Showing papers in "European journal of cancer in 2022"

Comparative assessment of early mortality risk upon immune checkpoint inhibitors alone or in combination with other agents across solid malignancies: a systematic review and meta-analysis.

Abstract: Background The early crossing of survival curves in randomised clinical trials (RCTs) with immune checkpoint blockers suggests an excess of mortality in the first months of treatment. However, the exact estimation of the early death (ED) rate, the comparison between ED upon immune checkpoint inhibitors (ICI) alone or in combination with other agents and the impact of tumour type, and PD-L1 expression on ED are unknown. Methods RCTs comparing ICI alone (ICI-only group) or in combination with other non-ICI therapies (ICI-OT group) (experimental arms) versus non-ICI treatments (control arm) were included. ED was defined as death within the first 3 months of treatment. The primary outcome was the comparison of ED between experimental and control arms, and the secondary outcome was the comparison of ED risk between ICI-only and ICI-OT. ED rates estimated by risk ratio (RR) were pooled by random effect model. Results A total of 56 RCTs (40,215 participants, 14 cancer types) were included. ED occurred in 14.2% and 6.7% of patients in ICI-only and ICI-OT groups, respectively. ED risk significantly increased with ICI-only (RR: 1.29, 95% CI 1.05–1.57) versus non-ICI therapies, while it was lower with ICI-OT versus non-ICI treatments (RR: 0.81, 95% CI 0.73–0.90). ED risk was significantly higher upon ICI-only compared to ICI-OT (RR: 1.57, 95% CI 1.26–1.95). Gastric and urothelial carcinoma were at higher risk of ED. PD-L1 expression and ICI drug classes were not associated with ED. Conclusions ED upon first-line ICI is a clinically relevant phenomenon across solid malignancies, not predictable by PD-L1 expression but preventable through the addition of other treatments to ICI.

Immunogenicity and risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection after Coronavirus Disease 2019 (COVID-19) vaccination in patients with cancer: a systematic review and meta-analysis

Abstract: Patients with cancer are considered a priority group for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination given their high risk of contracting severe Coronavirus Disease 2019 (COVID-19). However, limited data exist regarding the efficacy of immunisation in this population. In this study, we assess the immunologic response after COVID-19 vaccination of cancer versus non-cancer population.PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched from 01st March 2020 through 12th August 12 2021. Primary end-points were anti-SARS-CoV-2 spike protein (S) immunoglobulin G (IgG) seroconversion rates, T-cell response, and documented SARS-CoV-2 infection after COVID-19 immunisation. Data were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Overall effects were pooled using random-effects models.This systematic review and meta-analysis included 35 original studies. Overall, 51% (95% confidence interval [CI], 41-62) and 73% (95% CI, 64-81) of patients with cancer developed anti-S IgG above the threshold level after partial and complete immunisation, respectively. Patients with haematologic malignancies had a significantly lower seroconversion rate than those with solid tumours after complete immunisation (65% vs 94%; P < 0.0001). Compared with non-cancer controls, oncological patients were less likely to attain seroconversion after incomplete (risk ratio [RR] 0.45 [95% CI 0.35-0.58]) and complete (RR 0.69 [95% CI 0.56-0.84]) COVID-19 immunisation schemes. Patients with cancer had a higher likelihood of having a documented SARS-CoV-2 infection after partial (RR 3.21; 95% CI 0.35-29.04) and complete (RR 2.04; 95% CI 0.38-11.10) immunisation.Patients with cancer have an impaired immune response to COVID-19 vaccination compared with controls. Strategies that endorse the completion of vaccination schemes are warranted. Future studies should aim to evaluate different approaches that enhance oncological patients' immune response.

Global, regional and national burden of primary liver cancer by subtype

Abstract: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) are the two main histological subtypes of primary liver cancer. Estimates of the burden of liver cancer by subtype are needed to facilitate development and evaluation of liver cancer control globally. We provide worldwide, regional and national estimates of HCC and iCCA incidence using high-quality data.We used population-based cancer registry data on liver cancer cases by histological subtype from 95 countries to compute the sex- and country-specific distributions of HCC, iCCA and other specified histology. Subtype distributions were applied to estimates of total liver cancer cases for 2018 from the Global Cancer Observatory. Age-standardised incidence rates (ASRs) were calculated.There were an estimated 826,000 cases of liver cancer globally in 2018: 661,000 HCC (ASR 7.3 cases per 100,000); 123,000 iCCA (ASR 1.4) and 42,000 other specified histology (ASR 0.5). HCC contributed 80% of the world total liver cancer burden followed by iCCA (14.9%) and other specified histology (5.1%). HCC rates were highest in Eastern Asia (ASR 14.8), Northern Africa (ASR 13.2) and South-Eastern Asia (ASR 9.5). Rates of iCCA were highest in South-Eastern Asia (ASR 2.9), Eastern Asia (ASR 2.0), Northern Europe, the Caribbean and Central America and Oceania (ASR all 1.8).We have shown the importance of uncovering the distinct patterns of the major subtypes of liver cancer. The use of these estimates is critical to further develop public health policy to reduce the burden of liver cancer and monitor progress in controlling HCC and iCCA globally.

European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics: Update 2022.

Abstract: Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed with dermatoscopy. If a melanoma is suspected, a histopathological examination is always required. Sequential digital dermatoscopy and full body photography can be used in high-risk patients to improve the detection of early melanoma. Where available, confocal reflectance microscopy can also improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the American Joint Committee on Cancer classification. Thin melanomas up to 0.8 mm tumor thickness do not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC onwards whole-body examinations with computed tomography (CT) or positron emission tomography CT (PET-CT) in combination with brain magnetic resonance imaging are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to define the frequency and extent of examinations. A stage-based follow-up scheme is proposed which, according to the experience of the guideline group, covers the optimal requirements, but further studies may be considered. This guideline is valid until the end of 2024.

Evolution of low HER2 expression between early and advanced-stage breast cancer.

Abstract: Low human epidermal growth factor receptor 2 (HER2) expression is emerging as an actionable biomarker for the treatment of breast cancer (BC) with novel anti-HER2 drugs. However, the evolution of this biomarker during the course of disease is still poorly characterised, and controversial data exist on its prognostic implications.We reviewed data of patients with HER2-negative BC according to the latest ASCO/CAP guidelines referred between January 2014 and December 2020. We grouped patients based on the immunohistochemistry (IHC) expression of HER2, HER2-zero (IHC 0) and HER2-low subgroup (IHC 1+ or 2+/ISH-negative) and evaluated the evolution of HER2 expression between the primary tumour and the first biopsy collected in the advanced setting. Disease-free survival, overall survival and progression-free survival were compared between patients with HER2-zero and HER2-low expression on the primary tumour.232 patients were included in the analysis. Among the overall population, there was a relevant discordance in HER2 expression between the primary tumour and the matched biopsy (K = 0.33, 95%CI 0.21-0.44): 44% of the HER2-zero primary tumour showed an increased HER2 score on biopsy, and 22% of the HER2-low primary tumours turned into HER2-IHC 0. The findings in the sub-populations of hormone-receptors positive (K = 0.32, 95%CI 0.19-0.45) and triple-negative tumours (K = 0.18, 95%CI -0.09-0.46) were consistent with the primary analysis. No difference in survival outcomes was observed between HER2-low and HER2-zero primary tumours.HER2-low expression is dynamic in BC and may be enriched in the advanced-stage setting. No prognostic significance was demonstrated for HER2-low expression.

Neoadjuvant therapy or upfront surgery for resectable and borderline resectable pancreatic cancer: A meta-analysis of randomised controlled trials

Abstract: Neoadjuvant therapy may improve survival compared with upfront surgery in patients with resectable and borderline resectable pancreatic cancer, but high-quality evidence is lacking.We systematically searched for randomised trials comparing neoadjuvant therapy with upfront surgery for resectable and borderline resectable pancreatic cancer published since database inception until December 2020. The primary outcome was overall survival (OS) by intention-to-treat with subgroup analyses for resectability status. Meta-analyses using a random-effects model were performed. Certainty of evidence was assessed using the GRADE approach.Seven trials with 938 patients were included. All trials included a neoadjuvant gemcitabine-based chemo(radio)therapy arm. None of the studies used adjuvant FOLFIRINOX. Neoadjuvant therapy improved OS (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.52-0.85; P = 0.001; I2 = 46%) compared with upfront surgery. This represents an increase in median OS from 19 to 29 months. In the subgroup of resectable pancreatic cancer (i.e., venous contact ≤180°, no arterial contact), no statistically significant difference in OS was observed (HR 0.77, 95% CI 0.53-1.12; P = 0.18; I2 = 20%). In the subgroup of borderline resectable pancreatic cancer (i.e. venous contact >180°, any arterial contact), neoadjuvant therapy improved OS (HR 0.61, 95% CI 0.44-0.85; P = 0.004; I2 = 59%). The GRADE certainty of evidence was high for the outcome of OS.Neoadjuvant therapy improves OS compared with upfront surgery in patients with borderline resectable pancreatic cancer. More evidence is required on whether neoadjuvant therapy improves survival for patients with resectable pancreatic cancer.

Therapeutic vaccines for breast cancer: Has the time finally come?

Abstract: The ability to exploit the immune system as a weapon against cancer has revolutionised the treatment of cancer patients, especially through immune checkpoint inhibitors (ICIs). However, ICIs demonstrated a modest benefit in treating breast cancer (BC), with the exception of certain subsets of triple-negative BCs. An immune-suppressive tumour microenvironment (TME), typically present in BC, is an important factor in the poor response to immunotherapy.After almost two decades of poor clinical trial results, cancer vaccines (CVs), an active immunotherapy, have come back in the spotlight because of some technological advancements, ultimately boosted by coronavirus disease 2019 pandemic. In particular, neoantigens are emerging as the preferred targets for CVs, with gene-based and viral vector–based platforms in development. Moreover, lipid nanoparticles proved to be immunogenic and efficient delivery vehicles.Past clinical trials investigating CVs focused especially on the metastatic disease, where the TME is more likely compromised by inhibitory mechanisms. In this sense, favouring the use of CVs as monotherapy in premalignant or in the adjuvant setting and establishing combination treatments (i.e. CV plus ICI) in late-stage disease are promising strategies. This review provides a full overview of the past and current breast cancer vaccine landscape.

European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2022.

Abstract: A unique collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on the systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to 2-cm safety margins. Sentinel lymph node dissection shall be performed as a staging procedure in patients with tumor thickness ≥1.0 mm or ≥0.8 mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions in stage III/IV patients should be primarily made by an interdisciplinary oncology team ("tumor board"). Adjuvant therapies can be proposed in stage III/completely resected stage IV patients and are primarily anti-PD-1, independent of mutational status, or alternatively dabrafenib plus trametinib for BRAF mutant patients. In distant metastases (stage IV), either resected or not, systemic treatment is always indicated. For first-line treatment particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies shall be considered. In stage IV melanoma with a BRAF-V600 E/K mutation, first-line therapy with BRAF/MEK inhibitors can be offered as an alternative to immunotherapy. In patients with primary resistance to immunotherapy and harboring a BRAF-V600 E/K mutation, this therapy shall be offered as second-line therapy. Systemic therapy in stage III/IV melanoma is a rapidly changing landscape, and it is likely that these recommendations may change in the near future.

Third dose of anti-SARS-CoV-2 vaccine for patients with cancer: Should humoral responses be monitored? A position article

Abstract: Taking into account higher risk of severe coronavirus disease 2019 or death among patients with cancer, as well as impaired immunogenicity after anti-SARS-CoV-2 vaccines, in addition to waning immunity, booster dosing appears mandatory in this patient population. This review sought to provide reasonable evidence so as to assist oncologists in their daily practice, helping them decide when an anti-SARS-Cov2 antibody (Ab) dosage should be scheduled after a full two-dose vaccination and, if necessary, propose an early third dose (D3). Such D3 could apply to non-responder patients with anti-Spike (S) Abs titres <40 binding Ab unit (BAU)/mL. For lowresponder patients with anti-S Ab titres between 40 BAU/mL and 100/260 BAU/mL (suggested area of uncertainty), an early D3 may similarly be proposed. Nevertheless, this D3 could be administered in a less urgent manner, taking into account associated comorbidities and regional epidemic incidence rates. This latter strategy may comprise a monthly dosage of anti-S titres so as to better assess the kinetics of waning immunity. For responder patients with anti-S titres above 260 BAU/mL, we suggest to follow the recommendations outlined for the general population. Given this context, patients with anti-S titres above 1000 BAU/mL should be given the possibility to undergo anti-S titre control after three months, designed to assess rapid humoral waning immunity. We strongly recommend that patients with cancer be included into observational serological monitoring studies or clinical trials that are dedicated to severe immunocompromised patients without any humoral seroconversion after D3.

Third dose of SARS-CoV-2 vaccination in hemato-oncological patients and health care workers: immune responses and adverse events – a retrospective cohort study

Abstract: BackgroundDue to potentially immune-escaping virus variants and waning immunity, a third SARS-CoV-2 vaccination dose is increasingly recommended. However, data in patients with cancer are limited.Patients and methodsWe measured anti-SARS-CoV-2 spike protein antibody levels after the third vaccination dose in 439 patients with cancer and 41 health care workers (HCW) at an academic centre in Austria and a rural community hospital in Italy. Adverse events were retrieved from questionnaires.ResultsOverall, 439 patients and 41 HCW were included. SARS-CoV-2 infections were observed in 62/439 (14.1%) patients before vaccination and in 5/439 (1.1%) patients after ≥1 dose. Longitudinal analysis revealed a decrease of antibody levels between 3 and 6 months after second vaccination in patients with solid tumours (p < 0.001) and haematological malignancies without anti-B cell therapies (p < 0.001). After the third dose, anti-S levels increased compared to the first/second dose. Patients receiving B cell-targeted agents had lower antibody levels than patients with haematological malignancies undergoing other treatments (p < 0.001) or patients with solid tumours (p < 0.001). Moreover, anti-S levels correlated with CD19+ (B cell) and CD56+ (NK cell) counts in peripheral blood. The most frequent adverse events after the third dose were local pain (75/160, 46.9%), fatigue (25/160, 15.6%) and fever/chills (16/160, 10.0%). Patients with cancer had lower anti-S levels than HCW (p = 0.015).ConclusionsThis study in patients with cancer shows improved antibody levels after the third vaccination dose at an acceptable side-effect profile. Lower antibody levels than in controls underline the need for further follow-up studies and dedicated trials.

Long-term prognostic significance of HER2-low and HER2-zero in node-negative breast cancer.

Abstract: Background Recently, novel antibody––drug conjugates (ADCs) showed clinical activity in a subset of advanced human epidermal growth factor receptor 2 (HER2)-negative patients. We investigated the prognostic significance of HER2-low and HER2-zero tumours. Patients and methods The retrospective cohort study included 410 consecutive node-negative breast cancer patients without adjuvant systemic therapy treated between 1985 and 2000 (median follow-up: 16.73 [IQR 8.58–23.45] years). 351 (85.6%) were HER-2 negative and subdivided into HER2-zero (immunohistochemistry [IHC] score 0) and HER2-low (IHC score 1+ or 2+/in situ hybridisation [ISH]-negative). HER2 gene expression was available in 170 (48.4%) patients. Differences in HER2 status for immunohistochemistry, gene expression and clinico-pathologic parameters were assessed using Fisher's exact test, Pearson's correlation and Mann–Whitney test. Prognosis was investigated using the Kaplan–Meier method and Cox regression analyses. Results Of the 351 HER2-negative patients, 198 (56.4%) had HER2-low tumours and 153 (43.6%) were HER2-zero. Significant differences between HER2-zero and HER2-low tumours were found in histologic grading (P = 0.001), Ki-67 (P = 0.013) and HER2 gene expression (P = 0.002). HER2-low patients had significantly longer disease-free survival (DFS) (15-year rate: 67.5% [95% CI 61.0–74.7] vs. 47.3% [95% CI 39.9–56.1], P < 0.001) and overall survival (OS) (15-year rate: 75.4% [95% CI 69.4–81.9] vs. 66.8% [95% CI 59.5–74.9], P = 0.009). The OS difference was observed in hormone receptor (HR)-positive (P = 0.039) but not HR-negative (P = 0.086) tumours. The results of multivariable analyses confirmed the independent prognostic significance of HER2 status (DFS: HR, 0.546; 95% CI, 0.402–0.743; P < 0.001; OS: HR, 0.653; 95% CI, 0.458–0.932; P = 0.019). Conclusion HER2-low patients had a better survival than HER2-zero patients.

Diagnosis and treatment of Merkel cell carcinoma: European consensus-based interdisciplinary guideline - Update 2022.

Abstract: Merkel cell carcinoma (MCC) is a rare skin cancer, accounting for less than 1% of all cutaneous malignancies. It is found predominantly in white populations and risk factors include advanced age, ultraviolet exposure, male sex, immunosuppression, such as AIDS/HIV infection, haematological malignancies or solid organ transplantation, and Merkel cell polyomavirus infection. MCC is an aggressive tumour with 26% of cases presenting lymph node involvement at diagnosis and 8% with distant metastases. Five-year overall survival rates range between 48% and 63%. Two subsets of MCC have been characterised with distinct molecular pathogenetic pathways: ultraviolet-induced MCC versus virus-positive MCC, which carries a better prognosis. In both subtypes, there are alterations in the retinoblastoma protein and p53 gene structure and function. MCC typically manifests as a red nodule or plaque with fast growth, most commonly on sun exposed areas. Histopathology (small-cell neuroendocrine appearance) and immunohistochemistry (CK20 positivity and TTF-1 negativity) confirm the diagnosis. The current staging systems are the American Joint Committee on Cancer/Union for international Cancer control 8th edition. Baseline whole body imaging is encouraged to rule out regional and distant metastasis. For localised MCC, first-line treatment is surgical excision with postoperative margin assessment followed by adjuvant radiation therapy (RT). Sentinel lymph node biopsy is recommended in all patients with MCC without clinically detectable lymph nodes or distant metastasis. Adjuvant RT alone, eventually combined with complete lymph nodes dissection is proposed in case of micrometastatic nodal involvement. In case of macroscopic nodal involvement, the standard of care is complete lymph nodes dissection potentially followed by post-operative RT. Immunotherapy with anti-PD-(L)1 antibodies should be offered as first-line systemic treatment in advanced MCC. Chemotherapy can be used when patients fail to respond or are intolerant for anti-PD-(L)1 immunotherapy or clinical trials.

Deficient mismatch repair/microsatellite unstable colorectal cancer: Diagnosis, prognosis and treatment.

Abstract: Microsatellite unstable (MSI) colorectal cancers (CRCs) are due to DNA mismatch repair (MMR) deficiency and occurs in15% of non-metastatic diseases and 5% in the metastatic setting. Nearly 30% of MSI CRCs occur in a context of constitutional mutation of the MMR system (Lynch syndrome). Others are sporadic cancers linked to a hypermethylation of the MLH-1 promoter. The pathogenic alterations of MMR genes lead to the accumulation of frequent somatic mutational events and these tumours arbour a high antigen burden and are highly infiltrated with cytotoxic T-cell lymphocytes. Microsatellite instability/DNA mismatch repair deficiency (MSI/dMMR) status has prognostic and predictive implications in non-metastatic and metastatic CRCs. The prognostic value of MSI status in non-metastatic CRCs has been studied extensively, yet the data are more limited for its predictive value in terms of adjuvant chemotherapy efficacy. In both cases (metastatic and non-metastatic settings) treatment with immune check-point inhibitors (ICIs) have shown a remarkable effectiveness in the context of MSI/dMMR status. Indeed, recent data from prospective cohorts and randomised trials have shown a dramatical improvement of survival with immunotherapy (programmed death-ligand 1 [PD-(L)1] cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] blockage) in metastatic or non-metastatic MSI/dMMR CRC. In this review we report and discuss how and for whom to test for the MSI/dMMR phenotype, as well as the prognostic value of this phenotype and the new treatment recommendations options for this unique CRC population. Despite their efficacy, primary and secondary resistance to immune checkpoint inhibitors (ICIs) are observed in more than 50% MSI-H/dMMR CRC patients and in the future how to identify these patients and to overcome resistance will be an important challenge.

Probiotic supplement attenuates chemotherapy-related cognitive impairment in patients with breast cancer: a randomised, double-blind, and placebo-controlled trial

Abstract: Chemotherapy-related cognitive impairment (CRCI) is highly prevalent in patients with cancer and is associated with poor outcomes and quality of life. To date, the management of CRCI remains a clinical challenge. Herein, we aim to determine the preventive effects of probiotics on CRCI development and underlying mechanisms.We conducted a randomised, double-blind and placebo-controlled trial (ChiCTR-INQ-17014181) of 159 patients with breast cancer and further investigated the underlying mechanism in a pre-clinical setting. From 2018 to 2019, patients with breast cancer (Stage I-III) who needed adjuvant chemotherapy were screened, enrolled and randomly assigned to receive either probiotics or placebo (three capsules, twice/day) during chemotherapy. Their cognition, anxiety and depression were assessed with well-established assays; their plasma biomarkers, metabolites and faecal microbiota compositions were measured. In addition, the systemic effects of the metabolites found in the clinical trial on long-term potentiation, synapse injury, oxidative stress and glial activation were assessed in rats.Probiotics supplement significantly decreased the incidence of CRCI, improved the allover cognitive functions, changed the gut microbial composition and modulated nine plasma metabolite changes. Among these metabolites, p-Mentha-1,8-dien-7-ol, Linoelaidyl carnitine and 1-aminocyclopropane-1-carboxylic acid were negatively correlated with the occurrence of CRCI. Furthermore, probiotics supplement increased plasma p-Mentha-1,8-dien-7-ol in rats. Administration of exogenous p-Mentha-1,8-dien-7-ol significantly alleviated chemotherapy-induced long-term potentiation impairment, synapse injury, oxidative stress and glial activation in the hippocampus of rats.Our data indicated that probiotics supplement prevents the occurrence of CRCI in patients with breast cancer via modulating plasma metabolites, including p-Mentha-1,8-dien-7-ol.Chinese Clinical Trial Registry (ChiCTR-INQ-17014181) [http://www.chictr.org.cn/showproj.aspx?proj=24294].

Explainable artificial intelligence in skin cancer recognition: A systematic review.

Abstract: Due to their ability to solve complex problems, deep neural networks (DNNs) are becoming increasingly popular in medical applications. However, decision-making by such algorithms is essentially a black-box process that renders it difficult for physicians to judge whether the decisions are reliable. The use of explainable artificial intelligence (XAI) is often suggested as a solution to this problem. We investigate how XAI is used for skin cancer detection: how is it used during the development of new DNNs? What kinds of visualisations are commonly used? Are there systematic evaluations of XAI with dermatologists or dermatopathologists?Google Scholar, PubMed, IEEE Explore, Science Direct and Scopus were searched for peer-reviewed studies published between January 2017 and October 2021 applying XAI to dermatological images: the search terms histopathological image, whole-slide image, clinical image, dermoscopic image, skin, dermatology, explainable, interpretable and XAI were used in various combinations. Only studies concerned with skin cancer were included.37 publications fulfilled our inclusion criteria. Most studies (19/37) simply applied existing XAI methods to their classifier to interpret its decision-making. Some studies (4/37) proposed new XAI methods or improved upon existing techniques. 14/37 studies addressed specific questions such as bias detection and impact of XAI on man-machine-interactions. However, only three of them evaluated the performance and confidence of humans using CAD systems with XAI.XAI is commonly applied during the development of DNNs for skin cancer detection. However, a systematic and rigorous evaluation of its usefulness in this scenario is lacking.

Antibody titres before and after a third dose of the SARS-CoV-2 BNT162b2 vaccine in patients with cancer

Abstract: Patients with cancer are at increased risk for severe COVID-19 and have reduced humoral immune responses after SARS-CoV-2 infection and dual-dose BNT162b2 vaccination [1,2]. Recently, it was observed that the third dose of BNT162b2 is able to elicit higher SARS-CoV-2 anti-receptor-binding domain (RBD) IgG titres in solid-organ transplant patients and adults aged ≥60 years than two doses [3,4]. Initial reports with limited sample size also indicated that the third BNT162b2 vaccination dose would be beneficial for patients with solid tumour receiving active anti-neoplastic treatment [5–7].

Pathological complete response, long-term outcomes, and recurrence patterns in HER2-low versus HER2-zero breast cancer after neoadjuvant chemotherapy.

Abstract: BackgroundThe interest in HER2-low breast cancer (BC) has increased in recent years with the development of novel anti-HER2 antibody–drug conjugates. Here, we investigated the clinical outcomes and relapse patterns of patients with HER2-low or -zero BCs in an Asian population.MethodsWe retrospectively identified HER2-low or -zero BC patients with stage I–III tumours who were treated with neoadjuvant chemotherapy and underwent curative surgery, between 2014 and 2018 at Asan Medical Center, Seoul, Korea.ResultsA total of 818 and 754 HER2-zero and HER2-low BC patients, respectively, were consecutively included in this analysis. The HER2-low group had more hormone receptor [HR]-positive patients (81% versus 56%, P < 0.001). The HER2-zero group had a higher proportion of patients who achieved pathological complete response (pCR) (14.7% versus 9.8%, P = 0.003); however, no significant differences of pCR rate by HER2 status were identified in the HR-positive (P = 0.4) and HR-negative groups (P = 0.3) when analysed separately. The HER2-low BC cases had higher 5-year overall survival (OS) and disease-free survival (DFS) rates (P < 0.001 for OS; P = 0.002 for DFS); however, no differences were observed in terms of OS and DFS by HER2 status in the HR-positive group (P = 0.21 for OS and P = 0.66 for DFS).ConclusionsOur current findings do not support that HER2-low BC had different biology and clinical features compared to HER2-zero BC in patients who treated with neoadjuvant chemotherapy. However, the prognostic impact of HER2-low status in BC remains controversial; thus warranting further research.

Chemotherapy after immune checkpoint inhibitor failure in metastatic melanoma: a retrospective multicentre analysis

Abstract: Despite remarkably improved outcomes with immune checkpoint inhibition, many patients with metastatic melanoma will eventually require further therapy. Chemotherapy has limited activity when used first-line but can alter the tumour microenvironment and does improve efficacy when used in combination with immunotherapy in lung cancer. Whether chemotherapy after checkpoint inhibitor failure has relevant activity in patients with metastatic melanoma is unknown.Patients with metastatic melanoma treated with chemotherapy after progression on immunotherapy with checkpoint inhibitors were identified retrospectively from 24 melanoma centres. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety were examined.In total, 463 patients were treated between 2007 and 2017. Fifty-six per cent had received PD-1-based therapy before chemotherapy. Chemotherapy regimens included carboplatin + paclitaxel (32%), dacarbazine (25%), temozolomide (15%), taxanes (9%, nab-paclitaxel 4%), fotemustine (6%) and others (13%). Median duration of therapy was 7.9 weeks (0-108). Responses included 0.4% complete response (CR), 12% partial response (PR), 21% stable disease (SD) and 67% progressive disease (PD). Median PFS was 2.6 months (2.2, 3.0), and median PFS in responders was 8.7 months (6.3, 16.3), respectively. Twelve-month PFS was 12% (95% CI 2-15%). In patients who had received anti-PD-1 before chemotherapy, the ORR was 11%, and median PFS was 2.5 months (2.1, 2.8). The highest activity was achieved with single-agent taxanes (N = 40), with ORR 25% and median PFS 3.9 months (2.1, 6.2). Median OS from chemotherapy start was 7.1 months (6.5, 8.0). Subsequent treatment with checkpoint inhibitors achieved a response rate of 16% with a median PFS of 19.1 months (2.0-43.1 months). No unexpected toxicities were observed.Chemotherapy has a low response rate and short PFS in patients with metastatic melanoma who have failed checkpoint inhibitor therapy, although activity varied between regimens. Chemotherapy has a limited role in the management of metastatic melanoma.

A phase I/Ib study of regorafenib and nivolumab in mismatch repair proficient advanced refractory colorectal cancer.

Abstract: In contrast to mismatch repair deficient (dMMR) colorectal cancer (CRC), mismatch repair proficient (pMMR) CRC is usually unresponsive to anti-PD-1 immunotherapy. Recent preclinical data suggest that regorafenib may enhance the antitumor activity of anti-PD-1 immunotherapy. However, the safety and efficacy of regorafenib plus nivolumab have not been established in patients with refractory metastatic pMMR CRC. This study aimed to evaluate the safety and efficacy of regorafenib plus nivolumab in metastatic pMMR metastatic CRC.This was a phase I/Ib study with standard 3 + 3 design plus dose expansion of the maximum tolerated dose (MTD) in patients with refractory metastatic pMMR CRC. Patients were treated with regorafenib combined with nivolumab. The primary end-points were dose-limiting toxicity (DLT) and MTD. The secondary end-points were objective response rate, safety and overall survival (OS).A total of 52 patients were enrolled, and 51 patients received at least one dose of treatment. Three patients experienced DLT (all grade 3 rash). MTD was regorafenib 80 mg and nivolumab 240 mg every 2 weeks. Most common grade 3/4 treatment-related adverse events were hypertension (16%), rash (10%) and anaemia (6%). Among 40 evaluable patients, four (10%) achieved partial response, including one unconfirmed response, 21 (53%) achieved stable disease, and disease control rate was 63%. The median progression-free survival and OS were 4.3 and 11.1 months, respectively.Regorafenib plus nivolumab appears to be well tolerated with limited anticancer activity in metastatic pMMR CRC.ClinicalTrials.gov identifier: NCT03712943.

Integration of deep learning-based image analysis and genomic data in cancer pathology: A systematic review

Abstract: BackgroundOver the past decade, the development of molecular high-throughput methods (omics) increased rapidly and provided new insights for cancer research. In parallel, deep learning approaches revealed the enormous potential for medical image analysis, especially in digital pathology. Combining image and omics data with deep learning tools may enable the discovery of new cancer biomarkers and a more precise prediction of patient prognosis. This systematic review addresses different multimodal fusion methods of convolutional neural network-based image analyses with omics data, focussing on the impact of data combination on the classification performance.MethodsPubMed was screened for peer-reviewed articles published in English between January 2015 and June 2021 by two independent researchers. Search terms related to deep learning, digital pathology, omics, and multimodal fusion were combined.ResultsWe identified a total of 11 studies meeting the inclusion criteria, namely studies that used convolutional neural networks for haematoxylin and eosin image analysis of patients with cancer in combination with integrated omics data. Publications were categorised according to their endpoints: 7 studies focused on survival analysis and 4 studies on prediction of cancer subtypes, malignancy or microsatellite instability with spatial analysis.ConclusionsImage-based classifiers already show high performances in prognostic and predictive cancer diagnostics. The integration of omics data led to improved performance in all studies described here. However, these are very early studies that still require external validation to demonstrate their generalisability and robustness. Further and more comprehensive studies with larger sample sizes are needed to evaluate performance and determine clinical benefits.

COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study

Abstract: People living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated.This study is a population-scale real-world evaluation of the United Kingdom's third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess the third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population.The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5%, respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Patients with lymphoma had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at an increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01, respectively. p < 0.001 for both).Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous and lower than the general population. Many patients with cancer will remain at the increased risk of coronavirus infections even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit the disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.

Booster doses of COVID-19 vaccines for patients with haematological and solid cancer: a systematic review and individual patient data meta-analysis

Abstract: Patients with cancer have an increased risk of severe disease and mortality from COVID-19, as the disease and antineoplastic therapy cause reduced vaccine immunogenicity. Booster doses have been proposed to enhance protection, and efficacy data are emerging from several studies.To evaluate the proportion of COVID-19 primary vaccination non-responders with cancer who seroconvert after a booster dose.PubMed, EMBASE, CENTRAL and medRxiv were searched from 1st January 2021 to 10th March 2022. Quality was assessed using the Joanna Briggs Institute Critical Appraisal checklist.After the eligibility assessment, 22 studies were included in this systematic review and 17 for meta-analysis of seroconversion in non-responders, pooling a total of 849 patients with haematological cancer and 82 patients with solid cancer. Haematological cancer non-responders exhibited lower seroconversion at 44% (95% CI 36-53%) than solid cancer at 80% (95% CI 69-87%). Individual patient data meta-analysis found the odds of having a meaningful rise in antibody titres to be significantly associated with increased duration between the second and third dose (OR 1.02, 95% CI 1.00-1.03, P ≤ 0.05), age of patient (OR 0.960, 95% CI 0.934-0.987, P ≤ 0.05) and cancer type. With patients with haematological cancer as a reference, patients with lung cancer had 16.8 times the odds of achieving a meaningful increase in antibody titres (OR 16.8, 95% CI 2.95-318, P ≤ 0.05) and gastrointestinal cancer patients had 25.4 times the odds of achieving a meaningful increase in antibody titres (OR 25.4, 95% CI 5.26-492.21, P ≤ 0.05).administration of a COVID-19 vaccine booster dose is effective in improving seroconversion and antibody levels. Patients with haematological cancer consistently demonstrate poorer response to booster vaccines than patients with solid cancer.

Impact of COVID-19 and suspension of colorectal cancer screening on incidence and stage distribution of colorectal cancers in the Netherlands

Abstract: Many countries had to suspend their colorectal cancer (CRC) screening programme as a result of the COVID-19 pandemic. This eventually may lead to postponed diagnoses of premalignant lesions and CRC, resulting in increased incidence or more advanced CRCs rates. This study aimed to assess the impact of the COVID-19 pandemic on incidence and stage distribution of CRCs in the Netherlands, by monitoring CRC diagnoses and stage distribution in the months before, during and after the first COVID-19 wave. Data on incidence and stage distribution of CRCs of individuals aged 55-75 years in 25 hospitals in the Netherlands were extracted from the Netherlands Cancer Registry. The observed incidence after the suspension (March 2020-December 2020) was compared to the expected incidence in the same period. In the period April to June 2020, we observed the largest decrease in the total incidence of CRC. We found that 48% of the decrease was due to stage I, 23% due to stage II, 23% due to stage III and 5% due to stage IV. After gradually resuming screening mid May 2020, we observed an increase in CRC diagnoses from July 2020 onwards. As of October 2020, the observed number of diagnoses was higher than the expected number. As the decrease was mainly limited to stage I CRCs, it seems that the temporary suspension of the CRC screening programme due to the COVID-19 pandemic will have a minimal long-term impact on stage distribution and CRC mortality.

Definition of oligometastatic esophagogastric cancer and impact of local oligometastasis-directed treatment: A systematic review and meta-analysis.

Abstract: Local treatment (metastasectomy or stereotactic radiotherapy) for oligometastatic disease (OMD) in patients with esophagogastric cancer may improve overall survival (OS). The primary aim was to identify definitions of esophagogastric OMD. A secondary aim was to perform a meta-analysis of OS after local treatment versus systemic therapy alone for OMD.Studies and study protocols reporting on definitions or OS after local treatment for esophagogastric OMD were included. The primary outcome was the maximum number of organs/lesions considered OMD and the maximum number of lesions per organ (i.e. 'organ-specific' OMD burden). Agreement was considered to be either absent/poor (< 50%), fair (50%-75%), or consensus (≥ 75%). The secondary outcome was the pooled adjusted hazard ratio (aHR) for OS after local treatment versus systemic therapy alone. The ROBINS tool was used for quality assessment.A total of 97 studies, including 7 study protocols, and 2 prospective studies, were included. OMD was considered in 1 organ with ≤ 3 metastases (consensus). 'Organ-specific' OMD burden could involve bilobar ≤ 3 liver metastases, unilateral ≤ 2 lung metastases, 1 extra-regional lymph node station, ≤ 2 brain metastases, or bilateral adrenal gland metastases (consensus). Local treatment for OMD was associated with improved OS compared with systemic therapy alone based on 6 non-randomized studies (pooled aHR 0.47, 95% CI: 0.30-0.74) and for liver oligometastases based on 5 non-randomized studies (pooled aHR 0.39, 95% CI: 0.22-0.59). All studies scored serious risk of bias.Current literature considers esophagogastric cancer spread limited to 1 organ with ≤ 3 metastases or 1 extra-regional lymph node station to be OMD. Local treatment for OMD appeared associated with improved OS compared with systemic therapy alone. Prospective randomized trials are warranted.

Updated efficacy and safety of KEYNOTE-224: a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib.

Abstract: Pembrolizumab, a PD-1 inhibitor, demonstrated anti-tumour activity and tolerability in patients treated with sorafenib and with advanced hepatocellular carcinoma in KEYNOTE-224. Longer-term efficacy and safety after ∼2.5 years of additional follow-up are reported.Adults with confirmed hepatocellular carcinoma who experienced progression after or intolerance to sorafenib treatment received pembrolizumab 200 mg every 3 weeks for ≤35 cycles or until confirmed progression, unacceptable toxicity, withdrawal of consent or investigator decision. The primary end-point was objective response rate assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumours v1.1. The secondary end-points included duration of response, disease control rate, time to progression, progression-free survival, overall survival and adverse events.Efficacy and safety were assessed in 104 patients. The median time from first dose to data cutoff was 45.1 months (range, 41.3-49.3). Objective response rate was 18.3% (95% CI: 11.4-27.1), and median duration of response was 21.0 months (range, 3.1 to 39.5+). Disease control rate was 61.5%, and median time to progression was 4.8 months (95% CI: 3.9-7.0). Median progression-free survival was 4.9 months (95% CI: 3.5-6.7) and median overall survival was 13.2 months (95% CI: 9.7-15.3). Of 104 patients, 76 (73.1%) patients reported treatment-related adverse events; most were low grade in severity (grade 3-4, n = 26 [25.0%]; grade 5, n = 1 [1.0%]). Immune-mediated hepatitis occurred in 3 patients (all grade 3). No viral-induced hepatitis flares occurred.After ∼2.5 years of additional follow-up, pembrolizumab continued to provide durable anti-tumour activity and no new safety concerns were identified.NCT02702414.

Durvalumab consolidation in patients with unresectable stage III non-small cell lung cancer with driver genomic alterations.

Abstract: Durvalumab is the standard-of-care as consolidation therapy after chemo-radiotherapy in stage III unresectable non-small cell lung cancer (NSCLC); however, its activity across patients with NSCLC harbouring driver genomic alterations (dGA) is poorly characterised.Multicentre retrospective study including patients with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and October 2020 at 26 centres in Europe and America. Clinical and biological data were collected; dGA included: EGFR/BRAF/KRAS mutations (m) and ALK/ROS1 rearrangements (r). We evaluated progression-free survival (PFS) and overall survival (OS) based on dGA.Out of 323 patients included, 43 patients had one dGA: KRASm (n = 26; 8 G12C), EGFRm (n = 8; 6 del19/ex21), BRAFm (n = 5; 4 V600E) and ALKr (n = 4). The median age was 66 years [39-84], gender ratio 1:1, with 98% performance status (PS) 0-1 and 19% non-smokers; 88% had adenocarcinoma. PD-L1 was positive in 85% (n = 4 missing). In the whole cohort, the median PFS was 17.5 months (mo.) (95% CI, 13.2-24.9) and median OS 47 mo (95%CI, 47-not reached [NR]). No statistically significant differences in terms of the median PFS were observed between patients with dGA vs. non-dGA: 14.9 mo (95% CI, 8.1-NR) vs. 18 mo. (95% CI, 13.4-28.3) (P = 1.0); however, when analysed separately: the median PFS was NR (11.3-NR) in the KRASm G12C vs. 8.1 mo (5.8-NR) in the EGFRm del19/ex21 vs. 7.8 mo (7.7-NR) in the BRAFm V600E/ALKr (P = 0.02).We observed limited activity of durvalumab consolidation in patients with stage III unresectable NSCLC with EGFR/BRAFm and ALKr but not for those harbouring KRASm. Larger prospective studies are needed to confirm these findings.

Trastuzumab emtansine for patients with non–small cell lung cancer positive for human epidermal growth factor receptor 2 exon-20 insertion mutations

Abstract: Human epidermal growth factor receptor 2 (HER2) mutations are present in ∼3% of patients with non-small cell lung cancer (NSCLC), with exon-20 insertions accounting for ∼90% of such HER2 mutations and having been identified as driver oncogenic alterations. Antibody-cytotoxic drug conjugates including trastuzumab deruxtecan have shown an excellent efficacy for NSCLC with HER2 mutations. We have now performed a phase II study to evaluate the efficacy of ado-trastuzumab emtansine (T-DM1) for NSCLC positive for HER2 exon-20 insertion mutations.Eligible patients with HER2 exon-20 insertion mutations confirmed by next-generation sequencing or multiplex polymerase chain reaction platforms and a history of one or two lines of chemotherapy received T-DM1 (3.6 mg/kg) intravenously every 21 days. The primary end-point of the study was the objective response rate (ORR).Between February 2019 and July 2020, 22 patients were enrolled in the study. A775_G776insYVMA was the most frequent HER2 exon-20 insertion mutation, accounting for 19 (86.4%) of the 22 patients. The ORR was 38.1% (90% confidence interval, 23.0-55.9%), and the disease control rate was 52.4%. The median duration of response was 3.5 months, and the median progression-free survival and median overall survival were 2.8 and 8.1 months, respectively. Toxicity was mild, with the frequency of adverse events of grade ≥3 being low.T-DM1 is a potential treatment option for patients with NSCLC with HER2 exon-20 insertion mutations. Further investigation of biomarkers for T-DM1 is warranted to improve its efficacy for NSCLC with such mutations.JapicCTI-194620.

Tumour-agnostic circulating tumour DNA analysis for improved recurrence surveillance after resection of colorectal liver metastases: A prospective cohort study.

Abstract: Nearly 50% of patients recur within two years after curatively intended resection of colorectal cancer liver metastasis (CRLM). The optimal surveillance strategy is unknown due to the lack of evidence. Here, we explored the potential for improving postoperative CRLM surveillance by performing serial circulating tumour DNA (ctDNA) assessments parallel to standard-of-care surveillance.499 prospectively collected serial plasma samples from 96 patients undergoing CRLM resection were analysed using the tumour-agnostic methylation multiplex droplet-digital PCR test 'TriMeth'.Patients with ctDNA postoperatively or post adjuvant chemotherapy experienced a significant lower recurrence-free survival than patients without ctDNA (hazard ratio (HR) 4.5; P < 0.0001 and HR 8.4, P < 0.0001). ctDNA status was a stronger predictor of recurrence than standard clinical risk factors and carcinoembryonic antigen. Serial TriMeth analysis detected ctDNA before radiological recurrence in 55.6% of ctDNA-positive patients, with up to 10.6 months lead-time (median 3.1 months). During surveillance, 24% of patients had inconclusive CT scans, which was associated with a significant delay in recurrence diagnosis (median 3.5 months versus 1.0 month, P < 0.0001). Uniquely, ctDNA status at the time of inconclusive CT scans predicted recurrence with positive and negative predictive values of 100%, and 75% (P = 0.0003). Serial TriMeth analysis allowed ctDNA growth rate assessment and revealed that fast ctDNA growth was associated with poor overall survival (HR: 1.6, P = 0.0052).Serial postoperative ctDNA analysis has a strong prognostic value and is more sensitive for recurrence detection than standard-of-care CRLM surveillance tools. Altogether, TriMeth provides several opportunities for improving postoperative surveillance of CRLM patients.

UGT1A1 genotype-guided dosing of irinotecan: A prospective safety and cost analysis in poor metaboliser patients.

Abstract: AimTo determine the safety, feasibility, pharmacokinetics, and cost of UGT1A1 genotype-guided dosing of irinotecan.Patients and methodsIn this prospective, multicentre, non-randomised study, patients intended for treatment with irinotecan were pre-therapeutically genotyped for UGT1A1∗28 and UGT1A1∗93. Homozygous variant carriers (UGT1A1 poor metabolisers; PMs) received an initial 30% dose reduction. The primary endpoint was incidence of febrile neutropenia in the first two cycles of treatment. Toxicity in UGT1A1 PMs was compared to a historical cohort of UGT1A1 PMs treated with full dose therapy, and to UGT1A1 non-PMs treated with full dose therapy in the current study. Secondary endpoints were pharmacokinetics, feasibility, and costs.ResultsOf the 350 evaluable patients, 31 (8.9%) patients were UGT1A1 PM and received a median 30% dose reduction. The incidence of febrile neutropenia in this group was 6.5% compared to 24% in historical UGT1A1 PMs (P = 0.04) and was comparable to the incidence in UGT1A1 non-PMs treated with full dose therapy. Systemic exposure of SN-38 of reduced dosing in UGT1A1 PMs was still slightly higher compared to a standard-dosed irinotecan patient cohort (difference: +32%). Cost analysis showed that genotype-guided dosing was cost-saving with a cost reduction of €183 per patient.ConclusionUGT1A1 genotype-guided dosing significantly reduces the incidence of febrile neutropenia in UGT1A1 PM patients treated with irinotecan, results in a therapeutically effective systemic drug exposure, and is cost-saving. Therefore, UGT1A1 genotype-guided dosing of irinotecan should be considered standard of care in order to improve individual patient safety.

Predicting 10-year survival after resection of colorectal liver metastases; an international study including biomarkers and perioperative treatment.

Abstract: BackgroundThe aim of this study was to develop a prediction model for 10-year overall survival (OS) after resection of colorectal liver metastasis (CRLM) based on patient, tumour and treatment characteristics.MethodsConsecutive patients after complete resection of CRLM were included from two centres (1992–2019). A prediction model providing 10-year OS probabilities was developed using Cox regression analysis, including KRAS, BRAF and histopathological growth patterns. Discrimination and calibration were assessed using cross-validation. A web-based calculator was built to predict individual 10-year OS probabilities.ResultsA total of 4112 patients were included. The estimated 10-year OS was 30% (95% CI 29–32). Fifteen patient, tumour and treatment characteristics were independent prognostic factors for 10-year OS; age, gender, location and nodal status of the primary tumour, disease-free interval, number and diameter of CRLM, preoperative CEA, resection margin, extrahepatic disease, KRAS and BRAF mutation status, histopathological growth patterns, perioperative systemic chemotherapy and hepatic arterial infusion pump chemotherapy. The discrimination at 10-years was 0.73 for both centres. A simplified risk score identified four risk groups with a 10-year OS of 57%, 38%, 24%, and 12%.ConclusionsTen-year OS after resection of CRLM is best predicted with a model including 15 patient, tumour, and treatment characteristics. The web-based calculator can be used to inform patients. This model serves as a benchmark to determine the prognostic value of novel biomarkers.