bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of positron emission tomography (PET) scans on the management of cancers of unknown primary.
Authors: Chen Hao , Cheung Winson Y.
Published: March 2020

6066

Background: PET scans can be potentially useful in the diagnostic and staging workup of certain cancers. Although frequently ordered, its precise role in the investigation and management of cancers of unknown primary (CUP) remains poorly defined. Our main study aims were to 1) compare the utility of PET vs. CT scans in determining the primary site, lymph node status, and metastases for patients with CUP, and 2) describe the overall survival of patients for whom the primary site was determined by PET vs. those who were not. Methods: Patients diagnosed with CUP in British Columbia, Canada from 2006 to 2009, evaluated at 1 of 5 regional cancer centers in the province, and underwent a PET scan were reviewed. We measured concordance rates between PET and CT scans and constructed regression models to characterize the effect of PET scans on treatment and survival. Results: A total of 175 patients were included: median age was 60 years and 76% were men. PET scans were most commonly performed for the following indications: locating primary (45%); staging (42%); and others (13%). Among those in whom CT did not detect the primary site, PET revealed the location of the primary in 9% of cases. CTs and PETs were concordant in demonstrating nodal status and metastases in 91% and 95% of patients, respectively. PET scans were able to show additional nodal involvement and uncover metastatic disease in 9% and 5%, respectively, when compared to CT scans. Identification of the site of primary cancer by PET did not substantially modify subsequent therapy (p=0.37) and it also failed to significantly improve the median overall survival (10.1 vs. 7.3 months, p=0.57) when compared to those in whom the location of the primary was unconfirmed. Conclusions: In this retrospective cohort of CUP patients, CT and PET scans appear to provide a similar level of diagnostic and staging information. For a small proportion of CUP patients, PETs were superior in clarifying the primary site, nodal status, and metastases, but these did not alter therapy or increase overall survival. Based on these findings and considering the cost implications of intensive imaging studies, the diagnostic value of PET scans over CT scans appears limited to a small subset of patients with CUP.
Out-of-pocket (OOP) health care expenditure burden for Medicare beneficiaries with cancer.
Authors: Zuckerman Ilene H. , Pandya Naimish B. , Stuart Bruce C. , Shaffer Thomas , Erten Mujde Z. , Ke Xuehua , Shoemaker J. Samantha , Tai Ming-Hui , Davidoff Amy J.
Published: March 2020

6075

Background: Concern is increasing about the OOP burden faced by cancer patients (pts). Medicare beneficiaries have multiple comorbidities, have limited financial resources, and may face substantial cost sharing under traditional Medicare if they do not have generous supplemental coverage. We examined OOP spending and burden relative to income for Medicare beneficiaries with cancer, compared to a non-cancer comparison group. Methods: We used Medicare Current Beneficiary Survey data (1997-2007). Newly diagnosed cancer pts were selected using ICD-9CM codes on claims after a 12 mos washout period. OOP spending was assessed using self report for the index(diagnosis) and subsequent year. Pt characteristics were self reported. Generalized Linear Models estimated effects of pt characteristics on OOP spending; logistic regression identified pt characteristics associated with high burden, defined as OOP spending >20% of income. Results: The cohort included 1,869 beneficiaries with, and 10,057 beneficiaries without cancer. Relative to the non-cancer cohort, cancer pts were older, had greater comorbidities, and were more likely to lack supplemental coverage (22 vs 16%) (all at p<0.01).OOP spending was $4,727 or 11.4% of total spending for cancer pts. The unadjusted difference between cancer and non-cancer pts in OOP spending was $1,518 (p<.001); with adjustment for patient characteristics, cancer patients faced an incremental $956 (p<.01) in OOP spending. Median[mean] OOP/income was 10%[24%] for beneficiaries with, compared to 6%[14%] without cancer (p<.001). Over ¼ (28%) of beneficiaries with cancer spent 20% of their income OOP, compared to 16% of beneficiaries without cancer (p<.001). Supplemental insurance and higher income were protective against high OOP burden, whereas assets, comorbidity, and receipt of cancer-directed radiation and antineoplastic therapy were associated with higher OOP burden. Conclusions: Medicare beneficiaries with cancer face higher OOP burden than their counterparts without cancer; some of the higher burden was explained by higher comorbidity burden and lack of supplemental insurance. Financial pressures may discourage some elderly patients from pursuing treatment.
Surveillance after potentially curative breast cancer treatment: The impact of HMOs.
Authors: Avino Robert J. , Allam Emad S. , Margenthaler Julie A. , Chen Ling , Virgo Katherine S. , Johnson Frank E.
Published: March 2020

6079

Background: Over 230,000 new cases of breast cancer are diagnosed in the US annually. Most patients receive curative-intent treatment. Post-treatment surveillance is commonly done. We have previously documented dramatic variation in surveillance intensity among ASCO experts. The only surveillance modalities endorsed by ASCO for asymptomatic patients are office visit and mammogram. It is commonly believed that health maintenance organizations (HMOs) restrict test utilization. We sought to determine the effect of HMO penetration rate on the known variation in surveillance strategies. Methods: The 3245 ASCO members who indicated that breast cancer was a major clinical focus of their practice were surveyed regarding their surveillance practices. Members were asked to consider 4 idealized clinical vignettes and indicate their surveillance plan for each. A menu of 12 testing modalities was offered. Practice patterns were stratified by HMO penetration rate (0-14%, 14-22%, 22-33%, 33-61%) in each physician’s practice location. Repeated-measures ANOVA was employed for analysis. Results: Of the ASCO members surveyed, 1012 responded; 915 were evaluable. The modalities most frequently recommended were office visit, CBC, liver function tests (LFTs), and diagnostic mammogram. There was significant variation (p<0.05) in the recommended frequency of utilization of diagnostic mammogram, but in no other modalities. For example, in year 1, diagnostic mammogram was recommended 1.9 ± 1.8 (mean ±SD) times for the 0-14% penetration rate cohort and 1.5 ± 1.1 times for the 14-22% cohort. Conclusions: We found little evidence that HMOs restrict test utilization. The HMO penetration rate in the clinician’s practice location cannot account for the overall variation we have documented previously.
Physician age and surveillance intensity following curative-intent treatment for breast cancer patients.
Authors: Abboud Steven F. , Allam Emad S. , Margenthaler Julie A. , Chen Ling , Virgo Katherine S. , Johnson Frank E.
Published: March 2020

6081

Background: Breast carcinoma is a large health care concern for patients, physicians, and society. 2.5 million women have been treated for breast cancer and are candidates for surveillance in the US. We have documented dramatic variation in post-treatment surveillance strategies utilized by ASCO experts caring for such patients. Since it is often asserted that younger physicians order more tests than older physicians, we sought to measure the effect of clinician age on post-treatment surveillance intensity for breast cancer patients by analyzing a recent survey of ASCO members. Methods: We surveyed the 3245 ASCO members who indicated that breast cancer treatment was a major focus of their practice. 4 succinct clinical vignettes describing generally healthy women with breast cancer of varying prognoses and a menu of 12 surveillance modalities were offered. The menu was chosen after a literature search indicated that no other surveillance tests were commonly used. We analyzed data from one of the 4 idealized vignettes only (the patient with TNM IIA carcinoma) and stratified responses by clinician age. Practice patterns were compared by years after completion of training (0-10, 11-20, 21-30, 30-40, >40 years), a surrogate measure of physician age. Statistical analysis employed ANOVA. Results: There were 1012 responses; 915 were evaluable. Statistically significant differences were observed across age strata for CBC, liver function tests (LFTs), and serum CEA level only. For example, ASCO clinicians in practice for 0-10 years after completion of training recommended CBCs 1.3 + 1.4 (mean + SD) times in year 1. Those > 40 years after completion of training recommended CBCs 2.4 + 1.3 times in year 1 (p<0.001). Conclusions: Younger physicians recommend statistically significantly fewer CBCs, LFTs, and serum CEA levels during post-treatment surveillance than older physicians. However, the magnitude of the difference is clinically small for all 3 modalities and does not explain the known overall variation in surveillance practice among clinically active experts.
Comparison of drug approval between health Canada (HC) and the U.S. Food and Drug Administration (FDA).
Authors: Ezeife Doreen Anuli , Tang Patricia , Heng Daniel Yick Chin , Welch Stephen
Published: March 2020

6082

Background: Differences in drug approval processes between countries can impact patient access to new therapies. In Canada, patients can freely access a new treatment after regulatory approval by Health Canada (HC) followed by funding approval from the provincial government. The aims of this study were to delineate the Canadian drug approval timeline and to compare the time to drug approval between HC and the US FDA. Methods: Cancer drugs approved by the FDA from 1989 to 2011 were reviewed. For each drug, the following endpoints were determined: publication date of phase I and pivotal phase III trial, date of FDA and HC approval, HC submission date, and funding approval in Alberta (AB). Time intervals between the aforementioned endpoints were calculated. Results: Of 55 FDA-approved drugs, 51 drugs are approved by HC with 40 of these drugs funded in AB. HC approval occurs an average of 14.4 months post FDA approval (95% CI -36.9 to 66.1, sign rank test p<0.0001). However, there was no significant difference between the mean time from Phase I to FDA approval (48.5 months; 95% CI 21.2 to 75.8) and Phase I to HC approval (61.5 months; 95% CI 32.4 to 90.5). Most drugs (74%) were approved by the FDA prior to publication of the phase III trial. There was a trend towards faster drug approval from Phase III to FDA approval compared to HC (-14.97 versus 0.1 months, p = 0.05). HC submission occurs before FDA drug approval 77% of the time (mean 3.0 months prior; 95%CI: -59.1 to 43.4, p = 0.0206). HC approval occurs on average 17 months post HC submission. AB funding approval occurs on average 22 months after HC approval. The time interval from Phase I to AB funding approval was significantly shorter for targeted compared to cytotoxic agents (mean time 58 vs. 120 months; p = 0.039). Conclusions: HC drug approval lags behind FDA approval by about 14 months. Time from Phase III to drug approval tends to be shorter for the FDA compared to HC. This is the first documentation, to our knowledge, of the time required to bring a drug from phase I trial to provincial funding approval.
Chemotherapy in the oldest old: The feasibility of cytotoxic therapy in the 80+ population.
Authors: Sud Shelly , Lai Pamela , Balchin Katelyn , Clemons Mark , Wheatley-Price Paul
Published: March 2020

6083

Background: The incidence of most common malignancies increases with age. As life expectancy improves globally, more elderly cancer patients will be candidates for systemic therapy. There is little data investigating chemotherapy (CT) in those over 80 – the “oldest old”. Our hypothesis is that CT in the 80+ population may be associated with significant toxicities and is therefore not feasible for many patients. Methods: A retrospective chart review was undertaken to report outcomes of patients ≥80 years old who initiated CT for solid tumors at the Ottawa Hospital Cancer Center between Nov. 2005 and Jan. 2010. Baseline data on patient demographics, cancer type and CT were collected. Primary endpoints included: rates of CT dose reduction, omission, delay and discontinuation due to toxicity, hospitalization and blood transfusion rates. Results: CT was initiated on 212 occasions (32% lung, 31% GU, 24% GI, 13% other cancer). Median age was 83 (range 80-92) and 60% of patients were male. Where data were available, 60% had a good performance score (ECOG 0-1) and 63% were current or ex-smokers. 82% had Charlson risk index scores of ≥5, 37% had ≥6 baseline medications, 18% lived alone independently. At baseline, 11% were anemic, 12% had leukocytosis, and 45% had impaired renal function (eGFR<60). Most patients had stage 4 disease (76%), were treated with palliative intent (75%) and were receiving first line CT (77%). Initial dose was adjusted in 34% of cases. Therapy was discontinued due to toxicity in 30% of cases, and 53% of patients required dose reduction, omission or delay. In 38% of cases, patients were hospitalized during their course of therapy or within 30 days thereof. Blood transfusions were required in 24%. Factors associated with risk of hospitalization included baseline number of medications ≥6 (OR 1.96, 95% CI 1.1-3.5) and baseline anemia (OR 2.55, 95% CI 1.07-6.05). Initial dose reduction at cycle 1 did not significantly affect rates of hospitalization, transfusion or CT discontinuation. Conclusions: CT in the 80+ population is associated with a significant risk of hospitalization, transfusion and discontinuation due to toxicity, even when doses are adjusted from the outset. We plan to prospectively validate these findings.
Physical activity (PA) and physical function (PF) in adult cancer survivors (CS).
Authors: Birks Peter Crawford , Tashakkor Amir Yashar , Moghaddamjou Ali , Cheung Winson Y.
Published: March 2020

6085

Background: The longevity of CS is increasing, underscoring the importance of lifestyle modifications and preventive care, consisting of regular PA and maintenance of PF. Our aims were to 1) compare PA and PF among short-term CS, long-term CS and non-cancer controls (NCC) and 2) identify other clinical factors associated with decreased PA and PF. Methods: We identified CS and NCC from the US National Health and Nutrition Examination Survey (NHANES). CS were categorized into </=5 (short-term) and >5 years (long-term) based on date of diagnosis. Multivariate weighted regression models were constructed to examine for differences in 28 and 26 measures of PA and PF, respectively, while controlling for age, gender, ethnicity, education, income, and other confounders. We explored specific and general PA domains such as aerobic activity and decline from past activity level as well as PF areas including ADLs, IADLs and mobility. Results: In total, 26,185 subjects were identified: 968 short-term CS, 1,367 long-term CS, and 23,832 NCC. For the entire cohort, the mean age was 50 years, 52% were men, and 50% were white. Comparing across the 3 patient groups, CS were generally older than NCC (60 vs 45 years, p<0.01). In terms of PA, short-term CS reported less general activity compared to 1 year ago (OR 0.58, 95%, CI 0.46-0.73, p<0.01) than long-term CS and NCC. In comparison to NCC, both groups of CS also described less current activity than their baseline from 10 years ago (OR 0.63, 95% CI 0.48-0.82, P=0.001 and OR 0.67, 95% CI 0.55-0.83, P=<0.01). There were significant differences among patient groups in several areas of PF (Table). Other factors that were associated with lower PA and PF included advanced age, low education, and low income. Conclusions: PA between CS and NCC were similar, although current activity as compared to that of the preceding year or past decade appears lower in CS, which may reflect their older age. Impairments in several measures of PF were observed among CS, which could impact their quality and quantity of life. [Table: see text]
The NCI Community Cancer Centers Program (NCCCP): A model for reducing cancer health care disparities.
Authors: O'Brien Donna M. , Bright Mary Anne , Clauser Steven B. , Fennell Mary , Harness Jay K. , Hood Deborah D. , Johnson Maureen , Katurakes Nora C. , McCaskill-Stevens Worta , Zapka Jane , Adjei Brenda A. , Castro Kathleen M. , Dimond Eileen P. , St. Germain Diane C. , Springfield Sanya
Published: March 2020

6086

Background: In 2007, NCI launched the NCCCP, a public-private partnership with 16 community hospital cancer centers in 14 states, to explore methods to improve patient access to advanced cancer care in the community. With 40% of its NCI funding directed to reduce disparities across the cancer continuum, the NCCCP aims to: 1) Enhance access to care; 2) Improve quality of care; and 3) Increase clinical trials accrual. This approach supports priorities in the 2009 ASCO Policy Statement: Disparities in Cancer Care. Methods: A disparities workplan was developed to support the three aims. NCI and the sites worked as a learning collaborative to develop strategies and metrics for: race and ethnicity data tracking; near real-time reporting of adherence to Commission on Cancer (CoC) treatment quality measures; community outreach and patient navigation to increase cancer screening; and improved clinical trial underserved accrual. The tools and resources supporting these efforts will be discussed. ( http://ncccp.cancer.gov/About/Progress.htm ). Results: Evaluation of the 3 year pilot shows improvement for underserved populations: Concordance with CoC treatment quality measures for radiation therapy for breast conserving surgery among Medicaid patients improved from 59.5 percent to 84.8 percent (p<.05). Increased community screening events (from 992 to 1,585) and community partnerships focused on underserved populations (from 78 to 195). Increased accrual to NCI trials (minority accrual from 82 to 151 and elderly from 200 to 641). Conclusions: To be effective in reducing healthcare disparities, a multi-level approach is needed. This includes having: organizations which demonstrate a strong community-oriented mission; commitment by hospital management; engagement of private practice physicians; targeted training of staff; use of standardized data collection and metrics; involvement of strategic partners with aligned goals at the national and local level; support by relevant NCI experts; and sharing best practices across a learning collaborative. The NCCCP disparities model was used in a variety of community settings targeting different underserved populations and has demonstrated effect in care in the respective communities.
Unanticipated hospital admissions in patients undergoing radiotherapy with or without concurrent chemotherapy: Incidence and predictive factors.
Authors: Arastu Nabeel H. , Chen Ronald C. , Jackson Marianne , Green Rebecca L. , Qaqish Bahjat F. , Camporeale Jayne , Xu Zijie S. , Collichio Frances A. , Marks Lawrence Bruce
Published: March 2020

6093

Background: Unanticipated admissions are burdensome for patients and the healthcare system. An improved understanding of their frequency and predictive factors can inform initiatives to prevent such admissions and mitigate their associated human and financial costs. Methods: Electronic medical records of 500 patients undergoing external beam radiotherapy (RT) at our center in 2010 were reviewed. Unanticipated admission within 90 days of initiating RT, and associated clinical factors, were recorded. Chi-squared and uni- and multivariate logistic regression was used to examine factors associated with admission. Results: Unanticipated admissions occurred in 20% (101/500) of patients, mean length of stay was 4 days (range 1-16), and the mean interval between the start of RT and admission was 32 days (0-86 days). The most common indications for admissions were pain (19% of admissions), respiratory distress (15%), and neurologic symptoms (13%). On univariable analysis, 33% of patients treated for palliative intent were admitted (vs. 16% of curative intent patients, p<0.001), as were 26% of patients receiving concurrent chemotherapy (vs. 17% receiving RT alone, p=0.02). Multivariable analysis showed treatment intent, chemotherapy, and marital status to be associated with unplanned admissions (Table). A highly variable rate of unanticipated admission per diagnosis was observed (e.g. 4% for breast, 19% for GI/GU/GYN/ENT, and 37% for metastatic sites). Conclusions: Rates of unanticipated admissions are ≈20% in patients undergoing RT. Approximately 1/3 of patients receiving palliative RT, and more than 1/4 receiving concurrent chemoradiation, experienced an unplanned admission. Prophylactic measures should be studied in these high-risk patients to reduce admission rates, as unplanned admission may be an important quality of care indicator in oncology. [Table: see text]
Differential receipt of sentinel lymph node biopsy within practice-based research networks.
Authors: Meyer Anne-Marie , Reeder-Hayes Katherine Elizabeth , Liu Huan , Wheeler Stephanie B. , Penn Dolly , Weiner Bryan , Carpenter William Ruffin , Stitzenberg Karyn Beth
Published: March 2020

6104

Background: Sentinel lymph node biopsy (SLNB) for breast cancer was introduced into clinical practice in the late 1990s as an alternative to axillary lymph node dissection (ALND). Provider-based research networks (PBRNs) are believed to promote diffusion of innovations like SLNB into clinical practice; however, evidence of this association is limited. This study examines the diffusion of SLNB for early-stage breast cancer through the Community Clinical Oncology Program (CCOP), a community-based PBRN. Methods: We identified women undergoing breast conserving surgery with axillary staging for stage I or II breast cancer between January 2000 and December 2003 using Surveillance Epidemiology and End Results-Medicare data (n=6,226). The primary outcome was receipt of SLNB vs. ALND, and exposure was care received from CCOP physicians or institutions between diagnosis and surgery. Exposure was quantified as both a binary measure of ever seeing a CCOP, and as a proportion of all their claims associated with a CCOP. Covariates included race, age, marital status, education, Medicaid eligibility, comorbidity, tumor grade, stage, estrogen receptor status, year of diagnosis, SEER region, and other institutional characteristics such as NCI center designation, cooperative group, and medical school affiliation. Multivariable generalized linear modeling with generalized estimating equations was used to measure association between CCOP exposure and receipt of SLNB. Results: Women who received a higher proportion of their care from a CCOP-affiliated physician or hospital were more likely to receive SLNB. A 10% increase in the proportion of CCOP-affiliated claims was associated with a greater odds of receiving SLNB (OR 1.14; 95% CI 1.08, 1.20), after controlling for covariates. Similarly, sensitivity analysis of the binary indicator of CCOP exposure also showed greater odds of receiving SLNB (OR 1.32; 95%CI 1.01, 1.74). Conclusions: The quality of cancer care delivered in community settings can be influenced by provider-based research networks. Our findings contribute to the growing body of evidence that community-based PBRNs can facilitate adoption of cancer innovations outside of academic medical centers.
Frequency of cognitive impairment (CI) in elderly patients (pts) suffering from malignancies and impact on therapeutic decision.
Authors: De La Motte Rouge Thibault , Chaïbi Pascal , Vignot Stéphane , Boussion Helene , Cabel Luc , Geiss Romain , Delgado Francois-Michel , Khayat David , Chebib Amale , Spano Jean-Philippe
Published: March 2020

6110

Background: Therapeutic decision remains complex when a cancer is diagnosed in elderly pts. Our aim was to evaluate the frequency of CI in this population and its impact on therapeutic decision. Methods: An oncogeriatric evaluation including Comprehensive Geriatric Assessment (CGA) is systematically performed for all elderly cancer pts referred in our unit. We reviewed data of all pts assessed by geriatric oncologist at our institution from January 2009 to June 2011. Results: 378 pts were identified, among them a CI was noted in 87. Median age was 84 years (range 71 –94), 70 % ≥ 80 years. Most of the pts (78/87) were referred at the time of diagnosis. Metastatic disease was diagnosed in 32 pts (52%) and Diffuse Large B Cell Lymphoma stage III or IV in 21 pts (81 %). In 41 pts, CI was already diagnosed: Alzheimer disease (AD) (n=38) and Vascular Dementia (n=3). CGA help to identify CI in 46 additional pts: AD (n=36); Vascular Dementia (n=2) and Mild Cognitive Impairment (n=8). 45/87 pts (52 %) were dependant for at least one activity of daily living (ADL). As a result of CGA and benefit/risk oncologic assessment, best supportive care was recommended in 12 pts. Among them, only 4 pts presented with advanced metastatic disease (main reason for palliative care). Pts in whom “best supportive care” decision (n=12) was recommended were more dependants than those who received specific anticancer therapy (n=75): dependence for at least 2 ADL: 10/12 pts (83%) versus 16/75 (21%); and presented more AD already diagnosed (11/12 versus 30/75). In the remaining 75 pts, specific cancer therapy was proposed, including chemotherapy (n=67), surgery (n=5), radiotherapy (n=3) and hormonotherapy (n=9). Treatment was initiated as recommended in all but 4 pts (best supportive care decision taken following discussion with pts and relatives). During the follow-up, only 11/75 pts needed to be placed in nursing home because of loss of autonomy. A survival ≥ 1 year was observed in 27/75 (36%) pts. An update of cognitive performance will be presented. Conclusions: Our data support that even if CI is frequent in elderly pts with malignancies, specific anticancer therapy remains feasible and should be considered in most elderly pts with CI.
An integrated analysis of comprehensive geriatric assessment (CGA) in elderly patients with non-small cell lung cancer (NSCLC) (JCOG1115-A).
Authors: Katayama Hiroshi , Takeda Koji , Fukuda Haruhiko , Nakamura Shinichiro , Nakamura Kenichi , Mizusawa Junki , Saijo Nagahiro , Yokoyama Akira , Ohe Yuichiro , Shinkai Tetsu , Nakagawa Kazuhiko , Abe Tetsuya , Mitsuoka Shigeki , Ichinose Yukito , Okamoto Hiroaki , Yamamoto Nobuyuki , Yoshioka Hiroshige , Ando Masahiko , Tamura Tomohide
Published: March 2020

6112

Background: The number of elderly NSCLC patients is increasing all over the world. Actual age and ECOG PS is not always efficient to select "fit-elderly" for chemotherapy. We integrated the data from two phase III trial (JCOG0207, JCOG0803/WJOG4307L) and evaluated 4 CGA items as well as age and PS to determine whether they would predict survival, response and toxicities. Methods: Eligibility criteria of both trials included histologically or cytologically proven NSCLC; stage III/IV; age 70 or more; ECOG PS of 0-1; unfit for bolus cisplatin; no prior treatment; adequate organ function. Patients were randomized to receive either weekly docetaxel (D) or D plus cisplatin (DP) in J0207, and either 3-weekly D or DP in J0803/W4307L. This study included all eligible pts for whom all of 4 CGA items (Activity of Daily Living [ADL], Instrumental Activity of Daily Living [IADL], Mini-Mental State Examination [MMSE], Geriatric Depression Scale [GDS-15]) were assessed before treatment. Primary endpoint was overall survival (OS). Survival curves are estimated by Kaplan-Meier method and multivariate analysis for OS adjusting baseline factors were performed by using stratified Cox regression model. Results: This analysis included 331 pts (J0207/J0803-W4307L: 105/226) in total. The result of multivariate analysis for OS was shown in the table. After adjusting baseline factors, MMSE as well as sex and PS was significantly associated with OS. None of the CGA items were associated with response and toxicities. Conclusions: It is not actual age but MMSE and PS that is useful for predicting prognosis of elderly pts. MMSE should be taken into consideration to determine the indication of chemotherapy for elderly pts. [Table: see text]
Loss to follow-up of cancer patients in the poorest district of the United States.
Authors: Mangardich Antranik , Mamorska-Dyga Aleksandra , Paul Doru , Khan Ghulam , Vassel Svetlana , Gerber Linda , Guset Valentin , Segni Jessica
Published: March 2020

6123

Background: Loss to follow-up (LFU) of cancer patients is a serious dilemma, and has only been narrowly studied. Lincoln Medical and Mental Health Center (LMMHC) serves South Bronx (SB), the poorest district in the nation. The purpose of this study was to assess rates of LFU and correlate it with age, sex, ethnicity, race, cancer types, and stage at diagnosis. Methods: We collected data from 1,552 patients diagnosed with invasive cancer in LMMHC between 2006-2010. The data collected were age, sex, ethnicity, race, type of cancer, stage, LFU, treatment, and vital status. Results: From the 1,552 patients, roughly 25 % were LFU, with 50% receiving some initial form of treatment. The remaining percentages are shown below (Table). A higher rate of LFU was with patients younger than 65 (OR: 1.38, 95% CI: 1.08-1.76). There was no correlation between sex and LFU. Non-Hispanics were more likely to be LFU compared to Hispanics (OR: 1.39, 95% CI: 1.07 – 1.8). Blacks were more likely to be LFU compared to non-Blacks (OR: 1.43, 95% CI: 1.12–1.82). There was no significance between LFU and stage at diagnosis. Looking at cancer specific data, colon cancer (C) and head and neck cancers (HN) had the highest percentage of LFU (30% each). There was higher LFU rate for C compared to breast cancer (B) (OR: 1.7, 95% CI: 1.03-2.8), prostate cancer (P) (OR: 1.88, 95% CI: 1.18-3.02), and lung cancer (L) (OR: 1.64 95% CI: 0.94- 2.8). HN patients were more likely LFU compared to B (OR: 2.4, 95% CI: 1.13-5.2), P (OR: 2.69, 95 % CI: 1.28-5.68), and L (OR: 2.3, 95% CI: 1.05-5.19) patients. There was no significant difference between C and HN patients in respect to LFU. Conclusions: In the SB, LFU rates are related to age, ethnicity, race, and type of cancer. Younger patients, blacks, non-Hispanics, and those with C and HN cancers were most likely to be LFU, the latter likely due to the lack of a HN surgeon at LMMHC. We hope that with focus on race, ethnicity, and cancer-specific disparities in LFU rates, we will improve the retention rate of our cancer patients in the future. [Table: see text]
In-hospital mortality of patients admitted through the emergency department of a comprehensive cancer center.
Authors: Elsayem Ahmed F. , Gonzalez Carmen E. , Yeung S. J. , Merriman Kelly W. , Todd Knox H.
Published: March 2020

6125

Background: Cancer is a common presenting condition for emergency departments (EDs); however, there is limited information on outcomes of ED cancer patients subsequently admitted to the hospital. The purpose of this study is to describe outcomes of patients with hematologic malignancies versus those with solid tumors admitted through the ED of a comprehensive cancer center. Methods: We queried the ED database of The University of Texas MD Anderson Cancer Center for calendar year 2010 and linked it to our institutional data warehouse, including tumor registry data. We classified all leukemia and related disorders, lymphoma, multiple myeloma, and bone marrow transplant patients as hematologic malignancies, and remaining cancers as solid tumors. Descriptive statistics, including chi-square, and t-tests were used in two-sided comparisons. All statistical analyses were performed using SPSS version 15. Results: 20,732 total ED visits were made by 9,320 unique cancer patients. Of these, 5,364 (58%) were admitted to the hospital at least once (range 1-13 admits). ED admissions constituted 39% of total unique patients admitted (N=13,753). The main admission indications for solid tumor patients were infectious complications (particularly pneumonia), intractable pain, or dehydration. For hematologic malignancies, the main indication was neutropenic fever. 211/1656 (13%) of liquid tumor patients were admitted to the Intensive Care Unit (ICU) compared to 484/3708 (13%) of solid tumor patients (P=NS). Of all patients admitted through the ED, 587/5364 (10.9%) died during hospitalization. The hematologic hospital mortality rate was 225/1653 (13.6%) versus 362/3708 (9.8%) for solid tumors (P<0.001). Only 242/8389 (3%) of patients admitted directly from outpatient clinics died during the hospitalization (p<0.001). Conclusions: Patients admitted through the ED, particularly those with hematologic malignancies, have a high hospital mortality rate. ED-based palliative care interventions may be justified to improve quality of life and prevent unnecessary costly interventions and ICU admission. Further research should define predictors of poor outcomes in cancer patients admitted through the ED.
Caring for Alaska native prostate cancer survivors in primary care: A survey of Alaska Tribal Health System providers.
Authors: Tilburt Jon C. , Kim Simon P. , Kelley Stacey , James Katherine , DeCourtney Christine , Marino Gregory , McCormick Lynn
Published: March 2020

6126

Background: Little is known about the actual constraints of doing so in the distinctive geographic context of Alaska. We performed a survey of primary care providers (PCPs) within the Alaska Tribal Health System (ATHS) to learn more about their attitudes and practices surrounding prostate cancer (PC) survivorship care. Methods: We surveyed primary care physicians, nurse practitioners, and physician assistants practicing in the ATHS. We administered surveys to assess attitudes about PSA monitoring, responsibility for long-term surveillance, supporting emotional health and medical needs, their degree of confidence in managing patients on androgen deprivation therapy (ADT), as well as their comfort level in managing common side effects of treatment. Results: Of the 221 providers surveyed, 114 responded (52%). Most PCPs indicated a preference for annual PSA monitoring (69%), but several (27%) indicated monitoring every 6 months, and a few (4%) indicated monitoring every 24 months. Most (60%) thought PCPs should manage cancer surveillance, but many (40%) thought a specialist (urologist or medical oncologist) should perform that function. When asked about supporting patients’ emotional needs, PCPs indicated that support groups (63%) followed by survivorship clinics (16%) or on-site specialist visits (14%) were the most appropriate venues to address these concerns. Most respondents thought that medical needs of PC survivors could be addressed locally with appropriate specialty input (71%) or potentially through dedicated survivorship clinics (14%). Only 46% indicated being "moderately" or "very" confident managing ADT. Most PCPs indicated being moderately or very comfortable monitoring for recurrence (59%), managing erectile dysfunction (66%), addressing urinary incontinence (63%), and addressing emotional needs (61%). Conclusions: PCPs practicing in the ATHS express comfort with monitoring for PC recurrence, but express some concerns about the full range of issues in PC survivorship. Constructing cancer survivor care models in geographically dispersed and resource-limited contexts for Alaska Natives is an ongoing clinical and policy challenge.
Sociodemographic and patient disparities in use of first-line chemotherapy (CT) in older adult patients (pts) with advanced non-small cell lung cancer (AdvNSCLC): Analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data.
Authors: Feliciano Josephine Louella , Gardner Lisa , Edelman Martin J. , Davidoff Amy J.
Published: March 2020

6131

Background: Clinical trials have demonstrated that CT improves survival and quality of life in pts with AdvNSCLC. Our prior studies suggest that only 26% of older pts diagnosed with AdvNSCLC received CT through 2002. In this study, we examined more recent patterns, and the effect of socio-demographics, race, and age on receipt of CT in older pts with AdvNSCLC. Methods: Medicare pts diagnosed with AdvNSCLC from 2001-2005 were identified in SEER registries. Medicare enrollment data provided demographic information (age, race, sex, marital status), augmented with census tract level data on median household income. Comorbid conditions at baseline were identified by ICD9-CM diagnoses on claims. Receipt of 1st line CT was identified based on agent-specific procedure codes in claims. Logistic regression examined predictors of 1st line CT. Results: Of 31,341 pts with Adv NSCLC, 34% received 1st line CT. As reflected in the table, poor predicted PS (PredPS), multiple medical comorbidities, and black race were associated with lower likelihood of CT receipt. Being female, married, having higher income, and being diagnosed at a later year were associated with a higher likelihood of receiving CT. Conclusions: Even when controlling for factors such as PS, our results suggest the presence of age, race, and socio-economic disparities in the receipt of 1st line CT for older patients with AdvNSCLC. [Table: see text]
Predictors of retention in a cervical cancer survivorship study.
Authors: Wenzel Lari B. , Osann Kathryn , Hsieh Susie , Sappington Sandra , Marquez Diana , Chase Dana Meredith , Nelson Edward L.
Published: March 2020

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Background: Women with cervical cancer experience numerous quality of life (QOL) disruptions. A completed pilot study indicated that QOL and key biomarkers could be improved with psychosocial telephone counseling (PTC). A confirmatory trial has recently completed accrual.The purpose of this study is to identify predictors of retention in this large biobehavioral trial, and examine retention differences between the pilot and confirmatory trial. Methods: Women with stage I – III cervical cancer diagnosed 9 – 30 months earlier were randomized to either PTC or usual care. PROs and biological specimens were collected prior to randomization (N=204), and 3 (T2) and 9 months post baseline. Sociodemographic, clinical and QOL variables were evaluated from baseline to T2 to identify predictors of study retention. Multiple measures, including the PROMIS Depression and Anxiety scales were entered into a multivariate stepwise logistic regression model to predict study retention. Results: In the multivariate model, being randomized to counseling (OR=4.4, 95% CI: 1.5-12.6), having clinically significant depression, defined as >1 SD above the 50th percentile (OR=4.2, 95% CI:1.7-10.5) and being single (OR=3.4, 95% CI: 1.3-9.2) were the most significant predictors of drop-out in the study overall. Among those in the counseling arm, depression is the strongest predictor of dropout, with a five times higher dropout rate (OR=5.2, 95% CI:1.9-15.6) than those with low to moderate levels of depression, or no depression. However, retention rates improved substantially overall from the pilot study (72%) to the confirmatory study (84%), in both study arms, and retention increased among Latinas from 60% in the pilot study to 83% in the current study, and from 52% to 81% among those with less than a high school education. Conclusions: Results from this analysis of predictors of retention indicate that enhanced attention to sociocultural disparities can improve study retention. Attending to baseline clinical depression may be a further consideration.
Phase I/II trial of primary chemotherapy with nonpegylated liposomal doxorubicin, paclitaxel, and lapatinib in patients with HER2-positive, early-stage breast cancer.
Authors: Kuemmel Sherko , Aktas Bahriye , Krocker Jutta , Elling Dirk , Lantzsch Tilmann , Bischoff Joachim , Fersis Nikos , Boehme Michael , Belau Antje , Lampe Dieter , Schmid Peter
Published: March 2020

624

Background: Combinations of trastuzumab and anthracyclines in HER2-positive breast cancer are highly active but associated with a high incidence of cardiotoxicity. The risk of cardiac damage can be significantly reduced through liposomal encapsulation of anthracyclines. This phase I/II study was initiated to evaluate the combination of non-pegylated liposomal doxorubicin (NPLD), paclitaxel and lapatinib as primary treatment for patients with early stage, HER2-positive primary breast cancer. Methods: Patients with newly diagnosed HER2-positive (IHC 3+ or FISH+) early stage (T1c N1-2 or T2 N0-2) breast cancer were treated with NPLD (60mg/m2; day 1), paclitaxel (175mg/m2, day 1) and lapatinib (750-1500 mg orally daily) in 3-week intervals for up to 6 cycles. The primary endpoints were dose-limiting toxicities (DLT) and pathological complete response (pCR). Secondary endpoints include safety, incidence of cardiac events, and clinical response. Exploratory endpoints include molecular markers for sensitivity or resistance to chemotherapy and/or lapatinib evaluated. Results: A total of 84 patients have been included to date.No DLTs were observed and the maximum tolerated doses were NPLD 60mg/m2, paclitaxel 175mg/m2 and lapatinib 1500mg. Recommended phase 2 doses (P2D) were NPLD 60mg/m2, paclitaxel 175mg/m2 and lapatinib 1250mg. The treatment was generally well tolerated and associated with toxicities that were consistent with the known side-effects of the individual agents. No cardiac event has been observed to date. Preliminary efficacy data confirm a pCR breast rate of 41.7% and pCR rate in breast and lymph nodes of 37.5%, in 24 evaluable patients treated at ≥P2D. Conclusions: The combination of NPLD, paclitaxel and lapatinib is well tolerated and has high antitumour activity in patients with HER2-positive primary breast cancer. The phase II part of the study is ongoing and updated results will be presented.
Impact of single/dual HER2 inhibition and chemotherapy (CT) backbone upon pathologic complete response (pCR) in patients receiving neoadjuvant CT for operable/locally advanced breast cancer (O/LABC): A treatment-interaction analysis of randomized trials.
Authors: Furlanetto Jenny , Vaccaro Vanja , Caliolo Chiara , De Laurentiis Michele , Bonomi Maria , Pilotto Sara , Massari Francesco , Nortilli Rolando , Cianniello Daniela , Cognetti Francesco , Giannarelli Diana , Tortora Giampaolo , Bria Emilio
Published: March 2020

630

Background: Although the addition of trastuzumab to neoadjuvant CT for O/LABC have dramatically increased pCR, clinical research is moving forward to further improve the overall outcome. In this regard, the DUAL inhibition of the HER-2 pathway and the choice of the best CT backbone may represent an issue to be addressed. Methods: Phase II randomized/Phase III trials were considered. pCR events/rates were extracted from papers/presentation and cumulated (R[pCR]) according to a random-effect model; 95% confidence intervals (CI) were derived. A sensitivity analysis according to SINGLE/DUAL HER-2 inhibition and to administered CT (anthracyclines-taxanes: anthra-TAX; TAX alone) was accomplished, in order to test for interaction. Results: 7 trials (2155 pts) were gathered; 1855 pts were enrolled in arms where anti-HER-2 targeted therapy was administered. HER-2 inhibition was obtained with trastuzumab, lapatinib and pertuzumab (alone or combined). Results according to HER-2 inhibition follow in the table below. With regard to CT, a significant interaction (p=0.0001) in favour of the addition of Anthra to TAX was found in the context of SINGLE HER-2 inhibition subgroup (R[pCR] 46.5%, 95% CI 37-51, vs 26.9%, 95% CI 23-31), while no significant interaction was determined in the context of the DUAL subgroup (R[pCR] 49.0%, 95% CI 26-72, vs 49.0%, 95% CI 43-55). A significant interaction (p=0.0001) in favour of the addition of Anthra to TAX was found for pts receiving trastuzumab (R[pCR] 45.5%, 95% CI 37-53, vs 26.5%, 95% CI 21-32) as well. Conclusions: Although biases in the pCR definition, the DUAL inhibition of HER-2 pathway may significantly increase pCR, regardless of the CT backbone; if confirmed, this strategy allows to reduce toxicities by sparing Anthra. For pts receiving SINGLE HER-2 inhibition, Anthra-TAX-based CT should be still considered the best treatment option. [Table: see text]
Effect of acquired resistance to lapatinib in HER2-positive breast cancer cells on the Bcl-2 family members MCL-1 and BAX.
Authors: Eustace Alex J. , Browne Brigid , Madden Stephen F. , O'Driscoll Lorraine , McDermott Martina , O'Brien Neil A. , Watson William , Crown John , Walsh Naomi , O'Donovan Norma
Published: March 2020

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Background: Lapatinib (L) is approved for the treatment of trastuzumab (T) resistant HER2 positive metastatic breast cancer. Not all HER2 positive tumors respond to L and patients who initially respond frequently relapse, due to the development of resistance to L. Understanding the molecular changes associated with L resistance may lead to the identification of targets to overcome resistance. Methods: SKBR3 cells were treated with either 250 nM L, or 125nM L and 5 µg/ml T twice weekly for 6 months to establish the resistant cell lines SKBR3-L and -TL. We measured by TUNEL assay the effect of L on apoptotic induction in SKBR3, -L and -TL cells. Gene array analysis of the SKBR3, -L and -TL cells identified differences in the expression of apoptosis-related genes, which were validated by immunoblotting. Finally using combinations of obatoclax (O) and L were tested in L resistant cells. Results: In SKBR3 cells, L (500 nM) induces apoptosis (15.8 ± 2.0%) compared to untreated controls (4.6±2.7%), whilst in SKBR3-L and -TL cells L did not induce significant apoptosis compared to controls. Gene array analysis showed that BAX mRNA is down regulated 3.2 fold in SKBR3-L cells compared to the parental cells. In SKBR3-TL cells, MCL-1 mRNA expression is increased 2.1 fold, whilst BAX mRNA is down regulated 2.1 fold compared to the parental cells. Immunoblotting confirmed that BAX protein expression was reduced in the SKBR3-L (1.5 fold, p=0.058) and significantly reduced in SKBR3-TL cells (2.0 fold, p=0.039) compared to SKBR3. MCL-1 protein expression was significantly increased in the SKBR3-L (1.6 fold, p=0.035) and -TL cells (2.3 fold, p=0.031) compared to SKBR3. Combining O (200 nM) and L (500 nM) in both SKBR3 and SKBR3-L cells produced greater growth inhibition than either drug on its own (SKBR3: 86.9±1.0% vs 73.5±3.1% for L (p<0.01) and 44.7±7.7% for O, (p<0.01); SKBR3-L: 54.2± 8.6% vs 26.9±2.4% for L (p=0.027) and 33.8±10.7% for O (p=0.04)). Conclusions: Extended exposure to L in SKBR3-L and –TL cells alters the apoptotic response to L. O alone and in combination with L results in growth inhibition in L resistant cells.