Uncovering the Daily Experiences of People Living With Advanced Cancer Using an Experience Sampling Method Questionnaire: Development, Content Validation, and Optimization Study.

BACKGROUND: The experience sampling method (ESM), a self-report method that typically uses multiple assessments per day, can provide detailed knowledge of the daily experiences of people with cancer, potentially informing oncological care. The use of the ESM among people with advanced cancer is limited, and no validated ESM questionnaires have been developed specifically for oncology. OBJECTIVE: This study aims to develop, content validate, and optimize the digital Experience Sampling Method for People Living With Advanced Cancer (ESM-AC) questionnaire, covering multidimensional domains and contextual factors. METHODS: A 3-round mixed methods study was designed in accordance with the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) and the European Organization for Research and Treatment of Cancer guidelines. The study included semistructured interviews with 43 people with stage IV breast cancer or stage III to IV lung cancer and 8 health care professionals. Round 1 assessed the appropriateness, relative importance, relevance, and comprehensiveness of an initial set of ESM items that were developed based on the existing questionnaires. Round 2 tested the comprehensibility of ESM items. Round 3 tested the usability of the digital ESM-AC questionnaire using the m-Path app. Analyses included descriptive statistics and qualitative content analysis. RESULTS: Following the first round, we developed an initial core set of 68 items (to be used with all patients) and a supplementary set (optional; patients select items), both covering physical, psychological, social, spiritual-existential, and global well-being domains and concurrent contexts in which experiences occur. We categorized items to be assessed multiple times per day as momentary items (eg, "At this moment, I feel tired"), once a day in the morning as morning items (eg, "Last night, I slept well"), or once a day in the evening as evening items (eg, "Today, I felt hopeful"). We used participants' evaluations to optimize the questionnaire items, the digital app, and its onboarding manual. This resulted in the ESM-AC questionnaire, which comprised a digital core questionnaire containing 31 momentary items, 2 morning items, and 7 evening items and a supplementary set containing 39 items. Participants largely rated the digital questionnaire as "easy to use," with an average score of 4.5 (SD 0.5) on a scale from 1 ("completely disagree") to 5 ("completely agree"). CONCLUSIONS: We developed the ESM-AC questionnaire, a content-validated digital questionnaire for people with advanced breast or lung cancer. It showed good usability when administered on smartphone devices. Future research should evaluate the potential of this ESM tool to uncover daily experiences of people with advanced breast or lung cancer, explore its clinical utility, and extend its validation to other populations with advanced diseases.

Deep Inspiration Breath Hold in Left-Sided Breast Radiotherapy: A Balance Between Side Effects and Costs.

Background: Deep inspiration breath hold (DIBH) is an effective technique for reducing heart exposure during radiotherapy for left-sided breast cancer. Despite its benefits, cost considerations and its impact on workflow remain significant barriers to widespread adoption. Objectives: This study aimed to assess the cost-effectiveness of DIBH and compare its operational, financial, and clinical outcomes with free breathing (FB) in breast cancer treatment. Methods: Treatment plans for 100 patients with left-sided breast cancer were generated using both DIBH and FB techniques. Dosimetric data, including the average mean heart dose, were calculated for each technique and used to estimate the cardiotoxicity of radiotherapy. A state-transition microsimulation model based on SCORE2 (Systematic Coronary Risk Evaluation) algorithms projected the effects of DIBH on cardiovascular outcomes and quality-adjusted life-years (QALYs). Costs were calculated from a provider perspective using time-driven activity-based costing, applying a willingness-to-pay threshold of €40,000 for cost-effectiveness assessment. A discrete event simulation model assessed the impacts of DIBH vs FB on throughput and waiting times in the radiotherapy workflow. Results: In the base case scenario, DIBH was associated with an absolute risk reduction of 1.72% (95% CI: 1.67%-1.76%) in total cardiovascular events and 0.69% (95% CI: 0.67%-0.72%) in fatal cardiovascular events over 20 years. Additionally, DIBH was estimated to provide an incremental 0.04 QALYs (95% CI: 0.05-0.05) per left-sided breast cancer patient over the same time period. However, DIBH increased treatment times, reducing maximum achievable throughput by 12.48% (95% CI: 12.36%-12.75%) and increasing costs by €617 per left-sided breast cancer patient (95% CI: €615-€619). The incremental cost-effectiveness ratio was €14,023 per QALY. Conclusions: Despite time investments, DIBH is cost-effective in the Belgian population. The growing adoption of DIBH may benefit long-term cardiovascular health in breast cancer survivors.

Credentialing of stereotactic radiosurgery and stereotactic body radiation therapy programs for quality and safety: The Novalis Certified Program.

The expectation of quality and safety is a fundamental tenet in all areas of healthcare, and a cornerstone of best practice is a process of continuous learning and continuous improvement. Independent audits and peer review of radiotherapy programs are an important mechanism for identifying process or technology gaps, for highlighting areas for improvement, and for incorporating within continuous improvement processes. In the field of radiotherapy, independent certification programs exist within various national and/or professional spheres, yet few focus specifically on specialty procedures such as radiosurgery or brachytherapy, despite several recommendations for such programs. In this manuscript we describe a specialized SRS/SBRT credentialing program founded on national/international standards and guidelines. We also present the results of an anonymous survey from institutions who have completed the program.

A randomized phase II clinical trial of stereotactic body radiation therapy (SBRT) and systemic pembrolizumab with or without intratumoral avelumab/ipilimumab plus CD1c (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells in solid tumors.

BACKGROUND: Radiotherapy (RT) synergizes with immune checkpoint blockade (ICB). CD1c(BDCA-1)+/CD141(BDCA-3)+ myeloid dendritic cells (myDC) in the tumor microenvironment are indispensable at initiating effector T-cell responses and response to ICB. METHODS: In this phase II clinical trial, anti-PD-1 ICB pretreated oligometastatic patients (tumor agnostic) underwent a leukapheresis followed by isolation of CD1c(BDCA-1)+/CD141(BDCA-3)+ myDC. Following hypofractionated stereotactic body RT (3 × 8 Gy), patients were randomized (3:1). Respectively, in arm A (immediate treatment), intratumoral (IT) ipilimumab (10 mg) and avelumab (40 mg) combined with intravenous (IV) pembrolizumab (200 mg) were administered followed by IT injection of myDC; subsequently, IV pembrolizumab and IT ipilimumab/avelumab were continued (q3W). In arm B (contemporary control arm), patients received IV pembrolizumab, with possibility to cross-over at progression. Primary endpoint was 1-year progression-free survival rate (PFS). Secondary endpoints were safety, feasibility, objective response rate, PFS, and overall survival (OS). RESULTS: Thirteen patients (10 in arm A, eight non-small cell lung cancer, and five melanoma) were enrolled. Two patients crossed over. One-year PFS rate was 10% in arm A and 0% in arm B. Two patients in arm A obtained a partial response, and one patient obtained a stable disease as best response. In arm B, one patient obtained a SD. Median PFS and OS were 21.8 weeks (arm A) versus 24.9 (arm B), and 62.7 versus 57.9 weeks, respectively. An iatrogenic pneumothorax was the only grade 3 treatment-related adverse event. CONCLUSION: SBRT and pembrolizumab with or without IT avelumab/ipilimumab and IT myDC in oligometastatic patients are safe and feasible with a clinically meaningful tumor response rate. However, the study failed to reach its primary endpoint. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT04571632 (09 AUG 2020). EUDRACT: 2019-003668-32. Date of registration: 17 DEC 2019, amendment 1: 6 MAR 2021, amendment 2: 4 FEB 2022.

Quantifying societal burden of radiation-induced small bowel toxicity in patients with rectal cancer.

Introduction: Advancements in rectal cancer (RC) treatment not only led to an increase in lives saved but also improved quality of life (QoL). Notwithstanding these benefits, RC treatment comes at the price of gastrointestinal morbidity in many patients. Health economic modelling poses an opportunity to explore the societal burden of such side-effects. This study aims to quantify radiation-induced late small bowel (SB) toxicity in survivors of RC for Three-Dimensional Conformal Radiation Therapy (3D-CRT), Intensity Modulated Radiation Therapy (IMRT) and Intensity Modulated Radiation Therapy - Image Guided Radiation Therapy (IMRT/IGRT). Materials and methods: Materials and A model-based health economic evaluation was performed. The theoretical cohort consists of a case-mix of survivors of RC aged 25-99 years according to Belgian age-specific incidence rates. A societal perspective was adopted. The base case analysis was complemented with one-way deterministic analyses, deterministic scenario analyses and probabilistic sensitivity analysis (1,000 iterations). Results were presented as mean lifetime incremental cost (€) and utility (QALYs) per patient. Results: The analyses showed that the use of innovative radiotherapy (RT) improves lifetime QoL in survivors of RC by 0.11 QALYs and 0.05 QALYs by preferring IMRT/IGRT and IMRT over 3D-CRT, respectively. The use of IMRT/IGRT and IMRT results in an incremental cost-saving of €3,820 and €1,863 per patient, solely by radiation-induced SB toxicity, compared to 3D-CRT. Discussion and conclusion: It is important to consider late toxicity effects in decisions regarding investments and reimbursement as our analysis highlighted the potential long-term cost-savings and improved QoL of novel RT techniques in patients with rectal cancer.

Intensive Longitudinal Methods Among Adults With Breast or Lung Cancer: Scoping Review.

BACKGROUND: Intensive longitudinal methods offer a powerful tool for capturing daily experiences of individuals. However, its feasibility, effectiveness, and optimal methodological approaches for studying or monitoring experiences of oncology patients remain uncertain. OBJECTIVE: This scoping review aims to describe to what extent intensive longitudinal methods with daily electronic assessments have been used among patients with breast or lung cancer and with which methodologies, associated outcomes, and influencing factors. METHODS: We searched the electronic databases (PubMed, Embase, and PsycINFO) up to January 2024 and included studies reporting on the use of these methods among adults with breast or lung cancer. Data were extracted on population characteristics, intensive monitoring methodologies used, study findings, and factors influencing the implementation of these methods in research and clinical practice. RESULTS: We identified 1311 articles and included 52 articles reporting on 41 studies. Study aims and intensive monitoring methodologies varied widely, but most studies focused on measuring physical and psychological symptom constructs, such as pain, anxiety, or depression. Compliance and attrition rates seemed acceptable for most studies, although complete methodological reporting was often lacking. Few studies specifically examined these methods among patients with advanced cancer. Factors influencing implementation were linked to both patient (eg, confidence with intensive monitoring system) and methodology (eg, option to use personal devices). CONCLUSIONS: Intensive longitudinal methods with daily electronic assessments hold promise to provide unique insights into the daily lives of patients with cancer. Intensive longitudinal methods may be feasible among people with breast or lung cancer. Our findings encourage further research to determine optimal conditions for intensive monitoring, specifically in more advanced disease stages.

Ferroptosis: Frenemy of Radiotherapy.

Recently, it was established that ferroptosis, a type of iron-dependent regulated cell death, plays a prominent role in radiotherapy-triggered cell death. Accordingly, ferroptosis inducers attracted a lot of interest as potential radio-synergizing drugs, ultimately enhancing radioresponses and patient outcomes. Nevertheless, the tumor microenvironment seems to have a major impact on ferroptosis induction. The influence of hypoxic conditions is an area of interest, as it remains the principal hurdle in the field of radiotherapy. In this review, we focus on the implications of hypoxic conditions on ferroptosis, contemplating the plausibility of using ferroptosis inducers as clinical radiosensitizers. Furthermore, we dive into the prospects of drug repurposing in the domain of ferroptosis inducers and radiosensitizers. Lastly, the potential adverse effects of ferroptosis inducers on normal tissue were discussed in detail. This review will provide an important framework for subsequent ferroptosis research, ascertaining the feasibility of ferroptosis inducers as clinical radiosensitizers.

Compartmentalized role of xCT in supporting pancreatic tumor growth, inflammation and mood disturbance in mice.

xCT (Slc7a11), the specific subunit of the cystine/glutamate antiporter system xc-, is present in the brain and on immune cells, where it is known to modulate behavior and inflammatory responses. In a variety of cancers -including pancreatic ductal adenocarcinoma (PDAC)-, xCT is upregulated by tumor cells to support their growth and spread. Therefore, we studied the impact of xCT deletion in pancreatic tumor cells (Panc02) and/or the host (xCT-/- mice) on tumor burden, inflammation, cachexia and mood disturbances. Deletion of xCT in the tumor strongly reduced tumor growth. Targeting xCT in the host and not the tumor resulted only in a partial reduction of tumor burden, while it did attenuate tumor-related systemic inflammation and prevented an increase in immunosuppressive regulatory T cells. The latter effect could be replicated by specific xCT deletion in immune cells. xCT deletion in the host or the tumor differentially modulated neuroinflammation. When mice were grafted with xCT-deleted tumor cells, hypothalamic inflammation was reduced and, accordingly, food intake improved. Tumor bearing xCT-/- mice showed a trend of reduced hippocampal neuroinflammation with less anxiety- and depressive-like behavior. Taken together, targeting xCT may have beneficial effects on pancreatic cancer-related comorbidities, beyond reducing tumor burden. The search for novel and specific xCT inhibitors is warranted as they may represent a holistic therapy in pancreatic cancer.

Radiation-induced cutaneous vasculopathy of the breast: a rare case report.

BACKGROUND: Radiation therapy is often indicated as part of the treatment for breast cancer and is therefore used frequently worldwide. Vasculopathy is a general term used to describe any condition that affects blood vessels. We present a case report of a patient who presented with vasculopathy as a rare late side effect of radiation therapy to the breast. CASE PRESENTATION: This 66-year-old woman was initially treated with breast-conserving surgery for early-stage receptor-positive left breast carcinoma. She received postoperative radiation therapy and hormonal treatment with tamoxifen. She developed sudden spontaneous painless ecchymosis spread over the whole irradiated area 1.5 years after finishing her radiation therapy. Tumor relapse was excluded. There was no associated vasculitis. The cause was presumed to be multifactorial. She had a history of smoking and was known to have hyperlipidemia. She had undergone several surgical treatments at the left breast one year after her initial breast-conserving treatment and was taking tamoxifen. Anti-inflammatory medicine and treatments increasing local blood flow were prescribed. The ecchymosis resolved completely within one month. CONCLUSIONS: Vasculopathy can occur as a rare late side effect of radiation therapy. It can be reversible. Prevention begins with carefully treating precipitating factors.

Investigating experiences of people with advanced breast or lung cancer in their natural context: protocol for an experience sampling study.

INTRODUCTION: People with advanced cancer can experience a wide range of multidimensional symptoms or concerns, but little is known about when and how these fluctuate in daily life. Experience sampling methods (ESMs) involve repeated self-reports in people's natural contexts aimed at uncovering everyday life experiences. ESM has limited recall bias and good ecological validity but might be burdensome to patients. This study aims to pretest and evaluate the feasibility and clinical utility of a validated ESM and use it to explore everyday experiences of people living with advanced breast or lung cancer. METHODS AND ANALYSIS: In step 1, we will optimise our ESM method by pretesting it through usability interviews and a pilot ESM study. In step 2, we will evaluate and use the ESM method through an observational ESM study to investigate the daily experiences of people with advanced breast or lung cancer. Step 2 also includes interviews with healthcare professionals to determine the clinical utility of ESM in oncology. Participants will complete a digital questionnaire ten times per day, measuring momentary experiences in the physical, psychological, social, spiritual-existential domains and context. Multilevel regression models will analyse fluctuations and temporal relations among measured experiences and context. Analyses also include evaluation of compliance and participation rates. We will apply content analysis to the usability interviews and follow-up interviews of the pilot ESM study. ETHICS AND DISSEMINATION: We obtained approval from the ethics committees of the University Hospitals of Brussels (BUN: 1432023000043) and Ghent (ONZ-2023-0136). Results will be published in open-access, peer-reviewed journals and presented at conferences. If ESM appears feasible in this population, it could offer new insights into the daily experiences and help optimise support for people with advanced cancer.

Introduction of ultra-hypofractionation in breast cancer: Implications for costs and resource use.

PURPOSE: A shift towards (ultra-)hypofractionated breast irradiation can have important implications for the practice of contemporary radiation oncology. This paper presents a systematic analysis of the impact of different fractionation schedules on multiple key performance indicators, namely resource use, costs, work times, throughput and waiting times. MATERIALS AND METHODS: Time-driven activity-based costing (TD-ABC) is applied to calculate the costs and resources consumed where the perspective of the radiotherapy department in adopted. Three fractionation regimens are considered: ultra-hypofractionation (5 x 5.2 Gy, UHF), moderate hypofractionation (15 x 2.67 Gy, HF) and conventional fractionation (25 x 2 Gy, CF). Subsequently, a discrete event simulation (DES) model of the radiotherapy care pathway is developed and scenarios are compared in which the following factors are varied: distribution of fractionation regimens, patient volume and operating hours. RESULTS: The application of (U)HF can permit radiotherapy departments to reduce the use of scarce resources, realise work time and cost savings, increase throughput and reduce waiting times. The financial advantages of (U)HF are, however, reduced in cases of excess capacity and cost savings may therefore be limited in the short-term. Moreover, although an extension of operating hours has favourable effects on throughput and waiting times, it may also reduce cost differences between fractionation schedules by increasing the capacity of resources. CONCLUSION: By providing an in-depth analysis of the consequences associated with a shift towards (U)HF in breast cancer, the present study demonstrates how a DES model based on TD-ABC costing can assist radiotherapy professionals in making data-driven decisions.

Lung-heart toxicity in a randomized clinical trial of hypofractionated image guided radiation therapy for breast cancer.

Background: TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT). Methods: In a single center 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a composite four-items measure of the time to 10% alteration in any of patient-reported outcomes, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat. Results: At 12 years median follow-up, overall and disease-free survivals between randomized arms were comparable, while survival time free from alteration significantly improved with H-IGRT which showed a gain of restricted mean survival time of 1.46 years over CRT, P=0.041. Discussion: The finding establishes TomoBreast as a proof-of-concept that hypofractionated image-guided radiation-therapy can improve the sparing of lung-heart function in breast cancer adjuvant therapy without loss in disease-free survival. Hypofractionation is advantageous, conditional on using an advanced radiation technique. Multicenter validation may be warranted. Trial registration: https://clinicaltrials.gov/ct2/show/NCT00459628. Registered 12 April 2007.

Colorectal Cancer Immunotherapy: State of the Art and Future Directions.

Cancer immunotherapy has become an indispensable mode of treatment for a multitude of solid tumor cancers. Colorectal cancer (CRC) has been one of the many cancer types to benefit from immunotherapy, especially in advanced disease where standard treatment fails to prevent recurrence or results in poor survival. The efficacy of immunotherapy in CRC has not been without challenge, as early clinical trials observed dismal responses in unselected CRC patients treated with checkpoint inhibitors. Many studies and clinical trials have since refined immunotherapies available for CRC, solidifying immunotherapy as a powerful asset for CRC treatment. This review article examines CRC immunotherapies, from their foundation, through emerging avenues for improvement, to future directions.

A multi-centric evaluation of self-learning GAN based pseudo-CT generation software for low field pelvic magnetic resonance imaging.

Purpose/objectives: An artificial intelligence-based pseudo-CT from low-field MR images is proposed and clinically evaluated to unlock the full potential of MRI-guided adaptive radiotherapy for pelvic cancer care. Materials and method: In collaboration with TheraPanacea (TheraPanacea, Paris, France) a pseudo-CT AI-model was generated using end-to-end ensembled self-supervised GANs endowed with cycle consistency using data from 350 pairs of weakly aligned data of pelvis planning CTs and TrueFisp-(0.35T)MRIs. The image accuracy of the generated pCT were evaluated using a retrospective cohort involving 20 test cases coming from eight different institutions (US: 2, EU: 5, AS: 1) and different CT vendors. Reconstruction performance was assessed using the organs at risk used for treatment. Concerning the dosimetric evaluation, twenty-nine prostate cancer patients treated on the low field MR-Linac (ViewRay) at Montpellier Cancer Institute were selected. Planning CTs were non-rigidly registered to the MRIs for each patient. Treatment plans were optimized on the planning CT with a clinical TPS fulfilling all clinical criteria and recalculated on the warped CT (wCT) and the pCT. Three different algorithms were used: AAA, AcurosXB and MonteCarlo. Dose distributions were compared using the global gamma passing rates and dose metrics. Results: The observed average scaled (between maximum and minimum HU values of the CT) difference between the pCT and the planning CT was 33.20 with significant discrepancies across organs. Femoral heads were the most reliably reconstructed (4.51 and 4.77) while anal canal and rectum were the less precise ones (63.08 and 53.13). Mean gamma passing rates for 1%1mm, 2%/2mm, and 3%/3mm tolerance criteria and 10% threshold were greater than 96%, 99% and 99%, respectively, regardless the algorithm used. Dose metrics analysis showed a good agreement between the pCT and the wCT. The mean relative difference were within 1% for the target volumes (CTV and PTV) and 2% for the OARs. Conclusion: This study demonstrated the feasibility of generating clinically acceptable an artificial intelligence-based pseudo CT for low field MR in pelvis with consistent image accuracy and dosimetric results.

Preoperative Radiotherapy with a Simultaneous Integrated Boost Compared to Chemoradiotherapy for cT3-4 Rectal Cancer: Long-Term Results of a Multicenter Randomized Study.

BACKGROUND: Preoperative chemoradiotherapy (CRT) is the standard treatment for T3-4 rectal cancer. Here, we compared image-guided and intensity-modulated RT (IG-IMRT) with a simultaneous integrated boost (SIB) (instead of concomitant chemotherapy) versus CRT in a multi-centric randomized trial. METHODS: cT3-4 rectal cancer patients were randomly assigned to receive preoperative IG-IMRT 46 Gy/23 fractions plus capecitabine 825 mg/m² twice daily (CRT arm) or IG-IMRT 46 Gy/23 fractions with an SIB to the rectal tumor up to a total dose of 55.2 Gy (RTSIB arm). RESULTS: A total of 174 patients were randomly assigned between April 2010 and May 2014. Grade 3 acute toxicities were 6% and 4% in the CRT and RTSIB arms, respectively. The mean fractional change in SUVmax at 5 weeks after completion of preoperative RT were -55.8% (±24.0%) and -52.9% (±21.6%) for patients in the CRT arm and RTSIB arm, respectively (p = 0.43). The pathologic complete response rate was 24% with CRT compared to 14% with RTSIB. There were no differences in 5-year overall survival (OS), progression-free survival (PFS) or local control (LC). CONCLUSIONS: The preoperative RTSIB approach was not inferior to CRT in terms of metabolic response, toxicity, OS, PFS and LC, and could be considered an available option for patients unfit for fluorouracil-based CRT.

Gantry triggered x-ray verification during single-isocenter stereotactic radiosurgery: Increased certainty for a no-margin strategy.

BACKGROUND: Single-isocenter linac-based stereotactic radiosurgery (SRS) has emerged as a dedicated treatment option for multiple brain metastases. Consequently, image-guidance for patient positioning and motion management has become very important. The purpose of this study was to analyze intra-fraction errors measured with stereoscopic x-rays and their impact on the dose distribution. MATERIALS AND METHODS: Treatments were planned with non- coplanar dynamic conformal arcs for 33 patients corresponding to 127 brain lesions and 356 arcs. Intra-arc positioning errors were measuredusing stereoscopic x-rays (ExacTrac Dynamic, Brainlab), triggered during arc delivery. Couch corrections above 0.7 mm and 0.5° were always applied. Intra-arc positioning data was analyzed. The dose impact was evaluated by applying the measured errors to the dose given in each arc. RESULTS: Median residual errors were 0.10 mm, 0.13 mm and 0.08 mm for the lateral, longitudinal and vertical directions and 0.10°, 0.08° and 0.13° for the pitch, roll and yaw angles respectively. 90% of the treatment arcs showed shifts of less than 0.4 mm and 0.4°in all directions. Dosimetric impact of motion showed the largest losses in coverage on small targets. All targets achieved at least 95% of the prescription dose to 95% of their volume, even when planned without margins. CONCLUSIONS: Intra-fractional errors measured during beam delivery were found to be notably low with a dose impact that showed acceptable target coverage when applying these intra-arc errors to the dose distributions of the individual treatment arcs. Using an adequate immobilization and intra-fraction imaging prior to and during irradiation, no margins need to be added to compensate for intra-fraction motion.

Repurposing Sulfasalazine as a Radiosensitizer in Hypoxic Human Colorectal Cancer.

xCT overexpression in cancer cells has been linked to tumor growth, metastasis and treatment resistance. Sulfasalazine (SSZ), an FDA-approved drug for the treatment of rheumatoid sarthritis, and inflammatory bowel diseases, has anticancer properties via inhibition of xCT, leading to the disruption of redox homeostasis. Since reactive oxygen species (ROS) are pivotal for the efficacy of radiotherapy (RT), elevated levels of ROS are associated with improved RT outcomes. In this study, the influence of SSZ treatment on the radiosensitivity of human colorectal cancer (CRC) cells was investigated. Our principal finding in human HCT116 and DLD-1 cells was that SSZ enhances the radiosensitivity of hypoxic CRC cells but does not alter the intrinsic radiosensitivity. The radiosensitizing effect was attributed to the depletion of glutathione and thioredoxin reductase levels. In turn, the reduction leads to excessive levels of ROS, increased DNA damage, and ferroptosis induction. Confirmation of these findings was performed in 3D models and in DLD-1 xenografts. Taken together, this study is a stepping stone for applying SSZ as a radiosensitizer in the clinic and confirms that xCT in cancer cells is a valid radiobiological target.

Lung-Heart Outcomes and Mortality through the 2020 COVID-19 Pandemic in a Prospective Cohort of Breast Cancer Radiotherapy Patients.

We investigated lung-heart toxicity and mortality in 123 women with stage I-II breast cancer enrolled in 2007-2011 in a prospective trial of adjuvant radiotherapy (TomoBreast). We were concerned whether the COVID-19 pandemic affected the outcomes. All patients were analyzed as a single cohort. Lung-heart status was reverse-scored as freedom from adverse-events (fAE) on a 1-5 scale. Left ventricular ejection fraction (LVEF) and pulmonary function tests were untransformed. Statistical analyses applied least-square regression to calendar-year aggregated data. The significance of outliers was determined using the Dixon and the Grubbs corrected tests. At 12.0 years median follow-up, 103 patients remained alive; 10-years overall survival was 87.8%. In 2007-2019, 15 patients died, of whom 11 were cancer-related deaths. In 2020, five patients died, none of whom from cancer. fAE and lung-heart function declined gradually over a decade through 2019, but deteriorated markedly in 2020: fAE dipped significantly from 4.6-4.6 to 4.3-4.2; LVEF dipped to 58.4% versus the expected 60.3% (PDixon = 0.021, PGrubbs = 0.054); forced vital capacity dipped to 2.4 L vs. 2.6 L (PDixon = 0.043, PGrubbs = 0.181); carbon-monoxide diffusing capacity dipped to 12.6 mL/min/mmHg vs. 15.2 (PDixon = 0.008, PGrubbs = 0.006). In conclusion, excess non-cancer mortality was observed in 2020. Deaths in that year totaled one-third of the deaths in the previous decade, and revealed observable lung-heart deterioration.