bluuebunny/crossref_metadata_2025 huggingface dataset:
Disparities in preoperative imaging for breast cancer: Not so black and white.
Authors: Bleicher Richard J. , Ruth Karen , Sigurdson Elin R. , Evers Kathryn , Crivello Margaret Lord , Wong Yu-Ning , Boraas Marcia , Egleston Brian
Published: March 2020

6061

Background: Controversy exists about racial/ethnic differences in the care of breast cancer patients. Imaging plays a critical role in evaluation, but little national data exists on breast imaging by race. This study was performed to determine if imaging disparities exist in Medicare patients, when adjusting for socioeconomic (SE) factors. Methods: Surveillance Epidemiology and End Results (SEER) data linked to Medicare claims were reviewed for patients diagnosed with invasive nonmetastatic breast cancer between 2000 and 2005, undergoing surgery as their 1st treatment modality. Diagnostic imaging was reviewed during the interval between the 1st physician visit and surgery (“preoperative interval”[POI]) and imaging use was defined as ≥1 imaging-specific claim. SE factors included rural/urban setting, and education, poverty, and median income per census tract. Results: Among 39,790 patients, there were 34,774 White (87%), 2,341 Black (5.9%), 1,459 Hispanic (3.7%), and 1,216 Asian/Pacific Islander (3.1%) patients. Univariate racial differences were noted for all imaging types (p’s <0.0001 to 0.007). During the POI, when adjusting for demographics, tumor characteristics, and SE factors in multivariable analysis, use of mammogram, ultrasound (US), breast MRI, CT, and bone scan were not different between Blacks and Whites. Education level was a predictor for US (p=0.007), breast MRI (p<0.0001), CT (p=0.006) and bone scan use (p=0.002), but not mammography (p=0.90). There were varying correlations between Hispanics or Asians vs Whites for all imaging types. Stage, histology, U.S. region, and comorbidity index were most consistently predictive of imaging use of all types. When evaluating 6 mos prior to the 1st physician visit along with the POI, 96.4% of all patients had ≥1 mammogram, with 94.1% of Blacks having mammograms vs 96.5% of Whites (OR 0.7, 95% CI 0.6-0.9; p=0.001). Conclusions: There is little racial difference in imaging performed during the POI for Medicare patients having breast cancer, and efforts to determine causes of survival disparities in such patients should be focused elsewhere. Whether these findings apply to the privately insured or the uninsured requires additional exploration.
Prevalence and characteristics of patients with stage IV solid tumors who receive no anticancer therapy.
Authors: Small Alexander C. , Tsao Che-Kai , Moshier Erin L. , Gartrell Benjamin Adam , Wisnivesky Juan P. , Godbold James H. , Smith Cardinale B. , Sonpavde Guru , Oh William K. , Galsky Matt D.
Published: March 2020

6065

Background: Clinicians caring for patients with cancer are well aware that a subset of patients who present with metastatic solid tumors never receive anticancer therapy for reasons including poor functional status, comorbidities, and patient preference. The prevalence and characteristics of this population have not previously been described. Methods: The National Cancer Database was queried for patients diagnosed with metastatic (stage IV) solid tumors including breast, cervix, colon, kidney, small-cell and non-small cell lung [NSCLC and SCLC], prostate, rectum and uterus. Patients who received neither radiation therapy nor systemic therapy were identified. Other factors such as age, race, income, insurance status, and diagnosis year were assessed. In an exploratory analysis, log-binomial regression was used to estimate prevalence ratios (PR) for the proportion of untreated stage IV to treated stage IV cancer cases according to these factors. Results: From 2000-2008, 773,233 patients with stage IV cancer were identified of whom 159,284 (21%) received no anticancer therapy (Table). Patients with NSCLC accounted for 55% of untreated patients. Across all cancer types, older age (PR range 1.37-1.49, all p<0.001), black race (PR range 1.05-1.32, all p<0.001), lack of medical insurance (PR range 1.47-2.46, all p<0.001), and lower income (except uterus) (PR range 0.91-0.98 for every $10,000 income, all p<0.001) were associated with increased prevalence of not receiving treatment. Conclusions: Approximately 20% of patients who present with stage IV solid tumors never receive anticancer therapy. These findings have potential implications with regards to healthcare policy and access to care. [Table: see text]
Sown the seeds: An analysis of published trials in clinical oncology.
Authors: Spradlin Natalie M. , Johnson David H. , Horn Leora
Published: March 2020

6068

Background: Competition in the pharmaceutical marketplace has resulted in “seeding trials” which appear to serve little scientific purpose other than to gain a financial hold in the marketplace. Hallmarks of “seeding” clinical trials [Kessler, et al N Eng J Med 1994] include trial design that does not support stated research goals, industry sponsorship without novel findings or poor scientific rationale, and drugs introduced into an already crowded therapeutic class, i.e. “me too” drugs. We evaluated clinical trials published in high impact oncology journals to ascertain the prevalence of trials bearing the characteristics of a seeding trial. Methods: We conducted a PubMed search using “clinical trial”, “oncology”, published 2/2005 – 2/2010, in Ann Oncol, J Clin Oncol, Lancet, Lancet Oncol, or the N Engl J Med. All phase I/II, II and III studies were included. Phase I, hematology, radiation oncology, and pediatric studies were excluded. Data collected included disease site, phase, funding source, journal, and whether the trial fit criteria for “seeding” as previously defined. Results: 1781 articles have been evaluated to date. 528 met criteria for analysis. 130 were considered seed studies. Seed studies per journal were Ann Oncol 26 of 128, J Clin Oncol 88 of 340, Lancet 8 of 22, Lancet Oncol 5 of 16, and N Engl J Med 3 of 22. Studies published per disease site and percent seed studies were melanoma 19 and 31.6%, breast 106 and 30.2%, GI 126 and 20.6%, lung 101 and 29.7%, GU 65 and 24.6%, gynecology 40 and 30%, head and neck 24 and 12.5%, CNS 24 and 12.5%, sarcoma 11 and 18.2%, and advanced cancer 12 with zero seeds. Overall phase totals were phase I/II 16, phase II 272, and phase III 240. Seed studies per phase were phase II 28.7%, phase III 21.7% and zero for phase I/II. 210 studies were solely industry sponsored, and of these, 37.1% were seed studies. Funding was not listed for 73 studies. Conclusions: The integrity of clinical trials is challenged in the race to claim major market share. Our analysis of clinical trials published in high impact oncology journals found seeding trials account for 24.6% of publications. 37.1% of industry sponsored trials are seed studies. Seed studies are more common among the major disease sites or sites for which targeted therapies exist.
Burnout prevalence in medical and radiation oncologists at British Columbia Cancer Agency (BCCA).
Authors: Fitzgerald Catherine A. , Le Lyly H. , Petrik David W. , Murphy Kevin C.
Published: March 2020

6071

Background: Burnout, reported to affect 30-60% of oncology workers, is a syndrome of psychological distress typically manifesting in three dimensions: Emotional Exhaustion (EE), Depersonalization (DP) and Low Personal Accomplishment (PA). Causal factors include workload, dealing with terminally ill patients and difficulties maintaining a balance between professional and personal life. As workload rises due to increased complexity of therapy and increasing prevalence of cancer patients, burnout may increase, especially in times of financial constraint. We sought to determine the prevalence of burnout in medical and radiation oncologists working at BCCA, which provides all radiation and the majority of medical oncology services to BC’s 4.5 million people. Methods: In March 2011, BCCA oncologists were invited to participate in a confidential online survey consisting of basic demographics and the 22 item MasLach Burnout Inventory (MBI) instrument, the latter a validated tool measuring distress in the three main dimensions of burnout. Normative data for physicians were used to interpret the results. Results: Response rate was 59%, female:male 40:60% with similar response rates for medical and radiation oncology (60 v 59%). Of the 73 who indicated their age range, 34 (47%) were between 35 and 44 years old. Respondents indicated that they had considered reducing their Full Time Equivalent (FTE) (67%) or leaving BC (46%). In those with at least 2 scores at a severe level, these rates were 76% and 71% respectively. Conclusions: Over 60% of responding BCCA oncologists report burnout in at least one domain of the MBI tool. Many have considered leaving the province or reducing their hours. These data are consistent with Grunfeld’s survey of Ontario oncologists (CMAJ 2000), although the rate of burnout is higher in this survey. Further research into ways to lessen burnout in oncology is urgently needed. [Table: see text]
Deviations from guideline-based therapy for febrile neutropenia in cancer patients.
Authors: Wright Jason D. , Neugut Alfred I. , Lewin Sharyn Nan , Burke William M. , Lu Yu-Shiang , Herzog Thomas J. , Hershman Dawn L.
Published: March 2020

6078

Background: Febrile neutropenia (FN) is a common cause of morbidity in cancer patients. We examined guideline and non-guideline based care for cancer patients hospitalized with FN and examined how treatment influenced outcomes. Methods: The Perspective database was used to examine the treatment of solid tumor patients with FN from 2000-2010. To capture initial decision-making, we examined treatment within 48 hrs of admission. Based on evidence-based guidelines we determined the appropriate use of guideline-based antibiotics as well as use of treatments not routinely recommended, vancomycin and granulocyte-colony stimulating factors (GCSF). Hierarchical mixed effects models were developed to examine the influence of patient, physician, and hospital characteristics on the quality of treatment. Patients were stratified into low and high-risk groups and the effect of initial treatment on outcome (nursing home discharge and death) examined. Results: Among 25,231 patients with FN, within 48 hours of admission blood cultures were obtained in 90%, guideline-based antibiotic administered to 79%, vancomycin to 37%, and GCSF to 63%. Patients treated at high-volume hospitals, by high-volume physicians and patients managed by hospitalists were more likely to receive guideline-based antibiotics (p<0.05). Vancomycin use increased with time from 17% in 2000 to 55% in 2010 while GCSF use only decreased from 73% to 55%. Patients treated by internists and hospitalists were more likely to receive vancomycin; high-volume physicians were less likely to treat with both vancomycin and GCSF (p<0.05). Among patients who received GCSF, 15% received only one dose and 22% received 2 doses of filgrastim. Among low-risk patients prompt initiation of guideline-based antibiotics decreased the risk of discharge to a nursing facility (OR=0.78; 95% CI, 0.66-0.91) and death (OR=0.65; 95% CI, 0.50-0.85). Conclusions: There is substantial variability in the initial treatment for FN in cancer patients. While use of appropriate empiric antibiotics is high, use of non guideline-based treatments such as vancomycin and GCSF are common. Physician and hospital factors are the most important predictors of both guideline and non guideline-based treatment.
Use and duration of chemotherapy (CT) in patients (pts) with metastatic breast cancer (MBC) according to tumor subtype (TS) and line of therapy (tx).
Authors: Seah Davinia Shien , Luis Ines Maria Vaz Duarte , Olson Erin Macrae , Sohl Jessica , Litsas Georgia , Winer Eric , Lin Nancy U. , Burstein Harold J.
Published: March 2020

6089

Background: Benefits of CT vary widely in MBC pts. We aimed to describe the impact of breast cancer TS and line of tx on the duration of CT. Methods: In a retrospective analysis, we identified 205 pts treated with CT for MBC at the Dana-Farber Cancer Institute between 2005-8. TS were classified as hormone receptor (HR)+ (ER+/PR+/HER2-), triple negative (TN) (ER-/PR-/HER2-) or HER2+ (HER2+, any HR). CT duration was defined as "time from start of one CT line to the start of the next CT." Chi-square, Kruskal-Wallis, and Kaplan-Meier methods were used. Results: Median follow-up was 54 months (m). Most pts had received adjuvant tx, though 23% had MBC at diagnosis. Almost all HER2+ pts had concurrent anti-HER2 tx. CT duration was longest in 1st line with consecutive stepwise decrease. The proportion of pts who received CT beyond the 3rd line varied by TS: 52% of HER2+ pts received > 4 CT lines, compared with 37% of HR+ and 29% of TN pts. Duration in later CT lines also differed by TS. Median CT duration in HER2+ pts was > 4 m in all 6 lines, but HR+ and TN pts had a median CT duration of <4m from the 4th line onwards. Quartile estimates suggested a substantial fraction of HER2+ and HR+ pts receiving >6m of CT in 5th and 6th line; by contrast, CT duration for TN pts were consistently brief in later CT lines. Conclusions: TS determines the likely duration and number of lines of CT for MBC. Among HR+ and HER2+ pts who receive CT beyond 3rd line, there are substantial rates of prolonged tx suggesting clinical benefit. For TN pts, the opportunity for additional lines and the CT duration declined more dramatically. The true role of advanced (> 3rd) CT lines for all MBC in improving quality of life, survival, and the predictors of such benefit, warrant further study. [Table: see text]
Incidence and risk of central nervous system (CNS) metastases as a site of first recurrence in patients (pts) with HER2-positive (HER2+) breast cancer treated with adjuvant trastuzumab (T).
Authors: Olson Erin Macrae , Abdel-Rasoul Mahmoud , Wu Christina Sing-Ying , Maly Joseph , Pan Xueliang Jeff , Shapiro Charles L.
Published: March 2020

609

Background: T is the mainstay of adjuvant therapy in pts with HER2+ breast cancer. CNS disease as the site of first relapse after exposure to adjuvant T has been reported, although the overall incidence and relative risk (RR) of this remains unclear. We performed an up-to-date meta-analysis to determine the risk of CNS metastases as the first site of recurrence in pts with HER2+ breast cancer who received adjuvant T. Methods: Pubmed databases were searched for articles from 1966 to 2011. Abstracts presented at the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium were also searched for relevant clinical trials. Eligible studies include randomized trials with adjuvant T administered for 1 year in pts with HER2+ breast cancer who reported CNS metastases as first site of disease recurrence. Statistical analyses were conducted to calculate the summary incidence, RR, and 95% CIs using fixed effects inverse variance models. Results: A total of 9,020 pts were included. The incidence of CNS metastases as first site of disease recurrence in HER2+ pts receiving adjuvant T was 2.56% (95% CI 2.07% to 3.01%) compared to 1.94% (95% CI: 1.54% to 2.38%) in HER2+ pts who did not receive adjuvant T. The RR of CNS as first site of relapse in T-treated pts was 1.35 (95% CI 1.02 to 1.78, p=0.038) compared with control arms without T therapy. In subgroup analyses, there was no significant difference in CNS incidence or risk between pts treated with concurrent versus sequential T (p=0.29), weekly versus every 3 week T (p=0.56), and no difference in the T groups between studies due to median follow up time in years (p=0.68). No evidence of publication bias was observed (Q=1.78; P=0.62; I2 = 0.0%). Conclusions: This is the largest report to date demonstrating that adjuvant T is associated with an increased risk of CNS metastases as a site of first recurrence in HER2+ breast cancer pts.
Association between financial relationships with commercial interests and research merit at the ASCO Annual Meeting (AM).
Authors: Moy Beverly , Bradbury Angela R. , Helft Paul R. , Sheikh-Salah Moktar , Egleston Brian , Sands Colleen B. , Storm Courtney D. , Peppercorn Jeffrey M.
Published: March 2020

6095

Background: Financial relationships with commercial interests (COI) are common in cancer research. There are few data examining the correlation between COI and research merit. Meeting placement prominence (MP) and peer review score (PRS) are indicators of research merit. We examined the association between ASCO AM abstracts whose authors disclose COI and both MP and PRS. Methods: We reviewed abstracts presented at the ASCO AM in 2006 and 2008-2011. We evaluated associations between COI disclosed by any author and PRS and MP (order of prominence: plenary session (PS), clinical science symposium (CSS), oral presentation (OP), poster discussion session (PDS), vs. general poster session (GPS)). Chi-square tests, T-tests, and logistic regressions of COI were used to assess associations with MP, PRS, and year. Results: Of 12,446 total abstracts accepted for presentation, 78% of PS, 59% of CSS, 54% of OP, 52% of PDS, and 39% of GPS report at least one COI. Abstracts selected for PS, CSS, OP, and PDS had more COI compared to those selected for GPS (p < 0.05). Stock ownership COI were more frequently disclosed in PS (30%), CSS (30%), OP (22%), and PDS (22%) compared to GPS (16%) (p < 0.05). Employment COI were more frequently reported among abstracts presented at PS (39%), CSS (37%), OP (27%), and PDS (27%) compared to GPS (21%) (p < 0.05). Consultant COI were more likely to have higher MP than GPS placement (OR for PS=5.5; CSS=2.4; OP=2.2; PDS=1.9). Similarly, honoraria COI were more likely to have higher MP than GPS placement (OR for PS=3.9; CSS=1.8; OP=2.1; PDS=1.7). Better PRS was associated with COI (OR 0.17; p < 0.05). The relationship of better PRS with any COI strengthened over time from 2006, 2008-2011 (PRS times year interaction OR=0.65, p<0.001). Conclusions: ASCO abstracts whose authors report COI have higher merit as measured by MP and PRS. This suggests a dependence on industry relationships for access to important data that will lead to prominent cancer research. These relationships will require further investigation and ongoing management. To our knowledge, this is the first study examining the scientific merit of research with relation to COI.
Cost-effectiveness of adjuvant radiotherapy for older women with early hormone-receptor positive breast cancer.
Authors: Reeder-Hayes Katherine Elizabeth , Wheeler Stephanie B. , Biddle Andrea K
Published: March 2020

6096

Background: Radiation therapy (XRT) following breast conserving surgery decreases local recurrence at the expense of additional morbidity and treatment costs. However, its utility in elderly women at low risk of recurrence has been questioned. This study assessed the cost-effectiveness of adding XRT to hormonal therapy (HT) in women over 70 with stage I, hormone-receptor positive (HR+) breast cancer after breast conserving surgery. Methods: A decision tree model was used to assess the costs and benefits of XRT + HT versus HT alone in 10,000 women age 70+ with stage I HR+ breast cancer. Using a societal perspective, we considered medical costs and quality of life effects of initial treatment, recurrences, and metastatic disease as well as long-term XRT-associated complications including breast fibrosis, chronic pneumonitis and cardiac disease. Probabilities of recurrence and death were modeled on recent clinical trial results, while toxicity probabilities were taken from literature review. The primary health outcome was incremental quality-adjusted life years (QALYs) gained. One-way and probabilistic sensitivity analyses (PSA) were performed to assess the sensitivity of model results and conclusions to various parameter estimates. Results: In the base-case scenario, the incremental cost-effectiveness ratio (ICER) for the addition of XRT was $923,017/QALY. The ICER was highly sensitive to variations in utility weights, particularly those reflecting patient preferences for initial treatment with or without XRT and those reflecting the decrement in quality of life resulting from breast fibrosis. In PSA, XRT was associated with lower quality-adjusted life expectancy at higher cost in 58% of simulations. Conclusions: In women over 70 with stage I HR+ breast cancer, the addition of XRT to HT is not cost-effective at a willingness-to-pay threshold of $100,000/QALY, and is associated with little or no improvement in quality-adjusted life expectancy. Providers should be aware that the cost-effectiveness of XRT in this population is strongly influenced by patient preferences surrounding recurrence and toxicity risks, and should weigh these factors when making shared decisions with patients.
Phase I trial of pegylated liposomal doxorubicin and lapatinib in the treatment of metastatic breast cancer (MBC): Final results.
Authors: Cianfrocca Mary E. , Kaklamani Virginia G. , Rosen Steven T. , Von Roenn Jamie H. , Rademaker Alfred , Smith Deborah A. , Rubin Stephen D. , Meservey Caitlin , Uthe Regina , Gradishar William John
Published: March 2020

610

Background: Liposomal formulations including pegylated liposomal doxorubicin (PLD) were developed to improve the therapeutic index of anthracyclines (A). Lapatinib (L) is a selective, highly competitive inhibitor of ErbB1 and ErbB2 tyrosine kinases. Conventional doxorubicin plus trastuzumab was effective but with unacceptable cardiac toxicity. PLD plus L may be effective with less cardiac risk. Methods: This is a phase I, dose-escalation trial of PLD 20, 30, 45 and 60 mg/m2 IV every 4 weeks (maximum of 8 doses) and L, 1500 mg po daily until progression in patients (pts) with MBC. ErbB2 positivity was not required. Prior chemotherapy, endocrine therapy and trastuzumab were allowed. A subsequent amendment allowed prior L. Prior A use was limited to 240 mg/m2 of doxorubicin or 600 mg/m2 of epirubicin. Concomitant CYP3A4 inducers/ inhibitors were not allowed. A left ventricular ejection fraction (LVEF) of > 50% was required. The primary objective was to evaluate the safety (particularly cardiac), tolerability and feasibility of PLD and L. Results: 23 pts (PLD: 20 mg/m2 - 4 pts; 30 mg/m2 - 3 pts; 45 mg/m2 – 13 pts; 60 mg/m2- 3 pts) have been treated; total of 73 treatment cycles. Dose-limiting toxicity (DLT) was not reached. One pt had an LVEF drop to < 50% after 4 cycles accompanied by a pericardial effusion due to progressive disease. Treatment-related grade III/IV adverse events included: 4 pts with hand-foot-syndrome (HFS), 2 pts each with leukopenia, infection, and skin changes, 1 pt each with pain, fatigue, diarrhea, mucositis, hypoalbuminemia, anemia, cough, pleural effusion, and edema. Grade 3 HFS occurred in 2 of 3 pts in the 60 mg/m2 cohort. Response data in 21 evaluable pts: 4 PR, 5 SD, and 12 PD. Preliminary pharmacokinetic (PK) analyses (7 pts) indicate L has no effect on PLD (45 mg/m2) concentrations, but L concentrations were approximately 2-fold higher the day of PLD dosing. Conclusions: In 23 pts treated, PLD plus L was well tolerated with manageable toxicities and no treatment-related cardiac toxicity. DLT was not reached however grade 3 HFS occurred in 2 of 3 pts in the 60 mg/m2 cohort. Preliminary PK analyses demonstrate no effect of L on PLD, but an effect of PLD on L the day of PLD dosing.
Changes in adjuvant breast cancer chemotherapy regimen selection over time in the community.
Authors: Patt Debra A. , Espirito Janet L. , Turnwald Brian , Hoverman J. Russell , Neubauer Marcus A. , Cartwright Thomas H. , Busby Leslie T. , Brooks Barry Don , Sitarik Mark A. , Kolodziej Michael A. , Beveridge Roy A. ,   on behalf of the US Oncology Network Pathways Task Force
Published: March 2020

6109

Background: Adjuvant breast cancer (BC) chemotherapy (CT) treatment has evolved over time due to improved understanding of risk conveyed by pathology and patient (pt) characteristics, as well as emergence of new and mature data for survival and toxicity. We aimed to evaluate how CT regimen selection has changed in recent years in various subgroups. Methods: Using iKnowMed EHR data from The US Oncology Network, we retrospectively identified female pts diagnosed with stage I-III BC between 1/2007 and 12/2010 at practices with EHR data available at time of diagnosis. Pts with <5 office visits, those with a second primary or previous cancer diagnoses were excluded. Age, ER, HER2, nodal status, stage and year of diagnosis were captured. CT utilization was determined by the number of pts who received CT within 6 months of their diagnosis. Clinical trial pts were included. Regimens were categorized by the initial CT title and drugs assigned. Pts with metastatic regimens were excluded. CT regimens were analyzed by subgroups and trended over time. Results: During the time period, 26,095 stage I-III BC pts were identified. A CT regimen within 6 months of diagnosis was documented in 56% of pts. CT utilization was 83% in HER2+ pts, 85% in ER-/HER2- pts, and 45% in ER+/HER2- pts. CT utilization decreased overall with increasing pt age (71%, 64%, 51%, 33%, and 13% for pts in their 4th, 5th, 6th, 7th and ≥8th decade of life). In HER2+ pts, use of non-anthracycline containing regimens increased from 26 to 62%, and anthracyline-taxane combination regimens decreased from 33 to 15%. In HER2-/ER+ pts, the most used non-anthracycline regimen was docetaxel + cyclophosphamide (TC) at 41%. Anthracycline-taxane combinations were used more often in the HER2-/ER- group (32%). Conclusions: In the 4 year study period, this data suggests that ER and HER2 status may drive chemotherapy choice more than nodal status. Anthracycline containing regimens are being used less often possibly due to similar efficacy but less cardiac toxicity, particularly when combined with trastuzumab. These results suggest a change away from anthracyclines in specific subgroups with the controversy over the benefits of that change unsettled, and cost implications yet unquantitated.
Participation of teenagers and young adults (TYA) in cancer clinical trials (CCT): What can we learn from six years of accrual data in England?
Authors: Fern Lorna Anne , Lewandowski Jennifer Ann , Coxon Katy Marie , Fairbairn Elliann , Loucaides Eileen , Whelan Jeremy ,   National Cancer Research Institute's Teenage and Young Adults Clinical Studies Group
Published: March 2020

6115

Background: We reported underrepresentation of TYA in CTT in England, 2005-06. Since 2005 national healthcare policies and research initiatives aimed at increasing participation of TYA in CCT have been implemented. We aimed to determine if this has improved accrual rates (AR). Methods: We analyzed accrual by age during 2005-2010 to UK Cancer Research Network interventional trials recruiting newly diagnosed patients (pts) with leukaemia, lymphoma, bone/soft tissue sarcoma, central nervous system and germ cell tumours. AR were expressed as the ratio of pts entered onto trial compared to population incidence cases for 2005-08; for 2009-10, mean incidence of 2005-08 was used. Results: 2005-10 showed an AR increase of 10.3% for pts 10-14 yrs, 17.9% for pts 15-19 yrs but only 4.6% for pts 20-24 yrs (Table). In 2010 AR was 54.4% for pts 10-14 yrs, 43.3% for 15-19 yr olds and 20.6% for pts 20-24. Annual increases of AR were observed for pts 15-19 yrs, but in no other age groups, 0-59 yrs. We looked at AR for children and younger teenagers , 5-14 yrs, vs older TYA, 15-24 yrs. Overall, AR for 5-14 yr olds was greater, 53.7% vs 23.0% for pts 15-24 yrs; however, during 2005-10 AR increased by 9.7% for pts aged 15-24 compared to 7.8% for pts aged 5-14. Conclusions: AR for TYA has improved in between 2005-10. Most benefit is evident for older teenagers; AR for young adults remain disappointing. Changes relate to increased trial availability and access, centralisation of care for TYA, amendments to age eligibility criteria to reflect tumour biology and increased collaboration between adult and paediatric clinical research groups. Strategies to improve AR for young adults require further development. [Table: see text]
Prevalence and predictors of adherence to antiemesis prophylaxis in lung cancer: A population-based study.
Authors: Gomez Daniel Richard , Liao Kai-Ping Eric , Nguyen Hoang , Smith Benjamin D. , Elting Linda S.
Published: March 2020

6124

Background: Nausea/vomiting is a significant toxicity in the treatment of lung cancer, but barriers exist to the delivery of prophylaxis. We studied compliance and predictors of prophylactic antiemetics with chemotherapy in this setting. Methods: We used a Texas state registry of clinical data linked with Medicare claims from 2001-2007. Our study population was incident lung cancers treated with platinum agents within 12 months of diagnosis. To define guideline-adherent care, we assessed compliance to the American Society of Clinical Oncology recommended prophylactic agents dexamethasone and a 5-HT3 antagonist. Adherence was scored as a binary variable and defined as administration within 24 hours of the first day of the first cycle of chemotherapy. We utilized a logistic regression model to evaluate the role of the following factors in predicting adherence: concurrent radiation therapy (RT), race (black vs. white), histology (small cell vs. non-small cell), rural location, Charlson Comorbidity Index (CCI), household income (by quartiles [Q]), education, and treatment year (binary). Results: Of 31,762 patients in the database, 5155 patients met the above criteria. The adherence rate to dexamethasone and 5-HT3 antagonists increased over time, from 51.5% in 2001 to 71.6% in 2007. Patients treated in the years 2005-2007 were 1.739 times more likely to be adherent to prophylaxis than were those from 2001-2004. Variables that predicted adherence (adjusted odds ratio [OR], 95% confidence interval [CI]) were: age (OR=1.013, CI [1.001, 1.026]), treatment year (OR=1.756, CI [1.548, 1.991]), race (black vs. white OR=0.684, CI [0.548,0.853]), median income (higher vs. lower OR=1.83 [Q2 vs. Q1]; OR=1.296 [Q3 vs. Q1]; OR=1.496 [Q4 vs. Q1]), CCI (1+ vs. 0, OR=0.613, CI [0.530,0.709]), and concurrent RT [yes vs. no OR=1.358, CI [1.197,1.541]). Conclusions: Compliance with guidelines for prophylactic antiemetics is suboptimal, but increasing over time. Several characteristics predict for improved adherence, including white race, median income, advanced age, and the receipt of concurrent RT. These findings highlight substantial economic disparities in supportive care of lung cancer in the state of Texas.
Geographic and socioeconomic determinants of participation by elderly patients in surgical oncology trials.
Authors: Stewart John H. , Russell Greg B. , Howard-McNatt Marissa Michelle , Petro Robin M. , Levine Edward Allen , Bell Ronny A.
Published: March 2020

6127

Background: A recent report by our group demonstrated that <0.5% of elderly patients with breast, prostate and lung cancer participate in surgical oncology trials. However, little work to date has evaluated the roles of regional healthcare infrastructure and socioeconomic factors on clinical trial participation in this cohort. Methods: The NCI Cooperative Group Surgical Oncology Trial (CGSOT) database was queried for patients treated for breast, prostate and lung cancer cancer between 2000 and 2008 (n=13,541). Geographical Information Systems data were used to evaluate proximity to healthcare facilities while regional socioeconomic characteristics were obtained from the 2000 US Census and Area Resource file. Counts were used to create a proportion of respondents with the corresponding 95% confidence interval calculated using the central limit theorem. Independent t-tests were used to assess differences in outcome measures between the two age groups. Results: We found that 4136 participants in the NCI CGSOT database were 65 years of age or older. Interestingly, 92.7% of this cohort was white and 85.7% was female. Socioeconomic determinants of participation are shown in the table. Conclusions: The work presented herein suggests that elderly minority patients are less likely to participate in surgical oncology trials than their white counterparts. Furthermore, elderly participants tend to reside in less affluent areas. Future work will utilize interventions that improve the recruitment of elderly patients to these trials. [Table: see text]
Estrogen receptor (ER), Ki-67, p27Kip1, and histologic grade as predictors of pathologic complete response (pCR) in patients with HER2-positive breast cancer treated with neoadjuvant chemotherapy (NAC) using fluorouracil, epirubicin, and cyclophosphamide (FEC), taxanes, and trastuzumab.
Authors: Kurozumi Sasagu , Inoue Kenichi , Takei Hiroyuki , Matsumoto Hiroshi , Yoshida Takashi , Hayashi Yuji , Ninomiya Jun , Kubo Kazuyuki , Nagai Shigenori E , Oba Hanako , Kurosumi Masafumi , Tabei Toshio , Horiguchi Jun , Takeyoshi Izumi
Published: March 2020

613

Background: NAC with taxanes and FEC concurrently with trastuzumab is a potent regimen in patients with HER2-positive breast cancer (BC). Several studies revealed high pCR rates in BC patients treated with this regimen; however, predictive factors and a prognostic effect of pCR have been still unclear. In this study, we analyzed several factors including p27Kip1 (cyclin-dependent kinase inhibitor acting as tumor suppressor) for correlation with pCR. We also evaluated differences in recurrence-free survival (RFS) or overall survival (OS) between patients with pCR and non-pCR, and with positive and negative nodes after NAC. Methods: Our study included 129 Japanese women with invasive, HER2-positive BC who received 12 cycles of paclitaxel or 4 cycles of docetaxel followed by 4 cycles of FEC-75 with concomitant trastuzumab for 24 weeks. We analyzed the correlation of pCR (no invasive lesions in the breast) and nodal status after NAC with RFS and OS, and analyzed the baseline expressions of ER, Ki-67, and p27Kip1, and histological grade for correlation with pCR. Positive or high expression was defined by nuclear labeling index: ER ≥10%, p27Kip1 ≥75%, Ki-67 ≥30%. Results: In 129 patients, pCR was found in 85 (66%). Patients with pCR after NAC had significantly better RFS than those without pCR (median follow-up: 41 months). Furthermore, patients with pathologically negative nodes after NAC had significantly better OS than those with pathologically positive nodes. Negative ER (79% vs. 40%), high Ki-67 (72% vs. 47%), low p27Kip1 (71% vs. 50%), and histological grade 3 (70% vs. 39%) were significant predictors of pCR. Conclusions: In patients with HER2-positive BC, this regimen was effective achieving the high pCR rate. pCR and pathologically negative nodes after NAC were predictive of RFS and OS, respectively. The expressions of ER, Ki-67, and p27Kip1, and histological grade at baseline were predictive of pCR. p27Kip1, a new predictor of pCR after NAC needs to be further analyzed.
Patient satisfaction with participation in phase II/III NCCTG clinical trials: Was it worth it? (N0392).
Authors: Chauhan Cynthia , Atherton Pamela J. , Satele Daniel , Dueck Amylou C. , Soori Gamini S. , Johnson David B. , Mandrekar Sumithra J. , Buckner Jan C. , Sloan Jeff A.
Published: March 2020

6133

Background: Patient (pt) trial experience may give insight to quality of life (QOL) factors affecting accrual, retention and outcome. While pts are vital to clinical trial success, we know little about their post-trial opinions. This trial examined pt opinion of their trial and treatment decision making (TDM). Methods: Pts enrolled on designated North Central Cancer Treatment Group (NCCTG) phase II or III treatment trials completed the TDM Control Preferences Scale at baseline and the Was It Worth It (WIWI) satisfaction assessment at the ends of cycle 1 and active protocol treatment. The primary endpoint was the proportion of pts reporting worthwhile participation. Fisher Exact tests compared pt opinion across subgroups. Results: As of 01/15/2012, 264 pts were enrolled on 25 protocols and treated at 79 sites. 86% of pts were in phase II studies and 89% had stage IV disease. At the end of cycle 1, pts felt the trial was worthwhile (74%), would do it again (85%), and would recommend it to others (82%). 85% of pts reported undiminished QOL and only 7% rated the trial worse than expected. End of treatment responses were similar. Satisfaction rates varied by tumor site (p=0.04). 11% of pts having tumor response rated the trial as not worthwhile, and 66% of pts with progressive disease rated it worthwhile (see table). Pts with concordant preferred and actual TDM roles rated participation higher than pts with discordant TDM roles (see table). Conclusions: Most pts endorsed their clinical trial experience. Contrary to popular beliefs, treatment outcome did not have an overwhelming impact on pt satisfaction, and was just one of many factors such as TDM role discordance. Assessing pt satisfaction will inform future study design that can potentially improve pt accrual and retention. [Table: see text]
Patient-reported toxicity after treatment for cancers of the head and neck.
Authors: Hill-Kayser Christine E. , Vachani Carolyn , Hampshire Margaret K. , Di Lullo Gloria A. , Metz James M.
Published: March 2020

6135

Background: Patients with cancers of the head and neck (HNC) may be at risk for significant late effects after treatment. Quality of life may be altered significantly as a result. This Internet based study evaluates patient perceptions of toxicity after treatment for HNC. Methods: Patient-reported data were gathered via a convenience sample frame from HNC survivors voluntarily utilizing a publically available, free, Internet-based tool for creation of survivorship care plans. Available at www.livestrongcareplan.com and through the OncoLinkwebsite, the tool allows survivors to enter data regarding diagnosis, demographics, and treatments, and provides customized guidelines for future care. During use of the tool, HNC survivors are queried regarding late effects associated with specific treatments. All data have been maintained with IRB approval. Results: Of 3866 survivors using this tool between 4/2010 and 10/2011, 140 (4%) had undergone primary treatment for HNC. Median diagnosis age was 52y and median current age 56y. When queried regarding treatment received, 88% reported having undergone radiation, 73% surgery, and 67% chemotherapy. Many patient-reported late effects were associated with local tumor control, and included difficulty swallowing/speaking (83%), decreased saliva production (88%), dental problems (49%), thyroid problems (33%), decreased neck mobility (60%), eye and vision deficits (9%), and tinnitus (40%). In addition, 53% noted concerns regarding cognitive function. Users of the tool reported that they would share it with their healthcare team in 55% of cases. The most common reasons for not sharing it were “I did not think they would care,” and “ I did not want to upset or anger them.” Conclusions: Survivors using this tool anonymously and voluntarily report significant toxicity after treatment for HNC. Not all survivors appear comfortable discussing these issues with healthcare providers, despite major potential impact on quality of life. The data reported here may be of significant impact in future study of outcomes after HNC, as well as patient counseling and survivor care.
Prognostic role of HER2 loss after neoadjuvant therapy in patients with HER2-positive operable breast cancer.
Authors: Guarneri Valentina , Barbieri Elena , Piacentini Federico , Dieci Maria Vittoria , Omarini Claudia , Ficarra Guido , Bettelli Stefania Raffaella , Conte Pier Franco
Published: March 2020

631

Background: Emerging literature data are consistently showing that a change in HER2 status adversely affect the prognosis of breast cancer patients. Aim of the present analysis is to evaluate the prognostic impact of HER2 loss in breast cancer patients with HER2 positive disease treated with neoadjuvant therapy with or without anti-HER2 agents. Methods: A total of 94 HER2 positive patients were identified from a prospectively maintained database. The first cohort (A) includes 40 patients treated with chemotherapy alone (enrolled before 2005). The second cohort (B) includes 54 patients treated with neoadjuvant chemotherapy in combination with anti-HER2 agents (trastuzumab and/or lapatinib). HER2 expression was evaluated by IHC or FISH on pre-treatment core biopsy and on surgical specimen after neoadjuvant therapy. Patients were considered as having HER2 positive disease in case of IHC 3+ or FISH amplification. Results: No imbalance in terms of age, stage at diagnosis, tumor grade and expression of hormone receptor was observed in the two cohorts. In detail, 67% and 61% of the patients have a co-expression of HER2 and hormone receptor in cohort A and B, respectively. The rate of breast conservation was significantly higher in cohort B (chemotherapy+anti-HER2 agents) as compared to cohort A (chemotherapy alone) (59% vs 38%, p=0.048). Similarly, the rate of pathologic complete response (pCR) was significantly higher in cohort B (42.6% vs 7.5% in cohort A, p<0.001). A change in HER2 expression from biopsy to post-therapy samples was observed in 35% of the patients in cohort A vs 9% of the patients in cohort B (p=0.04). No patients achieving a pCR have recurred so far vs 25% of the patients with less than pCR (p=0.005). The rate of recurrence was significantly higher for patients experiencing a change in HER2 expression (47% vs 15% in patients with no change, p=0.007). At 5 years, 53% of the patients with Her2 change and 75% of the patients without Her2 change were alive and free of recurrence (log rank test: p=0.03). Conclusions: The rate of HER2 loss was significantly higher in patients not receiving anti-HER2 agents as a part of the neoadjuvant therapy. In this series, the change in HER2 status has a negative prognostic impact.
Effect of neratinib (N) alone and in combination with trastuzumab (T) in HER2-positive breast cancer (BC) cell lines.
Authors: Canonici Alexandra , Pedersen Kasper , Walsh Naomi , Crown John , O'Donovan Norma
Published: March 2020

632

Background: HER-2, a member of the transmembrane receptor tyrosine kinase ErbB family, is over-expressed in approximately 25% of BC. HER-2 targeted therapies, in particular, T, a monoclonal antibody targeting HER-2, and lapatinib (L), a reversible HER-2 tyrosine kinase inhibitor, have been shown to significantly improve the prognosis for HER-2 positive BC patients. However, resistance to T and/or L is a significant clinical problem. The aim of this study is to assess the activity of N (HKI-272), an irreversible HER-2 tyrosine kinase inhibitor, in HER-2 overexpressing BC cell lines, including T and/or L resistant cells. Methods: Using proliferation assays, the effect of N was assessed alone and in combination with T in HER-2 positive BC cell lines, including T and/or L resistant cell lines. The effect of N on HER-2 and downstream signalling molecules, Erk and Akt, was determined by immunoblotting. Results: HER-2 positive BC cell lines, including T and/or L resistant cells, are sensitive to N alone with IC50 values (concentration which inhibits 50% of growth) ranging from 1 to 280 nM. The combination of N and T has additive effects in SkBR3 and BT474 which are sensitive to T and also in SKBR3-Lwhich are resistant to L. In the cell lines HCC1954, HCC1954-L, MDA-MB-453, JIMT1 and SKBR3-HL which are resistant to T, combined treatment with T and N showed no enhancement compared to N alone. Finally, N decreased phosphorylation of HER-2, Erk and Akt in all cell lines tested. Conclusions: Our results suggest that N should be studied in patients with HER-2 positive BC, including patients with T and/or L resistant BC. We also demonstrate that N in combination with T may be more effective than either agent alone in T sensitive cells.
Adjuvant treatment of early-stage HER2+ elderly breast cancer patients: A retrospective, multicenter French study.
Authors: Barthelemy Philippe , Bassot Karine , Joly Florence , Ray Coquard Isabelle , Freyer Gilles , Dufour Patrick Regis , Campos France , Kurtz Jean Emmanuel
Published: March 2020

636

Background: Trastuzumab (T) is the standard of care for the adjuvant treatment of early stage, HER2+ breast cancer (BC). However, few data are available for elderly HER2+ breast cancer patients in this setting. In this current study, the patterns of care for elderly HER2+ early stage BC in 7 French cancer centres was evaluated. Methods: Medical records of all consecutive early stage HER2+ BC patients over 70 years old treated between 2006 and 2011 among participating centres were retrospectively reviewed. Specific factors such as age, comorbidities, tumor stage, grade, ER/PR and HER2 status, treatment characteristics, follow-up and cardiotoxicity data were analysed. Results: One hundred and two patients were identified, median age 75.4 (range 70-95). Elderly patients presented mostly (57%) large tumors (pT ≥2), and positive lymph node involvement (n=61). Trastuzumab-based adjuvant treatment was administered in 62% of patients (n=63). 54% of patients (n=55) received adjuvant chemotherapy whereas five patients received neoadjuvant chemotherapy. Chemotherapy without T was administered in 2 additional patients. Anthracyclines (A)-Taxanes (Ta) combination-based chemotherapy was given in 27% of patients (n=16), whereas 38% received a Ta-based chemotherapy (n=23), 35% (n=19) an A-based chemotherapy. Five patients received single-agent T. Treatment delays for T were required in 37% of patients (n=23) among whom 15 and 8 permanently or temporarily stopped T, respectively. The most frequent reason for interrupting or delaying therapy was cardiotoxicity (n=12) as well as patients refusal (n=7). A ≥ 10% decrease in LVEF was observed in 18/63 (29%) of patients, among whom T was stopped in 12. After a median 33 months follow-up, the median progression-free survival was not reached in patients receiving T-based therapy. The 2 and 3-year PFS rate were 94 and 89.5%, respectively. Conclusions: In routine practice only 62% of elderly early stage HER2+ BC patients are treated with a neoadjuvant or adjuvant T-based regimen. However, less than 50% of all patients completed their therapy. A-based chemotherapy was administered in around 60% of treated patients, and could explain cardiotoxicity in this setting.