Radiotherapy Prescription Research Articles

Peer Review in Radiation Oncology: Where Does the Middle East, North Africa, and Türkiye Region Stand?

This study aims to assess the status of radiation oncology peer review procedures across the Middle East, North Africa, and Türkiye (MENAT) region. A cross-sectional electronic survey was conducted among radiotherapy centers in the MENAT region in March 2024. It assessed peer review practices, departmental demographics, perceived importance of peer review, and potential barriers. Data from 177 radiation oncology centers revealed varying peer review implementation across the MENAT region. Egypt had the highest participation (16.4%) among all responders. Most centers (31%) treated 500-1,000 cases annually. The majority (77.4%) implemented peer review, with varying levels between countries and across different centers. Advanced radiotherapy techniques significantly correlated with implementation of peer review (P < .05). Peer review meetings were mostly scheduled on a weekly basis (46%) and organized by radiation oncologists (84.7%). Target volume contouring (89%) and radiotherapy prescription (82%) were frequently peer-reviewed. Respondents with peer review at their institutions significantly valued peer review for education, adherence to guidelines, improving planning protocols, and reducing variation in practice institutions without peer review (P < .05). The most frequently reported barriers to peer review were having a high number of patients (56%) and shortage of time (54%). Peer review is essential for improving the quality of practice in radiation oncology. Despite some discrepancies, numerous obstacles, and challenges in implementation, it is instrumental in the improvement of patient care in most centers throughout the region. Raising awareness among radiation oncologists about the importance of peer review is paramount to lead to better outcomes.

Insurance Denials and Patient Treatment in a Large Academic Radiation Oncology Center

Insurance barriers to cancer care can cause significant patient and clinician burden. To investigate the association of insurance denial with changes in technique, dose, and time to delivery of radiation oncology treatment. In this single-institution cohort analysis, data were collected from patients with payer-denied authorization for radiation therapy (RT) from November 1, 2021, to December 8, 2022. Data were analyzed from December 15, 2022, to December 31, 2023. Insurance denial for RT. Association of these denials with changes in RT technique, dose, and time to treatment delivery was assessed using χ2 tests. A total of 206 cases (118 women [57.3%]; median age, 58 [range, 26-91] years) were identified. Most insurers (199 [96.6%]) were commercial payers, while 7 (3.4%) were Medicare or Medicare Advantage. One hundred sixty-one patients (78.2%) were younger than 65 years. Of 206 cases, 127 (61.7%) were ultimately authorized without any change to the requested RT technique or prescription dose; 56 (27.2%) were authorized after modification to RT technique and/or prescription dose required by the payer. Of 21 cases with required prescription dose change, the median decrease in dose was 24.0 (range, 2.3-51.0) Gy. Of 202 cases (98.1%) with RT delivered, 72 (34.9%) were delayed for a mean (SD) of 7.8 (9.1) days and median of 5 (range, 1-49) days. Four cases (1.9%) ultimately did not receive any authorization, with 3 (1.5%) not undergoing RT, and 1 (0.5%) seeking treatment at another institution. In this cohort study of patients with payer-denied cases, most insurance denials in radiation oncology were ultimately approved on appeal; however, RT technique and/or effectiveness may be compromised by payer-mandated changes. Further investigation and action to recognize the time and financial burdens on clinicians and clinical effects on patients caused by insurance denials of RT is needed.

Elucidating the Mechanism of Radiation Therapy on Mesenchymal Cell Fate in Preventing Heterotopic Ossification.

Radiation therapy is a clinically proven, localized preventive measure for heterotopic ossification (HO). Despite its efficacy, there is a lack of standardization of radiation prescription dosing and fractionation, and the mechanism of the impact of radiation in HO prevention remains unknown. Here, using an established mouse model of traumatic HO induced by burn and tenotomy, we demonstrate that 7Gy in one fraction delivered to the injury site within 72 hours postoperatively significantly decreases HO formation and improves hindlimb range of motion. In-depth single-cell transcriptomic analyses, in combination with immunofluorescent staining, demonstrate decreased cellular numbers as well as aberrant endochondral differentiation and downregulation of associated upstream signaling pathways in irradiated mesenchymal progenitor cells. Our study provides the framework for future mechanistic and clinically relevant studies exploring radiation efficacy in preventing HO formation.

Safety and Tolerability of Online Adaptive High-Field Magnetic Resonance-Guided Radiotherapy.

In 2018, the first online adaptive magnetic resonance (MR)-guided radiotherapy (MRgRT) system using a 1.5-T MR-equipped linear accelerator (1.5-T MR-Linac) was clinically introduced. This system enables online adaptive radiotherapy, in which the radiation plan is adapted to size and shape changes of targets at each treatment session based on daily MR-visualized anatomy. To evaluate safety, tolerability, and technical feasibility of treatment with a 1.5-T MR-Linac, specifically focusing on the subset of patients treated with an online adaptive strategy (ie, the adapt-to-shape [ATS] approach). This cohort study included adults with solid tumors treated with a 1.5-T MR-Linac enrolled in Multi Outcome Evaluation for Radiation Therapy Using the MR-Linac (MOMENTUM), a large prospective international study of MRgRT between February 2019 and October 2021. Included were adults with solid tumors treated with a 1.5-T MR-Linac. Data were collected in Canada, Denmark, The Netherlands, United Kingdom, and the US. Data were analyzed in August 2023. All patients underwent MRgRT using a 1.5-T MR-Linac. Radiation prescriptions were consistent with institutional standards of care. Patterns of care, tolerability, and technical feasibility (ie, treatment completed as planned). Acute high-grade radiotherapy-related toxic effects (ie, grade 3 or higher toxic effects according to Common Terminology Criteria for Adverse Events version 5.0) occurring within the first 3 months after treatment delivery. In total, 1793 treatment courses (1772 patients) were included (median patient age, 69 years [range, 22-91 years]; 1384 male [77.2%]). Among 41 different treatment sites, common sites were prostate (745 [41.6%]), metastatic lymph nodes (233 [13.0%]), and brain (189 [10.5%]). ATS was used in 1050 courses (58.6%). MRgRT was completed as planned in 1720 treatment courses (95.9%). Patient withdrawal caused 5 patients (0.3%) to discontinue treatment. The incidence of radiotherapy-related grade 3 toxic effects was 1.4% (95% CI, 0.9%-2.0%) in the entire cohort and 0.4% (95% CI, 0.1%-1.0%) in the subset of patients treated with ATS. There were no radiotherapy-related grade 4 or 5 toxic effects. In this cohort study of patients treated on a 1.5-T MR-Linac, radiotherapy was safe and well tolerated. Online adaptation of the radiation plan at each treatment session to account for anatomic variations was associated with a low risk of acute grade 3 toxic effects.

Advanced nursing practice: key factors that have shaped its development in the Republic of Ireland

This article explores the development of advanced practice in the Republic of Ireland, highlighting its progressive journey and the key factors that have shaped it. From the initial proposal of advanced roles in nursing and midwifery in 1998 to the establishment of clinical specialist and advanced practice positions, the evolution of advanced practice has been influenced by significant reports, legislative changes, the development of a national educational framework at a MSc advanced nurse practitioner (ANP) level and close collaboration between stakeholders. The article also discusses the distinctions between ANPs and clinical nurse specialists, highlighting the inclusion of medicinal products and ionising radiation prescriptions within the scope of ANPs. Throughout the paper, the regulatory framework and educational standards governing advanced practice in Ireland are highlighted, along with the collaborative efforts of key stakeholders

A comparative dose-escalation analysis for reirradiated cancer patients with and without appropriate dose mapping.

This study aims to compare dose escalation between two groups of reirradiated cancer patients, one with the previous contour and radiotherapy plan available on the treatment planning system and the other without. First group is identified as DICOM-group, while the other one is called non-DICOM group. The current study included 89 patients, 57 in the DICOM, and 32 in the non-DICOM group, who received reirradiation for recurrent or second primary tumours between 2019 and 2021. For the DICOM group, doses to 0.2cc volume for spine, brainstem, and optic apparatus from first radiation were converted into structures and transferred to reirradiation CT using deformable registration. First, one radiotherapy plan was created using the doctor prescribed dose (baseline prescription RxD_B); further an escalated dose (RxD_E) plan, taking into account all the dose volume parameters from previous radiation, was created only for DICOM group. In non-DICOM group patients were planned only for RxD_B. The maximum accepted dose escalation was 21 Gy. Radiotherapy prescription dose during earlier (first) treatment in DICOM and non-DICOM groups were 61 ± 5.6 Gy and 30-66 Gy, respectively. DICOM and non-DICOM groups had nearly identical baseline doses: 52.5 ± 10.7 Gy and 50.6 ± 6.9 Gy (difference 1.9 ± 12.7 Gy). Dose escalation was possible for 51 out of 57 patients in the DICOM-group. Average escalated dose in DICOM-group was 59.2 ± 6.2 Gy, with an incremental dose of 6.7 ± 12.4 Gy from the baseline prescription. No dose escalation was opted for in the non-DICOM group due to the unavailability of dose volume information from previous radiation. Reirradiation for head and neck cases allowed for a moderate to high dose escalation, facilitated by the presence of pertinent DICOM information from the initial radiotherapy.

An Analysis of Clinical and Systemic Factors Associated with Palliative Radiotherapy Delivery and Completion at the End of Life in Alberta, Canada.

Radiotherapy (RT) is often utilized for symptom control at the end of life. Palliative RT (pRT) may not be taken to completion by patients, thus decreasing clinical benefits and adversely impacting resource allocation. We determined rates of incomplete pRT and examined predictors of non-completion using an electronic questionnaire. Methods: A questionnaire was embedded within the RT electronic prescribing system for all five cancer centers of Alberta, Canada, between 2017 and 2020. Prescribing radiation oncologists (ROs) were tasked with completing the questionnaire. Treatment variables were collected for 2040 patients prescribed pRT. Details on pRT courses delivered and completed were used to determine rates of incomplete RT. Electronic medical records of a subset of 367 patients randomly selected from the 2040 patients were then analyzed to examine for association of non-completion of RT with patient, disease, and therapy-related factors. Results: Overall, 10% of patients did not complete pRT. The rate of single fractions prescribed as a proportion of all RT fractions increased from 18% (pre-2017: pre-study era) to 29% (2017-2020: study era) (p < 0.0001). After conducting multivariate analysis on the overall group, multiple lifetime malignancies (OR:0.64) or increasing the number of pRT fractions (OR:0.08-0.17) were associated with non-completion. Being selected for stereotactic RT (OR:3.75) or survival > 30 days post-RT prescription (OR:2.20-5.02) were associated with greater rates of RT completion. The ROs' estimates of life expectancy at the time of RT prescription were not predictive of RT completion. In the multivariate analysis of the 367-patient subset, the presence of hepatic metastases (OR 2.59), survival 30-59 days (OR 6.61) and survival 90+ days (OR 8.18) post-RT prescription were associated with pRT completion. Only increasing pRT fractionation (OR:0.05-0.2) was associated with non-completion. Conclusion: One in ten patients prescribed pRT did not complete their treatment course. Decreasing pRT fractionation and improving prognostication in patients near the end of life may decrease rates of incomplete RT courses.

Incidence of Radiotherapy Induced Cardiac Implantable Electronic Devices Malfunction: Australian-Based Observation Study.

To assess the incidence rate of cardiac implantable electronic devices (CIED) malfunction with radiotherapy (RT) and identify factors resulting in CIED malfunction. The working hypothesis is that CIED malfunction is associated with higher photon beam energy, treatment anatomical location, device type and dose to device. This retrospective review involved 441 patients with CIED treated with RT. Clinical information, RT (prescription, dose to device, beam energy, anatomical regions treated etc.) and CIED details (type, manufacturer, and device malfunction) were collected from electronic medical records. A total of 344 patients (78%) had a permanent pacemaker (PPM), 44 patients (10%) had implantable cardioverter defibrillator (ICD), 44 patients (10%) had CRT-defibrillator (CRT-D) and 9 (2%) had cardiac resynchronization therapy-pacing (CRT-P). The median prescribed dose was 36 Gy (IQR 1.8-80 Gy). 17 out of 441 patients (3.9%) experienced an CIED malfunction event. This group had a higher prescribed median dose of 42.5 Gy (IQR 20-77 Gy) and beam energy of 14 MV (12-18 MV). None of the malfunctions resulted in clinical symptoms. Median dose to CIED was 0.28 Gy (IQR 0-3.3). No patents received dose to device ≥2 Gy. Using logistic regression, the predictors of CIED malfunction were photon beam energy use ≥10 MV (OR 5.73; 95% CI, 1.58-10.76), anatomical location of RT above the diaphragm (OR 5.2, 95% CI, 1.82-15.2), and having an ICD (OR 4.6, 95% CI, 0.75-10.2). We have demonstrated that photon beam energies ≥10 MV, RT to above the diaphragm and ICD devices are significantly associated with CIED malfunction. The recorded CIED malfunctions in this study were minor malfunctions which did not result in any clinical symptoms. Stringent adherence to the local institution's CIED treatment guidelines, utilization of safety measures and careful choice of beam energy are recommended to minimize risk of symptomatic CIED malfunctions.

Multicenter Multivendor Evaluation of Dose Volume Histogram Creation Consistencies for 8 Commercial Radiation Therapy Dosimetric Systems

PurposeTo evaluate dose volume histogram (DVH) construction differences across eight major commercial treatment planning systems (TPSs) and dose reporting systems (DRSs) for clinically treated plans of various anatomical sites and target sizes. Materials and MethodsDose files from ten selected clinically treated plans with a hypo-fractionation, stereotactic radiotherapy prescription or sharp dose gradients such as head and neck plans ranging from prescription doses of 18 Gy in 1 fraction to 70 Gy in 35 fractions, each calculated at 0.25 cm and 0.125 cm grid size, were created and anonymized in Eclipse TPS, and exported to seven other major TPS (Pinnacle, RayStation, Elements) and DRS (MIM, Mobius, ProKnow, and Velocity) systems for comparison. Dose-volume constraint points of clinical importance for each plan were collected from each evaluated system (D0.03cc[Gy], volume, and the mean dose were used for structures without specified constraints). Each reported constraint type and structure volume was normalized to the value from Eclipse for a pairwise comparison. A Wilcoxon Rank Sum test was used for statistical significance and a multivariable regression model was evaluated adjusting for plan, grid size, and distance to target center. ResultsFor all DVH points relative to Eclipse, all systems reported median values within 1.0% difference of each other, however they were all different from Eclipse. Considering mean values, Pinnacle, RayStation, and Elements averaged at 1.038, 1.046, 1.024 respectively, while MIM, Mobius, ProKnow, and Velocity reported 1.026, 1.050, 1.033 and 1.022 respectively relative to Eclipse. Smaller dose grid size improved agreement between the systems marginally without statistical significance. For structure volumes relative to Eclipse, larger differences are seen across all systems with a range in median values up to 3.0% difference and mean up to 10.1% difference. ConclusionLarge variations were observed between all systems. Eclipse generally reported, at statistically significant levels, lower values than all other evaluated systems. The non-significant change resulting from lowering the dose grid resolution indicates that this resolution may be less important than other aspects of calculating DVH curves, such as the 3D modeling of the structure.

Long-Term Safety and Efficacy of SAbR for Metastatic RCC.

Metastasis-directed stereotactic ablative radiation (SAbR) in metastatic renal cell carcinoma (mRCC) has been shown to prolong time to systemic therapy start/change. However, there is a paucity of data on the durability of local control by SAbR and long-term side effects, limiting its investigation in prospective trials. Here we report the long-term local control rates of SAbR for mRCC, focusing on factors that lead to local failure where dose escalation may be beneficial. We retrospectively reviewed 354 metastatic RCC patients who received SAbR to 902 lesions between 2005 and September 2021. Acute and late adverse events and their Common Terminal Criteria for Adverse Events (CTCAE) v. 5.0 grades were collected. RECIST v. 1.1 was used to evaluate treatment response. LC was estimated using the cumulative incidence function, with death as a competing risk. Local control (LC) was calculated using the Kaplan-Meier method. Lesions were followed for a median of 16 months; 136 lesions had >36 months of follow-up. The most common radiation prescription was 36 Gy in 3 fractions, and the median biological effective dose was 72 Gy10. 3-year local control was 80% (95% CI 75, 83). 3-year LC differed according to lesion location, ranging from 65% (95% CI 52, 75) in the spine to 93% (95% CI 80, 98) in the lungs. Radiation-induced adverse events were experienced by 101 patients: 79 had an acute (≤90 days of SAbR) grade 1-2 toxicity; 20 had an acute grade 3-4 toxicity; 59 had a late grade 1-2 toxicity; 15 had a late grade 3-4 toxicity. The most common acute grade 1-2 toxicity was pain (n = 32), followed by nausea (n = 22) and fatigue (n = 16). There were 7 occurrences of acute grade 3-4 pain, 4 of nausea, and 2 fractures. The most common late grade 1-2 toxicity was fracture (n = 16), followed by pain (n = 15) and pneumonitis (n = 12). Hyperglycemia was the only late grade 3-4 toxicity that occurred more than once (n = 2). SAbR offers durable LC of mRCC lesions with an acceptable toxicity profile. LC was affected by treated lesion location, with bone (including long bones and ribs) and spine locations experiencing less durable LC, corresponding to locations that received lower-BED treatments.

Assessing the Compliance and Accuracy of a National Australian Head and Neck Cancer (HNC) Database

Accurate cancer databases enable auditing of patient management, and this knowledge facilitates optimizing care. A multi-institutional organization, the largest single provider of radiation oncology services in Australia, has developed its own national database (ND). All patients are entered on the ND as a prerequisite for generating a radiotherapy prescription. A significant component of the ND is automated, but manual input from the treating radiation oncologist (RO) is also required. The purpose of this study was to assess the compliance and accuracy of the data entered on this ND for head and neck cancer (HNC) patients. We included all HNC patients with either oral cavity cancer or oropharynx cancer (ICD-10 coding) treated between September 2021 and September 2022 to assess compliance. We randomly selected 25% of these cases and assigned them to 3 HNC ROs to manually review the accuracy of all clinical data points. There were 166 HNC patients, 139 oropharynx and 27 oral cavity. Compliance in the 166 patients was excellent (94% or higher) for the majority of data points - age, gender, diagnosis ICD code, diagnosis date, laterality, TNM classification, radiotherapy dose, fractionation and technique and start and completion dates. Compliance was good (85% or more) for smoking history, use of chemotherapy, and p16 status (oropharynx). Compliance was poor (43%) for specific chemotherapy regimens. Accuracy was high (92% or higher) for diagnosis ICD code, smoking history, use of chemotherapy; good (87% or higher) for p16 status (oropharynx), laterality and histopathology; and poor for date of diagnosis (75%), TNM classification (62%) and specific chemotherapy regimens (29%). The ND is a powerful tool for assessing patient care. Overall, compliance was very good. Accuracy was very good for most items, and we have highlighted areas where improvements can be made. This study shows that a compliant and accurate ND is achievable and supports the next goal of additional items to be included in the ND, specifically patient outcome data.

Analysis of the Cancer Imaging Archive for Patterns of Locoregional Failure in Relation to the Mucous Membranes among Patients with Head and Neck Squamous Cell Carcinoma: Potential Organ at Risk that can be Spared?

Radiation-induced oral mucositis (RIOM), a painful inflammation and ulceration of the mucous membranes (MM), occurs as a common and severe side effect of radiation treatment (RT) for head and neck cancers. It worsens significant quality of life leading to treatment interruption or cancellation. In RIOM, radiation injury of the MM basal epithelial cells may be one of the critical pathophysiological mechanisms. However, it is unclear if advanced radiation treatments could spare MM, without compromise on tumor control. The purpose of this study is to determine whether the MM that do not overlap with the prescription target volumes are a common site of locoregional recurrence in head and neck cancers. A de-identified data collection of 215 head and neck cancer patients stored within The Cancer Imaging Archive was downloaded for analysis. Imaging series both before and after RT were downloaded, as well as RT structures and RT dosimetric data. Diagnostic CECT and/or PET/CT and/or MRI scans documenting the initial evidence of recurrence were co-registered with corresponding original planning CTs. Radiologically evident recurrent gross disease (rGTV) was manually contoured, as well as the MM (defined as an approximately 3mm thick wall of mucosa tissue lining the oral cavity and pharynx and excluding any overlap with the radiation prescription targets). Contoured MM structures were cross-referenced with the sites of recurrence by examining the overlap of the MM volumes with the rGTV volumes. A total of 40 patients had documented evidence of recurrence; 38 of which had images available for analysis. Overall, 23 (60.5%) were oropharynx cancer. Of the 38 recurrences, 35 (92%) were locoregional: 23 with only local (60.5%) recurrences, 9 with only regional (23.7%) recurrences and 3 (7.9%) with both local and regional recurrences. One patient (2.6%) had distant recurrence, one patient had both regional and distant recurrences concomitantly, and one patient had local, regional and distant recurrences simultaneously. Overall, 30 patients (78.9%) had recurrences located exclusively within prescription PTV volumes/isodose lines. Four patients (10.5%) had recurrences located outside prescription PTV volumes/isodose lines, four patients (10.5%) had recurrences located both within and outside prescription PTV volumes/isodose lines (i.e., 2 sites of concomitant recurrence). Importantly, 0 patients (0%) had recurrences located in the contoured MM (excluding any overlap with the radiation prescription targets). Based on this retrospective series, the MM (excluding the areas of overlap with radiation prescription targets) are a rare location of locoregional recurrence. Hence, sparing the MM using radiation advanced dosimetry techniques could be a reasonable approach to reducing the incidence/severity of radiation-induced oral mucositis, without compromising tumor control. However, this requires further prospective investigation.

Palliative radiotherapy in pancreatic cancer: a retrospective study of 100 cases and regional patterns of practice.

Pancreatic cancer is often incurable and can be associated with significant pain and abdominal symptoms. This study aims to characterize the symptomatic burden of patients with pancreatic cancer receiving palliative radiotherapy and the corresponding symptomatic and radiographic responses. Patients with pancreatic adenocarcinoma referred to BC Cancer for palliative radiation from 2006 to 2013 were retrospectively reviewed. Logistic regression and Cox proportional hazards model were used to evaluate variables predictive of symptomatic response and survival respectively. One hundred patients were identified. The majority had good performance status (Eastern Cooperative Oncology Group score 0-1, 82%), received only one line of chemotherapy (91%), and presented with pain (84%). The most common radiotherapy prescription was 30 Gy in 10 fractions (22%). Pain improved in 69%, early satiety and bloating improved in 59%, and hemostasis was achieved in 73% of cases. Treatment toxicity occurred in 47% of cases and were predominantly grade 1-2 with 1 case of grade 3 toxicity. Median survival was 5.1 months. Tumor size, radiotherapy dose, and concurrent chemotherapy were not predictive of symptomatic response nor prolonged survival. In the largest cohort to date evaluating palliative radiotherapy in pancreatic adenocarcinoma, radiation was efficacious in improving pain and gastrointestinal bleeding and was generally well-tolerated. Additional studies on the efficacy and optimal prescriptions for palliative radiotherapy are necessary in this population.

Safety and efficacy of durvalumab after concurrent chemoradiation in Black patients with locally advanced non-small cell lung cancer.

The PACIFIC trial established consolidative durvalumab after concurrent chemoradiation as standard-of-care in patients with stage III or unresectable non-small cell lung cancer (NSCLC). Black patients, however, comprised just 2% (n = 14) of randomized patients in this trial, warranting real-world evaluation of the PACIFIC regimen in these patients. This single-institution, multi-site study included 105 patients with unresectable stage II/III NSCLC treated with concurrent chemoradiation followed by durvalumab between 2017 and 2021. Overall survival (OS), progression-free survival (PFS), and grade ≥3 pneumonitis-free survival (PNFS) were compared between Black and non-Black patients using Kaplan-Meier and Cox regression analyses. A total of 105 patients with a median follow-up of 22.8 months (interquartile range, 11.3-37.3 months) were identified for analysis, including 57 Black (54.3%) and 48 (45.7%) non-Black patients. The mean radiation prescription dose was higher among Black patients (61.5 ± 2.9 Gy vs. 60.5 ± 1.9 Gy; p = .031), but other treatment characteristics were balanced between groups. The median OS (not-reached vs. 39.7 months; p = .379) and PFS (31.6 months vs. 19.3 months; p = .332) were not statistically different between groups. Eight (14.0%) Black patients discontinued durvalumab due to toxicity compared to 13 (27.1%) non-Black patients (p = .096). The grade ≥3 pneumonitis rate was similar between Black and non-Black patients (12.3% vs. 12.5%; p = .973), and there was no significant difference in time to grade ≥3 PNFS (p = .904). Three (5.3%) Black patients and one (2.1%) non-Black patient developed grade 5 pneumonitis. The efficacy and tolerability of consolidative durvalumab after chemoradiation appears to be comparable between Black and non-Black patients.

Brain radiotherapy in patients treated for a newly diagnosed primary central nervous system lymphoma: professional practice evaluation in 19 French centers

Introduction The objective of this study was a multicentric evaluation of professional practices, analyzing the irradiation technique itself and its impact on survival and recurrence sites, in primary central nervous system lymphomas (PCNSLs). Methods We retrospectively analyzed the technical and clinical records of 79 PCNSL patients included in the database of the national expert network for oculocerebral lymphoma (‘LOC’) who were treated with brain radiotherapy as first-line treatment for newly diagnosed primary central nervous system lymphoma between 2011 and 2018. Results The number of patients treated with brain radiotherapy gradually decreased over time. The heterogeneity of radiotherapy prescriptions was significant, and 55% of them did not comply with published recommendations in terms of irradiation dose and/or volume. The proportion of complete responders to induction chemotherapy treated with reduced-dose radiotherapy increased over time. Partial brain radiotherapy was associated with significantly lower overall survival in univariate analysis. In partial responders to induction chemotherapy, increasing the total dose to the brain >30 Gy and adding a boost to the WBRT induced a trend toward improved progression-free and overall survival. Five recurrences (13%) occurred exclusively in the eyes, all in patients whose eyes had been excluded from the irradiation target volume and including 2 patients without ocular involvement at diagnosis. Conclusion The visibility of recommendations for prescribing brain radiotherapy for the treatment of newly diagnosed primary central nervous system lymphoma needs to be improved to harmonize practices and improve their quality. We propose an update of the recommendations.

Preoperative radiotherapy for select T4 primary and locally recurrent colon cancers: Experience from an Australian quaternary centre.

e15656 Background: We report our experience with preoperative radiotherapy for select T4 primary or locally recurrent colon cancers in a single, quaternary institution. Methods: A total of 89 patients with T4 primary (n = 40) and locally recurrent (n = 49) adenocarcinoma of the colon ( &gt; 15 cm from the anal verge) underwent preoperative-intent radiotherapy in our centre from 2005 to 2020. Majority of the tumours arose from the sigmoid, 79% (n = 29) for the T4 primary group and 68% (n = 32) for the locally recurrent group. The most common tumour sites prior to preoperative radiotherapy in the locally recurrent group were the lateral pelvic brim (n = 24; left = 16; right = 8), and the proximal presacral area (n = 13). Of the evaluable patients, 95.8% (23/24) of the T4 primary group and 91.3% (21/23) of the locally recurrent group were MMR-proficient. Preoperative radiotherapy prescription was 45-50.4 Gy given in 1.8-2 Gy per fraction. Concurrent 5-FU based chemotherapy was given in 95% (n = 38) of the T4 primary group and 95.9% (n = 47) locally recurrent group. Median follow-up time was 48.9 months (range, 31.5- 80.7) for the T4 primary group and 43.1 months (range, 24.2- 74.1) for the locally recurrent group. Results: In the T4 primary group, downstaging of the pre-treatment clinical stage was documented in 57.5% (n = 23) and curative-intent surgery was possible in 90% (n = 36), 80.5% (n = 29) of which were R0 resections. On the other hand, curative-intent surgery was possible in 79.6% (n = 39) of the locally recurrent group, 64% (n = 25) of which were R0 resections. Of the patients who underwent surgery, 22% (n = 8) in the T4 primary group and 41% (n = 16) in the locally recurrent group avoided a multi-visceral resection. A pathologic complete response was achieved in 8.3% (n = 3) in the T4 primary group and in 10.3% (n = 4) in the locally recurrent group. For the T4 primary group, 13% had local failures (Hazard rate 3%, 95% CI 1-6%), 38% had any disease progression (Hazard Rate 9%; 95% CI 5-14), and 45% died (Hazard Rate 8%; 95% CI 5-13) during the follow-up period. For the locally recurrent group, 35% had local failures (Hazard Rate 13%, 95 CI 9-19), 61% had any disease progression (Hazard Rate 20%, 95% CI 14-29), and 60% died (13%, 95% CI 9-19) the follow-up period. Grade 1-2 anastomotic leak occurred in a total of 6 (8%) patients, 3 in each group. Readmission after surgery was needed in a total of 17 (22.6%) patients, 4 in the T4 primary group and 13 in the locally recurrent group. There was no 30-day mortality in the entire cohort. Conclusions: Curative-intent resection may be achieved after preoperative radiotherapy for select T4 primary and locally recurrent colon cancer, which may translate in encouraging clinical outcomes for an advanced cohort of patients. Careful patient selection is required to identify which colon cancer patients may benefit with preoperative radiotherapy.

SP-1002 2030: Towards histology-driven radiation prescription (imaging to pathology translation)

SP-1002 2030: Towards histology-driven radiation prescription (imaging to pathology translation)

Modelled biological effectiveness comparisons of low, high and ultra-high (FLASH) radiation dose rates

This article considers quantitative comparisons of radiation effectiveness across a large range of dose rates, including low (LDR), medium, conventional or high (HDR) and ultra-high (or FLASH) dose rates.For comparisons of different continuous radiotherapy prescriptions, the linear quadratic model was used to derive ‘biological effective dose’ (BED) equations which included time-dependent enzymatic DNA repair in the low to high dose rate range for monophasic or biphasic repair kinetics. In a recent publication, much higher dose rates, associated with increasing overall radioresistance, was thought to be governed by a cube root (or similar) function of dose rate (which expresses the intensification of micro-volumetric linear energy transfer per unit volume and correlates with average inter-track distances) with resultant increases in the apparent α/β ratios. Explicit equations for assessments of BED* (defined as the excess BED beyond the threshold BED) are presented for dose rates ranging from around 0.1–5 × 106 Gy per hr. The method can also be adapted for tumour control comparisons.Graphical presentations are used to determine iso-effective doses of similar BED* values at different dose rates, for specified radiation doses. The threshold BEDs for radio-tolerance reduce in proportion to the change in the α radiosensitivity parameter. For dose rates above the HDR range, the intrinsic α/β ratio, which is independent of dose rate, continues to influence the magnitude of the changes in BED and dose required for a specified bio-effect, but in a modified form.For further research purposes, these tentative methods can provide isoeffective dose estimates to guide radiation use at different dose rates, but require further specific experimental validation. The methods may seem complex and contain many pitfalls. Further research is also required to identify residual enigmas, such as the exact dose rate and dose at which biological FLASH effects begin to operate and to validate these isoeffective dose predictions.

Abstract P1-10-11: Optical stimulated luminescence dosimeters for skin dose measurements during accelerated partial breast brachytherapy: In vivo dosimetric validation and clinical outcomes

Abstract BACKGROUND: The role of multi-lumen catheter devices in the delivery of high dose rate (HDR) brachytherapy for adjuvant accelerated partial breast irradiation (APBI) for women with DCIS or early-stage breast cancer has been well established. In vivo dosimetry (IVD) using optically stimulating luminescence dosimeters (OSLD) is a feasible way to detect applicator instability that may cause translational and rotational inaccuracies during HDR brachytherapy delivery. Herein, we evaluate the accuracy and effectiveness of IVD to improve patient outcomes following APBI brachytherapy using the Strut Adjusted Volume Irradiation (SAVI) device. METHODS: Single-institution cohort study piloting the use of OSLD on the patient’s skin during HDR brachytherapy APBI to assess the estimated maximum skin dose (skin Dmax) and the achievable accuracy of OSLD for skin Dmax measurements. Women treated with SAVI-based APBI between November 1, 2018 and October 1, 2021 were eligible to enroll in our study. All patients met the American Society for Radiation Oncology “suitable” or “cautionary” criteria and were treated according to the American Brachytherapy Society consensus treatment planning guidelines. A SAVI preplan was created to estimate the probable point of skin Dmax. During CT simulation, a radiopaque marker was placed on the skin for visualization during treatment planning. Correction factors were applied to account for the OSLD tissue-air interface that is not present in the TG-43 expected dose calculations. Measured and calculated IVD doses were analyzed to assess agreement and cause for discrepancies found. Breast phantom IVD measurements repeated seven times with two independent dose points were analyzed to assess the best accuracy achievable under ideal conditions. RESULTS: We enrolled 41 patients with an average age of 68 years. Table 1 details the brachytherapy treatment delivery and dosimetry data. Higher skin Dmax as a percentage of the radiation prescription was associated with the occurrence of breast volume loss noted on subsequent clinical breast exams (OR 1.84 per each 5% increase in skin Dmax; 95% CI 1.21 – 3.32; p=0.016). The graphically estimated skin Dmax threshold was 80% with all cases of noted breast volume loss occurring above this threshold. The overall level of achievable IVD accuracy was ±3.32% based on breast phantom measurements. Under ideal conditions, all measurements were in the ±7% range. Three of 14 phantom measurement exceeded the 6% discrepancy range. Clinical IVD measurements detected 5 true positive cases (12.2% of cohort) that required intervention due to rotations in the SAVI applicator. For a ±7% tolerance criteria, 90.2% of the patients tested passed IVD. Of the eight patients that failed at the 7% level, IVD detected 3 OSLD placement errors, 2 rotational discrepancy cases, and 1 large air-gap at the point of measurement. CONCLUSIONS: Accuracy and reproducibility are imperative tenets of HDR brachytherapy APBI. IVD utilizing OSLD is an effective method for detecting treatment set-up and delivery errors for patients receiving SAVI-based APBI with dose accuracy within ±3.32%. Errors requiring intervention due to SAVI device rotation were detected in 12.2% of our cohort, and these errors would have likely gone undetected without IVD. Using OSLD as IVD to measure skin Dmax doses that may increase the risk of breast cosmetic defects should be investigated further. Table 1. Brachytherapy treatment delivery and dosimetry data. *PTV-Eval is a uniform 10 mm expansion on the CTV with exclusion of PTV within 5 mm of skin or chest wall. +Percent dose discrepancy refers to difference in dose between APBI plan calculations and IVD measurements. Citation Format: Tyler Gutschenritter, Afua Yorke, Nayak Polissar, Nirnaya Miljacic, Janice Kim, Lori Young. Optical stimulated luminescence dosimeters for skin dose measurements during accelerated partial breast brachytherapy: In vivo dosimetric validation and clinical outcomes [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-11.

Outcomes of Patients Treated in the UK Proton Overseas Programme: Central Nervous System Group

AimsIn 2008, the UK National Health Service started the Proton Overseas Programme (POP), to provide access for proton beam therapy (PBT) abroad for selected tumour diagnoses while two national centres were being planned. The clinical outcomes for the patient group treated for central nervous system (CNS), base of skull, spinal and paraspinal malignancies are reported here. Materials and methodsSince the start of the POP, an agreement between the National Health Service and UK referring centres ensured outcomes data collection, including overall survival, local tumour control and late toxicity data. Clinical and treatment-related data were extracted from this national patient database. Grade ≥3 late toxicities were reported following Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 definition, occurring later than 90 days since the completion of treatment. ResultsBetween 2008 and September 2020, 830 patients were treated within the POP for the above listed malignancies. Overall survival data were available for 815 patients and local control data for 726 patients. Toxicity analysis was carried out on 702 patients, with patients excluded due to short follow-up (<90 days) and/or inadequate toxicity data available. After a median follow-up of 3.34 years (0.06–11.58), the overall survival was 91.2%. The local control rate was 85.9% after a median follow-up of 2.81 years (range 0.04–11.58). The overall grade ≥3 late toxicity incidence was 11.97%, after a median follow-up of 1.72 years (0.04–8.45). The median radiotherapy prescription dose was 54 GyRBE (34.8–79.2). ConclusionsThe results of this study indicate the safety of PBT for CNS tumours. Preliminary clinical outcomes following PBT for paediatric/teen and young adult and adult CNS tumours treated within the POP are encouraging, which reflects accurate patient selection and treatment quality. The rate of late effects compares favourably with published cohorts. Clinical outcomes from this patient cohort will be compared with those of UK-treated patients since the start of the national PBT service in 2018.