Inter-fraction motion robustness in a prospective phase II trial on dose-escalated proton reirradiation for locally recurrent rectal cancer.

Background And Purpose: Intensity modulated proton therapy (IMPT) enables generation of conformal dose plans with organ at risk (OAR) sparing potential. However, pelvic IMPT robustness is challenged by inter-fraction motion caused by constant anatomical variations. In this study, the dosimetric impact of inter-fraction motion on target coverage and dose to OAR was quantified in the prospective phase II study ReRad-II on dose-escalated proton reirradiation for locally recurrent rectal cancer (LRRC).

Electron beam radiotherapy for the management of squamous cell carcinoma of the anal margin.

Purpose And Objective: Squamous cell carcinoma of the anal margin (SCCAM) is an uncommon lesion that comprises one-third to a quarter of all anal squamous cell carcinoma. Treatment involves surgery or exclusive radiotherapy for small tumours, whereas the preferred treatment for larger tumours is chemoradiotherapy. In our department, selected patients with SCCAM are treated with electron beam radiotherapy using one perineal field.

Treatment planning for patients with low rectal cancer in a multicenter prospective organ preservation study.

Background: Non-surgical management of rectal cancer relies on (chemo)radiotherapy as the definitive treatment modality. This study reports and evaluates the clinical high dose radiotherapy treatment plans delivered to patients with low resectable rectal cancer in a Danish multicenter trial.

Methods: The Danish prospective multicenter phase II Watchful Waiting 2 trial (NCT02438839) investigated definitive chemoradiation for non-surgical management of low rectal cancer.

Risk factors and outcome following salvage surgery for squamous cell carcinoma of the anus.

Background: Chemoradiotherapy is the primary treatment for anal cancer. 15-33% of patients will have persistent or recurrent disease after treatment requiring salvage surgery. Relapse after surgery, postoperative complications, and mortality as well as possible risk factors are not fully understood due to the rareness of the disease.

Delta tocotrienol as a supplement to FOLFOXIRI in first-line treatment of metastatic colorectal cancer. A randomized, double-blind, placebo-controlled phase II study.

Purpose: Triplet chemotherapy might be more effective than doublet chemotherapy in metastatic colorectal cancer (mCRC), but it may also be marked by increased toxicity. To investigate whether -tocotrienol, a vitamin E analogue, with possible neuroprotective and anti-inflammatory effects, reduces the toxicity of triplet chemotherapy, we conducted a randomized, double-blind, placebo-controlled trial in mCRC patients receiving first-line 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI).

Material And Methods: Seventy patients with mCRC were randomly assigned (1:1) to receive FOLFOXIRI plus either -tocotrienol or placebo at the Department of Oncology, Vejle Hospital, Denmark.

Nordic anal cancer (NOAC) group consensus guidelines for risk-adapted delineation of the elective clinical target volume in anal cancer.

To date, anal cancer patients are treated with radiotherapy to similar volumes despite a marked difference in risk profile based on tumor location and stage. A more individualized approach to delineation of the elective clinical target volume (CTVe) could potentially provide better oncological outcomes as well as improved quality of life. The aim of the present work was to establish Nordic Anal Cancer (NOAC) group guidelines for delineation of the CTVe in anal cancer.

Precision medicine applied to metastatic colorectal cancer using tumor-derived organoids and in-vitro sensitivity testing: a phase 2, single-center, open-label, and non-comparative study.

Background: Patients with colorectal metastatic disease have a poor prognosis, limited therapeutic options, and frequent development of resistance. Strategies based on tumor-derived organoids are a powerful tool to assess drug sensitivity at an individual level and to suggest new treatment options or re-challenge. Here, we evaluated the method's feasibility and clinical outcome as applied to patients with no satisfactory treatment options.

Gene Methylation in Circulating Tumor DNA as an Early Biomarker for Treatment Effect in Metastatic Colorectal Cancer.

Despite several limitations, the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) are still the gold standard in response evaluation of metastatic colorectal cancer (mCRC).

Intensified Induction Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Anus-A Population-Based Experience from the Danish Anal Cancer Group.

Locally advanced squamous cell carcinoma of the anus (LASCCA) has a poor prognosis with a high risk of treatment failure calling for intensified therapy. We present the long-term follow-up of a nationwide cohort of LASCCA treated with intensified induction chemotherapy (ICT). The study included patients with LASCCA (T3-4N0 or T1-4N+) treated with at least one cycle of ICT (cisplatin, ifosfamide, leucoverin, and 5-flourouracil) between 1998-2018.

Re-exposure to immunotherapy in metastatic colon cancer: A case report.

Re-exposure to immunotherapy in metastatic colorectal cancer may be indicated in selected patients that previously benefitted from immunotherapy with tolerable irAEs.

Nonplatinum-based therapy with Paclitaxel and Capecitabine for advanced squamous cell carcinomas of the anal canal: A population-based Danish anal cancer group study.

Background: First-line platinum-based therapy for advanced squamous cell carcinomas of the anal canal (SCCA) implies a risk of substantial side effects, and data on second-line treatment options are limited. Paclitaxel and Capecitabine are a well-known regimen with a moderate toxicity profile, but its efficacy has not been evaluated.

Methods: We conducted a retrospective study using Danish Hospital Registers of patients treated with Paclitaxel and Capecitabine for inoperable, recurrent, or advanced metastatic SCCA in Denmark, between January 2000 and July 2018.

Comprehensive Analysis of DNA Methylation and Prediction of Response to NeoadjuvantTherapy in Locally Advanced Rectal Cancer.

The treatment for locally advanced rectal carcinomas (LARC) is based on neoadjuvant chemoradiotherapy (nCRT) and surgery, which results in pathological complete response (pCR) in up to 30% of patients. Since epigenetic changes may influence response to therapy, we aimed to identify DNA methylation markers predictive of pCR in LARC patients treated with nCRT. We used high-throughput DNA methylation analysis of 32 treatment-naïve LARC biopsies and five normal rectal tissues to explore the predictive value of differentially methylated (DM) CpGs.

Gene Methylation as a Universal, Longitudinal Plasma Marker for Evaluating the Clinical Benefit from Last-Line Treatment with Regorafenib in Metastatic Colorectal Cancer.

There is a need for biomarkers to improve the clinical benefit from systemic treatment of colorectal cancer. We designed a prospective, clinical study where patients receiving regorafenib as last-line treatment had sequential blood samples drawn. Effect and toxicity was monitored.

Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response.

Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data.

Long-term results of a randomized trial in locally advanced rectal cancer: no benefit from adding a brachytherapy boost.

Purpose/objective(s): Mature data on tumor control and survival are presented from a randomized trial of the addition of a brachytherapy boost to long-course neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer.

Methods And Materials: Between March 2005 and November 2008, 248 patients with T3-4N0-2M0 rectal cancer were prospectively randomized to either long-course preoperative CRT (50.4 Gy in 28 fractions, per oral tegafur-uracil and L-leucovorin) alone or the same CRT schedule plus a brachytherapy boost (10 Gy in 2 fractions).

Phase II trial of temsirolimus alone and in combination with irinotecan for KRAS mutant metastatic colorectal cancer: outcome and results of KRAS mutational analysis in plasma.

Background: Patients with chemotherapy refractory metastatic colorectal cancer and KRAS mutations have no effective treatment option. The present study evaluated the efficacy of temsirolimus in chemotherapy refractory mCRC with KRAS mutations. Furthermore, we wanted to investigate if resistance to temsirolimus could be reversed by the addition of irinotecan.

Tumour hypoxia imaging with 18F-fluoroazomycinarabinofuranoside PET/CT in patients with locally advanced rectal cancer.

Objective: The aim of this study was to investigate the feasibility of F-fluoroazomycinarabinofuranoside (F-FAZA) positron emission tomography (PET)/computed tomography (CT) in patients with locally advanced rectal cancer.

Materials And Methods: The study included 14 patients with locally advanced rectal cancer. Before chemoradiotherapy, PET/CT with F-FAZA was performed with static 15 min images 2 h after injection of F-FAZA.

Single nucleotide polymorphisms in the HIF-1α gene and chemoradiotherapy of locally advanced rectal cancer.

The aim of this study was to investigate the predictive impact of polymorphisms in the HIF-1α gene on the response to chemoradiotherapy (CRT) in rectal cancer. This study included two cohorts of patients with locally advanced rectal cancer receiving long-course CRT. The HIF-1α C1772T (rs11549465), G1790A (rs11549467) and c(*)191T>C (rs2057482) polymorphisms were investigated in the test cohort (n=65), and HIF-1α c(*)191T>C was analysed in the validation cohort (n=198).

The influence of tissue ischemia on biomarker expression in colorectal cancer.

The aim of the present study was to investigate the influence of fixation delay and the perioperative ischemia on hypoxia inducible factor (HIF)-1α gene expression, HIF-1α protein expression, and immunohistochemical (IHC) expression of HIF-1α, GLUT-1, Bcl-2, and Ki-67 in colorectal cancer. The study included 25 surgically removed colorectal tumors. Three sets of samples were collected readily after removal and exposed to 0, 30, and 60 minutes of delay of fixation or freezing.

Immunohistological expression of HIF-1α, GLUT-1, Bcl-2 and Ki-67 in consecutive biopsies during chemoradiotherapy in patients with rectal cancer.

The aim of this study was to describe the dynamics of HIF-1α, GLUT-1, Bcl-2 and Ki-67 during chemoradiotherapy (CRT) of rectal cancer, and to investigate the fluctuation of these biomarkers in relation to pathological response to CRT. The study included 86 patients with rectal adenocarcinoma receiving preoperative CRT (>50.4 Gy and Uracil/Tegafur).

Pretreatment HIF-1α and GLUT-1 expressions do not correlate with outcome after preoperative chemoradiotherapy in rectal cancer.

Unlabelled: The aim of the present study was to investigate hypoxia-inducible factor 1α (HIF-1α) and glucose transporter-1 (GLUT-1) expressions as predictors of response and survival after chemoradiotherapy in pretreatment biopsy specimens from patients with rectal cancer.

Materials And Methods: The immunohistological expressions of HIF-1α and GLUT-1 were investigated in pretreatment biopsies from 86 patients with rectal cancer receiving long course preoperative chemoradiotherapy. The immunohistological stainings were scored semi-quantitatively (percentage of stained cells and staining intensity), and an immunoreactive score was calculated.