British Journal of Cancer

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ISSN / EISSN : 0007-0920 / 1532-1827
Current Publisher: Springer Science and Business Media LLC (10.1038)
Former Publisher: Elsevier BV (10.1054)
Total articles ≅ 25,959
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Baek-Yeol Ryoo, , Zhenggang Ren, Tae-You Kim, Hongming Pan, Kun-Ming Rau, , Joong-Won Park, Jee Hyun Kim, Chia Jui Yen, et al.
British Journal of Cancer pp 1-9; doi:10.1038/s41416-021-01380-3

Abstract:
Background This open-label, Phase 1b/2 study evaluated the highly selective MET inhibitor tepotinib in systemic anticancer treatment (SACT)-naive Asian patients with advanced hepatocellular carcinoma (aHCC) with MET overexpression. Methods In Phase 2b, tepotinib was orally administered once daily (300, 500 or 1,000 mg) to Asian adults with aHCC. The primary endpoints were dose-limiting toxicities (DLTs) and adverse events (AEs). Phase 2 randomised SACT-naive Asian adults with aHCC with MET overexpression to tepotinib (recommended Phase 2 dose [RP2D]) or sorafenib 400 mg twice daily. The primary endpoint was independently assessed time to progression (TTP). Results In Phase 1b (n = 27), no DLTs occurred; the RP2D was 500 mg. In Phase 2 (n = 90, 45 patients per arm), the primary endpoint was met: independently assessed TTP was significantly longer with tepotinib versus sorafenib (median 2.9 versus 1.4 months, HR = 0.42, 90% confidence interval: 0.26–0.70, P = 0.0043). Progression-free survival and objective response also favoured tepotinib. Treatment-related Grade ≥3 AE rates were 28.9% with tepotinib and 45.5% with sorafenib. Conclusions Tepotinib improved TTP versus sorafenib and was generally well tolerated in SACT-naive Asian patients with aHCC with MET overexpression. Trial registration ClinicalTrials.gov NCT01988493.
Jiaojiao Zheng, Giola Santoni, Shao-Hua Xie, Jesper Lagergren
British Journal of Cancer pp 1-7; doi:10.1038/s41416-021-01408-8

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Correction
Sarah Ouahoud, Rutger J. Jacobs, , G. M. Fühler, Jarom Heijmans, Sander Diks, Manon E. Wildenberg, Lukas J. A. C. Hawinkels, Liudmila L. Kodach, , et al.
British Journal of Cancer pp 1-1; doi:10.1038/s41416-021-01426-6

, On Behalf Of The Age Gap Tmg, , Malcolm W. R. Reed, Esther Herbert, Jenna L. Morgan, Michael Bradburn, Stephen J. Walters, Karen A. Collins, , et al.
British Journal of Cancer pp 1-11; doi:10.1038/s41416-021-01388-9

Abstract:
Background Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy. Methods A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage. Results Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19–0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20–0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08–0.49];BCSS: HR 0.12 [95% CI 0.03–0.44]).Transient negative quality-of-life impacts were observed. Conclusions Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient. Trial Registration ISRCTN 46099296
, Veline L’Esperance, Joanne Bayly, Kate Brain, Lorraine Dallas, John G. Edwards, Thomas Haswell, Crispin Hiley, Natasha Lovell, Julia McAdam, et al.
British Journal of Cancer pp 1-12; doi:10.1038/s41416-021-01361-6

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British Journal of Cancer pp 1-9; doi:10.1038/s41416-021-01402-0

Correction
OmPrakash Shriwas, , Sibasish Mohanty, Pallavi Mohapatra, Sugandh Kumar, Rachna Rath, Sandeep Rai Kaushik, Falak Pahwa, Krushna Chandra Murmu, Saroj Kumar Das Majumdar, et al.
British Journal of Cancer pp 1-1; doi:10.1038/s41416-021-01414-w

Gagandeep Singh, Sunil Manjila, Nicole Sakla, Alan True, Amr H. Wardeh, Niha Beig, Anatoliy Vaysberg, John Matthews, Prateek Prasanna, Vadim Spektor
British Journal of Cancer pp 1-17; doi:10.1038/s41416-021-01387-w

Abstract:
The natural history and treatment landscape of primary brain tumours are complicated by the varied tumour behaviour of primary or secondary gliomas (high-grade transformation of low-grade lesions), as well as the dilemmas with identification of radiation necrosis, tumour progression, and pseudoprogression on MRI. Radiomics and radiogenomics promise to offer precise diagnosis, predict prognosis, and assess tumour response to modern chemotherapy/immunotherapy and radiation therapy. This is achieved by a triumvirate of morphological, textural, and functional signatures, derived from a high-throughput extraction of quantitative voxel-level MR image metrics. However, the lack of standardisation of acquisition parameters and inconsistent methodology between working groups have made validations unreliable, hence multi-centre studies involving heterogenous study populations are warranted. We elucidate novel radiomic and radiogenomic workflow concepts and state-of-the-art descriptors in sub-visual MR image processing, with relevant literature on applications of such machine learning techniques in glioma management.
Francesca Salvianti, Stefania Gelmini, Irene Mancini, Mario Pazzagli, Serena Pillozzi, Elisa Giommoni, Marco Brugia, Francesco Di Costanzo, Francesca Galardi, Francesca De Luca, et al.
British Journal of Cancer pp 1-7; doi:10.1038/s41416-021-01399-6

Abstract:
Within the OMITERC prospective study (OMIcs application from solid to liquid biopsy for a personalised ThERapy of Cancer), we explored the prognostic role of liquid biopsy encompassing cell-free DNA (cfDNA) and circulating tumour cells (CTCs) in KRAS mutated metastatic colorectal cancer (mCRC). We defined a workflow including pre-analytical and analytical procedures collecting blood before therapy and every 3 months until disease progression (PD). CTCs were counted by CellSearch® and isolated by DEPArray™. NGS sequencing of CTCs and cfDNA was performed using a panel of cancer/CRC related genes respectively. KRAS mutational status was mostly concordant between tumour tissues and liquid biopsy. The percentage of cfDNA samples with mutations in CRC driver genes was in line with literature. In longitudinal monitoring circulating biomarkers anticipated or overlapped conventional diagnostic tools in predicting PD. The presence of CTCs at baseline was confirmed a negative prognostic marker. Cell-free DNA and CTCs are readily available candidates for clinical application in mCRC. While CTCs demonstrated a prognostic significance at baseline, cfDNA was confirmed an easily accessible material for monitoring the mutational status of the tumour over time. Moreover, in the longitudinal study, the two markers emerged as complementary in assessing disease progression.
Yuyao Yuan, Zitong Zhao, Liyan Xue, Guangxi Wang, Huajie Song, Ruifang Pang, Juntuo Zhou, , ,
British Journal of Cancer pp 1-7; doi:10.1038/s41416-021-01395-w

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