bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of palliative chemotherapy and targeted agents in elderly patients with metastatic colorectal cancer (mCRC).
Authors: Chan Matthew , Renouf Daniel John , Speers Caroline , Cheung Winson Y. 
Published: March 2020

6018 Background: Elderly patients are increasingly diagnosed with advanced cancers, but they are consistently underrepresented in clinical trials, which may lead to undertreatment. Our aims were to 1) evaluate the impact of advanced age on patterns of first-line chemotherapy and bevacizumab use in mCRC, 2) examine the reasons for treatment choices and 3) compare adverse events and treatment discontinuations in elderly vs young patients. Methods: A random sample of mCRC patients diagnosed from 2006 to 2007 and referred to any 1 of 5 regional cancer centers in British Columbia, Canada was reviewed. Summary statistics were used to describe treatment patterns between the elderly (>/=70 years) and young (<70 years). Cox regression was used to determine the effect of systemic therapy on overall survival, controlling for age and confounders. Results: We identified 800 patients: 43% elderly and 57% young; 56% men; and 26 / 36 / 38% ECOG 0 / 1 / 2+, respectively. Fewer elderly patients were given chemotherapy (52% vs 79%, p<0.001). Among those treated, most common first-line palliative regimens for elderly vs young included: capecitabine (50 vs 15%), FOLFIRI (26 vs 38%), and FOLFOX (15 vs 37%) (all p<0.001). Those aged >/=70 were also less likely to receive bevacizumab in their regimens (22 vs 50%, p<0.001). The most frequent reasons for no systemic therapy were similar between age groups: patient choice (31 vs 28%), poor ECOG (16 vs 17%), and significant co-morbidity (11 vs 13%). Risk of chemotherapy (p=0.30) and bevacizumab (p=0.39) adverse events were comparable between elderly and young as were rates of early chemotherapy (p=0.07) and bevacizumab (p=0.79) discontinuation. Receipt of systemic therapy +/- bevacizumab was associated with improved survival from mCRC (HR for death 0.50, 95% CI 0.31-0.62, p<0.001), regardless of advanced age (p interaction for age and treatment = 0.33). Conclusions: Elderly patients with mCRC are more likely to receive no chemotherapy, capecitabine monotherapy, or a regimen without bevacizumab. However, in carefully selected elderly patients, adverse events, treatment discontinuations, and overall survival benefit from treatment appear similar to those observed for younger patients.
Bias in reporting of endpoints of efficacy and toxicity in randomized clinical trials (RCTs) for women with breast cancer (BC).
Authors: Vera Badillo Francisco Emilio , Shapiro Roman , Ocana Alberto , Amir Eitan , Tannock Ian 
Published: March 2020

6043 Background: Phase III RCTs are designed to assess clinically important differences in endpoints that reflect benefit to patients. Accurate and unbiased reporting is essential to guide rational therapy. Here we evaluate the quality of reporting of the primary endpoint (PE) and of toxicity in RCTs for BC. Methods: PUBMED was searched from 1995-2011 to identify RCTs for BC. Scales for assessing bias in reporting of the PE and of toxicity were developed. For the PE, scales assessed whether the concluding statement of the abstract (CSAbs) was (a) based on the PE, (b) described appropriately a statistically positive or negative result for the PE, or (c) was based on secondary endpoints. Bias and completeness of reporting of toxicity was assessed using a hierarchy scale of whether reporting occurred in the CSAbs, elsewhere in the abstract, in the discussion of the article or only in the results. Association of bias with Journal Impact Factor (JIF); changes in the PE compared to protocol information in clinicaltrials.gov and funding source was also evaluated. Results: 164 trials were evaluated; 33% showed bias in reporting of the PE. The PE was more likely to be reported in the CSAbs if statistically significant [OR 5.2, 95% CI 1.9-14.3, p=0.001]. A statistically negative PE was not reported in the CSAbs in 27% of trials. Of the 30 trials where protocol information was available in clinicaltrials.gov, there were non-significant associations for the PE to show a positive result if had been changed, and for greater bias in reporting the PE if it was unchanged. 67% of studies showed bias in reporting of toxicity. Only 14% mentioned toxicity in CSAbs. When the PE was positive, bias in reporting of toxicity was more common [OR 2.0, 95% CI 1.0-3.9, p=0.04]. There was no apparent association between bias in reporting of either the PE or toxicity and JIF or funding source, but a non-significant association between change in the PE and industry funding. Conclusions: Bias in reporting of the PE is common especially for studies with a negative PE. Reporting of toxicity is poor especially for studies with a positive PE. Changing of the PE appears to be a strategy to increase the likelihood of observing a statistically significant result.
Treatment and treatment outcomes of advanced NSCLC patients in routine clinical care: Results of the retrospective LUCEOR study.
Authors: Agulnik Jason Scott , Chouaid Christos , Herder Judith , Ziske Carsten , Mitchell Paul , Vansteenkiste Johan F. , Eriksson Jennifer , Finnern Henrik W. , Lungershausen Juliane , Lester Jason ,   LUCEOR Study Group
Published: March 2020

6058 Background: Although NSCLC is the most common type of lung cancer, published data on both treatment patterns and outcomes in routine clinical care are scarce. Collecting this data systematically across countries will help to understand, compare and improve patient care. Methods: 1,490 patient charts were reviewed retrospectively from 40 sites in Australia, Belgium, Canada, France, Germany, Italy, Sweden, Turkey, the Netherlands and the UK, 1436 of those evaluable. Patients deceased before April 2010 were eligible if ≥18 years, diagnosed with advanced stage IIIb/IV NSCLC and had received active 1st line anti-cancer treatment. Demographic data, disease and, treatment history and resource use were collected from start of first line treatment until death. Results: Mean age at NSCLC diagnosis was 64 years [SD=10.6], 67% of patients had stage IV disease at diagnosis and 66% were male. Confirmed tumor histology was adenocarcinoma in 50% of patients, squamous and large cell carcinoma in 23% and 14%, respectively. Tumour histology was not available in 13% of patients. Mean number of treatment lines was 1.7 [range 1-8]. Biomarker analysis was performed in 19% of patients (of those 26% and 13% tested for EGFR and KRAS mutation, respectively) within less than one month of diagnosis. 1st line therapy included mainly platinum doublets (86%, mostly carboplatine/gemcitabine [23%]), 2nd line included erlotinib (35%) and pemetrexed (18%), and 3rd line included erlotinib (38%) and docetaxel (17%). Most treated patients had ECOG performance status of 1. Stable disease (based on RECIST) was highest during 1st line therapy with 30%. Median PFS from start of 1st line treatment was 3.8 months [SD=7.1], with a median OS of 7.1 months [SD=11.6]. Conclusions: The majority of patients were diagnosed with an adenocarcinoma and a number of patients were tested for EGFR or KRAS mutation. Overall treatment outcomes observed in routine care seem lower than those observed in clinical trials. Also current therapeutic options for NSCLC seem to provide limited clinical benefit, underpinning the need for new treatment alternatives to prolong PFS and OS.
The use of the word “cure” in oncology.
Authors: Miller Kenneth David , Abraham Joseph , Joshi Brijen L 
Published: March 2020

6067 Background: Use of the word “cure” in cancer care reflects a balance of physician and patient optimism, realism, medico-legal concerns, and even superstition. The purpose of this study was to survey a group of clinicians regarding the frequency and determinants of using the word “cure” in their practice. Methods: In 2011, 180 oncology clinicians at the Dana-Farber Cancer Institute were invited to complete a survey regarding the word “cure” in cancer care. Participants completed a 19 question survey regarding how commonly their patients are cured, how often they use the word cure, in what circumstances they would tell a patient that they are cured, the timing of telling a patient that they are cured, and hesitancy in using the word cure. Three patient case scenarios were presented to elicit participants’ views regarding whether patients were cured and whether they need continued follow-up. Results: The 117 participants who provided answers to the cure questions (65% of the original 180 invitees), were evenly divided between males and females,73% were medical doctors, and 56% had 10 or more years of experience since their training. Eighty-one percent of respondents were hesitant to tell a patient that they are cured and 63% would never tell a patient that they are cured. Only 7% feel that greater than 75% of their patients are, or will be, cured. This varied significantly by subspecialty (p<0.001). The participating clinicians reported that only 34% (sd: 30%) of patients ask if they are cured. In considering 20-year survivors of seminoma, large cell lymphoma, and estrogen positive breast cancer, 81%, 73%, and 47% of clinicians, respectively, believed that the patients were cured and 33%, 38%, and 52% recommended annual oncology follow-up of the patients. Twenty-three percent of clinicians believed that patients should never be discharged from the cancer center. Conclusions: Oncologists report that patients are hesitant to ask whether they are cured, and the clinicians are hesitant to tell, although this varied by cancer subspecialty. Annual oncology follow-up was frequently endorsed, even after 20 years in remission.
Correlation of quantitative p95HER2 and HER2 protein expression with pathologic complete response (pCR) in HER2-positive breast cancer patients (pts) treated with neoadjuvant (NEO) trastuzumab-containing therapy.
Authors: Villasboas Jose Caetano , Hurley Judith , Weidler Jodi Marie , Paquet Agnes , Fernandez Carmen Gomez , Cioffi Lavina Maureen , Sperinde Jeff , Chenna Ahmed , Haddad Mojgan , Lie Yolanda , Winslow John William , Huang Weidong , Petropoulos Christos J. , Pegram Mark D. 
Published: March 2020

608 Background: Elevated p95 [HER2-M611-CTF (carboxy-terminal-fragment) also known as p110 or p95HER2] expression has been correlated with poor outcomes in HER2+ pts with metastatic breast cancer treated with trastuzumab (T); however, limited data have been presented on the correlation between p95 and pCR to T in the NEO setting, where p95 was measured by immunohistochemistry. In the current study, we sought to determine whether quantitative p95 and HER2 expression correlated with pCR in pts treated with T + chemotherapy in the NEO setting. Methods: HER2 expression (H2T) was quantified by HERmark in 47 breast tumors using formalin-fixed, paraffin-embedded sections. Tissue remained in 40 cases to measure p95 by VeraTag and compare to a previously published cutoff (Clin Cancer Res 16:4226, 2010). pCR data were available for 45 cases. pCR was defined as the absence of invasive disease in the breast. Results: The overall pCR rate was 46.7% (ER+: 14.3% vs. ER-: 75%; Wilcoxon rank p<0.0001) and was significantly associated with higher H2T levels (p=0.02). In ER- subjects (N=24), no difference in H2T levels was observed between pCR vs non-pCR groups [median H2T=111.5 (IQR 63.4-162.2) vs 150.5 (IQR 43 – 226.2), respectively; p=0.721]. However, within the ER+ group (N=21), H2T levels were significantly higher in the pCR group vs non-pCR group [median H2T=254 (IQR 181.5-584.5) vs 37.3 (IQR 16.4-89); p=0.024]. Using multivariate logistic regression, increasing log(H2T) (p = 0.011), ER-negativity (p = 0.027) and low p95 (p = 0.074) were found to correlate or trend with pCR. Conclusions: pCR was significantly associated with high H2T expression in ER+ HER2+ breast cancer pts who received NEO therapy with T + chemotherapy. A trend towards pCR was seen in tumors that had low p95. These data suggest that quantitative H2T and p95 may provide additional information on response to T-based regimens in breast cancer, particularly ER+ breast cancer. Additional investigation into the possible relationship between quantitative levels of HER2 and p95 expression and T response in the NEO setting in larger cohorts is warranted.
Does drug cost drive drug adherence? The designer drug phenomenon.
Authors: Ebrahim Jalal , Han Dolly , Hogeveen Sophie , Trinkaus Martina , Fadhel Ehab , Hon Henrique , Kassam Zahra , Liu Geoffrey , Simmons Christine E. 
Published: March 2020

6084 Background: Cancer patients (pts) are on many medications, both for malignancy and supportive therapies. The cost of oral medications are funded by either the pt, public, or private mechanisms. Low adherence rates are observed in oral treatments, and non-adherence is the primary cause of treatment failures. To our knowledge, cost-related adherence to oral therapy in the context of malignancy has not been studied extensively in the existing literature. We assessed the relationships between oral medication costs and adherence rates. Methods: This cohort study enrolled 453 pts at 3 outpatient heme/onc clinics in the Greater Toronto Area. A 7-item survey was designed to assess pt demographics, self-reported adherence to oral medication, type of drug coverage (private payer, public payer, self payer) and patients' perceived cost of oral drugs. Oral medications were recorded and actual monthly costs were calculated. Descriptive statistics were used to describe frequencies. Spearman Rank Order Correlations and Chi-Square Analyses were used to examine relationships between variables. Results: Of 453 pts, 50% had a private drug plan, 24% paid out of pocket, 44% had government funding and 4% reported their physician had arranged funding. 51% of pts had oral drug costs of ≥ $100/month. Self reported adherence to prescribed oral medications was 80%. As the cost of prescribed medications increased, so did self reported adherence (r=0.144, p=0.002). There was also a significant relationship between drug coverage and oral drug costs (c²=23.78, df=12, p=0.02). Pts paying out of pocket were significantly less likely than all other pts to have oral drug costs of ≥$500/month (11% vs 19%) Conclusions: As oral drug costs increase, so does likelihood of adhering to prescribed regimen. This implies that further pt education about the efficacy and importance of medications may help with adherence, regardless of cost. It is possible that pts are provided with more education regarding newer and more expensive agents than they are regarding older and cheaper agents, regardless of efficacy. Disparities observed in medication costs between those with private drug plans vs. those without suggests financial restrictions may affect prescription patterns in this group.
Involvement of low- and middle-income countries (LMCs) in oncology randomized controlled trials (RCTs).
Authors: Wong Janice C. , Fernandes Kimberly A. , Amin Shubarna , Lwin Zarnie , Krzyzanowska Monika K. 
Published: March 2020

6087 Background: Lower costs and fewer regulatory barriers make clinical trials in LMCs attractive, but little is known about characteristics of such trials and roles of investigators from LMCs. We describe trends in participation of investigators from LMCs in oncology RCTs over a decade. Methods: We used Medline to identify all RCTs published in English between January 1 1998 and December 31 2008 evaluating treatment in five solid tumours (lung, breast, colorectal, stomach, liver) with high mortality in LMCs as per GLOBOCAN 2002. Data on author affiliations and roles (first, middle or corresponding author), trial characteristics, funding and study interventions were abstracted using an electronic form. Countries were stratified into low-, middle- and high-income using World Bank data. Interventions were categorized as requiring basic, limited, enhanced or maximal resources as per the Breast Health Global Initiative classification. Logistic regression identified factors associated with investigator participation from LMCs. Results: 454 trials were identified: lung (n=177), breast (n=165), colorectal (n=82), stomach (n=29), liver (n=7). The annual number of trials published increased from 10 trials in 1998 to 86 in 2008. The proportion of trials with at least one LMC author also increased over time from 20% in 1998 to 29% in 2008 (p=0.01), but almost all LMC authors were from middle-income countries. In 17% of trials involving LMC authors, they were first or corresponding authors. 67% of trials involving LMC investigators evaluated interventions requiring enhanced or maximal resources for implementation. Factors associated with LMC participation included industry funding (OR=3.57, p<0.0001), use of placebo arm (OR=2.59, p=0.02) and metastatic setting (OR=3.87, p=0.0003). Conclusions: An increasing number of oncology RCTs involve LMC investigators primarily in non-leadership roles. These trials are commonly industry-funded and often test interventions that require at least enhanced resources for implementation. To minimize concerns of exploitation and facilitate future collaboration it is crucial that interventions are locally feasible and investigators receive appropriate authorship.
Recruitment of cancer patients to National Institute for Health research cancer research network portfolio studies between 2001 and 2011.
Authors: Cooper Matthew , Poole Karen , Cameron David A. , Haward Robert , Selby Peter John , Kaplan Richard S. , Parmar Mahesh , Moser Rachel , Seymour Matthew T. 
Published: March 2020

6091 Background: The National Institute for Health Research Cancer Research Network (NCRN) was established in 2001 in England, United Kingdom to improve cancer patient outcomes by improving the coordination, integration and speed of cancer research. Methods: Baseline recruitment of cancer patients in England to clinical studies was around 4% of incident population. Research Networks were established initially in England (NCRN) and then across the UK, co-terminus with clinical cancer service networks, and a per capita based funding model used to provide a research infrastructure to support recruitment to a nationally defined research portfolio. Results: Within 3 years, as the networks were established, recruitment of patients to studies doubled from 10,000 to 20,000 cancer patients per year. Recruitment has continued to increase year on year, supported initially by underspend that had accrued from earlier years in the life of NCRN, and more recently from additional resources invested via the NIHR comprehensive networks. Data for 2010/11 show that over 45,000 cancer patients are now recruited into portfolio studies in England each year, with over 50,000 across the whole of the UK. Conclusions: Dedicated, targeted, clinician-led National Health Service investment into supporting national portfolio studies, has delivered an unprecedented five-fold increase in recruitment of cancer patients into clinical trials across the United Kingdom. This required coordinated research infrastructure, close cooperation with research funders, particularly Cancer Research UK and the National Cancer Research Institute, and the enthusiasm and hard work of many clinicians, patients and others working to deliver clinical cancer care in the National Health Service in the United Kingdom.
Utilization of bone densitometry and administration of bisphosphonates to prevent osteoporosis in patients with nonmetastatic prostate cancer receiving anti-androgen therapy.
Authors: Khan Muhammad Atif , Holt Abby E , Gujja Swetha , Govindarajan Rangaswamy 
Published: March 2020

6099 Background: Prostate cancer subjects with PSA relapse who are treated with androgen deprivation therapy (ADT) are recommended to have baseline and serial bone densitometry (BD) and receive intravenous bisphsphonates (BP). Utilization of BD and BP therapy was evaluated in a retrospective SEER Medicare database analysis. Methods: A cohort study of men aged aged ≥ 65 years with a nonmetastatic incident diagnosis of prostate cancer between 2004 and 2008 was conducted. Data were obtained from the Surveillance, Epidemiology and End Results (SEER) linked Medicare claims. Medicare claims were used to select prostate cancer cases who had ever received ADT and intravenous BP as part of their treatment. ADT was defined as an orchiectomy, goserelin, leuprolide, leuprolide implant, or triptorelin. BD and treatment with pamidronate or zoledronic acid were identified using Medicare HCPCS codes. One-sided exact binomial test of proportion was used to determine if the physician compliance rate is consistent with 80%; meaning equal to or higher than 80%. Results: 157,974 newly diagnosed prostate cancer cases were identified. Of those, 100,865 were age 65 and above and had no bone metastases. Subjects who did not have ADT claims were excluded. 30,846 patients were eligible for analysis. Cases were further stratified by use of BD and BP therapy. Results revealed 86.8% (N=26,774) on ADT did not receive either a BD or intravenous BP therapy. Approximately 2.9% (N=885) of the cases on ADT received BP treatment without ever receiving a BD. 9.3% (N=2,863) of the cases on ADT received a BD without receiving intravenous BP, while only 1.05% (N=324) of the cases on ADT received both a BD and BP. A compliance rate of 1.05%, those patients receiving both bone densitometries to screen for bone loss and preventive therapy, was well below the expected rate of 80%. Conclusions: Contrary to the recommendations, BD assessment and BP use is under utilized in men receiving ADT for non metastatic prostate cancer. Education of practicing physicians regarding better screening and preventative measures for osteoporosis in this population is warranted.