Critical evaluation of molecular tumour board outcomes following 2 years of clinical practice in a Comprehensive Cancer Centre

Abstract

Background: Recently, molecular tumour boards (MTBs) have been integrated into the clinical routine. Since their benefit remains debated, we assessed MTB outcomes in the Comprehensive Cancer Center Ostbayern (CCCO) from 2019 to 2021.

Methods and results: In total, 251 patients were included. Targeted sequencing was performed with PCR MSI-evaluation and immunohistochemistry for PD-L1, Her2, and mismatch repair enzymes. 125 treatment recommendations were given (49.8%). High-recommendation rates were achieved for intrahepatic cholangiocarcinoma (20/30, 66.7%) and gastric adenocarcinoma (10/16, 62.5%) as opposed to colorectal cancer (9/36, 25.0%) and pancreatic cancer (3/18, 16.7%). MTB therapies were administered in 47 (18.7%) patients, while 53 (21.1%) received alternative treatment regimens. Thus 37.6% of recommended MTB therapies were implemented (47/125 recommendations). The clinical benefit rate (complete + partial + mixed response + stable disease) was 50.0% for MTB and 63.8% for alternative treatments. PFS2/1 ratios were 34.6% and 16.1%, respectively. Significantly improved PFS could be achieved for m1A-tier-evidence-based MTB therapies (median 6.30 months) compared to alternative treatments (median 2.83 months; P = 0.0278).

Conclusion: The CCCO MTB yielded a considerable recommendation rate, particularly in cholangiocarcinoma patients. The discrepancy between the low-recommendation rates in colorectal and pancreatic cancer suggests the necessity of a weighted prioritisation of entities. High-tier recommendations should be implemented predominantly.

Fig. 1. Alterations as a foundation for MTB recommendations.

Oncoprint representation of alterations bearing relevance for MTB recommendations in ≥3.2% of patients (see Supplementary Fig. S1 for all alterations). Blue frames highlight individual alterations on which MTB recommendations were based for first-priority recommendations and orange frames for lower-priority recommendations. The percentage of first- and lower-priority recommendations is given on the right. The order of patients can be translated to PatID using Supplementary Table S3. The row “others” subsumes individual cases with BCL2 loss by IHC, androgen receptor expression, and FGF CNV. MSI microsatellite stability status, TMB tumour mutational burden in mutations per megabase, CUP carcinoma of unknown primary, Ca cancer, CCA cholangiocarcinoma, GIST gastrointestinal stromal tumour, HCC hepatocellular carcinoma, HNSCC head and neck squamous cell cancer, CRC colorectal cancer, NEC neuroendocrine carcinoma, RCC renal cell cancer.

Fig. 2. Comparison of MTB recommendations by the entity.

a Recommendation frequency by cancer type. The percentage of patients receiving treatment recommendations by the MTB is indicated. b Percentage of patients receiving either single or multiple MTB recommendations. c Evidence level of primary treatment recommendation by entity as NCT/DKTK grade. CRC colorectal cancer, iCCA intrahepatic cholangiocarcinoma, PDAC pancreatic ductal adenocarcinoma, Ca cancer, CUP carcinoma of unknown primary, pCCA perihilar cholangiocarcinoma, NSCLC non-small cell lung cancer, HNSCC head and neck squamous cell cancer, HGSC high-grade serous carcinoma, HCC hepatocellular carcinoma, NEC neuroendocrine carcinoma.

Fig. 3. Overview of best-observed responses.

a Stacked bar chart of best-observed responses to MTB-recommended therapies as opposed to alternative therapies. b Alluvial plot displaying the best-observed responses in relation to alteration type and NCT/DKTK evidence level.

Fig. 4. Survival outcome measures.

a Swimmer plot of 43 patients receiving an MTB-recommended therapy with available follow-up data. Blue bars indicate the duration of MTB-recommended therapy. b Comparison of the frequency of PFS2/1 ratios ≥1.3 and <1.3 between MTB-recommended and alternative therapies in evaluable patients. Progression-free survival (c) and overall survival (d) over the entire cohort comparing patients receiving MTB-recommended therapies, alternative therapies after the MTB, and patients without further therapies. Progression-free survival (e) and overall survival (f) achieved by tier m1A-based MTB therapies as opposed to all alternative non-MTB-recommended therapies. The P value was calculated by the log-rank test.