A deep learning-informed interpretation of why and when dose metrics outside the PTV can affect the risk of distant metastasis in SBRT NSCLC patients.

PURPOSE: Recent papers suggested a correlation between the risk of distant metastasis (DM) and dose outside the PTV, though conclusions in different publications conflicted. This study resolves these conflicts and provides a compelling explanation of prognostic factors. MATERIALS AND METHODS: A dataset of 478 NSCLC patients treated with SBRT (IMRT or VMAT) was analyzed. We developed a deep learning model for DM prediction and explainable AI was used to identify the most significant prognostic factors. Subsequently, the prognostic power of the extracted features and clinical details were analyzed using conventional statistical methods. RESULTS: Treatment technique, tumor features, and dosiomic features in a 3 cm wide ring around the PTV (PTV3cm) were identified as the strongest predictors of DM. The Hazard Ratio (HR) for Dmean,PTV3cm was significantly above 1 (p < 0.001). There was no significance of the PTV3cm dose after treatment technique stratification. However, the dose in PTV3cm was found to be a highly significant DM predictor (HR > 1, p = 0.004) when analyzing only VMAT patients with small and spherical tumors (i.e., sphericity > 0.5). CONCLUSIONS: The main reason for conflicting conclusions in previous papers was inconsistent datasets and insufficient consideration of confounding variables. No causal correlation between the risk of DM and dose outside the PTV was found. However, the mean dose to PTV3cm can be a significant predictor of DM in small spherical targets treated with VMAT, which might clinically imply considering larger PTV margins for smaller, more spherical tumors (e.g., if IGTV > 2 cm, then margin ≤ 7 mm, else margin > 7 mm).

High buttocks supine position to reduce small bowel exposure in gynecological radiotherapy.

PURPOSE: To minimize radiation exposure to the small bowel (SB) in patients undergoing treatment for gynecological tumors by adopting a comfortable positioning method. METHODS AND PATIENTS: All 76 women undergoing Intensity-Modulated Radiation Therapy (IMRT) were included in this study. Patients were immobilized in a supine position using a vacuum bag and thermoplastic cast formation. In the trial group (n = 36), patients raised their buttocks and a solid foam pad was placed under the sacral tail before immobilization. The control group (n = 40) received treatment in the standard supine position. The SB was delineated from the pubic symphysis to the total iliac bifurcation in computed tomography (CT) scans. RESULT: In the trial group, a significant reduction in SB volume within the pelvic cavity was observed (mean 399.17 ± 158.7 cc) compared to the control group (mean 547.48 ± 166.9 cc), with a p-value less than 0.001. The trial group showed a statistically significant reduction in the absolute volume of irradiated SB at each dose, ranging from the low dose (10 Gy) to the high dose (45 Gy). In the control group, a negative correlation was found between SB and bladder volumes (R = -0.411, P = 0.008), whereas in the trial group, this correlation was weaker (R = -0.286, P = 0.091), with no significant relationship observed between bladder volume and SB. CONCLUSION: The high buttocks supine position effectively reduces SB radiation exposure without the need for bladder distension. This positioning method holds promise for reducing SB irradiation in various pelvic tumors.

Sequential therapy for extramedullary plasmacytoma of the palate: a rare case report with seven years of follow-up and literature review.

BACKGROUND: Extramedullary plasmacytoma (EMP) is a rare solitary malignancy that accounts for 3% of plasma cell neoplasms, and EMP with a primary occurrence in the palate is extremely uncommon. Owing to the long course of EMP and the limited available data on treatment outcomes, there are no definitive guidelines for its management, especially for high-risk patients who are more susceptible to early progression to multiple myeloma. CASE PRESENTATION: In this study, we review nine relevant studies and describe a 54-year-old woman who presented with an asymptomatic nonulcerative mass localized in the palate. After initial radical surgical resection of the lesion, the patient was definitively diagnosed with EMP with minimal plasmacytosis in the bone marrow, and adjuvant intensity-modulated radiation therapy with a minimum dose of 39.6 Gy was administrated in the surgical area. There was no evidence of local recurrence, nodal metastasis or progression to multiple myeloma (MM) during the seven-year follow-up period. CONCLUSION: Given the atypical clinical features of palate EMP reported in the literature and the encouraging results of our patient, sequential therapy involving surgery and adjuvant radiotherapy for primary palatal lesions in high-risk EMP patients without nodal involvement could be an effective treatment modality.

Early recurrence as a pivotal event in nasopharyngeal carcinoma: identifying predictors and key molecular signals for survivors.

PURPOSE: The duration of response to treatment is a significant prognostic indicator, with early recurrence (ER) often predicting poorer survival outcomes in nasopharyngeal carcinoma (NPC) survivors. This study seeks to elucidate the factors contributing to the onset of ER following radiotherapy in NPC survivors. METHODS: This investigation encompassed 2,789 newly diagnosed NPC patients who underwent radical intensity-modulated radiotherapy. Ordinal logistic regression analysis was employed to evaluate the independent predictors of earlier recurrence. A machine learning-based prediction model of NPC recurrence patterns was developed. Tumorous RNA-sequencing (in-house cohort: N = 192) and biological tipping point analysis were utilized to infer potential molecular mechanisms associated with ER. RESULTS: Our results demonstrated that ER within 24 months post-initial treatment was the optimal time frame for identifying early malignant progression in NPC survivors. The ER cohort (150 of 2,789, 5.38%) exhibited a notably short median overall survival of 48.6 months. Multivariate analyses revealed that male gender, T4 stage, local or regional residual disease, detectable pre- and post-radiotherapy EBV DNA, and the absence of induction chemotherapy were significant predictors of earlier recurrence. The machine learning-based predictive model further underscored the importance of tumor-related factors in NPC recurrence. Moreover, ER emerged as a pivotal stage in NPC progression, with 15 critical transition signals identified potentially associated with the negative modulation of the immune response. CONCLUSIONS: Our comprehensive analysis of NPC recurrence patterns has unveiled insights into the key factors driving ER and provided novel insights into potential early warning biomarkers and the mechanisms underlying NPC progression.

The Dose Difference of Dominant Intraprostatic Lesions (DILs) Defined by Magnetic Resonance-Guided and arc-based Intensity Modulated Radiation Therapy (IMRT), and the Association between Dose Difference and Recurrent Prostate Cancer.

BACKGROUND: There is growing evidence that local recurrence after radiotherapy often occurs within the dominant intraprostatic lesions (DILs) in prostate cancer. This study aimed to evaluate the dose difference between DILs defined by Magnetic Resonance-guided and arc-based Intensity Modulated Radiation Therapy (IMRT) and to assess the association between the dose difference and biochemical recurrence-free survival. MATERIALS AND METHODS: Between 2015 and 2019, 48 prostate cancer patients with DILs visible from multiparametric Magnetic Resonance Imaging (mpMRI) underwent arc-based IMRT with 70 Gy (2.5 Gy each fraction) to the prostate gland. Pretreatment mpMRI DILs contoured the prostate gland retrospectively. RESULTS: Biochemical recurrence was 8.3%. There was a significant difference between the median dose of DILs from MRI-guided imaging, 69.22 Gy, and the median dose of the whole prostate from arc-based IMRT which was 67.09 Gy (p < 0.001*). The Kaplan-Meier survival curve compared by log-rank test showed an escalation dose of at least 2 Gy tends to improve biochemical recurrence-free survival. However, this tendency did not reach statistical significance (p = 0.2). CONCLUSIONS: The dose distribution within DILs defined by mpMRI is significantly higher than the whole prostate dose from arc-based IMRT. Escalation doses in DILs tend to improve biochemical recurrence-free survival, further validation in larger patient cohorts with extended follow-up is warranted.

Impact of Reference Selection on Gamma Analysis in Patient-Specific Quality Assurance for Monte Carlo-Based Treatment Planning Systems.

OBJECTIVE: Our study aimed to establish a standardized methodology for selecting "reference" and "evaluated" distributions in gamma analysis for Monte Carlo (MC) based intensity modulated treatment plans. Evaluation of importance of reference selection in MC based and non MC based treatment planning systems were analysed using a study classification. METHODS: Three categories were utilized to analyzed gamma passing rates across using different treatment planning systems (TPS) and detectors for thirty five patients. Category 1 utilized MC-based Monaco TPS plans and a 2 dimensional(2D) I'mRTMatriXX detector. Category 2 employed non-MC-based Eclipse TPS plans, assessed with a 2D I'mRTMatriXX detector. In Category 3, MC-based Monaco TPS plans were validated using a Dolphin detector. All plans were subjected to analysis using gamma criteria, which considered a dose difference of 3% and a distance to agreement of 3mm. Additionally, another set of gamma criteria was employed, with a dose difference of 3% and a distance to agreement of 2mm. An introduced Asymmetric factors in both 2D and 3D analysis will quantify the asymmetric nature of gamma based on the choice of "reference" distribution. RESULT: For 2D Gamma analysis, MC-based Monaco TPS and I'mRTMatriXX showed a consistent positive Zk2D trend for all patients, with significant p-values below 0.01 for both gamma passing criteria. In contrast, non-MC based Eclipse TPS exhibited varied Zk2D results, with non-significant p-values. In 3D Gamma analysis, all patients exhibited positive Zk3D values with significant p-values below 0.01 when "references" were swapped. The Pearson correlation between asymmetricity and isodose volumes was notably high at 0.99 for both gamma criteria. CONCLUSION: Our study highlights the imperative of using MC-based TPS as the definitive "reference" in gamma analysis for patient specific quality assurance of intensity modulated radiation therapy, emphasizing that variations can mislead results, especially given gamma analysis's sensitivity to MC calculation noise.

Dose tracking assessment for magnetic resonance guided adaptive radiotherapy of rectal cancers.

BACKGROUND: Magnetic resonance-guided adaptive radiotherapy (MRgART) at MR-Linac allows for plan optimisation on the MR-based synthetic CT (sCT) images, adjusting the target and organs at risk according to the patient's daily anatomy. Conversely, conventional linac image-guided radiotherapy (IGRT) involves rigid realignment of regions of interest to the daily anatomy, followed by the delivery of the reference computed tomography (CT) plan. This study aims to evaluate the effectiveness of MRgART versus IGRT for rectal cancer patients undergoing short-course radiotherapy, while also assessing the dose accumulation process to support the findings and determine its usefulness in enhancing treatment accuracy. METHODS: Nineteen rectal cancer patients treated with a 1.5 Tesla MR-Linac with a prescription dose of 25 Gy (5 Gy x 5) and undergoing daily adapted radiotherapy by plan optimization based on online MR-based sCT images, were included in this retrospective study. For each adapted plan ([Formula: see text]), a second plan ([Formula: see text]) was generated by recalculating the reference CT plan on the daily MR-based sCT images after rigid registration with the reference CT images to simulate the IGRT workflow. Dosimetry of [Formula: see text] and[Formula: see text]was compared for each fraction. Cumulative doses on the first and last fractions were evaluated for both workflows. The dosimetry per single fraction and the cumulative doses were compared using dose-volume histogram parameters. RESULTS: Ninety-five fractions delivered with MRgART were compared to corresponding simulated IGRT fractions. All MRgART fractions fulfilled the target clinical requirements. IGRT treatments did not meet the expected target coverage for 63 out of 94 fractions (67.0%), with 13 fractions showing a V95 median point percentage decrease of 2.78% (range, 1.65-4.16%), and 55 fractions exceeding the V107% threshold with a median value of 15.4 cc (range, 6.0-43.8 cc). For the bladder, the median [Formula: see text] values were 18.18 Gy for the adaptive fractions and 19.60 Gy for the IGRT fractions. Similarly the median [Formula: see text] values for the small bowel were 23.40 Gy and 25.69 Gy, respectively. No statistically significant differences were observed in the doses accumulated on the first or last fraction for the adaptive workflow, with results consistent with the single adaptive fractions. In contrast, accumulated doses in the IGRT workflow showed significant variations mitigating the high dose constraint, nevertheless, more than half of the patients still did not meet clinical requirements. CONCLUSIONS: MRgART for short-course rectal cancer treatments ensures that the dose delivered matches each fraction of the planned dose and the results are confirmed by the dose accumulation process, which therefore seems redundant. In contrast, IGRT may lead to target dose discrepancies and non-compliance with organs at risk constraints and dose accumulation can still highlight notable dosimetric differences.

Delineation of the "Oropharyngeal Mucosa" and Limiting its Dose in Head and Neck Cancer Patients Spares the Oropharynx Without Compromising Target Coverage.

OBJECTIVES: Radiation-induced oropharyngeal injury is a dose-limiting toxicity in head and neck cancer patients. Delineation of the "oropharyngeal mucosa" and limiting its dose to spare the oropharynx was investigated. METHODS: In this retrospective study, computed tomography imaging from eight patients with previously untreated head and neck cancer was employed. An adaptive contouring brush within the planning software Monaco was used to create an air cavity within the oropharynx, and then the air cavity was expanded uniformly 2 mm to create the "oropharyngeal mucosa". Three plans were independently generated for each patient: Plan1: dose constraint was applied for the oropharynx; Plan2: dose constraints were applied for the oropharynx and the "oropharyngeal mucosa"; Plan3: dose constraint was applied for the "oropharyngeal mucosa". T-tests were used to compare the dosimetry variables. RESULTS: All plans had adequate target coverage and there were no statistical differences among plans. The mean dose, D30%, D45%, D50%, D85%, D90%, D95%, D100%, V25 Gy, V30 Gy, V35 Gy, V40 Gy, and V45 Gy of the oropharynx and "oropharyngeal mucosa" in Plan1 were significantly higher than those in Plan2 and Plan3. There were no significant differences between Plan2 and Plan3. There were no significant differences in the dosimetric parameters of any other organs at risk. CONCLUSION: Delineation of the "oropharyngeal mucosa" and limiting its dose should be an easy and effective method to spare the oropharynx.

Radiation-induced oropharyngeal injury is dose-limiting toxicity in head and neck cancer patients. Delineation of "oropharyngeal mucosa" and limiting its dose should be an easy and effective method to spare the oropharynx.

Evaluating the Effects of Prostate Radiotherapy Intensified with Pelvic Nodal Radiotherapy and Androgen Deprivation Therapy on Myelosuppression: Single-Institution Experience.

BACKGROUND: Prostate cancer (PCa) management commonly involves the utilization of prostate radiotherapy (PRT), pelvic nodal radiotherapy (PNRT), and androgen deprivation therapy (ADT). However, the potential association of these treatment modalities with bone marrow (BM) suppression remains inadequately reported in the existing literature. This study is designed to comprehensively evaluate the risk of myelosuppression associated with PRT, shedding light on an aspect that has been underrepresented in prior research. MATERIALS AND METHODS: We conducted a retrospective analysis of 600 patients with prostate cancer (PCa) treated with prostate radiotherapy (PRT) at a single oncology center between 2007 and 2017. Patients were categorized into four cohorts: PRT alone (n = 149), PRT + ADT, (n = 91), PRT + PNRT (n = 39), and PRT + PNRT + ADT (n = 321). To assess the risk of myelosuppression, we scrutinized specific blood parameters, such as hemoglobin (HGB), white blood cells (WBCs), neutrophils (NEUT), lymphocytes (LYM), and platelets (PLT) at baseline, mid-treatment (mRT), immediately post-RT (pRT), 1 month post-RT (1M-pRT), and 1 year post-RT (1Y-pRT). The inter-cohort statistical significance was evaluated with further stratification based on the utilized RT technique {3D conformal radiotherapy (3D-CRT), and intensity-modulated radiation therapy (IMRT)}. RESULTS: Significant statistical differences at baseline were observed in HGB and LYM values among all cohorts (p < 0.05). Patients in the PRT + PNRT + ADT cohort had significantly lower HGB at baseline and 1M-pRT. In patients undergoing ADT, BMS had a significant impact at 1M-pRT {odds ratio (OR) 9.1; 95% Confidence Interval (CI) 4.8-17.1} and at 1Y-pRT (OR 2.84; CI 1.14-7.08). The use of 3D-CRT was linked to reduced HGB levels in the PRT + PNRT + ADT group at 1 month pRT (p = 0.015). Similarly, PNRT significantly impacted BMS at 1M-pRT (OR 6.7; CI 2.6-17.2). PNRT increased the odds of decreased WBC counts at 1Y-pRT (OR 6.83; CI: 1.02-45.82). Treatment with any RT techniques (3D-CRT or IMRT), particularly in the PRT + PNRT and PRT + PNRT + ADT groups, significantly increased the odds of low LYM counts at all time points except immediately pRT (p < 0.05). Furthermore, NEUT counts were considerably lower at 1M-pRT (p < 0.05) in the PRT + PNRT + ADT group. PLT counts were significantly decreased by PRT + PNRT + ADT at mRT (OR 2.57; 95% CI: 1.42-4.66) but were not significantly impacted by the RT technique. CONCLUSIONS: Treatment with PRT, ADT, PNRT, and 3D-CRT is associated with BMS. Despite this statistically significant risk, no patient required additional interventions to manage the outcome. While its clinical impact appears limited, its importance cannot be underestimated in the context of increased integration of novel systemic agents with myelosuppressive properties. Longer follow-up should be considered in future studies.

Single pre-operative radiation therapy (SPORT-CK) trial for low-risk breast cancer: Early results of a phase 2 study.

BACKGROUND AND PURPOSE: Preoperative partial breast irradiation (PBI) is a novel technique that can be used in patients with early-stage breast cancer with the goal of limiting the irradiated breast volume, toxicity and number of fractions. The aim of this trial is to assess the toxicity, surgical, oncologic and cosmetic outcomes of preoperative PBI. MATERIALS AND METHODS: In this single-arm phase II trial, we enrolled women ≥ 60 years, with unifocal low-risk breast invasive ductal carcinoma (cT1N0, grade 1-2, ER+, Her2-). Patients were treated with a single fraction of 20 Gy of preoperative PBI using volumetric modulated arc therapy (VMAT). Patients then underwent breast-conserving surgery (BCS) +/- sentinel lymph node biopsy within 72 h of radiation. Primary outcomes were rate of surgical complications and early toxicity. Secondary outcomes were cosmesis at 12 months, chronic toxicity and ipsilateral breast tumor recurrence. RESULTS: Twenty-five patients were recruited with a median age of 67 years, and a median follow-up of 60 months. Sentinel biopsy was positive in 1 out of 24 patients (4 %). Two patients received adjuvant RT for close margins or positive lymph nodes. Within the first 90 days, none of the patients had surgical complications; almost all had grade 0 to 1 acute and late RTOG skin toxicity. The cosmetic outcome was rated between good and excellent in all cases by physicians and patients, except for one patient who self-rated her cosmesis as fair as of the third year. There were no recurrences. CONCLUSION: Preoperative single-fraction PBI is a safe and feasible treatment for elderly patients with low-risk early-stage breast cancer, with no surgical complications, very low rates of acute and late radiation toxicity, and excellent cosmetic outcomes. Randomized controlled trials are needed to compare preoperative to adjuvant PBI in this patient population.

Clinical implementation of deep learning robust IMPT planning in oropharyngeal cancer patients: A blinded clinical study.

BACKGROUND AND PURPOSE: This study aimed to evaluate the plan quality of our deep learning-based automated treatment planning method for robustly optimized intensity-modulated proton therapy (IMPT) plans in patients with oropharyngeal carcinoma (OPC). The assessment was conducted through a retrospective and prospective study, blindly comparing manual plans with deep learning plans. MATERIALS AND METHODS: A set of 95 OPC patients was split into training (n = 60), configuration (n = 10), test retrospective study (n = 10), and test prospective study (n = 15). Our deep learning optimization (DLO) method combines IMPT dose prediction using a deep learning model with a robust mimicking optimization algorithm. Dosimetrists manually adjusted the DLO plan for individual patients. In both studies, manual plans and manually adjusted deep learning (mDLO) plans were blindly assessed by a radiation oncologist, a dosimetrist, and a physicist, through visual inspection, clinical goal evaluation, and comparison of normal tissue complication probability values. mDLO plans were completed within an average time of 2.5 h. In comparison, the manual planning process typically took around 2 days. RESULTS: In the retrospective study, in 10/10 (100%) patients, the mDLO plans were preferred, while in the prospective study, 9 out of 15 (60%) mDLO plans were preferred. In 4 out of the remaining 6 cases, the manual and mDLO plans were considered comparable in quality. Differences between manual and mDLO plans were limited. CONCLUSION: This study showed a high preference for mDLO plans over manual IMPT plans, with 92% of cases considering mDLO plans comparable or superior in quality for OPC patients.

Long-term results of induction chemotherapy for non-operable esophageal squamous cell carcinoma followed by concurrent chemoradiotherapy: a single-centre experience.

BACKGROUND: This study aimed to investigate the long-term clinical outcomes and toxicities of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) vs. CCRT alone in patients with non-operable esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Between 2008 and 2022, 271 ESCC patients who received definitive CCRT based on intensity modulated radiation therapy (IMRT)/volumetric modulated arc therapy (VMAT) were enrolled. Through a propensity score-matched (PSM) method, 71 patients receiving IC and CCRT were matched 1:1 to patients who received CCRT alone. The Kaplan-Meier method and Cox proportional hazards model were applied to analyze survival and prognosis. RESULTS: The IC + CCRT group had no improvement in 5-year overall survival (OS) rate, recurrence-free survival (RFS) rate, and distant metastasis-free survival (DMFS) rate (all p > 0.05) compared with the CCRT group. The 5-year OS rate (65.6% vs. 17.6% vs. 29.3%, p < 0.001), RFS rate (65.6% vs. 17.6% vs. 26.9%, p < 0.001), and DMFS rate (62.5% vs. 10.3% vs. 27.2%, p < 0.001) of the IC good responders were significantly higher than that of the IC poor responders and CCRT group. Multivariate analysis revealed that total radiotherapy time (≥ 49 days) and stage III/IV were independent predictive factors of OS, RFS, and DMFS. No significant differences were observed in the rates of grade 3-4 toxicities between both groups. CONCLUSIONS: Our results showed the addition of IC to CCRT was not superior to CCRT in unselected ESCC patients, while IC responders could benefit from this regime without an increase in toxicities.

Impact of the radiotherapy rhythm on prognosis in nasopharyngeal carcinoma.

OBJECTIVE: The role of chronoradiobiology in nasopharyngeal carcinoma (NPC) has not been fully elucidated. We sought to investigate the impact of radiotherapy rhythm on the survival outcomes of individuals to explore a chronomodulated radiation strategy to improve prognosis of NPC. METHODS: A cohort comprising non-metastatic NPC patients subjected to intensity-modulated radiotherapy at Fujian Cancer Hospital between Jan. 2016 and Dec. 2019 was assembled. Rhythmic fluctuation of radiotherapy (RFRT) was quantified based on the temporal distribution of radiation delivery. Cox proportional hazard model was performed to explore the impact of radiotherapy rhythm on all-cause mortality. The maximally selected rank statistics method was employed to discern an optimal cutoff. Sensitivity analyses were conducted to ensure the robustness of observed associations. RESULTS: Our analysis encompassed 2245 patients, with a median follow-up duration of 55 months, during which 315 individuals succumbed. Multivariate Cox regression analysis unveiled a significant correlation between prolonged RFRT and heightened mortality risk in NPC patients (HR, 1.17, 95% CI, 1.07-1.27, p < .001), a relationship robust to comprehensive adjustment for confounding variables. A cutoff value of 3 h was selected for potential clinical application, beyond which patients exhibited markedly poorer survival outcomes. Subgroup analyses consistently underscored the directional consistency of observed effects. CONCLUSION: Our study sheds light on the potential advantages of scheduling radiotherapy sessions at consistent times. These findings have implications for optimizing radiotherapy schedules and warrant further investigation into personalized chronotherapy approaches in NPC management.

Clinical significance of intensity-modulated radiotherapy (IMRT) to the distant metastatic lymph nodes for metastatic cervical cancer.

OBJECTIVE: To retrospectively explore the clinical significance of radiotherapy to the distant metastatic lymph nodes (cervical/ clavicular/ mediastinal et al.) in metastatic cervical cancer. Hereinto, these cervicothoracic lymph nodes were metastasized from IB1-IVA (initial stage at first treatment), and IVB initially had metastatic disease in these areas at diagnosis. METHODS: Metastatic cervical cancer only with the distant cervicothoracic metastatic lymph nodes (cervical/ clavicular/ mediastinal et al.), without distant parenchymal organs metastasis such as lung, liver, bone, and peritoneum, were enrolled in the analysis. These patients were classified into IB1-IVA and IVB based on their initial stage of first treatment. All patients received IMRT for the distant metastatic lymph nodes. The progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. RESULTS: Overall, the median PFS was 9 months, and the median OS was 27 months. The subgroup analysis showed that for IB1-IVA, the median PFS was 11 months, and the median OS was 30.5 months. For IVB, the median PFS was 8 months, and the median OS was 16 months. CONCLUSION: Radiotherapy is beneficial to the distant metastatic lymph nodes (cervical/ clavicular/ mediastinal et al.), and could effectively bring the longer PFS and OS for metastatic cervical cancer.

Study protocol: Optimising patient positioning for the planning of accelerated partial breast radiotherapy for the integrated magnetic resonance linear accelerator: OPRAH MRL.

BACKGROUND: Accelerated partial breast irradiation (APBI) is an accepted treatment option for early breast cancer. Treatment delivered on the Magnetic Resonance integrated Linear Accelerator (MRL) provides the added assurance of improved soft tissue visibility, important in the delivery of APBI. This technique can be delivered in both the supine and prone positions, however current literature suggests that prone treatment on the MRL is infeasible due to physical limitations with bore size. This study aims to investigate the feasibility of positioning patients on a custom designed prone breast board compared with supine positioning on a personalised vacuum bag. Geometric distortion, the relative position of Organs at Risk (OAR) to the tumour bed and breathing motion (intrafraction motion) will be compared between the supine and prone positions. The study will also investigate the positional impact on dosimetry, patient experience, and position preference. METHODS: Up to 30 patients will be recruited over a 12-month period for participation in this Human Research Ethics Committee approved exploratory cohort study. Patients will be scanned on the magnetic resonance imaging (MRI) Simulator in both the supine and prone positions as per current standard of care for APBI simulation. Supine and prone positioning comparisons will all be assessed on de-identified MRI image pairs, acquired using appropriate software. Patient experience will be explored through completion of a short, anonymous electronic survey. Descriptive statistics will be used for reporting of results with categorical, parametric/non-parametric tests applied (data format dependent). Survey results will be interpreted by comparison of percentage frequencies across the Likert scales. Thematic content analysis will be used to interpret qualitative data from the open-ended survey questions. DISCUSSION: The results of this study will be used to assess the feasibility of treating patients with APBI in the prone position on a custom designed board on the MRL. It may also be used to assist with identification of patients who would benefit from this position over supine without the need to perform both scans. Patient experience and technical considerations will be utilised to develop a tool to assist in this process. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN1262400067583. Registered 28th of May 2024. https://www.anzctr.org.au/ACTRN12624000679583.aspx.

Impact of interplay effects on spot scanning proton therapy with motion mitigation techniques for lung cancer: SFUD versus robustly optimized IMPT plans utilizing a four-dimensional dynamic dose simulation tool.

BACKGROUND: The interaction between breathing motion and scanning beams causes interplay effects in spot-scanning proton therapy for lung cancer, resulting in compromised treatment quality. This study investigated the effects and clinical robustness of two types of spot-scanning proton therapy with motion-mitigation techniques for locally advanced non-small cell lung cancer (NSCLC) using a new simulation tool (4DCT-based dose reconstruction). METHODS: Three-field single-field uniform dose (SFUD) and robustly optimized intensity-modulated proton therapy (IMPT) plans combined with gating and re-scanning techniques were created using a VQA treatment planning system for 15 patients with locally advanced NSCLC (70 GyRBE/35 fractions). In addition, gating windows of three or five phases around the end-of-expiration phase and two internal gross tumor volumes (iGTVs) were created, and a re-scanning number of four was used. First, the static dose (SD) was calculated using the end-of-expiration computed tomography (CT) images. The four-dimensional dynamic dose (4DDD) was then calculated using the SD plans, 4D-CT images, and the deformable image registration technique on end-of-expiration CT. The target coverage (V98%, V100%), homogeneity index (HI), and conformation number (CN) for the iGTVs and organ-at-risk (OAR) doses were calculated for the SD and 4DDD groups and statistically compared between the SD, 4DDD, SFUD, and IMPT treatment plans using paired t-test. RESULTS: In the 3- and 5-phase SFUD, statistically significant differences between the SD and 4DDD groups were observed for V100%, HI, and CN. In addition, statistically significant differences were observed for V98%, V100%, and HI in phases 3 and 5 of IMPT. The mean V98% and V100% in both 3-phase plans were within clinical limits (> 95%) when interplay effects were considered; however, V100% decreased to 89.3% and 94.0% for the 5-phase SFUD and IMPT, respectively. Regarding the significant differences in the deterioration rates of the dose volume histogram (DVH) indices, the 3-phase SFUD plans had lower V98% and CN values and higher V100% values than the IMPT plans. In the 5-phase plans, SFUD had higher deterioration rates for V100% and HI than IMPT. CONCLUSIONS: Interplay effects minimally impacted target coverage and OAR doses in SFUD and robustly optimized IMPT with 3-phase gating and re-scanning for locally advanced NSCLC. However, target coverage significantly declined with an increased gating window. Robustly optimized IMPT showed superior resilience to interplay effects, ensuring better target coverage, prescription dose adherence, and homogeneity than SFUD. TRIAL REGISTRATION: None.

Comparison of Different Head Tilt Angles in Tomotherapy and Volumetric Modulated Arc Therapy for Hippocampal-Avoidance Whole-Brain Radiotherapy.

PURPOSE: Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) planning can present challenges. This study examines the influence of head tilt angles on the dosimetric characteristics of target and organs at risk (OARs), aiming to identify the optimal tilt angle that yields optimal dosimetric outcomes using tomotherapy (TOMO). METHODS: Eight patients diagnosed with brain metastases underwent CT scans at five tilt angles: [0°, 10°), [10°, 20°), [20°, 30°), [30°, 40°), and [40°, 45°]. Treatment plans were generated using TOMO and volumetric modulated arc therapy (VMAT). Dosimetric parameters including conformity index (CI), homogeneity index (HI), D2cc, D98%, and Dmean of PTV, as well as Dmax, and Dmean of OARs were analyzed. Furthermore, a comparison was made between the dosimetric parameters of TOMO and VMAT plans. Finally, delivery efficiency of TOMO plans were assessed. RESULTS: For the PTV, [40°, 45°] tilt angle demonstrated significantly better conformity, homogeneity, lower D2cc, and lower Dmean for the PTV. Regarding the OARs, the [40°, 45°] head tilt angle demonstrated significantly lower Dmax and Dmean in hippocampus, eyes, optic chiasm, and optic nerves. The [40°, 45°] tilt angle also showed significantly lower Dmax for brainstem and cochleas, as well as a lower Dmean for lens. In the [40°,45°] tilt angle for HA-WBRT, TOMO showed superior performance over VMAT for the PTV. TOMO achieved lower Dmax for brainstem, cochleas, optic nerves, and optic chiasm, as well as a lower Dmean for hippocampus. Furthermore, a significant correlation was found between delivery time and the PTV projection length in the sagittal plane. CONCLUSION: The TOMO plan utilizing a tilt angle range of [40°, 45°] demonstrated superior PTV conformity and uniformity, along with enhanced OARs sparing. Furthermore, it exhibited a dosimetric advantage over VMAT for PTV and most OARs at the same angle range.

T lymphocyte and neutrophil/lymphocyte ratio in patients with radiation-induced oral mucositis after intensity-modulated radiation therapy for head and neck cancer: A retrospective single-center study.

To investigate T lymphocyte, neutrophil/lymphocyte ratio (NLR) and their impact on patients with radiation-induced oral mucositis (RIOM) after intensity-modulated radiotherapy for head and neck cancer. The clinical data of 148 patients diagnosed with head and neck cancer from January 2016 to January 2019 were retrospectively analyzed. Patients were divided into RIOM group (n = 42 cases) and non-RIOM group (n = 106 cases), based on whether they developed RIOM after intensity-modulated radiation therapy. The T lymphocyte and NLR of the 2 groups were analyzed before and after treatment; The correlation between T lymphocyte and NLR in RIOM group was analyzed. We used RTOG grading system to evaluate and scale the RIOM. The relationship between the grade of RIOM, T lymphocyte and NLR in RIOM group was analyzed. After treatment, the proportion of CD3 +, CD4 +, and CD8 + T lymphocytes in the 2 groups after treatment were decreased, and the RIOM group was significantly lower than non-RIOM group, P < .05. NLR in RIOM group was significantly higher than that in non-RIOM group, P < .05. The data of overall survival showed no significant differences between 2 groups (HR = 0.82, 95% CI: 0.43-1.59). Compared with RIOM group, patients in non-RIOM group showed a longer progress-free survival (HR = 0.57, 95% CI: 0.33-0.99). In RIOM group, NLR was negatively correlated with CD3 + (r = -0.433, P = .004), CD4 + (r = -0.644, P < .001) and CD8 + T cells (r = -0.665, P < .001). RIOM was positively correlated with NLR (R = 0.621, P < .001), negatively correlated with CD4 + T cell ratio (r = -0.449, P = .003) and CD8 + T cell ratio (r = -0.307, P = .048), but RIOM did not correlate with CD3 + T cell ratio (r = -0.225, P = .152). For patients with RIOM after intensity-modulated radiotherapy for head and neck cancer, T lymphocyte showed a downward trend, and NLR showed an upward trend. In addition, T lymphocyte and NLR are closely related to the RIOM, indicating that clinicians should be aware of the importance of T lymphocyte and NLR on patients received radiotherapy.