Circadian rhythm-based cancer therapy in randomised clinical trials.

INTRODUCTION: Since the 2017 Nobel Prize awarded to J. Hall, M. Rosbash and M.W. Young for their discoveries of molecular mechanisms behind the biological clock, circadian rhythm-based therapy, also known as chronotherapy, is receiving more attention in oncology and the number of anatomical sites of interest in this field is increasing. This observation is in line with the clinical evidence provided by trials on head and neck, lung, colorectal and cervical cancers, as well as the presently ongoing chronotherapy trials for breast and brain cancers. AREAS COVERED: The aim of this review was to collate all randomized trials conducted on chronotherapy for various tumor sites and to appraise the evidence for chrono-oncology to advance personalized therapy. Relevant literature was collected from Pubmed/Medline databases and from clinicatrials.gov. EXPERT OPINION: Current randomized clinical trials offer a certain level of evidence for the potential of chronotherapy to personalize oncologic treatment. However, comparison of trial results is hindered by the differences in timing of radiation/chemotherapy, the absence of harmonized recommendations for treatment outcome evaluation and not ultimately, the general lack of considering gender as a matched variable in trials, which was found to be a powerful factor influencing response to treatment.

Developments on tumour site-specific chrono-oncology towards personalised treatment.

Research into chronotherapy has seen notable developments over the past decades, with a clear focus on the identification of circadian clock genes as potential treatment targets. Moreover, new factors are investigated, such as gender and the role of cancer stem cells in influencing the outcome of chronomodulated treatments. These factors could add to the arsenal of parameters that assist with patient stratification and treatment personalisation. Literature analysis showed that certain anatomical sites received more attention and the associated studies reported clinically significant results, even though some findings are contradictory. The aim of this work was to review the existing studies on chrono-oncology using a tumour site-specific approach and to highlight the status of research in various cancers. Inconsistencies in data reporting, the nature of the studies and the highly heterogeneous patient characteristics, highlight the need for well-designed randomised controlled trials to elucidate the real potential of chronotherapy in oncology.

Improving therapeutic ratio in head and neck cancer with adjuvant and cisplatin-based treatments.

Advanced head and neck cancers are difficult to manage despite the large treatment arsenal currently available. The multidisciplinary effort to increase disease-free survival and diminish normal tissue toxicity was rewarded with better locoregional control and sometimes fewer side effects. Nevertheless, locoregional recurrence is still one of the main reasons for treatment failure. Today, the standard of care in head and neck cancer management is represented by altered fractionation radiotherapy combined with platinum-based chemotherapy. Targeted therapies as well as chronotherapy were trialled with more or less success. The aim of the current work is to review the available techniques, which could contribute towards a higher therapeutic ratio in the treatment of advanced head and neck cancer patients.