SAPHIR Radiochirurgie

This study aimed to determine the efficacy and safety of robotic-based fractionated stereotactic radiotherapy (FSRT) in the treatment of large brainstem metastases (BSMs). Ten BSM were treated in ten patients with FSRT between January 2012 and December 2018. The median age was 61 years (range, 53-74 years) with a median Karnofsky Performance Score of 80 (range, 70-90). Four patients (40%) had received whole-brain radiotherapy prior to FSRT. The median tumor volume was 4.2 cm3 (range, 1.35-8.18 cm3) with a median prescription dose of 24 Gy (range, 16-24 Gy) delivered in 3-5 fractions (median three fractions) to the 56%-83% isodose line (median 70.5%). 1Median follow-up for the entire cohort was 14.1 months (range, 4.6-19.3 months). Five local recurrences were documented. Local control (LC) rate at 6 and 12 months was 90% and 64.2%, respectively. The median tumor volume of patients developing local recurrence was 5.42 cm3. Three patients experienced intracranial out-of-field failure for a 12-month intracranial control rate of 78.7%. Median overall survival and time to extracranial progression were 14.7 and 16.8 months, respectively. Toxicity was low with only one patient developing a new hemiparesis. Robotic-based FSRT for BSM appears to be safe with favorable LC and low toxicity even for large tumors.

Simple SummaryMelanoma brain metastases (MBM) have a high propensity for hemorrhage (HA) after treatment. Our retrospective analysis evaluated factors associated with HA of MBM after robotic stereotactic radiosurgery (SRS) in the era of modern systemic therapy, and to the best of our knowledge, this is the first study focusing on this side effect. A total of 55 patients with 279 MBM were treated. The use of anticoagulants was the only predictive factor, both for radiologically evident HA and HA causing grade 3 toxicity. The interval between the administration of systemic therapy and SRS was also significant with regard to HA causing grade 1 toxicity, but it appears that the combination was safe, at least concerning grade 3 toxicity. We believe that our study is a useful contribution to the current literature, as it provides insights regarding the factors that correlate with HA.We aimed to evaluate the factors associated with hemorrhage (HA) of melanoma brain metastases (MBM) after Cyberknife stereotactic radiosurgery (SRS) in the modern era of systemic therapy. A total of 55 patients with 279 MBM were treated in 93 fractions. The median age, SRS dose, radiological follow-up, and time to HA were 60.4 years, 20 Gy, 17.7 months, and 10.7 months, respectively. Radiologically evident HA was documented in 47 (16.8%) metastases. Of the 55 patients, 25 (45.4%) suffered an HA. Among those, HA caused grade 3 toxicity in 10 patients (40%) and grade 1 symptoms in 5 patients (20%). Ten patients (40%) with HA experienced no toxicity. Logistic regression revealed the use of anticoagulants and the administration of systemic therapy within 7/15 days from SRS to be predictive for HA. When considering the HA causing grade 3 symptomatology, only the use of anticoagulants was significant, with the delivery of whole brain radiation therapy (WBRT) before the HA narrowly missing statistical significance. Our retrospective analysis showed that the administration of modern systemic therapy within 7/15 days from SRS may contribute to HA of MBM, though it appears safe, at least concerning grade 3 toxicity. The use of anticoagulants by the time of SRS significantly increased the risk of HA.

Simple SummaryIn this short communication, we present three cases of patients with symptomatic, synchronous brain metastases of otherwise locally limited non-small cell lung cancer. The patients received local ablative treatment of the brain metastases followed by neoadjuvant immunochemotherapy with pemetrexed, cisplatin, and pembrolizumab, and resection of the pulmonary lesion with curative intent. With two of the patients still alive and maintaining a good quality of life with a progression-free survival and overall survival of 28 and 35 months, respectively, this case series illustrates the potential of novel combinatorial treatment approaches.Brain metastases are a common finding upon initial diagnosis of otherwise locally limited non-small cell lung cancer. We present a retrospective case series describing three cases of patients with symptomatic, synchronous brain metastases and resectable lung tumors. The patients received local ablative treatment of the brain metastases followed by neoadjuvant immunochemotherapy with pemetrexed, cisplatin, and pembrolizumab. Afterwards, resection of the pulmonary lesion with curative intent was performed. One patient showed progressive disease 12 months after initial diagnosis, and passed away 31 months after initial diagnosis. Two of the patients are still alive and maintain a good quality of life with a progression-free survival and overall survival of 28 and 35 months, respectively, illustrating the potential of novel combinatorial treatment approaches.

This paper introduces the development of a VR program of interview scenes for nurse managers. The contents include four scenarios which nurse managers often encounter. Twenty-two nurse managers participated in its verification. Ninety percent of the participants answered “agree” or “strongly agree” regarding “helpful,” “useful for the future,” and “interesting.” Due to COVID-19, the participants watched the VR program either at their home or work places. All the discussions were held online. Even during the state of emergency, it is confirmed that a VR program can be useful tool for training and education.

BackgroundLocal treatment of metastases in combination with systemic therapy can prolong survival of oligo-metastasized patients. To fully exploit this potential, safe and effective treatments are needed to ensure long-term metastases control. Stereotactic body radiotherapy (SBRT) is one means, however, for moving liver tumors correct delivery of high doses is challenging. After validating equal in-vivo treatment accuracy, we analyzed a pooled multi-platform liver-SBRT-database for clinical outcome. MethodsLocal control (LC), progression-free interval (PFI), overall survival (OS), predictive factors and toxicity was evaluated in 135 patients with 227 metastases treated by gantry-based SBRT (deep-inspiratory breath-hold-gating; n = 71) and robotic-based SBRT (fiducial-tracking, n = 156) with mean gross tumor volume biological effective dose (GTV-BEDα/β=10Gy) of 146.6 Gy10. ResultsOne-, and five-year LC was 90% and 68.7%, respectively. On multivariate analysis, LC was significantly predicted by colorectal histology (p = 0.006). Median OS was 20 months with one- and two-year OS of 67% and 37%. On multivariate analysis, ECOG-status (p = 0.003), simultaneous chemotherapy (p = 0.003), time from metastasis detection to SBRT-treatment (≥2months; p = 0.021) and LC of the treated metastases (≥12 months, p < 0.009) were significant predictors for OS. One- and two-year PFI were 30.5% and 14%. Acute toxicity was mild and rare (14.4% grade I, 2.3% grade II, 0.6% grade III). Chronic °III/IV toxicities occurred in 1.1%. ConclusionsPatient selection, time to treatment and sufficient doses are essential to achieve optimal outcome for SBRT with active motion compensation. Local control appears favorable compared to historical control. Long-term LC of the treated lesions was associated with longer overall survival.

IntroductionCombination therapy for melanoma brain metastases (MM) using stereotactic radiosurgery (SRS) and immune checkpoint-inhibition (ICI) or targeted therapy (TT) is currently of high interest. In this collective, time evolution and incidence of imaging findings indicative of pseudoprogression is sparsely researched. We therefore investigated time-course of MRI characteristics in these patients.MethodsData were obtained retrospectively from 27 patients (12 female, 15 male; mean 61 years, total of 169 MMs). Single lesion volumes, total MM burden and edema volumes were analyzed at baseline and follow-up MRIs in 2 months intervals after SRS up to 24 months. The occurrence of intralesional hemorrhages was recorded.Results17 patients (80 MM) received ICI, 8 (62 MM) TT and 2 (27 MM) ICI + TT concomitantly to SRS. MM-localization was frontal (n = 89), temporal (n = 23), parietal (n = 20), occipital (n = 10), basal ganglia/thalamus/insula (n = 10) and cerebellar (n = 10). A volumetric progression of MM 2–4 months after SRS was observed in combined treatment with ICI (p = 0.028) and ICI + TT (p = 0.043), whereas MMs treated with TT showed an early volumetric regression (p = 0.004). Edema volumes moderately correlated with total MM volumes (r = 0.57; p < 0.0001). Volumetric behavior did not differ significantly over time regarding lesions’ initial sizes or localizations. No significant differences between groups were observed regarding rates of post-SRS intralesional hemorrhages.ConclusionReversible volumetric increases in terms of pseudoprogression are observed 2–4 months after SRS in patients with MM concomitantly treated with ICI and ICI + TT, rarely after TT. Edema volumes mirror total MM volumes. Medical treatment type does not significantly affect rates of intralesional hemorrhage.

We retrospectively evaluated the efficacy and toxicity of gross tumor volume (GTV) mean dose optimized stereotactic body radiation therapy (SBRT) for primary and secondary lung tumors with and without robotic real-time motion compensation. Between 2011 and 2017, 208 patients were treated with SBRT for 111 primary lung tumors and 163 lung metastases with a median GTV of 8.2 cc (0.3-174.0 cc). Monte Carlo dose optimization was performed prioritizing GTV mean dose at the potential cost of planning target volume (PTV) coverage reduction while adhering to safe normal tissue constraints. The median GTV mean biological effective dose (BED)10 was 162.0 Gy10 (34.2-253.6 Gy10) and the prescribed PTV BED10 ranged 23.6-151.2 Gy10 (median, 100.8 Gy10). Motion compensation was realized through direct tracking (44.9%), fiducial tracking (4.4%), and internal target volume (ITV) concepts with small (≤5 mm, 33.2%) or large (>5 mm, 17.5%) motion. The local control (LC), progression-free survival (PFS), overall survival (OS), and toxicity were analyzed. Median follow-up was 14.5 months (1-72 months). The 2-year actuarial LC, PFS, and OS rates were 93.1, 43.2, and 62.4%, and the median PFS and OS were 18.0 and 39.8 months, respectively. In univariate analysis, prior local irradiation (hazard ratio (HR) 0.18, confidence interval (CI) 0.05-0.63, p = 0.01), GTV/PTV (HR 1.01-1.02, CI 1.01-1.04, p < 0.02), and PTV prescription, mean GTV, and maximum plan BED10 (HR 0.97-0.99, CI 0.96-0.99, p < 0.01) were predictive for LC while the tracking method was not (p = 0.97). For PFS and OS, multivariate analysis showed Karnofsky Index (p < 0.01) and tumor stage (p ≤ 0.02) to be significant factors for outcome prediction. Late radiation pneumonitis or chronic rip fractures grade 1-2 were observed in 5.3% of the patients. Grade ≥3 side effects did not occur. Robotic SBRT is a safe and effective treatment for lung tumors. Reducing the PTV prescription and keeping high GTV mean doses allowed the reduction of toxicity while maintaining high local tumor control. The use of real-time motion compensation is strongly advised, however, well-performed ITV motion compensation may be used alternatively when direct tracking is not feasible.

To create an instrument for estimating the risk of new brain metastases after stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) alone in patients with renal cell carcinoma (RCC). In 45 patients with 1-3 brain metastases, seven characteristics were analyzed for association with freedom from new brain metastases (age, gender, performance score, number and sites of brain metastases, extra-cerebral metastasis, interval from RCC diagnosis to SRS/FSRT). Lower risk of subsequent brain lesions after RT was associated with single metastasis (p=0.043) and supratentorial involvement only (p=0.018). Scoring points were: One metastasis=1, 2-3 metastases=0, supratentorial alone=1, infratentorial with/without supratentorial=0. Scores of 0, 1 and 2 points were associated with 6-month rates of freedom from subsequent brain lesions of 25%, 74% and 92% (p=0.008). After combining groups with 1 and 2 points, 6-month rates were 25% for those with 0 points and 83% for those with 1-2 points (p=0.002). Two groups were identified with different risks of new brain metastases after SRS or FSRT alone. High-risk patients may benefit from additional whole-brain irradiation.

We retrospectively evaluated the patterns of failure for robotic guided real-time breathing-motion-compensated (BMC) stereotactic body radiation therapy (SBRT) in the treatment of tumors in moving organs. Between 2011 and 2016, atotal of 198 patients with 280 lung, liver, and abdominal tumors were treated with BMC-SBRT. The median gross tumor volume (GTV) was 12.3 cc (0.1-372.0 cc). Medians of mean GTV BEDα/β=10 Gy (BED= biological effective dose) was 148.5 Gy10 (31.5-233.3 Gy10) and prescribed planning target volume (PTV) BEDα/β=10 Gy was 89.7 Gy10 (28.8-151.2 Gy10), respectively. We analyzed overall survival (OS) and local control (LC) based on various factors, including BEDs with α/β ratios of 15 Gy (lung metastases), 21 Gy (primary lung tumors), and 27 Gy (liver metastases). Median follow-up was 10.4months (2.0-59.0 months). The 2‑year actuarial LC was 100 and 86.4% for primary early and advanced stage lung tumors, respectively, 100% for lung metastases, 82.2% for liver metastases, and 90% for extrapulmonary extrahepatic metastases. The 2‑year OS rate was 47.9% for all patients. In uni- and multivariate analysis, comparatively lower PTV prescription dose (equivalence of 3× 12-13 Gy) and higher average GTV dose (equivalence of 3× 18 Gy) to current practice were significantly associated with LC. For OS, Karnofsky performance score (100%), gender (female), and SBRT without simultaneous chemotherapy were significant prognostic factors. Grade3 side effects were rare (0.5%). Robotic guided BMC-SBRT can be considered asafe and effective treatment for solid tumors in moving organs. To reach sufficient local control rates, high average GTV doses are necessary. Further prospective studies are warranted to evaluate these points.