Standard radiation therapy (RT) for locally advanced nonsmall cell lung cancer (LA-NSCLC) employs a uniform dose of approximately 60 Gy. Recent trials demonstrated that RT dose escalation may not improve outcomes and may cause added toxicity. We previously performed a single-arm trial testing a personalized, risk-adapted, and deintensified RT strategy. We now report findings from a randomized trial testing this novel approach.

Patients with LA-NSCLC with Eastern Cooperative Oncology Group performance status 0-2 were eligible for this trial. Metabolic tumor volume for each pulmonary tumor and involved lymph node was calculated using fludeoxyglucose PET. Participants were randomly assigned 1:1 to receive standard RT (60 Gy in 30 fractions delivered to pulmonary tumors and involved lymph nodes) versus dose-painted RT (55 Gy delivered to tumors and lymph nodes with metabolic volume exceeding 20 cm3 and 44-48 Gy to other lesions, all in 20 fractions). Concurrent chemotherapy and standard adjuvant therapy were given in both arms. The primary objective was to characterize patient-reported outcomes using Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events. Secondary objectives included comparing outcomes between study arms.

Fifty patients were enrolled. The most common grade 3 patient-reported adverse events within 90 days of RT completion were dysphagia (38%), fatigue (38%), cough (32%), and wheezing (28%). The median progression-free survival duration is 18 months, and the median overall survival duration is 42 months. Progression-free survival and overall survival rates are similar across study arms (logrank P = .562 and .765, respectively). There have been 3 cases of in-field disease progression, with 1 in the control arm and 2 in the dose-painted arm. Grade 3-4 lymphopenia was reduced with dose-painted RT (48% vs 81%, chi-square P = .012).

High-grade patient-reported toxicity in patients with LA-NSCLC who are treated with concurrent chemoradiotherapy is common. We found no evidence that risk-adapted RT de-escalation compromises clinical outcomes. Follow-up studies testing the ability of this approach to improve the safety profile of chemoradiotherapy are warranted.

The incidence of cervical cancer has been increasing recently, becoming an essential factor threatening patients' health. Positron emission computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI) are multimodal molecular imaging methods that combine functional imaging (PET) and anatomical imaging (CT) with MRI fusion technology. They play an important role in the clinical management of patients with cervical cancer. Precision radiotherapy refers to the use of advanced intensive modulated radiotherapy (IMRT) to give different doses of radiation to different treatment areas to achieve the purpose of killing tumors and protecting normal tissues to the greatest extent. At present, pelvic target delineation is mostly based on CT and MRI, but these mostly provide anatomical morphological information, which is difficult to show the internal metabolism of tumors. PET/CT and PET/MRI combine information on biological function, metabolism and anatomical structure, thereby more accurately distinguishing the boundaries between tumor and non-tumor tissues and playing a positive guiding role in improving radiotherapy planning (RTP) for cervical cancer and evaluating treatment effect.

A higher estimated dose of radiation to immune cells (EDRIC) has been proposed as an explanation for failed attempts at thoracic radiation intensification as a part of concurrent chemoradiotherapy (cCRT) for locally advanced non-small-cell lung cancer (NSCLC), as lymphopenia in particular is a negative prognostic factor in this context. We studied the impact of EDRIC on survival in this secondary analysis of the prospective PET-Plan trial (ARO-2009-09; NCT00697333). Considering the immune system as an organ at risk for radiotherapy is of major importance in the current era of consolidation immunotherapy.

Eligible patients had previously received chemoradiotherapy up to 60-74 Gy with radiation treatment planning based on an 18F-FDG PET/CT targeting all CT positive lymph nodes plus 50 Gy elective nodal irradiation (arm A) versus targeting only PET-positive nodes (arm B). EDRIC was calculated with the original model by Jin et al. in addition to a modified score with cohort-specific weight parameters.

Sufficient data were available in 153 patients with a median follow-up time (95 % confidence interval [CI]) of 41.6 (34.6 - 53.7) months. Using the original model, the mean EDRIC (range) was 5.70 (3.23 - 8.44) Gy and showed a strong inverse correlation with PFS (hazard ratio [HR] = 1.77; 95 % CI 1.23-2.54; p = 0.002) and OS (HR = 1.72; 95 % CI 1.12-2.65; p = 0.01). The mean modified EDRIC (range) was 5.30 (3.01 - 8.38) Gy, again with a strong inverse correlation with PFS (HR = 1.66; 95 % CI 1.16-2.38; p = 0.006) but not OS (HR = 1.40; 95 % CI 0.91-2.15; p = 0.122). Neither radiation treatment allocation (arm A vs. B) nor technique (3D-CRT vs. IMRT) influenced EDRIC (p = 0.889 and p = 0.958, respectively) and EDRIC did not influence the rate of early or delayed hematological toxicity. On multivariate analysis, mean body dose (MBD) was the main contributing factor of the EDRIC equation to PFS and OS.

Higher doses of radiation to the immune system were associated with worse PFS in this secondary analysis of the PET-Plan trial. The omission of elective nodal irradiation did not influence EDRIC. MBD could potentially suffice as a surrogate for EDRIC, as it is more readily available and requires fewer calculations. Future trials should aim to refine existing models and investigate ways to reduce EDRIC to limit its effects in patients undergoing cCRT for locally advanced NSCLC.

The association of cardiac dosimetric parameters with survival in lung cancer patients is well established. However, most research has concentrated on patients undergoing definitive treatment. This study aims to investigate the relationship between cardiac dosimetric parameters and survival in patients receiving postoperative radiotherapy (PORT).

Sixty patients who received PORT between 2011 and 2021 were retrospectively evaluated. The substructures of the heart were delineated on the simulation computed tomography scans of the patients. Univariate and multivariate Cox regression analyses were conducted to investigate the correlation between dosimetric parameters and overall survival. The Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM Corp., Armonk, NY, USA) was utilized for statistical analyses.

Right atrium (RA) maximum dose (Dmax) was the only variable that was significantly associated with a shorter OS. Further receiver operating characteristic (ROC) analysis revealed that the optimum cut-off value for RA Dmax was 43.6 Gy, with a sensitivity of 69% and a specificity of 62%. In addition, inclusion of the upper right paratracheal (2R), lower right paratracheal (4R), left pulmonary ligament (9L), and right hilus (10R) lymphatic stations in the treatment field led to an increase in RA Dmax.

The results of this retrospective study show that RA Dmax appears to have an impact on overall survival in patients undergoing PORT. Limiting the RA Dmax dose to below 43.6 Gy and avoiding elective nodal irradiation might potentially enhance survival in this patient cohort.

PET is a versatile imaging modality widely used in oncology for diagnosing, staging, predicting outcomes, and surveillance for a variety of cancers. In radiation oncology, combining PET and computed tomography imaging can markedly enhance treatment planning through improved target volume delineation. This review examines data and clinical approaches across 3 major cancer types to evaluate the role of PET in target volume delineation, with data and current approaches for thoracic, genitourinary, and head and neck malignancies detailed. Additionally, it emphasizes various practical applications of PET in radiation therapy planning, several of which have been recently demonstrated in clinical trials.

The purpose of this study was to assess the prognostic value of 18F-FDG PET parameter variation between baseline and 42 Gy (PET2) of radiochemotherapy at 6 mo and 1 y of evaluation in patients with stage III inoperable nonsmall cell lung cancer based on RECIST 1.1. Methods: In total, 158 patients in a prospective multicenter phase II/III study were analyzed. Patients were randomized into 2 groups: an experimental arm (group A) and a standard arm (group B). Patients from group A with residual metabolism on PET2 (group A+) at 42 Gy received a radiation boost (74 Gy). Patients without residual uptake on 18F-FDG PET at 42 Gy (group A-) and patients in group B received a standard radiotherapy dose (66 Gy). We compared group A with group B. The 18F-FDG PET parameters SUVmax, SUVmean, SUVpeak, peak SUV normalized on lean body mass, mean SUV normalized on lean body mass, total lesion glycolysis, total metabolic tumor volume (MTV) (tumor and nodes), and tumor MTV were measured. All patients were evaluated with RECIST 1.1 using CT at 6 mo and 1 y after radiochemotherapy. Progression-free survival and overall survival were evaluated. Results: Except for the radiotherapy dose (P < 0.001), patient demographic characteristics were similar between the 2 groups (A vs. B). All 18F-FDG PET uptake and volume parameter measurements were correlated. Therefore, only the change in SUVmax (ΔSUVmax) and total MTV were selected for the analysis. There was no significant difference in any variable between the 2 groups. In the multivariate analysis, ΔSUVmax appeared to be the most important prognostic factor for overall survival, and SUVmax of PET2 appeared to be the most important prognostic factor for progression-free survival. Conclusion: 18F-FDG PET at 42 Gy can be used to identify good responders to radiochemotherapy in patients with inoperable stage III nonsmall cell lung cancer. The SUVmax of PET2 and ΔSUVmax are independent prognostic factors.

We previously reported unexpected high rates of severe esophageal toxicity (ET) in patients with stage II-III non-small cell lung cancer treated in the randomized ARTFORCE PET-Boost dose-escalation trial (clinicaltrials.gov: NCT01024829). The aim of this study is to evaluate clinical factors and dose metrics associated with ET in patients treated within the trial.

Patients received 24 fractions of 3.0-5.4 Gy, planned isotoxically to the primary tumor as a whole (>4 cm) or to an 18F-FDG-PET defined subvolume within the primary tumor. Lymph nodes received 24 × 2.75Gy. Radiation therapy was combined with concurrent or sequential chemotherapy, or given alone. We evaluated the incidence and time to grade ≥ 3 (G ≥ 3) ET, and patient-reported symptoms. Follow-up time was estimated using the reverse Kaplan-Meier method. Uni- and multivariable logistic regression analyses with Firth's penalization were performed to assess the associations between clinical variables, dose parameters, and the incidence of G ≥ 3 ET.

Median follow-up was 73.3 months. Of 107 patients randomized, 24(22.4%) experienced G ≥ 3 ET. There were 3 (2.8%) ET-related deaths, all esophageal fistulas. Median esophagus mean dose and D0.1% (EQD2) were 25.2 Gy (IQR, 18.9-33.2), and 69.5Gy (IQR, 66.4-75.4), respectively. G ≥ 3 ET occurred less frequently (19/54[35.2%] vs 5/53[9.4%]; P = .001) after a dose constraint for esophagus + 5 mm was introduced mid-trial (D0.1% < 70 Gy EQD2). Concurrent platinum-doublet chemotherapy, (compared with concurrent daily low-dose cisplatin or sequential/no chemotherapy) and higher esophageal doses, especially volume receiving >50 Gy, near maximum doses, and the equivalent uniform dose, were significantly associated with G ≥ 3 ET in multivariable regression.

Concurrent platinum-doublet chemotherapy, as well as high doses to the esophagus, was independently associated with risk of severe ET. Stricter dose constraints led to significant reduction in G ≥ 3 ET. Future dose-escalation studies should lower doses to the esophagus, especially when combined with concurrent chemotherapy.

This study aimed to develop and evaluate a novel fibroblast activation protein (FAP)-specific tracer, fluorine-18-labeled fibroblast activation protein inhibitor-FUSCC-07 ([18F]F-FAPI-FUSCC-07), for use in both preclinical and clinical settings. Preclinical evaluations were conducted to assess the stability and partition coefficient of [18F]F-FAPI-FUSCC-07. Experiments involving human glioma U87MG cells demonstrated its cellular uptake and inhibitory properties. Further investigations included biodistribution analysis and micropositron emission tomography/computed tomography (PET/CT) imaging in U87MG tumor-bearing mice, which revealed strong tumor uptake and prolonged retention. In the clinical setting, [18F]F-FAPI-FUSCC-07 was compared directly with [18F]F-FAPI-42 and [18F]F-FAPI-74 to evaluate its performance in imaging various cancers. By expanding the patient cohort, the study provided a more comprehensive assessment of tracer uptake in lesions. The findings demonstrated that [18F]F-FAPI-FUSCC-07 exhibited high stability in phosphate-buffered saline and fetal bovine serum, as well as hydrophilic properties. Clinical imaging results indicated significantly higher tumor uptake and improved target-to-blood pool ratios compared to the other tracers. Moreover, PET imaging of patients with diverse cancers showed that [18F]F-FAPI-FUSCC-07 consistently provided superior image contrast in most cases. These results represent the first clinical evidence supporting the feasibility of [18F]F-FAPI-FUSCC-07 for imaging across multiple tumor types. The study highlights its potential as a promising tracer for FAPI PET imaging, offering enhanced diagnostic precision and broader applicability in oncology.

Progression-free (PFS) and overall survival (OS) in UICC stage III non-small cell lung cancer (NSCLC) after definitive concurrent chemoradiotherapy (CRT) can be increased with consolidating immunotherapy. Recent studies have shown a strong predictive value of gross tumor volume (GTV) changes during CRT on OS. The TORCH trial investigated the prognostic impact of GTV changes during CRT as a predictor for a response to immunotherapy.

This retrospective non-interventional observational multicenter trial included n = 203 patients from 10 German university centers for radiation oncology with confirmed inoperable NSCLC in UICC stage III A-C. Patients had received CRT between 2015 and 2023 as a curative-intent treatment approach. Patient and tumor characteristics were collected anonymously via electronic case report forms. Initial GTVs before CRT (initial planning CT, GTV1) and at 40-50 Gy (re-planning CT for radiation boost, GTV2) were delineated. Absolute and relative GTV changes before/during CRT were correlated with OS to predict the response to CRT with sequential immunotherapy. Hazard ratios (HR) of survival analyses were estimated using adjusted Cox regression models.

The mean GTV1 before radiation therapy (RT) was 145.29 ml with the 25th, 50th, and 75th percentiles being 61.36 ml, 145.29 ml, and 204.93 ml, respectively. Before initiation of the radiation boost, the mean GTV2 was 99.58 ml, with the 25th, 50th, and 75th percentiles at 32.93 ml, 70.45 ml, and 126.85 ml. The HR for the impact of GTV1 on survival was 0.99 per ml (95% confidence interval [CI] 0.99-1.00; p = 0.49). For the absolute volume change between GTV1 and GTV2, the HR was 1.004 per ml (95% CI 0.997-1.011; p = 0.26). In a subgroup analysis of patients who were treated with durvalumab, absolute volume changes between GTV1 and GTV2 were associated with longer OS (HR = 0.955 per ml; 95% CI 0.916-0.996; p = 0.03). Overall, durvalumab treatment was positively associated with OS, demonstrating an HR of 0.454 (95% CI 0.209-0.990; p = 0.047).

Pretreatment GTV and absolute GTV volume changes did not significantly correlate with OS. However, the absolute volume change between the pretreatment and replanning GTV was associated with longer OS in patients treated with durvalumab. Histological subtype, grading, UICC stage, age at onset, pulmonary comorbidities, and smoking status had no significant association with OS. Durvalumab treatment was associated with improved OS.

Non-small cell lung cancers (NSCLC) account for 85 % of bronchopulmonary cancers and are most often diagnosed at an advanced stage. In case of resectable locally advanced NSCLC (LA-NSCLC) in a patient fit, surgery is the cornerstone of treatment in combination with perioperative treatment based on chemotherapy +/- immunotherapy. However, for a large proportion of LA-NSCLC, surgery is not a preferred option because the patient is medically inoperable or because of an unresectable disease. Since the early 2000s, the standard treatment for these patients who cannot benefit from surgical treatment had been a chemoradiotherapy, ideally given concurrently. The recent addition of consolidation immunotherapy following concurrent chemoradiotherapy has led to a clear improvement in median overall survival (OS) in this population. The objective of this article is to detail the standard treatment in 2024 of unresectable (or inoperable) LA-NSCLC and to discuss the main therapeutic perspectives in this indication, both regarding radiotherapy and systemic treatment and especially combination strategies with immunotherapy.

In the clinical management of lung cancer, radiotherapy remains a cornerstone of multimodal treatment strategies, often used alongside surgery or in combination with systemic therapies such as chemotherapy, tyrosine kinase inhibitors, and immune checkpoint inhibitors. While conventional imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) continue to play a central role in staging, response assessment, and radiotherapy planning, advanced imaging techniques, particularly [18F]FDG PET/CT, are being increasingly integrated into routine clinical practice. These advanced techniques address the limitations of standard imaging by providing insight into molecular and metabolic tumor characteristics, enabling precise tumor visualization, accurate target volume delineation, and early treatment response assessment. This review examines the role of radiotherapy in the multidisciplinary management of lung cancer, detailing current concepts of morphological and functional imaging for staging and treatment planning. It also highlights the growing importance of PET-based radiotherapy planning, emphasizing its contributions to target volume definition and predictive value for treatment outcomes. Recent methodological advances, including the integration of artificial intelligence (AI), radiomics, technical innovations, and novel PET ligands, are discussed, highlighting their potential to improve the precision, efficacy, and personalization of lung cancer radiotherapy planning.

Cancer associated fibroblasts have become a target of interest in different malignancies for positron emission tomography (PET) imaging, using positron emitter labelled fibroblast activation protein inhibitors (FAPI). New data underline the advanced imaging properties of FAPI-PET/CT for the staging of esophageal cancer compared to standard imaging. Potential benefits of FAPI-PET/CT in radiation therapy planning are the subject of this investigation.

Ten patients with newly diagnosed esophageal cancer treated with radiochemotherapy (RCT) were retrospectively analyzed. All patients underwent [68Ga]OncoFAP-PET/CT in treatment position to facilitate radiation treatment planning. Six patients received neoadjuvant RCT as part of a trimodal therapy and four patients underwent definitive RCT. In five cases, restaging after initial treatment was performed with FAPI-PET/CT.

[68Ga]OncoFAP-PET/CT based imaging showed a high correlation with the endoscopic staging for initial imaging. In three cases, new sites of disease were unmasked, not visible in CT- and endosonographic staging. [68Ga]OncoFAP-PET/CT based RT delineation offered good definition of clinical target volumes, especially in retro-/paracardial areas and the gastroesophageal junction.

[68Ga]OncoFAP-PET/CT may aid and improve radiation treatment planning for patients with esophageal cancer.

Lung cancer has a poor prognosis, and further improvements in outcomes are needed. Radiotherapy plays an important role in the treatment of unresectable lung cancer, and there have been recent developments in the field of radiotherapy for the management of lung cancer. However, to date, there have been few reviews on the improvement in treatment outcomes associated with high precision radiotherapy for lung cancer. Thus, this review aimed to summarize the recent developments in radiotherapy techniques and indicate the future directions in the use of radiotherapy for lung cancer. Stereotactic body radiotherapy (SBRT) for unresectable stage I lung cancer has been reported to improve local control rates without severe adverse events, such as radiation pneumonitis. For locally advanced lung cancer, a combination of chemoradiotherapy and adjuvant immune checkpoint inhibitors dramatically improves treatment outcomes, and intensity-modulated radiotherapy (IMRT) enables safer radiation therapy with less frequent pneumonitis. Particle beam therapy, such as carbon-ion radiotherapy and proton beam therapy, has been administered as advanced medical care for patients with lung cancer. Since 2024, it has been covered under insurance for early stage lung cancer with tumors ≤ 5 cm in size in Japan. In addition to chemotherapy, local ablative radiotherapy improves treatment outcomes in patients with oligometastatic stage IV lung cancer. A particular problem with radiotherapy for lung cancer is that the target location changes with respiratory motion, and various physical methods have been used to control respiratory motion. Recently, coronavirus disease has had a major impact on lung cancer treatment, and cancer treatment during situations, such as the coronavirus pandemic, must be performed carefully. To improve treatment outcomes for lung cancer, it is necessary to fully utilize evolving radiotherapy modalities, and the role of radiotherapy in lung cancer treatment is expected to increase.

Conventional radiotherapy (CRT) has limited local control and poses a high risk of severe toxicity in large lung tumors. This study aimed to develop an integrated treatment plan that combines CRT with lattice boost radiotherapy (LRT) and monitors its dosimetric characteristics.

This study employed cone-beam computed tomography from 115 lung cancer patients to develop a U-Net +  + deep learning model for generating synthetic CT (sCT). The clinical feasibility of sCT was thoroughly evaluated in terms of image clarity, Hounsfield Unit (HU) consistency, and computational accuracy. For large lung tumors, accumulated doses to the gross tumor volume (GTV) and organs at risk (OARs) during 20 fractions of CRT were precisely monitored using matrices derived from the deformable registration of sCT and planning CT (pCT). Additionally, for patients with minimal tumor shrinkage during CRT, an sCT-based adaptive LRT boost plan was introduced, with its dosimetric properties, treatment safety in high dose regions, and delivery accuracy quantitatively assessed.

The image quality and HU consistency of sCT improved significantly, with dose deviations ranging from 0.15% to 1.25%. These results indicated that sCT is feasible for inter-fraction dose monitoring and adaptive planning. After rigid and hybrid deformable registration of sCT and pCT, the mean distance-to-agreement was 0.80 ± 0.18 mm, and the mean Dice similarity coefficient was 0.97 ± 0.01. Monitoring dose accumulation over 20 CRT fractions showed an increase in high-dose regions of the GTV (P < 0.05) and a reduction in low-dose regions (P < 0.05). Dosimetric parameters of all OARs were significantly higher than those in the original treatment plan (P < 0.01). The sCT based adaptive LRT boost plan, when combined with CRT, significantly reduced the dose to OARs compared to CRT alone (P < 0.05). In LRT plan, high-dose regions for the GTV and D95% exhibited displacements greater than 5 mm from the tumor boundary in 19 randomly scanned sCT sequences under free breathing conditions. Validation of dose delivery using TLD phantom measurements showed that more than half of the dose points in the sCT based LRT plan had deviations below 2%, with a maximum deviation of 5.89%.

The sCT generated by the U-Net +  + model enhanced the accuracy of monitoring the actual accumulated dose, thereby facilitating the evaluation of therapeutic efficacy and toxicity. Additionally, the sCT-based LRT boost plan, combined with CRT, further minimized the dose delivered to OARs while ensuring safe and precise treatment delivery.

Staging of non-small cell lung cancer (NSCLC) is commonly based on [18F]FDG PET/CT, in particular to exclude distant metastases and guide local therapy approaches like resection and radiotherapy. Although it is hoped that PET/CT will increase the value of primary staging compared to conventional imaging, it is generally limited to the characterization of TNM. The first aim of this study was to evaluate the PET parameter metabolic tumor volume (MTV) above liver background uptake as a prognostic marker in lung cancer. The second aim was to investigate the possibility of incorporating MTV into the TNM classification system for disease prognosis in locally advanced NSCLC treated with chemoradiotherapy.

Retrospective evaluation of 235 patients with histologically proven, locally advanced NSCLC from the multi-centre randomized clinical PETPLAN trial and a clinical cohort from a hospital registry. The PET parameters SUVmax, SULpeak, MTV and TLG above liver background uptake were determined. Kaplan-Meier curves and stratified Cox proportional hazard regression models were used to investigate the prognostic value of PET parameters and TNM along with clinical variables. Subgroup analyses were performed to compare hazard ratios according to TNM, MTV, and the two variables combined.

In the multivariable Cox regression analysis, MTV was associated with significantly worse overall survival independent of stage and other prognostic variables. In locally advanced disease stages treated with chemoradiotherapy, higher MTV was significantly associated with worse survival (median 17 vs. 32 months). Using simple cut-off values (45 ml for stage IIIa, 48 ml for stage IIIb, and 105 ml for stage IIIc), MTV was able to further predict differences in survival for stages IIIa-c. The combination of TNM and MTV staging system showed better discrimination for overall survival in locally advanced disease stages, compared to TNM alone.

Higher metabolic tumor volume is significantly associated with worse overall survival and combined with TNM staging, it provides more precise information about the disease prognosis in locally advanced NSCLC treated with chemoradiotherapy compared to TNM alone. As a PET parameter with volumetric information, MTV represents a useful addition to TNM.

Although the integration of positron emission tomography into radiation therapy treatment planning has become part of clinical routine, the best method for tumor delineation is still a matter of debate. In this study, therefore, we analyzed a novel, radiomics-feature-based algorithm in combination with histopathological workup for patients with non-small-cell lung cancer.

A total of 20 patients with biopsy-proven lung cancer who underwent [18F]fluorodeoxyglucose positron emission/computed tomography (FDG-PET/CT) examination before tumor resection were included. Tumors were segmented in positron emission tomography (PET) data using previously reported algorithms based on three different radiomics features, as well as a threshold-based algorithm. To obtain gold-standard results, lesions were measured after resection. Pathological volumes and maximal diameters were then compared with the results of the segmentation algorithms.

A total of 20 lesions were analyzed. For all algorithms, segmented volumes correlated well with pathological volumes. In general, the threshold-based volumes exhibited a tendency to be smaller than the radiomics-based volumes. For all lesions, conventional threshold-based segmentation produced coefficients of variation which corresponded best with pathologically based volumes; however, for lesions larger than 3 ccm, the algorithm based on Local Entropy performed best, with a significantly better coefficient of variation (p = 0.0002) than the threshold-based algorithm.

We found that, for small lesions, results obtained using conventional threshold-based segmentation compared well with pathological volumes. For lesions larger than 3 ccm, the novel algorithm based on Local Entropy performed best. These findings confirm the results of our previous phantom studies. This algorithm is therefore worthy of inclusion in future studies for further confirmation and application.

NRG-RTOG0617 demonstrated a detrimental effect of uniform high-dose radiation in stage III non-small cell lung cancer. NRG-RTOG1106/ECOG-ACRIN6697 (ClinicalTrials.gov identifier: NCT01507428), a randomized phase II trial, studied whether midtreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can guide individualized/adaptive dose-intensified radiotherapy (RT) to improve and predict outcomes in patients with this disease.

Patients fit for concurrent chemoradiation were randomly assigned (1:2) to standard (60 Gy/30 fractions) or FDG-PET-guided adaptive treatment, stratified by substage, primary tumor size, and histology. All patients had midtreatment FDG-PET/CT; adaptive arm patients had an individualized, intensified boost RT dose to residual metabolically active areas. The primary therapeutic end point was 2-year centrally reviewed freedom from local-regional progression (FFLP), defined as no progression in or near the planning target volume and/or regional nodes. FFLP was analyzed on a modified intent-to-treat population at a one-sided Z-test significance level of 0.15. The primary imaging end point was centrally reviewed change in SUVpeak from baseline to midtreatment; its association with FFLP was assessed using the two-sided Wald test on the basis of Cox regression.

Of 138 patients enrolled, 127 were eligible. Adaptive-arm patients received a mean 71 Gy in 30 fractions, with mean lung dose 17.9 Gy. There was no significant difference in centrally reviewed 2-year FFLP (59.5% and 54.6% in standard and adaptive arms; P = .66). There were no significant differences in protocol-specified grade 3 toxicities, survival, or progression-free survival (P > .4). Median SUVpeak and metabolic tumor volume (MTV) in the adaptive arm decreased 49% and 54%, from pre-RT to mid-RT PET. However, ΔSUVpeak and ΔMTV were not associated with FFLP (hazard ratios, 0.997; P = .395 and .461).

Midtreatment PET-adapted RT dose escalation as given in this study was safe and feasible but did not improve efficacy outcomes.

Lung cancer, along with various other cancers, is characterized by increased glucose metabolism. The maximum standardized uptake value (SUVmax), derived from positron emission tomography-computed tomography (PET-CT), serves as an indicator of glucose metabolic activity in tumor lesions. This study aimed to evaluate the correlation between body mass index (BMI) and SUVmax in individuals with lung cancer.

This study included 41 patients with lung cancer, who were divided into two groups: Group 1 (n = 21), with a BMI greater than 22.4, and Group 2 (n = 20), with a BMI less than 22.4. All participants underwent 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging. The SUVmax was calculated by manually delineating the regions of interest. A t-test was performed to assess whether the differences in SUVmax between the two groups were statistically significant.

The mean SUVmax for Group 1 was 11.20 ± 5.45, while for Group 2 it was 10.65 ± 5.96. Although the mean SUVmax was higher in Group 1 compared to Group 2, the difference between the groups was not statistically significant (P = 0.757).

The findings indicate a non-significant difference in glucose metabolism in lung cancer lesions between patients with different BMI levels. These results offer valuable insights into the metabolic characteristics of lung cancer and contribute to a deeper understanding of its pathophysiology.

Locally advanced esophageal cancer (EC) has poor prognosis. Preliminary clinical studies have demonstrated the synergistic efficacy of radiotherapy combined with immunotherapy in EC. Adjusting the radiotherapy target volume to protect immune function favors immunotherapy. However, there is no clear consensus on the exact definition of the EC target volume.

Preclinical studies have provided a wealth of information on immunotherapy combined with different radiotherapy modalities, and several clinical studies have evaluated the impact of immunotherapy combined with radiotherapy on locally advanced EC. Here, we illustrate the rational target volume delineation for radiotherapy in terms of patient prognosis, pattern of radiotherapy failure, treatment-related toxicities, tumor-draining lymph nodes, and systemic immunity and summarize the clinical trials of radiotherapy combined with immunotherapy in EC.

We recommend applying involved-field irradiation (IFI) instead of elective nodal irradiation (ENI) for irradiated fields when immunotherapy is combined with chemoradiotherapy (CRT) for locally advanced EC. We expect that this target design will be evaluated in clinical trials to further explore more precise diagnostic modalities, long-term toxic responses, and quality of survival, and stratification factors for personalized treatment, and to provide more treatment benefits for patients.

The use of positron-emission tomography (PET)/computed tomography (CT) in radiation therapy (RT) has increased. Radiation oncologists (RadOncs) have access to PET/CT with a variety of tracers for different tumor entities and use it for target volume definition. The German Society of Nuclear Medicine (DGN) and the German Society of Radiation Oncology (DEGRO) aimed to identify current patterns of care in order to improve interdisciplinary collaboration.

We created an online survey on participating RadOncs' use of PET tracers for different tumor entities and how they affect RT indication, dose prescription, and target volume definition. Further topics were reimbursement of PET/CT and organizational information (fixed timeslots and use of PET with an immobilization device [planning/RT-PET]). The survey contained 31 questions in German language (yes/no questions, multiple choice [MC] questions, multiple select [MS] questions, and free-text entry options). The survey was distributed twice via the DEGRO member mailing list.

During the survey period (May 22-August 7, 2023) a total of 156 RadOncs (13% of respondents) answered the survey. Among these, 59% reported access to diagnostic PET/CT within their organization/clinic and 24% have fixed timeslots for their patients. 37% of survey participants can perform RT-PET and 29% have the option of providing a dedicated RT technician for planning PET. Besides [18F]-fluorodeoxyglucose (FDG; mainly used in lung cancer: 95%), diagnostic prostate-specific membrane antigen (PSMA)-PET/CT for RT of prostate cancer is routinely used by 44% of participants (by 64% in salvage RT). Use of amino acid PET in brain tumors and somatostatin receptor PET in meningioma is low (19 and 25%, respectively). Scans are reimbursed through private (75%) or compulsory (55%) health insurance or as part of indications approved by the German Joint Federal Committee (Gemeinsamer Bundesausschuss; 59%). 98% of RadOncs agree that PET impacts target volume definition and 62% think that it impacts RT dose prescription.

This is the first nationwide survey on the role of PET/CT for RT planning among RadOncs in Germany. We find high acceptance of PET results for treatment decisions and target volume definition. Planning PET comes with logistic challenges for different healthcare settings (e.g., private practices vs. university hospitals). The decision to request PET/CT is often based on the possibility of reimbursement.

PET/CT has become an important tool for RadOncs, with several indications. However, access is still limited at several sites, especially for dedicated RT-PET. This study aims to improve interdisciplinary cooperation and adequate implementation of current guidelines for the treatment of various tumor entities.

Dose-escalation in lung cancer comes with a high risk of severe toxicity. This study aimed to calculate the delivered dose in a Scandinavian phase-III dose-escalation trial.

The delivered dose was evaluated for 21 locally-advanced non-small cell lung cancer (LA-NSCLC) patients treated as part of the NARLAL2 dose-escalation trial. The patients were randomized between standard and escalated heterogeneous dose-delivery. Both treatment plans were created and approved before randomization. Daily cone-beam CT (CBCT) for patient positioning, and adaptive radiotherapy were mandatory. Standard and escalated plans, including adaptive re-plans, were recalculated on each daily CBCT and accumulated on the planning CT for each patient. Dose to the clinical target volume (CTV), organs at risk (OAR), and the effects of plan adaptions were evaluated for the accumulated dose and on each treated fraction scaled to full treatment.

For the standard treatment, plan adaptations reduced the number of patients with CTV-T underdosage from six to one, and the total number of fractions with CTV-T underdosage from 161 to 56; while for the escalated treatment, the number of patients was reduced from five to zero and number of fractions from 81 to 11. For dose-escalation, three patients had fractions exceeding trial constraints for heart, bronchi, or esophagus, and one had an accumulated heart dose above the constraints.

Dose-escalation for LA-NSCLC patients, using daily image guidance and adaptive radiotherapy, is dosimetrically safe for the majority of patients. Dose calculation on daily CBCTs is an efficient tool to monitor target coverage and OAR doses.

The aim of this secondary analysis of the prospective randomized phase 2 PET-Plan trial (ARO-2009-09; NCT00697333) was to evaluate the impact of mediastinal tumor burden and lymphatic spread in patients with locally advanced non-small-cell lung cancer (NSCLC).

All patients treated per protocol (n = 172) were included. Patients received isotoxically dose-escalated chemoradiotherapy up to a total dose of 60-74 Gy in 30-37 fractions, aiming as high as possible while adhering to normal tissue constraints. Radiation treatment (RT) planning was based on an 18F-FDG PET/CT targeting all lymph node (LN) stations containing CT positive LNs (i.e. short axis diameter > 10 mm), even if PET-negative (arm A) or targeting only LN stations containing PET-positive nodes (arm B). LN stations were classified into echelon 1 (ipsilateral hilum), 2 (ipsilateral station 4 and 7), and 3 (rest of the mediastinum, contralateral hilum). The endpoints were overall survival (OS), progression-free survival (PFS), and freedom from local progression (FFLP).

The median follow-up time (95 % confidence interval [CI]) was 41.1 (33.8 - 50.4) months. Patients with a high absolute number of PET-positive LN stations had worse OS (hazard ratio [HR] = 1.09; 95 % CI 0.99 - 1.18; p = 0.05) and PFS (HR = 1.12; 95 % CI 1.04 - 1.20; p = 0.003), irrespective of treatment arm allocation. The prescribed RT dose to the LNs did not correlate with any of the endpoints when considering all patients. However, in patients in arm B (i.e., PET-based selective nodal irradiation), prescribed RT dose to each LN station correlated significantly with FFLP (HR=0.45; 95 % CI 0.24-0.85; p = 0.01). Furthermore, patients with involvement of echelon 3 LN stations had worse PFS (HR = 2.22; 95 % CI 1.16-4.28; p = 0.02), also irrespective of allocation.

Mediastinal tumor burden and lymphatic involvement patterns influence outcome in patients treated with definitive chemoradiotherapy for locally advanced NSCLC. Higher dose to LNs did not improve OS, but did improve FFLP in patients treated with PET-based dose-escalated RT.

In lung cancer, one of the main limitations for the optimal integration of the biological and anatomical information derived from Positron Emission Tomography (PET) and Computed Tomography (CT) is the time and expertise required for the evaluation of the different respiratory phases. In this study, we present two open-source models able to automatically segment lung tumors on PET and CT, with and without motion compensation.

This study involved time-bin gated (4D) and non-gated (3D) PET/CT images from two prospective lung cancer cohorts (Trials 108237 and 108472) and one retrospective. For model construction, the ground truth (GT) was defined by consensus of two experts, and the nnU-Net with 5-fold cross-validation was applied to 560 4D-images for PET and 100 3D-images for CT. The test sets included 270 4D- images and 19 3D-images for PET and 80 4D-images and 27 3D-images for CT, recruited at 10 different centres.

In the performance evaluation with the multicentre test sets, the Dice Similarity Coefficients (DSC) obtained for our PET model were DSC(4D-PET) = 0.74 ± 0.06, improving 19% relative to the DSC between experts and DSC(3D-PET) = 0.82 ± 0.11. The performance for CT was DSC(4D-CT) = 0.61 ± 0.28 and DSC(3D-CT) = 0.63 ± 0.34, improving 4% and 15% relative to DSC between experts.

Performance evaluation demonstrated that the automatic segmentation models have the potential to achieve accuracy comparable to manual segmentation and thus hold promise for clinical application. The resulting models can be freely downloaded and employed to support the integration of 3D- or 4D- PET/CT and to facilitate the evaluation of its impact on lung cancer clinical practice.

We provide two open-source nnU-Net models for the automatic segmentation of lung tumors on PET/CT to facilitate the optimal integration of biological and anatomical information in clinical practice. The models have superior performance compared to the variability observed in manual segmentations by the different experts for images with and without motion compensation, allowing to take advantage in the clinical practice of the more accurate and robust 4D-quantification.

Lung tumor segmentation on PET/CT imaging is limited by respiratory motion and manual delineation is time consuming and suffer from inter- and intra-variability. Our segmentation models had superior performance compared to the manual segmentations by different experts. Automating PET image segmentation allows for easier clinical implementation of biological information.

Thoracic radiation intensification is debated in patients with stage III non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of a boost radiotherapy dose up to 74 Gy in a functional sub-volume given according to on-treatment [18F]fluorodeoxyglucose ([18F]FDG)-PET results.

In this multicentre, randomised, controlled non-comparative phase 2 trial, we recruited patients aged 18 years or older with inoperable stage III NSCLC without EGFR mutation or ALK rearrangement with an Eastern Cooperative Oncology Group performance status of 0-1, and who were affiliated with or a beneficiary of a social benefit system, with evaluable tumour or node lesions, preserved lung function, and who were amenable to curative-intent radiochemotherapy. Patients were randomly allocated using a central interactive web-response system in a non-masked method (1:1; minimisation method used [random factor of 0·8]; stratified by radiotherapy technique [intensity-modulated radiotherapy vs three-dimensional conformal radiotherapy] and by centre at which patients were treated) either to the experimental adaptive radiotherapy group A, in which only patients with positive residual metabolism on [18F]FDG-PET at 42 Gy received a boost radiotherapy (up to 74 Gy in 33 fractions), with all other patients receiving standard radiotherapy dosing (66 Gy in 33 fractions over 6·5 weeks), or to the standard radiotherapy group B (66 Gy in 33 fractions) over 6·5 weeks. All patients received two cycles of induction platinum-based chemotherapy cycles (paclitaxel 175 mg/m2 intravenously once every 3 weeks and carboplatin area under the curve [AUC]=6 once every 3 weeks, or cisplatin 80 mg/m2 intravenously once every 3 weeks and vinorelbine 30 mg/m2 intravenously on day 1 and 60 mg/m2 orally [or 30 mg/m2 intravenously] on day 8 once every 3 weeks). Then they concomitantly received radiochemotherapy with platinum-based chemotherapy (three cycles for 8 weeks, with once per week paclitaxel 40 mg/m2 intravenously and carboplatin AUC=2 or cisplatin 80 mg/m2 intravenously and vinorelbine 20 mg/m2 intravenously on day 1 and 40 mg/m2 orally (or 20 mg/m2 intravenously) on day 8 in 21-day cycles). The primary endpoint was the 15-month local control rate in the eligible patients who received at least one dose of concomitant radiochemotherapy. This RTEP7-IFCT-1402 trial is registered with ClinicalTrials.gov (NCT02473133), and is ongoing.

From Nov 12, 2015, to July 7, 2021, we randomly assigned 158 patients (47 [30%] women and 111 [70%] men) to either the boosted radiotherapy group A (81 [51%]) or to the standard radiotherapy group B (77 [49%)]. In group A, 80 (99%) patients received induction chemotherapy and 68 (84%) received radiochemotherapy, of whom 48 (71%) with residual uptake on [18F]FDG-PET after 42 Gy received a radiotherapy boost. In group B, all 77 patients received induction chemotherapy and 73 (95%) received radiochemotherapy. At the final analysis, the median follow-up for eligible patients who received radiochemotherapy (n=140) was 45·1 months (95% CI 39·3-48·3). The 15-month local control rate was 77·6% (95% CI 67·6-87·6%) in group A and 71·2% (95% CI 60·8-81·6%) in group B. Acute (within 90 days from radiochemotherapy initiation) grade 3-4 adverse events were observed in 20 (29%) of 68 patients in group A and 33 (45%) of 73 patients in group B, including serious adverse events in five (7%) patients in group A and ten (14%) patients in group B. The most common grade 3-4 adverse events were febrile neutropenia (seven [10%] of 68 in group A vs 16 [22%] of 73 in group B), and anaemia (five [7%] vs nine [12%]). In the acute phase, two deaths (3%) occurred in group B (one due to a septic shock related to chemotherapy, and the other due to haemotypsia not related to study treatment), and no deaths occurred in group A. After 90 days, one additional treatment-unrelated death occurred in group A and two deaths events occurred in group B (one radiation pneumonitis and one pneumonia unrelated to treatment).

A thoracic radiotherapy boost, based on interim [18F]FDG-PET, led to a meaningful local control rate with no difference in adverse events between the two groups in organs at risk, in contrast with previous attempts at thoracic radiation intensification, warranting a randomised phase 3 evaluation of such [18F]FDG-PET-guided radiotherapy dose adaptation in patients with stage III NSCLC.

Programme Hospitalier de Recherche Clinique National 2014.

Chemoradiotherapy (CRT) combined with immune checkpoint inhibitors (ICIs) is the standard of care for patients with unresectable and locally advanced non-small cell lung cancer. This study aimed to determine whether the addition of ICIs to CRT is associated with an increased risk of pneumonitis.

The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible studies published between January 1, 2015, and July 31, 2023. The outcome of interest was the incidence rate of pneumonitis. A random-effects model was used for statistical analysis.

A total of 185 studies with 24,527 patients were included. The pooled rate of grade ≥2 pneumonitis for CRT plus ICIs was significantly higher than that for CRT alone (29.6%; 95% CI, 25.7%-33.6% vs 20.2%; 95% CI, 17.7%-22.8%; P < .0001) but not that of grade ≥3 (5.7%; 95% CI, 4.8%-6.6% vs 5.6%; 95% CI, 4.7%-6.5%; P = .64) or grade 5 (0.1%; 95% CI, 0.0%-0.2% vs 0.3%; 95% CI, 0.1%-0.4%; P = .68). The results from the subgroup analyses of prospective studies, retrospective studies, Asian and non-Asian studies, concurrent CRT (cCRT), and durvalumab consolidation were comparable to the overall results. However, CRT or cCRT plus PD-1 inhibitors not only significantly increased the incidence of grade ≥2 but also that of grade ≥3 pneumonitis compared to CRT alone or cCRT plus PD-L1 inhibitors.

Compared with CRT alone, durvalumab consolidation after CRT appears to be associated with a higher incidence of moderate pneumonitis and CRT plus PD-1 inhibitors with an increased risk of severe pneumonitis. Nevertheless, these findings are based on observational studies and need to be validated in future large head-to-head studies.

Ionizing radiation can have a wide range of impacts on tumor-immune interactions, which are being studied with the greatest interest and at an accelerating pace by the medical community. Despite its undeniable immunostimulatory potential, it clearly appears that radiotherapy as it is prescribed and delivered nowadays often alters the host's immunity toward a suboptimal state. This may impair the full recovery of a sustained and efficient antitumor immunosurveillance posttreatment. An emerging concept is arising from this awareness and consists of reconsidering the way of designing radiation treatment planning, notably by taking into account the individualized risks of deleterious radio-induced immune alteration that can be deciphered from the planned beam trajectory through lymphocyte-rich organs. In this review, we critically appraise key aspects to consider while planning immunologically fitted radiotherapy, including the challenges linked to the identification of new dose constraints to immune-rich structures. We also discuss how pharmacologic immunomodulation could be advantageously used in combination with radiotherapy to compensate for the radio-induced loss, for example, with (i) agonists of interleukin (IL)2, IL4, IL7, IL9, IL15, or IL21, similarly to G-CSF being used for the prophylaxis of severe chemo-induced neutropenia, or with (ii) myeloid-derived suppressive cell blockers.

Fibroblast activation protein (FAP) is expressed in the tumor microenvironment (TME) of various cancers. In our analysis, we describe the impact of dual-tracer imaging with Gallium-68-radiolabeled inhibitors of FAP (FAPI-46-PET/CT) and fluorodeoxy-D-glucose (FDG-PET/CT) on the radiotherapeutic management of primary esophageal cancer (EC).

32 patients with EC, who are scheduled for chemoradiation, received FDG and FAPI-46 PET/CT on the same day (dual-tracer protocol, 71%) or on two separate days (29%) We compared functional tumor volumes (FTVs), gross tumor volumes (GTVs) and tumor stages before and after PET-imaging. Changes in treatment were categorized as "minor" (adaption of radiation field) or "major" (change of treatment regimen). Immunohistochemistry (IHC) staining for FAP was performed in all patients with available tissue.

Primary tumor was detected in all FAPI-46/dual-tracer scans and in 30/32 (93%) of FDG scans. Compared to the initial staging CT scan, 12/32 patients (38%) were upstaged in nodal status after the combination of FDG and FAPI-46 PET scans. Two lymph node metastases were only visible in FAPI-46/dual-tracer. New distant metastasis was observed in 2/32 (6%) patients following FAPI-4 -PET/CT. Our findings led to larger RT fields ("minor change") in 5/32 patients (16%) and changed treatment regimen ("major change") in 3/32 patients after FAPI-46/dual-tracer PET/CT. GTVs were larger in FAPI-46/dual-tracer scans compared to FDG-PET/CT (mean 99.0 vs. 80.3 ml, respectively (p < 0.001)) with similar results for nuclear medical FTVs. IHC revealed heterogenous FAP-expression in all specimens (mean H-score: 36.3 (SD 24.6)) without correlation between FAP expression in IHC and FAPI tracer uptake in PET/CT.

We report first data on the use of PET with FAPI-46 for patients with EC, who are scheduled to receive RT. Tumor uptake was high and not depending on FAP expression in TME. Further, FAPI-46/dual-tracer PET had relevant impact on management in this setting. Our data calls for prospective evaluation of FAPI-46/dual-tracer PET to improve clinical outcomes of EC.

The Ethos (Varian Medical Systems) radiotherapy device combines semi-automated anatomy detection and plan generation for cone beam computer tomography (CBCT)-based daily online adaptive radiotherapy (oART). However, CBCT offers less soft tissue contrast than magnetic resonance imaging (MRI). This work aims to present the clinical workflow of CBCT-based oART with shuttle-based offline MR guidance.

From February to November 2023, 31 patients underwent radiotherapy on the Ethos (Varian, Palo Alto, CA, USA) system with machine learning (ML)-supported daily oART. Moreover, patients received weekly MRI in treatment position, which was utilized for daily plan adaptation, via a shuttle-based system. Initial and adapted treatment plans were generated using the Ethos treatment planning system. Patient clinical data, fractional session times (MRI + shuttle transport + positioning, adaptation, QA, RT delivery) and plan selection were assessed for all fractions in all patients.

In total, 737 oART fractions were applied and 118 MRIs for offline MR guidance were acquired. Primary sites of tumors were prostate (n = 16), lung (n = 7), cervix (n = 5), bladder (n = 1) and endometrium (n = 2). The treatment was completed in all patients. The median MRI acquisition time including shuttle transport and positioning to initiation of the Ethos adaptive session was 53.6 min (IQR 46.5-63.4). The median total treatment time without MRI was 30.7 min (IQR 24.7-39.2). Separately, median adaptation, plan QA and RT times were 24.3 min (IQR 18.6-32.2), 0.4 min (IQR 0.3-1,0) and 5.3 min (IQR 4.5-6.7), respectively. The adapted plan was chosen over the scheduled plan in 97.7% of cases.

This study describes the first workflow to date of a CBCT-based oART combined with a shuttle-based offline approach for MR guidance. The oART duration times reported resemble the range shown by previous publications for first clinical experiences with the Ethos system.

Glioblastoma (GBM) systematically recurs after a standard 60 Gy radio-chemotherapy regimen. Since magnetic resonance spectroscopic imaging (MRSI) has been shown to predict the site of relapse, we analyzed the effect of MRSI-guided dose escalation on overall survival (OS) of patients with newly diagnosed GBM.

In this multicentric prospective phase III trial, patients who had undergone biopsy or surgery for a GBM were randomly assigned to a standard dose (SD) of 60 Gy or a high dose (HD) of 60 Gy with an additional simultaneous integrated boost totaling 72 Gy to MRSI metabolic abnormalities, the tumor bed and residual contrast enhancements. Temozolomide was administered concomitantly and maintained for 6 months thereafter.

One hundred and eighty patients were included in the study between March 2011 and March 2018. After a median follow-up of 43.9 months (95% CI [42.5; 45.5]), median OS was 22.6 months (95% CI [18.9; 25.4]) versus 22.2 months (95% CI [18.3; 27.8]) for HD, and median progression-free survival was 8.6 (95% CI [6.8; 10.8]) versus 7.8 months (95% CI [6.3; 8.6]), in SD versus HD, respectively. No increase in toxicity rate was observed in the study arm. The pseudoprogression rate was similar across the SD (14.4%) and HD (16.7%) groups. For O(6)-methylguanine-DNA methyltransferase (MGMT) methylated patients, the median OS was 38 months (95% CI [23.2; NR]) for HD patients versus 28.5 months (95% CI [21.1; 35.7]) for SD patients.

The additional MRSI-guided irradiation dose totaling 72 Gy was well tolerated but did not improve OS in newly diagnosed GBM.

NCT01507506; registration date: December 20, 2011. https://clinicaltrials.gov/ct2/show/NCT01507506?cond=NCT01507506&rank=1.