PURPOSE:Current electron field shaping methods, such as milled copper cutouts and Cerrobend plates, are limited by toxic materials, recurring costs, and long turnaround times. To circumvent these issues, we designed a 3-dimensional-printed electron multileaf collimator (eMLC) that uses tungsten-infused polyethylene terephthalate glycol (W-PETG), a filament developed specifically for radiation therapy, to create the leaves. This study described the feasibility assessment of this device to shape electron fields. METHODS AND MATERIALS:We first characterized the attenuation properties of W-PETG using stacks of variable thickness blocks (0.1-1 cm, flat 10 × 10 cm2) placed in a solid water phantom with a parallel plate chamber. Attenuation of 6 and 15 MeV electron beam energies was tested using various plate thicknesses. A prototype eMLC was designed to mount within a standard Elekta 14 × 14 cm² cone. The carriage was printed using generic PETG; interlocking leaves were printed using W-PETG. Interleaf and leaf-end leakage were evaluated using 1000 monitor units (MU) delivered through closed leaves. A clinical Cerrobend field was recreated with the eMLC, and both were compared using radiochromic film exposed to 200 MU using 6 and 15 MeV electron beams. RESULTS:W-PETG blocks of 1 cm thickness reduced 6 and 15 MeV electron beams to below 5% transmission. No measurable interleaf or end-to-end leaf leakage was detected at either energy using 1000 MU exposures. The eMLC resulted in a dose distribution nearly identical to Cerrobend. Compared with Cerrobend, the eMLC-generated fields demonstrated approximately 15% smaller penumbra and sharper field edges. CONCLUSIONS:This novel 3-dimensional-printed eMLC using W-PETG provides dose-shaping characteristics comparable with conventional cutouts, with no detectable leakage and improved edge definition. Fabricated with consumer-grade equipment, this device provides reusable, customizable field shapes that may be suitable for clinical use. Further study of its validation and implementation into clinical workflows is warranted.

Purpose Small cell carcinoma of the lung (SCLC) often presents with brain metastases, with most patients developing them within a few years of diagnosis. Prophylactic cranial irradiation (PCI) is commonly recommended. Extrapulmonary small cell carcinoma (EPSCC) is rare, and its metastatic pattern is not well understood. This study reviews brain metastases in EPSCC patients at a single institution, focusing on management and overall survival (OS). Materials We identified EPSCC patients and analyzed their characteristics, treatment, and outcomes. Brain metastases were assessed through diagnostic imaging. Extracranial progression-free survival (ePFS) was defined as the time from diagnosis to progression outside the brain, while OS was defined as the time from diagnosis to death from any cause. Kaplan-Meier methods and log-rank tests were used for time-to-event analyses, and the cumulative incidence of brain metastasis was estimated with the competing risk of death. Statistical significance was set at p < 0.05. Results Of the 68 EPSCC patients with a median follow-up of 7.1 months, 66% were male with a median age of 68 years old. Common primary sites included genitourinary (32%) and gastrointestinal/hepatobiliary (22%). Brain metastases occurred in 12 patients (18%): five at diagnosis and seven during follow-up. The treatment of brain metastases varied, with four patients receiving whole-brain radiotherapy (WBRT), two receiving stereotactic radiosurgery (SRS), and one receiving both WBRT and SRS. The median OS was 10.0 months, with no significant survival difference between patients with (10.8 months) and without (9.4 months) brain metastases (p = 0.89). Conclusion EPSCC has a lower incidence of brain metastases than SCLC, and brain metastases do not significantly impact OS. Further research on brain imaging, PCI, and management strategies is warranted.

Type-I and -III interferons play a central role in immune rejection of pathogens and tumors, thus promoting immunogenicity and suppressing tumor recurrence. Double strand RNA is an important ligand that stimulates tumor immunity via interferon responses. Differentiation of embryonic stem cells to pluripotent epithelial cells activates the interferon response during development, raising the question of whether epithelial vs. mesenchymal gene signatures in cancer potentially regulate the interferon pathway as well. Here, using genomics and signaling approaches, we show that Grainyhead-like-2 (GRHL2), a master programmer of epithelial cell identity, promotes type-I and -III interferon responses to double-strand RNA. GRHL2 enhanced the activation of IRF3 and relA/NF-kB and the expression of IRF1; a functional GRHL2 binding site in the IFNL1 promoter was also identified. Moreover, time to recurrence in breast cancer correlated positively with GRHL2 protein expression, indicating that GRHL2 is a tumor recurrence suppressor, consistent with its enhancement of interferon responses. These observations demonstrate that epithelial cell identity supports interferon responses in the context of cancer.

Purpose/Objective(s) Peer review (PR) is a critical component of radiation oncology practice, but the methods by which this is carried out are highly variable. There has been a substantial change in the format and structure of inter- and intra-disciplinary meetings with the recent rise in virtual/hybrid teleconferencing. We surveyed NCI National Community Oncology Research Program (NCORP) sites to better understand the format, structure, and content of radiation oncology PR. Materials/Methods A one-time survey was distributed to ROs across 42 NCORP community sites through the Wake Forest NCORP Research Base (UG1CA189824) between January and February 2024. The survey explored the routine PR practices of radiation oncologists. Results Twenty-eight radiation oncologists from 13 NCORP sites, all indicated that they participate in routine PR. Years of practice were 0-5 in 25%, 6-10 years in 36%, and >10 years in 39%. The frequency of PR meetings was weekly in 22 of 26, daily in 2, and every other week in 2. The participants were limited to radiation oncologists at all responding practices; no practices included interdisciplinary collaboration with radiologists in their PR. The format of PR was a hybrid of in-person/virtual at 13 practices, virtual only (no in-person/hybrid option) at 10, in-person only (no virtual/hybrid option) at 4, with 1 not reported. Six practices reported using some form of asynchronous PR (PR performed independently without the treating physician). The timing of PR was reported by 27 and included after treatment planning is complete (n = 19), after contouring but before plan creation/dose calculation (n = 2), and a mix of both (n = 6). For those reporting a mix of PR timing, the median percent of cases that underwent PR before dose calculation was 15% (range = 5-60) with the remaining 85% (range = 40-95) reviewed after plan completion. Components of the plans subject to PR (reported as the number reviewing each component, out of the 28 respondents) included contours (23), targets/organs at risk (25), dose distributions (26), dose-volume histograms (26), prescription dose/fractionation (27), diagnostic imaging (12), pathology data (13), and treatment intent (23). Other components reviewed included informed consent (1) and morbidity and mortality conference (1). Conclusion Peer review in radiation oncology is a universal practice with more heterogeneity in the meeting format than is in the content reviewed. Most practices are performing PR after treatment planning is complete. Additional focus on the timing and format of radiotherapy plan PR is necessary to develop best practices to optimize safety and ensure comprehensive PR.

Purpose/Objective(s) Multidisciplinary collaboration in radiation oncology is important to optimizing patient cancer care in both the pre and post treatment setting. Despite interest in collaboration and potential benefits, many barriers prevent effective and efficient communication, particularly between radiation oncologists (ROs) and radiologists. Materials/Methods A one-time survey was distributed to ROs across 42 NCORP regional network through the Wake Forest NCORP Research Base (UG1CA189824) hospitals between January and February 2024. The survey explored the frequency and nature of RO-radiologist collaboration during RT planning, peer review processes, perceived barriers to collaboration, discordance in post treatment imaging interpretation, and interest in interventions to improve multidisciplinary interactions. Results Among 28 radiation oncologists from 13 NCORP sites, 64% reported engaging with radiologists for feedback on contoured RT targets in the past year, yet no practices routinely included radiologists in standard pre-treatment chart rounds conferences. Significant barriers to collaboration were identified, including time constraints (43%), workflow disruptions (50%), challenges in sharing imaging comprehensively (61%), and difficulties in discussing target adjustments (39%). When asked “How often do you encounter discordant post treatment imaging interpretation between ROs and radiologists that requires discussion or amendments in the reported findings (the interpreting radiologist does not know that a region of interest was recently treated and interprets post treatment effect as progressive disease or vice versa), only one provider reported 0 cases, while 50% of respondents indicated discordance often (5-9 times per year) or very often (10 or more times per year). Three providers indicated this occurs greater than 30 times per year, while one provider indicated this occurs approximately 100 times per year. A notable 71% expressed high or very high interest in clinical trials aimed at improving collaboration between these two specialties. Conclusion There is considerable interest among community ROs for improving current methods of multi-disciplinary collaboration with radiologists during the pre and post treatment setting. Strategies to address common communication barriers have the potential to dramatically enhance cancer care delivery for providers and patients.

Purpose/Objective(s) Stereotactic body radiation therapy (SBRT) for peripheral lung tumors can result in high radiation doses to surrounding ribs. Pre-clinical studies have shown single fraction doses of 2-10 Gy increase osteoclast activity and lead to bone loss. We conducted a randomized, double-blind, placebo-controlled trial to evaluate whether early suppression of osteoclast activity could mitigate SBRT-induced rib fractures. Materials/Methods Between July 2019 and February 2022, 84 patients were enrolled. Eligible patients had lung tumors within 2 cm of chest wall and were randomized 1:1 to receive either a single dose of risedronate (150mg) or placebo delivered 7 to 21 days before SBRT (48-60 Gy in 3-10 fractions). Chest wall pain (CWP) was graded using modified CTCAE v5 assessed every 3 months after SBRT up to 1 year. Following a minimum period of one year post drug administration, a thoracic radiologist assessed all accessible imaging follow-up for fracture incidence. Results Seventy-six patients (38 placebo 38 risedronate) with 81 treated lung lesions were included in this analysis with a median follow-up of 26.3 months with a maximum of 43.4 months. Follow-up was measured from the end date of SBRT to the date of last available CT chest or date fracture detection. A total of 25 patients (33%) developed rib fractures. Median (range) values for rib (dose in EQD2, a/b = 3) and chest wall (3 cm thickness) structures are as follows: rib D0.03cc, 215 Gy (range = 52-373); rib D2cc, 101 (26-252); chest wall V30, 20 cc (0.5-314). There was no significant difference in fracture rates between risedronate and placebo groups - 13 risedronate group (34.2%) vs 12 in placebo arm (31.6%) (p = 0.2). Among those who fractured, the median time to fracture was 14.2 mo (95% CI = 9.8 - 16.9 mo) [range 5.9 - 43.4 mo] with 9 patients developing fracture within 1 year from the end of SBRT. Patients receiving risedronate had a significantly lower rate of grade 2+ CWP within 1 year post SBRT completion compared to patients who received placebo: 18% versus 42% respectively (P = 0.045), Among patients who did not develop a detectable fracture, the rate of G2+ CWP was (12 % vs 34.6% P = 0.06) favoring the risedronate arm, and similarly among those who did develop fractures, the incidence of G2+ CWP was 31% vs 58% (p = 0.17). Conclusion For patients receiving SBRT for peripheral lung tumors, the use of prophylactic risedronate, when compared to placebo, did not reduce the incidence of treatment-induced rib fractures. The use of risedronate, however, lowered the risk of G2+ CWP. The suggested protective impact of risedronate against G2 or higher CWP may point to a nerve and osteoclast cross talk mechanism contributing to the development of SBRT-induced CWP. Alternatively, risedronate may have partially reduced osteoclast activity, preventing the accumulation of microfractures that could have contributed to pain. Further investigations into the appropriate dose and type of antiresorptive agent to specifically counteract bone loss and prevent pain or fracture after thoracic SBRT are warranted

Figure S1. GRHL2 sensitizes MCF10A neoT cells to anoikis. A. Caspase 3/7 activation assay on 24 hour anoikis assay (zero hour subtracted). B. shRNA depletion of GRHL2 decreases anoikis sensitivity in MCF10A neoT cells. Figure S2. EMT causes a metabolic shift from glycolysis to oxidative phosphorylation, that is partially reversed by GRHL2. Figure S3. MSP cells are able to maintain ATP in spite of inhibition of glucose utilization with 2-deoxyglucose; reversal by GRHL2. Figure S4. Multiple carbon sources, including fatty acids, contribute to the elevated mitochondrial function in MSP cells. Figure S5. EMT decreases overall ROS and results in anoikis resistance, but elevates superoxide levels. Figure S6. Treatment of MSP+GRHL2 cells with antioxidant compounds results in elevated Î"Ψ. Figure S7. Depletion of CD44 with stable shRNA transduction increases anoikis and ROS. Figure S8. HMLE and MSP cells have similar levels of reduced glutathione. Figure S9. GRHL2 downregulates GLUD1 in MCF10A neoT cells and depletion of GLUD1 from HMLE+Twist-ER cells increases ROS and anoikis. Figure S10. Treatment of MSP+GRHL2 cells with DM-αKG (10 mM) results in decreased ROS and protection from anoikis.

Purpose: Brain metastases (BMs) are a common source of morbidity and mortality. Guidelines do not advise brain surveillance for locally advanced non-small cell lung cancer (LA-NSCLC). We describe the incidence, time to development, presentation, and management of BMs after definitive chemoradiotherapy (CRT). Methods and Materials: We reviewed records of patients with LA-NSCLC treated with CRT within the period from 2013 to 2020. Descriptive statistics were used to characterize the population and the Kaplan-Meier method was used to estimate time to BM. Fisher exact tests and Wilcoxon rank-sum tests were used to compare outcomes between symptomatic and asymptomatic patients. Results: A total of 219 patients were reviewed including 96 with squamous cell carcinoma, 88 with adenocarcinoma, and 35 with large cell/not otherwise specified (LC/NOS). Thirty-nine patients (17.8%) developed BMs: 35 (90%) symptomatic and 4 (10%) asymptomatic. The rate of BM was highest in LC/NOS (34.3%) and adenocarcinoma (23.9%). Ninety percent of BMs occurred within 2 years. All asymptomatic patients underwent stereotactic radiosurgery alone, compared with 40% of symptomatic patients (P = .04). Symptomatic patients were more likely to require hospitalization (65.7% vs 0%, P = .02), craniotomy (25.7% vs 0%, not significant), and steroids (91.4% vs 0%, P < .001). Cumulative BM volume was higher for symptomatic patients (4 vs 0.24 cm3, P < .001) as was median greatest axial dimension (2.18 vs 0.52 cm, P < .001). Conclusions: We identified a high rate of BMs, particularly in LC/NOS and adenocarcinoma histology NSCLC. The majority were symptomatic. These results provide rationale for post-CRT magnetic resonance imaging brain surveillance for patients at high risk of BM. & COPY; 2022 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Rationale and Objectives: The treatment of locally advanced lung cancer (LALC) with radiotherapy (RT) can be challenging. Multidisci-plinary collaboration between radiologists and radiation oncologists (ROs) may optimize RT planning, reduce uncertainty in follow-up imaging interpretation, and improve outcomes.Materials and Methods: In this prospective clinical treatment trial (clinicaltrials.gov NCT04844736), 37 patients receiving definitive RT for LALC, six attending ROs, and three thoracic radiologists were consented and enrolled across four treatment centers. Prior to RT plan finalization, repre-sentative computed tomography (CT) slices with overlaid outlines of preliminary irradiation targets were shared with the team of radiologists. The primary endpoint was to assess feasibility of receiving feedback no later than 4 business days of RT simulation on at least 50% of plans.Results: Thirty-seven patients with lung cancer were enrolled, and 35 of 37 RT plans were reviewed. Of the 35 patients reviewed, mean age was 69 years. For 27 of 37 plans (73%), feedback was received within 4 or fewer days (interquartile range 3-4 days). Thirteen of 35 cases (37%) received feedback that the delineated target potentially did not include all sites suspicious for tumor involvement. In total, changes to the RT plan were recommended for over-or undercoverage in 16 of 35 cases (46%) and implemented in all cases. Radiology review resulted in no treatment delays and substantial changes to irradiated volumes: gross tumor volume,-1.9 to +96.1%; planning target volume,-37.5 to +116.5%.Conclusion: Interdisciplinary collaborative RT planning using a simplified workflow was feasible, produced no treatment delays, and prompted substantial changes in RT targets.

EPSCC is a rare entity that is most commonly diagnosed in the genitourinary system. In contrast to SCLC, the incidence of brain metastases is uncommon. No difference in survival was observed between patients with or without brain metastases. While retrospective studies must be interpreted with caution, our data suggest that the risks of PCI may outweigh the benefits. Further studies investigating the role of brain imaging surveillance, as well as the optimal management of brain metastases, is warranted.

BACKGROUND:To describe intensity-modulated radiotherapy (IMRT) with Gamma Knife Radiosurgery (GKRS) boost for locally advanced head and neck cancer (HNC) with disease near dose-limiting structures. METHODS:Patients with HNC treated with IMRT/GKRS as part of a combined modality approach between 2011 and 2021 were reviewed. Local control, overall survival and disease-specific survival were estimated using the Kaplan Meier method. RESULTS:Twenty patients were included. Nineteen patients had T3-4 tumors. Median follow-up was 26.3 months. GKRS site control was 95%. Two patients progressed at the treated primary site, one patient failed at the edge of the GKRS treatment volume, with no perineural or intracranial failure. 2-year OS was 94.7% (95% CI: 85.2%-100%). Concurrent chemotherapy was given in nine patients (45%). One patient (5%) received induction/concurrent chemotherapy. Brain radionecrosis occurred in three patients, one of which was biopsy-proven. CONCLUSIONS:IMRT plus GKRS boost results in excellent disease control near critical structures with minimal toxicity.

Introduction In patients with metastatic disease involving weight-bearing bones, postoperative radiotherapy (PORT) is commonly administered following surgical stabilization of an impending or confirmed pathologic fracture to reduce the risk of a seeded local recurrence. The goal was to re-evaluate the beneficial effect of PORT in a modern cohort of patients and determine any potential clinical predictors of skeletal-related events (SREs) which were defined as a pathologic fracture or the necessity for radiation or surgery to the affected bone. Methods Consecutive patients undergoing surgical stabilization of metastatic disease to weight-bearing bones of the extremities between 2012 and 2019 were reviewed. Patient, disease, and treatment factors were abstracted. The cumulative incidence of SREs was determined using competing risks methodology; overall survival (OS) was estimated using the Kaplan-Meier method. Results A total of 82 patients were identified, 74% of whom had undergone intramedullary nail fixation and 26% internal fixation or replacement. The femur was the most commonly involved bone (94%). A majority (78%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1-2. Bone-strengthening agents were given to 38% and PORT to 54%. The median PORT dose was 30 Gy in 10 fractions and the median percent coverage of surgical hardware was 100% (range, 25-100). SREs occurred in 10 of 82 patients. There were no differences between no RT and RT groups for the two-year cumulative incidence of SREs (8.2% vs 11.5%, p=0.59) or two-year cumulative incidence of local failure (10.8% vs 4.6%, p=0.53). The only identified predictors of SREs were the use of bone-strengthening agents (hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.05-1.06, p=0.06) and malnutrition (HR 3.69, 95% CI 0.91-14.93, p=0.07). For patients treated with PORT, a biologically effective dose or percent coverage of surgical hardware was not associated with SREs. Conclusion In this series, the addition of PORT following surgery for metastatic disease involving weight-bearing bones does not significantly affect the rate of SREs. The use of bone-strengthening agents appears protective, and malnourished patients appear particularly at high risk for future SRE.

Purpose/Objective(s)Head and neck radiotherapy (RT) is complex, involving multiple targets and organs at risk (OARs). Routine RT plan peer review is often inadequate for thorough review of the head and neck targets and OARs.Materials/MethodsPatients treated between August 2020 and December 2021 were evaluated in a weekly structured head and neck RT plan peer review conference including at least one head and neck RT subspecialist. All plans were initially reviewed by the treating faculty member prior to presentation in contour review conference. Patient and disease factors were recorded, as were the results of the peer review discussion, including the number and nature of recommended RT plan modifications and the rate of implementation. A major change was defined as any modification to the high-dose planning target volume (PTV) or RT prescription or fractionation. A minor change was defined as modification to at least one of the intermediate-dose PTV, low-dose PTV, or any OAR.Results186 patients treated by 8 individual providers were prospectively recorded, 86.6% from the main site and 13.4% from 3 regional practices. The most common primary sites were oropharynx (29.6%), oral cavity (22%), cutaneous (16.7%), larynx/hypopharynx (16.1%). T3-4 disease was present in 68.3%, N2-3 in 37.6%. RT intent was definitive (44.6%), postoperative (49.5%), preoperative (1.6%), or palliative (4.3%). A major change was recommended in 14.5% (18 high-dose PTV, 7 prescription, 1 high-dose PTV and prescription) and implemented in 21 of 26 cases (80.8%). A minor change was recommended in 18.8% (20 low-dose PTV, 10 intermediate-dose PTV, 2 intermediate and low-dose PTV, 2 OAR, and 1 low-dose PTV and OAR) and implemented in 29 of 32 cases (90.6%). Additional workup was suggested in 2 cases (1.1%; 1 imaging study and 1 procedure) and was completed in both cases. Correction of plan changes was associated with a statistically significant delay of 1 day in overall treatment planning (p = 0.001).ConclusionA dedicated peer review conference for head and neck RT plans is feasible and well-accepted by providers. Peer review with structured review of head and neck RT contour volumes is associated with substantial rates of suggested and implemented modifications to the plan with minimal treatment delay.

Purpose: To describe a novel metric to aid clinical decision making between shorter versus longer palliative radiotherapy (PRT) regimens using objective patient factors. Materials and Methods: Patients receiving PRT at a single institution between 2014 and 2018 were reviewed. The time between PRT start and finish was calculated and divided by overall survival (in days from start of PRT) to generate the percent of remaining life (PRL). This value was compared across various clinical factors using the Kruskal-Wallis test. Factors identified with a significance level p < 0.01 were included in a novel Palliative Appropriateness Criteria Score (PACS) and were included in an online risk assessment tool to assist clinicians in patient-specific fractionation decisions. Results: Totally 1027 courses of PRT were analyzed. Median age was 64 years; Eastern Cooperative Oncology Group (ECOG) performance status was 3-4 in 22%. Primary malignancies included were lung (38%), breast (13.8%), prostate (9.3%), and other (39%). The indication for PRT was pain (61%), neurological (21%), or other (18%). Palliative regimens included 199 (19.4%) receiving single fraction, 176 (17.1%) receiving 2-5 fractions, and 652 (63.5%) receiving 10 fractions. Median follow-up was 83 days overall and 437 days for patients alive at last follow-up. Factors significantly associated with increased PRL (and included in the PACS) were male gender, ECOG 3-4, lung or "other" primary diagnosis (vs. breast or prostate), PRT indication (neurological dysfunction vs. pain/other), inpatient status, and extraosseous sites treatment. Death within 30 days was significantly associated with high-risk PACS categorization, regardless of fractionation scheme (p < 0.001). Conclusions: The PACS is a novel metric for evaluating the utility of PRT regimens to improve clinical decision making. Single fraction is associated with low PRL. When considering multifraction PRT regimens, the PACS identifies patients who may benefit from shorter courses of PRT and alternatively, low-risk patients for whom a more protracted course is reasonable. Prospective external validation is warranted.

Purpose/Objective(s)To describe the time course and likelihood of symptomatic presentation of brain metastases in the setting of locally advanced non-small cell lung cancer (LA-NSCLC) following definitive therapy.Materials/MethodsPatients with LA-NSCLC treated with chemoradiation as definitive therapy between 2013-2020 (n = 219) were reviewed. Features including histologic subtype, T, N and clinical prognostic stage, presence of brain metastases and symptoms at time of presentation were recorded. Descriptive statistics were used to characterize the patient population, including incidence of brain metastases by histology, and the method of Kaplan and Meier was used to estimate brain metastasis free survival at 24 months. Fisher's exact tests were used to compare proportions between symptomatic and asymptomatic patients.ResultsA total of 219 patients met inclusion criteria. Histology including squamous cell carcinoma (SCC) (96), adenocarcinoma (88), and NSCLC-Not Otherwise Specified (NOS) (35). Median age was 67 years; 210 (96%) were current/former smokers, T stage was T0 (11.9%), T1 (21.9%), T2 (26.5%), T3 (18.3%), and T4 (21.5%). The majority of patients were N2 or N3 at treatment: N0 (5%), N1 (14.2%), N2 (60.7%), and N3 (20.1%). In total, 39 patients (17.8%) developed brain metastases. Incidence by histology varied with NSCLC-NOS showing the highest incidence (34.3%), followed by adenocarcinoma (23.9%), and SCC (6.2%). Brain metastasis free survival at 24 months was 72.9% (95% CI: 62.5-84.9%) for adenocarcinoma, 92.2% (95% CI: 86.3 – 98.5%) for SCC, and 53.3% (95% CI: 35.4 – 80.1%) for NSCLC-NOS. Median time to development of brain metastasis was 7.7 months (adenocarcinoma), 5.7 months (SCC), and 8.3 months (NSCLC-NOS). Overall, 85% of brain metastases occurred within 1 year. Ninety percent of patients were diagnosed with brain metastases after development of neurologic symptoms. Only 4 total patients had brain metastases discovered without symptoms. For patients presenting with symptomatic brain metastases, 91.4% required steroids versus 0% for those without symptoms (p <0.001). Symptomatic patients were more likely to require hospitalization at presentation, 65.7% vs 0% (p = 0.02). All asymptomatic patients with brain metastases were able to undergo stereotactic radiosurgery (SRS) alone, while only 40% of symptomatic patients received SRS monotherapy (p = 0.04). There was no statistically significant difference brain metastasis incidence based on treatment with adjuvant immunotherapy vs none for any histology (17.1% vs 18.1%, p = 1).ConclusionBrain metastases are a common source of morbidity and mortality in the setting of LA-NSCLC; however, there is no standard recommendation for surveillance brain imaging following therapy. Presentation with symptomatic brain metastases was significantly associated with need for more invasive management. This could strengthen an argument for the potential utility of surveillance brain imaging in the post-definitive setting.

Importance:Assessment of response after radiotherapy (RT) using 18F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography (CT) is routine in managing head and neck squamous cell carcinoma (HNSCC). Freeform reporting may contribute to a clinician's misunderstanding of the nuclear medicine (NM) physician's image interpretation, with important clinical implications.Objective:To assess clinician-perceived freeform report meaning and discordance with NM interpretation using the modified Deauville score (MDS).Design, Setting, and Participants:In this retrospective cohort study that was conducted at an academic referral center and National Cancer Institute-designated Comprehensive Cancer Center and included patients with HNSCC treated with RT between January 2014 and December 2019 with a posttreatment PET/CT and 1 year or longer of follow-up, 4 masked clinicians independently reviewed freeform PET/CT reports and assigned perceived MDS responses. Interrater reliability was determined. Clinician consensus-perceived MDS was then compared with the criterion standard NM MDS response derived from image review. Data analysis was conducted between December 2021 and February 2022.Exposures:Patients were treated with RT in either the definitive or adjuvant setting, with or without concurrent chemotherapy. They then underwent posttreatment PET/CT response assessment.Main Outcomes and Measures:Clinician-perceived (based on the freeform PET/CT report) and NM-defined response categories were assigned according to MDS. Clinical outcomes included locoregional control, progression-free survival, and overall survival.Results:A total of 171 patients were included (45 women [26.3%]; median [IQR] age, 61 [54-65] years), with 149 (87%) with stage III to IV disease. Of these patients, 52 (30%) received postoperative RT and 153 (89%) received concurrent chemotherapy. Interrater reliability was moderate (κ = 0.68) among oncology clinicians and minimal (κ = 0.36) between clinician consensus and NM. Exact agreement between clinician consensus and the NM was 64%. The NM-rated MDS was significantly associated with locoregional control, progression-free survival, and overall survival.Conclusions and Relevance:The results of this cohort study suggest that considerable variation in perceived meaning exists among oncology clinicians reading freeform HNSCC post-RT PET/CT reports, with only minimal agreement between MDS derived from clinician perception and NM image interpretation. The NM use of a standardized reporting system, such as MDS, may improve clinician-NM communication and increase the value of HNSCC post-RT PET/CT reports.

Purpose:Head and neck (HN) radiotherapy (RT) is complex, involving multiple target and organ at risk (OAR) structures delineated by the radiation oncologist. Site-agnostic peer review after RT plan completion is often inadequate for thorough review of these structures. In-depth review of RT contours is critical to maintain high-quality RT and optimal patient outcomes. Materials and Methods:In August 2020, the HN RT Quality Assurance Conference, a weekly teleconference that included at least one radiation oncology HN specialist, was activated at our institution. Targets and OARs were reviewed in detail prior to RT plan creation. A parallel implementation study recorded patient factors and outcomes of these reviews. A major change was any modification to the high-dose planning target volume (PTV) or the prescription dose/fractionation; a minor change was modification to the intermediate-dose PTV, low-dose PTV, or any OAR. We analysed the results of consecutive RT contour review in the first 20 months since its initiation. Results:A total of 208 patients treated by 8 providers were reviewed: 86·5% from the primary tertiary care hospital and 13·5% from regional practices. A major change was recommended in 14·4% and implemented in 25 of 30 cases (83·3%). A minor change was recommended in 17·3% and implemented in 32 of 36 cases (88·9%). A survey of participants found that all (n = 11) strongly agreed or agreed that the conference was useful. Conclusion:Dedicated review of RT targets/OARs with a HN subspecialist is associated with substantial rates of suggested and implemented modifications to the contours.

Introduction Postoperative radiotherapy (PORT) is routinely recommended for patients with head and neck squamous cell carcinoma (HNSCC) based on pathologic risk factors (pRFs) such as perineural invasion (PNI). Patients with PNI as the sole pRF after resection of HNSCC are uncommon and their prognosis is less clear. The aim of this study is to assess the role of PNI as a sole risk factor in patients with otherwise pathologically low-risk HNSCC. Methods Patients with HNSCC of the oral cavity, pharynx, or larynx treated with primary surgical resection from 2013 to 2018 were identified from an institutional cancer registry. Those with pRFs (pathologic T3-4 disease, lymphovascular space invasion [LVSI], multiple positive lymph nodes, close [within 2 mm] or positive margins, extranodal extension [ENE], or recurrent disease) were excluded, yielding an otherwise pathologically low-risk cohort with or without incidental, pathologic PNI. Locoregional control (LRC), overall survival (OS) and disease-specific survival (DSS) were estimated and compared between PNI groups and by adjuvant therapy. Results A total of 1,058 patients were identified as having undergone surgical resection. Exclusion of patients with other pRFs, those with unknown PNI, and oral cavity patients with depth of invasion > 10 mm yielded a study cohort of 85 patients. Eight patients (10% of study group, <1% of all patients) had PNI as the sole pRF, none of which had clinical signs or symptoms of perineural tumor spread. The remaining 77 were negative for PNI and thus pathologically low risk. Patients with PNI were more likely to have oral cavity cancer, to be younger, and to have received PORT than those without PNI; no patient received concurrent chemotherapy. At a median follow-up of 46.4 months, two- and five-year LRC rates were 81.4% and 78.5%, respectively. No differences were noted between PNI-positive and PNI-negative groups (p=0.73) or PORT v. no-PORT groups (p=0.39). While the utility of PORT is not possible to assess given limited sample size, four patients with PNI who did not receive PORT did not experience locoregional failure. Seventeen patients overall experienced locoregional failure and 14 were ultimately salvaged. Five-year OS and DSS were 77.4% and 90.8%, respectively. Conclusion Patients with pathologically low-risk HNSCC after surgical resection experience high rates of LRC. In this large institutional cohort, PNI as the sole pRF was exceedingly rare, and the benefit of adjuvant therapies is difficult to assess. Within this limitation, PORT remains the standard of care for patients with PNI to reduce the risk of locoregional failure. Further collaborative studies are required to adequately assess the prognostic impact of PNI alone in resected HNSCC.

IMRT combined with planned GKRS conformal boost results in excellent LC with minimal additional toxicity. This paradigm represents a promising means of dose escalation for locally advanced HNC with extension to critical OAR.

PURPOSE: To correlate changes in urinary patient-reported outcomes including the International Prostate Symptom Score (IPSS), acute urinary retention and urethral stricture with urethral dose in those treated with low dose rate (LDR) prostate brachytherapy. MATERIALS AND METHODS: Patients treated with prostate LDR between 2012 and 2019 (n = 117) completed IPSS urinary symptom assessments prior to treatment and at each follow-up. CT simulation was obtained with urinary catheter 1-month post-implant for dosimetric analysis. 113 patients with pre- and >= 1 post-LDR IPSS score available were analyzed. Urethral dosimetric parameters including U75, U100, U125, U150 and U200 were abstracted from post-implant dosimetry and assessed for association with urinary toxicity using bivariate logistic regression and Spearman correlation. Outcomes included clinically significant change (CSC, defined as 4 or more points or 25% rise above baseline) in IPSS score at 6 and 12 months, acute urinary retention (AUR), and urethral stricture (US). RESULTS: 89 (79%) patients were treated with LDR monotherapy (145 Gy) and 24 (21%) with LDR boost (110 Gy) with external beam radiation therapy. Twenty (18%) had baseline IPSS >= 15. Median IPSS scores were: baseline 6 (3 -12; n = 113), 1-month 17 (10-25; n = 110), 6 months 12 (7-18; n = 77), 1 year 8 (5 -14; n = 52). CSC-6 was observed in 59 (77%), CSC-12 in 26 (50%), AUR in 12 (11%), and US in 4 (4%). No association was identified between urethral dose parameters and CSC-6, CSC-12, AUR, or US. No correlation between urethral dose and IPSS at 6- and 12-months was identified. The IPSS >= 15 group exhibited lower rates of CSC-12 (13% v. 57%, p = 0.05) but not CSC-6 (55% v. 80%, p = 0.12). CONCLUSIONS: We did not find a relationship between urethral dose and IPSS elevation, AUR or US. We did identify a significantly lower change in IPSS at 12 months for those with baseline IPSS >= 15 compared to those with low baseline scores. (C) 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.