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.

Dose escalation can maximize therapeutic potential of sunitinib in patients with metastatic renal cell carcinoma.

BACKGROUND: In patients with metastatic renal cell cancer, based on limited evidence, increased sunitinib exposure is associated with better outcome. The survival and toxicity data of patients receiving individualized dose escalated sunitinib therapy as compared to standard management were analyzed in this study. METHODS: From July 2013, the data of metastatic renal cell cancer patients with slight progression but still a stable disease according to RECIST 1.1 criteria treated with an escalated dose of sunitinib (first level: 62.5 mg/day in 4/2 or 2 × 2/1 scheme, second level: 75 mg/day in 4/2 or 2 × 2/1 scheme) were collected prospectively. Regarding characteristics, outcome, and toxicity data, an explorative retrospective analysis of the register was carried out, comparing treatments after and before July 1, 2013 in the study (selected patients for escalated dose) and control (standard dose) groups, respectively. RESULTS: The study involved 103 patients receiving sunitinib therapy with a median overall and progression free survival of 25.36 ± 2.62 and 14.2 ± 3.22 months, respectively. Slight progression was detected in 48.5% of them. First and second-level dose escalation were indicated in 18.2% and 4.1% of patients, respectively. The dosing scheme was modified in 22.2%. The median progression free survival (39.7 ± 5.1 vs 14.2 ± 1.3 months (p = 0.037)) and the overall survival (57.5 ± 10.7 vs 27.9 ± 2.5 months (p = 0.044)) were significantly better in the study group (with dose escalation) than in the control group. Patients with nephrectomy and lower Memorial Sloan Kettering Cancer Center (MSKCC) scores showed more favorable outcomes. After dose escalation, the most common adverse events were worsening or development of fatigue, hypertension, stomatitis, and weight loss of over 10%. CONCLUSIONS: Escalation of sunitinib dosing in selected patients with metastatic renal cell cancer, especially in case of slight progression, based on tolerable toxicity is safe and improves outcome. Dose escalation in 12.5 mg steps may be recommended for properly educated patients.

A simple clinical method for predicting the benefit of prone vs. supine positioning in reducing heart exposure during left breast radiotherapy.

BACKGROUND AND PURPOSE: The benefit of reduced radiation heart exposure in the prone vs. supine position individually differs. In this prospective cohort study, the goal was to develop a simple method for the operation of a validated model for the prediction of preferable treatment position during left breast radiotherapy. MATERIAL AND METHODS: In 100 cases, a single CT slice was utilized for the collection of the needed patient-specific data (in addition to body mass index, the distance of the LAD from the chest wall and the area of the heart included in the radiation fields at the middle of the heart in the supine position). Outcome was analyzed in relation to the full CT series acquired in both positions and dosimetric data. RESULTS: Great consistency was found between the tested and original method regarding sensitivity and specificity. The prioritization of LAD dose, and the use of heart dose and position-specific dose constraints as safety measures ensure sensitivity and specificity values of 82.8% and 87.3%, respectively. In an additional "routine clinical practice" series of 60 patients the new method seemed feasible in routine clinical practice. External testing on a 28-case series indicated similar accuracy. CONCLUSION: We consider this simple clinical tool appropriate for assisting individual positioning aiming at maximum heart protection during left breast irradiation.

[Therapeutic significance of sunitinib-induced "off-target" side effects]. / Sunitinib indukálta "off-target" mellékhatások terápiás jelentõsége.

Sunitinib is a basic medicine in the therapy of metastatic clear cell renal carcinoma. Our aim was to retrospectively evaluate the efficacy of sunitinib in the everyday clinical practice taking the most common side effects and clinical features into consideration. Data of ninety-four patients with metastatic, clear cell renal carcinoma, receiving sunitinib therapy were analyzed retrospectively, regarding efficacy and toxicity. Factors potentially influencing progression-free survival (PFS) and overall survival (OS) [age, nephrectomy, "off-target" side effects that are not connected to vascular endothelial growth factor receptor (VEGFR)] were studied. Complete remission, partial remission and stable disease occurred in 8 (8.5%), 30 (31.9%) and 50 (53.1%) patients, respectively. Objective tumor response developed in 38 (40.4%) cases. Median PFS and OS were 18.3 (95% CI 14.45-22.14) and 27.9 (95% CI 20.95-34.85) months, respectively. PFS and OS were more favorable in case of hypothyreosis (pPFS=0.005, pOS=0.043), hand-foot syndrome (pPFS=0.006, pOS=0.008), grade ≥2 neutropenia (pPFS=0.003, pOS=0.008) and thrombocytopenia (pPFS=0.01, pOS=0.011). Effective therapy of manageable side effects (most of which have potential predictive effect) is important for favorable survival results. Maintenance of dose intensity is also essential in order to compare the daily routine with the efficacy and safety results of clinical trials.

Radiation dose to the nodal regions during prone versus supine breast irradiation.

BACKGROUND: Prone positioning for breast radiotherapy is preferable when the aim is a reduction of the dose to the ipsilateral lung or the heart in certain left-sided cases. MATERIALS AND METHODS: In 100 breast cancer cases awaiting postoperative whole-breast radiotherapy, conformal radiotherapy plans were prospectively generated in both prone and supine positions. The axillary nodal region (levels I-III) and internal mammary (IM) lymph-node region in the upper three intercostal spaces were retrospectively contoured. The mean doses to the nodal regions and the volume receiving 25 Gy (V25Gy), V45Gy, and V47.5Gy were compared between the two treatment positions. RESULTS: In most cases, the doses to axillary levels I-III and the IM lymph nodes were inadequate, regardless of the treatment position. The nodal doses were significantly lower in the prone than in the supine position. The radiation doses to levels II-III and IM nodes were especially low. The V45Gy and V47.5Gy of the level I axillary lymph nodes were 54.6% and 40.2%, respectively, in the supine, and 3.0% and 1.7%, respectively, in the prone position. In the supine position, only 17 patients (17%) received a mean dose of 45 Gy to the axillary level I nodes. CONCLUSION: The radiation dose to the axillary and IM lymph nodes during breast radiotherapy is therapeutically insufficient in most cases, and is significantly lower in the prone position than in the supine position.

Individualized positioning for maximum heart protection during breast irradiation.

BACKGROUND: Prone positioning has been found feasible and appropriate for the reduction of radiation exposure of the lungs, but its effects on the heart dose remain controversial. Individual anatomical features were sought for the selection of optimal treatment positioning. MATERIAL AND METHODS: In 138 left-sided breast cancer cases awaiting postoperative whole-breast radiotherapy, conformal radiotherapy plans were generated in both prone and supine positions. RESULTS: The radiation doses to the left anterior descending coronary artery (LAD) and heart in the two positions differed individually, and were strongly related to the body mass index (BMI). Image fusion of the CT scans revealed that prone positioning was detrimental if the heart was situated distant from the chest wall in the supine position, but moved to the chest wall in the prone position. For characterization of the geography of the heart and the breast, the median distance between the LAD and the chest wall (dmedian), and the heart area included in the radiation field on a single CT scan at the middle of the heart in the supine position (Aheart) proved most appropriate. CONCLUSION: A validated statistical model, utilizing the BMI, dmedian and Aheart, permits individualized positioning for maximum heart protection.

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.

Role of systemic therapy in the development of lung sequelae after conformal radiotherapy in breast cancer patients.

PURPOSE: To analyze the risk of radiogenic lung damage in breast cancer patients after conformal radiotherapy and different forms of systemic treatment. METHODS AND MATERIALS: In 328 patients receiving sequential taxane-based chemotherapy, concomitant hormone therapy (tamoxifen or aromatase inhibitors), or no adjuvant systemic therapy, symptomatic and asymptomatic lung sequelae were prospectively evaluated via the detection of visible CT abnormalities, 3 months or 1 year after the completion of the radiotherapy. RESULTS: Significant positive associations were detected between the development of both pneumonitis and fibrosis of Grade 1 and patient age, ipsilateral mean lung dose, volume of the ipsilateral lung receiving 20 Gy, and irradiation of the regional lymph nodes. In multivariate analysis, age and mean lung dose proved to be independent predictors of early (odds ratio [OR] = 1.035, 95% confidence interval [CI] 1.011-1.061 and OR = 1.113, 95% CI 1.049-1.181, respectively) and late (OR = 1.074, 95% CI 1.042-1.107 and OR = 1.207, 95% CI 1.124-1.295, respectively) radiogenic lung damage, whereas the role of systemic therapy was significant in the development of Grade 1 lung fibrosis (p = 0.01). Among the various forms of systemic therapy, tamoxifen increased the risk of late lung sequelae (OR = 2.442, 95% CI 1.120-5.326, p = 0.025). No interaction was demonstrated between the administration of systemic therapy and the other above-mentioned parameters as regards the risk of radiogenic lung damage. CONCLUSIONS: Our analyses demonstrate the independent role of concomitant tamoxifen therapy in the development of radiogenic lung fibrosis but do not suggest such an effect for the other modes of systemic treatment.

The risk of early and late lung sequelae after conformal radiotherapy in breast cancer patients.

PURPOSE: To study the risks of early and late radiogenic lung damage in breast cancer patients after conformal radiotherapy. METHODS AND MATERIALS: Radiogenic lung sequelae were assessed prospectively in 119 patients by means of clinical signs, radiologic abnormalities, and the mean density change (MDC) of the irradiated lung on CT. RESULTS: Significant positive associations were detected between the development of lung abnormalities 3 months or 1 year after the radiotherapy and the age of the patient, the ipsilateral mean lung dose (MLD), the radiation dose to 25% of the ipsilateral lung (D(25%)) and the volume of the ipsilateral lung receiving 20 Gy (V(20 Gy)). The irradiation of the axillary and supraclavicular lymph nodes favored the development of pneumonitis but not that of fibrosis. No relation was found between the preradiotherapy plasma TGF-beta level and the presence of radiogenic lung damage. At both time points, MDC was strongly related to age. Significant positive associations were demonstrated between the risks of pneumonitis or fibrosis and the age of the patient, MLD, D(25%), and V(20 Gy). A synergistic effect of MLD, D(25%), and V(20 Gy) with age in patients older than 59 years is suggested. CONCLUSION: Our analyses indicate that the risks of early and late radiogenic lung sequelae are strongly related to the age of the patient, the volume of the irradiated lung, and the dose to it.