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Fluorescence-guided surgery is an intraoperative optical imaging method that provides surgeons with real-time guidance for the delineation of tumours. Currently, in phase 1 and 2 clinical trials, evaluation of fluorescence-guided surgery is primarily focused on its diagnostic performance, although the corresponding outcome variables do not inform about the added clinical benefit of fluorescence-guided surgery and are challenging to assess objectively. Nonetheless, the effect of fluorescence-guided surgery on intraoperative decision making is the most objective outcome measurement to assess the clinical value of this imaging method. In this Review, we explore the study designs of existing trials of fluorescence-guided surgery that allow us to extract information on potential changes in intraoperative decision making, such as additional or more conservative resections. On the basis of this analysis, we offer recommendations on how to report changes in intraoperative decision making that result from fluorescence imaging, which is of utmost importance for the widespread clinical implementation of fluorescence-guided surgery.

SummaryBackgroundp16 INK4a (p16) immunohistochemistry is the most widely used biomarker assay for inferring HPV causation in oropharyngeal cancer in clinical and trial settings. However, discordance exists between p16 and HPV DNA or RNA status in some patients with oropharyngeal cancer. We aimed to clearly quantify the extent of discordance, and its prognostic implications. MethodsIn this multicentre, multinational individual patient data analysis, we did a literature search in PubMed and Cochrane database for systematic reviews and original studies published in English between Jan 1, 1970, and Sept 30, 2022. We included retrospective series and prospective cohorts of consecutively recruited patients previously analysed in individual studies with minimum cohort size of 100 patients with primary squamous cell carcinoma of the oropharynx. Patient inclusion criteria were diagnosis with a primary squamous cell carcinoma of oropharyngeal cancer; data on p16 immunohistochemistry and on HPV testing; information on age, sex, tobacco, and alcohol use; staging by TNM 7th edition; information on treatments received; and data on clinical outcomes and follow-up (date of last follow-up if alive, date of recurrence or metastasis, and date and cause of death). There were no limits on age or performance status. The primary outcomes were the proportion of patients of the overall cohort who showed the different p16 and HPV result combinations, as well as 5-year overall survival and 5-year disease-free survival. Patients with recurrent or metastatic disease or who were treated palliatively were excluded from overall survival and disease-free survival analyses. Multivariable analysis models were used to calculate adjusted hazard ratios (aHR) for different p16 and HPV testing methods for overall survival, adjusted for prespecified confounding factors. FindingsOur search returned 13 eligible studies that provided individual data for 13 cohorts of patients with oropharyngeal cancer from the UK, Canada, Denmark, Sweden, France, Germany, the Netherlands, Switzerland, and Spain. 7895 patients with oropharyngeal cancer were assessed for eligibility. 241 were excluded before analysis, and 7654 were eligible for p16 and HPV analysis. 5714 (74·7%) of 7654 patients were male and 1940 (25·3%) were female. Ethnicity data were not reported. 3805 patients were p16-positive, 415 (10·9%) of whom were HPV-negative. This proportion differed significantly by geographical region and was highest in the areas with lowest HPV-attributable fractions ( r=–0·744, p=0·0035). The proportion of patients with p16+/HPV– oropharyngeal cancer was highest in subsites outside the tonsil and base of tongue (29·7% vs 9·0%, p<0·0001). 5-year overall survival was 81·1% (95% CI 79·5–82·7) for p16+/HPV+, 40·4% (38·6–42·4) for p16–/HPV–, 53·2% (46·6–60·8) for p16–/HPV+, and 54·7% (49·2–60·9) for p16+/HPV–. 5-year disease-free survival was 84·3% (95% CI 82·9–85·7) for p16+/HPV+, 60·8% (58·8–62·9) for p16–/HPV–; 71·1% (64·7–78·2) for p16–/HPV+, and 67·9% (62·5–73·7) for p16+/HPV–. Results were similar across all European sub-regions, but there were insufficient numbers of discordant patients from North America to draw conclusions in this cohort. InterpretationPatients with discordant oropharyngeal cancer (p16–/HPV+ or p16+/HPV–) had a significantly worse prognosis than patients with p16+/HPV+ oropharyngeal cancer, and a significantly better prognosis than patients with p16–/HPV– oropharyngeal cancer. Along with routine p16 immunohistochemistry, HPV testing should be mandated for clinical trials for all patients (or at least following a positive p16 test), and is recommended where HPV status might influence patient care, especially in areas with low HPV-attributable fractions. FundingEuropean Regional Development Fund, Generalitat de Catalunya, National Institute for Health Research (NIHR) UK, Cancer Research UK, Medical Research Council UK, and The Swedish Cancer Foundation and the Stockholm Cancer Society.

Knowledge about the efficacy of behavioural intervention technologies that can be used by cancer survivors independently from a health-care provider is scarce. We aimed to assess the efficacy, reach, and usage of Oncokompas, a web-based eHealth application that supports survivors in self-management by monitoring health-related quality of life (HRQOL) and cancer-generic and tumour-specific symptoms and obtaining tailored feedback with a personalised overview of supportive care options. In this non-blinded, randomised, controlled trial, we recruited patients treated at 14 hospitals in the Netherlands for head and neck cancer, colorectal cancer, breast cancer, Hodgkin lymphoma, or non-Hodgkin lymphoma. Adult survivors (aged ≥18 years) were recruited through the Netherlands Cancer Registry (NCR) and invited by their treating physician through the Patient Reported Outcomes Following Initial Treatment and Long term Evaluation of Survivorship (PROFILES) registry. Participants were randomly assigned (1:1) by an independent researcher to the intervention group (access to Oncokompas) or control group (access to Oncokompas after 6 months), by use of block randomisation (block length of 68), stratified by tumour type. The primary outcome was patient activation (knowledge, skills, and confidence for self-management), assessed at baseline, post-intervention, and 3-month and 6-month follow-up. Linear mixed models (intention-to-treat) were used to assess group differences over time from baseline to 6-month follow-up. The trial is registered in the Netherlands Trial Register, NTR5774 and is completed. Between Oct 12, 2016, and May 24, 2018, 625 (21%) of 2953 survivors assessed for eligibility were recruited and randomly assigned to the intervention (320) or control group (305). Median follow-up was 6 months (IQR 6−6). Patient activation was not significantly different between intervention and control group over time (difference at 6-month follow-up 1·7 [95% CI −0·8–4·1], p=0·41). Oncokompas did not improve the amount of knowledge, skills, and confidence for self-management in cancer survivors. This study contributes to the evidence for the development of tailored strategies for development and implementation of behavioural intervention technologies among cancer survivors. Dutch Cancer Society (KWF Kankerbestrijding).