Dosimetric impact of intrafraction motion under abdominal compression during MR-guided SBRT for (Peri-) pancreatic tumors

Objective. Intrafraction motion is a major concern for the safety and effectiveness of high dose stereotactic body radiotherapy (SBRT) in the upper abdomen. In this study, the impact of the intrafraction motion on the delivered dose was assessed in a patient group that underwent MR-guided radiotherapy for upper abdominal malignancies with an abdominal corset. Approach. Fast online 2D cine MRI was used to extract tumor motion during beam-on time. These tumor motion profiles were combined with linac log files to reconstruct the delivered dose in 89 fractions of MR-guided SBRT in twenty patients. Aside the measured tumor motion, motion profiles were also simulated for a wide range of respiratory amplitudes and drifts, and their subsequent dosimetric impact was calculated in every fraction. Main results. The average (SD) D 99%of the gross tumor volume (GTV), relative to the planned D 99%, was 0.98 (0.03). The average (SD) relative D 0.5 cc of the duodenum, small bowel and stomach was 0.99 (0.03), 1.00 (0.03), and 0.97 (0.05), respectively. No correlation of respiratory amplitude with dosimetric impact was observed. Fractions with larger baseline drifts generally led to a larger uncertainty of dosimetric impact on the GTV and organs at risk (OAR). The simulations yielded that the delivered dose is highly dependent on the direction of on baseline drift. Especially in anatomies where the OARs are closely abutting the GTV, even modest LRor APdrifts can lead to substantial deviations from the planned dose. Significance. The vast majority of the fractions was only modestly impacted by intrafraction motion, increasing our confidence that MR-guided SBRT with abdominal compression can be safely executed for patients with abdominal tumors, without the use of gating or tracking strategies

Planning target volume margin assessment for online adaptive MR-guided dose-escalation in rectal cancer on a 1.5 T MR-Linac

PURPOSE: This study assessed the margins needed to cover tumor intrafraction motion during an MR-guided radiotherapy (MRgRT) dose-escalation strategy in intermediate risk rectal cancer. METHODS: Fifteen patients with rectal cancer were treated with neoadjuvant short-course radiotherapy, 5x5 Gy, according to an online adaptive workflow on a 1.5 T MR-linac. Per patient, 26 3D T2 weighted MRIs were made; one reference scan preceding treatment and five scans per treatment fraction. The primary tumor was delineated on each scan as gross tumor volume (GTV). Target coverage margins were assessed by isotropically expanding the reference GTV until more than 95% of the voxels of the sequential GTVs were covered. A margin with a coverage probability threshold of 90% was defined as adequate. Intra- and interfraction margins to cope with the movement of the GTV in the period between scans were calculated to indicate the target volume margins. Furthermore, the margin needed to cover GTV movement was calculated for different time intervals. RESULTS: The required margins to cover inter- and intrafraction GTV motion were 17 mm and 6 mm, respectively. Analysis based on time intervals between scans showed smaller margins were needed for adequate GTV coverage as time intervals became shorter, with a 4 mm margin required for a procedure of 15 min or less. CONCLUSION: The shorter the treatment time, the smaller the margins needed to cover for the GTV movement during an online adaptive MRgRT dose-escalation strategy for intermediate risk rectal cancer. When time intervals between replanning and the end of dose delivery could be reduced to 15 min, a 4 mm margin would allow adequate target coverage

Timing of rectal cancer surgery after short-course radiotherapy: national database study

BACKGROUND: Previous randomized trials found that a prolonged interval between short-course radiotherapy (SCRT, 25 Gy in 5 fractions) and surgery for rectal cancer (4-8 weeks, SCRT-delay) results in a lower postoperative complication rate and a higher pCR rate than SCRT and surgery within a week (SCRT-direct surgery). This study sought to confirm these results in a Dutch national database. METHODS: Patients with intermediate-risk rectal cancer (T3(mesorectal fascia (MRF)-) N0 M0 and T1-3(MRF-) N1 M0) treated with either SCRT-delay (4-12 weeks) or SCRT-direct surgery in 2018-2021 were selected from a Dutch national colorectal cancer database. Confounders were adjusted for using inverse probability of treatment weighting (IPTW). The primary endpoint was the 90-day postoperative complication rate. Secondary endpoints included the pCR rate. Endpoints were compared using log-binomial and Poisson regression. RESULTS: Some 664 patients were included in the SCRT-direct surgery and 238 in the SCRT-delay group. After IPTW, the 90-day postoperative complication rate was comparable after SCRT-direct surgery and SCRT-delay (40.1 versus 42.3 per cent; risk ratio (RR) 1.1, 95 per cent c.i. 0.9 to 1.3). A pCR occurred more often after SCRT-delay than SCRT-direct surgery (10.7 versus 0.4 per cent; RR 39, 11 to 139). CONCLUSION: There was no difference in surgical complication rates between SCRT-delay and SCRT-direct, but SCRT-delay was associated with more patients having a pCR

Feasibility of online radial magnetic resonance imaging for adaptive radiotherapy of pancreatic tumors

BACKGROUND AND PURPOSE: Online adaptive magnetic resonance (MR)-guided treatment planning for pancreatic tumors on 1.5T systems typically employs Cartesian 3D T 2w magnetic resonance imaging (MRI). The main disadvantage of this sequence is that respiratory motion results in substantial blurring in the abdomen, which can hamper delineation accuracy. This study investigated the use of two motion-robust radial MRI sequences as main delineation scan for pancreatic MR-guided radiotherapy. MATERIALS AND METHODS: Twelve patients with pancreatic tumors were imaged with a 3D T 2w scan, a Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction (PROPELLER) scan (partially overlapping strips), and a 3D Vane scan (stack-of-stars), on a 1.5T MR-Linac under abdominal compression. The scans were assessed by three radiation oncologists for their suitability for online adaptive delineation. A quantitative comparison was made for gradient entropy and the effect of motion on apparent target position. RESULTS: The PROPELLER scans were selected as first preference in 56% of the cases, the 3D T 2w in 42% and the 3D Vane in 3%. PROPELLER scans sometimes contained a large interslice variation which would have compromised delineation. Gradient entropy was significantly higher in 3D T 2w patient scans. The apparent target position was more sensitive to motion amplitude in the PROPELLER scans, but substantial offsets did not occur under 10 mm peak-to-peak. CONCLUSION: PROPELLER MRI may be a superior imaging sequence for pancreatic MRgRT compared to standard Cartesian sequences. The large interslice variation should be mitigated through further sequence optimization before PROPELLER can be adopted for online treatment adaptation

Neoadjuvant Treatment for Resectable and Borderline Resectable Pancreatic Cancer:Chemotherapy or Chemoradiotherapy?

Worldwide, there is a shifting paradigm from immediate surgery with adjuvant treatment to a neoadjuvant approach for patients with resectable or borderline resectable pancreatic cancer (RPC or BRPC). Comparison of neoadjuvant and adjuvant studies is extremely difficult because of a great difference in patient selection. The evidence from randomized studies shows that overall survival by intention-to-treat improves after neoadjuvant gemcitabine-based chemoradiotherapy or chemotherapy (various regimens), as compared to immediate surgery followed by adjuvant chemotherapy. Radiotherapy appears to play an important role in mediating locoregional effects. Yet, since more effective chemotherapy regimens are currently available, in particular FOLFIRINOX and Gemcitabine/Nab-paclitaxel, these chemotherapy regimens should be investigated in future randomized trials combined with (stereotactic) radiotherapy to further improve outcomes of RPC and BRPC

Precision radiotherapy using MR-linac for pancreatic neuroendocrine tumors in MEN1 patients (PRIME): a protocol for a phase I-II trial, and systematic review on available evidence for radiotherapy of pNETs

BACKGROUND: Surgical resection is the standard of care for the treatment of pancreatic neuro-endocrine tumors (pNETs) in patients with Multiple Endocrine Neoplasia Type 1 (MEN1). However, surgery can cause significant short- and long-term morbidity. Magnetic resonance-guided radiotherapy (MRgRT) is a potential effective treatment with little side effects. With traditional radiotherapy techniques, irradiation of pancreatic tumors to high dose levels was hampered by poor visibility of the tumor during treatment. MRgRT uses onboard MRI to guide the treatment, thereby enabling delivery of ablative irradiation doses to the tumor, while sparing surrounding tissues. In this study, we describe results from a systematic review assessing efficacy of radiotherapy in pNET and present the protocol of the PRIME study. METHODS: PubMed, Embase and Cochrane Library were searched for articles assessing efficacy and side effects of radiotherapy for the treatment of pNETs. Risk of bias was assessed using the ROBINS-I Risk of Bias Tool for observational studies. Descriptive statistics were used to describe results of included trials. RESULTS: Four studies comprising of 33 patients treated by conventional radiotherapy were included. Despite the heterogeneity of studies, radiotherapy appeared to be effective for the treatment of pNETs with most patients responding (45.5%) or stabilizing (42.4%) in tumor size. CONCLUSION AND TRIAL DESIGN: Due to the limited literature available and concerns about damage to surrounding tissue, conventional radiotherapy is currently little used for pNETs. The PRIME study is a phase I-II trial with a single arm prospective cohort study design, investigating the efficacy of MRgRT in MEN1 patients with pNET. MEN1 patients with growing pNETs with a size between 1.0 and 3.0 cm without malignant features are eligible for inclusion. Patients are treated with 40 Gy in 5 fractions on the pNET, using online adaptive MRgRT on a 1.5T MR-linac. The primary endpoint is the change in tumor size at MRI 12 months follow-up. Secondary endpoints include radiotoxicity, quality of life, endocrine and exocrine pancreas function, resection rate, metastatic free and overall survival. When MRgRT is found effective with low radiotoxicity, it could reduce the need for surgery for pNET and preserve quality of life. SYSTEMATIC REVIEW REGISTRATION: PROSPERO https://clinicaltrials.gov/, (CRD42022325542)

Conventional versus Hepatic Arteriography and C-Arm CT-Guided Ablation of Liver Tumors (HepACAGA): A Comparative Analysis

Purpose: Hepatic Arteriography and C-Arm CT-Guided Ablation of liver tumors (HepACAGA) is a novel technique, combining hepatic–arterial contrast injection with C-arm CT-guided navigation. This study compared the outcomes of the HepACAGA technique with patients treated with conventional ultrasound (US) and/or CT-guided ablation. Materials and Methods: In this retrospective cohort study, all consecutive patients with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) treated with conventional US-/CT-guided ablation between 1 January 2015, and 31 December 2020, and patients treated with HepACAGA between 1 January 2021, and 31 October 2023, were included. The primary outcome was local tumor recurrence-free survival (LTRFS). Secondary outcomes included the local tumor recurrence (LTR) rate and complication rate. Results: 68 patients (120 tumors) were included in the HepACAGA cohort and 53 patients (78 tumors) were included in the conventional cohort. In both cohorts, HCC was the predominant tumor type (63% and 73%, respectively). In the HepACAGA cohort, all patients received microwave ablation. Radiofrequency ablation was the main ablation technique in the conventional group (78%). LTRFS was significantly longer for patients treated with the HepACAGA technique (p = 0.015). Both LTR and the complication rate were significantly lower in the HepACAGA cohort compared to the conventional cohort (LTR 5% vs. 26%, respectively; p < 0.001) (complication rate 4% vs. 15%, respectively; p = 0.041). Conclusions: In this study, the HepACAGA technique was safer and more effective than conventional ablation for HCC and CRLM, resulting in lower rates of local tumor recurrence, longer local tumor recurrence-free survival and fewer procedure-related complications

Oncology patients were found to understand and accept the Trials within Cohorts design

Background and Objective: The Trials within Cohorts design aims to reduce recruitment difficulties and disappointment bias in pragmatic trials. On cohort enrollment, broad informed consent for randomization is asked, after which cohort participants can be randomized to interventions or serve as controls without further notification. We evaluated patients' recollection, understanding, and acceptance of broad consent in a clinical oncology setting. Methods: We surveyed 610 patients with cancer participating in ongoing TwiCs; 482 patients (79%) responded, of which 312 patients shortly after cohort enrollment, 108 patients after randomization to an intervention (12-18 months after cohort enrollment), and a random sample of 62 cohort participants who had not been selected for interventions (1-6 months after cohort enrollment). Results: Shortly after providing cohort consent, 76% of patients (238/312) adequately remembered whether they had given broad consent for randomization. Of patients randomly offered interventions, 76% (82/108) remembered giving broad consent for randomization; 41% (44/108) understood they were randomly selected, 44% (48/108) were not interested in selection procedures, and 10% (11/108) did not understand selection was random. Among patients not selected for interventions, 42% (26/62) understood selection was random; 89% felt neutral regarding the scenario of "not being selected for an intervention while your data were being used in comparison with patients receiving interventions,"10% felt reassured (6/62) and 2% scared/insecure (2/62). Conclusion: Patients adequately remember giving broad consent for randomization shortly after cohort enrollment and after being offered an intervention, but recollection is lower in those never selected for interventions. Patients are acceptant of serving as control without further notifications. (c) 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Effect of Neoadjuvant Therapy and Rectal Surgery on Health-related Quality of Life in Patients With Rectal Cancer During the First 2 Years After Diagnosis

INTRODUCTION: Rectal cancer surgery with neoadjuvant therapy is associated with substantial morbidity. The present study describes the course of quality of life (QOL) in rectal cancer patients in the first 2 years after the start of treatment. PATIENTS AND METHODS: We performed a prospective study within a colorectal cancer cohort including rectal cancer patients who were referred for neoadjuvant chemoradiation or short-course radiotherapy and underwent rectal surgery. QOL was assessed using the European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30) and colorectal cancer questionnaire (EORTC QLQ-CR29) before treatment and after 3, 6, 12, 18, and 24 months. The outcomes were compared with the QOL scores from the Dutch general population and stratified by low anterior resection and abdominoperineal resection. Postoperative bowel dysfunction after low anterior resection was measured using the low anterior resection syndrome score. RESULTS: Of the 324 patients, 272 (84%) responded to at least 2 questionnaires and were included in the present study. Compared with pretreatment levels, the strongest decline was observed in physical, role, and social functioning at 3 and 6 months after the start of treatment. Global health and cognitive functioning declined to a lesser extend, and emotional functioning gradually improved over the time. Within 24 months, the QOL scores had recovered toward the pretreatment levels in most patients. Compared with the general population, physical, role, social, and cognitive functioning and symptoms of fatigue and insomnia remained significantly worse in patients on longer-term. After low anterior resection, major bowel dysfunction was reported by 44% to 60% of the patients. Increasing urinary incontinence and severe complaints of impotence were observed in patients who had undergone abdominoperineal resection. CONCLUSION: Rectal cancer treatment is associated with a significant decline in QOL during the first 6 months after the diagnosis. Within 2 years, most patients return toward pretreatment functioning but could still experience poorer functioning and treatment-related symptoms compared with the general population. These findings support shared decision-making and emphasize the need for postoperative supportive care and novel treatment approaches