Designing clinical trials based on modern imaging and metastasis-directed treatments in patients with oligometastatic breast cancer: a consensus recommendation from the EORTC Imaging and Breast Cancer Groups.

Breast cancer remains the most common cause of cancer death among women. Despite its considerable histological and molecular heterogeneity, those characteristics are not distinguished in most definitions of oligometastatic disease and clinical trials of oligometastatic breast cancer. After an exhaustive review of the literature covering all aspects of oligometastatic breast cancer, 35 experts from the European Organisation for Research and Treatment of Cancer Imaging and Breast Cancer Groups elaborated a Delphi questionnaire aimed at offering consensus recommendations, including oligometastatic breast cancer definition, optimal diagnostic pathways, and clinical trials required to evaluate the effect of diagnostic imaging strategies and metastasis-directed therapies. The main recommendations are the introduction of modern imaging methods in metastatic screening for an earlier diagnosis of oligometastatic breast cancer and the development of prospective trials also considering the histological and molecular complexity of breast cancer. Strategies for the randomisation of imaging methods and therapeutic approaches in different subsets of patients are also addressed.

Quantification and reduction of cross-vendor variation in multicenter DWI MR imaging: results of the Cancer Core Europe imaging task force.

OBJECTIVES: In the Cancer Core Europe Consortium (CCE), standardized biomarkers are required for therapy monitoring oncologic multicenter clinical trials. Multiparametric functional MRI and particularly diffusion-weighted MRI offer evident advantages for noninvasive characterization of tumor viability compared to CT and RECIST. A quantification of the inter- and intraindividual variation occurring in this setting using different hardware is missing. In this study, the MRI protocol including DWI was standardized and the residual variability of measurement parameters quantified. METHODS: Phantom and volunteer measurements (single-shot T2w and DW-EPI) were performed at the seven CCE sites using the MR hardware produced by three different vendors. Repeated measurements were performed at the sites and across the sites including a traveling volunteer, comparing qualitative and quantitative ROI-based results including an explorative radiomics analysis. RESULTS: For DWI/ADC phantom measurements using a central post-processing algorithm, the maximum deviation could be decreased to 2%. However, there is no significant difference compared to a decentralized ADC value calculation at the respective MRI devices. In volunteers, the measurement variation in 2 repeated scans did not exceed 11% for ADC and is below 20% for single-shot T2w in systematic liver ROIs. The measurement variation between sites amounted to 20% for ADC and < 25% for single-shot T2w. Explorative radiomics classification experiments yield better results for ADC than for single-shot T2w. CONCLUSION: Harmonization of MR acquisition and post-processing parameters results in acceptable standard deviations for MR/DW imaging. MRI could be the tool in oncologic multicenter trials to overcome the limitations of RECIST-based response evaluation. KEY POINTS: • Harmonizing acquisition parameters and post-processing homogenization, standardized protocols result in acceptable standard deviations for multicenter MR-DWI studies. • Total measurement variation does not to exceed 11% for ADC in repeated measurements in repeated MR acquisitions, and below 20% for an identical volunteer travelling between sites. • Radiomic classification experiments were able to identify stable features allowing for reliable discrimination of different physiological tissue samples, even when using heterogeneous imaging data.

AZTEK: Adaptive zero TE k-space trajectories.

PURPOSE: Because of short signal lifetimes and respiratory motion, 3D lung MRI is still challenging today. Zero-TE (ZTE) pulse sequences offer promising solutions as they overcome the issue of short T2∗ . Nevertheless, as they rely on continuous readout gradients, the trajectories they follow in k-space are not adapted to retrospective gating and inferred motion correction. THEORY AND METHODS: We propose AZTEK (adaptive ZTE k-space trajectories), a set of 3D radial trajectories featuring three tuning parameters, to adapt the acquisition to any moving organ while keeping seamless transitions between consecutive spokes. Standard ZTE and AZTEK trajectories were compared for static and moving phantom acquisitions as well as for human thoracic imaging performed on 3 volunteers (1 healthy and 2 patients with lung cancer). RESULTS: For the static phantom, we observe comparable image qualities with standard and AZTEK trajectories. For the moving phantom, spatially coherent undersampling artifacts observed on gated images with the standard trajectory are alleviated with AZTEK. The same improvement in image quality is obtained in human, so details are more delineated in the lung with the use of the adaptive trajectory. CONCLUSION: The AZTEK technique opens the possibility for 3D dynamic ZTE lung imaging with retrospective gating. It enables us to uniformly sample the k-space for any arbitrary respiratory motion gate, while preserving static image quality, improving dynamic image quality and guaranteeing continuous readout gradient transitions between spokes, which makes it appropriate to ZTE.

Can MRI differentiate surrounding vertebral invasion from reactive inflammatory changes in superior sulcus tumor?

OBJECTIVES: Vertebral invasion is a key prognostic factor and a critical aspect of surgical planning for superior sulcus tumors. This study aims to further evaluate MRI features of vertebral invasion in order to distinguish it from reactive inflammatory changes. METHODS: Between 2000 and 2016, a retrospective study was performed at a single institution. All patients with superior sulcus tumors undergoing surgery, including at least two partial vertebrectomies, were included. An expert radiologist evaluated qualitative and quantitative MRI signal intensity characteristics (contrast-to-noise ratio [CNR]) of suspected involved and non-involved vertebrae. A comparison of CNR of invaded and sane vertebrae was performed using non-parametric tests. Imaging data were correlated with pathological findings. RESULTS: A total of 92 surgical samples of vertebrectomy were analyzed. The most specific sequences for invasion were T1 and T2 weighted (92% and 97%, respectively). The most sensitive sequences were contrast enhanced T1 weighted fat suppressed and T2 weighted fat suppressed (100% and 80%). Loss of extrapleural paravertebral fat on the T1-weighted sequence was highly sensitive (100%) but not specific (63%). Using quantitative analysis, the optimum cut-off (p < 0.05) to distinguish invasion from reactive inflammatory changes was CNR > 11 for the T2-weighted fat-sat sequence (sensitivity 100%), CNR > 9 for contrast-enhanced T1-weighted fat-suppressed sequence (sensitivity 100%), and CNR < - 30 for the T1-weighted sequence (specificity 97%). Combining these criteria, 23 partial vertebrectomies could have been avoided in our cohort. CONCLUSION: Qualitative and quantitative MRI analyses are useful to discriminate vertebral invasion from reactive inflammatory changes. KEY POINTS: • Abnormal signal intensity in a vertebral body adjacent to a superior sulcus tumor may be secondary to direct invasion or reactive inflammatory changes. • Accurate differentiation between invasion and reactive inflammatory changes significantly impacts surgical planning. T1w and T2w are the best sequences to differentiate malignant versus benign bone marrow changes. The use of quantitative analysis improves MRI specificity. • Using contrast media improves the sensitivity for the detection of tumor invasion.

Incorporating radiomics into clinical trials: expert consensus endorsed by the European Society of Radiology on considerations for data-driven compared to biologically driven quantitative biomarkers.

Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. KEY POINTS: • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.

Intratumoural immunotherapies for unresectable and metastatic melanoma: current status and future perspectives.

The emergence of human intratumoural immunotherapy (HIT-IT) is a major step forward in the management of unresectable melanoma. The direct injection of treatments into melanoma lesions can cause cell lysis and induce a local immune response, and might be associated with a systemic immune response. Directly injecting immunotherapies into tumours achieves a high local concentration of immunostimulatory agent while minimising systemic exposure and, as such, HIT-IT agents are associated with lower toxicity than systemic immune checkpoint inhibitors (CPIs), enabling their potential use in combination with other therapies. Consequently, multiple HIT-IT agents, including oncolytic viruses, pattern-recognition receptor agonists, injected CPIs, cytokines and immune glycolipids, are under investigation. This review considers the current clinical development status of HIT-IT agents as monotherapy and in combination with systemic CPIs, and the practical aspects of administering and assessing the response to these agents. The future of HIT-IT probably lies in its use in combination with systemic CPIs; data from Phase 2 trials indicate a synergy between HIT-IT and CPIs. Data also suggest that the addition of HIT-IT to a CPI might generate responses in CPI-refractory tumours, thereby overcoming resistance and addressing a current unmet need in unresectable and metastatic melanoma for treatment options following progression after CPI treatment.

Association of the prognostic model iSEND with PD-1/L1 monotherapy outcome in non-small-cell lung cancer.

BACKGROUND: Accessible biomarkers are needed for immunotherapy in advanced non-small-cell lung cancer (NSCLC). We previously described a multivariate risk prediction model, the iSEND, which categorises advanced NSCLC patients treated with nivolumab into Good, Intermediate or Poor groups. This model was developed by using only clinical and analytical variables (sex, ECOG-performance status, neutrophil-to-lymphocyte ratio [NLR] and post-treatment delta NLR). METHODS: An international database of 439 patients who received post-platinum PD-1/L1 monotherapies was collected for validation. Performance of the iSEND to different PD-L1 groups was compared by using time-dependent positive predictive value (PPV) for their mortality events. RESULTS: Median follow-up was 18.2 months (95% CI: 15.9-19.6). The overall survival of the iSEND Good (HR = 0.31, 95% CI: 0.22-0.43, p < 0.0001) was superior to the iSEND Poor. Time-dependent PPV for mortality of iSEND Poor was superior to PD-L1 = 0% group at 12 (75 vs. 53%, p = 0.01) and 18 months (85 vs. 46%, p = 0.03). However, female gender did not independently associate with better outcome in the validation cohort. CONCLUSION: The iSEND model is associated with the outcome of post-platinum PD-1/L1 monotherapy in advanced NSCLC patients. The iSEND Poor demonstrated a superior performance to PD-L1 = 0% in negative prognostication. Prospective investigation and modelling with other significant parameters in a larger cohort are warranted.

Baseline metabolic tumor burden on FDG PET/CT scans predicts outcome in advanced NSCLC patients treated with immune checkpoint inhibitors.

PURPOSE: We aimed to evaluate if imaging biomarkers on FDG PET are associated with clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). METHODS: In this retrospective monocentric study, we included 109 patients with advanced NSCLC who underwent baseline FDG PET/CT before ICI initiation between July 2013 and September 2018. Clinical, biological (including dNLR = neutrophils/[leukocytes minus neutrophils]), pathological and PET parameters (tumor SUVmax, total metabolic tumor volume [TMTV]) were evaluated. A multivariate prediction model was developed using Cox models for progression-free survival (PFS) and overall survival (OS). The association between biomarkers on FDG PET/CT and disease clinical benefit (DCB) was tested using logistic regression. RESULTS: Eighty patients were eligible. Median follow-up was 11.6 months (95%CI 7.7-15.5). Sixty-four and 52 patients experienced progression and death, respectively. DCB was 40%. In multivariate analyses, TMTV > 75 cm3 and dNLR > 3 were associated with shorter OS (HR 2.5, 95%CI 1.3-4.7 and HR 3.3, 95%CI 1.6-6.4) and absence of DCB (OR 0.3, 95%CI 0.1-0.9 and OR 0.4, 95%CI 0.2-0.9). Unlike TMTV, dNLR was a significant prognostic factor for PFS (HR 1.9, 95%CI 1.1-3.3) along with anemia (HR 1.9, 95%CI 1.2-3.8). No association was observed between tumor SUVmax and PFS or OS. CONCLUSION: Baseline tumor burden (TMTV) on FDG PET/CT scans and inflammatory status (dNLR) were associated with poor OS and absence of DCB for ICI treatment in advanced NSCLC patients, unlike tumor SUVmax, and may be used together to improve the selection of appropriate candidates.

Association of metastatic pattern and molecular status in stage IV non-small cell lung cancer adenocarcinoma.

OBJECTIVES: The aim of our study was to investigate the association between driver oncogene alterations and metastatic patterns on imaging assessment, in a large cohort of metastatic lung adenocarcinoma patients. METHODS: From January 2010 to May 2017, 550 patients with stage IV lung adenocarcinoma with molecular analysis were studied retrospectively including 135 EGFR-mutated, 81 ALK-rearrangement, 47 BRAF-mutated, 141 KRAS-mutated, and 146 negative tumors for these 4 mutations (4N). After review of the complete imaging report by two radiologists (junior and senior) to identify metastatic sites, univariate correlation analyzes were performed. RESULTS: We found differences in metastatic tropism depending on the molecular alteration type when compared with the non-mutated 4N group: in the EGFR group, pleural metastases were more frequent (32% versus 20%; p = 0.021), and adrenal and node metastases less common (6% versus 23%; p < 0.001 and 11% versus 23%; p = 0.011). In the ALK group, there were more brain and lung metastases (respectively 42% versus 29%; p = 0.043 and 37% versus 24%; p = 0.037). In the BRAF group, pleural and pericardial metastases were more common (respectively 47% versus 20%; p < 0.001 and 11% versus 3%; p = 0.04) and bone metastases were rarer (21% versus 42%; p = 0.011). Lymphangitis was more frequent in EGFR, ALK, and BRAF groups (respectively 6%, 7%, and 15% versus 1%); p = 0.016; p = 0.009; and p < 0.001. CONCLUSION: The application of these correlations between molecular status and metastatic tropism in clinical practice may lead to earlier and more accurate identification of patients for targeted therapy. KEY POINTS: • Bone and brain metastasis are the most common organs involved in lung adenocarcinoma but the relative incidence of each metastatic site depends on the molecular alteration. • EGFR-mutated tumors preferentially spread to the pleura and less commonly to adrenals, ALK-rearrangement tumors usually spread to the brain and the lungs, whereas BRAF-mutated tumors are unlikely to spread to bones and have a serous (pericardial ad pleural) tropism. • These correlations could help in the clinical management of patients with metastatic lung adenocarcinoma.

Postoperative hepatic arterial chemotherapy in high-risk patients as adjuvant treatment after resection of colorectal liver metastases - a randomized phase II/III trial - PACHA-01 (NCT02494973).

BACKGROUND: After curative-intent surgery for colorectal liver metastases (CRLM), liver recurrence occurs in more than 60% of patients, despite the administration of perioperative or adjuvant chemotherapy. This risk is even higher after resection of more than three CRLM. As CRLM are mostly supplied by arterial blood flow, hepatic arterial infusion (HAI) of chemotherapeutic agents after resection of CRLM is an attractive approach. Oxaliplatin-based HAI chemotherapy, in association with systemic fluoropyrimidines, has been shown to be safe and highly active in patients with CRLM. In a retrospective series of 98 patients at high risk of hepatic recurrence (≥4 resected CRLM), adjuvant HAI oxaliplatin combined with systemic chemotherapy was feasible and significantly improved disease-free survival compared to adjuvant, 'modern' systemic chemotherapy alone. METHODS/DESIGN: This study is designed as a multicentre, randomized, phase II/III trial. The first step is a non-comparative randomized phase II trial (power, 95%; one-sided alpha risk, 10%). Patients will be randomly assigned in a 1:1 ratio to adjuvant systemic FOLFOX (control arm) or adjuvant HAI oxaliplatin plus systemic LV5FU2 (experimental arm). A total 114 patients will need to be included. The main objective of this trial is to evaluate the potential survival benefit of adjuvant HAI with oxaliplatin after resection of at least 4 CRLM (primary endpoint: 18-month hepatic recurrence-free survival rate). We also aim to assess the feasibility of delivering at least 4 cycles of HAI (or i.v.) oxaliplatin after surgical treatment of at least 4 CRLM, the toxicity (NCI-CTC v4.0) of adjuvant HAI plus systemic chemotherapy, including HAI catheter-related complications, compared to systemic chemotherapy alone, and the efficacy of adjuvant HAI on hepatic and extra-hepatic recurrence-free (survival and overall survival). DISCUSSION: If 18-month hepatic recurrence-free survival is greater than 50% in the experimental arm, the study will be pursued in phase III, for which the primary endpoint will be 3-year recurrence-free survival rate. Patients randomized in the phase II will be included in the phase III, with an additional number of 106 patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02494973 . Trial registration date: July 10, 2015.

Advances in oncological treatment: limitations of RECIST 1.1 criteria.

RECIST 1.1 criteria are the standard for the response assessment of most solid tumors on computed tomography (CT). Nevertheless, the emergence of new classes of treatment in the lasts decades has brought new challenges in the evaluation of response. A PubMed online database literature search was performed in order to identify papers in English with full text available published up to September 2017. Some oncologic treatments, such as antiangiogenic agents, immunotherapy and local treatments, have proven to be effective despite atypical patterns of response. In patients undergoing these treatments, size-based evaluations, such as RECIST1.1, show some limitations, since they often underestimate the response. Some modified criteria have been proposed to improve the response assessment in several specific settings, such in gastrointestinal stromal tumors treated by antiangiogenic agents, hepatocellular carcinoma treated by local ablation or solid tumors treated by immunotherapy. New techniques of image analysis and imaging modalities other than CT, such as magnetic resonance imaging and positron emission tomography, may provide additional information and amend some of the limitations of size-based criteria. The emergence of new treatment paradigms and the increasing trend toward personalizing treatment should be associated with a concomitant evolution of response assessment, in both research and clinical settings.

iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics.

Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden-a mainstay of evaluation of cancer therapeutics that provides key information about objective response and disease progression. A consensus guideline-iRECIST-was developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) in cancer immunotherapy trials, to ensure consistent design and data collection, facilitate the ongoing collection of trial data, and ultimate validation of the guideline. This guideline describes a standard approach to solid tumour measurements and definitions for objective change in tumour size for use in trials in which an immunotherapy is used. Additionally, it defines the minimum datapoints required from future trials and those currently in development to facilitate the compilation of a data warehouse to use to later validate iRECIST. An unprecedented number of trials have been done, initiated, or are planned to test new immune modulators for cancer therapy using a variety of modified response criteria. This guideline will allow consistent conduct, interpretation, and analysis of trials of immunotherapies.

SDHB mutations are associated with response to temozolomide in patients with metastatic pheochromocytoma or paraganglioma.

Cyclophosphamide-dacarbazine-vincristine regimen is recommended for the treatment of malignant pheochromocytoma and paraganglioma (MPP); however, dacarbazine is the only recognized active drug in neuroendocrine tumours. We investigated the therapeutic benefit of temozolomide (TMZ), an oral alternative to dacarbazine, in patients with MPP. This is a retrospective study of consecutive patients with documented progressive MPP. We examined the correlation between Succinate dehydrogenase B (SDHB) mutation and O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation and MGMT expression in the French nation-wide independent cohort of 190 pheochromocytomas or paragangliomas (PP). Progression-free survival (PFS) according to RECIST 1.1 and PERCIST 1.0 criteria was the primary end point. Fifteen consecutive patients with MPP were enrolled; ten (67%) carried a mutation in SDHB. The mean dose intensity of TMZ was 172 mg/m(2) /d for 5 days every 28 days. Median PFS was 13.3 months after a median follow-up of 35 months. There were five partial responses (33%), seven stable (47%) and three progressive diseases (20%). Grade 3 toxicities were lymphopenia in two patients and hypertension in one. Partial responses were observed only in patients with mutation in SDHB. MGMT immunohistochemistry was negative in tumour samples from four patients who responded to treatment. SDHB germline mutation was associated with hypermethylation of the MGMT promoter and low expression of MGMT in 190 samples of the French nation-wide independent cohort. This study demonstrates that TMZ is an effective antitumour agent in patients with SDHB-related MPP. The silencing of MGMT expression as a consequence of MGMT promoter hypermethylation in SDHB-mutated tumours may explain this finding.

Outcomes of right sleeve lower lobectomy vs. lower bilobectomy for lung malignancies.

OBJECTIVES: Lower bilobectomy (LBL) leaves a residual pleural space potentially associated with adverse postoperative outcomes. In selected patients, right sleeve lower lobectomy (RSLL) with anastomosis between the middle lobe bronchus and intermediate bronchus is feasible. The outcomes of RSLL and LBL have not been compared. The aim of this study was to compare post-operative and long-term outcomes of RSLL and LBL in patients with lung cancer. METHODS: We retrospectively included patients managed by RSLL or LBL at our referral chest-surgery institution between 2001 and 2019. Post-operative complications and mortality were compared. Kaplan-Meier curves were plotted to compare overall and disease-free survival rates. RESULTS: We identified 23 patients with RSLL and 96 with LBL. Postoperative mortality was 9 % after RSLL and 5 % after LBL (p = 0.41). Bronchial fistula developed in 3 (13 %) RSLL patients and 6 (6 %) LBL patients (p = 0.23). Pleural space complications were significantly less common after RSLL (4/23 [17 %] vs. 45/96 [47 %], p = 0.03). Long-term vital capacity was significantly higher in the RSLL group (91 % vs. 64 %, p < 0.01). Five-year survival did not differ significantly between groups (84 % vs. 72 %, p = 0.09). CONCLUSIONS: RSLL was associated with similar postoperative mortality and long-term survival compared to LBL. However, pleural space complications were less common and lung function was better after RSLL than after LBL. When feasible, RSLL may deserve preference over LBL in patients with lung cancer managed at highly experienced centres.

Detection and severity quantification of pulmonary embolism with 3D CT data using an automated deep learning-based artificial solution.

PURPOSE: The purpose of this study was to propose a deep learning-based approach to detect pulmonary embolism and quantify its severity using the Qanadli score and the right-to-left ventricle diameter (RV/LV) ratio on three-dimensional (3D) computed tomography pulmonary angiography (CTPA) examinations with limited annotations. MATERIALS AND METHODS: Using a database of 3D CTPA examinations of 1268 patients with image-level annotations, and two other public datasets of CTPA examinations from 91 (CAD-PE) and 35 (FUME-PE) patients with pixel-level annotations, a pipeline consisting of: (i), detecting blood clots; (ii), performing PE-positive versus negative classification; (iii), estimating the Qanadli score; and (iv), predicting RV/LV diameter ratio was followed. The method was evaluated on a test set including 378 patients. The performance of PE classification and severity quantification was quantitatively assessed using an area under the curve (AUC) analysis for PE classification and a coefficient of determination (R²) for the Qanadli score and the RV/LV diameter ratio. RESULTS: Quantitative evaluation led to an overall AUC of 0.870 (95% confidence interval [CI]: 0.850-0.900) for PE classification task on the training set and an AUC of 0.852 (95% CI: 0.810-0.890) on the test set. Regression analysis yielded R² value of 0.717 (95% CI: 0.668-0.760) and of 0.723 (95% CI: 0.668-0.766) for the Qanadli score and the RV/LV diameter ratio estimation, respectively on the test set. CONCLUSION: This study shows the feasibility of utilizing AI-based assistance tools in detecting blood clots and estimating PE severity scores with 3D CTPA examinations. This is achieved by leveraging blood clots and cardiac segmentations. Further studies are needed to assess the effectiveness of these tools in clinical practice.

A Patient-Centered Model of Fast-Track Lung Cancer Diagnosis.

INTRODUCTION: Despite the increasing importance of digital resources in modern life over the past decades, little is known about the impact of internet-based solutions on patient's health. We aimed to study the potential benefit of a digital platform helping patients to deal with abnormal chest CT scan revealing possible lung cancer. METHODS: We set up a fast-track lung cancer diagnosis pathway through a secure online platform. Patient-generated information combined with online review of their imaging enables preplanning of further investigations ahead of clinical assessment. We compared outcomes of "self-referred" patients (patient group), who directly fill out the online questionnaire, to general practitioner-driven patients (GP group), who were referred by their GP. RESULTS: From June 2021 to June 2022, we included 125 patients (61% males, median age 67 years, IQR 56.9-72.5): 41% in the patient group and 59% in the GP group. No difference was found between groups in terms of time from contact to first appointment (median 5 days in both groups, P = .6), percentage of pathways including prebooked tests (94% vs. 92%, P = .6), number of scheduled invasive procedures (median 1, IQR 1-2 vs. 2, IQR 1-2, P = .4) and in final cancer diagnosis (76% vs. 78%, P = .4). CONCLUSION: A lung cancer diagnosis pathway directly accessible by patients through a secure online platform was feasible and as efficient as the usual general practitioner pathway. It demonstrated the benefit of leaning on new digital tools in order to answer to the new challenges of a patient-centered health care system.

Hepatic arterial oxaliplatin plus intravenous 5-fluorouracil and cetuximab for first-line treatment of colorectal liver metastases: A multicenter phase II trial.

BACKGROUND: The efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown. METHODS: In this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR). RESULTS: 35 patients, mostly with bilateral (89%), multiple CRLM (>4, 86%; >10, 46%) were enrolled in eight centers. The ORR was 88% (95% CI, 71%-96%) among evaluable patients (n = 32), and 95% (95% CI 70-100%) among the 22 wild-type RAS/BRAF evaluable patients. After a median follow-up of 8.8 years (95% CI, 8.7-not reached), median progression-free survival was 17.9 months (95% CI, 15-23) and median overall survival (OS) was 46.3 months (95% CI, 40.0-not reached). 23 of the 35 patients (66%), including 22 (79%) of the 25 patients with wild-type RAS tumor, underwent curative-intent surgical resection and/or ablation of CRLM. HAI catheter remained patent in 86% of patients, allowing for a median of eight oxaliplatin infusions (range, 1-19). Treatment toxicity was manageable, without toxic death. CONCLUSION: HAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM and should be investigated further.