Radiation Modalities Research Articles

Brachytherapy for Soft Tissue Sarcoma: Maintaining Local Control While Minimizing Complications.

This study aims to assess the clinical and oncologic outcomes of high-dose brachytherapy (BRT) versus both preoperative and postoperative external beam radiation therapy (EBRT) in the setting of high-grade soft tissue sarcoma. This is a retrospective cohort study of 144 patients treated surgically for soft tissue sarcoma at the same institution from 2010 to 2021. Patients treated for a soft tissue sarcoma with surgery and radiation therapy in the form of BRT, Neoadjuvant EBRT (Neo-EBRT) or adjuvant EBRT (AD-EBRT) were included. 56 patients were treated with BRT, 42 with Neo-EBRT, and 46 with AD-EBRT. There was a greater incidence of grouped wound complications in Neo-EBRT with 50% compared to both BRT with 25% and AD-EBRT with 28.3% (p = 0.02). Univariate and multivariate analysis showed that there was an increased risk of wound complications with Neo-EBRT when compared to brachytherapy (p = 0.03 and p = 0.007, respectively). Univariate and multivariate analysis showed that there was no difference in risk of LR between treatment groups (p = 0.28). Brachytherapy is a valuable treatment modality that offers clinical and logistical advantages when compared to the conventional Neo-EBRT in soft tissue sarcomas. Brachytherapy offers a lower risk of wound complications and a comparable local control. This manuscript presents decision-making strategies for determining the appropriate radiation modality for specific circumstances.

NCOG-12. TREATMENT AND MORTALITY OF PRIMARY BRAIN TUMORS: A SINGLE CENTER OBSERVATIONAL STUDY OF GLIOBLASTOMAS AND ASTROCYTOMAS

Abstract Glioblastoma multiforme (GBM) is a WHO grade IV malignant tumor with a relatively poor prognosis (median survival of 15 months). Astrocytomas are WHO grade I-III tumors with a better prognosis than GBM; their median survival ranging from 2-10 years. We assessed the response to various mainstay treatment modalities in patients with GBM and astrocytoma, expecting to find that surgery and stereotactic radiation (SRS) treatment confer greater survival benefits than non-surgical and whole brain radiation (WBRT) options. We analyzed 108 patients at St. Luke’s University Health Network (SLUHN) who were previously diagnosed with a primary brain tumor consistent with GBM (90) or astrocytoma (18) prior to January 1, 2023. Mainstays of treatment were surgery with or without different radiation modalities (WBRT and SRS, and WBRT+SRS). Glioblastoma typically affected older patients (65.5), had mostly single lobe involvement (86.7%), and was predominantly located in the frontal (41.1%) and temporal lobes (37.7%). Astrocytoma was slightly younger (51.2), less often single lobe (72.2%), and mostly involved the frontal (44.4%), temporal (44.4%), and parietal lobes (33.3%). GBM found the greatest benefit from WBRT (without co-occurring SRS) with an increase of 16.4 months to 20.2 months (p=.789). Surgery, regardless of radiation status, appeared to provide the greatest benefit for patients with astrocytoma increasing average lifespan from 36.7 months to 53.6 months (p=.181). Patients with glioblastoma that underwent surgery also had increased survival of 18.2 months compared with nonsurgical patients at 12 months (p=0.097). While we were interested to see the impact these treatment modalities had on patient survival, our sample size was small and our results lacked statistical significance. Future studies with greater sample sizes would help determine whether statistical significance is correlated with meaningful clinical outcomes.

Real-world use of immune checkpoint inhibitors in advanced or recurrent endometrial cancer

ObjectiveThe aim of this study was to describe real-world use of immune checkpoint inhibitors for women with advanced or recurrent endometrial cancer.MethodsAdult women with advanced or recurrent endometrial cancer who...

Impact of Pre-pectoral Implant Placement and Radiation Modalities (Protons/Photons) in Mastectomy Patients undergoing Immediate Direct-to-Implant Breast Reconstruction

BackgroundFor breast cancer patients receiving mastectomy with direct-to-implant (DTI) immediate breast reconstruction, placing the implant in the pre-pectoral or subpectoral plane remains debatable; especially in settings of postmastectomy radiotherapy (PMRT). Materials/MethodsWe reviewed 3,039 patients who underwent mastectomy and reconstruction at our institution between 2005 and 2020. Patients receiving DTI with and without PMRT were included. PMRT was delivered either with photon (3D-conformal or VMAT) or proton therapy mainly with pencil beam scanning. All patients received conventional fractionation (50-50.4Gy in 25-28fractions). Primary endpoints were reconstruction complications defined as infection/necrosis requiring debridement; capsular-contracture requiring capsulotomy; absolute-reconstruction-failure entailing permanent removal of the implant without replacement (i.e: no salvage reconstruction) and overall-reconstruction-failure (removal of implant for any complication with and without salvage reconstruction). Different subgroups analyses were done. Results815 patients met inclusion criteria, with an overall median follow-up of 6.2 years. We found that there is no significant difference between pre-pectoral vs sub-pectoral for infection/necrosis (OR:1.5, p=0.3); capsular-contracture (OR:0.97, p=0.9); absolute-reconstruction-failure (OR:1.9, p=0.12) and overall-reconstruction-failure (OR:1.2, p=0.5). Findings were confirmed using both logistic regression, time-to-event analysis and multivariable analyses for the entire cohort and subgroups with and without PMRT. There was no significant difference between Protons and Photons in terms of infection/necrosis (OR:1.6, p=0.4) and absolute-reconstruction-failure (OR: 1.2, p=0.7), but significantly higher risks for capsular-contracture with protons (OR:4.4, p<0.001) and overall-reconstruction-failure when compared to photon(OR:2.0, p=0.05). We did not find significant correlation pattern between different dosimetry factors (Dmean, Dmax, volume in cc) in either reconstructed-chest-wall target or the skin structure, to reconstruction complications; whether for protons or photons patients. ConclusionFor patients receiving single-stage DTI reconstruction with and without PMRT, pre-pectoral implant placement had similar rates of complications and reconstruction failure compared to subpectoral reconstruction. Protons compared to Photons did not increase the risk of infection/necrosis but significantly increased capsular-contracture risks.

Patient-Reported Factors Impacting Memory and Cognition Among Women Currently or Previously Receiving Treatment for Breast Cancer.

Objectives Cognitive impairments associated with cancer and cancer treatments have yet to determine definitive causes, gold-standard assessments, or effective treatments to offset or mitigate symptoms. The purpose of the current study was to determine relationships between women with breast cancer and the negative memory impact of treatment and other factors. Materials and methods This online study included 171 participants receiving at least one type of treatment for breast cancer. This descriptive correlational study used two measures to assess memory and one for stress. The survey included demographics, treatments received, and memory. Results Results indicated increased perceived impairments among variables of age, stress, surgery, chemotherapy, radiation, and hormonal treatment modalities. Discussion This study established relationships between memory/cognitive impairments and the variables of age, four treatment modalities, three agents, and stress. Conclusion The results from this study demonstrate the importance of developing standardized assessments to identify the presence and severity of cancer and treatment-related cognitive impairments. The study will be used as a first step to developing a memory support strategy using a web-based nursing intervention considering the impact of stress.

Effect of Ultrahigh Dose Rate on Biomolecular Radiation Damage.

Dose rate is one of the important parameters in radiation-induced biomolecular damage. The effects of dose rate have been known to modify radiation toxicity in biological systems. The rate and extent of sublethal DNA damage (e.g., base damage and single-strand breaks) repair and those of cell proliferation have been manifested by dose rate. However, the recent preclinical application of ultrahigh dose rate [(UHDR) ca. 40 Gy/s and higher] radiation modalities have been shown to lower the type and extent of radiation damage to biological systems. At these UHDR, radiation-induced physicochemical and chemical processes are expected to differ from those observed after irradiation at conventional dose rates (CONV). It is unclear whether these UHDR conditions can affect the quality (type) and quantity (extent) of biomolecular damage such as DNA lesions. Here, we comparatively study the influence of indirect effects of CONV and UHDR on the formation of DNA strand breaks and clustered damage including densely accumulated lesions in an aerated and an anoxic dilute aqueous solution of a plasmid DNA model under low and high hydroxyl radical (•OH) scavenging conditions. Aqueous solutions of purified supercoiled plasmid DNA (pUC19) were prepared in either air- or nitrogen-saturated conditions, with Tris buffer added as the radiation-produced •OH scavenger at low and high scavenging capacities. These DNA samples were irradiated using kV X-ray systems at CONV (0.1 Gy/s) and high dose rate (HDR, 25 Gy/s) as well as UHDR (55 and 125 Gy/s) under different scavenging and environmental conditions. DNA lesions including strand breaks and clustered damage including densely accumulated lesions were quantified by gel electrophoresis and the yields of these lesions were calculated from the dose-response curve. Non-DSB clustered damage including densely accumulated lesions were evaluated by treating DNAs using bacterial endonuclease enzymes (Fpg and Nth) prior to gel electrophoresis. UHDR of 55 and 125 Gy/s induced lower amounts of both isolated strand breaks and clustered DNA damage including densely accumulated lesions at doses >40 Gy in the presence of oxygen, compared to the abundance of these lesions induced by 0.1 and 25 Gy/s irradiation under the same dose conditions. Overall, the strand break and clustered damage including densely accumulated lesions yields decreased by factors of 1.3-3.5 after UHDR. We did not observe these differences either via •OH scavenging or by removing oxygen from the solution. In addition, our results point out that the inter-track recombination reactions did not contribute to the observed dose-rate effects on DNA damage. The effects of dose rate on DNA damage are highly dependent on the total dose, as expected, but also on the •OH scavenging capacity that is employed in the aqueous DNA solutions. These important variables may be relevant in biological systems as well. On a practical level, our in vitro plasmid DNA model, which permits to precisely vary the scavenging capacity and gassing conditions (air saturated vs. N2 saturated) can help to differentiate dose-rate effects on biomolecular damage. Our results indicate that the radical-radical reactions are important in understanding the dose-rate effect on DNA damage.

Isotopically Enriched Lithium Fluoride Crystals for Detection of Neutrons with the Fluorescent Track Technique.

In this work, the properties of LiF crystals grown using Li of different isotopic compositions are described from the standpoint of their application as fluorescent nuclear track detectors used in measurements in the neutron radiation fields. The crystals were grown using two techniques: the Czochralski method and the micro-pulling-down method. Three isotopic compositions of Li were studied: natural, highly enriched in 6Li, and highly enriched in 7Li. It was found that 6LiF detectors are about six times more sensitive to thermal (low energy) neutrons than natural LiF, which significantly decreases the lower detection limit. 7LiF detectors are insensitive to thermal neutrons, which makes it easier to detect tracks due to other radiation modalities, such as energetic ions or nuclei recoiled in collisions with high-energy neutrons. Besides the response to neutron radiation, no other significant differences in the crystal properties were identified, irrespective of the isotopic composition and crystal growth method employed.

Real world clinical outcomes from targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer: data from a large cohort at a national cancer institute.

Randomised evidence supports the use of partial breast irradiation (PBI) with targeted intraoperative radiotherapy (TARGIT-IORT) for early stage breast cancer, but prospective data from real-world adoption of this technique is also important. The aim of this study was to determine if the outcome reported in TARGIT-A trial could be replicated in large cohort of early stage breast cancer treated with TARGIT-IORT. This prospective observational study analysed all patients treated with TARGIT-IORT between 2004 and 2021 in a single national cancer institute. TARGIT-IORT during lumpectomy was performed according to the risk-adapted TARGIT-A protocol using the Intrabeam® device. We analysed the completeness of follow up, 5-year in-breast-tumour-recurrence (IBTR), long term local recurrence free survival, distant disease-free survival, overall survival and breast-cancer-related survival, using the Kaplan-Meier method. A covariate analysis was performed to investigate risk factors for IBTR. We also analysed high grade toxicity events. The study included 814 patients and the a median follow up was 72 months. The majority of patients (60.3%) received TARGIT-IORT as PBI modality ("exclusive IORT" group); 39.7% received additional EBRT. There was no significant difference between the 5 years IBTR for the whole study population and the "exclusive IORT" cohort (1.6% (95%CI=1.1-2.1%) and 2.5% (95%CI=1.7%-3.3%) respectively). 5 years overall survival and tumour related survival were >95%. In 21% of patients with recurrence, breast was preserved. Radiotherapy toxicity (CTCAE Grade>2) was very rare (0.9%). This large single institute study found that breast cancer control and survival outcomes with TARGIT-IORT were consistent with TARGIT-A trial results. This "real world" experience confirmed that the randomised evidence showing the value of TARGIT-IORT as partial breast irradiation modality that can be replicated in routine clinical practice.

Utility of learning health systems in radiation oncology.

413 Background: Current health information systems lack a robust framework for longitudinal integration of internal experiences and external evidence into existing workflows. The result is labor intensive, error-prone and fragmented systems plagued with process gaps. Learning health systems (LHS) can be a potential solution to address these gaps. We created and implemented a novel LHS framework in radiation oncology (RO). We hypothesize that this framework can be leveraged to identify and implement opportunities for improvement using a patient-oriented endpoint of time from radiation simulation to treatment start (RSTS). Methods: An RO-LHS was developed through a collaboration between an academic, multi-facility radiation oncology department and an industry partner (Medlever). The end-to-end clinical workflow was embedded into the Medlever platform following an interdisciplinary, iterative analysis with representatives from key teams (clerical, finance and clinical). A novel nomenclature was created to label standardized, customizable templates, which choreograph logic-driven tasks that cover all sub-steps of RSTS. The primary endpoint of RSTS was compared pre- and post-implementation, stratified by key variables, such as facility, staff member, and radiation treatment modality. Results: The iterative workflow analysis identified &gt;700 variables and decision points necessary for &gt;200 cancer and benign conditions routinely managed in RO. &gt;450 treatment protocols were templated.180 logic-driven tasks were created and linked to key parameters, resulting in a choregraphed precision workflow for each patient. Using the first iteration of the build, a total of 512 patients were managed during a 50-day period (03/01/2024-04/20/2024) and were compared to 2875 patients treated prior to implementation. Post-implementation, RSTS was shortened by 36.4% (p&lt;0.001). We identified significant differences in RSTS by radiation modalities (protons vs all others), across facilities, and by providers (p&lt;0.01 for all). Analysis of fractional domain of RSTS, 56% of the time was driven by physician-directed tasks, while 44% was comprised of physics and dosimetry-driven work. Physician-directed tasks had the greatest heterogeneity in time to completion. The biggest variation was noted for the contouring completion task. Significant differences were identified by provider (p&lt;0.001) in nearly each step of the process, including steps not directly tied to physician’s work. Conclusions: Through an inter-disciplinary implementation of the first iteration of a LHS in our RO department, we have significantly shortened RSTS. The implementation and analysis has also enabled us to better understand underlying heterogeneities and identify further opportunities for optimization of RSTS. An LHS framework provides a generalizable solution that could be adapted in other RO clinics.

Lymphopenia associated with whole-brain radiotherapy and its effects on clinical outcomes of patients with brain metastases

There is increasing awareness of radiotherapy’s potential side effects, such as lymphopenia. Therefore, this study aimed to establish the association between WBRT and the development of lymphopenia in patients with brain metastases undergoing brain radiotherapy (RT), along with evaluating the corresponding clinical outcomes. Including 116 patients with brain metastases undergoing brain radiotherapy, the study collected the absolute lymphocyte counts (ALC) within 2 weeks before brain radiotherapy (pre-radiotherapy, pre-RT), as well as ones at 1 and 2 months after completing RT (post-RT). Univariate and multivariate analyses were performed to identify associations between radiation modality and post-RT ALC. The relationships between post-RT ALC and overall survival were evaluated with Kaplan–Meier analysis and a multivariate Cox regression model. The median ALC definitely decreased at 1 month post-RT, but at 2 months post-RT, gradually rose but not to the pre-RT ALC. The multivariate analysis identified WBRT and lower pre-RT ALC as independent risk factors associated with the decrease in post-RT ALC at 1 month. It also revealed more than 4 brain metastases, G3-4 lymphopenia at 1 month and lower post-RT ALC at 2 months exhibited significantly worse prognosis regardless of the radiation modality. However, there was indeed an independent correlation between radiation modality and the outcome of intracranial progression-free survival (PFS). To approach the feasibility and reasonableness of treatment, clinicians should carefully consider various factors to achieve long-term survival of patients.

Innovative nano-shielding for minimizing stray radiation dose in external radiation therapy: A promising approach to enhance patient safety

This study investigates the effectiveness of novel nanocomposite shielding materials in reducing out-of-field radiation doses during radiation therapy, employing Geant4 Monte Carlo (MC) simulations alongside an anthropomorphic female phantom. The research focuses on two radiation modalities: 6 MV beams with and without flattening filters. Utilizing the Geant4 MC code, detailed simulations of a Varian Clinac 2100C/D linear accelerator and an ICRP-145 mesh-type human phantom were conducted to estimate the doses to out-of-field organs from unintended secondary radiation. This involved simulating a comprehensive linac model, including all relevant beam-line components, and assessing the shielding effects of three different nanocomposites doped with metal nanoparticles at various thicknesses. The nanocomposites, comprising Polytetrafluoroethylene (PTFE), with PtO2, IrO2, and Bi2O3 nanoparticles, were evaluated for their potential to reduce patient organ doses from stray photon doses. The results showed that these materials could significantly lower radiation exposure to non-target tissues.

Contrast enhanced ultrasound of liver lesions in patients treated for childhood malignancies

BackgroundPatients treated for cancer have a higher incidence of focal liver lesions than the general population and there is often concern for a malignant etiology. This can result in patient, caregiver and physician anxiety and is managed by a “wait and watch” approach, or immediate additional imaging, or biopsy, depending on the degree of clinical concern. Because it is a low-cost, easily accessible, radiation and sedation free modality, we investigated the value of contrast enhanced ultrasound (CEUS) to accurately distinguish benign from malignant liver lesions in patients treated for childhood malignancies.MethodsWe performed an IRB approved retrospective study of 68 subjects who were newly diagnosed, on treatment or off treatment for a pediatric malignancy and had liver lesions discovered on CT, MRI or non-contrast ultrasound and subsequently underwent CEUS between September 2013 and September 2021. Two experienced pediatric radiologists and a radiology trainee, blinded to the etiology of the liver lesions, independently reviewed the CEUS examinations and categorized lesions as benign, indeterminate, or malignant. The reference standard was biopsy for 19 lesions and clinical follow-up for 49. The sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of CEUS were calculated using only the benign and malignant CEUS classifications. Inter-reviewer agreement was assessed by Cohen’s kappa statistic.ResultsThere were 26 males and 42 females, mean age, 14.9 years (range, 1–52 years). Fifty subjects were off therapy, twelve receiving treatment, and six with newly diagnosed cancer. By the reference standard, 59 (87%) lesions were benign and 9 (13%) were malignant. Sensitivities of CEUS for the three reviewers ranged from 83 to 100% (95% CI, 35.9-100%), specificities from 93.1 to 96.0% (95% CI, 83.5-99.6%), PPV 60.0-71.4% (95% CI, 29.0-96.3%), NPV 98.0-100% (95% CI, 89.2-100%) and accuracy from 93.8 to 94.6% (95% CI, 85.1-99.7%). The kappa statistic for agreement between the two experienced radiologists was moderate at 0.58.ConclusionsCEUS is highly accurate in distinguishing benign from malignant etiologies of liver lesions in patients treated for pediatric malignancies.

Secondary Cancer in Prostate Cancer Patients Treated With Advanced External Beam Radiation Therapy

PurposePrevious studies have shown that external beam radiation therapy is associated with an increased risk of second primary cancer (SPC) among prostate cancer (PCa) patients, but the relative risks associated with newer and advanced radiation modalities such as proton beam therapy (PBT) and stereotactic body radiation therapy (SBRT) are unclear. This study aimed to assess the relative probability of SPC among patients treated with these newer modalities compared to intensity-modulated radiation therapy (IMRT). Patients and MethodsUsing the National Cancer Database (NCDB), N0M0 PCa cases diagnosed between 2004 and 2018 were identified. Second primary cancer probabilities were compared among those treated with curative-intent PBT, SBRT, and IMRT. Multivariable logistic regression and inverse probability of treatment weighting were used to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). ResultsIn total, 133 898 patients were included, with a median age of 69 years and median follow-up of 6.4 years. As their first course of treatment, 3420 (2.6%) received PBT, 121 211 (90.5%) received IMRT, and 9267 (6.9%) received SBRT. Compared with IMRT, PBT and SBRT were associated with lower SPC risk (aORs and 95% CIs, PBT: 0.49 [0.40-0.60], SBRT: 0.57 (0.51-0.63), P < .001). Inverse probability of treatment weighting analyses corroborated these results. ConclusionIn this large national cohort, PBT and SBRT performed similarly and were associated with reduced SPC risk compared to IMRT when used as the first course of treatment.

Early Inflammation and Interferon Signaling Direct Enhanced Intestinal Crypt Regeneration after Proton FLASH Radiotherapy.

Ultra-high dose rate ("FLASH") radiotherapy (>40-60 Gy/s) is a promising new radiation modality currently in human clinical trials. Previous studies showed that FLASH proton radiotherapy (FR) improves toxicity of normal tissues compared to standard proton radiotherapy (SR) without compromising anti-tumor effects. Understanding this normal tissue sparing effect may offer insight into how toxicities from cancer therapy can be improved. Here, we show that compared to SR, FR resulted in improved acute weight recovery and survival in mice after whole-abdomen irradiation. Improved morbidity and mortality after FR were associated with greater proliferation of damage-induced epithelial progenitor cells followed by improved tissue regeneration. FR led to the accelerated differentiation of revival stem cells (revSCs), a rare damage-induced stem cell required for intestinal regeneration, and to qualitative and quantitative changes in activity of signaling pathways important for revSC differentiation and epithelial regeneration. Specifically, FR resulted in greater infiltration of macrophages producing TGF-β, a cytokine important for revSC induction, that was coupled to augmented TGF-β signaling in revSCs. In pericryptal fibroblasts, FR resulted in greater type I IFN (IFN-I) signaling, which directly stimulates production of FGF growth factors supporting revSC proliferation. Accordingly, the ability of FR to improve epithelial regeneration and morbidity was dependent on IFN-I signaling. In the context of SR, however, IFN-I had a detrimental effect and promoted toxicity. Thus, a tissue-level signaling network coordinated by differences in IFN-I signaling and involving stromal cells, immune cells, and revSCs underlies the ability of FLASH to improve normal tissue toxicity without compromising anti-tumor efficacy.

Selection for proton radiotherapy of grade 1–3 glioma patients

BackgroundFor adult patients with grade 1–3 gliomas, identifying patients with an indication for proton therapy (PT) can be challenging due to sparse evidence supporting its benefits. In this study, we aimed to ensure national consensus and develop a decision support tool to aid clinicians in identifying patients with grade 1–3 gliomas eligible for PT. MethodsSixty-one historic patients referred for postoperative radiotherapy for glioma grade 1–3 were included in this study and had new photon therapy and PT plans calculated. These plans along with clinical parameters were presented to neurooncologists with experience in treating brain tumours. The patients were presented at three workshops (WSs), where each neurooncologist individually had to choose between photon and proton therapy. Important parameters were selected using cross validation. Multivariable logistic regression was used to predict the neurooncologists’ treatment modality choice. ResultsAt the three WSs 23, 24 and 19 randomly selected patients were presented. Seventy-five percent of the neurooncologists agreed for 14 patients (61%), 16 patients (67%) and 15 patients (79%) at WS1, WS2 and WS3. Age at radiotherapy and difference in mean dose (ΔDmean) to the residual brain were significant predictors of the choice of treatment modality, p < 0.001. Model coefficients were: βage = 0.07 per year (95% confidence interval [CI] = 0.05–0.09), and βΔdose = -0.27 per Gy (95% CI=-0.36--0.18). ConclusionHigher degree of agreement was reached. Age and ΔDmean to the residual brain significantly predicted the choice of radiation modality. We have developed a decision support model which may aid in the selection of patients with glioma grade 1–3 to PT.

472 Advancing patient care: The expanding role of RTTs in advanced radiation modalities

472 Advancing patient care: The expanding role of RTTs in advanced radiation modalities

Impact of proton versus photon adjuvant radiotherapy on overall survival in the management of skull base and spinal chordomas: a National Cancer Database analysis.

Chordomas are rare tumors that originate from undifferentiated remnants of the notochord. Currently, there are no established guidelines regarding the choice of adjuvant radiation modality for patients surgically treated for chordomas. Using a nationwide, multicenter database, the authors aimed to compare long-term survival outcomes associated with the use of proton or photon adjuvant therapy for the management of chordomas of skull base and spine. The National Cancer Database (NCDB) was queried for chordoma cases from 2004 to 2017. Patient, tumor, and treatment characteristics were extracted from the database. The primary outcome was overall survival (OS). Kaplan-Meier survival analyses were conducted to investigate differences in outcome on propensity score-matched cohorts of patients treated with proton or photon adjuvant radiotherapy. Of the 3490 patients available, 424 met the inclusion criteria for this study. In the prematching analysis, patients receiving adjuvant photon therapy were significantly older (median age 57.0 vs 45.0 years, p < 0.001) and were more commonly male (61% vs 43%, p < 0.001) compared with those receiving proton therapy. Races were equally distributed among radiotherapy modalities (p = 0.64). Patients with chordomas of the mobile spine or sacrum were less likely to receive proton compared with photon therapy (37% vs 58%). Patients receiving proton therapy were more often represented among private insurance holders (69% vs 52%, p < 0.001) as well as in the highest income quartile (52% vs 40%, p = 0.008). Patients traveled farther to receive proton, as opposed to photon, therapy (median 59.0 vs 34.9 miles, p < 0.001). On postmatching Kaplan-Meier analysis encompassing all chordoma cases, no difference in OS between photon and proton therapy was revealed (HR 0.75, 95% CI 0.39-1.44; p = 0.39). A Kaplan-Meier analysis only including patients with skull base chordomas reached similar results (HR 0.83, 95% CI 0.31-2.22; p = 0.71). In patients with spine chordomas, however, a significant difference was found, as proton therapy exhibited a superior OS over photon therapy (HR 0.28, 95% CI 0.09-0.81; p = 0.012). Based on this nationwide analysis, patients with private insurance and higher income were more likely to receive proton adjuvant radiotherapy, while those with spinal or sacral chordomas were less likely to receive this modality. Despite this disparity, an OS benefit was observed in patients with chordomas of the spine and sacrum who received adjuvant proton therapy, in comparison with a matched cohort of patients treated with photon therapy. Conversely, this advantageous outcome was not evident in cases of chordomas located at the skull base.

Proton Pencil Beam Scanning Facilitates the Safe Treatment of Extended Radiation Targets for Hodgkin Lymphoma: A Report from the Proton Collaborative Group Registry.

Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose. Using the Proton Collaborative Group registry, we identified patients with HL treated with PBT to both their mediastinum and axilla, for which DICOM-RT was available. All patients were treated with PBS. To evaluate the dosimetric impact of PBS, we compared delivered PBS plans with VMAT butterfly photon plans optimized to have the same target volume coverage, when feasible. Between 2016 and 2021, twelve patients (median 26 years) received PBS ETRT (median 30.6 Gy (RBE)). Despite the large superior/inferior (SI, median 22.2 cm) and left/right (LR, median 22.8 cm) extent of the ETRT targets, all patients were treated with one isocenter except for two patients (both with SI and LR > 30 cm). Most commonly, anterior beams, with or without posterior beams, were used. Compared to photons, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving lower doses to the lungs and heart, but not to the breast. No acute grade 3+ toxicities were reported, including pneumonitis. Proton ETRT in this small cohort was safely delivered with PBS and was associated with an improved sparing of the heart and lungs compared to VMAT.

Spatially fractionated radiotherapy (Lattice SFRT) in the palliative treatment of locally advanced bulky unresectable head and neck cancer

ObjectivesLocally advanced bulky unresectable head neck cancer causes significant tumor mass effects, leading to severe symptoms. This study aims to report the safety and outcomes in patients undergoing Lattice spatially fractionated radiotherapy (Lattice SFRT) for locally advanced bulky unresectable head and neck cancer. MethodsPatients with bulky head and neck cancer received Lattice SFRT between June 2022 and June 2023. Lattice SFRT was administered in 2–3 fractions of 12 Gy (Gy) using 6-megavolt (MV) photon beams through a multileaf collimator (MLC) based on VMAT technology. The primary endpoints were symptomatic and tumor response rates. Secondary endpoints were overall survival, local control, and acute and late toxicity rates. Results19 consecutive patients meeting the study criteria were identified, predominantly with squamous cell carcinoma histology. The median patient age was 62 years (range 39–79 years), and the median tumor volume was 208 cc (cc) (range 48–701 cc). All patients completed radiotherapy. Among all investigated patients, 16 of 19 (84.2 %) patients achieved an objective response, including 10 individuals achieved a partial response (PR), with 3 of them exhibiting regression exceeding 75 %. 17 patients showed symptom improvement to varying degrees. Acute toxicity of Radiation Therapy Oncology Group (RTOG) grade 1 or higher occurred in 5 patients, while no grade 3 adverse events was observed. ConclusionsLattice SFRT proves to be a viable treatment option for the palliative management of bulky head and neck cancer. In the palliative setting, Lattice SFRT offers timely symptom relief, enhancing patient quality of life. Treatment toxicity remains within an acceptable range. Continued optimization of Lattice SFRT delivery and patient selection can benefit from further data on the feasibility and efficacy of this radiation modality.

Radiation-Induced Lymphopenia is a Causal Mediator of Survival After Chemoradiation Therapy for Esophagus Cancer

Purpose: Radiation-induced lymphopenia (RIL) is common during chemoradiotherapy. Severe lymphopenia is associated with reduced survival. Proton beam therapy (PBT), with its substantially more compact dose distributions, spares circulating lymphocytes and immuno-organs at risk to a greater extent than does photon therapy. Recent studies comparing PBT to photon radiotherapy, specifically intensity-modulated radiation therapy (IMRT), for esophageal cancer (EC) showed that the incidence of grade 4 RIL (G4RIL) is significantly reduced among patients receiving PBT for esophageal cancer. However, whether the extent of this reduction has a direct causative link with improved survival is unknown. This study applies causal mediation analysis to answer this question. Methods and Materials: We retrospectively assessed 734 patients treated with concurrent chemoradiotherapy for biopsy-proven EC from 2004 through 2017. To address the potential for bias in the choice of radiation modality, propensity score analysis was used to evaluate and reduce imbalances between the PBT and IMRT cohorts. Causal mediation analysis was applied to decompose the total effect of radiation modality on overall survival (OS) into indirect (mediated through G4RIL) and direct effects. Results: We found that PBT was associated with significantly lower incidence of G4RIL and prolonged OS compared with IMRT (odds ratio [OR]= 0.41, 95% confidence interval [CI] 0.28 to 0.60, P<0.001). In the propensity-matched cohort of 506 patients (253 PBT, 253 IMRT), G4RIL risk reduction with PBT vs. IMRT translated into a 5% reduction in the relative rate of death (P=0.032). Mediation of G4RIL explained ∼14.5% of the difference in OS. Conclusions: G4RIL was found to mediate survival; however, statistically significant direct effect of PBT on survival was not observed. In other words, the survival benefit from protons over photons in this EC cohort was lost in the absence of G4RIL risk reduction.