Initial RT Research Articles

Estimating the two consecutive epidemic waves of SARS-CoV-2 Omicron in Shenzhen, China from November 2022 to July 2023: a modeling study based on multi-source surveillance and mobility data

Unlike many countries that have experienced multiple COVID-19 waves since January 2020, China’s stringent measures left most of the population without natural immunity to SARS-CoV-2. After lifting controls, China experienced two distinct Omicron waves from November 2022 to July 2023. However, no reliable study has yet elucidated the transmission dynamics of these two consecutive Omicron waves in China’s megacities, nor the phenomenon of reinfection due to immune escape. To address this gap, this study proposes a hybrid epidemic modeling framework based on multi-source surveillance and mobility data, including nucleic acid tests, wastewater surveillance, case reports from Notifiable Infectious Diseases Surveillance System of China (NIDSS), and intra-urban travel intensity data. In this hybrid modeling framework, a four-stage compartmental model stratified by age is developed, integrating human mobility and Omicron reinfection mechanisms. This model is further corrected by an agent-based model to address the overestimation of infections by the compartmental model, forming a comprehensive hybrid framework. Based on the simulation results, several new findings are drawn. The attack rate of the first wave in Shenzhen was 88.5% (95% confidence interval (CI): 72.1%-99.6%), lower than other models’ predictions. The peak of the second wave occurred on May 18, 2023, with a higher reinfection rate compared to those observed in other countries and regions. The effective reproduction number (Rt) for the first wave peaked at 5.44 (95% CI: 5.26-5.48), while for the second wave, the initial Rt was 1.28 (95% CI: 1.27-1.29). The first infections provide a 0.549 (95% CI: 0.544-0.554) protective effect against XBB reinfection within six months. In conlusion, this study presents an advanced modeling framework for accurately assessing epidemic spread in urban environments using multi-source surveillance data.

Hypofractionated re-irradiation for diffuse intrinsic pontine glioma.

Re-irradiation (reRT) increases survival in locally recurrent diffuse intrinsic pontine glioma (DIPG). There is no standard dose and fractionation for reRT, but conventional fractionation (CF) is typically used. We report our institutional experience of reRT for DIPG, which includes hypofractionation (HF). We reviewed pediatric patients treated with brainstem reRT for DIPG at our institution from 2012 to 2022. Patients were grouped by HF or CF. Outcomes included steroid use, and overall survival (OS) was measured from both diagnosis and start of reRT. Of 22 patients who received reRT for DIPG, two did not complete their course due to clinical decline. Of the 20 who completed reRT, the dose was 20-30Gy in 2-Gy fractions (n=6) and 30-36Gy in 3-Gy fractions (n=14). Median age was 5years (range: 3-14), median interval since initial RT was 8months (range: 3-20), and 12 received concurrent bevacizumab. Median OS from diagnosis was 18months [95% confidence interval: 17-24]. Median OS from start of reRT for HF versus CF was 8.2 and 7.5months, respectively (p=.20). Thirteen (93%) in the HF group and three (75%) in the CF group tapered pre-treatment steroid dose down or off within 2months after reRT due to clinical improvement. There was no significant difference in steroid taper between HF and CF (p=.4). No patients developed radionecrosis. reRT with HF achieved survival duration comparable to published outcomes and effectively palliated symptoms. Future investigation of this regimen in the context of new systemic therapies and upfront HF is warranted.

A Multifaceted Approach to Interpreting Reaction Time Deficits After Adolescent Concussion.

Reaction time (RT) is a critical element of return to participation (RTP), and impairments have been linked to subsequent injury after a concussion. Current RT assessments have limitations in clinical feasibility and in the identification of subtle deficits after concussion symptom resolution. To examine the utility of RT measurements (clinical drop stick, simple stimulus-response, single-task Stroop, and dual-task Stroop) to differentiate between adolescents with concussion and uninjured control individuals at initial assessment and RTP. Prospective cohort study. A pediatric sports medicine center associated with a regional tertiary care hospital. Twenty-seven adolescents with a concussion (mean age = 14.8 ± 2.1 years; 52% female; tested 7.0 ± 3.3 days postconcussion) and 21 uninjured control individuals (mean age = 15.5 ± 1.6 years; 48% female). Participants completed the Post-Concussion Symptoms Inventory (PCSI) and a battery of RT tests: clinical drop stick, simple stimulus-response, single-task Stroop, and dual-task Stroop. The concussion group demonstrated slower clinical drop stick (β = 58.8; 95% CI = 29.2, 88.3; P < .001) and dual-task Stroop (β = 464.2; 95% CI = 318.4, 610.0; P < .001) RT measures at the initial assessment than the uninjured control group. At 1-month follow up, the concussion group displayed slower clinical drop stick (238.9 ± 25.9 versus 188.1 ± 21.7 milliseconds; P < .001; d = 2.10), single-task Stroop (1527.8 ± 204.5 versus 1319.8 ± 133.5 milliseconds; P = .001; d = 1.20), and dual-task Stroop (1549.9 ± 264.7 versus 1341.5 ± 114.7 milliseconds; P = .002; d = 1.04) RT than the control group, respectively, while symptom severity was similar between groups (7.4 ± 11.2 versus 5.3 ± 6.5; P = .44; d = 0.24). Classification accuracy and area under the curve (AUC) values were highest for the clinical drop stick (85.1% accuracy, AUC = 0.86, P < .001) and dual-task Stroop (87.2% accuracy, AUC = 0.92, P < .002) RT variables at initial evaluation. Adolescents recovering from concussion may have initial RT deficits that persist despite symptom recovery. The clinical drop stick and dual-task Stroop RT measures demonstrated high clinical utility given high classification accuracy, sensitivity, and specificity to detect postconcussion RT deficits and may be considered for initial and RTP assessment.

Single patient learning for adaptive radiotherapy dose prediction.

Throughout a patient's course of radiation therapy, maintaining accuracy of their initial treatment plan over time is challenging due to anatomical changes-for example, stemming from patient weight loss or tumor shrinkage. Online adaptation of their RT plan to these changes is crucial, but hindered by manual and time-consuming processes. While deep learning (DL) based solutions have shown promise in streamlining adaptive radiation therapy (ART) workflows, they often require large and extensive datasets to train population-based models. This study extends our prior research by introducing a minimalist approach to patient-specific adaptive dose prediction. In contrast to our prior method, which involved fine-tuning a pre-trained population model, this new method trains a model from scratch using only a patient's initial treatment data. This patient-specific dose predictor aims to enhance clinical accessibility, thereby empowering physicians and treatment planners to make more informed, quantitative decisions in ART. We hypothesize that patient-specific DL models will provide more accurate adaptive dose predictions for their respective patients compared to a population-based DL model. We selected 33 patients to train an adaptive population-based (AP) model. Ten additional patients were selected, and their respective initial RT data served as single samples for training patient-specific (PS) models. These 10 patients contained an additional 26 ART plans that were withheld as the test dataset to evaluate AP versus PS model dose prediction performance. We assessed model performance using Mean Absolute Percent Error (MAPE) by comparing predicted doses to the originally delivered ground truth doses. We used the Wilcoxon signed-rank test to determine statistically significant differences in terms of MAPE between the AP and PS model results across the test dataset. Furthermore, we calculated differences between predicted and ground truth mean doses for segmented structures and determined statistical significance in the differences for each of them. The average MAPE across AP and PS model dose predictions was 5.759% and 4.069%, respectively. The Wilcoxon signed-rank test yielded two-tailed p-value= , indicating that the MAPE differences between the AP and PS model dose predictions are statistically significant, and 95% confidence interval=[-2.1610, -1.0130], indicating 95% confidence that the MAPE difference between the AP and PS models for a population lies in this range. Out of 24 total segmented structures, the comparison of mean dose differences for 12 structures indicated statistical significance with two-tailed p-values<0.05. Our study demonstrates the potential of patient-specific deep learning models in application to ART. Notably, our method streamlines the training process by minimizing the size of the required training dataset, as only a single patient's initial treatment data is required. External institutions considering the implementation of such a technology could package such a model so that it only requires the upload of a reference treatment plan for model training and deployment. Our single patient learning strategy demonstrates promise in ART due to its minimal dataset requirement and its utility in personalization of cancer treatment.

Neurologic Events and Outcomes in Patients Receiving Proton and Photon Reirradiation for High Grade Non-Codeleted Gliomas

Patients undergoing reirradiation (ReRT) for high grade glioma are at risk for tumor progression, pseudoprogression, and radiation necrosis. We investigated factors associated with neurologic events and disease control after re-irradiation with protons and photons at a single academic center. We reviewed records and MRIs of patients receiving scanning beam proton (since center opening in 2016) and photon (since 2015) reirradiation in ≥10 fractions for grade 3 anaplastic astrocytoma (AA) and grade 4 glioblastoma (GBM), excluding 1p19q co-deleted oligodendrogliomas and extensive multifocal/leptomeningeal disease. The primary endpoint was time from ReRT to ≥ grade 2 pseudoprogression or radiation necrosis (PsP/RN, grade 2: moderate symptoms requiring outpatient steroids/bevacizumab, grade 3: severe symptoms leading to admission or surgical intervention). Dose was converted to EQD2 using a/b = 3. Cox proportional hazards model was used to calculate survival and time to PsP/RN. A total of 53 patients were included (26 protons, 27 photons, median KPS 80). Patients receiving protons had more favorable features. Compared to the photons, the proton group was younger (48 vs. 58) and more likely to have AA (46% vs. 22%) and resection within 3 months (42% vs 26%). The proton group also had a longer interval from prior RT (57 vs. 39 months) and were less likely to receive bevacizumab at reRT (15% vs. 59%). CTV was 130 cc for protons vs 99 cc for photons, and most had active disease at time of ReRT identified on planning MRI (76% protons, 85% photons). Median OS was 10.5 months (14.1 months protons, 8.1 months photons), with time from initial RT the only significant factor on multivariate analysis. Median PFS was 9.4 months (9.8 months protons, 6.2 months photons). 9 patients (18%) had ≥ grade 3 PsP/RN (8 proton, 1 photon) and 21 patients (41%) had ≥ grade 2 PsP/RN (16 proton, 5 photon). Grade 3 events included 1 seizure (photon group), 1 hemorrhage, 1 thalamic stroke, 1 shunt placement, 1 re-resection, and PSP4 4 PsP/RN requiring admission. Protons were associated shorter time to ≥ grade 2 PsP/RN (4 months vs. not reached, p = 0.027). When accounting for bevacizumab use at time of reRT, the association between protons and PsP/RN lost significance but there remained a trend (grade 2, p = 0.095, HR 2.4; grade 3, p = 0.105, HR 5.8). CTV, MGMT status, EQD2, and interval from prior RT were not associated with PsP/RN. High grade neurologic events were common in patients with predominantly active, unresected high grade gliomas receiving ReRT. Though ascertainment and survival bias are significant limitations, pseudoprogression and necrosis appeared to be more prominent in patients receiving protons. These results contribute to ongoing efforts to both optimize ReRT for high grade glioma and investigate biologic effects of proton therapy.

Constructing passivation film on plain carbon steel similar to that on 316L stainless steel

A high corrosion-resistant passivation film with cerium-molybdenum-chromium-nickel ions has been synthesized on plain carbon steel rebar through a chemical transformation method which significantly lowered the pitting susceptibility of the rebar in the chloride-containing concrete environment. The results indicated that the prepared film has a re-passivation self-healing property in a concrete environment with a concentration of 0.1 M NaCl, which is similar to the behavior of 316L stainless steel. The charge transfer resistance increased markedly with the extension of immersion time, reaching 3.70 × 106 Ω cm2 in about 1500 h of immersion (about 10 times of the initial Rt value). The high corrosion resistance mechanism of the film was discussed here in depth.

A Multi-SCALE Community Network-Based SEIQR Model to Evaluate the Dynamic NPIs of COVID-19.

Regarding the problem of epidemic outbreak prevention and control, infectious disease dynamics models cannot support urban managers in reducing urban-scale healthcare costs through community-scale control measures, as they usually have difficulty meeting the requirements for simulation at different scales. In this paper, we propose combining contact networks at different spatial scales to study the COVID-19 outbreak in Shanghai from March to July 2022, calculate the initial Rt through the number of cases at the beginning of the outbreak, and evaluate the effectiveness of dynamic non-pharmaceutical interventions (NPIs) adopted at different time periods in Shanghai using our proposed approach. In particular, our proposed contact network is a three-layer multi-scale network that is used to distinguish social interactions occurring in areas of different sizes, as well as to distinguish between intensive and non-intensive population contacts. This susceptible-exposure-infection-quarantine-recovery (SEIQR) epidemic model constructed based on a multi-scale network can more effectively assess the feasibility of small-scale control measures, such as assessing community quarantine measures and mobility restrictions at different moments and phases of an epidemic. Our experimental results show that this model can meet the simulation needs at different scales, and our further discussion and analysis show that the spread of the epidemic in Shanghai from March to July 2022 can be successfully controlled by implementing a strict long-term dynamic NPI strategy.

NIMG-01. PREDICTING POST-STEREOTACTIC RADIOTHERAPY MAGNETIC RESONANCE IMAGE OUTCOMES OF BREAST CANCER METASTASES TO THE BRAIN

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is a cornerstone in the management of Breast Cancer Metastases to the Brain (BCMB). While control rates are high following SRS, radiation necrosis is a rare but potentially devastating long-term toxicity. There is a clinical need for automated/semi-automated methods to assess tumor response and optimize the RT plans for local control with minimal long-term toxicity. Multiparametric MRI (mpMRI), particularly Apparent Diffusion Coefficient of water (ADC) maps, contain information that is mechanistically relatable to voxel-level tumor response to RT. We report a deep learning-based approach to predict post-SRS ADC maps, FLAIR, T2-weighted (T2W), T1-weighted unenhanced (T1W) and contrast-enhanced (T1WCE) images, from pre-SRS T1W, T1WCE, T2W and FLAIR images, ADC maps, and the delivered RT dose map. These “forward models” will enable the radiation oncologist to simulate radiologic outcomes and iteratively optimize RT plans for local control with minimal toxicity. METHODS We trained a variant of the pix2pix Generative Adversarial Network (GAN) on MRI and RT dose map data from 18 BCMB patients treated with stereotactic radiation with confirmed controlled and locally recurrent metastases. Patients were treated with stereotactic radiation dose of 1-40 Gy between 2013-2019. RESULTS On test data from 6 BCMB patients, the trained forward model predicted post-SRS ADC values within the Gross Tumor Volume (GTV) that were broadly in agreement with ground truth post-SRS ADC maps. In agreement with expectations, the forward model also predicts increasing post-RT ADC within the GTV with increasing simulated RT doses in the range of 1-71 Gy. We have also explored an inverse model to predict the RT dose map required to produce “prescribed” post-SRS ADC values within the GTV. CONCLUSIONS We envision that the forward models will assist the radiation oncologist in initial RT dose plan optimization, while the inverse model may be useful for daily RT plan optimization.

Definitive Proton Re-Irradiation for Locally Advanced Lung Cancer in the Immunotherapy Era

<h3>Purpose/Objective(s)</h3> Despite advances in the treatment of NSCLC and SCLC, locoregional recurrences or second primary tumors after irradiation (RT) remain a therapeutic challenge due to the toxicity of re-RT and limited efficacy of systemic therapy alone. We evaluated safety and efficacy of definitive intent re-RT with intensity-modulated proton therapy (IMPT). <h3>Materials/Methods</h3> In this single institution retrospective cohort study, consecutive patients with biopsy-confirmed recurrent or second primary NSCLC or SCLC received IMPT re-RT (dose in GyE) after initial definitive intent photon RT (dose in Gy). Univariate associations between variables of interest were examined with ANOVA for categorical variables and Pearson correlation coefficient for continuous variables. Time-to-event variables were estimated using the Kaplan-Meier method and associations modeled by Cox proportional hazards model and log-rank test. <h3>Results</h3> We identified 22 patients with recurrent or second primary NSCLC (n=20) or SCLC (n=2) treated from April 2019 to May 2021. Median initial RT dose was 60 Gy (range 45-70 Gy) with 10 patients (45%) receiving immunotherapy after initial RT. Re-RT started median 28.2 mo (range 8.8-172.9 mo) after initial RT. The median age at re-RT was 71 (range 54-85) with median ECOG performance status 1 (range 0-2). One patient had an actionable mutation and 5 patients had PD-L1 >1%. Most patients had locally advanced recurrences with 50% rT3-4 (n=11) and 59% rN1-3 (n=13). Median re-RT dose was 60 GyE (range 44-60 GyE) frequently in 30 fractions (n=9) or 15 fractions (n=7). With re-RT, 8 patients (36%) received concurrent chemotherapy. Four patients (18%) had immunotherapy after re-RT. Re-RT median lung V20 GyE was 8% (range 2%-26%), lung mean dose was 5.3 GyE (range 0.9-13.9 GyE), heart mean dose was 2.5 GyE (range 0-24.4 GyE), and esophagus mean dose was 6.6 GyE (range 0.2-24.2 GyE). With median follow-up 7.4 months after completion of re-RT, 1-yr OS was 68%, 1-yr PFS was 45%, 1-yr DMFS was 60%, and 1-yr LC was 80%. Higher re-RT and initial RT mean lung doses were significantly associated with worse OS, and there was trend for worse OS among patients with re-RT doses below 50 GyE (Table). Two patients (9%) developed grade 3 toxicities, 1 patient had grade 2 toxicity (5%), and 5 patients (23%) had Grade 1 toxicities. No grade 4 or 5 toxicities were observed. No significant dosimetric correlates were identified with toxicity. <h3>Conclusion</h3> Definitive IMPT re-RT for NSCLC and SCLC can prolong disease control with limited toxicity, particularly in the modern era with routine use of PD-L1 inhibitors. However, careful patient selection and planning are needed for optimal outcomes.

Reirradiation with Photon Radiotherapy for Recurrent or New Primary Breast Cancer after Prior Breast Irradiation

<h3>Purpose/Objective(s)</h3> Recurrent or new primary breast cancer may benefit from the local and/or regional recurrence risk reduction provided by RT, but delivery of a repeat course of RT is challenging due to risks of potential serious toxicities to organs at risk. This has led to limited use and heterogeneous practice patterns of salvage RT delivery. We hypothesize that breast cancer reirradiation (reRT) may be feasible using modern photon treatment techniques, and we present clinical outcomes and toxicities from a large single institution cohort. <h3>Materials/Methods</h3> In an IRB-approved retrospective study, all consecutive patients with recurrent or new primary non-metastatic breast cancer treated with breast or chest wall (CW) RT and photon reRT from a single institution were identified. Patient and tumor characteristics, treatment parameters, clinical outcomes and toxicities were collected. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) were defined from reRT start to date of any recurrence, distant recurrence, and death or last follow-up and estimated using Kaplan-Meier methodology. <h3>Results</h3> In total, 126 consecutive patients treated with reRT from 2013-2020 met criteria for analysis. Median age at reRT was 65 years (range 39-88). ReRT was delivered with 3DCRT in 47.6%, VMAT in 46.0%, and static IMRT in 6.4%. Median first, second, and cumulative prescription doses were 60.0 Gy, 46.4 Gy, and 105.0 Gy, respectively. Most received whole breast (WB) (80.2%) or partial breast (PB) (8.7%) initial RT. At reRT, 30.9% were treated to the PB, 11.1% WB/CW, 37.3% WB/CW with comprehensive regional lymph nodes (LN), and 12.8% WB/CW with partial regional LN. Median time between RT courses was 95 months (range 10-361). At a median follow-up of 26.5 months, 9 patients had died. Locoregional, distant, and any recurrence developed in 15 (11.9%), 22 (17.5%), and 28 (22.2%) patients, respectively. Estimated 3-year RFS was 80.7%, DMFS was 80.9%, and OS was 93.2%. Eleven (8.7%) patients developed grade 3 (G3) toxicities (dermatitis (n=8), acute (n=1) and late (n=1) CW pain, decreased joint range of motion (ROM) (n=1)); no G4 or G5 toxicities occurred. Five (4.0%) patients developed rib fracture. Of 23 patients retreated to a reconstructed CW, 30.4% and 34.8% developed Baker G1-2 or G3-4 implant contracture, respectively. Four patients had significant brachial plexus overlap, of whom 1 developed G2 decreased joint ROM and G2 soft tissue fibrosis and 1 developed G3 decreased joint ROM. <h3>Conclusion</h3> In the largest institutional experience to date on the use of photon reRT for recurrent or new primary breast cancer, reRT is associated with low rates of severe adverse events. In this high-risk population, locoregional and distant disease control rates are high. Further prospective study is needed to define the optimal treatment volume, prescription dose selection, and cumulative dose constraints with reRT to maximize the likelihood for successful and safe salvage therapy.

Characteristics of Patients Who Survived More than 5 Years after Diagnosis of Melanoma Brain Metastases

<h3>Purpose/Objective(s)</h3> Patients with melanoma brain metastases (mBM) have historically demonstrated poor overall survival (OS). However, the prognosis of metastatic melanoma has improved dramatically in the era of immunotherapy. At our institution, we have a substantial cohort of patients who received intracranial RT and survived more than five years after diagnosis of mBM. We performed a descriptive study to characterize this cohort. <h3>Materials/Methods</h3> Patients who received intracranial RT for mBM at our institution were identified retrospectively. Those with OS greater than five years after diagnosis of mBM were included. Patient, disease, and treatment characteristics were collected. Kaplan-Meier analysis was used to estimate OS and intracranial progression-free survival (iPFS). Patients with histologically proven radiation necrosis (RN) were identified. <h3>Results</h3> Forty-five patients with 127 mBM at diagnosis received RT between 2006 and 2017 and survived more than 5 years. The median age at mBM diagnosis was 59 years (range, 32 to 73), and 69% were male. The primary tumor was cutaneous in 76% and unknown in 24%. BRAF V600 mutations were identified in 51% of patients. The median number of mBM at diagnosis was 2 (range, 1 to 14), and the median largest dimension was 2.3 cm (range, 0.3 to 5.4). Thirty-one mBM (24%) in 27 patients (60%) were resected prior to RT. Forty patients (89%) had stereotactic radiosurgery and 5 patients (11%) had whole brain RT as their initial RT modality. At mBM diagnosis, 31% had no evidence of disease (NED) extracranially. Most patients (91%) received immunotherapy. This was delivered concurrently with RT (47%), prior to RT (16%), or after RT (33%). At a median of 85 months of follow-up, 9 patients (20%) were deceased, including only 2 with clear evidence of intracranial progression, and 31 (69%) were alive and NED. Median OS was 156 months. Intracranial progression was observed in 19 patients (42%) at a median of 134 months. Histologically proven RN was identified in 11 patients (24%). <h3>Conclusion</h3> To our knowledge, these 45 patients constitute the largest report of mBM patients with OS exceeding 5 years. Most of this cohort was alive and NED at the time of analysis. The burden of intracranial disease at diagnosis was low, and a third of patients had no extracranial disease. Nearly all patients received immunotherapy, of whom half had immunotherapy concurrent with RT. Nearly half of patients who survived more than 5 years did so despite having intracranial progression after initial RT for their mBM. Nearly a quarter of patients had histologically proven RN, suggesting an enhanced immune response to RT in this cohort. Prior studies suggest a correlation between RN and increased intracranial response to RT. Future efforts should characterize the post-treatment radiographic features and other correlatives that differentiate this cohort from the general population with mBM. These results demonstrate an astounding outcome in some patients with limited volume mBM treated in the modern era.

Effectiveness and Toxicity of Re-Irradiation after Breast Conserving Surgery for Recurrent Breast Cancer: A Multi-Institutional Study

<h3>Purpose/Objective(s)</h3> Breast re-irradiation (reRT) after repeat breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy in women presenting with low risk in-breast tumor recurrence (IBTR). However, there is limited data on optimal patient selection and safety of different fractionation regimens. This multi-institutional study reports safety and efficacy in a large cohort of women with IBTR treated with repeat BCS and reRT. <h3>Materials/Methods</h3> Using electronic medical record search tools, we identified all patients who underwent repeat BCS followed by breast reRT from 2015-2021 at 2 institutions. Univariate logistic regression models were used to identify clinical and dosimetric factors associated with development of acute and late toxicities. All statistical tests were two-sided, and the null hypothesis was rejected for p<0.05. Kaplan Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS) and locoregional recurrence-free survival (LR-RFS). <h3>Results</h3> We identified 66 patients with an IBTR treated with repeat BCS. In the initial RT course, 55% received whole breast RT (WBI) with conventional fractionation (≤2 Gy/fraction[fx]), 29% WBI with hypofractionation (2.6-2.7 Gy/fx), 6% partial breast irradiation (PBI) ultrahypofractionation (6-8 Gy/fx) and 11% had unavailable treatment details. There was a median of 11 years between initial breast cancer and IBTR. At time of recurrence, 36% of patients had tumors located in the same quadrant as the initial cancer, 41% had invasive carcinoma with ductal carcinoma in situ (DCIS), 41% had invasive carcinoma alone, 18% had DCIS alone, 92% had tumors < 2 cm, 68% had low-intermediate grade tumors and all were clinically node negative. For reRT, 95% received PBI (57.5% 45 Gy/1.5 Gy twice daily; 27% 45 Gy/1.8 Gy daily; 10.5% hypofractionation), and 5% received WBI (45-46.8 Gy in 1.8 Gy/fx), all of whom had received PBI for the initial course. Nine patients (13%) underwent adjuvant chemotherapy and 44 (67%) adjuvant hormone therapy. Median follow-up was 16 months (range 3-60). Twenty-one patients (32%) experienced any acute ≥ grade 2 events, and 17 (26%) experienced any late ≥ grade 2 toxicities. One patient experienced grade 3 fibrosis and one patient experienced grade 3 telangiectasia at 36 months. None had grade 4 or higher late adverse events. We found no association between fractionation of reRT or cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%. <h3>Conclusion</h3> In this large multi-institutional series of patients with recurrent breast cancer, second breast conservation surgery followed by reRT was effective with no local recurrences and excellent disease control outcomes, and toxicity appears to be acceptable. Longer follow-up and more prospective study are needed to further inform patient selection and establish the efficacy and tolerability of repeat breast conservation therapy in the setting of limited, low-risk recurrence.

Radiotherapy Physics Quality Assurance and Management Practices in Less Resourced Facilities: An Initial Pilot Survey in Six Countries Followed by an Onsite Visit and Audit of Radiotherapy Centers in a Lower Middle-Income Country (LMIC)

<h3>Purpose/Objective(s)</h3> To assess physics quality assurance (PQA) and practices in less resourced RT clinics to improve the quality of care. <h3>Materials/Methods</h3> An initial survey was conducted in 2020 to thirteen select RT centers in six countries. In 2021, from the survey outcome, our team conducted onsite visits to all the RT-centers in one of the countries: one private, and two public (Public-1- and –2). Public-1 in the capital and Public-2 in a regional capital. Follow-up surveys were sent to 17 medical physicists. Questions centered on the topic of equipment, institutional practice, physics quality assurance, management, and safety practices. Qualitative and descriptive methods were used for data analysis. We accessed operational challenges using a 5-point Likert system: machine downtime, patient related issues, power outage and staffing. <h3>Results</h3> We received a 100% response rate. Six (6/17) had 1-3 years of experience and two (2/17) have over 15 years of experience. Over 80% of respondents had experience with a treatment planning system. Private and public-1 have CT simulators located in RT clinic. Breast, genitourinary, Gynecologic, H&N were the most treated diseases in all three centers. All three (3) clinics have 3D conformal RT (3D-CRT), the private and public-2 have electron treatment modalities and only public-1 have IMRT treatment available. An audit during the visit showed that no single point diode patient specific QA is done for 3D-CRT patients and none of the institutions had a functioning diode to carry out this QA process. The average daily patient workload on external beam device for each clinic was LINAC: Private = 25, public-1 = 55, public-2 = 40; Co- 60: public-1 = 45, Public-2 = 25. Public-1 and-2 lacked the equipment necessary to conform to best practices in TG-142 and 198. Public-2 reported significant challenges in the operational challenges above with values of 4.5, 3 and 2.75 and 2.25. Notably Public-1 and-2 have peer review chart rounds which are attended by clinical oncologists, medical physicists, physicians, and physics trainees. All (17/17) responded to having a system of documenting, tracking, and trending patient related safety incidents but only one (1/17) physicist reported using a voluntary incident reporting system. Although not quantifiable audits during site visits show education and training remains the most important need in operating successful local PQA and management programs. In the initial survey RT centers in lower GNIpc country there was a direct correlation between QA needs and the country index. <h3>Conclusion</h3> The initial study showed a direct correlation between QA needs and the development index of a country which has led to the first of a continent-wide survey intended to spotlight PQA practices in LIMCs, the challenges faced, lessons learned, to help understand the gaps and needs to better support their local PQA and management programs.

Outcomes and Toxicity Following Three or More Definitive Courses of Thoracic Radiation Therapy

<h3>Purpose/Objective(s)</h3> Lung cancer patients are living longer but remain at risk for developing new or recurrent disease. Salvage re-irradiation can be considered for definitive management, but balancing efficacy with associated toxicity poses difficulty with retreatment. <h3>Materials/Methods</h3> This retrospective study evaluates patients who underwent three or more courses of definitive RT for thoracic malignancies at our cancer center from 2012 through 2021. All patients underwent multidisciplinary evaluation and restaging prior to retreatment. Toxicity was scored via CTCAE v5.0, and outcomes were estimated via Kaplan-Meier. <h3>Results</h3> Fifty-nine patients underwent a total of 190 definitive courses (13 having received 4 courses) for new or recurrent thoracic malignancies (88% non-small cell lung cancer). Of these courses, 141 (74%) entailed SBRT for localized lesions (most commonly to 50-Gy in 4-fractions), while the remaining 49 (26%) consisted of conventional fractionation (most often delivered with concurrent chemotherapy), with 22 patients (37%) receiving SBRT for every course. Median follow-up time was 7-years and 20-months from initial diagnosis and last RT course, respectively. All patients maintained excellent performance status (ECOG 0-2 or KPS 70-90) from first to last treatment. Median age at initial diagnosis and at last course of thoracic RT was 68.5 and 71 years, respectively, corresponding to median interval from initial RT to last RT course of 4 years. Twenty-eight patients (47%) had history of pulmonary disease, while 19 (32%) had history of prior lobectomy. Following last thoracic RT, median overall survival (OS) and progression-free survival (PFS) were still 2.4 years (95% CI: 1-4) and 12-months (95% CI 7-18), respectively. Actuarial OS at 1-year and 2-years was 73% and 54%, corresponding to PFS of 50% and 27%. However, 47 patients (80%) ultimately had evidence of progression, including distant metastases among 20 (43%), isolated locoregional recurrences in 19 (40%), and both as first progression for 8 (17%). Following last RT, the incidence of Grade 3 toxicity was only 5% (pulmonary and esophageal), with no Grade 4-5 events. There were no cardiac, neurological, or vascular toxicities directly attributable to RT. <h3>Conclusion</h3> Re-RT often remains a safe and effective local control modality (despite prior treatment) and should be considered as a potential option when planning multidisciplinary salvage therapy. For isolated failures, multiple courses of thoracic RT (notably SBRT) can be delivered sequentially with minimal toxicity.

Long-term survivor of hepatocellular carcinoma treated with repeated carbon ion radiotherapy and transarterial chemoembolization: a case report

Hepatocellular carcinoma (HCC) often recurs in the liver and requires multiple rounds of treatment. Thus, less-invasive multidisciplinary approaches are essential for preserving liver function, especially in elderly patients. Here, we report a case of an 86 year-old Japanese male patient with HCC who was successfully treated with repeated carbon ion radiotherapy (C-ion RT) and transarterial chemoembolization (TACE). The patient had alcoholic liver cirrhosis with a 60 mm HCC lesion and a satellite lesion in segment 6. The patient underwent initial C-ion RT but developed primary tumor recurrence (segment 6) and a new lesion (segment 2) 24 months later. The patient received TACE for each lesion, followed by an increased dose of C-ion RT for the recurrent primary tumor. Although the primary tumor lesion was well controlled, the patient subsequently developed new lesions, and TACE was repeated. The patient died of bacterial pneumonia 88 months after the initial treatment. His general condition and liver function were well preserved, and no severe adverse events were observed throughout the course of treatment. These results suggest that a less-invasive multidisciplinary approach involving repeated C-ion RT combined with TACE enables preservation of liver function, which may contribute to long-term survival in elderly patients with HCC.

Toxicity and Survival Outcomes From Intensity Modulated Proton Therapy-Based Re-Irradiation in Patients With Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Cumulative radiation doses to organs-at-risk is the primary limiting factor when delivering thoracic reirradiation (reRT). Intensity-modulated proton therapy (IMPT) offers a unique dosimetric advantage allowing for dose-escalation while limiting normal tissue irradiation. Given the limited published data, we analyzed toxicity and survival outcomes of non-small cell lung cancer (NSCLC) patients with prior radiation history undergoing IMPT-based definitive reRT. <h3>Materials/Methods</h3> A single-institution retrospective IRB-approved analysis was conducted of 62 consecutive patients treated with IMPT-reRT between from 2016-2020. Median dose of prior RT was 60.2 Gy EQD2 (range 30-126 Gy EQD2). Median time between initial and reirradiation courses was 30 months (range 3.5 – 562 months). Median IMPT-reRT dose was 62.2 Gy (RBE) EQD2 (range 40.1 – 99.7 Gy RBE EQD2). Patients received conventionally fractioned (n=37), twice-daily (n=6), or hypofractionated (n=19) reirradiation. The majority had full overlap with the previous radiation field (N=49, 79%), were centrally located (N=42, 58%), and involved nodal irradiation (N=47, 76%). Concurrent chemotherapy was delivered in 27 (44%) patients. Treatment related toxicities were analyzed in relationship to re-RT dosimetric parameters in 30 patients whose initial RT plan was available. Kaplan-Meier method and Cox Proportional Hazard was used to estimate overall survival (OS) and freedom from local progression (FFLP) calculated from the start of reRT. <h3>Results</h3> Grade 3 acute toxicities were seen in 6 (9%) patients (pulmonary [N=3], esophageal/skin/fatigue [N=1 each]). With a median follow-up from the start of reirradiation of 12.5 months, 8 (13%) patients experienced a grade 3 late toxicity (esophageal [N=4], pulmonary [N=3] and cardiac [N=1]). Two (3%) grade 5 toxicities were observed. None of the analyzed dosimetric parameters (lung, heart, esophageal, target) correlated with grade 3 or more toxicity. CTV size greater than 150 cm³ exhibited a trend of association with grade 3+ toxicity HR = 3.2 (95% CI: 0.88 – 12.1; p=0.08). Median FFLP was not reached and median OS was 22.6 months (95% CI, 16.5 – 22.1 months). On univariate analysis variables associated with improved OS were higher reirradiation dose, cumulative radiation dose >135 Gy, and smaller CTV (< 150 cc). However, on MVA only CTV size retained statistical significance (HR = 3.56; 95% CI, 1.10 – 11.48; p=0.03). <h3>Conclusion</h3> This is the largest series to date reporting outcomes for NSCLC patients treated with IMPT-reRT which demonstrated acceptable risk (<15%) of grade 3 or higher late toxicity with durable local control and prolonged survival. In contrast to limited published literature, no specific dosimetric parameters were significantly correlated with risk of toxicity.

Is fractionated robotic stereotactic body radiosurgery optional salvage treatment for the re-irradiation of locally recurrent nasopharyngeal carcinoma?

Recurrent nasopharyngeal carcinoma (NPC) after previous radiation therapy is a significant problem. This study was to determine the potential benefits from re-irradiation by fractionated stereotactic body radiotherapy (FSRT) on survival benefits and effects of severe late toxicities. Between 2009 and 2018, treatment outcomes were evaluated retrospectively in 26 patients with locally recurrent NPC treated using FSRT with CyberKnife. Five patients who had metastatic disease and one who had second recurrence were excluded from the study, and the remaining 20 patients were analyzed. The median age was 52 years (range, 28-80 years); re-treatment T stage was as follows: 6 (30%) - T2, 5 (25%) - T3, and 9 (45%) - T4. The median time from initial RT to recurrence was 22 months (range, 8-159 months). The median re-irradiation FSRT dose was 30 Gy in 5 fractions. The median follow-up was 44 months; the overall survival (OS), local failure-free survival, and disease progression-free survival rates at 3 years were 89%, 73%, and 53%, respectively. All patients were evaluated for response after treatment: 9 (45%) had complete, 3 (15%) had partial, and 6 (30%) had no response. Univariate analysis demonstrated that higher cumulative total radiotherapy dose, gross tumor volume, and recurrent time interval were prognostic factors for local failure-free survival. The recurrent time interval was also an independent factor for progression-free survival and OS. The incidence of temporal lobe necrosis and trismus was 10% and 20%, respectively. One patient had Grade 5 toxicity to treatment-related bleeding. Tumor dose coverage is important for treating recurrent NPC, and treatment-related mortality was vascular in nature. FSRT is a promising treatment modality for recurrent NPC.

Personalized Treatment Selection Leads to Low Rates of Local Salvage Therapy for Bone Metastases

Local therapy for patients with nonspine bone metastases is evolving, with data supporting the use of single-fraction treatments, and more recently, showing possible benefit from stereotactic body radiation therapy (SBRT). However, the rate of local salvage therapy (LST) after each technique has not been characterized in real-world clinic settings where patients are selected at physician discretion. We examined rates of LST in patients with nonspine bone metastases. We reviewed records of RT for nonspine bone metastases at our institution from January 1, 2016, to December 31, 2018. We defined LST as the first occurrence of RT or surgery for oncologic progression to a bone metastasis after initial RT. Cumulative incidence functions for retreatment were generated. We conducted multivariate analysis to identify variables associated with LST. A total of 1754 patients were analyzed, with median follow-up of 16.2 months (range, 0-36.8 months). Of all episodes of RT, 51.5% were multifraction external beam radiation therapy (EBRT), 7.0% were single-fraction EBRT, and 41.4% were SBRT. Altogether, 88 patients (5.0%) required LST, with an incidence at 6 months of 2.5%. Incidence of LST at 6 months was 2.1% for SBRT, 5.3% for single-fraction conventional regimens, and 2.4% for multifraction conventional regimens (P=.26). Patients of younger age, who had a higher Karnofsky performance status, and/or who had lesions in the pelvis had a higher risk of retreatment. In this large institutional cohort, the rate of LST was low, with no difference between RT techniques. The findings indicated that SBRT for patients at high risk for treatment failure may reduce the rate of retreatment overall. When treatment modality was selected based on patient characteristics, rates of LST were lower than when treatment was randomly selected.

Low Rate of Local Salvage Therapy Following Radiation Therapy for Non-Spine Bone Metastases ― An Indication for Appropriate Patient Selection

<h3>Purpose/Objective(s)</h3> Local therapy for patients with non-spine bone metastases is evolving, with recent data suggesting that stereotactic body radiotherapy (SBRT) may improve pain response in the palliative setting. However, the rate of local salvage therapy (LST) after SBRT compared to conventional RT is unknown. We therefore characterized rates and risk factors for LST in patients with non-spine bone metastases. <h3>Materials/Methods</h3> We reviewed records of all courses of RT for non-spine bone metastases at our institution from 1/1/2016 to 12/31/2018. LST was defined as the first occurrence of either RT or surgery for progression to a bone metastasis following initial RT. Functions of the cumulative incidence of re-treatment were generated for each RT technique. We identified associations with various predictors using the Fine and Gray method for competing risk regression. <h3>Results</h3> Of the 1,754 patients included, 2,648 bone metastases were treated with RT and analyzed with a median follow up of 15 months (IQR = 6.4 – 25.0 months). 51% of episodes were multi-fraction EBRT, 10% were single fraction EBRT, and 39% were SBRT. Of the treated metastases, 120 (4.5%) episodes required LST (median time to LST = 6.2 months, range = 0.3-35.6 months), with a cumulative incidence at 6 and 12 months of 2.4% and 3.9%, respectively. Cumulative incidence of re-treatment at 6 months was 2.6% for SBRT, 3.5% for single-fraction conventional, and 2.1% for multi-fraction conventional regimens (<i>P</i> = 0.76). On multivariable analysis, younger age, higher Karnofsky performance status (KPS), and location of the metastasis in the pelvis had higher hazard of re-treatment (Table 1). There was no significant difference in hazard of LST among RT techniques (<i>P</i> = 0.44), nor was there a significant interaction between RT technique and radioresistant histology (<i>P</i> = 0.33). <h3>Conclusion</h3> In our large institutional cohort, the rate of LST was low, with no difference between RT techniques. Our results suggest that judicious selection of patients at high risk for eventual treatment failure (i.e., those with longer expected survival) for SBRT may reduce the rate of retreatment rate in the population. When patients are appropriately selected for single fraction conventional RT, such as those who are older or have poor KPS, rates of LST remain low. Further studies to validate our findings are warranted to help clinicians to select the appropriate treatment technique for patients with bone metastases.

The importation and establishment of community transmission of SARS-CoV-2 during the first eight weeks of the South African COVID-19 epidemic.

BackgroundWe describe the epidemiology of COVID-19 in South Africa following importation and during implementation of stringent lockdown measures.MethodsUsing national surveillance data including demographics, laboratory test data, clinical presentation, risk exposures (travel history, contacts and occupation) and outcomes of persons undergoing COVID-19 testing or hospitalised with COVID-19 at sentinel surveillance sites, we generated and interpreted descriptive statistics, epidemic curves, and initial reproductive numbers (Rt).FindingsFrom 4 March to 30 April 2020, 271,670 SARS-CoV-2 PCR tests were performed (462 tests/100,000 persons). Of these, 7,892 (2.9%) persons tested positive (median age 37 years (interquartile range 28–49 years), 4,568 (58%) male, cumulative incidence of 13.4 cases/100,000 persons). Hospitalization records were found for 1,271 patients (692 females (54%)) of whom 186 (14.6%) died. Amongst 2,819 cases with data, 489/2819 (17.3%) travelled internationally within 14 days prior to diagnosis, mostly during March 2020 (466 (95%)). Cases diagnosed in April compared with March were younger (median age, 37 vs. 40 years), less likely female (38% vs. 53%) and resident in a more populous province (98% vs. 91%). The national initial Rt was 2.08 (95% confidence interval (CI): 1.71–2.51).InterpretationThe first eight weeks following COVID-19 importation were characterised by early predominance of imported cases and relatively low mortality and transmission rates. Despite stringent lockdown measures, the second month following importation was characterised by community transmission and increasing disease burden in more populous provinces.