Radiation Oncology最新文献

Introduction: Growth differentiation factor 15 (GDF15) is a cytokine of the TGFβ family. Here, we analyzed GDF15 levels in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who participated in OCOG-ALMERA (NCT02115464), a phase II randomized clinical trial, that investigated metformin in combination with standard of care concurrent chemoradiotherapy (cCRT). OCOG-ALMERA was not able to demonstrate benefit in the metformin arm. Therefore, biomarker studies are needed to better define stratification parameters for future trials.

Methods: Patients were randomized to treatment with platinum-based chemotherapy and concurrent chest radiotherapy (60-66 Gy), with or without metformin (2000 mg/d). The trial collected tumor volume parameters, survival outcomes, and patient blood plasma at baseline, during (weeks 1 and 6) and 6 months after cCRT. Plasma GDF15 levels were assayed with the ELISA method. Statistical analyses explored associations between GDF15, survival outcomes, and radiotherapy tumor volumes.

Results: Baseline plasma levels of GDF15 were elevated in study patients, they increased during cCRT (p < 0.001), and the addition of metformin was associated with a further increase (week 6, p = 0.033). Baseline GDF15 levels correlated with the radiotherapy gross target volume (GTV, p < 0.01), while week 1 of radiotherapy levels correlated with radiotherapy planned target volume (PTV, p < 0.006). In multivariate analysis, baseline plasma GDF15 was prognostic for poor relapse-free (RFS) and overall survival (OS) (p = 0.005 and p = 0.002, respectively).

Conclusions: GDF15 is a plasma marker that responds to the treatment of unresected LA-NSCLC with cCRT and metformin. GDF15 levels correspond with tumor volume and increased GDF15 levels predict for poor RFS and OS. These results require validation in larger clinical trial datasets.

Background: Tyrosine Kinase Inhibitors (TKIs) is an important therapy for patients with oncogene-mutated Non-Small Cell Lung Cancer (NSCLC). However, acquired resistance remains a major challenge. The efficacy of TKIs plus thoracic radiotherapy (RT) in oncogene-mutated NSCLC patients is uncertain. Therefore, we performed a meta-analysis to comprehensively evaluate the efficacy and safety of thoracic RT plus TKIs in oncogene-mutated NSCLC patients.

Methods: The following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane Library. Studies comparing the efficacy and safety of TKIs plus RT with TKIs alone in oncogene-mutated NSCLC patients were included in this analysis. Outcomes were median progression-free survival (mPFS), median overall survival (mOS), and incidence of adverse events (AEs). This analysis performed a subgroup analysis of the efficacy of first-line TKIs in combination with RT.

Results: This meta-analysis included 12 studies with 2936 patients (n = 823 patients with TKIs plus thoracic RT, n = 2113 patients with TKIs alone). The results showed that patients who received treatment with TKIs plus thoracic RT were associated with superior mPFS and mOS than those who were treated with TKIs alone (hazard ratio [HR]: 0.42, 95% CI 0.30-0.59, p < 0.00001; HR: 0.56, 95% CI 0.41-0.70, p < 0.00001, respectively). Subgroup analyses showed that TKIs plus thoracic RT as first-line treatment was associated with better mPFS and OS (HR: 0.37, 95% CI 0.26-0.52, p < 0.00001; HR: 0.47, 95% CI 0.31-0.70, p = 0.0002, respectively). Although the combination of TKIs with thoracic RT was associated with an increased risk of total AEs (odds ratio [OR]: 1.17, 95% CI 1.06-1.29, P = 0.002), there was no significant difference in serious AEs (grade ≥ 3) (OR: 1.06, 95% CI 0.58-1.92, P = 0.86). The most frequently occurring radiation-related AEs were radiation pneumonitis, radiation esophagitis, and radiation dermatitis, with overall rates of 41.3%, 15.4%, and 11.1%, respectively. The incidence of severe radiation pneumonitis and radiation esophagitis was 4.5% and 6.2%, respectively.

Conclusions: In comparison to TKIs alone, TKIs plus thoracic RT are associated with survival benefits, especially as a first-line treatment option. Although TKIs plus thoracic RT may increase the risk of total AEs, it did not increase the risk of severe AEs. Therefore, TKIs plus thoracic RT may be a promising therapeutic regimen for oncogene-mutated NSCLC patients.

Background: In locally advanced rectal cancer, the prediction of tumor response during and after neoadjuvant treatment remains challenging. In terms of organ preservation, adaptive radiotherapy, and intensified (total) neoadjuvant therapies, biomarkers are desirable for patient stratification.

Methods: In 16 patients, weekly blood samples (n = 86) to detect cell-free tumor DNA (ctDNA) during long-course neoadjuvant chemoradiotherapy were analyzed. Data were correlated with initial tumor volumes, MRI response in week 2 and 5 of radiotherapy as well as with pathologic tumor response after resection and outcome parameters.

Results: Most patients showed decreasing ctDNA during the course of radiochemotherapy. However, we found heterogenous dynamics of ctDNA and could identify three groups: (1) decline (2) no clear decline and/or late shedding (3) persistence of ctDNA. In seven patients we could detect significant amounts of ctDNA in week 5 or week 6 of treatment. In our pilot cohort, we did not find significant correlations of ctDNA dynamics with pathologic response or outcome parameters. However, patients with distinct decline of ctDNA had larger tumor volumes prior to treatment, and MRI imaging in week 2 and 5 revealed bigger absolute decrease of tumor volumes. If significant levels of ctDNA were found in week 5 and / or 6, patients showed less absolute tumor volume decrease in week 2 and 5.

Conclusions: Weekly measurement of ctDNA during radiochemotherapy is feasible and might represent a promising biomarker. Bigger initial primary tumors showed different ctDNA shedding profiles compared with smaller primary tumors and correlations of ctDNA dynamics with early imaging response were found.

Objective: This study aims to evaluate the efficacy and safety of 3D printing technology in brachytherapy for cervical cancer, comparing its outcomes with conventional free hand implantation brachytherapy.

Methods: A total of 50 cervical cancer patients treated at the First Affiliated Hospital of Gannan Medical College from January 2019 to July 2023 were included in this study. Patients were divided into two groups: 25 patients received intensity-modulated radiotherapy (IMRT) combined with 3D-printed brachytherapy, and 25 patients underwent IMRT combined with free hand brachytherapy implantation. Key indicators analyzed included short-term therapeutic effects, survival outcomes, operation times, the number of CT scans, the number of needles inserted, dosimetric parameters, and complications.

Results: The use of 3D-printed brachytherapy significantly improved the safety of radiation therapy operations, especially for large tumors (≥ 30 mm), by providing more precise dose distribution and reducing the radiation doses received by critical organs such as the bladder and rectum. Compared to the artificial implant group (88% prevalence), the 3D-printed brachytherapy group showed a significantly lower incidence of radiation enteritis (29.2% prevalence, p < 0.001). There were no significant differences in other complications between the two groups. For instance, the incidence of radiation cystitis was relatively high in the 3D-printed brachytherapy group (79.2% prevalence) compared to the artificial implant group (64% prevalence, p = 0.240). The median follow-up period in this study was 22.5 months [IQR 18-29]. Among the 49 patients included, 43 had cervical squamous carcinoma and 6 had cervical adenocarcinoma. Short-term therapeutic response rates were comparable, with no significant difference in overall survival observed between the two groups.

Conclusion: 3D-printed brachytherapy offers a more effective and safer therapeutic option for patients with cervical cancer, particularly for those with large tumors or complex anatomical structures.

Background: Complex high-precision radiotherapy, such as stereotactic body radiotherapy (SBRT), should only be offered to patients with sufficiently long survival. In the context of bone metastases radiotherapy, low rates of treatment close to the end of life, e.g. last 30 days (RT30), may serve as a quality of care indicator. While traditional, pain-relieving short-course regimens have been studied comprehensively, real-world SBRT results are still limited.

Methods: Retrospective analysis (2010-2023, n = 1117 episodes) of patients with bone metastases treated with traditional single-fraction (8 Gy × 1) or multi-fraction regimens (often 4 Gy × 5 or 3 Gy × 10) compared to stereotactic single-fraction (12-16 Gy × 1) or multi-fraction regimens.

Results: Except for gender, almost all baseline variables were uneven distributed. Failure to complete fractionated radiotherapy was uncommon in the stereotactic (4%) and non-stereotactic group (3%), p = 1.0. With regard to RT30, relevant differences emerged (19% for 8-Gy single-fraction versus 0% for stereotactic single-fraction, p = 0.01). The corresponding figures were 11% for multi-fraction non-stereotactic and 2% for multi-fraction stereotactic, p = 0.08. Median overall survival was shortest after 8-Gy single-fraction irradiation (4.2 months) and longest after stereotactic multi-fraction treatment (13.9 months). Neither stereotactic radiotherapy nor multi-fraction treatment improved survival in multivariate Cox regression analysis. Factors significantly associated with longer survival included better performance status, lower LabBM score (5 standard blood test results), stable disease outside of irradiated area(s), metachronous distant metastases, longer time interval from metastatic disease to bone irradiation, and outpatient status.

Conclusion: The implementation of SBRT for selected patients has resulted in low rates of non-completion and RT30. Optimal selection criteria remain to be determined, but in current clinical practice we exclude patients with poor performance status, unfavorable blood test results (high LabBM score) and progressive disease sites not amenable to SBRT. Established, guideline-endorsed short-course regimens, especially 8-Gy single-fraction treatment, continue to represent an important palliative approach.

Background: Head and neck squamous cell carcinoma (HNSCC) negative for Human Papillomavirus (HPV) has remained a difficult to treat entity, whereas tumors positive for HPV are characterized by radiosensitivity and favorable patient outcome. On the cellular level, radiosensitivity is largely governed by the tumor cells` ability to repair radiation-induced DNA double-strand breaks (DSBs), but no biomarker is established that could guide clinical decision making. Therefore, we tested the impact of the expression levels of ATM, the central kinase of the DNA damage response as well as DNA-PKcs and Ku80, two major factors in the main DSB repair pathway non-homologous end joining (NHEJ).

Methods: A tissue microarray of a single center HNSCC cohort was stained for ATM, DNA-PKcs and Ku80 and the expression scored based on staining intensity and the percentages of tumor cells stained. Scores were correlated with clinicopathological parameters and survival.

Results: Samples from 427 HNSCC patients yielded interpretable stainings and were scored following an established algorithm. The majority of tumors showed strong expression of both NHEJ factors, whereas the expression of ATM varied more. The expression scores of ATM and DNA-PKcs were not associated with patient survival. For HPV-negative HNSCC, the minority of tumors without strong Ku80 expression trended towards superior survival when treatment included radiotherapy. Focusing stronger on staining intensity to define the subgroup with lowest and therefore potentially insufficient expression levels in the HPV-negative subgroup, we observed significantly better overall survival for patients treated with radiotherapy but not with surgery alone.

Conclusions: Our data suggest that HPV-negative HNSCC with particularly low Ku80 expression represent a highly radiosensitive subpopulation. Confirmation in independent cohorts is required.

Background and purpose: Magnetic resonance imaging is indispensable for the preoperative diagnosis of glioma. This study aimed to investigate the role of the apparent diffusion coefficient values as predictors of survival in patients with gliomas.

Methods and materials: A retrospective analysis was conducted on 101 patients with gliomas who underwent surgery between 2015 and 2020. Diffusion-weighted MRI was performed before the surgery. The regions of interest were categorized into parenchymal area, non-enhancing peritumoral area, and necrotic or cystic area. All the patients were divided into three subgroups: the parenchyma group, the non-enhancing peritumoral signal abnormality group, and the necrosis or cyst group. Univariate and multivariate analyses were performed using COX regression.

Results: In the parenchymal group, Ki67, P53, IDH, and the high or low ADC values were identified as independent prognosticators for disease-free survival, while Ki67, IDH, and the high or low ADC values for overall survival. In the non-enhancing peritumoral signal abnormality group, Ki67, P53, IDH, and the ADC _{parenchymal area}/ADC _{non-enhancing peritumoral area} ratio were identified as independent prognostic factors for disease-free survival, while Ki67, IDH, and the ADC _{parenchymal area}/ADC _{non-enhancing peritumoral area} ratio for overall survival. In the necrosis or cyst group, Ki67 was significantly associated with disease-free survival, while Ki67 and the ADC value of the necrotic or cystic area for overall survival.

Conclusions: The ADC values, including the ADC value in the parenchymal area, the ADC _{parenchymal area}/ADC _{non-enhancing peritumoral area} ratio, and the ADC value in the necrotic or cystic area, can serve as an efficient and potential index for predicting the survival of patients with glioma.

Background and introduction: Increasing evidence suggests that a subgroup of patients with oligometastatic cancer might achieve a prolonged disease-free survival through local therapy for all active cancer lesions. Our aims are to investigate the impact of brain metastases on the classification, treatment, and outcome in these patients.

Materials and methods: We analyzed a total of 7,000 oncological positron emission tomography scans to identify patients with extracranial oligometastatic disease (defined as ≤ 5 intra- or extra-cranial metastases). Concurrent magnetic resonance imaging brain was assessed to quantify intracranial tumor burden. We investigated the impact of brain metastases on oligometastatic disease state, therapeutic approaches, and outcome. Predictors for transitioning from oligo- to polymetastatic states were evaluated using regression analysis.

Results: A total of 106 patients with extracranial oligometastases and simultaneous brain metastases were identified, primarily originating from skin or lung/pleura cancers (90%, n = 96). Brain metastases caused a transition from an extracranial oligometastatic to a whole-body polymetastatic state in 45% (n = 48) of patients. While oligometastatic patients received systemic therapy (55% vs. 35%) more frequently and radiotherapy for brain metastases was more often prescribed to polymetastatic patients (44% vs. 26%), the therapeutic approach did not differ systematically between both sub-groups. The oligometastatic sub-group had a median overall survival of 28 months compared to 10 months in the polymetastatic sub-group (p < 0.01).

Conclusion: In patients with brain metastases, a low total tumor burden with an oligometastatic disease state remained a significant prognostic factor for overall survival. Presence of brain metastases should therefore not serve as exclusion criterion for clinical trials in the field of oligometastatic disease. Moreover, it underscores the importance of considering a multimodality treatment strategy in oligometastatic cancer patients.

Background: This study aims to assess the clinical efficacy of elective neck irradiation (ENI) in patients with esthesineuroblastoma (ENB), a rare malignant neoplasm, who are clinically node-negative.

Methods: We conducted a retrospective analysis of 178 patients newly diagnosed with ENB at our institution between 2009 and 2021. Propensity score matching (PSM) was employed to compare node-negative patients treated with and without ENI. We extensively examined survival outcomes and treatment failure.

Results: Of the 178 participants, 149 (83.7%) were lymph node-negative and staged in Modified Kadish A-C. 96 patients underwent ENI treatment, while 53 did not. At baseline, patients who received ENI differed from those who did not in terms of radiotherapy technique, staging, orbital invasion, surgical mode, and chemotherapy. After PSM, 43 pairs were available for analysis. ENI was observed to extend overall survival (OS, 5-year 73.9% vs. 84.0%; 3-year 76.9% vs. 97.1%, p = 0.022), progression-free survival (PFS, 5-year 38.5% vs. 84.6%; 3-year 50.5% vs. 94.5%, p < 0.001) and locoregional relapse-free survival (LRFS, 5-year 42.7% vs. 84.6%, p = 0.023; 3-year 57.3% vs. 94.5%, p < 0.001) in node-negative ENI patients. Failure pattern analyses revealed that ENI, which included level Ib, II, VIIa, significantly reduced the treatment failure rate. Furthermore, ENI did not significantly impact the prognosis of T1-2 patients, indicating potential clinical value of ENI in T3-4 patients.

Conclusions: Our findings suggested that ENI decreased regional failure and significantly enhanced LRFS and PFS. ENI may be considered as an integral part of the initial treatment strategy for locally advanced node-negative ENB patients.