bluuebunny/crossref_metadata_2025 huggingface dataset:
The negative predictive value (NPV) of FDG-PET/CT in the Head and Neck Squamous Cell Carcinoma (HNSCC) N0 patient, the first report of the ACRIN 6685 trial.
Authors: Stack Brendan C. , Duan Fenghai , Sicks JoRean , Romanoff Justin , Opanowski Adam , Horng Dunstan , Mahon Irene , Hollenbeak Christopher S.
Published: September 2018

6041

Background: This study evaluated the negative predictive value for node negativity in HNSCC. Methods: Patients were enrolled from 8/10 until 12/16 from 38 centers in the US and 1 center in China. This was a prospective, non-randomized trial. The study was designed to recruit 292 patients; however, 287 were enrolled by study closure. Inclusion criteria were newly diagnosed cT2-T4 SCC patients from the head and neck with one side cN0 who were willing to undergo an elective neck dissection. CN0 was determined by a negative neck CT or MR scan. Exclusions included non-SCC, non-surgical candidates, skin, nasopharynx or sinus primaries. PET/CT imaging reading performed centrally and pathology were analyzed at the neck level (left or right). To estimate confidence intervals, we used a nonparametric bootstrap to account for the correlation of data between sides of neck of the same patient. Correlative data and other image analyses will be reported separately. Results: PET/CT scans and pathology were available for 211 (table) N0 sides of neck for review at last interim analysis. NPV estimate with 95% CI for bilateral necks: 0.896 (0.831, 0.950) and specific to the N0 sides: 0.922 (0.862, 0.973). Conclusions: FDG PET/CT has high NPV for node negativity in HNSCC. This may obviate the need for elective neck dissection in N0 HNSCC patients. This trial was open about three times longer than planned, and a major obstacle to accrual was the generalized assumption among the oncology community that PET/CT had a high NPV. Therefore, patients sent to study centers for further diagnosis and treatment often had their PET/CT scans performed on non-ACRIN certified equipment. This required investigators to forgo offering the trial or the PET/CT was repeated. Our results may suggest application for pre-operative PET/CT nodal imaging of other primaries/lymphatic basins staged cN0. Funding from the National Cancer Institute through the grants U01 CA079778, U01 CA080098, CA180820, CA180794. Clinical trial information: NCT00983697. [Table: see text]
Association of DRB1 and DRBQ haplotype 04:01~03:01 with HPV positive head and neck squamous cell carcinoma.
Authors: Khattri Arun , Zuo Zhixiang , Tan Y-H Carol , Agrawal Nishant , Lingen Mark W. , Vokes Everett E. , Seiwert Tanguy Y.
Published: September 2018

6054

Background: The incidence of human papilloma virus (HPV) associated oropharyngeal head and neck cancer (HNC) is increasing rapidly in the US, Europe, and Asia. HPV16 is etiologic in 90-95% of HPV+ HNC. Sexual transmission and inability to clear infection leading to viral genome integration or chronic presence of episomal HPV16 DNA are precursors to HPV+ HNC carcinogenesis. However it remains unclear why a majority of HPV16 exposed individuals are able to clear the initial infection and avoid the risk of cancer. We hypothesized that difference in the ability eradicate infection may be mediated by certain HLA haplotypes. Methods: HPV(+) HNC patients from the TCGA cohort were HLA-typed based on available exome sequencing data. HLA typing was performed using the ATHLATES algorithm. We compared the distribution of alleles and haplotypes of classical HLA genes (A, C, B, DRB1 and DQB1) among HPV(+) HNC patients with those found in HPV(-) patients. Furthermore we evaluated enrichment of candidate alleles compared to publically available data in Caucasian non-cancer individuals. Results: Out of 528 HNC samples in the TCGA cohort, 450 were of Caucasian ancestry. The DRB1~DQB1 haplotype 04:01~03:01 was significantly increased in HPV(+) HNSCC patients compared to normal, non-cancer individuals ( p-value = 0.0045, OR = 2.52, 95% CI = 1.2–5.03). This was not the case for HPV(-) HNC patients. The number of African American samples in TCGA was comparably small (N = 48, with N = 5 being HPV+) however the frequency of DRB1~DQB1 haplotype 04:01~03:01 in the general African American population is significantly lower. Conclusions: DRB1~DQB1 haplotype 04:01~03:01 associates with an elevated risk for HPV+ HNC. Similar findings were reported 17 years ago for cervical cancer (Br J Cancer, 82(7), 1348–1352), and further validate our findings across tumor types. Mechanistic studies to understand potential DRB1~DQB1 haplotype 04:01~03:01 HPV specific immune dysfunction, as well as evaluation in different risk and racial populations are indicated.
PTEN and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC).
Authors: Da Costa Alexandre Andre B. A. , Costa Felipe D'Almeida , de Oliveira Andrea Cruz Ferraz , Stecca Carlos , Oliveira Audrey , Alves Ana Caroline Fonseca , Camandaroba Marcos Pedro Guedes , Araujo Daniel Vilarim , Machado Larissa , Cordeiro De Lima Vladmir Claudio
Published: September 2018

6061

Background: Platinum-based chemotherapy in association to cetuximab is the standart first-line treatment for metastatic HNSCC. There is no established biomarker for cetuximab efficacy in HNSCC. We have previously shown that PTEN loss of expression is a bad prognostic factor for patients treated with platinum-based chemotherapy and cetuximab. The aim of the present study was evaluate the prognostic impact of PTEN loss of expression in patients treated with or without cetuximab and to evaluate its predictive value to cetuximab benefit. Methods: One hundred and nineteen patients with metastatic or locally recurrent HNSCC were included. Clinical data on treatment and outcomes was retroespectively colected from medical charts. Tissue micro-array was constructed to evaluate PTEN protein expression through immunohistochemistry. Citoplasmatic staining was evaluated using H-score. Tumors with H-score < 10 were considered to present PTEN loss of expression. Results: From the 119 patients 72 were treated with chemotherapy plus cetuximab while 47 were treated with chemotherapy alone. Median overall survival (mOS) was 9.2 months and median progression free survival (PFS) was 4.6 months. Patients treated with cetuximab compared to those who were not treated with cetuximab had a mOS of 11.4 vs 7.0 months (p = 0.770) and a median PFS of 6.2 vs 3.0 months (p = 0.249). Patients with PTEN loss of expression had a worse OS and PFS with mOS of 5.8 vs 10.5 months (p = 0.002) months and mPFS of 3.2 vs 5.2 (p = 0.015). On multivariate analysis including PTEN loss of expression and ECOG performance status both remained independently associated to survival with HR 2.25 (CI95% 1.28-3.97, p = 0.005) for PTEN loss of expression and a HR 1.63 (CI95% 1.07-2.50, p = 0.023) for ECOG. Negative prognostic impact of PTEN loss of expression was seen only in the cetuximab treated patients (mOS 7.3 vs 13.0 months; p = 0.002) but not in the chemotherapy only group (mOS 3.2 vs 7.5 months; p = 0.051). Interaction test for treatment group and PTEN loss of expression showed a p = 0.418. Conclusions: The present study confirms PTEN as a prognostic factor for metastatic HNSCC and suggests PTEN expression should be studied in larger cohorts to evaluate its predictive value to cetuximab response.
Disparities in supportive therapy for head and neck cancer and impact on missed radiation days and weight loss.
Authors: Ramey Stephen , Perlow Haley , Silver Ben , Jaffe Adam , Kwon Deukwoo , Chinea Felix , Samuels Stuart , Yechieli Raphael
Published: September 2018

6077

Background: National guidelines emphasize the importance of speech and swallowing (SS) and nutrition services (NS) for head and neck cancer patients (pts). This study evaluates influences of demographic and treatment factors on receipt of SS and NS at a safety-net hospital (SH) and an adjacent private hospital (PH). It also examines associations between lack of these services and negative outcomes. Methods: This retrospective analysis included non-metastatic laryngeal or oropharyngeal cancer pts treated with radiotherapy (RT) at a PH or SH. Univariate (UVA) and multivariable (MVA) analyses utilized linear regression, logistic regression, and zero-inflated Poisson regression. Covariates included race, ethnicity, preferred language, insurance status, immigration status, gender, age, treating hospital, comorbidity score, primary treatment modalities, time to treatment initiation (TTI), and stage. Potential negative outcomes of not receiving SS and/or NS were analyzed only among pts treated with chemoradiation (CRT). Results: Of 239 pts (PH = 138 pts; SH = 56 pts), 28.6% of SH pts received SS pre-RT vs 54.1% at the PH (p < 0.001). Receipt of pre-RT NS did not differ significantly between SH (14.3%) and PH (19.7%) but was low at both. On MVA, SH care (OR 0.29; p = 0.029) and longer TTI (OR 0.99; p = 0.033) were associated with decreased pre-RT SS. In contrast, surgery before RT (OR 10.1; p = 0.002) and surgery before CRT (OR 10.7; p = 0.001) vs RT alone were associated with increased pre-RT SS. No covariates were significantly associated with receipt of NS on MVA. For pts receiving CRT, pre-RT SS was associated with less weight loss during RT (mean difference = 2%; p = 0.036). Receiving both pre-RT SS and NS was associated with fewer missed RT days (RR 0.49; p = 0.004). Receipt of SS and/or NS were not associated with gastric tube placement, emergency room visits, or non-chemotherapy admission days during or within 90 days of CRT. Conclusions: SS was received less often at a SH vs a PH. NS were delivered at a low level at both centers. Lack of supportive services was associated with increased missed RT days and increased weight loss during CRT. Quality metrics to establish supportive care benchmarks may help reduce disparities.
A phase 1 trial of NBTXR3 nanoparticles activated by intensity-modulated radiation therapy (IMRT) in the treatment of advanced-stage head and neck squamous cell carcinoma (HNSCC).
Authors: Le Tourneau Christophe , Calugaru Valentin , Jouffroy Thomas , Rodriguez Jose , Hoffmann Caroline , Dodger Bernard , Moreno Victor , Calvo Emiliano
Published: September 2018

6080

Background: Functionalized hafnium oxide nanoparticles (NBTXR3) have been developed as selective radioenhancers, which may represent a breakthrough approach for the local treatment of solid tumors. The high electron density of the nanoparticles, when exposed to radiotherapy (RT), allow the absorption/deposition of a high radiation dose within the tumor cells, to physically kill the cells and possibly improve outcome. A phase I trial was implemented for the treatment of locally advanced HNSCC in patients (pts) older than 65 years who cannot receive cisplatin. Methods: Pts received a single intratumor (IT) injection of NBTXR3, volume dose levels escalated at 5%, 10%, 15% and 22% of baseline tumor volume, followed by RT (IMRT, 70Gy/ 35 fractions / 7 weeks). Primary endpoints included feasibility of the IT implantation and safety. Secondary endpoints included IT residency of NBTXR3 using CT scan and RECIST 1.1 response. Results: Enrollment was completed for volume 5%, 10%, and 15% (11 pts) and 1 patient at volume dose level 22%. Feasibility of the IT injection was confirmed. The treatment was easily administered, was safe with no SAE, or early DLT, which allowed the pts for completion of the planned RT schedule. Adverse events related to the injection procedure included grade 1-2 injection pain (1 pt), and tumor hemorrhage (1 pt). Results demonstrated that a single injection of NBTXR3 provides adequate bioavailability of NBTXR3 IT over seven weeks of RT. No leakage of NBTXR3 to the adjoining healthy tissues was observed. Preliminary results of antitumor activity according to RECIST 1.1 are presented below: 11 evaluable pts, 10 showed complete or partial response (RECIST 1.1) including, 1/5 complete response at dose levels ≤ 10% and 3/6 complete responses at dose levels > 10% Follow up results with duration of response and tolerance will be disclosed. Conclusions: Injection of NBTXR3 was safe and well tolerated. All pts received the planned RT. Clinical trial information: NCT01946867.
RNAseq analysis of the sorafenib phase III DECISION trial in differentiated thyroid cancer (DTC): Correlation with clinical outcome.
Authors: Capdevila Jaume , Matos Garcia Ignacio , Mancuso Francesco M , Iglesias Carmela , Nuciforo Paolo , Zafon Carles , Palmer Hector G. , Ogbah Zighereda , Muiños Laura , Pena Carol Elaine , Brose Marcia S. , Schlumberger Martin , Vivancos Ana
Published: September 2018

6083

Background: In DECISION, sorafenib significantly impacted progression-free survival (PFS) and response rate (RR) in radioactive-iodine refractory DTC. The aim of this biomarker study was to identify RNA expression profiles related with PFS, overall survival (OS) and RR and to describe the expression profiles of DTC histologies. Methods: Of the 417 patients in the trial, 247 had sufficient formalin fixed paraffin embedded archival tumor material for RNAseq. We generated on average 77 million paired-end reads for each sample on HiSeq2000 (Illumina). RNAseq reads were mapped against the human reference genome (GRCh38) with STAR (v2.5.1b) using ENCODE parameters. 125 samples had sufficient quality to be included in the analysis. Results: The analysis subset included 68 sorafenib and 57 placebo patients (PFS 10.3 vs 7.4 months, HR: 0.62 CI 95% 0.38-0.99, p = 0.046). Unsupervised clustering using the 100 most variable genes identified 3 groups: BRAF-like (included most of the BRAF-mutated tumors), RAS-like (included most of the RAS mutated tumors) and non-BRAF-non-RAS-like group (included most wild-type tumors). These groups, based on the mutational profile, can be correlated with tumor type: the papillary BRAF-mutant, the follicular wild-type, and a third group with papillary, follicular and poorly differentiated with predominant RAS mutations. A Student t-test comparing papillary and follicular histologies revealed a signature of 283 genes with significantly different expression that, within the papillary tumors, identifies a subset with an expression profile more similar to follicular. No RNA signatures correlating with benefit from sorafenib were identified. Conclusions: While papillary and follicular thyroid cancers have significantly different RNA expression profiles, a subset of papillary has been identified with an expression profile more similar to follicular. In addition, a unified RAS-like expression profile spans subsets of papillary, follicular, and poorly differentiated thyroid cancers, suggesting that tumor biology can be similar across histologies. Clinical trial information: NCT00984282.
Do the American Society of Clinical Oncology (ASCO) Value Framework and the European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale measure the same construct of clinical benefit?
Authors: Cheng Sierra , McDonald Erica , Cheung Matthew C. , Arciero Vanessa Sarah , Qureshi Mahin Iqbal , Jiang Di Maria , Ezeife Doreen Anuli , Sabharwal Mona , Chambers Alexandra , Han Dolly , Leighl Natasha B. , Sabarre Kelley-Anne , Chan Kelvin K.
Published: September 2018

6509

Background: Whether the American Society of Clinical Oncology (ASCO) Value Framework and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) measure similar constructs of clinical benefit is unclear. It is also unclear how they relate to quality-adjusted life-years (QALYs) and funding recommendations in the UK and Canada. Methods: Randomized clinical trials (RCTs) of oncology drug approvals by the Food and Drug Administration, European Medicines Agency and Health Canada between January 2006 and August 2015 were identified and scored using the ASCO version 1 (v1) framework (August 10, 2015), ASCO version 2 (v2) framework (May 31, 2016) and ESMO-MCBS (May 30, 2015) by at least two independent reviewers. Spearman correlation coefficients were calculated to assess construct (between frameworks) and criterion validity (against incremental QALYs from the National Institute of Clinical Excellence (NICE) and the pan-Canadian Oncology Drug Review (pCODR)). Associations between scores and NICE/pCODR recommendations were examined by logistic regression models. Inter-rater reliability was assessed using intra-class correlation coefficients. Results: From 109 included RCTs, 108 ASCOv1, 111 ASCOv2 and 83 ESMO scores were determined. Correlation coefficients for ASCOv1 vs. ESMO, ASCOv2 vs. ESMO, and ASCOv1 vs. ASCOv2 were 0.36 (95% CI 0.15-0.54), 0.17 (95% CI -0.06-0.37) and 0.50 (95% CI 0.35-0.63), respectively. Compared with NICE QALYs, correlation coefficients were 0.45 (ASCOv1), 0.53 (ASCOv2) and 0.46 (ESMO); with pCODR QALYs, coefficients were 0.19 (ASCOv1), 0.20 (ASCOv2) and 0.36 (ESMO). None of the frameworks were significantly associated with NICE/pCODR recommendations. Inter-rater reliability was good for all frameworks. Conclusions: The weak-to-moderate correlations between the ASCO frameworks and ESMO-MCBS, with QALYs, and with NICE/pCODR funding recommendations suggest different constructs of clinical benefit measured. Construct convergent validity with the ESMO-MCBS in fact did not increase with the updated ASCO framework.
Trends in the geographic distribution of cancer clinical trials in the US: 2008-2015.
Authors: Bennette Caroline Savage , Wang Wei-Jhih , Ramsey Scott David , McDougall Jean A.
Published: September 2018

6515

Background: Access to and patient enrollment in cancer clinical trials is likely strongly impacted by where trial enrollment sites are located. Our objective was to evaluate temporal trends in the geographic location of cancer clinical trials launched in the US. Methods: We obtained the recruiting location(s) of all public- and privately-funded phase II/ III cancer clinical trials launched in the US between 2008 and 2015 from the ClinicalTrials.gov database. We linked the recruiting location(s) of each trial to the relevant hospital service area (HSA), which are defined by ZIP codes as local health care markets for hospital care (n = 3436). We estimated the number of cancer clinical trial sites in each HSA each year between 2008 and 2015. We also calculated a statistical measure of inequality, the Gini coefficient. The Gini coefficient would be 0 if all hospital service areas launched the same number of cancer clinical trials, and would be 1 if all cancer clinical trials were launched in only a single hospital service area. Results: 62% of HSAs (n = 2133) did not launch a single cancer clinical trial between 2008 and 2015. There was a small and non-statistically significant decline in the overall number of cancer clinical trial sites in the United States between 2008 and 2015 (-1.6% per year [95% CI: -4.0, 0.9]). During this same period of time, however, inequality in the geographic distribution of cancer clinical trial sites considerably deepened. For example, in 2008-09, no trials were launched in 68% of HSAs while 19% of trial sites were in only 1% of HSAs. Trials launched in 2014-15 were even more concentrated: no new trials were launched in 74% of HSAs while 25% of trial sites were in the top 1% of HSAs. The Gini coefficient increased significantly from 0.683 (95% CI: 0.666, 0.700) for trials launched in 2008-09 to 0.726 (95% CI: 0.706, 0.746) for those launched in 2014-15. Conclusions: Our findings indicate increased inequality in the geographic distribution of cancer clinical trials launched in the United States since 2008. The underlying causes and consequences of such increasing concentration warrant further analysis given the importance in ensuring equitable geographic access to cancer clinical trials in the US.
A multicenter analysis of patient reported risk factors for not working during cancer therapy.
Authors: Blinder Victoria Susana , Eberle Carolyn E. , Aviki Emeline , Schleicher Stephen Matthew , Patil Sujata , Basch Ethan M. , Sloan Jeff A. , Bennett Antonia Vickery
Published: September 2018

6523

Background: Treatment for most types of cancer results in work disruptions. The aim of this study is to identify risk factors for not working during cancer therapy using a patient-reported outcome tool. Methods: Patients of all cancer types, who were undergoing treatment with curative or palliative intent, were enrolled in a survey-based study at Memorial Sloan Kettering Cancer Center and the North Carolina Cancer Hospital from 1/2014 to 7/2015. All patients working full- or part- time at the time of cancer diagnosis were included in this analysis. Patient reported outcomes were collected using a survey tool at any time during active cancer treatment. The primary outcome of this analysis was self-reported work status at the time of survey completion. Results: Of 119 patients who were working before their cancer diagnosis, 68% were working at the time of survey completion. The mean age was 52.9 (range 20-80). Younger age was associated with working: 82% of patients age < 40 were working during treatment vs. 31% of patients age > 65 (p=0.01). The number of days patients reported being completely unable to work in the past month was significantly associated with work status; only 26% of patients who missed > 10 days continued to work compared to 69% who missed ≤ 10 days (p<0.01). Patients who report having a flexible work schedule were 23% more likely to continue to work during treatment (69% vs. 46%, p=0.01). In a multivariable model controlling for having an employer contingent health plan, and household income > 200% of the federal poverty level (fpl), only age, having a flexible work schedule, and inability to work > 10 days were independently associated with work status during treatment (Table). Conclusions: Having a flexible work schedule allowed for more work interruptions without job loss. Patients who are likely to miss more than 10 days of work and who have inflexible work schedules are at high risk of unemployment and should be targeted for employment retention initiatives. [Table: see text]
Disparities in access to breast cancer treatment: An observational study based on insurance status.
Authors: Kailasam Karthik , Omaira Mohammad , Ravichandar Marie , Sivsammye Suceil
Published: September 2018

6534

Background: Breast cancer is the second leading cause of cancer death in Caucasians and African-Americans, and the most common cause of cancer death in Hispanic women. Methods: A retrospective analysis was done with data obtained from 1473 hospitals by National cancer database (NCDB) for the years 2004-2014. Patients with breast cancer were analyzed for differences in treatment offered based on their insurance status. Patients in the insurance group were enrolled under either Private, Medicare, Medicaid or other government insurance. Treatments offered were surgery, chemotherapy, radiation therapy or a combination of the above. Patients with unspecified insurance status and those who were on active surveillance were excluded from the analysis. Results: A total of 2,245,259 patients with breast cancer from all age groups were identified from the registry. 47,294 patients did not have insurance; among which 3275 (7.4%) were not offered any treatment. Among 2,093,809 patients with insurance, 58,726 (2.8%) patients were not offered any treatment. Hence, patients without insurance were twice (OR 2.65; CI 2.55-2.75 p < 0.0001) more likely to not receive any first course treatment. Sub-group analysis for different stages of breast cancer showed; carcinoma in-situ (OR 2.44; CI 2.20-2.71 p < 0.0001), stage1 (OR 2.68; CI 2.43-2.96 p < 0.0001), stage2 (OR 2.86; CI 2.61-3.12 p < 0.0001), and stage 3 (OR 2.56; CI 2.25-2.92 p < 0.0001) have similar odds for not being offered any treatment. However, the odds of receiving treatment were better for stage 4 breast cancer (OR 1.44; CI 1.32-1.55 p < 0.0001). Uninsured Caucasians (OR 2.70; CI 2.56-2.85 p < 0.0001) were less likely to receive any treatment compared to uninsured African-Americans (OR 2.16; CI 2.00-2.33 p < 0.0001) and uninsured Hispanics (OR 1.66; CI 1.52-1.82 p < 0.0001) Conclusions: With the recent suggested changes in health care policy, we can expect the number of uninsured patients to rise and therefore more patients might not have access to breast cancer treatment.
Exploring the time delay between regulatory approval and health techonology assessments (HTAs) of oncology therapies in France, Germany, England, Scotland, Canada, and Australia.
Authors: Jaksa Ashley , Pontynen Anson , Bastian Alexander
Published: September 2018

6545

Background: Drugs in the USA become available from the moment of FDA approval. Access to oncology therapies outside of the USA may be delayed by regulatory and additional payer HTA processes. This study aimed to examine the time from regulatory approval to an HTA reimbursement decision in countries with mandatory HTA. Methods: Oncology HTAs (N=569) for medicines approved by the EMA, Health Canada, and the Therapeutic Goods Administration (Australia) were matched on indication with HTAs from France, Germany, Canada, England, Scotland, and Australia. Resubmissions were excluded. The date of the first reimbursement decision was subtracted from the date of the regulatory approval to determine the time taken to complete HTA and to issue reimbursement decision. Trends by country were examined. Results: Time between regulatory approval and HTA reimbursement required a mean of 321 days (Median=214 days; Std.Dev. 330 days). Access in England took the longest, on average, (547 days) to issue a decision compared to the other countries. This time was two to three times longer than any other country. Australia had the shortest time to issue a reimbursement decision, which was approximately 6 months. Conclusions: Approximately one additional year is required after regulatory approval for oncology medicines to complete HTA and receive a reimbursement decision, potentially delaying patient access to oncology medicines outside the USA. The large variability in time to a reimbursement decision by country is likely due to varying processes. Additional research is needed to clarify the impact of these delays on access to care and patient outcomes. [Table: see text]
Asian representation in clinical trials of new drugs for the treatment of cancer.
Authors: Fashoyin-Aje Lola A. , Fernandes Laura L. , Lemery Steven , Keegan Patricia , Sridhara Rajeshwari , Bull Jonca C. , Pazdur Richard
Published: September 2018

6564

Background: In the US, statistics for Asians are often aggregated with other racial groups. This poses challenges in estimating the cancer burden and in defining cancer clinical trial enrollment targets in this demographic subgroup. ‘Asian‘ refers to persons with origins in the Far East, Southeast Asia, or the Indian sub-continent. Asians comprise 6% of the US population and the largest Asian subgroups in the US are of Chinese (22%), Filipino (19%), Asian Indian (19%), Vietnamese (10%), Korean (9%), and Japanese (7%) descent. The representation of Asian patients in global clinical trials may not be reflective of the Asian subgroups in the US. FDA conducted an analysis to describe patients categorized as ‘Asian’ in clinical trials supporting the approval of new drugs. Methods: We reviewed the marketing applications of 33 new molecular entities approved for the treatment of solid tumor malignancies between 2011- 2016 to identify trials that provided the primary evidence of safety and efficacy. Results: A total of 29,941 patients were enrolled; 17 % were Asian. Most Asian patients were enrolled in Korea (20%), Taiwan (20%), mainland China (20%), Japan (16%), and US (5%). Few patients were enrolled in India (3%); the Philippines (1%); Vietnam (0). In the US, Asian patients comprised 3% of the total number of patients enrolled. Conclusions: Asian patients represented a heterogeneous mix. A large proportion was enrolled in Taiwan (20%) and Korea (20%), whereas the largest proportion of US Asians have origins in mainland China (22%), the Philippines (19%), India (19%), and Vietnam (10%). Nevertheless, although Asians share a common ancestry, it is not clear whether data from global clinical trials are generalizable to Asian patients in the US. Therefore, strategies to improve the enrollment of US Asian patients in clinical trials are needed. Among patients enrolled in the US, 3% were Asians, a proportion that is below US Asian population estimates (6%). While most site-specific cancer incidence and death rates are lower in US Asians compared to Whites, the rates of some cancers (e. g., stomach and liver) are higher in this group. Therefore, studies are needed to determine adequate enrollment targets in this demographic subgroup.
Audit study of cancer research mentorship opportunities by NCI-funded PIs: Analysis of a pathway barrier for diversity.
Authors: Robinson Jeffrey D. , Dieckmann Nathan , Withers Elizabeth , Hassouneh Dena , Thomas Charles R.
Published: September 2018

6566

Background: The pipeline of diverse cancer researchers is critical. Audit studies suggest that racial discrimination disadvantages black (vs. white) people with respect to educational/professional advancement (Milkman, 2012). We hypothesized that prospective Black (B) male doctoral students would experience greater disparity in responses when seeking access to NCI-funded PIs compared to prospective Caucasian (W) males. Primary aim: To explore response and acceptance rates for B (vs. W) men seeking cancer-research mentorship. We also explore similar differences when considering evaluators’ race and sex. Methods: Between 9-9:30 am (local time) during a Monday in Oct 2015, identical emails were sent to 1028 randomly selected PIs affiliated with 65 NCI-designated cancer centers. PIs were randomly assigned to receive emails from either ‘Brad Anderson’ (W; n = 513) or ‘Lamar Washington’ (B; n = 515). Primary outcomes: (1) any response within one week (yes/no); and (2) type of response if received (agree to meet/not agree to meet). Logistic regression was used to examine unadjusted and adjusted effects of condition (W/B) on the primary outcomes. In adjusted models, PI sex and time zone were included as covariates (PIs identified as African American = 1.2%). Results: Approximately 50.0% and 48.3% of the sample responded to ‘Brad’ and ‘Lamar,’ respectively. Condition was not a significant predictor of ‘any response’ in either unadjusted (p = .62, odds ratio 95% CI = 0.83-1.35) or adjusted (p = .62, odds ratio 95% CI = 0.83-1.36) models. In the adjusted model, neither PI sex nor time zone were significant predictors of ‘any response.’ For those who responded, 43.7% and 40.9% ‘agreed’ to meet with Brad and Lamar, respectively. Condition was not a significant predictor of ‘response type’ in either unadjusted (p = .53, odds ratio 95% CI = 0.78-1.61) or adjusted (p = .51, odds ratio 95% CI = 0.78-1.64) models. In the adjusted model, only PI sex was a significant predictor of ‘response type’ (p = .03, odds ratio 95% CI = 1.04-2.29), with males (45.8%) being more likely to ‘agree to meet' than female PIs (35.6%). Conclusions: We did not find strong evidence of bias by NCI-funded PIs against B (vs. W) prospective Ph.D. students.
Associations between cancer patients' advance care and financial planning and surviving spouses' financial well-being.
Authors: Wright Alexi A. , Keating Nancy Lynn , Nicholas Lauren Hersch
Published: September 2018

6567

Background: The “financial toxicity” associated with cancer treatment, including high out-of-pocket expenses and lost earnings, may have lasting financial effects for surviving spouses. Although advance care planning (ACP) is used as a cancer quality metric, the value of financial planning is unknown. Methods: We examined associations between cancer patients’ written ACP and financial planning (will) and surviving spouses’ financial well-being using prospective, nationally representative data from the 2004-2014 waves of the Health and Retirement Study. We assessed change in household, non-housing (financial) wealth, including debt, among 962 surviving spouses of cancer decedents. Because wealth varies widely in the US, we fit multivariable quantile regression models at the 25th, 50th, and 75th percentiles to examine associations between cancer decedents’ ACP, financial planning, and wealth, adjusting for sociodemographic characteristics. Results: Among cancer decedents, 33% completed both ACP and a will, 27% only a will, 10% only ACP, and 30% neither. The median wealth of surviving spouses was $22,309 (25th percentile = $0, 75th percentile = $134,238). Among spouses of cancer decedents in the 25th percentile of wealth before death, completion of ACP and a will was associated with $5,348 (95% CI = $1,172-$9,523) more financial wealth after death compared with no planning. Use of ACP and a will was also associated with $46,851 (95% CI = $2,810-$90,891) more financial wealth at the 75th percentile. There were no differences in the wealth of surviving spouses after death between patients who completed only a will, only ACP, or no planning (Ps > .09). Conclusions: Completion of ACP and financial planning was associated with greater wealth among both affluent and non-affluent surviving spouses compared with no planning. Efforts to sensitively incorporate financial planning into cancer patients’ care have the potential to improve surviving family members’ financial well-being.
Universal testing for hormonal status in breast cancer: Are we choosing wisely?
Authors: Goller Taylor Maxwell , De Luca-Johnson Javier , Rehman Hibba tul , Ambaye Abiy Berhie
Published: September 2018

6583

Background: Characterizing estrogen receptor (ER) and progesterone receptor (PR) status has long been standard practice with newly diagnosed breast cancers. ER and PR expression suggests a more favorable prognosis and predicts tumor responsiveness to hormonal therapy. However, this testing comes with considerable cost. At our institution, the Medicare reimbursement rate for a single ER/PR assay is $310. With over 300,000 newly diagnosed breast cancers in the US each year, the total cost of ER/PR testing is close to 100 million dollars. Furthermore, the 2010 American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) guidelines suggest that up to 20% of ER/PR testing worldwide may be inaccurate with potential for false negative results. A falsely negative result could lead clinicians to not offer treatment with hormonal therapies. The purpose of this study was to investigate whether nuclear grade could be used to predict ER status, thus saving cost and reducing the potential for false negative test results and the inappropriate withholding of beneficial treatment. Methods: A retrospective analysis of prospectively collected data from the University of Vermont Breast Cancer Database identified all newly diagnosed breast cancers of any histologic type with available data on nuclear grade and ER status (2/2008-10/2016). The relationship between nuclear grade and ER status was analyzed (Table). Results: Nuclear grades 1 and 2 were associated with a significantly higher proportion of ER positive results than high nuclear grades (chi-square test p <.001). Conclusions: Nuclear grade 1 and 2 breast cancers are nearly universally ER positive (99% and 97%, respectively). Thus, ER testing may be redundant in these tumors. Elimination of ER testing in nuclear grade 1 and 2 tumors could save tens of millions of dollars each year in the US alone. It could also reduce the potential for false negative test results and the inappropriate withholding of beneficial treatment. [Table: see text]
Phone call for chemotherapy validation in outpatient unit as a way to optimize health care without compromising patients' satisfaction and quality of life.
Authors: Marino Patricia , Touzani Rajae , Palomares Myriam , Cappiello Maria-Antonietta , Bouhnik Anne Deborah , Guelmani Najoua , Provansal Magali , Vittot Martine , Dermeche Slimane , Braham Farida , Launay Simon , Goncalves Anthony , Ries Pauline , Extra Jean-Marc , Gilabert Marine , Moulin Jean Francois , Gravis Gwenaelle
Published: September 2018

6588

Background: Patients’ satisfaction is known to be closely linked to the time spent with the physician. However, longer waiting times may be a source of dissatisfaction as well as organizational dysfunctions of the outpatient unit. Is a validation of chemotherapy by phone call instead of a medical consultation with a senior physician before chemotherapy (CT) is feasible without compromising patients’ satisfaction and quality of life? Methods: Pts with OMS < 1, able to respond to phone call, < 76 years, receiving day 8 and or d15 of CT were included. We enrolled 343 pts in a before/after study between 2013 and 2016. In the “before” step (control arm), 168 pts had a systematic physician consultation the same day before CT administration. In the intervention arm 175 pts received a phone call by a junior physician the day preceding CT administration. A specific questionnaire for CT -related toxicity of the previous cycle was recorded and CT was validated or not by physician. The day after, pts received prepared CT without appointment with the oncologist and delay in administration for already prepared CT. At the end of CT protocol, socio demographics, patients’ satisfaction (In-PatSat32) and health status (EQ-5D) questionnaires were completed by patients. Results: Questionnaires were completed by 83% and 74% in before and after step respectively, 241 questionnaires were analyzed. Satisfaction with care showed similar In-PatSat32 scores between arms, for satisfaction with: physician, nurse, organization and services. No differences of perceived health status and toxicity were observed between both groups, but patients’ time spent in hospital was lower in the intervention group versus the control group, (p = 0.007). Conclusions: An alternative care pathway implementing phone calls before CT administration if feasible without compromising pts’ satisfaction, quality of life and toxicity. We believe that saving time of pts, physicians and pharmacists is a way to optimize the model of care in outpatient unit, particularly in the immunotherapy area with more pts received intra venous treatment, probably for a long time.
Concordance assessment of a cognitive computing system in Thailand.
Authors: Suwanvecho Suthida , Suwanrusme Harit , Sangtian Montinee , Norden Andrew D , Urman Alexandra , Hicks Annette , Dankwa-Mullan Irene , Rhee Kyu , Kiatikajornthada Narongsak
Published: September 2018

6589

Background: IBM Watson for Oncology (WFO) was trained by Memorial Sloan Kettering and is a cognitive computing system that uses natural language processing to ingest patient data in structured and unstructured formats. The system provides physicians with treatment options that are derived from established guidelines, the medical literature, and training from patient cases. In this study, we assessed the degree of concordance between treatment recommendations proposed by WFO and oncologists at Bumrungrad International Hospital (BIH). BIH is a 580-bed multispecialty hospital in Bangkok, Thailand. Methods: Data from breast, colorectal, gastric, and lung cancer patients treated at BIH were entered into WFO in 2015 and 2016. Retrospective cases were entered after a treatment plan had been determined, and prospective cases were entered during patients’ treatment planning sessions. WFO recommendations were provided in 3 categories: “Recommended”, “For Consideration”, and “Not Recommended.” Concordance was analyzed by comparing the decisions made by the oncologists to those proposed by WFO. Concordance was achieved when the oncologist’s treatment suggestion was in the “Recommended” or “For Consideration” categories given by WFO. Results: A total of 211 cases were assessed, 92 were retrospective and 119 were prospective. The overall concordance rate was 83%; 89% for colorectal, 91% for lung, 76% for breast, and 78% for gastric cancer. Similar concordance rates were observed when retrospective and prospective cases were analyzed separately. Discordance was attributable in part to local oncologists’ preferences for non-U.S. guidelines for certain cancers, especially gastric cancer. Conclusions: There was a high degree of concordance between WFO treatment options and the decisions made by local oncologists. Similar results were recently reported in a breast cancer concordance study conducted using WFO in India (San Antonio Breast Cancer Symposium 2016, Somashekhar et al). WFO’s capabilities as a cognitive decision support tool can be further improved by incorporating regional guidelines. Future work will analyze reasons for discordance such as cost, insurance requirements, and patient and physician preference.
Estimating the optimal rate of adjuvant chemotherapy utilization in stage III colon cancer.
Authors: Karim Safiya , Brennan Kelly , Peng Yingwei , Mackillop William J. , Booth Christopher M.
Published: September 2018

6591

Background: Identifying optimal chemotherapy utilization rates can drive improvements in quality of care. We report a benchmarking approach to estimate the optimal rate of adjuvant chemotherapy (ACT) for stage III colon cancer. Methods: The Ontario Cancer Registry was linked to electronic chemotherapy records to identify ACT utilization among a random 25% sample of patients with stage III colon cancer diagnosed during 2002-2008 in Ontario, Canada. We explored whether hospital factors (teaching status, regional cancer centre, medical oncologist on-site) were associated with ACT rates. The benchmark population included hospitals with the highest ACT rates that accounted for 10% of the patient population. Hospital ACT rates were adjusted for case mix in a multi-level model accounting for random variation at the hospital level. A Monte Carlo simulation was used to estimate the proportion of observed ACT rate variation that could be due to chance alone. Results: The study population included 2,801patients with stage III colon cancer; ACT was delivered to 66% (1861/2801) of patients. There was no difference in hospital ACT rate by teaching status (64% academic vs 67% non-academic, p = 0.107), comprehensive cancer centre status (65% cancer centre vs 67% non-cancer centre, p = 0.362), or having medical oncology on site (67% on site vs 66% not on site, p = 0.840). After excluding hospitals that had case volumes less than 10 (N = 150), unadjusted ACT rates varied across hospitals (range 44% to 91%, p = 0.017). The unadjusted benchmark ACT rate was 81% (95%CI 76%-86%); utilization rate in non-benchmark hospitals was 65% (95%CI 63%-66%). When using adjusted ACT rates in a multi-level model significant variation remained across hospitals (p < 0.001). The adjusted benchmark ACT rate was 74% (95%CI 63%-83%); non-benchmark hospital ACT rate was 65% (95%CI 53%-75%). The simulation analysis suggested that the non-random component of ACT rate variation across hospitals was 1.5%. Conclusions: There is significant variation in ACT rates across hospitals in routine practice. The estimated benchmark ACT rate is 74%. However, simulation analyses suggest that most of the variation in ACT utilization across hospitals may be due to chance alone.
Code status transitions from full code to do-not-resuscitate (DNR) among hospitalized patients with advanced cancer.
Authors: Lau-Min Kelsey S. , Nipp Ryan David , D'Arpino Sara , Moran Samantha M.C. , Hochberg Ephraim , Traeger Lara N. , Jackson Vicki , Cashavelly Barbara J. , Martinson Holly S , Ryan David P. , Greer Joseph , Temel Jennifer , El-Jawahri Areej
Published: September 2018

6592

Background: Code status discussions ensure the delivery of preference-concordant care. However, the processes by which hospitalized patients with advanced cancer change their code status from full code to DNR are unknown. Methods: We conducted a mixed-methods study on a prospective cohort of patients with advanced cancer who were hospitalized from 9/14-10/15. Two physicians used a consensus-driven medical record review to characterize processes leading to code status transitions from full code to DNR. We explored factors associated with these processes using χ2 and Kruskal-Wallis tests. Results: We reviewed 1,047 hospitalizations among 728 patients. Admitting physicians did not address code status in 52.1% of these hospitalizations, leading code status orders to be presumed full. 273 patients (37.5%) transitioned from full code to DNR; 132 (48.4%) of them had erroneous presumed full code status orders on admission. We identified three additional processes leading to transitions from full code to DNR: acute clinical deterioration (15.4%), discontinuation of cancer-directed therapy (17.2%), and hypothetical discussions regarding the futility of CPR (15.4%). Among these processes, code status transitions due to acute clinical deterioration were associated with less patient involvement, shorter time to death, and higher likelihood of inpatient death. Changes due to hypothetical discussions were more likely to involve palliative care. Conclusions: Half of code status transitions among hospitalized patients with advanced cancer were due to erroneous full code orders, underscoring a greater need to discuss patient CPR preferences. Transitions due to acute clinical deterioration were associated with less patient engagement and higher likelihood of inpatient death. [Table: see text]
Cost-effectiveness of front-line trials in metastatic colorectal cancer: Integrating the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) with the costs of drugs.
Authors: Bonetti Andrea , Giuliani Jcopo
Published: September 2018

6622

Background: In Western Countries, colorectal cancer (CRC) is the second most common cause of death from cancer. In light of the relevant expenses of drugs it might be interesting to make a balance between the cost of the drugs and clinical parameters of interest such as progression free survival (PFS). Methods: Phase III randomized clinical trials (RCTs) that compared at least two front-line chemotherapy regimens for mCRC patients were evaluated. Differences in PFS between the different arms were calculated and compared with the pharmacological costs (at the Pharmacy of our Hospital) needed to get one month of PFS. Subsequently we applied the ESMO-MCBS (a 1 to 5 scale) to the above phase III RCTs. Results: Overall 28 phase III RCTs, including 19 958 patients, were analyzed. The FOLFOX resulted the least expensive (56 € per month of PFS gained) while the addition of irinotecan to FOLFOX (FOLFOXIRI) increased only marginally the costs (90 € per month of PFS gained). Treatments including the monoclonal antibodies showed a cost per month of PFS gained of 2823 € (FOLFIRI with cetuximab in KRAS wild-type patients and liver-only metastases), of € 15 822 (FOLFOX with panitumumab in KRAS wild type) and of 13 383 € (FOLFOX with bevacizumab). According to the ESMO-MCBS the treatments including an EGFR-inhibitor (cetuximab or panitunumab) were associated with a score of 4 while the inclusion of bevacizumab reached a score of 3. The remaining phase III RCTs obtained a low (grade 1-2) score.Dividing the costs per month of PFS gained with the grade of ESMO-MCBS, for each RCTs, we obtained the costs of each point of ESMO-MCBS per month of PFS gained. FOLFOX was confirmed as being the least expensive (18.7 €) while among treatments including a targeted biological agent panitunumab in combination with FOLFOX in K-RAS wild type patients was less expensive (3955 €) than the combinations FOLFOX-bevacizumab (13 383 €) and FOLFIRI-cetuximab in K-RAS wild type patients (21 854.6 €). Conclusions: Our data demonstrate a huge difference in cost per month of PFS gained and per each point of the ESMO-MCBS in modern front line treatments in mCRC.