Survival analysis after stereotactic ablative radiotherapy for early stage non-small cell lung cancer: a single-institution cohort study.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC), but which patients benefit from stereotactic radiotherapy is unclear. The aim of this study was to analyze prognostic factors for early mortality. METHODS: From August 2010 to 2022, 617 patients with medically inoperable, peripheral or central ES-NSCLC were treated with SABR at our institution. We retrospectively evaluated the data from 172 consecutive patients treated from 2018 to 2020 to analyze the prognostic factors associated with overall survival (OS). The biological effective dose was > 100 Gy10 in all patients, and 60 Gy was applied in 3-5 fractions for a gross tumor volume (GTV) + 3 mm margin when the tumor diameter was < 1 cm; 30-33 Gy was delivered in one fraction. Real-time tumor tracking or an internal target volume approach was applied in 96% and 4% of cases, respectively. In uni- and multivariate analysis, a Cox model was used for the following variables: ventilation parameter FEV1, histology, age, T stage, central vs. peripheral site, gender, pretreatment PET, biologically effective dose (BED), and age-adjusted Charlson comorbidity index (AACCI). RESULTS: The median OS was 35.3 months. In univariate analysis, no correlation was found between OS and ventilation parameters, histology, PET, or centrality. Tumor diameter, biological effective dose, gender, and AACCI met the criteria for inclusion in the multivariate analysis. The multivariate model showed that males (HR 1.51, 95% CI 1.01-2.28; p = 0.05) and AACCI > 5 (HR 1.56, 95% CI 1.06-2.31; p = 0.026) were significant negative prognostic factors of OS. However, the analysis of OS showed that the significant effect of AACCI > 5 was achieved only after 3 years (3-year OS 37% vs. 56%, p = 0.021), whereas the OS in one year was similar (1-year OS 83% vs. 86%, p = 0.58). CONCLUSION: SABR of ES-NSCLC with precise image guidance is feasible for all medically inoperable patients with reasonable performance status. Early deaths were rare in our real-life cohort, and OS is clearly higher than would have been expected after best supportive care.

HPV and RAD51 as Prognostic Factors for Survival in Inoperable Oral and Oropharyngeal Cancer in Patients Unfit for Chemotherapy Treated with Hyperfractionated Radiotherapy.

INTRODUCTION: The incidence of advanced oral cavity and oropharyngeal cancers is generally high. Treatment outcomes for patients, especially those unfit for comprehensive cancer treatment, are unsatisfactory. Therefore, the search for factors to predict response to treatment and increase overall survival is underway. OBJECTIVE: This study aimed to analyze the presence of 32 HPV genotypes in tumor samples of 34 patients and the effect of HPV status and RAD51 on overall survival. METHOD: Tumor samples of 34 patients with locally advanced oropharyngeal or oral cavity cancer treated with accelerated radiotherapy in monotherapy were analyzed using reverse hybridization and immunohistochemistry for the presence of HPV and RAD51. Its effect on overall survival was examined. RESULTS: Only two types of HPV were identified-HPV 16 (dominant) and HPV 66 (two samples). The HPV positivity was associated with a borderline insignificant improvement in 2-year (p = 0.083), 5-year (p = 0.159), and overall survival (p = 0.083). Similarly, the RAD51 overexpression was associated with borderline insignificant improvement in 2-year (p = 0.083) and 5-year (p = 0.159) survival. CONCLUSION: We found no statistically significant differences but detected trends toward improvement in the survival of HPV-positive and RAD51 overexpressing patients unfit for surgical treatment or chemotherapy treated with hyperfractionated radiotherapy. The trends, however, indicate that in a larger group of patients, the effects of these two parameters would likely be statistically significant.

Stereotactic radiotherapy for spinal hemangioblastoma - disease control and volume analysis in long-term follow up.

Background: This retrospective analysis evaluated the long-term outcome of spinal stereotactic body radiotherapy (SBRT) treatment for hemangioblastomas. Materials and methods: Between 2010 and 2018, 5 patients with 18 Von-Hippel Lindau-related pial-based spinal hemangioblastomas were treated with fractionated SBRT. After precisely registering images of all relevant datasets, we delineated the gross tumor volume, spinal cord (including intramedullary cysts and/or syrinxes), and past radiotherapy regions. A sequential optimization algorithm was used for dose determinations, and patients received 25-26 Gy in five fractions or 24 Gy in three fractions. On-line image guidance, based on spinal bone structures, and two orthogonal radiographs were provided. The actuarial nidus control, surgery-free survival, cyst/syrinx changes, and progression-free survival were calculated with the Kaplan-Meier method. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Results: The median follow-up was 5 years after SBRT. Patients displayed one nidus progression, one need of neurosurgery, and two cyst/syrinx progressions directly connected to symptom worsening. No SBRT-related complications or acute adverse radiation-related events occurred. However, one asymptomatic radiological sign of myelopathy occurred two years after SBRT. All tumors regressed; the one-year equivalent tumor volume reduction was 0.2 mL and the median volume significantly decreased by 28% (p = 0.012). Tumor volume reductions were not correlated with the mean (p = 0.19) or maximum (p = 0.16) dose. Conclusions: SBRT for pial-based spinal hemangioblastomas was an effective, safe, viable alternative to neurosurgery in asymptomatic patients. Escalating doses above the conventional dose-volume limits of spinal cord tolerance showed no additional benefit.

Prostate deformation during hypofractionated radiotherapy: an analysis of implanted fiducial marker displacement.

BACKGROUND: To report prostate deformation during treatment, based on an analysis of fiducial marker positional differences in a large sample. MATERIAL AND METHODS: This study included 144 patients treated with prostate stereotactic body radiation therapy after implantation in each of 4 gold fiducial markers (FMs), which were located and numbered consistently. The center of mass of the FMs was recorded for every pair of X-ray images taken during treatment. The distance between each pair of fiducials in the live X-ray images is calculated and compared with the respective distances as determined in the CT volume. The RBE is the difference between these distances. Mean RBE and intrafraction and interfraction RBE were evaluated. The intrafraction and intefraction RBE variability were defined as the standard deviation, respectively, of all RBE during 1 treatment fraction and of the mean daily RBE over the whole treatment course. RESULTS: We analyzed 720 treatment fractions comprising 24,453 orthogonal X-ray image acquisitions. We observed a trend to higher RBE related to FM4 (apex) during treatment. The fiducial marker in the prostate apex could not be used in 16% of observations, in which RBE was > 2.5 mm. The mean RBEavg was 0.93 ± 0.39 mm (range 0.32-1.79 mm) over the 5 fractions. The RBEavg was significantly lower for the first and second fraction compared with the others (P < .001). The interfraction variability of RBEavg was 0.26 ± 0.16 mm (range 0.04-0.74 mm). The mean intrafraction variability of all FMs was 0.45 ± 0.25 mm. The highest Pearson correlation coefficient was observed between FM2 and FM3 (middle left and right prostate) (R = 0.78; P < .001). Every combination with FM4 yielded lower coefficients (range 0.66-0.71; P < .001), indicating different deformation of the prostate apex. CONCLUSIONS: Ideally, prostate deformation is generally small, but it is very sensitive to rectal and bladder filling. We observed RBE up to 11.3 mm. The overall correlation between FMs was affected by shifts of individual fiducials, indicating that the prostate is not a "rigid" organ. Systematic change of RBE average between subsequent fractions indicates a systematic change in prostate shape.

Dose escalation in advanced floor of the mouth cancer: a pilot study using a combination of IMRT and stereotactic boost.

PURPOSE: We evaluated the efficiency and toxicity of stereotactic hypofractionated boost in combination with conventionally fractionated radiotherapy in the treatment of advanced floor of the mouth cancer. METHODS: Thirty-seven patients with advanced stage of the floor of the mouth cancer, histologically confirmed squamous cell carcinoma (p16 negative) ineligible for surgical treatment, were indicated for radiochemotherapy or hyperfractionated accelerated radiotherapy (HART). The radiotherapy protocol combined external beam radiotherapy (EBRT) and a stereotactic hypofractionated boost to the primary tumor. The dose delivered from EBRT was 70-72.5 Gy in 35/50 fractions. The hypofractionated boost followed with 10 Gy in two fractions. For the variables-tumor volume, stage and grade a multivariate analysis was performed to find the relationship between overall survival, local progression and metastasis. Toxicity was evaluated according to CTCAE scale version 4. RESULTS: After a median follow-up of 16 months, 23 patients (62%) achieved complete remission. The median time to local progression and metastasis was 7 months. Local control (LC) at 2 and 5-years was 70% and 62%, respectively. Progression-free survival (PFS) and overall survival (OS) were 57% and 49% at 2 years and 41% and 27% at 5 years, respectively. Statistical analysis revealed that larger tumors had worse overall survival and a greater chance of metastasis. Log-Rank GTV > 44 ccm (HR = 1.96; [95% CI (0.87; 4.38)]; p = 0.11). No boost-related severe acute toxicity was observed. Late osteonecrosis was observed in 3 patients (8%). CONCLUSION: The combination of EBRT and stereotactic hypofractionated boost is safe and seems to be an effective option for dose escalation in patients with advanced floor of the mouth tumors who are ineligible for surgical treatment and require a non-invasive approach.

The use of a battery of examination methods for detection of cervical metastases in squamous cell carcinoma of the oral cavity.

INTRODUCTION: In patients with squamous cell carcinoma of the orofacial area, the presence of cervical metastases represents a single most significant prognostic factor. This fact underlines the importance of thorough examination of the cervical lymph nodes for potential tumor involvement. To verify this, the most common investigative methods are physical examination (PE), sonography (US) and computed tomography (CT), which have also been used to assess the stage of the disease in the patients in our research. OBJECTIVE: To evaluate the performance of individual methods (physical examination, sonography, computed tomography) and combinations. METHOD: Patients with squamous cell carcinoma of the oral cavity, who had undergone physical, US and CT examinations at our department followed by radical neck dissection were included in this retrospective study. A total of 57 patients were included. RESULTS: The sensitivity of PE, US and CT were 38%, 69% and 61%, respectively, however CT+US combination yielded 83% sensitivity and combination of all these methods 86% sensitivity. The number of false positives was however relatively high with specificity of the 3-way combination at 65%. CONCLUSION: A combination of our three widely available inexpensive methods detected 86% of metastases in cervical nodes. The large number of false positives however indicates that the method should rather be used for screening in selecting patients who need additional and more expensive imaging than for diagnosing cervical metastases. Also, as 14% of cervical metastases pass undetected using our method, we would recommend an additional examination at least by US+PE several weeks to a few months after the initial examination.

Evaluation of spine structure stability at different locations during SBRT.

BACKGROUND AND AIMS: Modern stereotactic body radiotherapy (SBRT) techniques and systems that use online image guidance offer frameless radiotherapy of spinal tumors and the ability to control intrafraction motion during treatment. These systems allow precise alignment of the patient during the entire treatment session and react immediately to random changes in this alignment. Online tracking data provide information about intrafractional changes, and this information can be useful for designing treatment strategies even if online tracking is not being used. The present study evaluated spine motion during SBRT treatment to assess the risk of verifying patient alignment only prior to starting treatment. METHODS: This study included 123 patients treated with spine SBRT. We analyzed different locations within the spine using system log files generated during treatment, which contain information about differences in the pretreatment reference spine positions by CT versus positions during SBRT treatment. The mean spine motion and intra/interfraction motion was evaluated. We defined and assessed the spine stability and spine significant shifts (SSHs) during treatment. RESULTS: We analyzed 462 fractions. For the cervical (C) spine, the greatest shifts were in the anterior-posterior (AP) direction (2.48 mm) and in pitch rotation (1.75 deg). The thoracic (Th) spine showed the biggest shift in the AP direction (3.68 mm) and in roll rotation (1.66 deg). For the lumbar-sacral (LS) spine, the biggest shift was found for left-right (LR) translation (3.81 mm) and roll rotation (3.67 deg). No C spine case exceeded 1 mm/1 deg for interfraction variability, but 7 of 54 Th spine cases exceeded 1 mm interfraction variability for translations (maximum value, 2.5 mm in the AP direction). The interfraction variability for translations exceeded 1 mm in 2 of 24 LS spine cases (maximum value, 1.7 mm in the LR direction). Only 13% of cases had no SSHs. The mean times to SSH were 6.5±3.9 min, 8.1±5.9 min, and 8.8±7.1 min for the C, Th, and LS spine, respectively, and the mean recorded SSH values were 1.6±0.66, 1.43±0.33, and 1.46±0.47 mm/deg, respectively. CONCLUSION: Positional tracking during spine SBRT treatments revealed low mean translational and rotational shifts. Patient immobilization did not improve spine shifts compared with our results for the Th and LS spine without immobilization. For the most precise spine SBRT, we recommend checking the patient's position during treatment.