrolled in the cohort are included in this analysis. Median age at diagnosis was 36 years (range 17–40). 79% of women initially identified their cancers through breast self exam. Only 6% were initially identified by clinical breast exam, 14% by breast imaging, 1% by systemic symptoms. While the median time between initial sign and seeking medical attention was 10 days (range 0–3,600), 54 women had >30 days between initial sign and medical attention (median 102, range 44–3,600). Similarly, median time from seeking medical attention to diagnosis was 21 days (range 0–2,970), yet 59 women had >30 days from attention to diagnosis (median 70, range 33–2,970). Preliminary comparison of women with and without delays did not reveal significant differences in age, race, education, marital status, or gravidity. Analyses will be updated and psychosocial factors, tumor subtype, and stage at diagnosis will be evaluated. Conclusions: In this large modern cohort of young women with breast cancer, nearly 80% presented with a self-detected breast abnormality, and most were diagnosed soon after they developed a sign/symptom. However, nearly 25% delayed seeking medical attention and 25% experienced a delay in diagnosis after seeking medical attention. Further research is warranted to compare delays between younger and older women, to evaluate delays in more diverse populations, to explore predictors of delays, and to assess for prognostic implications of delays in order to improve outcomes in young women. No significant financial relationships to disclose.
Effect of social or health insurance status on outcome of patients with early breast cancer
Authors: Jueckstock J. K. , Scholz C. , Brandelik A. , Rack B. K. , Sommer H. L. , Janni W. J. , Friese K. 
Published: August 2020

6609 Background: Recent studies in the US showed a relationship between state of social or health insurance of cancer patients and their overall survival (OAS). ([1] Banerjee M et al, Cancer. 2007;110:2169–2177. [2] Griggs JJ et al, J Clin Oncol. 2007;25:2522–2527. [3] Brookfield KF et al, Cancer. 2008.) In Germany 91% of all women have a compulsory health insurance whereas 9% have private health coverage. There are no pts without health insurance in Germany. Methods: In a retrospective analysis of 1846 German early breast cancer pts correlation between state of social and health insurance and OAS was investigated. 59.6% of the pts had a social insurance whereas 40.4% had none. 69.1% of the pts carried compulsory health insurance while 30.9% had private coverage. Among the pts with compulsory health insurance 56.6% had had a professional education and 41.5% were working whereas among the pts with private coverage 66.2% were professionally experienced and 43.9% were working. Age, tumor size, lymph node metastases, and tumor grading were well balanced between the two groups. 25.4% of all pts had undergone mastectomy and 72.6% had had a breast conserving therapy. In 2.0% of the pts no breast surgery was performed. 33.6% of all pts received adjuvant chemotherapy while endocrine therapy or radiotherapy was administered to 40.1% and 61.1% respectively. Results: OAS as expected was strongly correlated to established prognostic factors like age, tumor size, lymph node status, and grading (p < 0.001 respectively). However, OAS of the pts did not correlate to either social (p = 0.110) or health (p = 0.659) insurance state. Neither mattered the professional education of the pts concerning OAS (p = 0.217). Conclusions: Unlike the American results there was no correlation seen between state of social or health insurance for German early breast cancer pts. Thus, although pts with private coverage are supposed to receive more intensive medical care outcome for these pts concerning OAS does not exceed that of pts with compulsory insurance. No significant financial relationships to disclose.
Cost-effectiveness analysis of a randomized study with stereotactic radiosurgery (SRS) alone versus SRS plus whole brain radiation therapy (WBRT) for patients with brain metastasis
Authors: Lal L. S. , Chang E. L. , Franzini L. , Arbuckle R. B. , Miller L. , Reasonda L. G. , Feng C. , Swint J. M. 
Published: August 2020

6624 Background: This paper illustrates the incremental cost-effectiveness ratio (ICER) and cost-utility comparison of SRS alone versus SRS plus WBRT for brain metastasis. Methods: A decision analysis model, including subsequent treatment for recurrences, was developed and populated with data from patients randomized to either SRS alone (SA) versus SRS plus WBRT (SW), using costs from the healthcare institution perspective and outcomes based on actual life years saved (LYS) and quality-adjusted-life-years (QALYs). Utilities were captured through a time-trade -off methodology, utilizing three time horizons: 10 years, 5 years, and 1 year. Tornado diagrams and one-way sensitivity analyses were conducted to determine robustness of the model. Results: Fifty-eight patients were included in the final analysis, with 31 patients in the SA arm and 27 patients in the SW arm. The average cost of the SA arm is $119,000 versus $74,000 for the SW arm. The average effectiveness for the SA arm was 1.64 LYS versus 0.60 LYS for the SW arm. The ICER for total costs per LYS and QALYs were: $43,986 per LYS; $42,136 per QALY (10year); $43, 719 per QALY (5year); $44,686 (1year) for the SA arm. The surgical cost per LYS was $7,131 for the SA arm, and the radiation cost per LYS analysis was dominated. Tornado diagrams revealed that the following variables had the highest impact on the ICER: probability of being alive with SA in recursive partitioning analysis (RPA) class 2 and no recurrence; probability of no recurrence in RPA class 2 with SA; probability of being alive with SA in RPA class 2 and being treated for recurrence; probability of no recurrence in RPA class 1 with SA; and probability of being alive with no recurrence in RPA class 1 with SA. One-way sensitivity analysis exhibited a wide range variation for the first three of the above mentioned probabilities, with the final two having less variation. Conclusions: Compared to other interventions in the $50,000 to $100,000 per QALY cost-effectiveness range from an economic perspective, the application of SA, with subsequent surgical management of recurrences, is shown to be a reasonable treatment modality for brain metastasis. No significant financial relationships to disclose.