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.

Evaluating contouring accuracy and dosimetry impact of current MRI-guided adaptive radiation therapy for brain metastases: a retrospective study.

BACKGROUND: Magnetic resonance imaging (MRI) guided adaptive radiotherapy (MRgART) has gained increasing attention, showing clinical advantages over conventional radiotherapy. However, there are concerns regarding online target delineation and modification accuracy. In our study, we aimed to investigate the accuracy of brain metastases (BMs) contouring and its impact on dosimetry in 1.5 T MRI-guided online adaptive fractionated stereotactic radiotherapy (FSRT). METHODS: Eighteen patients with 64 BMs were retrospectively evaluated. Pre-treatment 3.0 T MRI scans (gadolinium contrast-enhanced T1w, T1c) and initial 1.5 T MR-Linac scans (non-enhanced online-T1, T2, and FLAIR) were used for gross target volume (GTV) contouring. Five radiation oncologists independently contoured GTVs on pre-treatment T1c and initial online-T1, T2, and FLAIR images. We assessed intra-observer and inter-observer variations and analysed the dosimetry impact through treatment planning based on GTVs generated by online MRI, simulating the current online adaptive radiotherapy practice. RESULTS: The average Dice Similarity Coefficient (DSC) for inter-observer comparison were 0.79, 0.54, 0.59, and 0.64 for pre-treatment T1c, online-T1, T2, and FLAIR, respectively. Inter-observer variations were significantly smaller for the 3.0 T pre-treatment T1c than for the contrast-free online 1.5 T MR scans (P < 0.001). Compared to the T1c contours, the average DSC index of intra-observer contouring was 0.52‒0.55 for online MRIs. For BMs larger than 3 cm3, visible on all image sets, the average DSC indices were 0.69, 0.71 and 0.64 for online-T1, T2, and FLAIR, respectively, compared to the pre-treatment T1c contour. For BMs < 3 cm3, the average visibility rates were 22.3%, 41.3%, and 51.8% for online-T1, T2, and FLAIR, respectively. Simulated adaptive planning showed an average prescription dose coverage of 63.4‒66.9% when evaluated by ground truth planning target volumes (PTVs) generated on pre-treatment T1c, reducing it from over 99% coverage by PTVs generated on online MRIs. CONCLUSIONS: The accuracy of online target contouring was unsatisfactory for the current MRI-guided online adaptive FSRT. Small lesions had poor visibility on 1.5 T non-contrast-enhanced MR-Linac images. Contour inaccuracies caused a one-third drop in prescription dose coverage for the target volume. Future studies should explore the feasibility of contrast agent administration during daily treatment in MRI-guided online adaptive FSRT procedures.

Definitive radiotherapy for meningeal brainstem melanocytoma: a case report.

Meningeal melanocytomas are rare, benign tumours of the central nervous system arising from the melanocytes of the leptomeninges. First-line treatment consists of either gross or subtotal resection with or without radiotherapy. However, given the sensitive locations of these tumours, alternative treatment options such as definitive radiotherapy may be warranted in patients deemed high-risk or without accessible tumours. A 67-year-old male presenting with spastic gait, frequent falls, and vertical gaze palsy was diagnosed with a 2.4 cm primary meningeal melanocytoma arising from the interpeduncular fossa. Given the critical tumour position within the brainstem, definitive radiotherapy was recommended. He received fractionated stereotactic radiotherapy (FSRT) to a total dose of 54 Gy in 27 fractions, resulting in a gradual improvement in gait and ocular range of motion. Follow-up imaging over the next three years revealed largely stable disease and an increase in edema with mild upper extremity weakness that improved with steroids. He was followed for three years and expired four years after treatment due to pneumonia. For patients unable to receive surgical resection, definitive RT may provide local control with minimal morbidity.

Technological quality requirements for stereotactic radiotherapy : Expert review group consensus from the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy.

This review details and discusses the technological quality requirements to ensure the desired quality for stereotactic radiotherapy using photon external beam radiotherapy as defined by the DEGRO Working Group Radiosurgery and Stereotactic Radiotherapy and the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy. The covered aspects of this review are 1) imaging for target volume definition, 2) patient positioning and target volume localization, 3) motion management, 4) collimation of the irradiation and beam directions, 5) dose calculation, 6) treatment unit accuracy, and 7) dedicated quality assurance measures. For each part, an expert review for current state-of-the-art techniques and their particular technological quality requirement to reach the necessary accuracy for stereotactic radiotherapy divided into intracranial stereotactic radiosurgery in one single fraction (SRS), intracranial fractionated stereotactic radiotherapy (FSRT), and extracranial stereotactic body radiotherapy (SBRT) is presented. All recommendations and suggestions for all mentioned aspects of stereotactic radiotherapy are formulated and related uncertainties and potential sources of error discussed. Additionally, further research and development needs in terms of insufficient data and unsolved problems for stereotactic radiotherapy are identified, which will serve as a basis for the future assignments of the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy. The review was group peer-reviewed, and consensus was obtained through multiple working group meetings.

Stereotactic radiosurgery and radiotherapy for acoustic neuromas.

Neuromas are benign intracranial tumors with indolent natural history. Surgery is the mainstay of treatment and only after the introduction of single-fraction stereotactic radiosurgery (SRS), radiotherapy emerged as an alternative viable option. In this review, we focused on SRS or conventionally fractionated stereotactic radiotherapeutic (FSRT) approaches. We described the results of different doses used for SRS and FSRT, the current status, and a comparison between the two radiotherapy approaches. Stereotactic radiotherapy techniques aim to control tumor growth with minimal toxicity. SRS using either a cobalt unit or a linear accelerator has given high rates of tumor control and of cranial nerve function preservation with marginal doses range of 12-14 Gy. Fractionated stereotactic radiotherapy (FSRT) is optimal for tumors larger than 3 cm. Doses as low as 50.4 Gy provide excellent control rates and low morbidity. Overall, both SRS and FSRT are equally effective and safe options for neuroma patients who do not need immediate surgical decompression.

Stereotactic radiosurgery versus stereotactic radiotherapy in the management of intracranial meningiomas: a systematic review and meta-analysis.

OBJECTIVEStereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have been used as a primary treatment or adjuvant to resection in the management of intracranial meningiomas (ICMs). The aim of this analysis is to compare the safety and long-term efficacy of SRS and SRT in patients with primary or recurrent ICMs.METHODSA systematic review of the literature comparing SRT and SRS in the same study was conducted using PubMed, the Cochrane Library, Google Scholar, and EMBASE from January 1980 to December 2018. Randomized controlled trials, case-control studies, and cohort studies (prospective and retrospective) analyzing SRS versus SRT for the treatment of ICMs in adult patients (age > 16 years) were included. Pooled and subgroup analyses were based on the fixed-effect model.RESULTSA total of 1736 patients from 12 retrospective studies were included. The treatment modality used was: 1) SRS (n = 306), including Gamma Knife surgery (n = 36), linear accelerator (n = 261), and CyberKnife (n = 9); or 2) SRT (n = 1430), including hypofractionated SRT (hFSRT, n = 268) and full-fractionated SRT (FSRT, n = 1162). The median age of patients at the time of treatment was 59 years. The median follow-up duration after treatment was 35.5 months. The median tumor volumes at the time of treatment with SRS, hFSRT, and FSRT were 2.84 cm3, 5.45 cm3, and 12.75 cm3, respectively. The radiographic tumor control at last follow-up was significantly worse in patients who underwent SRS than SRT (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27-0.82, p = 0.007) with 7% less volume of tumor shrinkage (OR 0.93, 95% CI 0.61-1.40, p = 0.72). Compared to SRS, the radiographic tumor control was better achieved by FSRT (OR 0.46, 95% CI 0.26-0.80, p = 0.006) than by hFSRT (OR 0.81, 95% CI 0.21-3.17, p = 0.76). Moreover, SRS leads to a significantly higher risk of clinical neurological worsening during follow-up (OR 2.07, 95% CI 1.06-4.06, p = 0.03) and of immediate symptomatic edema (OR 4.58, 95% CI 1.67-12.56, p = 0.003) with respect to SRT. SRT could produce a better progression-free survival at 4-10 years compared to SRS, but this was not statistically significant (p = 0.29).CONCLUSIONSSRS and SRT are both safe options in the management of ICMs. However, SRT carries a better radiographic tumor control rate and a lower incidence of posttreatment symptomatic worsening and symptomatic edema, with respect to SRS. However, further prospective studies are still needed to validate these results.

Impact of 68Ga-DOTATOC PET/MRI on robotic radiosurgery treatment planning in meningioma patients: first experiences in a single institution.

OBJECTIVEFor stereotactic radiosurgery (SRS) planning, precise contouring of tumor boundaries and organs at risk is of utmost importance. Correct interpretation of standard neuroimaging (i.e., CT and MRI) can be challenging after previous surgeries or in cases of skull base lesions with complex shapes. The aim of this study was to evaluate the impact of 68Ga-DOTATOC PET/MRI on treatment planning for image-guided SRS by CyberKnife.METHODSThe authors retrospectively identified 11 meningioma treatments in 10 patients who received a 68Ga-DOTATOC PET/MRI prior to SRS. The planning target volume (PTV) used for the patients' treatment was defined as the reference standard. This was contoured by a treating radiosurgeon (RS0) using fused planning CT and PET/MRI data sets. The same tumors were then contoured by another experienced radiosurgeon (RS1) and by a less-experienced radiosurgeon (RS2), both blinded to PET data sets. A comparison of target volumes with focus on volume-based metrics and distance to critical structures was performed. RS1 and RS2 also filled in a questionnaire analyzing the confidence level and the subjective need for the implementation of PET data sets for contouring.RESULTSAnalysis showed a subjective personal preference for PET/MRI in all cases for both radiosurgeons, particularly in proximity to critical structures. The analysis of the planning volumes per physician showed significantly smaller RS2-PTV in comparison to RS1-PTV and to RS0-PTV, whereas the median volumes were comparable between RS1-PTV and RS2-PTV (median: RS0: 4.3 cm3 [IQR 3.4-6.5 cm3] and RS1: 4.5 cm3 [IQR 2.7-6 cm3] vs RS2: 2.6 cm3 [IQR 2-5 cm3]; p = 0.003). This was also reflected in the best spatial congruency between the 2 experienced physicians (RS0 and RS1). The percentage of the left-out volume contoured by RS1 and RS2 compared to RS0 with PET/MRI demonstrated a relevant left-out-volume portion in both cases with greater extent for the less-experienced radiosurgeon (RS2) (RS1: 19.1% [IQR 8.5%-22%] vs RS2: 40.2% [IQR 34.2%-53%]). No significant differences were detected regarding investigated critical structures.CONCLUSIONSThis study demonstrated a relevant impact of PET/MRI on target volume delineation of meningiomas. The extent was highly dependent on the experience of the treating physician. This preliminary study supports the relevance of 68Ga-DOTATOC PET/MRI as a tool for radiosurgical treatment planning of meningiomas.

Early intervention using high-precision radiotherapy preserved visual function for five consecutive patients with optic nerve sheath meningioma.

BACKGROUND: There has been a paradigm shift in the treatment for optic nerve sheath meningioma (ONSM) from surgery to fractionated stereotactic radiotherapy (FSRT) in other countries. However, FSRT has seldom been performed in Japan. The purpose of this retrospective study is to reconfirm the effectiveness of early intervention with precision radiotherapy for ONSM reported in our previous study. METHODS: Five consecutive patients with ONSM were retrospectively analyzed. All patients underwent intensity-modulated radiotherapy (IMRT) or FSRT. They received the early interventions between 1.5 and 7 months after deterioration of the disease. The median dose was 52.8 Gy (range 46.0-59.4 Gy) and the median number of fractions was 25 (range 22-33). RESULTS: All patients experienced reestablishment of vision at the median follow-up time of 36 months (range 18-54 months). Four of them noted early improvement of visual deficits during the treatment course (range 2-4 weeks) and the remaining patient improved 3 weeks after completion of IMRT. The median tumor reduction was 53% (range 39-75%). One patient with diabetes mellitus developed retinal bleeding as a result of radiation retinopathy 16 months after IMRT, although the doses were acceptable. The remaining 4 patients have no late toxicity at the follow-up time of 31-54 months. CONCLUSIONS: A paradigm shift is necessary from surgery to early intervention using precision radiotherapy for the treatment of ONSM in Japan.

Outcome of radiotherapy for pituitary adenomas.

AIM: The aim of this study was to analyze the outcome and toxicities and its correlation to patient related and treatment related factors. BACKGROUND: Pituitary adenomas are treated by radiation therapy (RT) as one of the modalities along with surgery and medical therapy. RT to pituitary adenomas is a challenge due to adjacent dose limiting structures such as optic apparatus and hypothalamus. MATERIALS AND METHODS: Between January 2004 and December 2010, 94 patients treated for pituitary adenoma with RT who had hospital records of a minimum follow-up of 1 year were included in the analysis. Tests of correlation were done with regards to treatment factors. RESULTS: Male preponderance was noted in our patient population. Nonfunctioning and functioning tumors were equal in number in this series. Hypopituitarism was associated in 58.5% of patients prior to RT. Radiological tumor progression was seen in one patient (1/94) who had a nonfunctioning tumor. Among functioning tumors, biochemical remission was seen in 93.6% of patients at a median follow-up of 6 years. CONCLUSIONS: Visual complication was seen in 5.3% of patients and worsening or new onset hypopituitarism was seen in 6.4%. Conventional 3-field technique was associated with significantly more visual complication compared to Stereotactic Radiation Therapy (SRT) technique. Doses ≤50.4 Gy showed a trend of reduced rate of visual and endocrine complications with no compromise in efficacy.

Nelson's syndrome: a review of the clinical manifestations, pathophysiology, and treatment strategies.

Nelson's syndrome is a rare clinical manifestation that occurs in 8%-47% of patients as a complication of bilateral adrenalectomy, a procedure that is used to control hypercortisolism in patients with Cushing's disease. First described in 1958 by Dr. Don Nelson, the disease has since become associated with a clinical triad of hyperpigmentation, excessive adrenocorticotropin secretion, and a corticotroph adenoma. Even so, for the past several years the diagnostic criteria and management of Nelson's syndrome have been inadequately studied. The primary treatment for Nelson's syndrome is transsphenoidal surgery. Other stand-alone therapies, which in many cases have been used as adjuvant treatments with surgery, include radiotherapy, radiosurgery, and pharmacotherapy. Prophylactic radiotherapy at the time of bilateral adrenalectomy can prevent Nelson's syndrome (protective effect). The most promising pharmacological agents are temozolomide, octreotide, and pasireotide, but these agents are often administered after transsphenoidal surgery. In murine models, rosiglitazone has shown some efficacy, but these results have not yet been found in human studies. In this article, the authors review the clinical manifestations, pathophysiology, diagnostic criteria, and efficacy of multimodal treatment strategies for Nelson's syndrome.

Fractionated stereotactic radiotherapy plus bevacizumab after response to bevacizumab plus irinotecan as a rescue treatment for high-grade gliomas.

AIM: To evaluate the possibility of implementing a new scheme of rescue treatment after relapse or progression of high-grade glioma (HGG) treated at the first-line with bevacizumab and irinotecan (BVZ+CPT11), evaluating the response and toxicity of associating BVZ and fractionated stereotactic radiotherapy (BVZ+FSRT). MATERIALS AND METHODS: We retrospectively analysed data from 59 patients with relapse of HGG. Nine patients with HGG relapse after treatment using the Stupp protocol that were treated with BVZ+CPT11 for progression between July 2007 and August 2012, after which the response was assessed according to the Revised Assessment in Neuro-Oncology (RANO) criteria. BVZ was administered at a dose of 10 mg/kg and FSRT up to a prescribed dose of 30 Gy, 500 cGy per fraction, three days a week. The median follow-up was 38 months. RESULTS: The treatment was well-tolerated by all patients. The response after nuclear magnetic resonance imaging (MRI) at 3-6 months was progression in two patients, stable disease in four, and three patients had a partial response. The median overall survival (OS) from diagnosis until death or the last control was 36.8 months. The median progression-free survival (PFS) was 10.8 months. The results from tumour sub-group analysis indicated that the PFS was not statistically significant although it seemed that it was higher in grade-III. The OS was higher in grade-III gliomas. CONCLUSIONS: The combination of BVZ+FSRT as a second-line HGG relapse rescue treatment is well-tolerated and seems to offer promising results. We believe that multi-centre prospective studies are needed to determine the long-term efficacy and toxicity of this therapeutic approach.

A prospective randomized study comparing two frameless immobilization systems for cranial stereotactic radiotherapy.

Introduction: The Dual Shell Encompass Fibreplast™ System (DS-Encompass) by CQ Medical™ is validated for frameless immobilization in stereotactic brain radiotherapy. An alternative mask model has been proposed with the rear shell replaced by a Moldcare® cushion (M-Encompass). To validate the use of this model in our cranial stereotactic workflow method including HyperArc™, we performed a prospective randomized study comparing inter-and intrafractional motion and patients comfort between both masks. Materials & Methods: A prospective randomized study between DS-Encompass and M-Encompass was conducted involving 60 participants. Stratification between DS-Encompass and M-Encompass was carried out based on the fractionation scheme. Treatment plans were created with HyperArc™. During treatment, surface guidance was used for patient positioning and monitoring. A pre-treatment cone-beam CT (CBCT) was acquired to correct interfractional motion and a post-treatment CBCT was acquired to quantify the intrafractional motion. Patients reported comfort was analyzed with a Likert-scale at the end of the treatment. Unpaired t-tests were conducted to determine the level of significance. Results: No significant difference in interfractional translations is present. A significant difference is revealed in roll-axis rotation, where DS-Encompass allows for smaller deviations. Since interfractional motion can be corrected through daily CBCT-scans and 6D-couch corrections, they are clinically irrelevant. Intrafractional motion does not differ significantly and remains below 0.5 mm and 0.5° for both systems. There is no statistical difference in patient-reported comfort. Conclusion: We conclude that Encompass with Moldcare offers a safe alternative to Duall Shell Encompass for non-coplanar stereotactic brain radiotherapy. There is no significant difference in intrafractional motion nor difference in comfort levels.

Reirradiation of metastases of the central nervous system: part 1-brain metastasis.

Because of improved survival of cancer patients, more patients irradiated for brain metastases develop intracerebral recurrences requiring subsequent courses of radiotherapy. Five studies focused on reirradiation with whole-brain radiation therapy (WBRT) after initial WBRT for brain metastases. Following the second WBRT course, improvement of clinical symptoms was found in 31-68% of patients. Rates of neurotoxicity, such as encephalopathy or cognitive decline, were reported in two studies (1.4% and 32%). In another study, severe or unexpected adverse events were not observed. Survival following the second WBRT course was generally poor, with median survival times of 2.9-4.1 months. The survival prognosis of patients receiving two courses of WBRT can be estimated by a scoring tool considering five prognostic factors. Three studies investigated reirradiation with single-fraction stereotactic radiosurgery (SF-SRS) following primary WBRT. One-year local control rates were 74-91%, and median survival times ranged between 7.8 and 14 months. Rates of radiation necrosis (RN) after reirradiation were 0-6%. Seven studies were considered that investigated re-treatment with SF-SRS or fractionated stereotactic radiation therapy (FSRT) following initial SF-SRS or FSRT. One-year local control rates were 60-88%, and the median survival times ranged between 8.3 and 25 months. During follow-up after reirradiation, rates of overall (asymptomatic or symptomatic) RN ranged between 12.5% and 30.4%. Symptomatic RN occurred in 4.3% to 23.9% of cases (patients or lesions). The risk of RN associated with symptoms and/or requiring surgery or corticosteroids appears lower after reirradiation with FSRT when compared to SF-SRS. Other potential risk factors of RN include the volume of overlap of normal tissue receiving 12 Gy at the first course and 18 Gy at the second course of SF-SRS, maximum doses ≥40 Gy of the first or the second SF-SRS courses, V12 Gy >9 cm3 of the second course, initial treatment with SF-SRS, volume of normal brain receiving 5 Gy during reirradiation with FSRT, and systemic treatment. Cumulative EQD2 ≤100-120 Gy2 to brain, <100 Gy2 to brainstem, and <75 Gy2 to chiasm and optic nerves may be considered safe. Since most studies were retrospective in nature, prospective trials are required to better define safety and efficacy of reirradiation for recurrent or progressive brain metastases.

Radiotherapy in Prostate Brain Metastases: A Review of the Literature.

Brain metastases in prostate cancer are infrequent. Treatment of brain metastases includes radiotherapy. The aim of this literature review was to study whole brain radiotherapy, radiosurgery, and fractionated stereotactic radiotherapy and its applications in the treatment of prostate brain metastasis. We searched MEDLINE and PUBMED for articles published in the last 5 years and identified 153 articles. After examining them, 31 articles met the selection criteria and were included. Most were retrospective studies. MeSH terms used in the search included: prostate cancer OR prostate brain metastases AND radiotherapy, brain metastases AND radiotherapy AND prostate cancer. English language articles with information on the type of radiotherapy, doses and fractionation, indications, local control, toxicities, and survival of radiotherapy in prostate brain metastasis were included in this review. All articles were assessed for validity and relevant content. The usual treatment of prostate brain metastasis involves whole brain radiotherapy; however, the current trend in the metastases of prostate cancer and of other origins is the use of radiosurgery techniques or stereotactic body radiotherapy.

Five-Fraction Stereotactic Radiotherapy for Brain Metastases-A Retrospective Analysis.

PURPOSE: To determine the safety and outcome profile of five-fraction stereotactic radiotherapy (FSRT) for brain metastases (BM), either as a definitive or adjuvant treatment. METHODS: We assessed clinical data of patients receiving five fractions of 7 Gy each (cumulative physical dose of 35 Gy) to BM or surgical cavities. The primary endpoints were toxicity and radiation necrosis (RN) rates. Secondary endpoints were 1-year cumulative local control rate (LCR) and estimated overall survival (OS). RESULTS: A total of 36 eligible patients receiving FSRT to a total of 49 targets were identified and included. The median follow up was 9 (1.1-56.2) months. The median age was 64.5 (34-92) years, the median ECOG score was 1, and the median Diagnostic-Specific Graded Prognostic Assessment (DS-GPA) score was 2. Treatment was well tolerated and there were no grade 3 adverse events or higher. The overall RN rate was 14.3% and the median time to RN was 12.9 (1.8-23.8) months. RN occurrence was associated with immunotherapy, young age (≤45 years), and large PTV. The cumulative 1-year local control rate was 83.1% and the estimated median local progression free-survival was 18.8 months. The estimated median overall survival was 11 (1.1-56.2) months and significantly superior in those patients presenting with RN. CONCLUSIONS: FSRT with 5 × 7 Gy represents a feasible, safe, and efficient fast track approach of intensified FSRT with acceptable LC and comparable RN rates for both the adjuvant and definitive RT settings.

Early Versus Delayed Fractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma.

BACKGROUND: Fractionated stereotactic radiotherapy (FSRT) is a common modality used to treat pituitary adenomas with good control rates. It is not known whether FSRT should be performed early or delayed until progression occurs. We compared FSRT in treating nonfunctional pituitary adenomas (NFPA) as an adjuvant (ADJ) or on-progression (PRG) therapy. METHODS: A retrospective review of patients who underwent FSRT for an NFPA between January 2004 and December 2022 at a single institution was performed. We compared endocrinologic, ophthalmologic, and radiographic outcomes in FSRT delivered as ADJ and PRG treatment. RESULTS: Seventy-five patients were analyzed, with a median follow-up of 53 months. FSRT was administered to 35 and 40 patients as ADJ and PRG, with a median time to treatment of 5.5 and 40 months, respectively. The tumor control rate was 94.3% for ADJ and 95.0% for PRG. Treatment resulted in 4 (11.4%) versus 7 (17.5%) new endocrinopathies and 2 (5.7%) versus 1 (2.5%) new visual deficits for ADJ versus PRG. A survival analysis of time to new endocrinopathy showed no difference between the 2 cohorts. The median time from surgery to new endocrinopathy was significantly different between ADJ and PRG, at 15.5 and 102.0 months, respectively. CONCLUSIONS: FSRT is effective in treating NFPA for residual and progressive tumors, with excellent tumor control rates and a low risk of developing new endocrinopathies and visual deficits. Delaying treatment delayed the development of new endocrinopathies, suggesting that observation with FSRT on tumor progression may delay the onset of hypopituitarism and maintain similar effectiveness in tumor control.

Pretreatment lymphocyte-to-monocyte ratio as a prognostic factor and influence on dose-effect in fractionated stereotactic radiotherapy for oligometastatic brain metastases in non-small cell lung cancer patients.

Background: Studies on the prognostic factors for patients with brain oligo-metastasis treated with fractionated stereotactic radiotherapy (FSRT) usually focus on the size of metastatic tumor and radiation dose. Some inflammatory indicators have predictive value in non-small cell lung cancer (NSCLC) with brain metastasis receiving stereotactic radiotherapy. However, the prognostic value of inflammatory indicators in NSCLC patients with brain oligo-metastasis treated with FSRT, and their effect on radiotherapy dose is unknown. Methods: A total of 95 advanced NSCLC patients with brain oligo-metastasis who had undergone FSRT treatment at Ningbo Medical Center Lihuili Hospital between January 2015 and April 2022 were enrolled into the study. Neutrophil to lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), tumor diameter and biologically effective dose (BED10) were analyzed using Chi-square test. Univariate and multivariate Cox regressions were used to identify predictors of survival. Results: Tumor diameter (< 2 cm), BED10 (≥ 48Gy) and LMR (≥ 4) were found to be independently associated with good intracranial local control survival (i-LCS) through multivariate analysis. The median i-LCS was longer in patients with 2 independent risk factors (tumor diameter ≥ 2 and LMR < 4) administered with BED10 > 53.6Gy compared with patients administered with BED10 ≤ 53.6Gy (20.7 months vs 12.0 months, P = 0.042). LMR ≥ 4 (P = 0.019) and positivity for driver gene mutations (P = 0.011) were independently associated with better overall survival (OS). Conclusions: LMR is an independent prognostic factor of i-LCS and OS in NSCLC patients with brain oligo-metastasis treated with FSRT. Patients with tumor diameter ≥ 2 and LMR < 4 should be treated with BED10 greater than 53.6Gy.

Radiation of meningioma dural tail may not improve tumor control rates.

Introduction: Dural tails are thickened contrast-enhancing portions of dura associated with some meningiomas. Prior studies have demonstrated the presence of tumor cells within the dural tail, however their inclusion in radiation treatment fields remains controversial. We evaluated the role of including the dural tail when treating a meningioma with stereotactic radiation and the impact on tumor recurrence. Methods: This is a retrospective, single-institution, cohort study of patients with intracranial World Health Organization (WHO) grade 1 meningioma and identified dural tail who were treated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) from January 2012 to December 2018. SRS and FSRT subgroups were categorized based on coverage or non-coverage of the dural tail by the radiation fields, as determined independently by a radiation oncologist and a neurosurgeon. Demographics, tumor characteristics, radiation plans, and outcomes were evaluated. High grade tumors were analyzed separately. Results: A total of 187 WHO grade 1 tumors from 177 patients were included in the study (median age: 62 years, median follow-up: 40 months, 78.1% female) with 104 receiving SRS and 83 receiving FSRT. The dural tail was covered in 141 (75.4%) of treatment plans. There was no difference in recurrence rates (RR) or time to recurrence (TTR) between non-coverage or coverage of dural tails (RR: 2.2% vs 3.5%, P = 1.0; TTR: 34 vs 36 months, P = 1.00). There was no difference in the rate of radiation side effects between dural tail coverage or non-coverage groups. These associations remained stable when SRS and FSRT subgroups were considered separately, as well as in a high grade cohort of 16 tumors. Conclusion: Inclusion of the dural tail in the SRS or FSRT volumes for meningioma treatment does not seem to reduce recurrence rate. Improved understanding of dural tail pathophysiology, tumor grade, tumor spread, and radiation response is needed to better predict the response of meningiomas to radiotherapy.

Plan Quality Assessment of Fractionated Stereotactic Radiotherapy Treatment Plans in Patients With Brain Metastases.

Background and Purpose: The treatment options available in the management of brain metastases includes fractionated stereotactic radiotherapy (FSRT) and stereotactic radiosurgery (SRS) treatments. FSRT treatments have proved to be useful mainly in the treatment of larger volumes. This study aims to evaluate the FSRT treatment technique used in our department based on various plan quality indices. Methods and Materials: 24 treatment plans of 23 patients were analyzed. Volumetric modulated arc therapy (VMAT) plans were generated in line with the department protocol. The following parameters were extracted: Radiation Therapy Oncology Group conformity index (RTOG CI), Paddick conformity index (Paddick CI), gradient index (GI), quality index (Q), homogeneity index (HI), and V24.4 volume as a parallel index of V12 used at SRS plan evaluation. Results: Plan conformity was acceptable, RTOG CI mean was 0.942; Paddick CI mean was 0.824. The mean GI value was 6.146. The mean of HI and Q indices were 1.263 and 0.94, respectively. V24.4 mean was 33.434 cm3. All plans achieved clinically acceptable organs-at-risk (OAR) constraints. PTV volumes were clustered into either 10 cm3 or 15 cm3 bins depending on the plan quality metric we used. The mean values show a balanced distribution of plan indices along the various PTV bins. Discussion: Our results based on the derived indices show that our FSRT approach can achieve clinically acceptable treatment plans. Furthermore, the clustering of PTV volumes show that these plan quality metrics remain acceptable for a wide spectrum of PTV volumes.

Whole Brain Irradiation or Stereotactic RadioSurgery for five or more brain metastases (WHOBI-STER): A prospective comparative study of neurocognitive outcomes, level of autonomy in daily activities and quality of life.

AIMS: To evaluate neurocognitive performance, daily activity and quality of life (QoL), other than usual oncologic outcomes, among patients with brain metastasis ≥5 (MBM) from solid tumors treated with Stereotactic Brain Irradiation (SBI) or Whole Brain Irradiation (WBI). METHODS: This multicentric randomized controlled trial will involve the enrollment of 100 patients (50 for each arm) with MBM ≥ 5, age ≥ 18 years, Karnofsky Performance Status (KPS) ≥ 70, life expectancy > 3 months, known primary tumor, with controlled or controllable extracranial disease, baseline Montreal Cognitive Assessment (MoCA) score ≥ 20/30, Barthel Activities of Daily Living score ≥ 90/100, to be submitted to SBI by LINAC with monoisocentric technique and non-coplanar arcs (experimental arm) or to WBI (control arm). The primary endpoints are neurocognitive performance, QoL and autonomy in daily-life activities variations, the first one assessed by MoCa Score and Hopkins Verbal Learning Test-Revised, the second one through the EORTC QLQ-C15-PAL and QLQ-BN-20 questionnaires, the third one through the Barthel Index, respectively. The secondary endpoints are time to intracranial failure, overall survival, retreatment rate, acute and late toxicities, changing of KPS. It will be considered significant a statistical difference of at least 30% between the two arms (statistical power of 80% with a significance level of 95%). DISCUSSION: Several studies debate what is the decisive factor accountable for the development of neurocognitive decay among patients undergoing brain irradiation for MBM: radiation effect on clinically healthy brain tissue or intracranial tumor burden? The answer to this question may come from the recent technological advancement that allows, in a context of a significant time saving, improved patient comfort and minimizing radiation dose to off-target brain, a selective treatment of MBM simultaneously, otherwise attackable only by WBI. The achievement of a local control rate comparable to that obtained with WBI remains the fundamental prerequisite. TRIAL REGISTRATION: NCT number: NCT04891471.