An integrated interpreting service normalizes access to care for culturally and linguistically diverse (CALD) patients with colorectal cancer

Aim

To compare access to the initial management and overall survival with colorectal cancer for limited English proficient (LEP) patients compared with patients from an English background.

Methods

All newly diagnosed patients from 2017 with colorectal cancer from a single health service with a highly multicultural catchment area and a well-developed and integrated translation and language support (TALS) department were recruited. Time from referral to: biopsy, date seen by a surgeon, oncologist, discussion at a multidisciplinary meeting (MDM), and day of commencement of the first treatment modality, and overall survival were analyzed.

Results

One hundred sixty-two patients were analyzed, including 57 LEP patients from 22 countries of birth. Interpreters were present at 687/782 appointments with LEP patients. There were no differences in demographics or cancer staging. There were no differences between English background and LEP patients with regard to times from referral to biopsy (1 vs. 0 days), specialist review (surgical: 4 vs. 6 days, oncological: 45 vs. 57 days), MDM discussion (23 vs. 15 days), or commencement of treatment (32 vs. 28.5 days). There were no differences in treatment for colorectal cancer, although a higher rate of stomas was noted in LEP patients. There was no difference in overall survival between groups.

Conclusion

Time to critical initial checkpoints and overall survival were similar in LEP and English background patients with colorectal cancer. An integrated TALS department may abrogate the language and cultural barriers that are known to disadvantage LEP patients and may contribute to normalizing care for the culturally and linguistically diverse community.     

Interventions to improve patient participation in the treatment process for culturally and linguistically diverse people with cancer: A systematic review

Disparities in cancer outcomes for people from culturally and linguistically diverse (CALD) groups are well known. Improving CALD patients' active participation in treatment processes holds potential to improve outcomes, but little is known of effective strategies to facilitate this. This systematic review investigated interventions to improve three aspects of participation in cancer care among CALD groups, namely involvement in decision‐making, communication with health providers and treatment adherence. A comprehensive search of electronic bibliographic databases was conducted to identify intervention studies that reported outcomes relevant to patient participation for CALD groups. Two reviewers independently critically appraised the studies and abstracted data. Of 10 278 potential articles, seven met the inclusion criteria, including three randomized controlled, three non‐randomized and one mixed‐method experimental studies. Interventions included the use of patient navigators, videos and decision aids. The impact on patient participation was varied. The effect of a decision aid and patient navigator interventions on communication with health providers was positive. While the use of a decisions aid successfully facilitated shared decision‐making and patients' perception of treatment adherence, the use of patient navigators was ineffective. A computer support system was found to improve general patient participation; however little clarification of what this involved was provided. This systematic review identified few rigorous evaluations of interventions to improve treatment participation for CALD people with cancer, highlighting the lack of a robust evidence base to improve this crucial aspect of care. The development and evaluation of interventions for diverse populations remains a priority.     

Differences in trial knowledge and motives for participation among cancer patients in phase 3 clinical trials

While participants in clinical oncology trials are essential for the advancement of cancer therapies, factors decisive for patient participation have been described but need further investigation, particularly in the case of phase 3 studies. The aim of this study was to investigate differences in trial knowledge and motives for participation in phase 3 clinical cancer trials in relation to gender, age, education levels and former trial experience. The results of a questionnaire returned from 88 of 96 patients (92%) were analysed using the Mann–Whitney U‐test. There were small, barely relevant differences in trial knowledge among patients when stratified by gender, age or education. Participants with former trial experience were less aware about the right to withdraw. Male participants and those aged ≥65 years were significantly more motivated by a feeling of duty, or by the opinions of close ones. Men seem more motivated than women by external factors. With the awareness that elderly and single male participants might be a vulnerable group and participants with former trial experience are less likely to be sufficiently informed, the information consent process should focus more on these patients. We conclude that the informed consent process seems to work well, with good results within most subgroups.     

Overcoming barriers to cancer clinical trial accrual: impact of a mass media campaign

BACKGROUND: Annually, only 3% of adult patients participate in cancer clinical trials (CCT). Accrual barriers include lack of CCT awareness and uncertain third-party coverage. In 2002, a California law (SB37) required all insurers to reimburse costs related to CCT. The objective of the current study was to increase awareness of CCT and SB37 through a mass multimedia campaign (MMC) in the University of California (UC) Davis (UCD) Cancer Center catchment area. The authors assessed willingness to participate in and accrual to CCT. METHODS: Changes in CCT/SB37 awareness and willingness to participate were investigated before the MMC versus after the MMC and in UCD respondents versus UC San Diego (UCSD) catchment respondents-a control group that was not exposed to the MMC-by Pearson chi-square and logistic regression analyses. RESULTS: Of 1081 post-MMC respondents, 957 were from UCD, and 124 from UCSD. UCD respondents had a greater awareness of CCT (59% vs 65%; P < .01) and SB37 (17% vs 32%; P < .01) compared with UCSD respondents. Willingness to participate did not change in either cohort. Awareness level predicted willingness (odds ratio, 2.3; P < .01). Blacks, Asians, and lowest income (<$25 K per year) groups were the least willing to participate (P < .01, P < .04, and P < .02, respectively). The CCT accrual rate at UCD was unchanged. CONCLUSIONS: CCT and SB37 awareness increased significantly in the UCD cohort after the MMC. However, it was unclear whether this increase was attributable entirely to the MMC or to varying demographic variables. Enhancing patient willingness and accrual will require targeting other variables, such as physician or resource barriers, rather than just CCT and reimbursement awareness.     

Systematic review of barriers and facilitators to clinical trial enrollment among adolescents and young adults with cancer: Identifying opportunities for intervention

Adolescents and young adults (AYAs) are underrepresented in cancer clinical trials (CCTs). Limited trial enrollment slows progress in improving survival rates and prevents the collection of valuable biospecimens. A systematic literature review was conducted to assess barriers and facilitators to AYA enrollment in CCTs and to identify opportunities to improve enrollment. The PubMed MEDLINE, Web of Science, Scopus, and PsycINFO databases were searched to identify studies relevant to AYA CCT enrollment. Eligibility criteria included the qualitative and/or quantitative evaluation of barriers and facilitators to AYA enrollment. One hundred fifty-five unique publications were identified; 13 were included in the final analysis. Barriers to AYA enrollment in CCTs included a lack of existing trials applicable to the patient population, limited access to available CCTs, and a lack of physician awareness of relevant trials. Facilitators of enrollment included optimizing the research infrastructure, improving the awareness of available CCTs among providers, and enhancing communication about CCTs between providers and patients. In conclusion, the limited available research reports institution- and patient-level barriers and facilitators to AYA CCT enrollment. Because of persistent disparities in AYA enrollment, there is an urgent need to further identify the barriers and facilitators to AYA CCT enrollment to determine actionable areas for intervention.     

Attitudes, knowledge and barriers to participation in cancer clinical trials among rural and remote patients

Aim: To assess the knowledge of randomized clinical trials and willingness and barriers to participation among rural, remote and regional cancer patients of North Queensland. Methods: A survey was conducted in medical oncology outpatient clinics at the Townsville and Mt Isa hospitals on patients, following their informed consent, using questionnaires. Rurality was defined according to the rural remote and metropolitan area classification. Results: Of the 180 patients approached, 178 participated. The median distance to the regional trial center for rural participants was 180 km (range 80–1300 km). 45.4% lived in rural or remote areas and the rest lived in Townsville, a regional metropolitan center. Their overall knowledge was low, with a median knowledge score of 3 (inter‐quartile ranges n = 2.5). For randomized controlled trials there were no significant relationships between willingness to participate and rurality or education level (P = 0.981). Cost of travel (41.1% rural or remote; 23.5% regional; P < 0.001) and the need for family or friends to accompany them (38.9% rural or remote; 24.1% regional, P = 0.021) were more important for rural/remote than regional patients as factors affecting participation. Conclusion: Rural and remote patients are as interested in participating in randomized clinical trials as regional patients. Their knowledge of trials is poor and education earlier in the consultations is needed. Since cost of travel and the need for family members to accompany them are important for rural patients trial budgets should include the cost of travel to encourage participation.     

Clinical trial spots for cancer patients by tumour type: The cancer trials portfolio at clinicaltrials.gov

BackgroundAlthough participation in cancer clinical trials is low, little is known about the number of available clinical trials, and open spots for patients. Moreover, it is unclear what the relationship is between clinical trial openings and the incidence and mortality of cancer subtypes.MethodologyWe identified the number of phase I, phase II and phase III registered at clinicaltrials.gov by cancer (tumour) type. All counts were over the preceding 5 years (2008–2013). We compared these counts against the incidence and prevalence of disease reported by Surveillance, Epidemiology and End Results (SEER) database for 32 common cancers.ResultsFrom 2008 to 2013, 3879 phase I trials, 4982 phase II trials and 1379 phase III trials concerning a cancer subtype were registered in clinicaltrials.gov. These trials had a cumulative proposed recruitment of 203,396, 421,502 and 697,787 patients, respectively. Trial enrolment varied by tumour type, with both over and under-representation occurring.ConclusionOpportunities to enrol in clinical trials vary by phase and tumour type. Oncologists must remain committed to clinical trials.     

Challenges in the recruitment of adolescents and young adults to cancer clinical trials

The adolescent and young adult (AYA) oncology population has seen inferior progress in cancer survival compared with younger children and older adults over the past 25 years. Previously, AYAs had the best survival rates due to the prevalence of highly curable diseases including Hodgkin lymphoma and germ cell tumors, yet today AYAs have inferior survival rates to children and some adult cohorts. Survival rates are particularly poor for AYA-specific diseases such as sarcomas. Research involving children and adults diagnosed with common malignancies such as acute lymphoblastic leukemia has resulted in improved survival rates. However, AYAs have not directly benefited from such research due to low rates of access to and accrual on clinical trials. AYAs are less likely to have insurance or access to healthcare, are more likely to see providers who are not part of research institutions, and are less likely to be referred to or to join clinical trials, all of which may contribute to worse outcomes. Few clinical trials target AYA-specific diseases, leading to little information regarding how these diseases behave and what role the host plays. Tumor samples for this population are underrepresented in national tumor banks. Coupled with the need for more clinical trials that focus on AYA-specific cancers, better collaboration between adult and pediatric cooperative groups as well as increased education among community oncologists and primary care providers will be needed to enhance participation in clinical trials with the goal to increase survival and improve quality of that survival.     

Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients

Background

Our previous individual patient data (IPD) meta-analysis showed that chemotherapy improved survival in patients curatively treated for non-metastatic head and neck squamous cell carcinoma (HNSCC), with a higher benefit with concomitant chemotherapy. However the heterogeneity of the results limited the conclusions and prompted us to confirm the results on a more complete database by adding the randomised trials conducted between 1994 and 2000.

Methods

The updated IPD meta-analysis included trials comparing loco-regional treatment to loco-regional treatment + chemotherapy in HNSCC patients and conducted between 1965 and 2000. The log-rank-test, stratified by trial, was used to compare treatments. The hazard ratios of death were calculated.

Results

Twenty-four new trials, most of them of concomitant chemotherapy, were included with a total of 87 trials and 16,485 patients. The hazard ratio of death was 0.88 (p < 0.0001) with an absolute benefit for chemotherapy of 4.5% at 5 years, and a significant interaction (p < 0.0001) between chemotherapy timing (adjuvant, induction or concomitant) and treatment. Both direct (6 trials) and indirect comparisons showed a more pronounced benefit of the concomitant chemotherapy as compared to induction chemotherapy. For the 50 concomitant trials, the hazard ratio was 0.81 (p < 0.0001) and the absolute benefit 6.5% at 5 years. There was a decreasing effect of chemotherapy with age (p = 0.003, test for trend).

Conclusion

The benefit of concomitant chemotherapy was confirmed and was greater than the benefit of induction chemotherapy.     

Leukocytosis and neutrophilia as independent prognostic immunological biomarkers for clinical outcome in the CAO/ARO/AIO-04 randomized phase 3 rectal cancer trial

Peripheral blood leukocytosis and neutrophilia reflect cancer inflammation and have been proposed as prognostic immunological biomarkers in various malignancies. However, previous studies were limited by their retrospective nature and small patient numbers. Baseline peripheral blood leukocytes, neutrophils, hemoglobin, platelets, lactate dehydrogenase and carcinoembryonic antigen (CEA) were correlated with clinicopathologic characteristics, and clinical outcome in 1236 patients with rectal cancer treated with 5-FU-based preoperative chemoradiotherapy (CRT) alone or with oxaliplatin followed by surgery and adjuvant chemotherapy within the CAO/ARO/AIO-04 randomized phase 3 trial. Multivariable analyses were performed using Cox regression models. After a median follow-up of 50 months, baseline leukocytosis remained an independent adverse prognostic factor for disease-free survival (DFS; HR 1.457; 95% CI 1.163–1.825; p = 0.001), distant metastasis (HR 1.696; 95% CI 1.266–2.273; p < 0.001) and overall survival (OS; HR 1.716; 95% CI 1.264–2.329; p = 0.001) in multivariable analysis. Similar significant findings were observed for neutrophilia and high CEA levels. Conversely, treatment-induced leukopenia correlated with favorable DFS (p = 0.037), distant metastasis (p = 0.028) and OS (p = 0.012). Intriguingly, addition of oxaliplatin to 5-FU CRT resulted in a significant DFS improvement only in patients with neutrophilia and leukocytosis (p = 0.028 and p = 0.002). Our findings have important clinical implications and provide high-level evidence on the adverse prognostic role of leukocytes and neutrophils, and the impact of chemotherapy in the context of these biomarkers. These data could help guide patient stratification and should be further validated within prospective studies.     

An individual patient data meta-analysis of adjuvant therapy with uracil-tegafur (UFT) in patients with curatively resected rectal cancer

Uracil-Tegafur (UFT), an oral fluorinated pyrimidine chemotherapeutic agent, has been used for adjuvant chemotherapy in curatively resected colorectal cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with rectal cancer. The objective of this study was to perform a reappraisal of randomised clinical trials conducted in this field. We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of UFT for curatively resected rectal cancer in terms of overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS). We analysed individual patient data of five adjuvant therapy randomised clinical trials for rectal cancer, which met the predetermined inclusion criteria. These five trials had a combined total of 2091 patients, UFT as adjuvant chemotherapy compared to surgery-alone, 5-year follow-up, intention-to-treat-based analytic strategy, and similar endpoints (OS and DFS). In a pooled analysis, UFT had significant advantage over surgery-alone in terms of both OS (hazard ratio, 0.82; 95% confidence interval (CI), 0.70-0.97; P=0.02) and DFS (hazard ratio, 0.73; 95%CI, 0.63-0.84; P<0.0001). This individual patient-based meta-analysis demonstrated that oral UFT significantly improves both OS and DFS in patients with curatively resected rectal cancer.     

A randomised controlled trial of forward-planned radiotherapy (IMRT) for early breast cancer: Baseline characteristics and dosimetry results

Background and purpose

This large trial was designed to investigate whether correction of dose inhomogeneities using intensity-modulated radiotherapy (IMRT) reduces late toxicity and improves quality of life in patients with early breast cancer. This paper reports baseline characteristics of trial participants and dosimetry results.

Materials and methods

Standard tangential plans of 1145 trials were analysed. Patients with inhomogeneous plans, defined by ICRU recommendations, were randomised to forward-planned IMRT or standard radiotherapy.

Results

Twenty-nine percentage of patients had adequate dosimetry with standard 2D radiotherapy. In the randomised patients, the decreases in mean volumes receiving greater than 107% (Vol > 107) and less than 95% (Vol < 95) of the prescribed dose in the IMRT compared with the control group were 34.0 cm³ (95% CI 26.4-41.6; P < 0.0001) and 48.1 cm³ (95% CI 34.4-61.9; P < 0.0001), respectively. In this study, 90% of patients who had a breast separation greater ?21 cm had Vol > 107 > 2 cm³ on standard radiotherapy plans.

Conclusion

This large trial, in which patients with all breast sizes were eligible, confirmed that breast dosimetry can be significantly improved with a simple method of forward-planned IMRT and has little impact on radiotherapy resources. It is shown that patients with larger breasts are more likely to have dose inhomogeneities and breast separation gives some indication of this likelihood. Photographic assessment of patients at 2 years after radiotherapy, as the next part of this randomised controlled trial, will show whether these results for IMRT translate into improved cosmetic outcome in patients with early breast cancer. This would provide impetus for the widespread adoption of 3D planning and IMRT.     

Value of a molecular screening program to support clinical trial enrollment in Asian cancer patients: The Integrated Molecular Analysis of Cancer (IMAC) Study

The value of precision oncology initiatives in Asian contexts remains unresolved. Here, we review the institutional implementation of prospective molecular screening to facilitate accrual of patients into biomarker‐driven clinical trials, and to explore the mutational landscape of advanced tumors occurring in a prospective cohort of Asian patients (n = 396) with diverse cancer types. Next‐generation sequencing (NGS) and routine clinicopathological assays, such as immunohistochemistry, copy number analysis and in situ hybridization tests, were performed on tumor samples. Actionable biomarker results were used to identify eligibility for early‐phase, biomarker‐driven clinical trials. Overall, NGS was successful in 365 of 396 patients (92%), achieving a mean depth of 1,943× and coverage uniformity of 96%. The median turnaround time from sample receipt to return of genomic results was 26.0 days (IQR, 19.0–39.0 days). Reportable mutations were found in 300 of 365 patients (82%). Ninety‐one percent of patients at study enrollment indicated consent to receive incidental findings and willingness to undergo genetic counseling if required. The most commonly mutated oncogenes included KRAS (19%), PIK3CA (16%), EGFR (5%), BRAF (3%) and KIT (3%); while the most frequently mutated tumor suppressor genes included TP53 (40%), SMARCB1 (12%), APC (8%), PTEN (6%) and SMAD4 (5%). Among 23 patients enrolled in genotype‐matched trials, median progression‐free survival was 2.9 months (IQR, 1.5–4.0 months). Nine of 20 evaluable patients (45%; 95% CI, 23.1–68.5%) derived clinical benefit, including 3 partial responses and 6 with stable disease lasting ≥ 8 weeks.