A study demonstrating users' preference for the adapted-REQUITE patient-reported outcome questionnaire over PRO-CTCAE® in patients with lung cancer.

Introduction: The use of patient-reported outcomes (PROs) has been shown to enhance the accuracy of symptom collection and improve overall survival and quality of life. This is the first study comparing concordance and patient preference for two PRO tools: Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) and the adapted-REQUITE Lung Questionnaire. Materials and Methods: Patients with lung cancer were recruited to the study while attending outpatient clinics at a tertiary cancer centre. Clinician-reported outcomes were generated through initial patient assessment with CTCAE v4.03. Participants then completed the PRO-CTCAE® and adapted-REQUITE questionnaires. Concordance between the 2 questionnaires was assessed by calculating Pearson correlation coefficient. PRO-CTCAE® and CTCAE concordance was demonstrated by calculating Pearson correlation coefficient from the linear predictors of an ordinal logistic regression. P-values were also calculated. Results: Out of 74 patients approached, 65 provided written informed consent to participate in the study. 63 (96.9%) patients completed both PRO-CTCAE® and adapted-REQUITE questionnaires. Pearson correlation coefficient between PRO tools was 0.8-0.83 (p <.001). Correlation between CTCAE and PRO-CTCAE® ranged between 0.66-0.82 (p <.001). Adapted-REQUITE and CTCAE correlation was higher for all symptoms ranging between 0.79-0.91 (p <.001). Acceptable discrepancies within one grade were present in 96.8%-100% of symptom domains for REQUITE and in 92.1%-96.8% for all domains in the PRO-CTCAE®. 54% of the total participant cohort favored the adapted-REQUITE questionnaire due to reduced subjectivity in the questions and ease of use. Conclusion: The adapted-REQUITE questionnaire has shown a superior correlation to clinician-reported outcomes and higher patient preference than the PRO-CTCAE®. The results of this study suggest the use of the REQUITE questionnaire for patients with lung cancer in routine clinical practice.

Service Evaluation of MyChristie-MyHealth, an Electronic Patient-Reported Outcome Measure Integrated Into Clinical Cancer Care.

PURPOSE: Electronic patient-reported outcome measures (ePROMs) are digitalized health questionnaires used to gauge patients' subjective experience of health and disease. They are becoming prevalent in cancer care and have been linked to a host of benefits including improved survival. MyChristie-MyHealth is the ePROM established at the Christie NHS Foundation Trust in 2019. We conducted an evaluation of this service to understand user experiences, as well as strategies to improve its functioning. METHODS: Data collection: Patients who had opted never to complete MyChristie-MyHealth (n = 87), and those who had completed at least one (n = 87) were identified. Demographic data included age, sex, ethnicity, postcode, diagnosis, treatment intent, and trial status. Semistructured interviews were held with noncompleters (n = 30) and completers (n = 31) of MyChristie-MyHealth, as well as clinician users (n = 6), covering themes such as accessibility, acceptability and usefulness, and open discourse on ways in which the service could be improved. RESULTS: Noncompleters of MyChristie-MyHealth were older (median age 72 v 66 years, P = .005), receiving treatment with curative rather than palliative intent (odds ratio [OR], 1.45; P = .045), and less likely to be enrolled on a clinical trial (OR, 0.531; P = .011). They were less likely to own a smartphone (33% v 97%) or have reliable Internet access (45% v 100%). Satisfaction with MyChristie-MyHealth was high in both groups: 93% (n = 29) of completers and 87% (n = 26) noncompleters felt generally happy to complete. Completers of MyChristie-MyHealth wanted their results to be acknowledged by their clinicians. Clinicians wanted results to be displayed in a more user-friendly way. CONCLUSION: We have broadly characterized noncompleters of the Christie ePROM to identify those in need of extra support or encouragement in the clinic. An action plan resulting from this review has been compiled and will inform the future development of MyChristie-MyHealth.

Exploring the Advantages and Challenges of MR-Guided Radiotherapy in Non-Small-Cell Lung Cancer: Who are the Optimal Candidates?

The landscape of lung radiotherapy (RT) has rapidly evolved over the past decade with modern RT and surgical techniques, systemic therapies, and expanding indications for RT. To date, 2 MRI-guided RT (MRgRT) units, 1 using a 0.35T magnet and 1 using a 1.5T magnet, are available for commercial use with more systems in the pipeline. MRgRT offers distinct advantages such as real-time target tracking, margin reduction, and on-table treatment adaptation, which may help overcome many of the common challenges associated with thoracic RT. Nonetheless, the use of MRI for image guidance and the current MRgRT units also have intrinsic limitations. In this review article, we will discuss clinical experiences to date, advantages, challenges, and future directions of MRgRT to the lung.

Patient and clinician-reported experiences of using electronic patient reported outcome measures (ePROMs) as part of routine cancer care.

BACKGROUND: Cancer and its treatment can have significant impacts on health status, quality of life and functioning of patients. Direct information from patients regarding these aspects can be collected via electronic platforms in the form of electronic Patient Reported Outcome Measures (ePROMs). Research has shown that the use of ePROMS in cancer care leads to improved communication, better symptom control, prolonged survival and a reduction in hospital admissions and emergency department attendance. Acceptability and feasibility of routine ePROM collection has been reported by both patients and clinicians but to date their use has predominantly been limited to clinical trials. MyChristie-MyHealth is an initiative from a UK comprehensive cancer centre The Christie NHS Foundation Trust which incorporates the regular collection of ePROMs into routine cancer care. This study, carried out as part of a service evaluation, explores patient and clinician experiences of using the MyChristie-MyHealth ePROMs service. RESULTS: 100 patients with lung and head and neck cancers completed a Patient Reported Experience questionnaire. All patients reported that MyChristie-MyHealth was easy to understand and, almost all found it timely to complete and easy to follow. Most patients (82%) reported it improved their communication with their oncology team and helped them to feel more involved with their care (88%). A large proportion of clinicians (8/11) felt ePROMs helped communication with their patients and over half (6/10) felt they led to consultations being more patient focused. Clinicians also felt that the use of ePROMs resulted in patients being more engaged in consultations (7/11) and their cancer care in general (5/11). Five clinicians reported that the use of ePROMs altered their clinical decision making. CONCLUSIONS: Regular ePROMs collection as part of routine cancer care is acceptable to both patients and clinicians. Both patients and clinicians feel their use improved communication and increased the feeling of patient involvement with their care. Further work is needed to explore the experiences of patients that did not complete the ePROMs as part of the initiative and to continue to optimize the service for both patients and clinicians.

Experience With the Routine Use of Electronic Patient-Reported Outcome Measures for Patients With Lung Cancer.

PURPOSE: The Christie NHS Foundation Trust launched their electronic patient-reported outcome measures (ePROMs) service in January 2019 in the routine clinical setting. The lung cancer questionnaires consist of 14 symptom items, adapted from the Common Terminology Criteria for Adverse Events (version 5.0) and the EuroQol EQ-5D-5L quality-of-life (QoL) tool. Patients with lung cancer are invited to complete questionnaires assessing their symptoms and QoL using an online platform. METHODS: The ePROM responses and clinical, pathologic, and treatment data for patients who completed the questionnaires between January 2019 and December 2020 were extracted from electronic medical records. The symptom and QoL scores of patients who completed baseline pretreatment ePROMs and also those who completed ePROMs pre- and postpalliative lung systemic anticancer therapy (SACT) or radical thoracic radiotherapy were evaluated. Pretreatment questionnaires were analyzed according to age, Eastern Cooperative Oncology Group performance status (ECOG PS), and Adult Comorbidity Evaluation-27 (ACE-27) comorbidity score. RESULTS: One thousand four hundred eighty patients with lung cancer were included. There were no statistically significant differences in symptoms and QoL scores between age groups. Cough (P = .006) and EQ-5D-5L mobility scores (P = .006) were significantly worse for patients with an ECOG PS of 0-1. Dyspnea (P = .035), hemoptysis (P = .023), nausea (P = .041), mobility (P = .004), and self-care (P = .0420) were significantly worse for those with higher ACE-27 scores (2-3 v 0-1). Palliative SACT was associated with a significant improvement in cough (P < .001) and hemoptysis (P = .025), but significantly negatively affected mobility (P = .013). Patients receiving radical thoracic radiotherapy reported a significant improvement in hemoptysis (P = .042) but worse pain (P = .002) and fatigue (P = .01). Other changes in symptom and QoL scores were not significant. CONCLUSION: The symptoms and QoL reported at baseline and before and after both palliative SACT and radical thoracic radiotherapy are clinically relevant and meaningful. We have demonstrated that routine implementation of ePROMs into clinical practice is feasible and can inform clinical practice and future research.

Impact of Introducing Intensity Modulated Radiotherapy on Curative Intent Radiotherapy and Survival for Lung Cancer.

Background: Lung cancer survival remains poor. The introduction of Intensity-Modulated Radiotherapy (IMRT) allows treatment of more complex tumours as it improves conformity around the tumour and greater normal tissue sparing. However, there is limited evidence assessing the clinical impact of IMRT. In this study, we evaluated whether the introduction of IMRT had an influence on the proportion of patients treated with curative-intent radiotherapy over time, and whether this had an effect on patient survival. Materials and Methods: Patients treated with thoracic radiotherapy at our institute between 2005 and 2020 were retrospectively identified and grouped into three time periods: A) 2005-2008 (pre-IMRT), B) 2009-2012 (selective use of IMRT), and C) 2013-2020 (full access to IMRT). Data on performance status (PS), stage, age, gross tumour volume (GTV), planning target volume (PTV) and survival were collected. The proportion of patients treated with a curative dose between these periods was compared. Multivariable survival models were fitted to evaluate the hazard for patients treated in each time period, adjusting for PS, stage, age and tumour volume. Results: 12,499 patients were included in the analysis (n=2675 (A), n=3127 (B), and n=6697 (C)). The proportion of patients treated with curative-intent radiotherapy increased between the 3 time periods, from 38.1% to 50.2% to 65.6% (p<0.001). When stage IV patients were excluded, this increased to 40.1% to 58.1% to 82.9% (p<0.001). This trend was seen across all PS and stages. The GTV size increased across the time periods and PTV size decreased. Patients treated with curative-intent during period C had a survival improvement compared to time period A when adjusting for clinical variables (HR=0.725 (0.632-0.831), p<0.001). Conclusion: IMRT was associated with to more patients receiving curative-intent radiotherapy. In addition, it facilitated the treatment of larger tumours that historically would have been treated palliatively. Despite treating larger, more complex tumours with curative-intent, a survival benefit was seen for patients treated when full access to IMRT was available (2013-2020). This study highlights the impact of IMRT on thoracic oncology practice, accepting that improved survival may also be attributed to a number of other contributing factors, including improvements in staging, other technological radiotherapy advances and changes to systemic treatment.

Switchable Induced-Transmission Filters Enabled by Vanadium Dioxide.

An induced-transmission filter (ITF) uses an ultrathin metallic layer positioned at an electric-field node within a dielectric thin-film bandpass filter to select one transmission band while suppressing other bands that would have been present without the metal layer. We introduce a switchable mid-infrared ITF where the metal can be "switched on and off", enabling the modulation of the filter response from a single band to multiband. The switching is enabled by the reversible insulator-to-metal phase transition of a subwavelength film of vanadium dioxide (VO2). Our work generalizes the ITF─a niche type of bandpass filter─into a new class of tunable devices. Furthermore, our fabrication process─which begins with thin-film VO2 on a suspended membrane─enables the integration of VO2 into any thin-film assembly that is compatible with physical vapor deposition processes and is thus a new platform for realizing tunable thin-film filters.

Outcomes of curative-intent radiotherapy in non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD).

Outcomes of non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD n = 587) and interstitial lung disease (ILD n = 34) treated with curative-intent radiotherapy were retrospectively investigated. Presence of ILD but not decreased forced expiratory volume in 1-second correlated with poor overall survival. Increased breathlessness and oxygen requirements after radiotherapy were observed in severe/very severe COPD and ILD.

Comparison of Whole-Body MRI, CT, and Bone Scintigraphy for Response Evaluation of Cancer Therapeutics in Metastatic Breast Cancer to Bone.

Background CT and bone scintigraphy have limitations in evaluating systemic anticancer therapy (SACT) response in bone metastases from metastatic breast cancer (MBC). Purpose To evaluate whether whole-body MRI enables identification of progressive disease (PD) earlier than CT and bone scintigraphy in bone-only MBC. Materials and Methods This prospective study evaluated participants with bone-only MBC between May 2016 and January 2019 (ClinicalTrials.gov identifier: NCT03266744). Participants were enrolled at initiation of first or subsequent SACT based on standard CT and bone scintigraphy imaging. Baseline whole-body MRI was performed within 2 weeks of entry; those with extraosseous disease were excluded. CT and whole-body MRI were performed every 12 weeks until definitive PD was evident with one or both modalities. In case of PD, bone scintigraphy was used to assess for bone disease progression. Radiologists independently interpreted images from CT, whole-body MRI, or bone scintigraphy and were blinded to results with the other modalities. Systematic differences in performance between modalities were analyzed by using the McNemar test. Results Forty-five participants (mean age, 60 years ± 13 [standard deviation]; all women) were evaluated. Median time on study was 36 weeks (range, 1-120 weeks). Two participants were excluded because of unequivocal evidence of liver metastases at baseline whole-body MRI, two participants were excluded because they had clinical progression before imaging showed PD, and one participant was lost to follow-up. Of the 33 participants with PD at imaging, 67% (22 participants) had PD evident at whole-body MRI only and 33% (11 participants) had PD at CT and whole-body MRI concurrently; none had PD at CT only (P < .001, McNemar test). There was only slight agreement between whole-body MRI and CT (Cohen κ, 0.15). PD at bone scintigraphy was reported in 50% of participants (13 of 26) with bone progression at CT and/or whole-body MRI (P < .001, McNemar test). Conclusion Whole-body MRI enabled identification of progressive disease before CT in most participants with bone-only metastatic breast cancer. Progressive disease at bone scintigraphy was evident in only half of participants with bone progression at whole-body MRI. © RSNA, 2020 Online supplemental material is available for this article.

Revised estimates of ocean-atmosphere CO2 flux are consistent with ocean carbon inventory.

The ocean is a sink for ~25% of the atmospheric CO2 emitted by human activities, an amount in excess of 2 petagrams of carbon per year (PgC yr-1). Time-resolved estimates of global ocean-atmosphere CO2 flux provide an important constraint on the global carbon budget. However, previous estimates of this flux, derived from surface ocean CO2 concentrations, have not corrected the data for temperature gradients between the surface and sampling at a few meters depth, or for the effect of the cool ocean surface skin. Here we calculate a time history of ocean-atmosphere CO2 fluxes from 1992 to 2018, corrected for these effects. These increase the calculated net flux into the oceans by 0.8-0.9 PgC yr-1, at times doubling uncorrected values. We estimate uncertainties using multiple interpolation methods, finding convergent results for fluxes globally after 2000, or over the Northern Hemisphere throughout the period. Our corrections reconcile surface uptake with independent estimates of the increase in ocean CO2 inventory, and suggest most ocean models underestimate uptake.

Assessment of the Spatial Heterogeneity of Breast Cancers: Associations Between Computed Tomography and Immunohistochemistry.

BACKGROUND: Tumour heterogeneity is considered an important mechanism of treatment failure. Imaging-based assessment of tumour heterogeneity is showing promise but the relationship between these mathematically derived measures and accepted 'gold standards' of tumour biology such as immunohistochemical measures is not established. METHODS: A total of 20 women with primary breast cancer underwent a research dynamic contrast-enhanced computed tomography prior to treatment with data being available for 15 of these. Texture analysis was performed of the primary tumours to extract 13 locoregional and global parameters. Immunohistochemical analysis associations were assessed by the Spearman rank correlation. RESULTS: Hypoxia-inducible factor-1α was correlated with first-order kurtosis (r = -0.533, P = .041) and higher order neighbourhood grey-tone difference matrix coarseness (r = 0.54, P = .038). Vascular maturity-related smooth muscle actin was correlated with higher order grey-level run-length long-run emphasis (r = -0.52, P = .047), fractal dimension (r = 0.613, P = .015), and lacunarity (r = -0.634, P = .011). Micro-vessel density, reflecting angiogenesis, was also associated with lacunarity (r = 0.547, P = .035). CONCLUSIONS: The associations suggest a biological basis for these image-based heterogeneity features and support the use of imaging, already part of standard care, for assessing intratumoural heterogeneity.

Radiotherapy in the control of bleeding from primary and secondary lung tumours.

This literature review clarifies the role of radiotherapy in the management of low-volume haemoptysis. Embase and Medline were interrogated, and PRISMA guidelines were then used to select relevant articles. Seventy-eight articles were considered relevant and manually reviewed. The evidence suggests that external beam radiotherapy is more effective than endobronchial brachytherapy at controlling low-volume haemoptysis. There is no evidence to recommend a combination of the two techniques. Different doses and fractionations appear equally effective, with a potential survival advantage of higher dose regimens for fitter patients. Palliative radiotherapy is effective at controlling low-volume haemoptysis. External beam radiotherapy is the first-line treatment, with endobronchial brachytherapy recommended following external beam radiotherapy failure. Choice of dose and fractionation should take into account the patient's performance status.

Asymmetric transfer of CO2 across a broken sea surface.

Most estimates of the climatically-important transfer of atmospheric gases into, and out of, the ocean assume that the ocean surface is unbroken by breaking waves. However the trapping of bubbles of atmospheric gases in the ocean by breaking waves introduces an asymmetry in this flux. This asymmetry occurs as a bias towards injecting gas into the ocean where it dissolves, and against the evasion/exsolution of previously-dissolved gas coming out of solution from the oceans and eventually reaching the atmosphere. Here we use at-sea measurements and modelling of the bubble clouds beneath the ocean surface to show that the numbers of large bubbles found metres below the sea surface in high winds are sufficient to drive a large and asymmetric flux of carbon dioxide. Our results imply a much larger asymmetry for carbon dioxide than previously proposed. This asymmetry contradicts an assumption inherent in most existing estimates of ocean-atmosphere gas transfer. The geochemical and climate implications include an enhanced invasion of carbon dioxide into the stormy temperate and polar seas.

Is heterogeneity in stage 3 non-small cell lung cancer obscuring the potential benefits of dose-escalated concurrent chemo-radiotherapy in clinical trials?

The current standard of care for the management of inoperable stage 3 non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (cCRT) using radiotherapy dose-fractionation and chemotherapy regimens that were established 3 decades ago. In an attempt to improve the chances of long-term control from cCRT, dose-escalation of the radiotherapy dose was assessed in the RTOG 0617 randomised control study comparing the standard 60 Gy in 30 fractions with a high-dose arm receiving 74 Gy in 37 fractions. Following the publication of this trial the thoracic oncology community were surprised to learn that there was worse survival in the dose-escalated arm and that for now the standard of care must remain with the lower dose. In this article we review the RTOG 0617 paper with subsequent analyses and studies to explore why the use of dose-escalated cCRT in stage 3 NSCLC has not shown the benefits that were expected. The overarching theme of this opinion piece is how heterogeneity between stage 3 NSCLC cases in terms of patient, tumour, and clinical factors may obscure the potential benefits of dose-escalation by causing imbalances in the arms of studies such as RTOG 0617. We also examine recent advances in the staging, management, and technological delivery of radiotherapy in NSCLC and how these may be employed to optimise cCRT trials in the future and ensure that any potential benefits of dose-escalation can be detected.

The use of volunteers to implement electronic patient reported outcomes in lung cancer outpatient clinics.

BACKGROUND: Treatment related toxicity is common after chemotherapy and radiotherapy. Our group has developed and validated an electronic Patient Reported Outcome questionnaire (ePRO) to assess symptoms and toxicity in lung cancer patients receiving (chemo)radiotherapy treatment. We assessed the need for volunteer support in clinics to assist patients in completing ePROs. METHODS: Lung Cancer patients attending outpatient or radiotherapy clinics at The Christie NHS Foundation Trust, Manchester were consented and asked to complete a Patient Reported Outcomes questionnaire using an electronic device (a touchscreen). Trained volunteers were available if patients required help such as verbal or physical assistance. The primary objective was to determine the need for volunteers to assist lung cancer patients in completing ePROs. RESULTS: 27/86 (31.4%) of patients who consented to this study required assistance to complete the ePRO. After questioning, we found that only 7/86 (8.1%) would have relied on volunteers for assistance as the majority of patients had a companion that could have provided help. 81/86 (94.2%) of patients were satisfied with the use of a touchscreen tablet to complete the ePRO. CONCLUSION: Our results demonstrate that the introduction of ePROs in lung cancer outpatient clinics is feasible, even without the use of volunteers for the majority of patients. The implementation of ePROs would allow large volumes of high quality (chemo)radiotherapy toxicity data to be collected accurately and quickly. This is essential for the development of predictive models of outcome using population-based data, which could allow the personalisation of (chemo)radiotherapy treatment for lung cancer patients.

The addition of whole-body magnetic resonance imaging to body computerised tomography alters treatment decisions in patients with metastatic breast cancer.

AIM: Accurate evaluation of distribution of disease and response to systemic anti-cancer therapy (SACT) is important in the optimal management of metastatic breast cancer. Whole-body magnetic resonance imaging (WB-MRI) has increased accuracy over computerised tomography of the chest, abdomen and pelvis (CT-CAP) for detecting liver and bone disease, but its effect on patient management is largely unexplored. This study investigates the effects of using WB-MRI alongside CT-CAP on SACT decisions in standard clinical practice for patients with metastatic breast cancer. METHODS: Metastatic breast cancer patients who had undergone WB-MRI within 14 d of CT-CAP were studied. Data on distribution and extent of disease and SACT response assessment from original WB-MRI and CT-CAP reports were compared. Contemporaneous medical records provided data on therapy decisions at each time point. RESULTS: Analyses were performed on 210 pairs of WB-MRI and CT-CAP in 101 patients. In 53.3% of episodes, WB-MRI reported additional sites of disease not reported on CT-CAP. Differences in SACT assessment were found in 28.0% of episodes, most commonly due to progressive disease (PD) on WB-MRI being reported as stable disease on CT-CAP (18.9%). Discordant SACT assessments were less common in first-line SACT than in subsequent lines of SACT (15.0% versus 41.6%; p = 0.0102). In 34.7% of episodes when SACT was changed, PD had been reported on WB-MRI only. CONCLUSIONS: SACT decisions in routine practice were altered by the use of WB-MRI. Further research is required to investigate whether earlier identification of PD by WB-MRI leads to improved patient outcomes.

Splenic Enlargement and Bone Marrow Hyperplasia in Patients Receiving Trastuzumab-Emtansine for Metastatic Breast Cancer.

BACKGROUND: An association between trastuzumab-emtansine (T-DM1) and splenic enlargement is reported in preclinical data, and has been noted anecdotally in patients receiving T-DM1 at our institution. Use of whole-body MRI examinations (WB-MRI) allows for detailed bone marrow assessment and semi-automated splenic volume calculations. OBJECTIVE: To retrospectively evaluate changes in splenic volume versus evidence of bone marrow hyperplasia and/or changes in portal venous pressure in patients receiving T-DM1 for metastatic breast cancer. PATIENTS AND METHODS: Twelve metastatic breast cancer patients underwent 29 WB-MRIs before and during T-DM1 therapy. Splenic volume, portal vein diameter, bone marrow diffusion-weighted normalised signal intensity (nSI), quantitative water diffusivity (apparent diffusion coefficient, ADC) and fat fraction (rF%) were measured and correlated. RESULTS: Splenic volume increases were observed in 92% of patients. Mean splenic volume increased from 144 cm3 (95% CI 110-177 cm3) to 209 cm3 (95% CI 161-257 cm3) on T-DM1 therapy (p = 0.006). Splenic volume increases correlated with treatment duration (r2 = 0.43). Bone marrow hyperplasia was evidenced by an increase in bone marrow nSI (3.5 to 4.8, p = 0.12), and decreases in rF% (64.3% to 57.3%, p = 0.12) and ADC (655 µm2/s to 543 µm2/s, p = 0.11). No changes to portal vein diameter were seen. CONCLUSIONS: Previously unreported increases in splenic volume and bone marrow hyperplasia are observed on WB-MRI in patients on T-DM1 therapy. Caution must be applied to avoid misinterpreting T-DM1-induced bone marrow hyperplasia as diffuse disease progression in bone.

Arterial input functions in dynamic contrast-enhanced magnetic resonance imaging: which model performs best when assessing breast cancer response?

OBJECTIVE: To evaluate the performance of six models of population arterial input function (AIF) in the setting of primary breast cancer and neoadjuvant chemotherapy (NAC). The ability to fit patient dynamic contrast-enhanced MRI (DCE-MRI) data, provide physiological plausible data and detect pathological response was assessed. METHODS: Quantitative DCE-MRI parameters were calculated for 27 patients at baseline and after 2 cycles of NAC for 6 AIFs. Pathological complete response detection was compared with change in these parameters from a reproduction cohort of 12 patients using the Bland-Altman approach and receiver-operating characteristic analysis. RESULTS: There were fewer fit failures pre-NAC for all models, with the modified Fritz-Hansen having the fewest pre-NAC (3.6%) and post-NAC (18.8%), contrasting with the femoral artery AIF (19.4% and 43.3%, respectively). Median transfer constant values were greatest for the Weinmann function and also showed greatest reductions with treatment (-68%). Reproducibility (r) was the lowest for the Weinmann function (r = -49.7%), with other AIFs ranging from r = -27.8 to -39.2%. CONCLUSION: Using the best performing AIF is essential to maximize the utility of quantitative DCE-MRI parameters in predicting response to NAC treatment. Applying our criteria, the modified Fritz-Hansen and cosine bolus approximated Parker AIF models performed best. The Fritz-Hansen and biexponential approximated Parker AIFs performed less well, and the Weinmann and femoral artery AIFs are not recommended. ADVANCES IN KNOWLEDGE: We demonstrate that using the most appropriate AIF can aid successful prediction of response to NAC in breast cancer.