Impact of Cochlear Dose on Hearing Preservation Following Stereotactic Radiosurgery in Treatment of Vestibular Schwannomas: A Multi-Center Study.

OBJECTIVE: Stereotactic radiosurgery (SRS) is a well-established treatment for vestibular schwannomas (VS). Hearing loss remains a main morbidity of VS and its treatments, including SRS. The effects of radiation parameters of SRS on hearing remain unknown. The goal of this study is to determine the effect of tumor volume, patient demographics, pretreatment hearing status, cochlear radiation dose, total tumor radiation dose, fractionation, and other radiotherapy parameters on hearing deterioration. METHODS: Multicenter retrospective analysis of 611 patients who underwent SRS for VS from 1990-2020 and had pre- and post-treatment audiograms. RESULTS: Pure tone averages (PTAs) increased and word recognition scores (WRSs) decreased in treated ears at 12-60 months while remaining stable in untreated ears. Higher baseline PTA, higher tumor radiation dose, higher maximum cochlear dose, and usage of single fraction resulted in higher post radiation PTA; WRS was only predicted by baseline WRS and age. Higher baseline PTA, single fraction treatment, higher tumor radiation dose, and higher maximum cochlear dose resulted in a faster deterioration in PTA. Below a maximum cochlear dose of 3 Gy, there were no statistically significant changes in PTA or WRS. CONCLUSIONS: Decline of hearing at one year in VS patients after SRS is directly related to maximum cochlear dose, single versus 3-fraction treatment, total tumor radiation dose, and baseline hearing level. The maximum safe cochlear dose for hearingtbrowd preservation at one year is 3 Gy, and the use of 3 fractions instead of one fraction was better at preserving hearing.

Development of Predictive Models for the Response of Vestibular Schwannoma Treated with Cyberknife®: A Feasibility Study Based on Radiomics and Machine Learning.

PURPOSE: to predict vestibular schwannoma (VS) response to radiosurgery by applying machine learning (ML) algorithms on radiomic features extracted from pre-treatment magnetic resonance (MR) images. METHODS: patients with VS treated with radiosurgery in two Centers from 2004 to 2016 were retrospectively evaluated. Brain T1-weighted contrast-enhanced MR images were acquired before and at 24 and 36 months after treatment. Clinical and treatment data were collected contextually. Treatment responses were assessed considering the VS volume variation based on pre- and post-radiosurgery MR images at both time points. Tumors were semi-automatically segmented and radiomic features were extracted. Four ML algorithms (Random Forest, Support Vector Machine, Neural Network, and extreme Gradient Boosting) were trained and tested for treatment response (i.e., increased or non-increased tumor volume) using nested cross-validation. For training, feature selection was performed using the Least Absolute Shrinkage and Selection Operator, and the selected features were used as input to separately build the four ML classification algorithms. To overcome class imbalance during training, Synthetic Minority Oversampling Technique was used. Finally, trained models were tested on the corresponding held out set of patients to evaluate balanced accuracy, sensitivity, and specificity. RESULTS: 108 patients treated with Cyberknife® were retrieved; an increased tumor volume was observed at 24 months in 12 patients, and at 36 months in another group of 12 patients. The Neural Network was the best predictive algorithm for response at 24 (balanced accuracy 73% ± 18%, specificity 85% ± 12%, sensitivity 60% ± 42%) and 36 months (balanced accuracy 65% ± 12%, specificity 83% ± 9%, sensitivity 47% ± 27%). CONCLUSIONS: radiomics may predict VS response to radiosurgery avoiding long-term follow-up as well as unnecessary treatment.

Image-guided LINAC radiosurgery in hypothalamic hamartomas.

Introduction: Hypothalamic hamartomas (HH) are developmental malformations that are associated with mild to severe drug-refractory epilepsy. Stereotactic radiosurgery (SRS) is an emerging non-invasive option for the treatment of small and medium-sized HH, providing good seizure outcomes without neurological complications. Here, we report our experience treating HH with frameless LINAC SRS. Materials and methods: We retrospectively collected clinical and neuroradiological data of ten subjects with HH-related epilepsy that underwent frameless image-guided SRS. Results: All patients underwent single-fraction SRS using a mean prescribed dose of 16.27 Gy (range 16-18 Gy). The median prescription isodose was 79% (range 65-81 Gy). The mean target volume was 0.64 cc (range 0.26-1.16 cc). Eight patients experienced complete or near complete seizure freedom (Engel class I and II). Five patients achieved complete seizure control within 4 to 18 months after the treatment. Four patients achieved Engel class II outcome, with stable results. One patient had a reduction of seizure burden superior to 50% (Engel class III). One patient had no benefit at all (Engel class IV) and refused further treatments. Overall, at the last follow-up, three patients experience class I, five class II, one class III and one class IV outcome. No neurological complications were reported. Conclusions: Frameless LINAC SRS provides good seizure and long-term neuropsychosocial outcome, without the risks of neurological complications inherently associated with microsurgical resection.

Image-Guided Stereotactic Radiosurgery for the Treatment of Spasticity and Pain: A Preliminary Experience.

Background Spasticity is a major health problem worldwide. Response to current medical and rehabilitation treatments is often poor. Surgical treatment is available only for a very limited number of patients. Aim We recently reported the application of stereotactic radiosurgery as a treatment option for spasticity and related pain. This paper describes a larger experience using image-guided stereotactic radiosurgery targeting the cervical or lumbar spinal roots to relieve spasticity and pain in four patients. Methods All the patients had refractory spasticity and related pain, one patient had additional paroxystic neuralgic pain. The cause of spasticity and pain was a traumatic brain and/or spinal cord injury, brain and/or spinal cord surgery, and stroke. Symptoms affected the right superior limb in one patient, and the inferior limbs in three patients (unilaterally in two, bilaterally in one). According to the symptoms, one patient was treated at the cervical level (C7 right sensory root) and three patients at lumbar level (right L4, left S1, and L2 roots bilaterally). The target was selected on constructive interference in steady-state (CISS) MR, focusing the irradiation on the postganglionic sensory segment of the cervical root or the intra-foraminal dorsolateral sensory portion of the lumbar roots. Appropriate spasticity and pain scales were used to assess the patient's status after the treatment. Results The treatments were tolerated well. Marked symptomatic relief was found in all the treated patients. Improvements in spasticity and pain scales were observed up to the latest follow-up. After 2 years, the mean reduction of the visual analog scale (VAS) and Modified Ashworth Scale (MAS) was 64.3% and 43.7%, respectively, while the median reduction of MAS score was 50%. Conclusions Except for a previous case report, this is the first study describing a novel noninvasive technique based on image-guided radiosurgery to treat severe spasticity and pain due to brain and spinal cord injury. This novel technique appears to be safe and effective and deserves to be studied further.

Metastatic salivary gland carcinoma: A role for stereotactic body radiation therapy? A study of AIRO-Head and Neck working group.

OBJECTIVES: The role of radiotherapy (RT) for oligometastases is currently established in different oncological settings but data on salivary gland cancer (SGC) are lacking. We evaluated the role of RT in oligometastatic SGC patients, focusing on stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: We performed a retrospective, multicentric study of oligometastatic SGC treated with palliative RT or SBRT. Endpoints included response evaluation and local control (LC). RESULTS: Between 2006 and 2016, 64 patients were collected from 9 Italian Cancer Centers, on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Head and Neck Working Group. 37 patients (57.8%) were suffering from adenoid cystic carcinoma (ACC) and 27 patients (42.2%) had non-ACC. Thirty-four patients underwent palliative RT (53,1%), and 30 received SBRT (46,9%). Most common metastatic sites were bone for palliative RT and lung for SBRT. Among patients treated with SBRT, an objective response or a stability was observed in all treated lesions. After a median follow-up of 29.2 months (range 2.3-117.1), LC at 12 months was 57.5% for patients treated with SBRT and was higher in ACC subgroup. CONCLUSION: We confirmed the potential role of SBRT in the management of oligometastatic SGC patients to control limited burden of disease considering the absence of effective systemic therapies.

Almost one year of COVID-19 pandemic: how radiotherapy centers have counteracted its impact on cancer treatment in Lombardy, Italy. CODRAL/AIRO-L study.

Lombardy has represented the Italian and European epicenter of the coronavirus disease 2019 (COVID-19) pandemic. Although most clinical efforts within hospitals were diverted towards the care of virally infected patients, therapies for patients with cancer, including radiotherapy (RT), have continued. During both the first and second pandemic waves, several national and regional organizations provided Italian and Lombardian RT departments with detailed guidelines aimed at ensuring safe treatments during the pandemic. The spread of infection among patients and personnel was limited by adopting strict measures, including triage procedures, interpersonal distance, and adequate implementation of personal protective equipment (PPE). Screening procedures addressed to both the healthcare workforce and patients, such as periodic nasopharyngeal swabs, have allowed the early identification of asymptomatic or pauci-symptomatic COVID-19 cases, thus reducing the spread of the infection. Prevention of infection was deemed of paramount importance to protect both patients and personnel and to ensure the availability of a minimum number of staff members to maintain clinical activity. The choice of treating COVID-19-positive patients has represented a matter of debate, and the risk of oncologic progression has been weighted against the risk of infection of personnel and other patients. Such risk was minimized by creating dedicated paths, reserving time slots, applying intensified cleaning procedures, and supplying personnel and staff with appropriate PPE. Remote working of research staff, medical physicists, and, in some cases, radiation oncologists has prevented overcrowding of shared spaces, reducing infection spread.

Immunotherapy in association with stereotactic radiotherapy for non-small cell lung cancer brain metastases: results from a multicentric retrospective study on behalf of AIRO.

BACKGROUND: To define efficacy and toxicity of Immunotherapy (IT) with stereotactic radiotherapy (SRT) including radiosurgery (RS) or hypofractionated SRT (HFSRT) for brain metastases (BM) from non-small cell lung cancer (NSCLC) in a multicentric retrospective study from AIRO (Italian Association of Radiotherapy and Clinical Oncology). METHODS: NSCLC patients with BM receiving SRT + IT and treated in 19 Italian centers were analyzed and compared with a control group of patients treated with exclusive SRT. RESULTS: One hundred patients treated with SRT + IT and 50 patients treated with SRT-alone were included. Patients receiving SRT + IT had a longer intracranial Local Progression-Free Survival (iLPFS) (propensity score-adjusted P = .007). Among patients who, at the diagnosis of BM, received IT and had also extracranial progression (n = 24), IT administration after SRT was shown to be related to a better overall survival (OS) (P = .037). A multivariate analysis, non-adenocarcinoma histology, KPS = 70 and use of HFSRT were associated with a significantly worse survival (P = .019, P = .017 and P = .007 respectively). Time interval between SRT and IT ≤7 days (n = 90) was shown to be related to a longer OS if compared to SRT-IT interval >7 days (n = 10) (propensity score-adjusted P = .008). The combined treatment was well tolerated. No significant difference in terms of radionecrosis between SRT + IT patients and SRT-alone patients was observed. The time interval between SRT and IT had no impact on the toxicity rate. CONCLUSIONS: Combined SRT + IT was a safe approach, associated with a better iLPFS if compared to exclusive SRT.

A case of sudden brain metastases progression after temporary targeted therapy discontinuation: when to regret a drug holiday.

Targeted therapy improves outcomes in BRAF V600-mutant metastatic melanoma with active brain metastases. We present the case of a patient with rapid brain disease progression upon temporary targeted therapy discontinuation and unusual rapid disease response upon treatment resumption. This report presents a 78-year-old woman with metastatic BRAF V600E positive melanoma (bladder and brain localizations). The patient started first-line dabrafenib and trametinib with good tolerability and evidence of complete response (CR). After 8 months of maintained CR, the patient took a drug holiday for 14 days. Brain MRI performed after treatment pause showed extensive disease progression, whereas extracranial staging was negative. The patient was asymptomatic: she restarted targeted therapy and underwent evaluation for whole-brain radiotherapy. Brain computed tomography scan and subsequent MRI performed to plan radiotherapy showed brain CR after only 10 days of targeted therapy resumption. The patient continued treatment, and radiotherapy indication was withheld. Repeated brain MRI confirmed maintained CR. Treatment with dabrafenib and trametinib is ongoing with excellent tolerability. Rapid intracranial progression is a well-known finding after discontinuation of combined targeted therapy in the case of extracranial progressive disease. This is the first report of documented disease progression upon temporary treatment discontinuation for reasons other than toxicity, with an unusual response after retreatment. Caution should be used in tailoring treatment during targeted therapy, allowing pauses for reasons other than toxicity. Strict adherence to treatment is paramount to guarantee disease control.

Back to (new) normality-A CODRAL/AIRO-L survey on cancer radiotherapy in Lombardy during Italian COVID-19 phase 2.

BACKGROUND: Italy experienced one of the world's severest COVID-19 outbreak, with Lombardy being the most afflicted region. However, the imposed safety measures allowed to flatten the epidemic curve and hence to ease the restrictions and inaugurate, on the 4th of May 2020, the Italian phase (P) 2 of the pandemic. The present survey study, endorsed by CODRAL and AIRO-L, aimed to assess how radiotherapy (RT) departments in Lombardy have dealt with the recovery. MATERIALS AND METHODS: A questionnaire dealing with the management of pandemic was developed online and sent to all CODRAL Directors on the 10th of June 2020. Answers were collected in full anonymity one week after. RESULTS: All the 33 contacted RT facilities (100%) responded to the survey. Despite the scale of the pandemic, during P1 14 (42.4%) centres managed to safely continue the activity (≤ 10% reduction). During P2, 10 (30.3%) centres fully recovered and 14 (42.4%) reported an increase. Nonetheless, 6 (18.2%) declared no changes and, interestingly, 3 (9.1%) reduced activities. Overall, 21 centres (63.6%) reported suspected or positive cases within healthcare workforce since the beginning of the pandemic. Staff units were quarantined in 19 (57.6%) and 6 (18.2%) centres throughout P1 and P2, respectively. In the two phases, about two thirds centres registered positive or suspected cases amongst patients. CONCLUSION: The study revealed a particular attention to anti-contagion measures and a return to normal or even higher clinical workload in most RT centres in Lombardy, necessary to carry out current and previously deferred treatments.

Stereotactic Dorsolateral Irradiation of Spinal Nerve Roots: A Novel Technique for the Treatment of Spasticity and Pain.

Selective dorsal rhizotomy is an established surgical treatment to improve the neurological and functional status of children with spastic cerebral palsy and adults with spasticity and pain caused by a variety of brain and spinal injuries. This procedure requires a dorsolumbar laminectomy to expose the appropriate dorsal rootlets, which are sectioned according to the presence of sustained electromiographic discharges. Image-guided robotic radiosurgery targeting the intracisternal sensory root of the trigeminal nerve has been described as a safe and effective non-invasive treatment for trigeminal neuralgia, a paroxystic pain disorder which often responds poorly to medical therapy. Image-guided radiosurgery requires no frame placement and can treat brain or spinal targets with submillimetric precision. This technique can be used to treat cervical or lumbar dorsal roots. A 44-year-old patient with von Hippel-Lindau disease developed severe spastic tetraparesis following multiple brain and spinal procedures. Spasticity and related pain mostly affected the right leg, with sustained electromiographic discharges originating from the right L4 nerve root. Response to medical therapy with baclofen and cannabinoids was poor. Due to geographical and logistical issues, the patient declined the placement of an intrathecal baclofen pump. Considering the poor general condition of the patient and his decision to avoid invasive procedures, a novel treatment option was offered to provide relief from spasticity and pain: stereotactic image-guided irradiation delivered to the sensory root. The patient underwent a right intraforaminal dorsolateral L4 root stereotactic irradiation with a delivered dose of 45 Gy prescribed to the 82% isodose. The treatment was well tolerated, without side effects. Resolution of spasticity and related pain in the right leg was found six months after the procedure. A marked reduction of spasticity and pain was also evident in the contralateral leg. These improvements have been stable over the last 18 months. So far, two additional patients underwent stereotactic dorsolateral spinal root irradiation (one delivered to a cervical, the other to a lumbar), with similar positive outcomes. These preliminary results suggest that spinal root stereotactic image-guided irradiation, a novel treatment option in the neurosurgical armamentarium, is a safe and effective procedure and deserves further investigation.

Factors affecting outcome in frameless non-isocentric stereotactic radiosurgery for trigeminal neuralgia: a multicentric cohort study.

BACKGROUND: Stereotactic radiosurgery (SRS) is an effective treatment for trigeminal neuralgia (TN). Nevertheless, a proportion of patients will experience recurrence and treatment-related sensory disturbances. In order to evaluate the predictors of efficacy and safety of image-guided non-isocentric radiosurgery, we analyzed the impact of trigeminal nerve volume and the nerve dose/volume relationship, together with relevant clinical characteristics. METHODS: Two-hundred and ninety-six procedures were performed on 262 patients at three centers. In 17 patients the TN was secondary to multiple sclerosis (MS). Trigeminal pain and sensory disturbances were classified according to the Barrow Neurological Institute (BNI) scale. Pain-free-intervals were investigated using Kaplan Meier analyses. Univariate and multivariate Cox regression analyses were performed to identify predictors. RESULTS: The median follow-up period was 38 months, median maximal dose 72.4 Gy, median target nerve volume 25 mm3, and median prescription dose 60 Gy. Pain control rate (BNI I-III) at 6, 12, 24, 36, 48, and 60 months were 96.8, 90.9, 84.2, 81.4, 74.2, and 71.2%, respectively. Overall, 18% of patients developed sensory disturbances. Patients with volume ≥ 30 mm3 were more likely to maintain pain relief (p = 0.031), and low integral dose (< 1.4 mJ) tended to be associated with more pain recurrence than intermediate (1.4-2.7 mJ) or high integral dose (> 2.7 mJ; low vs. intermediate: log-rank test, χ2 = 5.02, p = 0.019; low vs. high: log-rank test, χ2 = 6.026, p = 0.014). MS, integral dose, and mean dose were the factors associated with pain recurrence, while re-irradiation and MS were predictors for sensory disturbance in the multivariate analysis. CONCLUSIONS: The dose to nerve volume ratio is predictive of pain recurrence in TN, and re-irradiation has a major impact on the development of sensory disturbances after non-isocentric SRS. Interestingly, the integral dose may differ significantly in treatments using apparently similar dose and volume constraints.

Radiosurgery and fractionated stereotactic radiotherapy in oligometastatic/oligoprogressive non-small cell lung cancer patients: Results of a multi-institutional series of 198 patients treated with "curative" intent.

OBJECTIVES: stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) are a therapeutic option for Oligometastatic/Oligoprogressive (OM/OP) NSCLC. This retrospective multicentre analysis aims to analyse clinical outcomes and treatment related toxicity of patients treated to all sites of know disease with SRS and/or FSRT for OM/OP NSCLC in 8 Italian radiation oncology centres. MATERIALS AND METHODS: From January 2016 to January 2017 198 OM/OP NSCLC patients (pts) were treated in 8 Centres. Inclusion criteria were as follows: 1-5 lesions at onset or after previous systemic treatment; Pts must have all metastatic lesions treated. Endpoints analysed were local progression free survival (LPFS); out-of-field recurrence free survival (OFPS); progression free survival (PFS); overall survival (OS). Time to New systemic Therapy free survival (TNT) and toxicity were also analysed. RESULTS: At the time of radiotherapy, 119 pts (60 %) were treated for a single lesion, 49 (25 %) for 2 lesions, 30 (15 %) for 3-5 metastases. Total number of lesions treated was 333: 204 brain, 68 lung, 24 bone, 16 nodal, 12 adrenal, 8 liver and 1 soft tissue. 83/198 pts (41.8 %) had the primary tumour controlled at the time of the SRT. After a median follow-up of 18 months, median OS and PFS were 29.6 months and 10.6 months, respectively. One year LPFS and OPFS were 90 % and 47 %, respectively. Median TNT was 10 months. At univariate analysis factors associated with better OS were PS 0-1; controlled primary tumour, 1-2 lesions; extracranial metastasis. Multivariate analysis confirmed number of lesions <3 and extracranial metastasis to be related with better survival (Relative Risk 0.4 and 0.41, respectively). Two cases of death possibly related to brain radionecrosis were observed. CONCLUSION: OM/OP NSCLC pts treated with an ablative SRT to all metastatic sites have fair outcomes with acceptable toxicity. Better results might be achieved in case of low disease burden and extracranial possibly when primary tumour is controlled.

Cyberknife Radiosurgery for Trigeminal Neuralgia.

Introduction Image-guided robotic radiosurgery is an emerging minimally-invasive treatment option for trigeminal neuralgia (TN). Our group has treated 560 cases up to date, and report here the clinical outcomes of 387 treatments with three years follow-up. This study represents the largest single-center experience on CyberKnife radiosurgery for the treatment of TN so far reported. Methods CyberKnife radiosurgery treatment was offered to patients with drug-resistant TN, after the failure of other treatments or refusal of invasive procedures. A second treatment was offered to patients with a poor response after the first treatment or with recurrent pain. Treatment protocol required the non-isocentric delivery of 60 Gy prescribed to the 80% isodose to a 6 mm retrogasserian segment of the affected trigeminal nerve. Retreatments typically received 45 Gy, again prescribed to the 80% isodose. The final plan was developed accordingly to individual anatomy and dose distribution over the trigeminal nerve, gasserian ganglion, and brainstem. Clinical outcomes such as pain control and hypoesthesia/numbness have been evaluated after 6, 12, 24, and 36 months.  Results Our group has treated 527 patients with Cyberknife radiosurgery at Centro Diagnostico Italiano (CDI), Milan, Italy, during the last decade. A minimum follow-up of six months was available on 496 patients. These patients received 560 treatments: 435 patients (87.7%) had a single treatment, 60 patients (12.1%) had two treatments, and one patient (0.2%) had five treatments (two on the right side, three on the left side). Twenty four patients had multiple sclerosis (4.8%). Four hundred and forty-three patients (84%) received the treatment without previous procedures, while 84 patients (16%) underwent radiosurgery after the failure of other treatments. A neurovascular conflict was identified in 59% of the patients. Three hundred and forty-three patients (receiving a total of 387 treatments) had a minimum of 36 months follow up. Pain relief rate at 6, 12, 18, 24, 30 and 36 months was respectively 92, 87, 87, 82, 78 and 76%. Forty-four patients out of 343 (12.8%) required a second treatment during the observed period. At 36 months post-treatment, 21 patients (6,1%) reported the presence of bothering facial hypoesthesia. Eighteen patients out of 21 (85.7%) developed this complication after a repeated treatment.  Conclusions Frameless image-guided robotic radiosurgery in experienced hands is a safe and effective procedure for the treatment of TN, providing excellent pain control rates in the absence of major neurological complications. Repeated treatments due to recurrent pain are associated with restored pain control but at the price of a higher rate of sensory complications.

Multisession radiosurgery for perioptic meningiomas: medium-to-long term results from a CyberKnife cooperative study.

PURPOSE: Most recent literature has confirmed the efficacy of single-session radiosurgery (sRS) in the treatment of intracranial meningioma. Unfortunately, sRS is not always applicable due to large tumor volume and the proximity of the tumor to critical structures. When sRS is not recommended, multi-session radiosurgery (mRS) can be the solution. The best treatment schedule for mRS, however, is not well established. The aim of the present retrospective study is to validate the effectiveness of one approach, 25 Gy delivered in 5 fractions in 5 consecutive days, to treat skull base meningiomas. METHODS: This is a retrospective multicenter study. Patients with an anterior or a medium skull base meningioma that could not be treated by sRS due to large volume or proximity to the anterior optic pathways (AOPs) underwent 5-fraction mRS. Only patients with at least 36 months follow-up were included in the analysis. Local control and visual outcomes were investigated. RESULTS: One-hundred-sixty-seven patients were included in the analysis. One-hundred-one patients underwent RS as a primary indication and 66 were treated after a previous surgery. The median follow-up period was 51 months (range 36-129 months). Progression-free survival at 3, 5 and 8 years were, respectively, 98%, 94% and 90%. Excluding the progressive disease patients, the visual worsening rate was 3.7%. The 42% of the patients with a pre-treatment visual deficit experienced improvement in vision. CONCLUSION: 25 Gy delivered in 5 fractions is an effective modality for meningiomas that are near the AOP or are too large to be treated by sRS. The treatment schedule controlled the tumors while sparing visual function.

Localization accuracy of robotic radiosurgery in 1-view tracking.

PURPOSE: When a lung lesion is detected by only one couple of X-ray tube and image detector integrated with CyberKnife®, the fiducial-less tracking is limited to 1-view (34% of lung treatments at Centro Diagnostico Italiano). The aim of the study was mainly to determine the margin needed to take into account the localization uncertainty along the blind view (out-of-plane direction). METHODS: 36 patients treated in 2-view tracking modality (127 fractions in total) were included in the study. The actual tumor positions were determined retrospectively through logfile analysis and were projected onto 2D image planes. In the same plots the planned target positions based on biphasic breath-hold CT scans were represented preserving the metric with respect to the imaging center. The internal margin necessary to cover in out-of-plane direction the 95% of the target position distribution in the 95% of cases was calculated by home-made software in Matlab®. A validation test was preliminarily performed using XLT Phantom (CIRS) both in 2-view and 1-view scenarios. RESULTS: The validation test proved the reliability of the method, in spite of some intrinsic limitations. Margins were estimated equal to 5 and 6 mm for targets in upper and lower lobe respectively. Biphasic breath-hold CT led to underestimate the target movement in the hypothetical out-of-plane direction. The inter-fractional variability of spine-target distance was an important source of uncertainty for 1-view treatments. CONCLUSION: This graphic comparison method preserving metric could be employed in the clinical workflow of 1-view treatments to get patient-related information for customized margin definition.

Equipment, staffing, and provision of radiotherapy in Lombardy, Italy: Results of three surveys performed between 2012 and 2016.

INTRODUCTION:: Several efforts are being implemented at the European level to measure provision of up-to-date radiation treatments across the continent. METHODS:: A snapshot survey involving all radiation oncology centers within Lombardy, Italy, was performed in 2012 and repeated in 2014 and 2016, in cooperation with regional governmental officers. Centers were asked to provide detailed information concerning all individual patients being treated on the index day, and to report data on available local resources. RESULTS:: We observed an increase in the number of centers and of megavoltage units (MVU) (from 76 to 87, i.e., 8.7 MVU per million inhabitants in 2016). Mean number of MVU per center was 2.5. Average age of MVU increased from 5.3 to 7.5 years and patients on the waiting list also increased. Conformal 3D radiotherapy (RT) treatments decreased from 56% to 42% and were progressively replaced by intensity-modulated RT treatments (from 39% to 49%). Waiting times were overall satisfactory. Radiation oncologists treated on average 152 and radiation therapists 100 RT courses per year. Average reimbursement per course was €4,879 (range €2,476-€8,014). CONCLUSIONS:: The methodology of snapshot survey proved feasible and provided valuable information about radiation oncology provision and accessibility in Lombardy.

Staged Image-guided Robotic Radiosurgery and Deferred Chemotherapy to Treat a Malignant Glioma During and After Pregnancy.

A 26-year-old pregnant woman with a fast-growing malignant deep-seated brain glioma was offered a therapeutic abortion to allow subsequent surgical resection. This option was refused by the mother, but the fast tumor growth placed the life of both mother and child at risk. A staged CyberKnife radiosurgery treatment was then planned, aiming to provide at least temporary tumor growth control and allow a safe delivery while keeping the doses received by the fetus well below the allowed doses. Growth control and the safe delivery of a healthy child were achieved after this first treatment. An intensive chemotherapy program based on the combination of Avastin, irinotecan, and Temodal was then started. Recurring tumor growth was treated with a second CyberKnife procedure while continuing the above chemotherapy protocol. At 43 months after the second CyberKnife procedure, the tumor had disappeared on magnetic resonance imaging. Neither mother nor child showed the neurological sequelae. Staged radiosurgery and deferred chemotherapy proved to be a safe and effective treatment to allow the delivery of a healthy child and the long-term control of an aggressive brain glioma.

Image-Guided Robotic Radiosurgery for Trigeminal Neuralgia.

BACKGROUND: Frameless, non-isocentric irradiation of an extended segment of the trigeminal nerve introduces new concepts in stereotactic radiosurgery for medically resistant trigeminal neuralgia (TN). OBJECTIVE: To report the results of the largest single-center experience about image-guided robotic radiosurgery for TN. METHODS: A cohort of 138 patients treated with CyberKnife® (Accuray Incorporated, Sunnyvale, California) radiosurgery with a minimum follow-up of 36 mo were recruited. Pain relief, medications, sensory disturbances, rate and time of pain recurrence were prospectively analyzed. RESULTS: Median follow-up was 52.4 mo; median dose 75 Gy; median target length 5.7-mm; median target volume 40 mm³; median prescription dose 60 Gy (80% isodose line). Actuarial pain control rate (Barrow Neurological Institute [BNI] class I-IIIa) at 6, 12, 24, and 36 mo were 93.5%, 85.8%, 79.7%, and 76%, respectively. Overall, 33 patients (24%) required a second treatment. Overall, 18.1% developed sensory disturbances after 16.4 ± 8.7 mo. One patient (0.7%) developed BNI grade IV dysfunction; 6 (4.3%) developed BNI grade III (somewhat bothersome) hypoesthesia after retreatment; BNI grade II (not bothersome) hypoesthesia was reported by 18 patients (11 after retreatment). Shorter nerve length (<6 mm vs 6 mm), smaller nerve volume (<30 mm3 vs >30 mm3), and lower prescription dose (<58 vs >58 Gy) were associated with treatment failure (P = .01, P = .02, P = .03, respectively). Re-irradiation independently predicted sensory disturbance (P < .001). CONCLUSION: Targeting a 6-mm segment of the trigeminal nerve with a prescribed dose of 60 Gy appears safe and effective. Persistent pain control was achieved in most patients with acceptable risk of sensory complications, which were typically found after re-irradiation.

Multi-institutional application of Failure Mode and Effects Analysis (FMEA) to CyberKnife Stereotactic Body Radiation Therapy (SBRT).

BACKGROUND: A multidisciplinary and multi-institutional working group applied the Failure Mode and Effects Analysis (FMEA) approach to assess the risks for patients undergoing Stereotactic Body Radiation Therapy (SBRT) treatments for lesions located in spine and liver in two CyberKnife® Centres. METHODS: The various sub-processes characterizing the SBRT treatment were identified to generate the process trees of both the treatment planning and delivery phases. This analysis drove to the identification and subsequent scoring of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system. Novel solutions aimed to increase patient safety were accordingly considered. RESULTS: The process-tree characterising the SBRT treatment planning stage was composed with a total of 48 sub-processes. Similarly, 42 sub-processes were identified in the stage of delivery to liver tumours and 30 in the stage of delivery to spine lesions. All the sub-processes were judged to be potentially prone to one or more failure modes. Nineteen failures (i.e. 5 in treatment planning stage, 5 in the delivery to liver lesions and 9 in the delivery to spine lesions) were considered of high concern in view of the high RPN and/or severity index value. CONCLUSIONS: The analysis of the potential failures, their causes and effects allowed to improve the safety strategies already adopted in the clinical practice with additional measures for optimizing quality management workflow and increasing patient safety.

125I brachytherapy for localized prostate cancer: a single institution experience.

AIMS AND BACKGROUND: To evaluate the clinical outcome of a cohort of localized prostate cancer patients treated with 125I permanent brachytherapy at the University of Turin. METHODS AND STUDY DESIGN: A retrospective analysis was carried out on 167 consecutive patients with early stage prostate adenocarcinoma who underwent 125I brachytherapy between January 2003 and December 2010. A minimum follow-up of ≥ 12 months was mandatory for inclusion. Biochemical disease-free survival (defined on the basis of the ASTRO definition and the ASTRO-Phoenix definition) was chosen as the primary end point. Secondary end points were gastrointestinal and genitourinary toxicity (acute and late, defined according to the RTOG scale). RESULTS: With a median follow-up of 42 months (range, 13.5-90.7), biochemical disease-free survival at 3 and 5 years was respectively 91.1% and 85.7%, according to the ASTRO definition and 94.5% and 85.1% according to ASTRO-Phoenix definition (for statistical purposes, only the ASTRO definition was used). Hormone treatment and nadir PSA (cutoff of 0.35 ng/ml) were the only factors affecting biochemical disease-free survival both on univariate (P = 0.02 and P = 0.001, respectively) and multivariate analysis (HR 0.024; P = 0.021 and HR 21.6; P = 0.006, respectively). Only 3.6% of patients experienced ≥ grade 3 acute urinary toxicity and 5% ≥ grade 3 late urinary toxicity. Prior transurethral prostate resection was the only independent predictor of grade 3 late urinary toxicity on multivariate analysis (HR 0.13; P = 0.009). CONCLUSIONS: This mono-institutional series confirmed that brachytherapy is an effective and safe treatment modality for localized prostate cancer, with acceptable short- and long-term morbidity rates.