The definition of international CG for RC delineation endorsed by international experts might support a future homogeneous comparison between clinical trial outcomes.

After neoadjuvant radiochemotherapy (RCT) for locally advanced rectal cancer, 15-27% of the patients experience a pathological complete response (pCR). This observation raises the question as to whether invasive surgery could be avoided in a selected cohort of patients who obtain a clinical complete response after preoperative RCT. In this respect, there has been growing interest in functional imaging techniques to improve clinical response assessment. This systematic review focuses on the role of diffusion-weighted imaging (DWI) and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the prediction of pCR after RCT for rectal cancer. A total of 14 publications on DWI and 25 on (18)F-FDG PET/CT were retrieved. Pooled analysis of individual patient data shows both imaging modalities have a low positive predictive value in the prediction of pCR (mean PPV of 54% and 39% for DWI- and (18)F-FDG PET/CT-based parameters respectively). Especially pre-RCT imaging is unable to predict pCR with overall accuracies of 68-72% for DWI and 44% for (18)F-FDG PET/CT. Qualitative DWI assessment 5-10weeks after the end of RCT may outperform apparent diffusion coefficient (ADC)-based DWI-parameters (overall accuracy of 87% vs. 74-78%). Although few data are available, early changes in FDG-uptake seem promising in the prediction of pCR and the role of (18)F-FDG PET/CT during RCT should be further investigated. Quantitative and qualitative (18)F-FDG PET/CT measurements are equally effective in the assessment of pCR after RCT. The major strength of DWI and (18)F-FDG PET/CT lies in the identification of non-responders who are not candidates for organ preservation. Up to now, DWI and (18)F-FDG PET/CT are not accurate enough to safely select patients for organ-sparing strategies. Future research must focus on the integration of functional imaging with clinical data and molecular biomarkers.

The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep-learning algorithms for whole-slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorise patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver-metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting preclinical and clinical research perspectives.

With the implementation of total mesorectal excision surgery and neoadjuvant (chemo) radiotherapy, the outcome of rectal cancer patients has improved and a substantial proportion of them have become long-term survivors. These advances come at the expense of radiation- and chemotherapy-related toxicity which remains an underestimated problem. Radiation-induced early toxicity in rectal cancer treatment mainly includes diarrhea, cystitis, and perineal dermatitis, while bowel dysfunction, fecal incontinence, bleeding, and perforation, genitourinary dysfunction, and pelvic fractures constitute the majority of late toxicity. It is now generally accepted that short-course radiotherapy (SCRT) and immediate surgery is associated with less early toxicity compared to conventionally fractionated chemoradiotherapy with delayed surgery. There are no significant differences in late toxicity between both treatment regimens. While there is hardly an increase in early toxicity after preoperative SCRT with immediate surgery, late toxicity is substantial compared to surgery alone. Early toxicity is more frequent when a longer interval between SCRT and surgery is used and is comparable to the toxicity observed with conventionally fractionated radiotherapy except that it occurs after the end of the radiotherapy. So far, randomized phase III trials failed to demonstrate a substantial gain in tumoural response when oxaliplatin or molecular agents are added to the multimodality treatment. Moreover, the addition of these drugs increases toxicity and remains therefore experimental.