Survival Benefit of Stereotactic Radiotherapy in the Complex Management of Metastatic Melanoma.

BACKGROUND/AIM: Targeted therapy and immunotherapy, with additional stereotactic radiation therapy (SRT) have revolutionized the management of metastatic malignant melanoma (mMM). We aimed to analyze the effectiveness and safety of SRT and determine its role in the complex management of mMM. PATIENTS AND METHODS: We treated 24 patients with solitary metastasis, 15 with oligometastatic disease and one with multiple metastases. The primary endpoint was to investigate the possible effect of stereotactic radiotherapy for metastatic lesions on patients' survival taking the systemic therapy into consideration. RESULTS: The median overall survival (OS) for the entire group was 30.07 months; 50% of them received immunotherapy, 32% received targeted therapy. Complete remission of the irradiated lesions was observed in six patients, partial tumor response was achieved in 13, while stable disease was detected in 10; tumor progression occurred in four cases. Compartmental recurrence (recurrence in the brain in a not previously irradiated region) developed in seven patients. OS was significantly longer in those with extracranial metastases treated with stereotactic body radiotherapy in comparison to brain SRT. We found a strong correlation between tumor response and mean OS (42.5 months after complete or partial remission versus 11.8 months in those with stable or progressive disease). No OS difference was observed according to the number of irradiated lesions or type of systemic therapy before SRT (no therapy: 43.6 months, with therapy: 25.7 months). Significant OS advantage was shown when immunotherapy was administered post-SRT (mean OS: with immunotherapy: 39.6 months, no immunotherapy: 18.5 months). CONCLUSION: In the case of oligometastatic MM, SRT can be used safely and with good efficiency in addition to targeted therapy/anti-programmed cell death protein 1 therapy. Improved survival warrants including SRT in the complex management of mMM, however, further studies are needed for SRT optimization.

Prostate-specific membrane antigen-based imaging for stereotactic irradiation of low-volume progressive prostate cancer: a single-center experience.

Introduction: Prostate-specific membrane antigen (PSMA) is a transmembrane protein that may be expressed on the surface of prostate cancer (PC) cells. It enables a more sensitive and specific diagnosis PC, compared to conventional anatomical imaging. Aim: The integration of PSMA-based imaging in the personalized radiotherapy of PC patients and the evaluation of its impact on target volume definition if stereotactic body radiotherapy (SBRT) is planned for locally recurrent or oligometastatic disease. Patients and methods: The data from 363 examinations were analyzed retrospectively. Inclusion criteria were histologically verified PC and clinical data suggesting local recurrence or distant metastasis. Whole-body 99mTc-PSMA-I&S single-photon emission computed tomography (SPECT)/CT or 18F-JK-PSMA-7 positron emission tomography/computer tomography (PET/CT) was carried out, and the evaluation of the scans and biological tumor volume contouring was performed at the Department of Nuclear Medicine. The target volume delineation on topometric CT (TCT) scan was performed at the Department of Oncotherapy. The comparison of the two volumes was performed by image fusion and registration. Results: From 363 PSMA isotope-based examinations, 84 lesions of 64 patients were treated with SBRT. In 50 patients, 70 lesions were examined for intermodality comparison. The target volume defined by the PSMA density was significantly smaller than the tumor size defined by the TCT scan: GTVCT (gross tumor volume on the TCT), 27.58 ± 46.07 cm3; BTVPSMA (biological target volume on the PSMA-based examination), 16.14 ± 29.87 cm3. During geometrical analyses, the Dice similarity coefficient (DSC) was 0.56 ± 0.20 (0.07-0.85). Prostate-specific antigen (PSA) control was performed to evaluate the response: mean pre-radiotherapy (pre-RT) PSA was 16.98 ng/ml ( ± SD: 33.81), and post-RT PSA at 3 months after SBRT was 11.19 ng/ml ( ± SD: 32.85). Three-month post-therapy PSMA-based imaging was performed in 14 cases, in which we observed a decrease or cessation of isotope uptake. Conventional imaging control was performed in 42 cases (65.6% of all cases): 22 (52.4%) complete remissions, 14 (33.3%) partial remissions, four (9.5%) stable diseases, and two (4.8%) progressive diseases were described. Conclusion: PSMA-based imaging is a promising diagnostic method for specifying the stage and detecting the low-volume progression. Our results suggest that PSMA-based hybrid imaging can influence treatment decisions and target volume delineation for SBRT.

Adaptive Radiotherapy for Glioblastoma Multiforme - The Impact on Disease Outcome.

BACKGROUND/AIM: To study the changes of glioblastoma multiforme during chemoradiotherapy (CRT) and to evaluate the impact of changes on dosimetry and clinical outcomes. PATIENTS AND METHODS: Forty-three patients underwent volumetric imaging-based replanning. Prognostic factors and gross tumor volume changes in relation to overall survival and the effect of adaptive replanning were statistically analyzed. RESULTS: Patients with total tumor removal, with shorter time to CRT (<27 days), with methylated O-6 methylguanine DNA methyltransferase and good performance status (>60%) had better survival. Tumor shrinkage in 24 patients resulted in improved survival compared to 19 in whom tumor was unchanged or progressed (25.3 vs. 11.1 months, p=0.04). Adapted planning target volume allowed a reduction in irradiated volume, while increasing survival (12.06 vs. 28.98 months, p=0.026). CONCLUSION: Tumor response during CRT has significant impact on the outcome. Adaptation of the planning target volume to the tumor changes proved to be beneficial and warrants further investigation.

Low Fraction Size Re-irradiation for Large Volume Recurrence of Glial Tumours.

The aim of the present study was to evaluate the efficacy of re-irradiation (re-RT) in patients with advanced local relapses of glial tumours and to define the factors influencing the result of the hyper-fractionated external beam therapy on progression after primary management. We have analysed the data of 55 patients with brain tumours (GBM: 28) on progression, who were re-irradiated between January 2007 and December 2018. The mean volume of the recurrent tumour was 118 cm3, and the mean planning target volume (PTV) was 316 cm3, to which 32 Gy was delivered in 20 fractions at least 7.7 months after the first radiotherapy, using 3D conformal radiotherapy (CRT) or intensity modulated radiotherapy (IMRT). The median overall survival (mOS) from the re-RT was 8.4 months, and the 6-month and the 12-month OS rate was 64% and 31%, respectively. The most important factors by univariate analysis, which significantly improved the outcome of re-RT were the longer time interval between the diagnosis and second radiotherapy (p = 0.029), the lower histology grade (p = 0.034), volume of the recurrent tumour (p = 0.006) and Karnofsky performance status (KPS) (p = 0.009) at the re-irradiation. Our low fraction size re-irradiation ≥ 8 months after the first radiotherapy proved to be safe and beneficial for patients with large volume recurrent glial tumours.

Boost Irradiation Integrated to Whole Brain Radiotherapy in the Management of Brain Metastases.

Our retrospective analysis aimed to evaluate the clinical value of dose intensification schemes: WBRT and consecutive, delayed, or simultaneous integrated boost (SIB) in brain metastasis (BM) management. Clinical data and overall survival (OS) of 468 patients with BM from various primaries treated with 10 × 3 Gy WBRT (n = 195), WBRT+ 10 × 2 Gy boost (n = 125), or simultaneously 15 × 2.2 Gy WBRT+0.7 Gy boost (n = 148) during a 6-year period were statistically analysed. Significant difference in OS could be detected with additional boost to WBRT (3.3 versus 6.5 months) and this difference was confirmed for BMs of lung cancer and melanoma and both for oligo- and multiplex lesions. The OS was prolonged for the RPA 2 and RPA3 categories, if patients received escalated dose, 4.0 vs. 7.7 months; (p = 0.002) in class RPA2 and 2.6 vs. 4.2 months; (p < 0.0001) in the class RPA 3 respectively. The significant difference in OS was also achieved with SIB. The shortened overall treatment time of SIB with lower WBRT fraction dose exhibited survival benefit over WBRT alone, and could be applied for patients developing BM even with unfavourable prognostic factors. These results warrant for further study of this approach with dose escalation using the lately available solutions for hippocampus sparing and fractionated stereotactic irradiation. The simultaneous delivery of WBRT with reduced fraction dose and boost proved to be advantageous prolonging the OS with shortened treatment time and reduced probability for cognitive decline development even for patients with poor performance status and progressing extracranial disease.

Subventricular zone volumetric and dosimetric changes during postoperative brain tumor irradiation and its impact on overall survival.

PURPOSE: The aim of this retrospective study was to investigate the relationship between the dose to the subventricular zone (SVZ) and overall survival (OS) of 41 patients with glioblastoma multiforme (GBM), who were treated with an adaptive approach involving repeated topometric CT and replanning at two-thirds (40 Gy) of their course of postoperative radiotherapy for planning of a 20 Gy boost. METHODS: We examined changes in the ipsilateral lateral ventricle (LV) and SVZ (iLV and iSVZ), as well as in the contralateral LV and SVZ (cLV and cSVZ). We evaluated the volumetric changes on both planning CT scans (primary CT1 and secondary CT2). The survival of the GBM patients was analyzed using the Kaplan-Meier method; the multivariate Cox regression was also performed. RESULTS: Median follow-up and OS were 34.5 months and 17.6 months, respectively. LV and SVZ structures exhibited significant volumetric changes on CT2, resulting in an increase of dose coverage. At a cut-off point of 58 Gy, a significant correlation was detected between the iSVZ2 mean dose and OS (27.8 vs 15.6 months, p = 0.048). In a multivariate analysis, GBM patients with a shorter time to postoperative chemoradiotherapy (<3.8 weeks), with good performance status (≥70%) and higher mean dose (≥58 Gy) to the iSVZ2 had significantly better OS. CONCLUSIONS: Significant anatomical and dose distribution changes to the brain structures were observed, which have a relevant impact on the dose-effect relationship for GBM; therefore, involving the iSVZ in the target volume should be considered and adapted to the changes.

Prone Positioning on a Belly Board Decreases Rectal and Bowel Doses in Pelvic Intensity-Modulated Radiation Therapy (IMRT) for Prostate Cancer.

The presence of normal tissues in the irradiated volume limits dose escalation during pelvic radiotherapy (RT) for prostate cancer. Supine and prone positions on a belly board were compared by analyzing the exposure of organs at risk (OARs) using intensity modulated RT (IMRT). The prospective trial included 55 high risk, localized or locally advanced prostate cancer patients, receiving definitive image-guided RT. Computed tomography scanning for irradiation planning was carried out in both positions. Gross tumor volume, clinical and planning target volumes (PTV) and OARs were delineated, defining subprostatic and periprostatic rectal subsegments. At the height of the largest antero-posterior (AP) diameter of the prostate, rectal diameters and distance from the posterior prostate wall were measured. IMRT plans were generated. Normal tissue exposure and structure volumes were compared between supine and prone plans using paired t-test. In the volumes of the prostate, PTV, colon and small bowel, no significant differences were found. In prone position, all rectal volumes, diameters, and rectum-prostate distance were significantly higher, the irradiated colon and small bowel volume was lower in dose ranges of 20-40 Gy, and the exposure to all rectal segments was more favorable in 40-75 Gy dose ranges. No significant difference was found in the exposure of other OARs. Prone positioning on a belly board is an appropriate positioning method aiming rectum and bowel protection during pelvic IMRT of prostate cancer. The relative reduction in rectal exposure might be a consequence of the slight departure between the prostate and rectal wall.

Daily Setup Accuracy, Side-effects and Quality of Life During and After Prone Positioned Prostate Radiotherapy.

BACKGROUND/AIM: Exposure of organs at risk with prostate radiotherapy (RT) is lower in the prone position. This study is a prospective evaluation of setup accuracy, side-effects, and quality of life (QOL) during and after prone positioned RT. PATIENTS AND METHODS: Image-guided (IG) intensity-modulated (IM) RT was administered in prone position on belly-board to 55 high-risk prostate cancer (PC) patients. Rectum diameters were measured in two areas of the symphysis at the beginning of RT and during it. Side-effects, QOL, and prostate specific symptoms (PSS) were evaluated. RESULTS: Setup accuracy was similar to that reported in the literature. In the upper area of symphysis rectal diameters were significantly changed during treatment, but in the prostate region, no difference was detected. No change was detected in patients' QOL and PSS during treatment, but after RT, they improved. CONCLUSION: Prone positioned IG-IMRT is feasible with tolerable side-effects for high-risk PC patients. Changes in QOL and PSS are insignificant during RT, while improvement after RT suggests a rapid recovery.

Moving gantry method for electron beam dose profile measurement at extended source-to-surface distances.

A novel method has been put forward for very large electron beam profile measurement. With this method, absorbed dose profiles can be measured at any depth in a solid phantom for total skin electron therapy. Electron beam dose profiles were collected with two different methods. Profile measurements were performed at 0.2 and 1.2 cm depths with a parallel plate and a thimble chamber, respectively. 108cm × 108 cm and 45 cm × 45 cm projected size electron beams were scanned by vertically moving phantom and detector at 300 cm source-to-surface distance with 90° and 270° gantry angles. The profiles collected this way were used as reference. Afterwards, the phantom was fixed on the central axis and the gantry was rotated with certain angular steps. After applying correction for the different source-to-detector distances and incidence of angle, the profiles measured in the two different setups were compared. Correction formalism has been developed. The agreement between the cross profiles taken at the depth of maximum dose with the 'classical' scanning and with the new moving gantry method was better than 0.5 % in the measuring range from zero to 71.9 cm. Inverse square and attenuation corrections had to be applied. The profiles measured with the parallel plate chamber agree better than 1%, except for the penumbra region, where the maximum difference is 1.5%. With the moving gantry method, very large electron field profiles can be measured at any depth in a solid phantom with high accuracy and reproducibility and with much less time per step. No special instrumentation is needed. The method can be used for commissioning of very large electron beams for computer-assisted treatment planning, for designing beam modifiers to improve dose uniformity, and for verification of computed dose profiles.

Clinical course of central neurocytoma with malignant transformation-an indication for craniospinal irradiation.

Central neurocytoma is generally considered to be a benign tumor and the literature suggests that a cure may be attained by surgery ± adjuvant focal irradiation. However, there is a need for change in the therapeutic strategy for the subgroup of patients with aggressive central neurocytoma. An example case is presented and the literature on central neurocytoma cases with malignant features and dissemination via the cerebrospinal fluid is reviewed and the radiotherapeutic strategies available for central neurocytoma treatment is discussed. Nineteen cases including the present report with a malignant course and cerebrospinal fluid dissemination have been described to date, most of them involving an elevated MIB-1 labeling index. Our case exhibited atypical central neurocytoma with an initially elevated MIB-1 labeling index (25-30 %). The primary treatment included surgery and focal radiotherapy. Three years later the disease had disseminated throughout the craniospinal axis. A good tumor response and symptom relief were achieved with repeated radiation and temozolomide chemotherapy. Central neurocytoma with an initially high proliferation activity has a high tendency to spread via the cerebrospinal fluid. The chemo- and radiosensitivity of the tumor suggest a more aggressive adjuvant therapy approach. Cases with a potential for malignant transformation should be identified and treated appropriately, including irradiation of the entire neuroaxis and adjuvant chemotherapy may be considered.

Acute oesophageal toxicity related to paclitaxel-based concurrent chemoradiotherapy for non-small cell lung cancer.

BACKGROUND: Dosimetric data and acute oesophageal toxicity (AET) during chemoradiotherapy (CRT) were evaluated in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty patients were treated with paclitaxel-based conformal CRT with a mean ± SD dose of 60.7 ± 9.8 Gy. The oesophageal toxicity was prospectively registered and evaluated in relation to the maximal dose (Dmax), mean dose (D(mean)), length and volume of oesophagus irradiated with 35-60 Gy (V(35-60Gy)), and according to the seriousness of AET. RESULTS: Dmax and D(mean) to the oesophagus were 57.0 ± 10.8 Gy and 24.9 ± 9.0 Gy, respectively. AET of grade 1, 2 and 3 developed in 16 (32%), 14 (28%) and three (6%) cases, respectively. The Dmax, D(mean), length and the V(35-60Gy) were all related to dysphagia (p<0.001). V(45Gy) was the most reliable predictor of AET of grade 2 or more. CONCLUSION: Our results indicate that keeping oesophageal V(45Gy) below 32.5% can prevent severe AET during CRT of NSCLC.

A prospective study of supine versus prone positioning and whole-body thermoplastic mask fixation for craniospinal radiotherapy in adult patients.

PURPOSE: To evaluate neuroaxis irradiation for adults in the supine position using head body thermoplastic mask fixation, from the aspects of dose distribution, patient comfort and set-up accuracy. METHODS AND MATERIALS: Nine of the 12 adult patients were positioned for craniospinal axis irradiation in both prone and supine positions. After mask fixation and planning CTs in both positions, a questionnaire relating to the comfort was completed. The doses to the target and to the organs at risk of the 3D conformal plans in the supine and prone positions were compared. Portal images of all 12 patients irradiated in the supine position were evaluated, the van Herk formulas being used to calculate the systemic and random errors. RESULTS: No significant difference was found between the prone and supine positions target coverage, the dose homogeneity and the dose to the organs at risk. The supine position was considered more comfortable by the patients (scores of 2.8 versus 4.29), with a vector random error of 3.27 mm, and a systematic error of 0.32 mm. The largest random set-up error was observed in the lateral direction: 4.83 mm. CONCLUSIONS: The more comfortable supine position is recommended for craniospinal irradiation in adult patients. Whole-body thermoplastic mask immobilization provides excellent repositioning accuracy.

[Vertebral metastasis from malignant degeneration of urethro-perineal fistula. A case report]. / Urethro-perinealis fisztula tumoros elfajulásának diagnosztikája ágyéki csigolya metasztázisa alapján. Esetismertetés.

Adenocarcinoma mucinusum of the anal canal is a rare tumour, which may appear as a fistula. The fistula has an effect on quality of life and besides it may lead to tumour formation. Early recognition and regular check-up are important, and early operation is recommended. Early surgical excision combined with chemo- and radiotherapy may be effective, with 5 year recurrence rate lower than 37%. The prognosis of late treatment is poor with 1 year average survival. Our case report presents evidence that the key to successful therapy and improved quality of life is early diagnosis and combined surgical-oncological treatment.