First clinical experience with a multiple region of interest registration and correction method in radiotherapy of head-and-neck cancer patients

Purpose

To discuss the first clinical experience with a multiple region of interest (mROI) registration and correction method for high-precision radiotherapy of head-and-neck cancer patients.

Materials and methods

12-13 3D rectangular-shaped ROIs were automatically placed around bony structures on the planning CT scans (n = 50 patients) which were individually registered to subsequent CBCT scans. mROI registration was used to quantify global and local setup errors. The time required to perform the mROI registration was compared with that of a previously used single-ROI method. The number of scans with residual local setup error exceeding 5 mm/5° (warnings) was scored together with the frequency ROIs exceeding these limits for three or more consecutive imaging fractions (systematic errors).

Results

In 40% of the CBCT scans, one or more ROI-registrations exceeded the 5 mm/5°. Most warnings were seen in ROI “hyoid”, 31% of the rotation warnings and 14% of the translation warnings. Systematic errors lead to 52 consults of the treating physician. The preparation and registration time was similar for both registration methods.

Conclusions

The mROI registration method is easy to use with little extra workload, provides additional information on local setup errors, and helps to select patients for re-planning.     

ExacTrac X-ray 6 degree-of-freedom image-guidance for intracranial non-invasive stereotactic radiotherapy: Comparison with kilo-voltage cone-beam CT

Background and purpose

To compare the residual setup errors measured with ExacTrac X-ray 6 degree-of-freedom (6D) and cone-beam computed tomography (CBCT) for a head phantom and patients receiving intracranial non-invasive fractionated stereotactic radiotherapy (SRT).

Materials and methods

Setup data were collected on a Novalis Tx treatment unit for an anthropomorphic head phantom and 18 patients with intracranial tumors. Initial corrections were determined and corrected with the ExacTrac system only, and then the residual setup error was determined by means of three different procedures. These procedures included registrations of ExacTrac X-ray images with the corresponding digitally reconstructed radiographs (DRRs) using the ExacTrac 6D fusion, and registrations of CBCT images with the planning CT using both online 3D fusion and offline 6D fusion. The difference in residual setup errors between ExacTrac system and CBCT was computed. The impact of rotations on the difference was evaluated.

Results

A modest difference in residual setup errors was found between ExacTrac system and CBCT. The root-mean-square (RMS) of the differences observed for translations was typically <0.5 mm for phantom, and <1.5 mm for patients, respectively. The RMS of the differences for rotation(s) was however <0.2 degree for phantom, and <1.0 degree for patients, respectively. The impact of rotation on the setup difference was minor but not negligible.

Conclusions

This study indicates that there is a general agreement between ExacTrac system and CBCT.     

Potential of image-guidance, gating and real-time tracking to improve accuracy in pulmonary stereotactic body radiotherapy

Purpose

To evaluate the potential of image-guidance, gating and real-time tumor tracking to improve accuracy in pulmonary stereotactic body radiotherapy (SBRT).

Materials and methods

Safety margins for compensation of inter- and intra-fractional uncertainties of the target position were calculated based on SBRT treatments of 43 patients with pre- and post-treatment cone-beam CT imaging. Safety margins for compensation of breathing motion were evaluated for 17 pulmonary tumors using respiratory correlated CT, model-based segmentation of 4D-CT images and voxel-based dose accumulation; the target in the mid-ventilation position was the reference.

Results

Because of large inter-fractional base-line shifts of the tumor, stereotactic patient positioning and image-guidance based on the bony anatomy required safety margins of 12 mm and 9 mm, respectively. Four-dimensional image-guidance targeting the tumor itself and intra-fractional tumor tracking reduced margins to <5 mm and <3 mm, respectively. Additional safety margins are required to compensate for breathing motion. A quadratic relationship between tumor motion and margins for motion compensation was observed: safety margins of 2.4 mm and 6 mm were calculated for compensation of 10 mm and 20 mm motion amplitudes in cranio-caudal direction, respectively.

Conclusion

Four-dimensional image-guidance with pre-treatment verification of the target position and online correction of errors reduced safety margins most effectively in pulmonary SBRT.     

The accuracy of frameless stereotactic intracranial radiosurgery

Purpose

To determine the accuracy of frameless stereotactic radiosurgery using the BrainLAB ExacTrac system and robotic couch by measuring the individual contributions such as the accuracy of the imaging and couch correction system, the linkage between this system and the linac isocenter and the possible intrafraction motion of the patient in the frameless mask.

Materials and methods

An Alderson head phantom with hidden marker was randomly positioned 31 times. Automated 6D couch shifts were performed according to ExacTrac and the deviation with respect to the linac isocenter was measured using the hidden marker. ExacTrac-based set-up was performed for 46 patients undergoing hypofractionated stereotactic radiotherapy for 135 fractions, followed by verification X-rays. Forty-three of these patients received post-treatment X-ray verification for 79 fractions to determine the intrafraction motion.

Results

The hidden target test revealed a systematic error of 1.5 mm in one direction, which was corrected after replacement of the system calibration phantom. The accuracy of the ExacTrac positioning is approximately 0.3 mm in each direction, 1 standard deviation. The intrafraction motion was 0.35 ± 0.21 mm, maximum 1.15 mm.

Conclusion

Intrafraction motion in the BrainLAB frameless mask is very small. Users are strongly advised to perform an independent verification of the ExacTrac isocenter in order to avoid systematic deviations.     

Target volume shape variation during hypo-fractionated preoperative irradiation of rectal cancer patients

Purpose

To quantify the day-to-day target volume shape variation in rectal-cancer patients treated with preoperative 5 × 5 Gy radiotherapy.

Materials and methods

For 27 patients a prone position plan-CT (pCT) and five daily pre-treatment cone-beam-CT (CBCT) scans were acquired. A sub-region of the CTV (MesoRect, anus up to the cranial end of the mesorectal-fascia) was delineated on all scans. The MesoRect deformation was quantified by the distance between pCT- and CBCT-delineations and was stored in surface-maps. Finally, the influence of bladder and rectum filling on MesoRect deformation was evaluated. Data were analyzed for male and female patients separately.

Results

A large range of systematic and random deformations, 1-7 mm (1SD), on different areas of the MesoRect were found. The maximum deformations were located at the upper-anterior-side of the MesoRect. For females the errors were up to 3 mm larger than for males. Small correlations, r² ? 0.4, were found with changes in bladder volume. Larger correlations, r² ? 0.7, were found for rectal volume in a distinctive area in the upper-half of the MesoRect.

Conclusions

Substantial and heterogeneous deformations of the MesoRect were found. Therefore different PTV margins in positions along the cranio-caudal axis, in the anterior-posterior direction. Margins should also be larger for female patients compared to male patients.     

Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: Safety profile for RTOG 0933

Background and purpose

RTOG 0933 is a phase II clinical trial of hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) to prevent radiation-induced neurocognitive decline. By quantifying baseline incidence of perihippocampal or hippocampal metastasis, we sought to estimate the risk of developing metastases in the hippocampal avoidance region (the hippocampus plus 5 mm margin).

Materials/methods

Patients with ?10 brain metastases treated at two separate institutions were reviewed. Axial images from pre-treatment, post-contrast MRIs were used to contour each metastasis and hippocampus according to a published protocol. Clinical and radiographic variables were correlated with perihippocampal metastasis using a binary logistical regression analysis, with two-sided p < 0.05 for statistical significance.

Results

1133 metastases were identified in 371 patients. Metastases within 5 mm of the hippocampus were observed in 8.6% of patients (95% CI 5.7-11.5%) and 3.0% of brain metastases. None of the metastases lay within the hippocampus. A 1-cm³ increase in the aggregate volume of intra-cranial metastatic disease was associated with an odds ratio of 1.02 (95% CI 1.006-1.034, p = 0.003) for the presence of perihippocampal metastasis.

Conclusion

With an estimated perihippocampal metastasis risk of 8.6%, we deem HA-WBRT safe for clinical testing in patients with brain metastases as part of RTOG 0933.     

The role of replanning in fractionated intensity modulated radiotherapy for nasopharyngeal carcinoma

Background and purpose

Anatomic changing frequently occurred during fractionated radiotherapy. The aims of this study were to model the potential benefit of adaptive IMRT replanning during fractionated radiotherapy and its potential advantage over clinical outcome in patients with nasopharyngeal carcinoma.

Materials and methods

Thirty-three patients with repeat CT imaging and replanning were retrospectively analyzed. 66 case-matched control patients without replanning were identified by matching for AJCC stage, gender, and age. Hybrid IMRT plans were generated to evaluate the dosimetric changing. Mann-Whitney-Wilcoxon tests were used to evaluate the effect of replanning on volumetric and dosimetric outcomes within individuals. Kaplan-Meier estimators were used to estimate the survival function of patients with or without replanning.

Results

The mean volume of the ipsilateral and contralateral parotid glands decreased during the treatment. The hybrid IMRT plans showed decreased doses to target volumes and increased doses to normal structures in replanning. The clinical outcome comparison indicated that the IMRT replanning improved the 3 years local progression-free survival for patients who had AJCC staged more than T₃ (T_3,4N_x) and ease the late effects for patients who had large lymph nodes (AJCC stage T_xN_2,3).

Conclusion

Repeat CT imaging and IMRT replanning were recommendatory for specific nasopharyngeal carcinoma patients.     

Daily online bony correction is required for prostate patients without fiducial markers or soft-tissue imaging

Aim

To compare online position verification strategies with offline correction protocols for patients undergoing definitive prostate radiotherapy.

Materials and methods

We analysed 50 patients with implanted fiducial markers undergoing curative prostate radiation treatment, all of whom underwent daily kilovoltage imaging using an on-board imager. For each treatment, patients were set-up initially with skin tattoos and in-room lasers. Orthogonal on-board imager images were acquired and the couch shift to match both bony anatomy and the fiducial markers recorded. The set-up error using skin tattoos and offline bone correction was compared with online bone correction. The fiducial markers were used as the reference.

Results

Data from 1923 fractions were analysed. The systematic error was ≤1 mm for all protocols. The average random error was 2-3 mm for online bony correction and 3-5 mm for skin tattoos or offline-bone. Online-bone showed a significant improvement compared with offline-bone in the number of patients with >5 mm set-up errors for >10% (P < 0.001) and >20% (P < 0.003) of their fractions.

Conclusions

Online correction to bony anatomy reduces both systematic and random set-up error in patients undergoing prostate radiotherapy, and is superior to offline correction methods for those patients not suitable for fiducial markers or daily soft-tissue imaging.     

Toxicity after reirradiation of pulmonary tumours with stereotactic body radiotherapy

Purpose

To assess toxicity and feasibility of reirradiation with stereotactic body radiotherapy (SBRT) after prior lung SBRT for primary lung cancer or lung metastases.

Patients and materials

Twenty-nine patients reirradiated with SBRT on 32 lung lesions (11 central, 21 peripheral) were retrospectively reviewed. Median follow-up time was 12 months (range 1-97). The primary endpoint was toxicity, secondary endpoints were local control and overall survival time. Toxicity was scored according to the NCI-CTCAE version 3.

Results

Grade 3-4 toxicity was scored 14 times in eight patients. Three patients died because of massive bleeding (grade 5). Larger clinical target volumes (CTV) and central tumour localization were associated with more severe toxicity. There was no correlation between mean lung dose (MLD) and lung toxicity. Local control at 5 months after reirradiation was 52%, as assessed by CT-scan (n = 12) or X-thorax (n = 3). A larger CTV was associated with poorer local control. Kaplan-Meier estimated 1- and 2-year survival rates were 59% and 43%, respectively.

Conclusions

Reirradiation with SBRT is feasible although increased risk of toxicity was reported in centrally located tumours. Further research is warranted for more accurate selection of patients suitable for reirradiation with SBRT.     

Increased organ sparing using shape-based treatment plan optimization for intensity modulated radiation therapy of pancreatic adenocarcinoma

Purpose

To develop a model to assess the quality of an IMRT treatment plan using data of prior patients with pancreatic adenocarcinoma.

Methods

The dose to an organ at risk (OAR) depends in large part on its orientation and distance to the planning target volume (PTV). A database of 33 previously treated patients with pancreatic cancer was queried to find patients with less favorable PTV-OAR configuration than a new case. The minimal achieved dose among the selected patients should also be achievable for the OAR of the new case. This way the achievable doses to the OARs of 25 randomly selected pancreas cancer patients were predicted. The patients were replanned to verify if the predicted dose could be achieved. The new plans were compared to their original clinical plans.

Results

The predicted doses were achieved within 1 and 2 Gy for more than 82% and 94% of the patients, respectively, and were a good approximation of the minimal achievable doses. The improvement after replanning was 1.4 Gy (range 0-4.6 Gy) and 1.7 Gy (range 0-6.3 Gy) for the mean dose to the liver and the kidneys, respectively, without compromising target coverage or increasing radiation dose to the bowel, cord or stomach.

Conclusions

The model could accurately predict the achievable doses, leading to a considerable decrease in dose to the OARs and an increase in treatment planning efficiency.     

Outcomes of stereotactic ablative radiotherapy following a clinical diagnosis of stage I NSCLC: Comparison with a contemporaneous cohort with pathologically proven disease

Introduction

As a finding of benign disease is uncommon in Dutch patients undergoing surgery after a clinical diagnosis of stage I NSCLC, patients are also accepted for stereotactic ablative radiotherapy (SABR) without pathology. We studied outcomes in patients who underwent SABR after either a pathological (n = 209) or clinical diagnosis (N = 382).

Materials and methods

Five hundred and ninety-one patients with a single pulmonary lesion underwent SABR after either a pathological- or a clinical diagnosis of stage I NSCLC based on a ¹⁸FDG-PET positive lesion with CT features of malignancy. SABR was delivered to a total dose of 60 Gy in 3, 5 or 8 fractions, and outcomes were compared between groups with and without pathological diagnosis.

Results

Patients with pathology had significantly larger tumor diameters (p < .001) and higher predicted FEV1% values (p = .025). No significant differences were observed between both groups in overall survival (p = .99) or local control (p = .98). Regional and distant recurrence rates were also similar.

Conclusions

In a population with a low incidence of benign ¹⁸FDG-PET positive lung nodules, clinical SABR outcomes were similar in large groups of patients with or without pathology. The survival benefits reported after the introduction of SABR are unlikely to be biased by inclusion of benign lesions.     

Treatment of stage I NSCLC in elderly patients: A population-based matched-pair comparison of stereotactic radiotherapy versus surgery

Background

Elderly patients with stage I NSCLC who undergo surgical resection are at high risk of treatment-related toxicity. Stereotactic body radiation therapy (SBRT) may provide an alternative treatment with a favorable toxicity profile.

Methods

A population-based registry in North-Holland was used to conduct a matched-pair analysis of overall survival (OS) after surgery versus SBRT for elderly patients (age ?75) who were diagnosed between 2005 and 2007. Patients were matched by age, stage, gender, and treatment year; co-morbidity data was not available. SBRT was delivered at two centers; 17 centers provided surgery.

Results

A total of 120 patients could be matched (60 surgery, 60 SBRT). Median age was 79 years, 67% were male, and 64% had T1 disease. Median follow-up was 43 months. Thirty-day mortality was 8.3% after surgery and 1.7% after SBRT. OS at one- and three-years was 75% and 60% after surgery, and 87% and 42% after SBRT, respectively (log-rank p = 0.22). Limiting the analysis to SBRT patients with pathological confirmation of disease and their matches revealed no significant difference between groups.

Conclusion

Similar OS outcomes are achieved with surgery or SBRT for stage I NSCLC in elderly patients. Comorbidity data and outcomes from centralized surgical programs are needed for more robust conclusions.     

Dosimetric consequences of uncorrected setup errors in helical Tomotherapy treatments of breast-cancer patients

Background and purpose

The Tomotherapy Hi-Art II system allows acquisition of pre-treatment MVCT images to correct patient position. This work evaluates the dosimetric impact of uncorrected setup errors in breast-cancer radiation therapy.

Materials and methods

Breast-cancer patient-positioning errors were simulated by shifting the patient computed-tomography (CT) dataset relative to the planned photon fluence and re-computing the dose distributions. To properly evaluate the superficial region, film measurements were compared against the Tomotherapy treatment planning system (TPS) calculations. A simulation of the integrated dose distribution was performed to evaluate the setup error impact over the course of treatment.

Results

Significant dose differences were observed for 11-mm shifts in the anterolateral and 3-mm shifts in the posteromedial directions. The results of film measurements in the superficial region showed that the TPS overestimated the dose by 14% at a 1-mm depth, improving to 3% at depths ?5 mm. Significant dose reductions in PTV were observed in the dose distributions simulated over the course of treatment.

Conclusions

Tomotherapy’s rotational delivery provides sufficient photon fluence extending beyond the skin surface to allow an up to 7-mm uncorrected setup error in the anterolateral direction. However, the steep dose falloff that conforms to the lung surface leads to compromised dose distributions with uncorrected posteromedial shifts. Therefore, daily image guidance and consequent patient repositioning is warranted for breast-cancer patients.     

Early pulmonary toxicity following lung stereotactic body radiation therapy delivered in consecutive daily fractions

Background and purpose

Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days.

Material and methods

A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0.

Results

With a median follow-up of 15.8 months (range 2.5-28.6), the median age at SBRT was 71.8 years (range 23.8-87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48 Gy in 4 Fx, and most peripheral lesions with 54 Gy in 3 Fx. The incidence of grade ?2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54 Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy.

Conclusions

Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity.     

Predictors of acute bowel toxicity in patients treated with IMRT whole pelvis irradiation after prostatectomy

Purpose/objective

Whole pelvis irradiation with IMRT (WPRT-IMRT) after prostatectomy is efficient in reducing acute toxicity: however, a number of patients still experience moderate acute bowel toxicity.

Materials and methods

Ninety-six patients treated with WPRT-IMRT after prostatectomy with adjuvant or salvage intent were analysed. A number of parameters were individually recovered, including the DVHs of the intestinal cavity outside PTV and of the loops referred to both the WPRT phase and the whole treatment. Correlation between clinical-dosimetric parameters and acute bowel toxicity was investigated by logistic analyses. Best predictive cut-off values for continuous variables were assessed by ROC curves.

Results

15/96 (15.6%) Patients experienced grade 2 toxicity (no grade 3). Best dose-volume predictors were the fraction of loops receiving more than 45, 50 and 55 Gy (respectively, V45TL ? 50 cc, V50TL ? 13 cc, V55TL ? 3 cc; p-values ranging from 0.005 to 0.027). Age, GU acute toxicity, rectal acute toxicity and time between prostatectomy and IMRT were also predictors of acute bowel toxicity. Multivariate analysis showed that the most predictive independent parameters were age (OR: 1.13; 95%CI: 1.02-1.25; p = 0.021) and V50TL (?13 cc, OR: 8.2; 95%CI: 1.7-40; p = 0.009).

Conclusions

The risk of moderate acute uGI toxicity during WPRT-IMRT for post-operatively treated patients increases with age; the risk is substantially reduced in patients with small overlap between PTV and loops.     

Adjuvant chemoradiotherapy with or without intraoperative radiotherapy for the treatment of resectable locally advanced gastric adenocarcinoma

Purpose

To document the long-term efficacy of intraoperative electron radiotherapy (IOERT) followed by concurrent chemotherapy and external-beam radiotherapy (EBRT) in the management of locally advanced gastric cancer.

Materials and methods

A total of 97 consecutive patients with T3/4 or N+ gastric adenocarcinoma were enrolled. Fifty-one patients received adjuvant chemoradiotherapy (EBRT group) and 46 received IOERT (dose range, 12-15 Gy) followed by chemoradiotherapy (EBRT + IOERT group).

Results

The 5-year locoregional control rates were 50% and 35% in the two groups with or without IOERT, respectively (p = 0.04). Two patients had recurrence within the IOERT field in the EBRT + IOERT group and 14 patients recurred in the same area in the EBRT group (p = 0.02). Multivariate analyses revealed that adjuvant IOERT was an independent prognosticator for both local-regional control (p = 0.02) and disease-free survival (p = 0.05). G3/4 late toxicity was observed in 5 patients in the EBRT + IOERT group, but none in the EBRT group (p = 0.02).

Conclusions

Higher radiation dose may contribute to the improvement of local control, especially in the field encompassed by IOERT. The addition of IOERT to surgery and adjuvant chemoradiation deserves further investigation in a randomized trial.     

Radiological and pathological response following pre-operative radiotherapy for soft-tissue sarcoma

Purpose

To report radiological and pathological response to neo-adjuvant radiotherapy for extremity and trunk soft-tissue sarcomas.

Materials/methods

Fifty patients were identified retrospectively. All patients had MRI imaging pre and post neo-adjuvant external beam radiotherapy. Tumor volumes were measured in 3D on T1 Gadolinium enhanced sequences. Pathological treatment response was quantified in terms of percentage of treatment-related necrosis for each case.

Results

Histopathologic responses to treatment varied from 0% to 100%. The median pathological treatment response was 67.5% for low-grade sarcomas and 50% for high-grade sarcomas. The median decrease in tumor volume was 13.8% for non-myxoid low-grade sarcomas, 82.1% for myxoid liposarcomas and <1% for high-grade sarcomas. A partial response on MRI (volume reduction ? 50%) was highly predictive of a good pathological response (p < 0.001). Patients with stable disease on imaging or volumetric progression had wide ranging pathological responses.

Conclusions

Soft-tissue sarcomas show significant pathological treatment responses in the form of hyaline fibrosis, necrosis and granulation tissue. Despite this, there is minimal early volumetric response to radiation, especially for high-grade tumors. Although radiological partial response was predictive of pathological response, the significance of radiological progression was unclear. Myxoid liposarcoma tumor type was predictive of both pathological and radiological tumor response.     

Volumetric modulated arc therapy versus conventional intensity modulated radiation therapy for stereotactic spine radiotherapy: A planning study and early clinical data

Background and purpose

Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiation therapy (SBRT). As target geometry is complex, we compared SBRT plans using volumetric modulated arc radiotherapy (RapidArc®, RA) and conventional intensity-modulated radiotherapy (IMRT).

Materials and methods

RA and IMRT plans to deliver a fraction of 16 Gy to at least 90% of planning target volume (PTV) were compared for PTV coverage, normal organ sparing and estimated delivery times. Group 1 consisted of PTVs to only vertebral body (n = 3), while group 2 had PTVs encompassing the entire vertebra (n = 4). Finally, RA delivery parameters in four patients were assessed.

Results

Both techniques delivered 16 Gy to a mean of 95% and 85% of the PTV in groups 1 and 2, respectively. Spinal cord sparing was comparable; mean V_{10-partial cord} for RA and IMRT in group 1 was 3.6%, and was 9.4% versus 11.5%, respectively, in group 2. Estimated mean treatment times for RA with 2-3 arcs and IMRT were comparable. Clinical RA beam-on times ranged from 11 to 15.4 min.

Conclusions

Both RA and conventional IMRT plans deliver high quality vertebral SBRT, but plan quality was poorer when the PTV consisted of the entire vertebra.     

Impact of PARP-1 and DNA-PK expression on survival in patients with glioblastoma multiforme

Purpose

To analyze, whether higher tumor levels of DNA repair enzymes contribute to worse treatment results of glioblastoma multiforme (GBM) patients after postoperative radiotherapy.

Materials and methods

Thirty four patients with GBM received postoperative radiotherapy. Tumor sections were examined for poly-ADP ribose polymerase-1 (PARP-1) and DNA protein kinase (DNA-PK) expression. Immunohistochemical staining intensities of PARP-1 and DNA-PK were determined (score 0-3) and expression levels were correlated with patients overall survival.

Results

Median survival time of the whole study group was 10.0 months (95% CI 8.1-11.9). Median survival of patients with high and low (?median and <median) tumor PARP-1 levels were 10.0 months (95% CI 7.9-12.1) and 12.0 months (95% CI 8.3-15.7), respectively (p = 0.93). In contrast, median survival of patients with high and low tumor DNA-PK levels were 9.0 months (95% CI 7.2-10.8) and 13.0 months (95% CI 10.7-15.3), respectively (p = 0.02). In multivariate analysis, DNA-PK expression emerged as a significant independent predictor for overall survival (HR 3.9, 95% CI 1.5-10.7, p = 0.01).

Conclusion

This hypothesis generating study showed that high tumor levels of DNA-PK correlate with poor survival of GBM patients. Further studies are needed to confirm these results and to clarify whether DNA-PK inhibitors might have a potential to radiosensitize GBM and improve the treatment outcome of this devastating disease.