Heterogeneity in response to neoadjuvant radiotherapy between soft tissue sarcoma histotypes: associations between radiology and pathology findings.

Objective: To investigate imaging biomarkers of tumour response by describing changes in imaging and pathology findings after neoadjuvant radiotherapy (nRT) and exploring their correlations.

Materials And Methods: Tumour diameter, volume, and tumour-to-muscle signal intensity (SI) ratio were collected before and after radiotherapy in a cohort of 107 patients with intermediate/high-grade STS and were correlated with post-radiotherapy pathology findings (percentage of necrosis, viable cells, and fibrosis) using Spearman Rank test. Pathological complete response (pCR) was defined as no residual viable cells present, whereas the presence of < 10% viable cells was defined as near-complete pathologic response (near-pCR).

Platinum retention in plasma, urine, and normal colonic mucosa in cisplatin-treated testicular cancer survivors.

Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have increased cancer risk. Platinum retention in healthy tissue may contribute to carcinogenesis. We assessed total platinum concentrations in plasma, urine, and normal colonic mucosa samples in TCS treated with cisplatin.

Karyotype evolution in response to chemoradiotherapy and upon recurrence of esophageal adenocarcinomas.

The genome of esophageal adenocarcinoma (EAC) is highly unstable and might evolve over time. Here, we track karyotype evolution in EACs in response to treatment and upon recurrence through multi-region and longitudinal analysis. To this end, we introduce L-PAC (low-purity inference of absolute copy-number alterations [CNAs]), a bio-informatics technique that allows inference of absolute CNAs of low-purity samples by leveraging the information of high-purity samples from the same cancer.

Variation in the detection of lymphovascular invasion in T1 colorectal cancer and its impact on treatment: A nationwide Dutch study.

Background: Lymphovascular invasion (LVI) plays an important role in determining the risk of lymph node metastasis (LNM) in T1 colorectal cancer (CRC) patients and influencing treatment decisions and patient outcomes.

Objective: This study evaluated how the detection of LVI varies between Dutch laboratories and investigated its impact on the treatment and oncological outcomes of T1 CRC patients.

Methods: Pathology reports and clinical data of T1 CRC patients who underwent local resection between 2015 and 2019 were obtained from the Dutch nationwide pathology databank (Palga cohort, n = 5513).

Added value of body MRI to detect primary abdominal malignancies in the diagnostic work-up of patients with adenocarcinoma of unknown primary.

Purpose: This study aimed to evaluate the added benefit of body MRI (covering the chest, abdomen, and pelvis) to detect the primary tumour in patients with adenocarcinoma of unknown primary (ACUP) and a suspected abdominal malignancy in whom previous diagnostic work-up with CT and/or FDG-PET/CT did not yield a primary tumour diagnosis.

Methods: Thirty ACUP patients with a suspected primary tumour in the abdomen/pelvis (based on pathology and/or pattern of disease) underwent MRI (T2-weighted, DWI, pre- and post-contrast T1-weighted) after completion of their initial diagnostic work-up with CT and/or PET/CT. Effects of MRI to establish a primary tumour diagnosis (and to detect additional metastatic sites) were documented.

Non-invasive CT radiomic biomarkers predict microsatellite stability status in colorectal cancer: a multicenter validation study.

Background: Microsatellite instability (MSI) status is a strong predictor of response to immunotherapy of colorectal cancer. Radiogenomic approaches promise the ability to gain insight into the underlying tumor biology using non-invasive routine clinical images. This study investigates the association between tumor morphology and the status of MSI versus microsatellite stability (MSS), validating a novel radiomic signature on an external multicenter cohort.

The mode of circumferential margin involvement in rectal cancer determines its impact on outcomes: A population-based study.

Background: The clinical value of different modes of CRM involvement in rectal cancer patients is unclear. This study aims to determine the clinical impact of different modes of circumferential resection margin (CRM) involvement in patients with a locally advanced rectal carcinoma.

Patients And Methods: A cohort of patients who were diagnosed with stage III rectal cancer between June 2014 and June 2020 was selected from the prospective Dutch nationwide pathology databank (PALGA).

Identifying the primary tumour in patients with cancer of unknown primary (CUP) using [F]FDG PET/CT: a systematic review and individual patient data meta-analysis.

Purpose: In this systematic review and individual patient data (IPD) meta-analysis, we analysed the diagnostic performance of [F]FDG PET/CT in detecting primary tumours in patients with CUP and evaluated whether the location of the predominant metastatic site influences the diagnostic performance.

Methods: A systematic literature search from January 2005 to February 2024 was performed to identify articles describing the diagnostic performance of [F]FDG PET/CT for primary tumour detection in CUP. Individual patient data retrieved from original articles or obtained from corresponding authors were grouped by the predominant metastatic site.

Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer.

Background: Mismatch repair-deficient (dMMR) tumors can be found in 10 to 15% of patients with nonmetastatic colon cancer. In these patients, the efficacy of chemotherapy is limited. The use of neoadjuvant immunotherapy has shown promising results, but data from studies of this approach are limited.

Efficacy-effectiveness analysis on survival in a population-based real-world study of BRAF-mutated metastatic colorectal cancer patients treated with encorafenib-cetuximab.

Background: Encorafenib-cetuximab has been approved for pretreated BRAF-mutated metastatic colorectal cancer (mCRC) patients based on efficacy demonstrated in the randomized phase III BEACON trial. The aim of this real-world effectiveness study is to improve knowledge on the generalizability of trial results.

Methods: This population-based real-world study includes all mCRC patients in the Netherlands treated with encorafenib-cetuximab since approval.

Characterization of discordance between mismatch repair deficiency and microsatellite instability testing may prevent inappropriate treatment with immunotherapy.

In the Drug Rediscovery Protocol (DRUP), patients with cancer are treated based on their tumor molecular profile with approved targeted and immunotherapies outside the labeled indication. Importantly, patients undergo a tumor biopsy for whole-genome sequencing (WGS) which allows for a WGS-based evaluation of routine diagnostics. Notably, we observed that not all biopsies of patients with dMMR/MSI-positive tumors as determined by routine diagnostics were classified as microsatellite-unstable by subsequent WGS.

Exploiting a subtype-specific mitochondrial vulnerability for successful treatment of colorectal peritoneal metastases.

Peritoneal metastases (PMs) from colorectal cancer (CRC) respond poorly to treatment and are associated with unfavorable prognosis. For example, the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery in resectable patients shows limited benefit, and novel treatments are urgently needed. The majority of CRC-PMs represent the CMS4 molecular subtype of CRC, and here we queried the vulnerabilities of this subtype in pharmacogenomic databases to identify novel therapies.

Improving diagnostic accuracy of identifying gastric cancer patients with peritoneal metastases: tumor-guided cell-free DNA analysis of peritoneal fluid.

Detection of peritoneal dissemination (PD) in gastric cancer (GC) patients remains challenging. The feasibility of tumor-guided cell-free DNA (cfDNA) detection in prospectively collected peritoneal fluid (ascites and peritoneal lavage) was investigated and compared to conventional cytology in 28 patients. Besides conventional cytology, next generation sequencing was performed on primary tumor DNA and cell-free DNA from peritoneal fluid.

Imaging in the era of risk-adapted treatment in colon cancer.

The treatment landscape for patients with colon cancer is continuously evolving. Risk-adapted treatment strategies, including neoadjuvant chemotherapy and immunotherapy, are slowly finding their way into clinical practice and guidelines. Radiologists are pivotal in guiding clinicians toward the most optimal treatment for each colon cancer patient.

Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study.

Background: Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy (HAIP-SYS) for liver-only colorectal liver metastases (CRLMs) has shown promising results but has not been adopted worldwide. This study evaluated the feasibility of HAIP-SYS in the Netherlands.

Methods: This was a single-arm phase II study of patients with CRLMs who received HAIP-SYS consisting of floxuridine with concomitant systemic FOLFOX or FOLFIRI.

Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity of such aberrant signaling. Although inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of protein phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells.

Size and depth of residual tumor after neoadjuvant chemoradiotherapy in rectal cancer - implications for the development of new imaging modalities for response assessment.

With the shift towards organ preserving treatment strategies in rectal cancer it has become increasingly important to accurately discriminate between a complete and good clinical response after neoadjuvant chemoradiotherapy (CRT). Standard of care imaging techniques such as CT and MRI are well equipped for initial staging of rectal tumors, but discrimination between a good clinical and complete response remains difficult due to their limited ability to detect small residual vital tumor fragments. To identify new promising imaging techniques that could fill this gap, it is crucial to know the size and invasion depth of residual vital tumor tissue since this determines the requirements with regard to the resolution and imaging depth of potential new optical imaging techniques.

Development and multicenter validation of a multiparametric imaging model to predict treatment response in rectal cancer.

Objectives: To develop and validate a multiparametric model to predict neoadjuvant treatment response in rectal cancer at baseline using a heterogeneous multicenter MRI dataset.

Methods: Baseline staging MRIs (T2W (T2-weighted)-MRI, diffusion-weighted imaging (DWI) / apparent diffusion coefficient (ADC)) of 509 patients (9 centres) treated with neoadjuvant chemoradiotherapy (CRT) were collected. Response was defined as (1) complete versus incomplete response, or (2) good (Mandard tumor regression grade (TRG) 1-2) versus poor response (TRG3-5).

Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial.

Introduction: Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4-8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy.

Correction: Groen et al. Use of Image-Guided Surgical Navigation during Resection of Locally Recurrent Rectal Cancer. 2022, , 645.

The authors wish to make the following corrections to this paper [...

The clinical impact of testing for biomarkers in gastric cancer patients: a real-world cohort.

Background And Aims: In gastric cancer (GC), HER2 was the first biomarker for guided therapy registered for clinical use. Considering the recent approvals of immune check-point blockade (ICB) in gastro-oesophageal cancers, testing for mismatch repair deficiency (dMMR), Epstein-Barr virus (EBV) and PD-L1 combined positive score (CPS) is becoming increasingly important. Here we describe a real-world cohort on biomarker assessment in GC patients.

MRI anatomy of the rectum: key concepts important for rectal cancer staging and treatment planning.

A good understanding of the MRI anatomy of the rectum and its surroundings is pivotal to ensure high-quality diagnostic evaluation and reporting of rectal cancer. With this pictorial review, we aim to provide an image-based overview of key anatomical concepts essential for treatment planning, response evaluation and post-operative assessment. These concepts include the cross-sectional anatomy of the rectal wall in relation to T-staging; differences in staging and treatment between anal and rectal cancer; landmarks used to define the upper and lower boundaries of the rectum; the anatomy of the pelvic floor and anal canal, the mesorectal fascia, peritoneum and peritoneal reflection; and guides to help discern different pelvic lymph node stations on MRI to properly stage regional and non-regional rectal lymph node metastases.

Correlation of radiological and histopathological response after neoadjuvant radiotherapy in soft tissue sarcoma.

Background: The aim of this study was to assess the association between radiological and histopathological response after neoadjuvant radiotherapy (nRT) in soft tissue sarcoma (STS), as well as the prognostic value of the different response evaluation methods on the oncological outcome.

Methods: A retrospective cohort of patients with localized STS of the extremity and trunk wall, treated with nRT followed by resection were included. The radiological response was assessed by RECIST 1.