Comparing robust proton versus online adaptive photon radiotherapy for short-course treatment of rectal cancer.

Background And Purpose: Image-guided proton beam therapy (IG-PBT) and cone-beam CT (CBCT)-based online adaptive photon radiotherapy (oART) have potentials to restrict radiation toxicity. They are both hypothesised to reduce therapy limiting bowel toxicity in the multimodality treatment of locally advanced rectal cancer (LARC). This study aimed to quantify the difference in relevant dose-volume metrics for these modalities.

Complement is increased in treatment resistant rectal cancer and modulates radioresistance.

Resistance to neoadjuvant chemoradiation therapy (neo-CRT) is a significant clinical problem in the treatment of locally advanced rectal cancer. Identification of novel therapeutic targets and biomarkers predicting therapeutic response is required to improve patient outcomes. Increasing evidence supports a role for the complement system in resistance to anti-cancer therapy.

Evaluation of magnetic resonance imaging derived synthetic computed tomography for proton therapy planning in prostate cancer.

Background And Purpose: Magnetic resonance imaging (MRI)-only workflow is used in photon radiotherapy (RT) today, but not yet for protons. To bring MRI-only proton RT into clinical use, proton dose calculation on MRI-derived synthetic CT (sCT) must be validated. We evaluated proton dose calculation accuracy of prostate cancer proton plans using a commercially available sCT generator already validated for photon planning.

Interim F-FDG-PET based response-adaptive dose escalation of proton therapy for head and neck cancer: a treatment planning feasibility study.

Background: Image-driven dose escalation to tumor subvolumes has been proposed to improve treatment outcome in head and neck cancer (HNC). We used F-fluorodeoxyglucose (FDG) positron emission tomography (PET) acquired at baseline and into treatment (interim) to identify biologic target volumes (BTVs). We assessed the feasibility of interim dose escalation to the BTV with proton therapy by simulating the effects to organs at risk (OARs).

Quantitative MRI-based radiomics analysis identifies blood flow feature associated to overall survival for rectal cancer patients.

Radiomics objectively quantifies image information through numerical metrics known as features. In this study, we investigated the stability of magnetic resonance imaging (MRI)-based radiomics features in rectal cancer using both anatomical MRI and quantitative MRI (qMRI), when different methods to define the tumor volume were used. Second, we evaluated the prognostic value of stable features associated to 5-year progression-free survival (PFS) and overall survival (OS).

Next-generation sequencing reveals mitogenome diversity in plasma extracellular vesicles from colorectal cancer patients.

Background: Recent reports have demonstrated that the entire mitochondrial genome can be secreted in extracellular vesicles (EVs), but the biological attributes of this cell-free mitochondrial DNA (mtDNA) remain insufficiently understood. We used next-generation sequencing to compare plasma EV-derived mtDNA to that of whole blood (WB), peripheral blood mononuclear cells (PBMCs), and formalin-fixed paraffin-embedded (FFPE) tumor tissue from eight rectal cancer patients and WB and fresh-frozen (FF) tumor tissue from eight colon cancer patients.

Methods: Total DNA was isolated before the mtDNA was enriched by PCR with either two primer sets generating two long products or multiple primer sets (for the FFPE tumors), prior to the sequencing.

In vitro and in vivo characterization of [Cu][Cu(elesclomol)] as a novel theranostic agent for hypoxic solid tumors.

Purpose: Hypoxic tumors are associated with therapy resistance and poor cancer prognosis, but methods to detect and counter tumor hypoxia remain insufficient. Our purpose was to investigate Cu(II)-elesclomol ([Cu][Cu(ES)]) as a novel theranostic agent for hypoxic tumors, by implementing an improved production method and assessing its therapeutic and diagnostic potential compared to the established Cu-64 radiopharmaceuticals [Cu]CuCl and [diacetyl-bis(N4-methylthiosemicarbazone) [Cu][Cu(ATSM)].

Methods: Cu-64 was produced using a biomedical cyclotron at 12 MeV with the reaction Ni(p,n)Cu, followed by synthesis of [Cu]CuCl, [Cu][Cu(ATSM)], and [Cu][Cu(ES)].

Combined RBE and OER optimization in proton therapy with FLUKA based on EF5-PET.

Introduction: Tumor hypoxia is associated with poor treatment outcome. Hypoxic regions are more radioresistant than well-oxygenated regions, as quantified by the oxygen enhancement ratio (OER). In optimization of proton therapy, including OER in addition to the relative biological effectiveness (RBE) could therefore be used to adapt to patient-specific radioresistance governed by intrinsic radiosensitivity and hypoxia.

Energy Metabolism Is Altered in Radioresistant Rectal Cancer.

Resistance to neoadjuvant chemoradiation therapy is a significant clinical challenge in the management of rectal cancer. There is an unmet need to identify the underlying mechanisms of treatment resistance to enable the development of biomarkers predictive of response and novel treatment strategies to improve therapeutic response. In this study, an in vitro model of inherently radioresistant rectal cancer was identified and characterized to identify mechanisms underlying radioresistance in rectal cancer.

Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcome.

Background And Purpose: Measuring rectal tumour response to radiation is pivotal to restaging patients and for possibly stratification to a watch-and-wait strategy. Recognizing the importance of the tumour microenvironment, we investigated a less explored quantitative imaging marker assessing tumour blood flow (BF) for its potential to predict overall survival (OS).

Materials And Methods: 24 rectal cancer patients given curative-intent neoadjuvant radiotherapy underwent a multi-echo dynamic magnetic resonance imaging (MRI) sequence with gadolinium contrast for quantification of tumour BF before either 25x2 Gy (n = 18) with concomitant chemotherapy or 5x5 Gy (n = 6).

Hypoxia adapted relative biological effectiveness models for proton therapy: a simulation study.

In proton therapy, a constant relative biological effectiveness (RBE) factor of 1.1 is applied although the RBE has been shown to depend on factors including the Linear Energy Transfer (LET). The biological effectiveness of radiotherapy has also been shown to depend on the level of oxygenation, quantified by the oxygen enhancement ratio (OER).

Potential of Deep Learning in Quantitative Magnetic Resonance Imaging for Personalized Radiotherapy.

Quantitative magnetic resonance imaging (qMRI) has been shown to provide many potential advantages for personalized adaptive radiotherapy (RT). Deep learning models have proven to increase efficiency, robustness and speed for different qMRI tasks. Therefore, this article discusses the current state-of-the-art and potential future opportunities as well as challenges related to the use of deep learning in qMRI for target contouring, quantitative parameter estimation and also the generation of synthetic computerized tomography (CT) data based on MRI in personalized RT.

Semi-automatic tumor segmentation of rectal cancer based on functional magnetic resonance imaging.

Background And Purpose: Tumor delineation is required both for radiotherapy planning and quantitative imaging biomarker purposes. It is a manual, time- and labor-intensive process prone to inter- and intraobserver variations. Semi or fully automatic segmentation could provide better efficiency and consistency.

Development of an automated production process of [ Cu][Cu (ATSM)] for positron emission tomography imaging and theranostic applications.

Cyclotron-produced copper-64 radioisotope tracers offer the possibility to perform both diagnostic investigation by positron emission tomography (PET) and radiotherapy by a theranostic approach with bifunctional chelators. The versatile chemical properties of copper add to the importance of this isotope in medicinal investigation. [ Cu][Cu (ATSM)] has shown to be a viable candidate for imaging of tumor hypoxia; a critical tumor microenvironment characteristic that typically signifies tumor progression and resistance to chemo-radiotherapy.

The 3 ESTRO-EFOMP core curriculum for medical physics experts in radiotherapy.

Purpose: To update the 2011 ESTRO-EFOMP core curriculum (CC) for education and training of medical physics experts (MPE)s working in radiotherapy (RT), in line with recent EU guidelines, and to provide a framework for European countries to develop their own curriculum.

Material And Methods: Since September 2019, 27 European MPEs representing ESTRO, EFOMP and National Societies, with expertise covering all subfields of RT physics, have revised the CC for recent advances in RT. The ESTRO and EFOMP Education Councils, all European National Societies and international stakeholders have been involved in the revision process.

MRI-based automatic segmentation of rectal cancer using 2D U-Net on two independent cohorts.

Background: Tumor delineation is time- and labor-intensive and prone to inter- and intraobserver variations. Magnetic resonance imaging (MRI) provides good soft tissue contrast, and functional MRI captures tissue properties that may be valuable for tumor delineation. We explored MRI-based automatic segmentation of rectal cancer using a deep learning (DL) approach.

Professional practice changes in radiotherapy physics during the COVID-19 pandemic.

Background And Purpose: The COVID-19 pandemic has imposed changes in radiotherapy (RT) departments worldwide. Medical physicists (MPs) are key healthcare professionals in maintaining safe and effective RT. This study reports on MPs experience during the first pandemic peak and explores the consequences on their work.

Sex disparities in vitamin D status and the impact on systemic inflammation and survival in rectal cancer.

Background: We reported previously that rectal cancer patients given curative-intent chemotherapy, radiation, and surgery for non-metastatic disease had enhanced risk of metastatic progression and death if circulating levels of 25-hydroxyvitamin D [25(OH) D] were low. Here we investigated whether the association between the vitamin D status and prognosis pertains to the general, unselected population of rectal cancer patients.

Methods: Serum 25(OH) D at the time of diagnosis was assessed in 129 patients, enrolled 2013-2017 and representing the entire range of rectal cancer stages, and analyzed with respect to season, sex, systemic inflammation, and survival.

The circulating soluble form of the CD40 costimulatory immune checkpoint receptor and liver metastasis risk in rectal cancer.

Background: In colorectal cancer, the inflamed tumour microenvironment with its angiogenic activities is immune- tolerant and incites progression to liver metastasis. We hypothesised that angiogenic and inflammatory factors in serum samples from patients with non-metastatic rectal cancer could inform on liver metastasis risk.

Methods: We measured 84 angiogenic and inflammatory markers in serum sampled at the time of diagnosis within the population-based cohort of 122 stage I-III patients.

Alexithymia and professional quality of life in radiation oncology: The moderator effect of the professional profile.

Background And Purpose: Cancer care can be taxing. Alexithymia, a personality construct characterized by difficulties in identifying and describing feeling and emotions, an externally-oriented thinking style and scarcity of imagination and fantasy, is significantly correlated with higher levels of both secondary traumatic stress (STS) and burnout and lower levels of compassion satisfaction in medical professionals in radiation oncology. In this study, we aimed to assess the difference in professional quality of life (QoL) and the association with alexithymia in this multidisciplinary field depending on the specific profession (radiation/clinical oncologist, RO; medical physicist, MP; radiation therapist, RTT).

Uptake of circulating extracellular vesicles from rectal cancer patients and differential responses by human monocyte cultures.

Extracellular vesicles (EVs) released by tumor cells can directly or indirectly modulate the phenotype and function of the immune cells of the microenvironment locally or at distant sites. The uptake of circulating EVs and the responses by human monocytes in vitro may provide new insights into the underlying biology of the invasive and metastatic processes in cancer. Although a mixed population of vesicles is obtained with most isolation techniques, we predominantly isolated exosomes (small EVs) and microvesicles (medium EVs) from the SW480 colorectal cancer cell line (established from a primary adenocarcinoma of the colon) by sequential centrifugation and ultrafiltration, and plasma EVs were prepared from 22 patients with rectal adenoma polyps or invasive adenocarcinoma by size-exclusion chromatography.

From multisource data to clinical decision aids in radiation oncology: The need for a clinical data science community.

Big data are no longer an obstacle; now, by using artificial intelligence (AI), previously undiscovered knowledge can be found in massive data collections. The radiation oncology clinic daily produces a large amount of multisource data and metadata during its routine clinical and research activities. These data involve multiple stakeholders and users.