International Journal of Radiation Oncology Biology Physics最新文献

Radiation therapy for locally advanced pancreatic cancer (LAPC) continues to be controversial. Advances in both systemic therapy and radiation therapy techniques have changed the landscape of LAPC management in recent years. Clinical outcomes of ablative radiation therapy have been encouraging and randomized clinical trials may clarify the role of radiation therapy for LAPC. We present a contemporary critical review of key aspects regarding optimal patient selection, radiation dose escalation techniques, novel radiosensitizers and radioprotectors, and treatment response assessment for LAPC.

Purpose: CT simulation is required for centers performing 3D conformal radiotherapy and intensity modulated radiation therapy. Therefore, CT simulator downtime is likely to lead to delays in patient care. We sought to characterize CT simulator downtime within the African context.

Materials and methods: A pilot clinician survey was developed to evaluate CT simulator downtime frequency, causes, and workflow impact over the last year. It was distributed to African Organization for Research and Training in Cancer (AORTIC) Conference attendees in November 2023 and through radiotherapy networks on the African continent. Descriptive statistics were used to summarize data.

Results: Responses were obtained for 22 CT scanners in 16 centers across 9 African countries. Nigeria (n=6) and South Africa (n=3) had the most centers represented. Most centers (n=10, 63%) had a single CT scanner capable of simulation, five (31%) had two, and one (6%) had three scanners. For the 19 CT simulators with downtime information available, 11 (58%) were down for at least 15 days in the last year. Median downtime per episode was 3.5 days [IQR 1 - 9.75]. Three CT simulators were down all year, two of which were the only CT simulator at their respective centers. CT simulators were down due to intrinsic causes for median 8 days [IQR 3 - 37.5] and extrinsic causes for median 1 day [IQR 0 - 7.5]. Most machines (n=17, 77%) were under an active maintenance contract. Most centers (n=11, 69%) lacked access to an alternate CT scanner for simulation during downtime, while three (19%) maintained normal workflow.

Conclusions: CT simulator downtime is highly variable across the African continent and can cause significant disruptions in radiotherapy treatment at some centers. Intrinsic causes led to most downtime. These results suggest reducing CT simulator downtime frequency and duration or implementing simulation-free workflows may decrease patient delays.

Purpose/objective: We correlated regional near-surface dose with toxic effects and implant complications in patients receiving breast or chest wall irradiation. We also compared toxic effects and implant complications between patients receiving photon or proton irradiation with prospective near-surface dose optimization.

Materials/methods: Patients at a single institution who received conventionally fractionated breast or chest wall and regional nodal irradiation from 2017-2022 were included. Near-surface rinds (SR3, defined as the volume bound by the breast or chest wall PTV and 3 mm in from the skin) were generated for all patients for analysis. SR3 volumes were used prospectively during proton treatment. SR3 volumes were retrospectively subdivided into axillary SR3, non-axillary SR3, and inframammary SR3 regions. The discrimination performance of near-surface dosimetry for skin and implant toxicity was evaluated using the area under the receiver operating curve (AUC). CTCAE toxicity was compared between patients receiving photon versus proton irradiation using the Pearson's Chi-squared test.

Results: Of 223 patients, 157 and 66 received photon and proton irradiation, respectively. Axillary SR3 D2cc was the strongest dosimetric predictor of moist desquamation (AUC=0.657, p=0.007) and implant failure (AUC=0.880, p=0.017), driven by a stronger predictive ability for moist desquamation in the axillary fold (AUC=0.728, p<0.001). With axillary SR3 D2cc ≤ 48 Gy versus > 48 Gy, rates of moist desquamation were 25.8% versus 48.5% (p<0.001), respectively, and rates of implant failure were 0% versus 20% (p=0.006). Rates of moist desquamation (38.2% versus 27.3%, p=0.12), unplanned reconstructive surgery (35.1% versus 18.8%, p=0.21), and implant failure (8.8% versus 6.3% p>0.99) were similar between patients receiving photon versus proton irradiation.

Conclusions: Near-surface dose predicts moist desquamation and implant failure in patients receiving either photon or proton irradiation of the breast or chest wall. Consideration should be given to limit axillary SR3 D2cc ≤ 48 Gy in appropriately selected patients considered low-risk for skin involvement of cancer.

Background and purpose: The integration of MRI and linear accelerator (MRI-Linac) enables daily imaging during radiation therapy (RT). This study implements MRI-Linac relaxometry to evaluate quantitative imaging changes in glioblastoma patients during RT and identify associations with disease progression and survival outcomes.

Materials and methods: Thirty-eight glioblastoma patients were treated on a 0.35T MRI-Linac with Strategically Acquired Gradient Echo (STAGE) and T2 multi-echo acquisitions every other day. Per voxel changes in tumor T2, T2*, and T1 values were assessed by parametric response mapping comparing each treatment fraction with pre-RT baselines. Statistical analyses included the Wilcoxon test for group comparisons and Cox proportional hazards models for survival associations.

Results: Progressors had higher proportions of voxels with increased T2 values at week 2 (49% vs. 40%, p = 0.008) and week 6 (58% vs. 43%, p = 0.012) and higher T2* values at week 1 (47% vs. 43%, p = 0.016), week 2 (48% vs. 43%, p = 0.016), week 3 (50% vs. 44%, p = 0.012), and the final week (53% vs. 43%, p = 0.021). Cox modelling linked increased T2 values at week 4 with overall survival (HR = 4.72, 95% CI: 1.24-12.9) and progression-free survival (HR = 9.26, 95% CI: 1.88-24.5). Increased T2* values at weeks 2 and 3 correlated with progression-free survival (HR = 5.02, 95% CI: 1.44-17.6; HR = 6.04, 95% CI: 1.59-22.9) and overall survival at week 3 (HR = 3.09, 95% CI: 0.94-10.1).

Conclusion: Quantitative changes in T2 and T2* values during RT, particularly in weeks 3-4, were associated with progression and survival outcomes. Early detection of poor responders may enable therapy adaptation, improving glioblastoma treatment outcomes.

Purpose: To develop and validate a prediction model for major adverse cardiac events (MACE) in hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT).

Methods and materials: We retrospectively identified 1893 HCC patients who received SBRT at two institutions, with one serving as the development cohort (n=1473) and the other as the validation cohort (n=420). MACE was defined as any cardiac event classified as grade 3 or higher, according to the Common Terminology Criteria for Adverse Events, version 5.0. We evaluated 15 clinical and 88 dosimetric parameters using bootstrapped forward selection and area under the curve (AUC) to identify significant predictors for MACE. Based on these factors, we constructed the Cardiac Event Index (CEI) model, categorizing patients into distinct risk groups. Model performance was assessed for discrimination, efficiency, and calibration.

Results: The occurrence rate of MACE was 5.8% in the development cohort and 6.7% in the validation cohort. Five parameters were selected for predicting MACE and were incorporated into the CEI model using the following equation: CEI = age score + hypertension + current smoking + (2 × history of cardiac disease) + (0.05 × heart-V5 [%]), which yielded an AUC of 0.770 for MACE and 0.750 for coronary artery disease. The CEI model stratified patients into low-, intermediate-, and high-risk groups that had MACE incidence rates of 0.4%, 4.9%, and 22.8%, respectively. The impact of heart-V5 on MACE was minimal in low- and intermediate-risk groups but pronounced in the high-risk group. In the validation cohort, the CEI model yielded an AUC of 0.809 for MACE and 0.793 for coronary artery disease.

Conclusions: The CEI model demonstrated robust performance in predicting MACE, revealing the significant influence of clinical factors and the minimal impact of SBRT. This model can inform evidence-based decisions regarding cardiac dose optimization in SBRT planning.

Purpose/objective(s): Consolidation radiation therapy (RT) is often recommended in diffuse large B-cell lymphoma (DLBCL). The current recommended dose of 30 Gy was established in the pre-rituximab and PET-CT era. We hypothesized that following a complete response (CR) to modern systemic therapy, as determined by PET-CT, a lower dose of RT would be equally effective.

Materials/methods: Patients with DLBCL or primary mediastinal B-cell lymphoma (PMBL) achieving a CR by PET-CT (Deauville 1-3) after ≥4 cycles of R-CHOP or R-EPOCH were eligible. Consolidation RT dose was 19.5-20 Gy. The primary endpoint of the original study was 5-year freedom from local recurrence (FFLR).

Results: From 2010-2016, 62 patients were enrolled. Stage distribution was: I-II (n=49, 79%) and III-IV (n=13, 21%). Bulky disease (≥7.5 cm) was present in 24 patients (39%). Most (n=58, 94%) received R-CHOP. Four cycles were administered to 34% of patients while 66% received 5-6 cycles. Median follow up was 9 years. Overall, 1 patient experienced local recurrence with FFLR of 98% at both 5 and 10 years (95% CI 88-99%). 7 patients progressed outside of the RT field. Progression-free survival and overall survival at 10 years were 77% (95% CI 62-87%) and 80% (95% CI 64-89%), respectively.

Conclusion: Long-term results of this phase 2 study, with a median follow-up of 9 years, did not demonstrate late local failures when patients received ∼20 Gy consolidation RT. A larger (n=240) confirmatory study from the International Lymphoma Radiation Oncology Group evaluating ∼20 Gy of RT after ≥ 3 cycles of chemoimmunotherapy completed accrual in 2023.

Purpose: The purpose of this Phase II clinical study is to investigate the safety and feasibility of a single fraction Stereotactic Partial Breast Irradiation (S-PBI) for early-stage breast cancer (BC) in the pre-operative setting and to evaluate tumor response to a single large radiation dose through pathological examination and immunohistochemistry analysis of the surgical specimen.

Materials and methods: This single arm, phase II clinical trial includes patients in post-menopausal status, over the age of 50, with early-stage (cT1-T2 cN0) BC, luminal type, any grade, unifocal tumor, suitable for breast-conserving surgery (BCS). The gross tumor volume (GTV) includes the tumor. The clinical target volume (CTV) corresponds to GTV. The planning target volume (PTV) is created by adding 3 mm symmetrical margins from the CTV. Treatment is delivered through GammaPod technology as single fraction radiosurgery, to a total dose of 30-36 Gy. Surgery is performed 8 to 28 weeks after S-PBI. Pathological response is classified as complete response (pCR), near complete response (nCR) with less than 10% of residual disease, partial response (pPR) with 10% to 90% of residual disease, or stable disease with more than 90% of residual disease. We further group pCR and nCR together as "Major Response".

Results: From January 2022 to November 2023, 49 patients were enrolled and underwent S-PBI followed by BCS. The rate of Major Response was 37%, including pCR in 18% of cases. The mean Ki-67 index was reduced from 9.5% pre-S-PBI to 2% post-S-PBI.

Conclusion: Pre-operative single fraction S-PBI appears to be associated with a promising rate of 'Major Response,' including cases of complete response.

Background: Radiation necrosis(RN) is a dose-limiting toxicity of stereotactic radiosurgery(SRS) for brain metastases. Oral corticosteroids are not optimal for long-term management given multiple side effects. Boswellia serrata(BS) is an over-the-counter supplement traditionally known for anti-inflammatory properties and recently shown to reduce cerebral edema. We evaluated the response rates with BS in a series of patients with RN after SRS for brain metastases.

Methods: We identified patients who developed any grade RN after SRS and received BS for ≥2 months, at a target dose of 4050-4500 mg daily. Primary endpoint was objective response rate(ORR), including complete response(CR) or partial response(PR), defined as ≥30% decrease in edema volume on T2-FLAIR MRI from baseline.

Results: 100 patients received BS of which 94 patients with adequate follow-up were included. Median SRS dose was 24 Gy in 3 fractions, and 44%, 47% and 9% patients had grade 1, 2, and 3 RN, respectively. The best response was CR in 12% and PR in 48%, while 28% had stable edema(SE) and 12% had progression of edema. The overall ORR was 59.6% (95% CI: 48.9 - 69.6%). ORR was 62%, 63%, and 33%, respectively for grade 1, 2, and 3, RN. The median duration of response in patients with CR or PR was 13.9 months (IQR 9 - 23). Among 69 patients (73%) who never received steroids, received prior steroids only, or had a stable or decreasing steroid requirement of ≤4 mg per day of Dexamethasone for at least >1 week prior to starting Boswellia, the ORR was 63.8%. 14% patients had CTCAE grade 1, and 2% had grade 2 gastrointestinal toxicity. 67% patients remained on BS at last follow-up.

Conclusion: Our study suggests BS is a safe and feasible treatment option for grade 1-3 RN after SRS. Further prospective studies comparing BS with placebo are warranted.

Background: The outcome of proton therapy for head and neck cancer (HNC) varies considerably. We investigated the feasibility of adapting proton therapy plans based on ¹⁸F-FDG-PET-defined biologic tumor volumes (BTV) reflecting remaining aggressive tumor subvolumes two weeks into treatment (interim). Recognizing the potential to improve proton therapy response with increasing linear energy transfer (LET), we simulated a combined dose-LET escalation to the BTVs and compared it to pure dose escalation. In addition, the impact of relative biological effectiveness (RBE) was evaluated by comparing the constant RBE of 1.1 (RBE_1.1) with a variable-RBE model.

Methods and materials: A semiautomated method was used to segment the BTV from ¹⁸F-FDG-PET for nine HNC patients, assuming high standardized uptake value at interim to reflect tumor radioresistance. An in-house Monte Carlo-based recalculation and reoptimization tool simulated proton therapy plans with both constant RBE_1.1 and variable-RBE, aimed to deliver 68 Gy(RBE) to high-risk target volumes, 10% dose escalation to the BTV, and a LET boost to the BTV. Dose distributions were prioritized over LET optimization goals. Results were quantified by dose and LET distributions to target volumes and organs at risk (OARs), as well as normal tissue complication probabilities (NTCPs) for xerostomia and dysphagia.

Results: Dose-LET adapted proton therapy plans achieved 10% dose escalation and mean dose-averaged LET (LET_d) increases to the BTV above 1.0 keV/μm, with no significant LET increases to OARs. NTCP for xerostomia and dysphagia from dose-LET and dose-only escalation were similar. However, NTCPs increased 6-10% when variable-RBE was used instead of the constant RBE_1.1.

Conclusion: Our in silico study showed that dose-LET escalation in proton therapy integrating a variable-RBE model may improve proton therapy for HNC patients. Clinical evaluation of such a biological image-based dose-LET escalation in proton therapy of HNC remains to be investigated.

Objective: This study is aimed to identify biomarkers for symptomatic radiation pneumonitis (RP) in patients with lung cancer treated with immune checkpoint inhibitors (ICIs).

Methods: This multicenter, prospective study enrolled lung cancer patients receiving thoracic radiotherapy (RT) between 2021 and 2023. Plasma cytokines were measured using Luminex assays. Cox proportional hazards model was used to identify risk factors and biomarkers for RP. Sensitivity analysis was conducted using Fine-Gray competing risk analyses. Receiver operating characteristic (ROC) curves were used to assess the predictive value of the cytokines.

Results: A total of 214 patients receiving thoracic RT were included in this study, with 75 (31.12%) patients developing symptomatic RP. Among the 71 patients with prior ICI treatment, 32 (45.07%) developed symptomatic RP. Patients with prior ICI treatment had higher incidence of symptomatic RP and plasma chemokines than those without prior ICI treatment. For patients with prior ICI treatment, plasma CXCL10 before RT (hazard ratio[HR]=1.29, 95% confidence interval[CI]: 1.03-1.64) and at 2 weeks (HR=1.28, 95%CI: 1.03-1.59) and 4 weeks during RT (HR=1.65, 95%CI: 1.19-2.28) were significant associated with RP. The area under the curves (AUC) of plasma CXCL10 at baseline, 2w and 4w during RT were 0.625, 0.680, and 0.679, respectively. Plasma CXCL14 before RT and CXCL2 during RT were also predictors of RP. A risk score integrating CXCL10, CXCL14, CXCL2, and mean lung dose (MLD) showed better predictive performance than individual factors (AUC=0.757).

Conclusions: In this prospective study, plasma chemokines predict future risk of symptomatic RP in patients with lung cancer who have received prior immunotherapy. Despite with moderate AUC, the scoring system based on plasma chemokines and MLD is a feasible tool for predicting symptomatic RP, aiding in tailoring personalized and optimal treatment for patients.