Fractionated stereotactic radiotherapy in craniopharyngiomas: A systematic review and single arm meta-analysis.

INTRODUCTION: Numerous studies have demonstrated Fractionated Stereotactic Radiotherapy's (FSRT) effectiveness in tumor control post-resection for craniopharyngiomas. Nevertheless, past literature has presented conflicting findings particularly regarding endocrine and visual function outcomes. This study aims to elucidate FSRT's efficacy and safety for this population. METHODS: Adhering to PRISMA, a systematic review and meta-analyses was conducted. Included studies had to report the effects of FSRT for treating craniopharyngiomas in a sample greater than four patients, addressing at least one of the outcomes of interest: improvement in visual acuity or field, new-onset hypopituitarism, effectiveness, and tumor progression. Relative risk with 95% confidence intervals were used to assess the outcomes. RESULTS: After retrieving a total of 1292 studies, 10 articles met the predefined criteria and thus were finally selected, amounting to a total of 256 patients. The improvement in visual acuity was estimated at 45% (95% CI: 6-83%), while the improvement in the visual field was 22% (95% CI: 0-51%). Regarding endocrine function, the new-onset hypopituitarism rate was found to be 5% (95% CI: 0-11%). Relative to FSRT effectiveness, the pooled estimate of the complete tumor response rate was 17% (95% CI: 4-30%), and the tumor progression rate was 7% (95% CI: 1-13%). Also, a 3-year progression-free survival rate of 98% (95% CI: 95-100%) was obtained. CONCLUSION: Despite limitations and risks, FSRT shows promise as a viable therapeutic option for craniopharyngiomas, offering notable benefits for visual functions and tumor control. Further research is required to better understand the associated risks, benefits, and clinical utility.

Surface guided radiation therapy with an innovative open-face mask and mouth bite: patient motion management in brain stereotactic radiotherapy.

INTRODUCTION: To guarantee treatment reproducibility and stability, immobilization devices are essential. Additionally, surface-guided radiation therapy (SGRT) serves as an accurate complement to frameless stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) by aiding patient positioning and real-time monitoring, especially when non-coplanar fields are in use. At our institute, we have developed a surface-guided SRS (SG-SRS) workflow that incorporates our innovative open-face mask (OM) and mouth bite (MB) to guarantee a precise and accurate dose delivery. METHODS: This study included 40 patients, and all patients were divided into closed mask (CM) and open-face mask (OM) groups according to different positioning flow. Cone beam computed tomography (CBCT) scans were performed, and the registration results were recorded before and after the treatment. Then Bland-Altman method was used to analyze the consistency of AlignRT-guided positioning errors and CBCT scanning results in the OM group. The error changes between 31 fractions in one patient were recorded to evaluate the feasibility of monitoring during treatment. RESULTS: The median of translation error between stages of the AlignRT positioning process was (0.03-0.07) cm, and the median of rotation error was (0.20-0.40)°, which were significantly better than those of the Fraxion positioning process (0.09-0.11) cm and (0.60-0.75)°. The mean bias values between the AlignRT guided positioning errors and CBCT were 0.01 cm, - 0.07 cm, 0.03 cm, - 0.30°, - 0.08° and 0.00°. The 31 inter-fractional errors of a single patient monitored by SGRT were within 0.10 cm and 0.50°. CONCLUSIONS: The application of the SGRT with an innovative open-face mask and mouth bite device could achieve precision positioning accuracy and stability, and the accuracy of the AlignRT system exhibits excellent constancy with the CBCT gold standard. The non-coplanar radiation field monitoring can provide reliable support for motion management in fractional treatment.

The role of stereotactic body radiotherapy in switching systemic therapy for patients with extracranial oligometastatic renal cell carcinoma.

BACKGROUND: Targeting oligometastatic lesions with metastasis-directed therapy (MDT) using stereotactic-body radiotherapy (SBRT) may improve treatment outcomes and postpone the need for second-line systemic therapy (NEST). We looked at the results of oligometastatic renal cell carcinoma (RCC) patients who had five or fewer lesions and were treated with SBRT. METHODS: We examined the treatment outcomes of 70 extracranial metastatic RCC (mRCC) patients treated at two oncology centers between 2011 and 2020. The clinical parameters of patients with and without NEST changes were compared. The prognostic factors for overall survival (OS), progression-free survival (PFS), and NEST-free survival were evaluated. RESULTS: Median age was 67 years (range 31-83 years). Lung and bone metastasis were found in 78.4% and 12.6% of patients, respectively. With a median follow-up of 21.1 months, median OS was 49.1 months and the median PFS was 18.3 months. Histology was a prognostic factor for OS, BED, and treatment switch for PFS in univariate analysis. In multivariate analysis, the significant predictor of poor OS was clear cell histology, and a lower BED for PFS. Following SBRT for oligometastatic lesions, 19 patients (27.2%) had a median NEST change of 15.2 months after MDT completion. There were no significant differences in median OS or PFS between patients who had NEST changes and those who did not. No patient experienced grade ≥ 3 acute and late toxicities. CONCLUSIONS: The SBRT to oligometastatic sites is an effective and safe treatment option for ≤ 5 metastases in RCC patients by providing favorable survival and delaying NEST change.

Local ablative therapy of brain metastasis from non-small cell lung cancer: benefits and limitations.

Brain metastases (BMs) are the most common intracranial tumors and non-small cell lung cancer (NSCLC) are responsible for BM more than any other solid tumor. Its frequency is increasing due to of the availability of new imaging techniques, earlier diagnosis and improvement in treatment techniques and survival rates. NSCLC patients with BM represent heterogeneous prognostic group. The possibility of better prognostic stratification associated with more systemic therapy options and imaging and radiation technology advances have led to an increment of evaluation and indication of local ablative radiotherapy. The definite increment in quality of life and the potential overall survival (OS) benefit of its indication must be balanced with eventual higher risk of brain disseminated disease when whole brain irradiation is postponed. Therefore, a multidisciplinary evaluation is recommended to refine and personalize the therapeutic approach. The development of clinical nomograms or evaluation of circulating tumor cells/tumoral DNA that predict the survival free of new lesions may be the tools that will warranty further optimization of the treatment of NSCLC patients with BM. In this review, we report the main aspects of diagnosis, prognosis and therapeutic options and dilemmas evolving local ablative radiotherapy essentially based on seminal, updated prospective studies and ongoing trials.

Efficacy of salvage stereotactic radiotherapy (SRT) for locally recurrent brain metastases after initial SRT and characteristics of target population.

OBJECTIVES: Due to a steadily growing use of stereotactic radiotherapy (SRT) for treatment of brain metastases (BMs), the in-field failure after an initial stereotaxy is an increasingly frequent problem. Repeat stereotactic radiotherapy (re-SRT) shows encouraging results in terms of local control. However, the evidence on prognostic factors limiting the overall survival (OS) of re-treated patients is scarce. Here, we sought to analyze the patients' and treatment characteristics influencing the survival outcomes after re-SRT. METHODS: Data of all patients with local failure of initial SRT treated from 2012 to 2019 were retrospectively reviewed and cases treated with salvage SRT were analyzed. We analyzed the impact of patients' and treatment characteristics on overall survival after re-SRT by Kaplan-Meier method and Cox regression models. Local and distant brain control, cause of death, and radionecrosis rate were also assessed. RESULTS: Forty-seven patients with 55 BMs treated with re-SRT were evaluated. Median OS after re-SRT was 9.2 months and the overall local control was 83.6%. Nine BMs (16.4%) presented local relapse (LR), 12 (21.8%) radionecrosis, while 21 patients (44.7%) developed new BMs. Only absence of extracranial metastases at BMs diagnosis (HR 0.42, CI 95%; 0.18-0.97), extracranial disease progression (HR 2.39, CI 95%; 1.06-5.38) and distant brain failure (HR 3.94, CI 95%; 1.68-9.24) after re-SRT were significantly associated with patients' survival. Extracranial progression following re-SRT was an independent prognosticator of worse OS. CONCLUSION: Re-SRT after LR presented excellent local control with acceptable RN rate and improved patients' survival, limited mainly by extracranial and distant brain progression.

Positioning error analysis of the fraxion localization system in the intracranial stereotactic radiotherapy of tumors.

OBJECTIVE: To investigate positioning error analysis of the Fraxion localization system in the intracranial stereotactic radiotherapy of tumors. METHODS: 64 patients were divided into two groups: a control group (36 patients with the standard thermoplastic mask) and a model group (28 patients with the Fraxion localization system). 3D images of the treated position were obtained by cone-beam computed tomography (CBCT). Positioning errors were obtained by, respectively, registering these two sets of CBCT images to planning CT images, using a 6°-freedom robotic patient positioning system (HexaPOD Evo RT System). The changes in positioning errors with the Fraxion localization system and with the standard thermoplastic mask were analyzed. RESULTS: CBCT scan results of the model group showed that the mean of linear error of three directions [superior-inferior (SI), lateral (LAT), and anterior-posterior (AP)] was 0.710 ± 0.676 mm, 0.817 ± 0.687 mm, and 0.710 ± 0.685 mm, respectively. The corresponding PTV was 1.23 mm, 1.26 mm, and 1.36 mm. The differences between the 3D images and the planned CT images were significant (p < 0.001). CONCLUSION: The Fraxion radiotherapy system can not only improve the positioning accuracy and reduce positioning errors but also narrow the PTV margin and reduce the radiated volume of normal tissue.

Brain metastases treated with radiosurgery or hypofractionated stereotactic radiotherapy: outcomes and predictors of survival.

INTRODUCTION: To assess treatment outcome and prognostic factors associated with prolonged survival in patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (HFSRT). METHODS/PATIENTS: This study retrospectively reviewed 200 patients with 324 BM treated with one fraction (15-21 Gy) or 5-10 fractions (25-40 Gy) between January 2010 and August 2016. 26.5% of patients received whole brain radiotherapy (WBRT) and 25% initial surgery. Demographics, prognostic scales, systemic and local controls, patterns of relapse and rescue, toxicity, and cause of death were analyzed. A stratified analysis by primary tumor was done. RESULTS: Median overall survival (OS) was 8 months from SRS/HFSRT. Breast cancer patients had a median OS of 17 months, followed by renal (11 months), lung (8 months), colorectal (5 months), and melanoma (4 months). The univariate analysis showed improved OS in females (p 0.004), RPA I-II (p < 0.001) initial surgery (p < 0.001), absence of extracranial disease (p 0.023), and good disease control (p 0.002). There were no differences in OS or local control between SRS and HFSRT or in patients receiving WBRT. Among 44% of brain recurrences, 11% were in field. 174 patients died, 10% from confirmed intracranial progression. CONCLUSIONS: SRS and HSFRT are equally effective and safe for the treatment of BM, with no exceptions among different primary tumors. Disease control, surgery, age, and prognostic scales correlated with OS. However, the lack of survival benefit regarding WBRT might become logical evidence for its omission in a subset of patients.

Benefit of ablative versus palliative-only radiotherapy in combination with nivolumab in patients affected by metastatic kidney and lung cancer.

PURPOSE: Here, we present the results from a retrospective analysis, with the purpose of evaluating the safety and feasibility of nivolumab and radiotherapy (RT) concomitant association in metastatic kidney and lung cancer patients. MATERIALS AND METHODS: From August 2015 until September 2017, we retrospectively observed 20 patients with metastatic lung and renal cell carcinoma who had been initiated therapy with nivolumab and underwent concomitant RT. RT was administered either as an ablative therapy in the oligometastatic/oligoprogressive setting or as palliative-only treatment for symptomatic patients. Data on progression-free and overall survival (PFS and OS), treatment response and adverse events were collected and reported. Comparison between palliative-only and ablative treatments was performed. RESULTS: PFS and OS were 7 and 12.5 months in the entire population, respectively. Oligoprogressive patients treated with ablative intent, compared to patients undergoing RT with palliative-only intent, had statistically longer PFS (11.5 vs 5.2 months, HR 0.42, CI 0.18-0.98, p 0.03) and OS (17.9 vs 10.31 months, HR 0.41 CI 0.16-1.02, p 0.04). Considering only patients treated with ablative intent, 87.5% showed response to treatment, and complete response was reported in 37.5% of cases. Adverse G2-G3 related to combination treatment were reported as follows: 1 gastrointestinal (nausea), 4 breakthrough pain. CONCLUSIONS: Our data showed significant advantage for oligoprogressive patients treated with RT during nivolumab therapy. No safety alert emerged. These results underline the potential synergistic effects of RT and Immune therapy combination. Our analysis prompts further prospective studies exploring the benefit of integrated treatment strategies.

Hypofractionated Stereotactic Radiosurgery and Radiotherapy to Large Resection Cavity of Metastatic Brain Tumors.

OBJECTIVE: To evaluate the efficacy of postoperative fractionated stereotactic radiosurgery (FSRS) and hypofractionated stereotactic radiotherapy (SRT) to large surgical cavities after gross total resection of brain metastases. METHODS: A retrospective analysis of 41 patients who had received tumor-bed FSRS (5 fractions) or SRT (10 fractions) after resection of brain metastasis between 2005 and 2015 was performed. All resection cavities were treated with a frameless linear accelerator-based system. Patients who underwent subtotal resection, single-dose SRS to the resection cavity, or were treated with a fractionation schedule other than 5 or 10 fractions, were excluded. RESULTS: Twenty-six patients were treated with 5 fractions and 15 patients with 10 fractions. The median planning target volume was 19.78 cm3 (12.3-28 cm3) to the 5-fraction group and 29.79 cm3 (26.3-47.6 cm3) to the 10-fraction group (P = 0.020). The 1-year and 2-year local control rates for all patients were 89.4% and 77.1%, respectively, and 89.6% and 78.6% were free from distant intracranial progression, respectively. No difference was observed in local control or freedom from distant intracranial progression between the 5-fraction or 10-fraction groups. The median overall survival was 28.27 months (95% confidence interval, 19.42-37.12) for all patients. No patient developed necrosis at the resection cavity. CONCLUSIONS: Fractionation offers the potential to exploit the different biological responses between neoplastic and normal tissues to ionizing radiation. The use of 5 daily doses of 5-6 Gy or 10 daily doses of 3 Gy is a good strategy to have a reasonable local control and avoid neurotoxicity.

Radiotherapy and radiosurgery for Cushing's disease

Patients with residual or recurrent Cushing's disease receive external beam radiotherapy (RT) with the aim of achieving long-term tumour control and normalization of elevated hormone levels. Treatment is given either as conventional radiotherapy using conformal techniques or as stereotactic radiotherapy, which is either used as fractionated treatment (SCRT) or as single fraction radiosurgery (SRS). We describe the technical aspects of treatment and report a systematic review of the published literature on the efficacy and toxicity of conventional RT, SCRT and SRS. There are no studies directly comparing the different radiation techniques and the reported results are inevitably of selected patients by investigators with interest in the treatment tested. Nevertheless the review of the published literature suggests better hormone and tumour control rates after fractionated irradiation compared to single fraction radiosurgery. Hypopituitarism represents the most commonly reported late complication of radiotherapy seen after all treatments. Although the incidence of other late effects is low, the risk of radiation injury to normal neural structures is higher with single fraction compared to fractionated treatment. Stereotactic techniques offer more localized irradiation compared with conventional radiotherapy, however longer follow-up is necessary to confirm the potential reduction of long-term radiation toxicity of fractionated SCRT compared to conventional RT. On the basis of the available literature, fractionated conventional and stereotactic radiotherapy offer effective treatment for Cushing's disease not controlled with surgery alone. The lower efficacy and higher toxicity of single fraction treatment suggest that SRS is not the appropriate therapy for the majority of patients with Cushing's disease.

Pacientes com doença de Cushing residual ou recorrente recebem radioterapia externa em feixe (RT) com o objetivo de alcançar um controle tumoral prolongado e a normalização dos níveis hormonais elevados. O tratamento é realizado tanto com RT convencional, usando técnicas conformacionais, ou com RT estereotáxica, que é usada tanto como tratamento fracionado (RTF) ou como radiocirurgia em procedimento único (RCU). Descreveremos os aspectos técnicos do tratamento e mostraremos uma revisão sistemática da literatura sobre a eficácia e toxicidade da RT convencional, da RTF e da RCU. Não existem estudos comparando diretamente as diferentes técnicas de radiação, e os resultados reportados são inevitavelmente os de pacientes selecionados pelos investigadores com interesse no tratamento testado. De qualquer maneira, a revisão dos dados publicados sugere que há melhores taxas de controle hormonal e tumoral após RTF em comparação com RCU. O hipopituitarismo representa a complicação tardia mais comumente relatada da RT, vista após todos os tipos de tratamento. Embora a incidência de outros efeitos tardios seja baixa, o risco de a radiação comprometer estruturas neurais normais é mais elevado com RCU do que com RTF. Técnicas estereotáxicas oferecem irradiação mais localizada se comparadas com a RT convencional, embora um acompanhamento prolongado seja necessário para confirmar a possível redução da toxicidade continuada da radiação na RTF em comparação com a RT convencional. Com base na literatura disponível, a RT fracionada convencional e a estereotáxica oferecem tratamento efetivo para a doença de Cushing não controlada isoladamente pela cirurgia. A baixa eficácia e alta toxicidade do tratamento em dose única sugere que a RCU não seja a terapia mais apropriada para a maioria dos pacientes com doença de Cushing.