Radiation Oncology最新文献

Aim: To characterize the differences of dynamic changes for absolute lymphocyte count (ALC) among esophageal squamous cell carcinoma (ESCC) patients treated with neoadjuvant chemoradiotherapy (nCRT) with or without pembrolizumab, as well as to investigate the clinical and lymphocyte-related organs dosimetric parameters that would impact ALC nadir during nCRT.

Materials and methods: A total of 216 ESCC patients who received nCRT (with pembrolizumab 144; without pembrolizumab: 72) were identified from a prospective cohort. Weekly and 1-month post-nCRT ALC were identified. lymphocyte-related organs at risk (LOARs) were delineated. linear and logistic regression analysis was used to analyze the association between G4 lymphopenia/lymphopenia nadir and clinical/DVHs factors. Receiver-operating characteristic curves were used to derive optimal dosimetric planning constraints. Grade 4 (G4) lymphopenia was defined as ALC < 0.2 × 10⁹/L during nCRT.

Results: G4 lymphopenia was observed in 35 ESCC patients (16.2%) during neoadjuvant treatment. Compared to nCRT alone, the addition of pembrolizumab to nCRT significantly improve lymphopenia recovery in the 1-months after nCRT (p = 0.0003), but the ALC at other time point during nCRT and ALC nadir was comparable between the two groups. A total of 198 patients finally received surgery. Of them, 98 patients archived pCR (49.5%), with 50.4% (68/135 patients) in nCRT with pembrolizumab and 47.6% (30/63) in nCRT alone(p = 0.94), respectively. The mean ALC nadir in the pCR group was significantly higher than those without (p = 0.0003). Multivariable linear and logistic regression analysis indicated that TVB mean dose, TVB V5, TVB V10, TVB V20, mean cardiopulmonary dose, mean ribs dose, mean whole body dose, mean spleen dose, V5, V10, and V20 of spleen dose were significantly associated with developing grade 4 lymphopenia. Dosimetric analysis showed that lymphocyte-sparing photon or proton irradiation was feasible while did not compromise clinically acceptable objectives.

Conclusion: The addition of pembrolizumab to nCRT improved lymphopenia recovery for ESCC after trimodality therapy. ALC nadir was significantly associated with pCR and RFS after nCRT. Sparing of LOARs using advanced radiation techniques might reduce the risk of developing lymphopenia and improve treatment response in the era of immunotherapy.

Purpose: In this retrospective study, we aimed to evaluate the efficacy and incidence of radiation-induced brain necrosis (RBN) after volumetric modulated arc therapy-based stereotactic irradiation (VMAT-STI) for brain metastases.

Methods: In the 220 brain metastatic lesions included between January 2020 and June 2022, there were 1-9 concurrently treated lesions (median 1). A biologically effective dose (BED)10 of 80 Gy and a reduced BED10 of 50 Gy were prescribed to the gross tumor volume (GTV) and planning target volume (PTV) (PTV = GTV + 3 mm) margins, respectively. The number of fractions was adjusted from 3 to 15 to accommodate different GTV sizes; for larger tumor volumes, this was increased while maintaining the BED10 values comparable to those for GTV and PTV margins.

Results: Of the total patients, 16 (7%) exhibited locally progressive lesions; local tumor recurrence was observed in 2 (1%) patients, while RBN was noted in 14 (6%) patients. RBN was significantly more prevalent in the deep white matter around the lateral ventricles (DWM-LV) than in other sites, occurring in 9/22 (41%) lesions of metastases in the DWM-LV. The 2-year actuarial incidence risk of developing RBN was significantly higher in the DWM-LV (69%) than at other sites (5%).

Conclusion: The recurrence rate of brain metastases was low, and the incidence of RBN was lower in tumor sites other than the DWM-LV. However, the frequency of RBN was significantly higher in the DWM-LV region. Additional VMAT-STI-prescribed dose protocols are necessary to reduce RBN incidence in DWM-LVs.

Background: Patients with non-small cell lung cancer (NSCLC) are prone to developing brain metastases (BMs), particularly those with epidermal growth factor receptor (EGFR) mutations. In clinical practice, treatment-naïve EGFR-mutant NSCLC patients with asymptomatic BMs tend to choose EGFR-tyrosine kinase inhibitors (TKIs) as first-line therapy and defer intracranial radiotherapy (RT). However, the effectiveness of upfront intracranial RT remains unclear.

Methods: This was a retrospective study including 217 patients from two institutions between January 2018 and December 2022. Clinical data of NSCLC patients with BMs who received EGFR-TKIs were collected. The patients were assigned to one of the three groups according to the therapeutic modality used: the upfront TKI + stereotactic radiosurgery (SRS) / fractionated stereotactic radiotherapy (fSRS) group (upfront TKI + SRS/fSRS ), the upfront TKI + whole-brain radiotherapy (WBRT) group (upfront TKI + WBRT) and the upfront TKI group.

Results: As of March 8, 2023, the median follow-up duration was 37.3 months (95% CI, 32.5-42.1). The median overall survival (OS) for the upfront TKI + SRS/fSRS, upfront TKI + WBRT, and upfront TKI groups were 37.8, 20.7, and 24.1 months, respectively (p = 0.015). In subgroup analysis, the upfront TKI + SRS/fSRS group demonstrated longer OS compared to the upfront TKI + WBRT and upfront TKI groups in patients treated with first or second-generation EGFR-TKIs (p = 0.021) and patients with L858R mutation (p = 0.017), whereas no survival benefit was observed in three-generation EGFR-TKIs or 19del subgroup. In the multivariable analysis, metachronous BMs, EGFR L858R mutation and nonclassic EGFR mutation were identified as independent risk factors for OS, while a DS-GPA score of 2.0-4.0 was the only independent protective factor.

Conclusions: This study demonstrated that upfront addition of SRS/fSRS to EGFR-TKIs was associated with longer OS compared to upfront WBRT or upfront TKI alone in EGFR-mutant NSCLC patients with BMs. This improvement was more significant in patients with L858R mutation and those treated with first or second-generation EGFR-TKIs. Further research with a larger sample size is warranted.

Purpose: Based on the demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G2/M phase in the afternoon and at night, the present study evaluated the severity of acute radiation esophagitis and treatment outcomes in esophageal squamous cell carcinoma patients receiving radiotherapy (RT) in the daytime versus in the evening.

Methods: From the 488 eligible patients of esophageal squamous cell carcinoma receiving concurrent chemoradiotherapy (CCRT), 369 patients received RT in the daytime (before 19:00) and 119 patients received RT in the evening (after 19:00). The grades of radiation esophagitis (Common Terminology Criteria for Adverse Events version 5.0) and survival outcomes were compared in the two groups. Analyses were performed by using ordinal logistic regression and Cox proportional hazard regression.

Results: The median follow-up was 27 months. In multivariate logistic regression models, evening treatment (after 19:00) (odds ratio, 1.660 [95% CI 1.094-2.518]), tumor length ≥ 5 cm (odds ratio, 1.632 [95% CI 1.102-2.416]), PGTV dose ≥ 59.34 Gy (odds ratio, 1.702 [95% CI 1.099-2.635]), female sex (odds ratio, 2.241 [95% CI 1.475-3.405]), and tumor location in cervical segment and upper thoracic (odds ratio, 1.665 [95% CI 1.043-2.658]) were associated with higher odds of radiation esophagitis. There was no difference in the overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) (all p > 0.05) between the daytime treatment group and evening treatment group. The results of the subgroup analysis showed that no significant difference was found in radiation esophagitis between the two groups with PGTV dose < 59.34 Gy, while there was a higher odds for the Grade 2 or higher radiation esophagitis in the evening treatment group than the daytime treatment group (odds ratio, 1.675 [95% CI 1.062-2.643]) with PGTV dose ≥ 59.34 Gy.

Conclusion: RT in the evening (after 19:00) was associated with higher odds to present esophagitis for esophageal squamous cell carcinoma patients, especially with higher radiation doses, but treatment outcomes did not differ according to the time of RT.

Introduction: Stage IV non-small cell lung carcinoma (NSCLC) with oligometastases is potentially curable by radical treatment. This study aimed to evaluate the efficacy and safety of chemoradiotherapy (CRT) for thoracic disease, including the primary lesion and lymph node metastases, combined with local consolidative therapy (LCT) for oligometastases.

Methods: This was a multicenter Phase II trial for patients with Stage IV NSCLC with oligometastases for whom CRT for thoracic disease was feasible. The treatment procedures included CRT containing platinum-doublet for thoracic disease and LCT for oligometastases within 8 weeks of starting or completing CRT. The primary endpoint was the 2-year survival rate.

Results: We enrolled 19 patients between June 2016 and May 2020. The median age was 68 (range: 51-74) years. Twelve patients had adenocarcinoma, and 6 had squamous cell carcinoma. The metastasis sites included the brain, bone, adrenal gland, lung, and cervical lymph node (n = 9, 7, 2, 1, and 1, respectively). All patients completed CRT concurrently with LCT for all oligometastases. There were 11 partial responses, resulting in a response rate of 58% (95% confidence interval [CI] 33.5-79.7%). Median progression-free survival and overall survival were 8.6 (95% CI 7.0-10.2) and 42.1 (80% CI 13.6-not reached) months, respectively. The 2-year survival rate was 68.4% (80% CI 52.6%-79.9%). Fourteen patients (74%) showed progression with newly observed lesions. There were no severe adverse events, and toxicities were tolerable.

Conclusion: Chemotherapy in combination with aggressive LCT for NSCLC with oligometastases might extend survival and achieve local control.

Clinical trial registration: University Hospital Medical Information Network, Japan (protocol identification number: UMIN000022431, first registration date: 01/JUN/2016).

Introduction: Locoregional recurrence (LR) is common in locally advanced head and neck cancer (HNSCC), posing challenges for treatment. We analysed outcome parameters and toxicities for patients being treated with radiotherapy (RT) for LR-HNSCC and investigated patient and disease related prognostic factors in this prognostically unfavourable group.

Methods: This analysis includes 101 LR-HNSCC patients treated with RT, radio-chemotherapy (RCT) or radio-immunotherapy (RIT) between 2010 and 2018 at a high-volume tertiary centre. Patient characteristics, tumour and treatment details were retrospectively collected. Overall survival (OS), progression-free survival (PFS) and toxicities according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 were assessed.

Results: 62% of patients were radiotherapy-naïve (initial RT group) while 38% were re-irradiated at site of LR (re-RT group). Median OS for initial RT was 24 months, for re-RT 12 months (p < 0.01). In the RCT subgroup, patients with initial RT had significantly longer OS with 35 months compared to re-RT 12 months (p < 0.05). Patients with UICC grade IV tumours and percutaneous endoscopic gastrostomy (PEG) tube had significantly shorter OS in multivariate analysis: initial RT 13 vs. re-RT 32 months and initial RT 12 vs. re-RT 32 months respectively. Salvage surgery before RT at recurrence was a positive prognostic factor for OS (initial RT 35 vs. re-RT 12 months). Other significant factors for longer OS in univariate analysis included low inflammatory status (Glasgow Prognostic Score 0) and radiation doses ≥ 50 Gy. We detected 37 (15%) ≥ CTCAE Grade 3 events for initial RT and 19 (15%) for re-RT patients.

Conclusion: In this analysis, we identified key prognostic factors including PEG tube and inflammation status that could guide treatment decision. Our findings suggest salvage surgery as preferred treatment option with postoperative RT at LR. Adverse events due to re-RT were acceptable. A radiation dose of ≥ 50 Gy should be administered to achieve better outcomes.

Background and purpose: Timely identification of local failure after stereotactic radiotherapy for brain metastases allows for treatment modifications, potentially improving outcomes. While previous studies showed that adding radiomics or Deep Learning (DL) features to clinical features increased Local Control (LC) prediction accuracy, their combined potential to predict LC remains unexplored. We examined whether a model using a combination of radiomics, DL and clinical features achieves better accuracy than models using only a subset of these features.

Materials and methods: We collected pre-treatment brain MRIs (TR/TE: 25/1.86 ms, FOV: 210 × 210 × 150, flip angle: 30°, transverse slice orientation, voxel size: 0.82 × 0.82 × 1.5 mm) and clinical data for 129 patients at the Gamma Knife Center of the Elisabeth-TweeSteden Hospital. Radiomics features were extracted using the Python radiomics feature extractor and DL features were obtained using a 3D ResNet model. A Random Forest machine learning algorithm was employed to train four models using: (1) clinical features only; (2) clinical and radiomics features; (3) clinical and DL features; and (4) clinical, radiomics, and DL features. The average accuracy and other metrics were derived using K-fold cross validation.

Results: The prediction model utilizing only clinical variables provided an Area Under the receiver operating characteristic Curve (AUC) of 0.85 and an accuracy of 75.0%. Adding radiomics features increased the AUC to 0.86 and accuracy to 79.33%, while adding DL features resulted in an AUC of 0.82 and accuracy of 78.0%. The best performance came from combining clinical, radiomics, and DL features, achieving an AUC of 0.88 and accuracy of 81.66%. This model's prediction improvement was statistically significant compared to models trained with clinical features alone or with the combination of clinical and DL features. However, the improvement was not statistically significant when compared to the model trained with clinical and radiomics features.

Conclusion: Integrating radiomics and DL features with clinical characteristics improves prediction of local control after stereotactic radiotherapy for brain metastases. Models incorporating radiomics features consistently outperformed those utilizing clinical features alone or clinical and DL features. The increased prediction accuracy of our integrated model demonstrates the potential for early outcome prediction, enabling timely treatment modifications to improve patient management.

Purpose: To investigate the early predictive value of dynamic magnetic resonance imaging (MRI)-based radiomics for progression and prognosis in locally advanced cervical cancer (LACC) patients treated with concurrent chemoradiotherapy (CCRT).

Methods and materials: A total of 111 LACC patients (training set: 88; test set: 23) were retrospectively enrolled. Dynamic MR images were acquired at baseline (MRI_pre), before brachytherapy delivery (MRI_mid) and at each follow-up visit. Clinical characteristics, 2-year progression-free survival (PFS), and 2-year overall survival (OS) were evaluated. The least absolute shrinkage and selection operator (LASSO) method was applied to extract features from MR images as well as from clinical characteristics. The support vector machine (SVM) model was trained on the training set and then evaluated on the test set.

Results: Compared with single-sequence models, multisequence models exhibited superior performance. MRI_mid-based radiomics models performed better in predicting the prognosis of LACC patients than the post-treatment did. The MRI_pre-, MRI_mid- and the ΔMRI_mid (variations in radiomics features from MRI_pre and MRI_mid) -based radiomics models achieve AUC scores of 0.723, 0.750 and 0.759 for 2-year PFS and 0.711, 0.737 and 0.789 for 2-year OS in the test set. When combined with the clinical characteristics, the ΔMRI_mid-based predictive model also performed better than the other models did, with an AUC of 0.812 for progression and 0.868 for survival.

Conclusion: We built machine learning models from dynamic features in longitudinal images and found that the ΔMRI_mid-based model can serve as a non-invasive indicator for the early prediction of prognosis in LACC patients receiving CCRT. The integrated models with clinical characteristics further enhanced the predictive performance.

Background: Local recurrence of rectal cancer (LRRC) previously treated with radiotherapy is associated with a poor prognosis. Historically, the integration of radiotherapy (RT) with surgery has improved the likelihood of complete resections (R0) and, consequently, enhanced survival. Unfortunately, many LRRC cases are not amenable to surgical intervention. The inclusion of chemotherapy (CHT) alongside advanced RT techniques including proton and carbon ion RT (CIRT) and stereotactic body radiation therapy (SBRT), has generated new treatment options. Therefore, there is a need for improved stratification of LRRC patients to enhance treatment outcomes. The RETRY is an integrated trial with the primary aim to explore if combining CHT with RT in all available modalities can enhance local control (LC) in LRRC patients, consequently improving survival.

Methods: Experts from Italian centers specializing in rectal cancer and LRRC management collaborated to design a prospective multicenter observational study within the AIRO group for gastrointestinal malignancies. Eligible participants are adult LRRC patients who previously had pelvic RT, meet specific criteria, and are affiliated with the participating Italian centers. Specific criteria must be met for CIRT referral. A total of 88 patients will be enrolled over three years. The primary objective is to determine the 3-year LC rate. Secondary outcomes include assessing survival, quality of life, and R0 resection rates in surgery cases. A minimum dose of 40 Gy, conventional fractionation with concomitant fluoropyrimidine-with/without oxaliplatin-based CHT (CRT) is prescribed in neoadjuvant setting. Alternatively, the dose will vary from 35 to 40 Gy in 5 fractions based on clinical judgment, by SBRT. Both proton and photon therapies will be evaluated in these approaches. Surgery will be considered if deemed operable. In inoperable cases, CIRT with a dose of 40-60 Gy relative biological effectiveness (RBE) will be administered with a daily dose fraction ranging between 3 and 4.8 Gy RBE.

Discussion: The RETRY trial aims to investigate the combined effects of RT and CHT and when feasible the addition of surgery, to determine whether this comprehensive approach can result in improved survival and quality of life for LRRC patients. Trial registration number ClinicalTrials.gov (No. NCT05984576).

Background: Rectal cancer patients are potential beneficiaries of adaptive radiotherapy (ART) which demands considerable resources. Currently, there is no definite guidance on what kind of patients and when will benefit from ART. This study aimed to develop and validate a methodology for estimating ART requirements in rectal cancer before treatment course.

Methods and materials: This study involved 66 rectal cancer patients from center 1 and 27 patients from center 2. The ART requirements were evaluated by comparing 8 dose volume histogram (DVH) metrics of targets and organs at risk (OARs) between planning and treatment fractions. Tolerance ranges of deviation of DVH metrics were derived from 10 patients and applied to assess fractional variability. Eighteen features, encompassing diagnostic, dosimetric, and time-related information, were utilized to formulate a stepwise logistic regression model for fraction-level ART requirement estimation. The super parameters were determined through 5-fold cross-validation with 250 training fractions and the methodology was validated with 109 internal testing fractions and 134 external testing fractions.

Results: The area under the curve (AUC) of training dataset was 0.74 (95% CI: 0.61 to 0.85), while in the internal and external testing, the AUC achieved 0.76 (95% CI: 0.60-0.90) and 0.68 (95% CI: 0.56-0.81). Using a best (or clinical applicable) cut-off value of 33.4% (11%), the predictive model achieved a sensitivity of 46.2% (69.2%) and specificity of 97.9% (68.7%). During the modeling, 5 features were retained: Homogeneity index (OR = 6.06, 95% CI: 2.93-14.8), planning target volume (OR = 1.77, 95% CI: 1.17-2.69), fraction dose (OR = 45.37, 95% CI: 5.74-469), accumulated dose (OR = 2.29, 95% CI: 1.35-4.14), and whether neoadjuvant chemoradiotherapy (OR > 1000).

Conclusion: ART requirements are associated with target volume, target dose homogeneity, fraction dose, dose accumulation and whether neoadjuvant radiotherapy. The predictive model exhibited the capability to predict fraction-level ART requirements.