bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain and tumor penetration of carbon-11–labeled lapatinib ([11C]Lap) in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC).
Authors: Saleem Azeem , Searle Graham , Kenny Laura M. , Huiban Mickael , Waldman Adam , Downie Louise , Lau Mike , Murphy Philip S , Kozlowski Kasia , Lewis Yvonne , Woodley Laura , Hill Sam , Kamalakaran Aruloly , Hirschberg Sandra , Kaneko Tomomi , Aboagye Eric , Marini Luca , Coombes R. Charles 
Published: March 2020

635 Background: About a third of HER2-overexpressing (HER2+) breast cancer pts will develop brain metastases in the course of their disease. Drug access to normal brain and brain metastases is therefore key to prevention and treatment of cerebral metastases. To provide direct evidence of Lap drug access and evaluate whether therapeutic doses of Lap act as a substrate for efflux transporters, thereby increasing Lap concentrations, we performed positron emission tomography (PET) studies with [11C]Lap. Methods: Pts with HER2+ MBC with an ECOG of <3 were grouped into 2 cohorts: with at least one 1-cm diameter brain metastasis or without brain metastases and underwent 90-minute dynamic cranial PET-CT scans after IV administration of a microdose (<1 mg) of [11C]Lap before and after 8 days of oral Lap (1500 mg once daily). Arterial blood samples were performed to assess [11C]Lap radioactivity contribution in blood and plasma, and the fraction of plasma [11C] radioactivity corresponding to metabolites. Tissue time-radioactivity curves (TACs) were generated and [11C]Lap exposure (AUC; area under TAC) derived for normal brain and brain metastases. Signal dissection of the total image activity was performed to remove the contribution of blood volume to the image and the actual tissue contribution due to [11C]Lap obtained. Results: 6 pts (3 with brain metastasis) were recruited. Arterial plasma analysis revealed that [11C]Lap contributed to >80% of activity in plasma at 60 minutes. Tissue data revealed [11C]Lap signal in normal brain was low with no appreciable uptake observed when corrected for blood volume contribution. [11C]Lap uptake was higher in brain metastases compared with normal brain and appreciable, even after correction for tissue blood volume contribution. Uptake was also observed in extra-cranial normal tissue. There was no difference in [11C]Lap uptake in normal brain and metastases between treatment-naïve and post-treatment scans. Conclusions: [11C]Lap uptake in brain metastases was higher than in normal brain. [11C]Lap drug access to brain metastases might therefore indicate possible efficacy against HER2+ brain metastases. Clinical trial information: NCT01290354.
Liposome-encapsulated doxorubicin plus cyclophosphamide followed by trastuzumab plus docetaxel as neoadjuvant therapy for HER2-positive breast cancer (BC): A multicenter single-arm phase II study.
Authors: Saracchini Silvana , Foltran Luisa , Sulfaro Sandro , Tuccia Fausto , Del Conte Alessandro , Bertola Manuela , Bassini Anna , Micheli Elvia , Manente Stefania , Gusso Giuseppina , Baresic Tania , Tumolo Salvatore 
Published: March 2020

641 Background: Trastuzumab combined to sequential chemotherapy with taxanes and anthracyclines as primary treatment achieved high rates of pathologic complete response (pCR) in HER2 positive BC. Liposome-encapsulated doxorubicin (DLNP) shown equal efficacy but minor cardiotoxicity compared to doxorubicin. This phase II study aimed to evaluate the activity and safety of trastuzumab associated with chemotherapy for early or locally advanced HER2 positive BC. Methods: Primary objective of the study was pCR defined as the absence of residual invasive cancer both in the breast and regional nodes. Preoperative treatment included DLNP (60 mg/mq iv) plus cyclophosphamide (600 mg/mq iv) every 3 weeks for 4 cycles followed by docetaxel (35 mg/mq iv) plus trastuzumab (4 mg/mq loading dose iv, then 2 mg/mq iv) weekly for 16 weeks. Patients (pts) were scheduled to receive adjuvant trastuzumab (8 mg/mq loading dose, then 6 mg/mq iv) every 3 weeks for 12 cycles and radiation and hormonal therapy according to guidelines. Results: From December 2005 to September 2011, 43 pts were treated at 3 centers in Italy. 39 out of 43 pts were evaluable for the purpose of the study. Median age was 53 years (range: 31-78). The majority of pts had cT2 (63%), grade 3 (93%), N+ (77%) ER positive (56%) and MIB-1 ≥20% (77%). pCR was reported in 19 (49%) of 39 pts. The histological regression score (Von Minckwitz G, J Clin Oncol 2012) is shown in the Table. A significant correlation between MIB-1 ≥20% at baseline and pCR was observed (p=0.018). Pts with pCR had a time to response (29.4 weeks, 95% CI 28-31) lower than pts without pCR (32.9 weeks, 95% CI 27-39). No cardiac toxicity or discontinuation of trastuzumab was reported. After a median follow-up of 30 months only 2 pts relapsed, both with pCR. Conclusions: This study confirms the high activity of trastuzumab combined with chemotherapy based on anthracyclines and taxanes as primary treatment for HER2 positive BC. DLNP is an active and safe option to minimize cardiotoxicity. [Table: see text]
Association between high-cost imaging and hospice use at the end of life of cancer patients.
Authors: Dinan Michaela A , Setoguchi Soko , Curtis Lesley H , Cheung Winson Y. 
Published: March 2020

6504 Background: Use of high cost imaging modalities can inform prognosis and potentially de-escalate unnecessary care at the end of life of cancer patients, but it may also be associated with increased health care expenditures. This analysis investigated the association of hospital-level use of advanced imaging studies with aggressiveness of care near death, as measured by hospice enrollment. Methods: Using SEER-Medicare, patients who died from common solid tumors between 2002 and 2007 were identified and hospital-level utilization of CT, MRI and PET scans were categorized into quartiles. Patients were assigned to the hospital at which they spent the majority of their inpatient days during the last 6 months of life. Multivariate-adjusted logistic regression models based on tumor type were constructed to correlate imaging use with late as well as all hospice admissions, defined as enrollment within 3 days and 18 months of death, respectively. Results: A total of 7,876 breast, 31,933 lung, 12,877 colorectal and 9,137 prostate cancer patients were included. High cost imaging varied across tumor types with rates being highest for lung cancer (mean of 2.29 CT, 0.58 MRI and 0.21 PET scans per patient) and lowest for prostate cancer (mean of 1.25 CT, 0.41 MRI, and 0.01 PET scans per patient) in the 6 months before death. Overall hospice use was least frequent in colorectal cancer (50% of patients) while late hospice admission was most common in lung cancer (11% of patients). Hospitals within the top quartile of imaging use generally had decreased odds of hospice utilization and higher likelihood of late hospice enrollment across most cancer types (Table). Conclusions: In this large cohort, receipt of care near end of life in hospitals with the highest rates of advanced imaging use was associated with lower use of and later enrollment to hospice. High cost imaging is not correlated with de-escalation of aggressive care. [Table: see text]
Determining value of high cost cancer therapies and discussing cost of cancer care: The patient perspective.
Authors: Rajguru Saurabh , Carmichael Lakeesha , Cetnar Jeremy Paul 
Published: March 2020

6512 Background: A trend in cancer treatment is the growing number of high-priced therapies which offer marginal clinical benefits. This has led ASCO to issue guidelines stressing the importance of discussing treatment costs with patients. There are many identified barriers which limit communication of cost including oncologists’ fears that patients may view this discussion as inappropriate. We attempted to assess cancer patients’ views on discussion of treatment costs with their oncologists, as well as, their views on high-cost drugs (HCDs), including the belief that there is a cohort of patients who would forgo high-priced treatment even if there was no out-of-pocket expense. Methods: We surveyed patients with advanced prostate cancer. The survey consisted of demographic information and an 11-item questionnaire. We also gave them a hypothetical scenario in which they were asked how much they would be willing-to-pay (WTP) for a $100K drug that would improve survival on average by four months with minimal side-effects (modeled after Provenge). The survey was administered to patients in clinic prior to their visit. Results: Of the patients approached, 169 responded (88% response rate). Seventeen percent stated they would not want treatment with HCDs even if they had no out-of-pocket expenses (more likely to be older (>70) and have an annual household income of >$60K). Another 21% stated they would accept treatment only if they had no out-of-pocket expenses. The median WTP for the hypothetical drug was $20K. Most patients (79%) agree that a discussion of costs with their physician is appropriate and 69% would want to have this discussion. Most patients (82%) agree that prognosis is important when making treatment decisions however 66% of patients did not know their cancer stage. Only 37% agree that the oncologist or the patient should consider the country’s healthcare costs when making treatment decisions. Conclusions: Prostate cancer patients clearly want to have discussions regarding costs-of-care with their oncologists. There is a group who would forgo treatment with high-cost drugs that yield only modest survival benefits. Their motivation is unknown, but is hypothesized to reflect a value-based judgment.
Adoption of robot-assisted surgery and its impact on treatment patterns for newly diagnosed localized prostate cancer.
Authors: Shih Ya-Chen T. , Hu Jim C. , Shen Chan , Eggener Scott E. 
Published: March 2020

6513 Background: With the rapid increase of robotic surgical systems in hospitals, it is important to understand the impact on treatment patterns for localized prostate cancer. The objective of this study is to determine whether the presence of robotic surgical systems independently influenced rates of surgery, radiation, and active surveillance for localized prostate cancer. Methods: We conducted an observational study using National Cancer Database (NCDB) state-level data, 2002-2010. Our study cohort includes patients newly diagnosed with clinical stage I-III prostate cancer from 48 states and Washington D.C. in the United States. The number of robotic systems installed in each state over time was obtained from publicly available information on-line. We characterized the state-level treatment pattern as the proportion of patients having surgery, radiation and active surveillance as their first course of treatment. Results: Between 2002 and 2010, the average number of robotic surgical systems per state increased from 2 to 26.3, while the unadjusted rate of surgery increased from 37.5% to 52.4%, radiation therapy decreased from 43.3% to 30.2%, and active surveillance increased from 7.0% to 9.3%. For every 10 additional robotic systems installed in a state, there would be a 2.5% increased rate of surgery (p<0.01), accompanied by a 1.3% (p=0.04) and 1.0% (p<0.01) decrease in the rate of radiation and active surveillance, respectively. Subgroup analyses suggest that the robotic adoption crowding out effect on radiation and active surveillance was driven primarily by men with stage I-II prostate cancer. If the adoption trajectory for robotic systems continues, the increased cost of treating localized prostate cancer in 2012 will be close to $27 million. Conclusions: During a period of rapid acquisition of robotic surgical systems, we found the number of robotic systems available at the state-level is significantly and directly associated with a higher rate of surgery for localized prostate cancer, and lower rates of radiation therapy and active surveillance.
The cost per patient of deviations from evidence-based standards of oncology care.
Authors: Forastiere Arlene A. , Flood William A. , Yedwab Erik , Kozlovsky Vlad , Whyler Elaine , Alley Evan W. , Frick Kevin D. 
Published: March 2020

6515 Background: Practice variation contributes to the high cost of healthcare and wasteful spending; by contrast, adherence to evidence-based (EB) clinical guidelines is advocated to improve quality and potentially lower cost. We sought to estimate the average cost per patient associated with unjustified deviations from EB national standards for use of chemotherapy, supportive drugs, and radiotherapy. Methods: The ITA Partners/eviti, Inc. database of oncology treatment plans (TPs) reviewed for payers for adherence to national guideline recommendations (e.g. ASCO, ASTRO, NCI, NCCN Compendium, FDA) was used to calculate the variance in cost between submitted TPs with unwarranted deviations from EB standards and EB care. For prospective reviews, the final EB treatment given was known and for retrospective reviews, the variance was estimated based on the EB alternative with the lowest cost. AWP pricing was used to calculate chemotherapy and supportive drug costs, and Medicare pricing for radiotherapy. First order savings were calculated. An annual trend of 8% was applied from the mid-data period to 2013 (Milliman Client Report 2010). Results: From March 2009 to March 2012, a total of 2775 consecutive patients had TPs submitted and of these, 730 patients had unjustified, non-EB TPs. All cancer types, stage and treatment intent (curative, non-curative) were included. The cost of EB treatment was less than the submitted TP for 622 (85%) patients, more for 9 (1%), and zero (could not be taken due to payer plan definitions) for 99 (14%). Descriptive statistics for the cost per patient of non-EB TPs trended to 2013 showed: mean $25,579, median $13,882, standard deviation $40,958. Conclusions: In this unselected population comprising all cancers, 26% had TPs that did not conform to EB standards or could not be medically justified. Our conservative estimate of the average per patient overspend (first order) on inappropriate treatment validates the potential for quality care to lower cost and deliver huge value to patients, physicians, and payers. [Table: see text]
Sensitivity of Medicare claims to identify recurrence.
Authors: Warren Joan L , Mariotto Angela , Melbert Danielle , Schrag Deborah , Doria-Rose Paul , Penson David F. , Yabroff K. Robin 
Published: March 2020

6522 Background: Cancer registries do not collect recurrence data. As a result, researchers have used health claims to impute recurrence for cancer patients by identifying cancer therapy or metastatic disease after initial treatment. The validity of this approach has not been established. We used the linked SEER- Medicare data to assess the sensitivity of Medicare claims for cancer recurrence. Methods: Although the SEER-Medicare data do not explicitly capture recurrence, we applied criteria to identify patients likely to have had a recurrence, defined as patients diagnosed with Stage II/III colorectal (CRC) and female breast cancers from 1994-2003 who received initial cancer surgery, had at least a 90-day break in treatment following initial treatment, who then died from cancer in 1994-2008. For these patients, we reviewed all claims from the end of the treatment break to death for indicators of recurrence. Indicators included additional therapy (cancer surgery, chemotherapy, RT), diagnosis codes for metastasis, and end-of-life care. We used multivariate logistic regression analysis to evaluate patient factors associated with receipt of additional cancer therapy. Results: The first indicator of recurrence for CRC patients (n=6,910) and breast patients (n=3,826) was additional therapy (38.8% and 35.2%), metastasis diagnosis codes (36.0% and 45.7 %), or end-of-life care (16.7% and 12.8 %). Eight percent of patients had no indicator of recurrence before death; 40% of patients had no additional cancer therapy before death. Patients age 70 and older were less likely to have additional therapy (p<0.05), in adjusted analyses. Conclusions: Identifying recurrence through additional cancer therapy will miss about 40 percent of patients with recurrences; particularly older patients. Over 20% of patients with recurrence were first identified by hospice admission, late in the course of their illness, or had no indicator of recurrence in the claims. We conclude that Medicare data have limited potential to identify cancer recurrence. These findings may not apply to younger cancer patients, who are more likely to undergo additional cancer treatment for recurrence.
Impact of care at NCI-designated comprehensive cancer centers (NCICCC) on outcome in adolescents and young adults (AYA) with central nervous system tumors (CNSt).
Authors: Wolfson Julie Anna , Sun Can-Lan , Kang Tongjun , Bhatia Smita 
Published: March 2020

6537 Background: AYA (15-39y) have not seen survival improvement as in younger or older ages with similar cancer diagnoses, leaving an AYA Gap. Pediatric protocol use is associated with superior survival among 15-21y-olds, but impact of site of care for complex diseases with poor prognosis (such as CNSt) that require multidisciplinary, evidence-based care available at NCICCC, are unstudied. Methods: We constructed a cohort of 746 AYA with newly diagnosed CNSt, reported to the LA cancer registry from 1998-2008; 133 (18%) were treated at the 3 NCICCC in LA county. We examined clinical (WHO grade, diagnosis (dx) year, site of care) and demographic (age at dx, gender, SES, insurance, race/ethnicity) variables univariately; we included only those with p<0.1 in the final multivariable model (retaining WHO and NCICCC). Analysis was stratified by time from dx (≤2y, n=746; >2y, n=493) to examine impact of care at NCICCC among AYA with aggressive disease (resulting in death within 2y from dx) vs. those who survived 2y from dx – representing disease likely amenable to new strategies for control. Results: 5y overall survival (OS) was 59% and did not differ by site of care (p=0.2). Multivariable analysis restricted to the first 2y revealed an increased risk of death among those with high WHO grade (HR 4.7, p<.0001); public/no insurance (HR 1.7, p=0.0006); and African American/Asian (HR 2.1, p=0.0006) or Hispanic (HR 1.4, p=0.08) origin; site of care did not impact mortality. Among 2-y survivors, high WHO grade (HR 1.7, p=0.002) continued to be associated with increased risk of death. However, receipt of care at non-NCICCC site (HR 1.6, p=0.056) was also associated with increased risk of death. Examination of access to care at NCICCC revealed that after adjusting for WHO grade and gender, older age (22-39y (OR 0.3, p<0.0001), low SES (OR 0.6, p=0.04), and non-white ethnicity (OR 0.5, p=0.004), decreased likelihood of care at NCICCC. Conclusions: Population-based data reveal better OS in 2-y AYA survivors of CNSt receiving care at NCICCC. Older AYAs from low SES and non-white backgrounds are less likely to use NCICCC. AYA barriers to accessing NCICCC care are currently being explored.
The cost implications of prostate cancer screening in the Medicare population.
Authors: Ma Xiaomei , Wang Rong , Long Jessica B. , Ross Joseph S. , Soulos Pamela R. , Yu James B. , Makarov Danil V. , Gold Heather Taffet , Gross Cary Philip 
Published: March 2020

6549 Background: Recent debate about prostate specific antigen (PSA)-based testing for prostate cancer screening among older men has rarely considered the cost associated with screening. Methods: We assembled a population-based cohort of male Medicare beneficiaries aged 66-99 years who had never been diagnosed with prostate cancer at the end of 2005 (n = 84,699) and followed them for two years to assess the cost of PSA screening and downstream procedures (biopsy, pathology, and hospitalization due to biopsy complications) at both the national and the hospital referral region (HRR) level. The relation of screening cost to stage of prostate cancer at diagnosis at the HRR level was analyzed using multivariate Poisson models. We also evaluated the initial treatment cost of Medicare fee for service beneficiaries diagnosed with prostate cancer during 2006-2007 (n = 31,653). Results: Approximately 42.8% of the 84,699 men received PSA screening tests during the two-year study period, with 2.4% undergoing biopsy. The annual expenditures by the national fee for service Medicare program were $454 million for screening and $1.79 billion for initial treatment (in 2009 US dollars). The mean annual screening cost at the regional (HRR) level ranged from $16 to $65 per beneficiary. Downstream biopsy-related procedures (biopsy, pathology, and hospitalization due to biopsy complications) accounted for 73% of the overall screening costs and varied significantly across regions. Compared with men residing in HRRs that were in the lowest quartile for screening expenditures, men living in the highest HRR quartile were significantly more likely to be diagnosed with prostate cancer of any stage [incidence rate ratio (IRR) = 1.23, 95% confidence interval (CI): 1.07-1.42] and localized cancer (IRR = 1.31, 95% CI: 1.13-1.53). Conclusions: Medicare prostate cancer screening-related expenditures are substantial, vary considerably across regions, and are positively associated with rates of cancer diagnosis.
Longitudinal trends in costs for palliative radiation for metastatic prostate cancer.
Authors: Robinson Timothy J , Dinan Michaela A , Li Yanhong , Lee Robert , Reed Shelby D. 
Published: March 2020

6554 Background: Prostate cancer is a leading contributor to cancer health care costs, with end of life care composing a substantial portion of overall costs. In recent years, palliative treatment of metastases has been characterized by the use of more complex radiation planning and delivery systems. However, little is known about how costs of palliative radiation treatment in patients with metastatic prostate cancer have changed over this period. Methods: Retrospective analysis of SEER-Medicare data of men aged 66 and older who died from metastatic prostate cancer between 2000 and 2007. Inclusion criteria included all fee-for-service beneficiaries treated with radiation therapy for bony metastases in the last year of life. Direct costs were obtained by summing Medicare carrier and outpatient facility payments for all radiation treatment claims following an initial radiation treatment claim for bony metastases and adjusted to 2008 dollars using Consumer Price Indexes for medical care. Results: A total of 1,705 men met study inclusion criteria. Median age at diagnosis was 74, median time from diagnosis to death was 47 months, and 37% of men had distant metastatic disease at the time of diagnosis. Total Medicare payments for radiation therapy for bony metastases increased from an average of $2,763 to $3,989 for men who died from prostate cancer in 2000 vs. 2007. Outpatient facility claims for radiation therapy increased relative to carrier claims, composing 48% ($1,316) and 57% ($2,276) of all radiation treatment Medicare payments in 2000 vs. 2007 (All P < 0.001). Conclusions: Between 2000 and 2007, average Medicare payments for palliative radiation therapy for bony prostate cancer metastases increased by roughly a third. The majority of increased costs were observed within outpatient facility claims, suggesting a shift in the administration of palliative radiation therapy from free-standing clinics to hospital-based outpatient facilities. Changes in end of life palliative radiation therapy for men with prostate cancer may impact future increases in Medicare health care expenditures.