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The integration of multidisciplinary tumor boards (MTBs) is fundamental in delivering state-of-the-art cancer treatment, facilitating collaborative diagnosis and management by a diverse team of specialists. Despite the clear benefits in personalized patient care and improved outcomes, the increasing burden on MTBs due to rising cancer incidence and financial constraints necessitates innovative solutions. The advent of artificial intelligence (AI) in the medical field offers a promising avenue to support clinical decision-making. This review explores the perspectives of clinicians dedicated to the care of cancer patients—surgeons, medical oncologists, and radiation oncologists—on the application of AI within MTBs. Additionally, it examines the role of AI across various clinical specialties involved in cancer diagnosis and treatment. By analyzing both the potential and the challenges, this study underscores how AI can enhance multidisciplinary discussions and optimize treatment plans. The findings highlight the transformative role that AI may play in refining oncology care and sustaining the efficacy of MTBs amidst growing clinical demands. [ABSTRACT FROM AUTHOR]

Herein, we present a misleading case of advanced papillary thyroid carcinoma with lung, node, and pleural metastases, initially diagnosed as metastatic lung adenocarcinoma with papillary features, based on the histological and immunohistochemical analysis of a pleural biopsy. Between August 2019 and August 2020, the patient received 2 ineffective lines of systemic therapy, including a first line of chemotherapy with cisplatin and pemetrexed, and a second line of immunotherapy with atezolizumab. Comprehensive genomic profiling by next-generation sequencing on the archival pleural biopsy revealed an NTRK1-TMP3 fusion and comutation of the TERT promoter, commonly found in papillary thyroid carcinoma. After palliative partial thyroidectomy that confirmed the diagnosis of papillary thyroid carcinoma, in February 2021, the patient was enrolled in the STARTRK-2 GO40782 basket trial and received entrectinib, an oral pan-TRK inhibitor specifically targeting NTRK- rearranged tumors. After initially experiencing drug-related grade 2 anorexia, dysgeusia, and neurotoxicity and grade 3 asthenia, the dose was reduced, and an excellent and durable objective response was observed. [ABSTRACT FROM AUTHOR]

Background: Tumors with homologous recombination deficiency (HRD) show high sensitivity to platinum salts and poly(ADP-ribose) polymerase-inhibitors in several malignancies. In colorectal cancer (CRC), the role of HRD alterations is mostly unknown.Methods: Next-generation sequencing, whole transcriptome sequencing, and whole exome sequencing were conducted using CRC samples submitted to a commercial Clinical Laboratory Improvement Amendments certified laboratory. Tumors with pathogenic and/or presumed pathogenic mutations in 33 genes involved in the homologous recombination pathway were considered HRD, the others were homologous recombination proficient (HRP). Furthermore, tumor samples from patients enrolled in the phase III TRIBE2 study comparing upfront FOLFOXIRI+bevacizumab vs FOLFOX+bevacizumab were analyzed with next-generation sequencing. The analyses were separately conducted in microsatellite stable or proficient mismatch repair (MSS/pMMR) and microsatellite instable-high or deficient mismatch repair (MSI-H/dMMR) groups. All statistical tests were 2-sided.Results: Of 9321 CRC tumors, 1270 (13.6%) and 8051 (86.4%) were HRD and HRP, respectively. HRD tumors were more frequent among MSI-H/dMMR than MSS/pMMR tumors (73.4% vs 9.5%; P  < .001; q < 0.001). In MSS/pMMR group, HRD tumors were more frequently tumor mutational burden high (8.1% vs 2.2%; P  < .001; q < 0.001) and PD-L1 positive (5.0% vs 2.4%; P  < .001; q = 0.001), enriched in all immune cell and fibroblast populations and genomic loss of heterozygosity-high (16.2% vs 9.5%; P = .03). In the TRIBE2 study, patients with MSS/pMMR and HRD tumors (10.7%) showed longer overall survival compared with MSS/pMMR and HRP tumors (40.2 vs 23.8 months; hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.45 to 0.98; P = .04). Consistent results were reported in the multivariable model (HR = 0.67, 95% CI = 0.45 to 1.02; P = .07). No interaction effect was evident between homologous recombination groups and treatment arm.Conclusions: HRD tumors are a distinctive subgroup of MSS/pMMR CRCs with specific molecular and prognostic characteristics. The potential efficacy of agents targeting the homologous recombination system and immune checkpoint inhibitors in this subgroup is worthy of clinical investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune-checkpoint inhibitors (ICI) show modest activity and efficacy in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients harbouring a proficient mismatch repair system (pMMR). Recently, two phase 2 trials -AtezoTRIBE and MAYA- have challenged this dogma through the administration of an intense first-line chemotherapy backbone consisting of FOLFOXIRI/bevacizumab in patients unselected for their microsatellite status, and immune priming with temozolomide in chemorefractory pMMR/MSS patients with silencing of O6-methylguanine-DNA methyltransferase (MGMT), respectively, reporting promising results. We here present the founding biological rationale of these two studies and their main findings. At the same time, we stress their strengths and drawbacks and open questions still to be address in future clinical investigations. In metastatic colorectal cancer (mCRC), remarkable advances have been achieved with immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4, only in a small subset of tumours (4–5%), harbouring a deficient mismatch repair system (dMMR)/microsatellite instability–high (MSI-H) or mutations in the catalytic subunit of polymerase epsilon (POLE). Within this framework, several combination strategies have been investigated to sensitize proficient mismatch repair (pMMR)/microsatellite stable (MSS) mCRC to ICIs, with disappointing results so far. However, at the last ESMO meeting, two phase II trials AtezoTRIBE and MAYA provided promising results in this field. In the comparative AtezoTRIBE trial, the addition of atezolizumab to FOLFOXIRI (5-fluoruracil, oxaliplatin and irinotecan) and bevacizumab led to a significant advantage in terms of progression free survival (PFS) in a population of untreated mCRC patients, not selected according to MMR/MSI status. In the single-arm MAYA trial, immune priming with temozolomide in pMMR/MSS chemo-resistant mCRC patients with silencing of O6-methylguanine-DNA methyltransferase (MGMT) allowed reporting signals of sensitivity to the subsequent therapy with nivolumab and a low dose of ipilimumab in some patients. Here, we discuss the rationale, results, criticisms and research perspectives opened by these two studies. [ABSTRACT FROM AUTHOR]

Background: Tumors with homologous recombination deficiency (HRD) show high sensitivity to platinum salts and poly(ADP-ribose) polymerase-inhibitors in several malignancies. In colorectal cancer (CRC), the role of HRD alterations is mostly unknown., Methods: Next-generation sequencing, whole transcriptome sequencing, and whole exome sequencing were conducted using CRC samples submitted to a commercial Clinical Laboratory Improvement Amendments certified laboratory. Tumors with pathogenic and/or presumed pathogenic mutations in 33 genes involved in the homologous recombination pathway were considered HRD, the others were homologous recombination proficient (HRP). Furthermore, tumor samples from patients enrolled in the phase III TRIBE2 study comparing upfront FOLFOXIRI+bevacizumab vs FOLFOX+bevacizumab were analyzed with next-generation sequencing. The analyses were separately conducted in microsatellite stable or proficient mismatch repair (MSS/pMMR) and microsatellite instable-high or deficient mismatch repair (MSI-H/dMMR) groups. All statistical tests were 2-sided., Results: Of 9321 CRC tumors, 1270 (13.6%) and 8051 (86.4%) were HRD and HRP, respectively. HRD tumors were more frequent among MSI-H/dMMR than MSS/pMMR tumors (73.4% vs 9.5%; P  < .001; q < 0.001). In MSS/pMMR group, HRD tumors were more frequently tumor mutational burden high (8.1% vs 2.2%; P  < .001; q < 0.001) and PD-L1 positive (5.0% vs 2.4%; P  < .001; q = 0.001), enriched in all immune cell and fibroblast populations and genomic loss of heterozygosity-high (16.2% vs 9.5%; P = .03). In the TRIBE2 study, patients with MSS/pMMR and HRD tumors (10.7%) showed longer overall survival compared with MSS/pMMR and HRP tumors (40.2 vs 23.8 months; hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.45 to 0.98; P = .04). Consistent results were reported in the multivariable model (HR = 0.67, 95% CI = 0.45 to 1.02; P = .07). No interaction effect was evident between homologous recombination groups and treatment arm., Conclusions: HRD tumors are a distinctive subgroup of MSS/pMMR CRCs with specific molecular and prognostic characteristics. The potential efficacy of agents targeting the homologous recombination system and immune checkpoint inhibitors in this subgroup is worthy of clinical investigation., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: EGFR amplification occurs in about 1% of metastatic colorectal cancers (mCRCs) but is not routinely tested as a prognostic or predictive biomarker for patients treated with anti-EGFR monoclonal antibodies. Herein, we aimed to characterize the clinical and molecular landscape of EGFR-amplified mCRC., Methods: In this multinational cohort study, we compared clinical data of 62 patients with EGFR-amplified vs 1459 EGFR nonamplified mCRC, as well as comprehensive genomic data of 35 EGFR-amplified vs 439 EGFR nonamplified RAS/BRAF wild-type and microsatellite stable (MSS) tumor samples. All statistical tests were 2-sided., Results: EGFR amplification was statistically significantly associated with left primary tumor sidedness and RAS/BRAF wild-type status. All EGFR-amplified tumors were MSS and HER2 nonamplified. Overall, EGFR-amplified samples had higher median fraction of genome altered compared with EGFR-nonamplified, RAS/BRAF wild-type MSS cohort. Patients with EGFR-amplified tumors reported longer overall survival (OS) (median OS = 71.3 months, 95% confidence interval [CI] = 50.7 to not available [NA]) vs EGFR-nonamplified ones (24.0 months; 95% CI = 22.8 to 25.6; hazard ratio [HR] = 0.30, 95% CI = 0.20 to 0.44; P < .001; adjusted HR = 0.46, 95% CI = 0.30 to 0.69; P < .001). In the subgroup of patients with RAS/BRAF wild-type mCRC exposed to anti-EGFR-based therapy, EGFR amplification was again associated with better OS (median OS = 54.0 months, 95% CI = 35.2 to NA, vs 29.1 months, 95% CI = 27.0 to 31.9, respectively; HR = 0.46, 95% CI = 0.28 to 0.76; P = .002)., Conclusion: Patients with EGFR-amplified mCRC represent a biologically defined subgroup and merit dedicated clinical trials with novel and more potent EGFR-targeting strategies beyond single-agent monoclonal antibodies., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)