International Journal of Radiation Oncology Biology Physics最新文献

Background: There remains considerable uncertainty regarding normal tissue tolerances to reirradiation for recurrent brain tumours. This systematic review aimed to collate reirradiation constraints, planned cumulative organ at risk (OAR) doses and corresponding toxicity outcomes for adults treated with reirradiation for recurrent glioma.

Evidence acquisition: A systematic review was performed, searching Medline, Embase, Cochrane, Web of Science and Scopus for studies published up to 1^st July 2025. To allow comparison between constraints, where necessary, equivalent doses in 2Gy fractions were calculated.

Evidence synthesis: 27 studies were included. Most patients had glioblastoma. Of the 24 studies that reported constraints, 17 employed flat constraints (i.e. applied to the reirradiation treatment alone), and 11 employed cumulative constraints (i.e. applied across the original and reirradiation treatments), without the use of tissue recovery factors (TRFs). None of the included studies used TRFs. Constraints were highly heterogenous. Planned cumulative doses were reported in seven studies and were also heterogeneous. No serious optic pathway, eye or brainstem toxicities were reported. Radionecrosis was infrequently reported, but severe cases did occur. No clear patterns emerged between cumulative constraints or planned cumulative doses and the occurrence of radionecrosis. Given the heterogeneity, it is not possible to recommend definitive OAR constraints for glioma reirradiation. That said, in patients with recurrent glioblastoma, for optic pathways and brainstem, candidate cumulative maximum or near-maximum EQD2Gy limits (α/β=2Gy) of 75-80Gy and 85-100Gy, respectively, are suggested as being associated with <5% risk of severe toxicity. For normal brain, 100-110Gy might be reasonable though larger volume constraints are likely relevant but, as yet, are undefined.

Conclusions: There is heterogeneity in glioma reirradiation constraints. The lack of data on larger volume normal brain constraints and toxicity outcomes from centres using cumulative constraints with TRFs represent substantial gaps. Trials and standardisation of reporting are means to better define dose-toxicity relationships.

Purpose: The optimal number of induction chemotherapy (IC) cycles for locally advanced nasopharyngeal carcinoma (LA-NPC) is uncertain. This retrospective study proposes and validates a strategy combining clinical staging with post-cycle-two plasma Epstein-Barr virus (EBV) DNA status to guide IC cycle selection.

Methods and materials: Patients with LA-NPC from XXX (center 1) formed the training cohort, and those from XXX (center 2) comprised the external validation cohort. All received 2-3 IC cycles plus (chemo-)radiotherapy, with plasma EBV-DNA measured after cycle-two (post-IC2-EBV-DNA). Failure-free survival (FFS) was compared between two-cycle vs three-cycle IC and stratified by recursive partitioning analysis.

Results: The training and validation cohorts comprised 794 and 448 patients, evenly divided between three- and two-cycle IC. In the training cohort, recursive partitioning analysis stratified patients into three distinct prognostic groups. Among low-risk group (undetectable post-IC2-EBV-DNA), FFS was comparable between the three-cycle and two-cycle IC (83.8% vs 87.3%, p=0.647). In the detectable cohort, stage IVA patients (high-risk group) received three-cycle IC had improved 5-year FFS vs two-cycle (74.0% vs 56.8%, p=0.013), whereas no difference was observed in stage III (intermediate-risk group) (75.9% vs 83.1%, p=0.269). Findings were confirmed in the external validation cohort.

Conclusions: This retrospective study indicates that stage IVA LA-NPC patients with detectable EBV-DNA after two IC cycles benefit from a third cycle, whereas no clear benefit of a third cycle is observed in stage III patients or those with undetectable post-IC2-EBV-DNA.

Purpose: Concurrent chemoradiotherapy (CCRT) is the standard therapy for limited-stage small-cell lung cancer (LS-SCLC) but induces cancer therapy-induced thrombocytopenia (CTIT), which leads to treatment delays. This study aims to assess the efficacy and safety of prophylactic recombinant human thrombopoietin (rhTPO) in preventing CTIT in this patient population.

Methods and materials: This prospective, multicenter, phase II trial was conducted across 14 Chinese centers. LS-SCLC patients receiving etoposide plus cisplatin (EP) or carboplatin (EC) chemotherapy with concurrent radiotherapy were given subcutaneous rhTPO (300 IU/kg/day) on Days 1-5, 8-12, and 15-19 during radiotherapy. rhTPO treatment was stopped if platelet count reached ≥300 × 10⁹/L or increased by ≥100 × 10⁹/L from baseline. Primary endpoints were the nadir and peak platelet count.

Results: From March 8, 2024, to October 10, 2024, 56 LS-SCLC patients were enrolled. During rhTPO treatment period, nadir platelet count (× 10⁹/L) was 128.54 ± 54.15, and peak platelet count reached 409.23 ± 173.50. Overall incidence of CTIT was 33.9% (19/56) including 8.9% (5/56) Grade 3 and no Grade 4-5 events. A total of 78.9% of patients (15/19) experienced platelet count recovery to ≥100 × 10⁹/L during the rhTPO treatment period. Median time for platelet count recovery from <100 × 10⁹/L to ≥100 × 10⁹/L was 8 days (95% CI: 6-14). Multivariable logistic regression analysis revealed that low baseline platelet count (< 150 × 10⁹/L) was an independent risk factor for developing CTIT [OR = 4.26, 95% CI: 1.08-16.78; p = 0.038]. No patients required platelet transfusions or experienced radiotherapy interruptions, and only one patient required a reduction in the dose of chemotherapy throughout entire study. Moreover, no serious adverse events were reported. rhTPO-related adverse reactions were infrequent and predominantly Grade 1 (e.g., transient platelet elevation).

Conclusions: Prophylactic rhTPO during CCRT for patients with LS-SCLC demonstrated a potential benefit in maintaining platelet counts with a low incidence of CTIT. These findings support further investigation of rhTPO as a preventive strategy for high-risk CTIT patients.

Background: Radiation necrosis (RN) is an adverse event following stereotactic radiosurgery (SRS) for brain metastases (BMs). The planning target volume (PTV) size is a potential yet suboptimal predictor of RN, that unlike V12, remains independent of the number of fractions delivered. Prior authors demonstrated that radiation-induced brain injury can be traced in peripheral blood. This study aimed to identify predictive biomarkers of symptomatic RN at the time of SRS to develop a risk prediction model based on inflammatory proteomic plasma markers and the PTV as dosimetric surrogate.

Methods: A retrospective study design was conducted using plasma samples from BMs patients treated with SRS (stereotactic radiosurgery, single fraction) or FSRT (fractionated stereotactic radiotherapy, 3-6 fractions). The Olink 96 Target Immuno-Oncology Panel was performed to analyze 92 related human proteins using oligonucleotide-bound antibodies and real-time polymerase-chain reaction. Statistical analyses included ROC curves and multivariable Cox proportional hazards (PH) regression to evaluate clinical parameters, PTV, and blood biomarkers to predict RN risk. Multiplex immunophenotyping was performed on available RN tissue samples to assess immune infiltration.

Results: A total of 47 BMs patients were analyzed (21 cases with RN and 26 without). Cox regression analysis identified PTV and the inflammation-related blood biomarkers MUC-16 and CXCL11 as independent predictors of RN. A high Necrosis Prediction Index (NPI) combining PTV with MUC-16 and CXCL11 was significantly associated with higher risk (HR=2.543 [1.615 - 4.005], p<0.0001) of RN development. ROC analysis demonstrated that the NPI effectively distinguished patients with RN, achieving an AUC of 0.808. An exploratory independent analysis found that baseline levels of other proinflammatory blood biomarkers (i.e. CD8a and IL-8) could also be associated with RN. Tissue analysis confirmed a pro-inflammatory microenvironment in RN compared to tumor recurrence.

Conclusions: This hypothesis-generating study suggests the combination of PTV, CXCL11 and MUC-16 may predict development of RN, warranting further validation.

Purpose: For children treated for medulloblastoma, reducing the radiation dose to specific brain substructures may be crucial for preserving cognitive function. However, it remains unclear which substructures are most critical and what the optimal dose levels should be. Voxel-based analysis (VBA) enables the study of dose-response relationships in patients, without requiring a priori hypotheses about which substructures are most relevant.

Methods: In a cohort of 141 children treated for medulloblastoma with photon radiotherapy between 1996 and 2013, we employed VBA to investigate the relationship between radiation dose and neurocognitive outcomes. Specifically, the outcomes of interest were the decline of cognitive test scores, representing the longitudinal change in processing speed or working memory.

Results: VBA identified an association between a decline in processing speed and increased radiation dose in a region in the frontal lobe and anterior midline structures. This relationship remained significant in multivariable analysis, with a change in the age-adjusted processing speed decline per year of -0.11 units/year per Gy increase in dose to the region. Additionally, older age at treatment was found to be protective, while the use of a shunt for managing hydrocephalus was associated with a decline in processing speed. However, no association was found between radiation dose and working memory.

Conclusion: Our analysis shows the potential of VBA in identifying new dose-response relationships in paediatric brain tumour radiotherapy. Improving our understanding of which brain regions are more sensitive to radiation could help inform future radiotherapy planning. Alongside considerations of disease control and other treatment effects, this could support the preservation of cognitive function in long-term survivors.

Background: NRG/RTOG 1016 was a phase III randomized non-inferiority de-escalation trial comparing cetuximab vs cisplatin, concurrent with accelerated radiation (RT) 70 Gy/6 weeks, in p16+ oropharyngeal cancer (OPC). Quality of life (QOL) was a secondary endpoint.

Methods: Eligible/consenting patients among the first 400 entered completed the EORTC QLQ-C30/H&N35 at baseline, end of treatment, 3, 6, and 12 months post-treatment, to provide 90% power to detect an effect size of 0.5 in the between-arm change in QOL scores from baseline to 6 months. We report completion, responsiveness, and patterns over time across domains between arms, considering a difference of > 10 points as clinically significant.

Results: Consent to the QOL substudy was 91%, with analyzable data in 375 patients. No significant differences in patient/tumor characteristics were found by QOL participation status. Completion at the 5 timepoints did not differ by arm (IMRT+cisplatin/cetuximab) and was: 92/94%, 74/77%, 76/81%, 76/81%, and 73/74%. No significant difference was observed between arms for the 6-month change from baseline on any domain. At the end of treatment, all domains showed statistically and clinically significant mean worsening across both arms except Emotional Functioning, Dyspnea, Financial Difficulties, Diarrhea, and Teeth. By 6 months, drops > 10 points remained for: Senses, Social Eating, Opening Mouth, Dry Mouth, Sticky Saliva; and at 12 months for Senses, Trouble with Social Eating, Opening Mouth, Dry Mouth, Sticky Saliva, Pain Killers, and Weight Gain. Pain Killer reduced at both 6 and 12 months.

Conclusion: Although replacing concurrent IMRT+cisplatin with IMRT+cetuximab did not improve global health status or swallowing at 6 months, this study supports the responsiveness of the EORTC QLQ-C30/H&N35 to the effects of IMRT+systemic therapy for OPC. Dry Mouth, Sticky Saliva, and Senses showed large, significant, and persistent impairment, whereas domains related to eating (Swallowing, Appetite, Nutritional Supplements, Social Eating, and Weight Loss) did not show sustained significant impairment in this study.

Purpose: Computed tomography ventilation imaging (CTVI) has great potential for clinical translation and has been validated in numerous studies. However, previous studies focused on image comparisons, and little is known about dosimetric implications of "good" or "poor" image correlations or agreements in radiotherapy (RT). This study assessed the agreement of dose-function metrics between CTVI and hyperpolarized ³He magnetic resonance imaging (³He MRI) as a reference.

Methods and materials: This study included 27 patients with non-small-cell lung cancer who were randomized in a phase 2 trial examining ³He MRI-guided functional avoidance RT. All patients underwent 4-dimensional CT and ³He MRI. CTVI was retrospectively created. Pearson correlation and Bland-Altman analyses were performed to assess the agreements between ³He MRI- and CTVI-based well-ventilated lung dose-function metrics, including functional V_20Gy (fV_20Gy) and functional mean lung dose (fMLD), of RT plans. To assess the associations between dose-function metrics and clinical outcomes, we dichotomized patients by a clinically meaningful decline in Functional Assessment of Cancer Therapy-Lung: Lung Cancer Subscale (LCS) (≥ 3-point) and the occurrence of grade ≥ 2 Radiation pneumonitis (RP), and compared the dose-function metrics between the two groups.

Results: Correlation coefficients of dose-function metrics were 0.80-0.82 for both fV_20Gy and fMLD. Bland-Altman analyses showed mean difference < 1% for fV_20Gy with 95% limits of agreement of 8-10% indicating that agreements varied among patients. Among LCS-evaluable patients (n = 20), those with a ≥ 3-point decline (n = 8) had higher fV_20Gy than those without (CTVI: 28.2% vs. 21.9%, p = 0.05; ³He MRI: 26.2% vs. 22.3%, p = 0.24). Patients with grade ≥ 2 RP (n = 4) also showed higher values than those without (CTVI: 28.2% vs 24.2%, p = 0.34; ³He MRI: 27.0% vs 23.5%, p = 0.25).

Conclusions: CTVI demonstrated strong correlations and small bias in dose-function metrics with ³He MRI, including fV_20Gy and fMLD. These findings support CTVI as a ventilation surrogate for functional avoidance RT.

Extranodal natural killer/T-cell lymphomas (NKTCL) is a rare and aggressive extranodal non-Hodgkin lymphoma. These evidence-based recommendations for NKTCL by the American Radium Society were developed by a multidisciplinary panel of medical oncologists and radiation oncologists to propose treatment approaches. This guideline was based on a literature review with a consensus methodology to rate the appropriateness of treatment recommendations for each NKTCL clinical presentation. Six variants highlight the recommended treatment strategies.