Application of the NSE score (Neurology-Stability-Epidural compression assessment) to establish the need for surgery in spinal metastases of elderly patients: a multicenter investigation.

PURPOSE: This retropective multicentric study aims to investigate the clinical applicability of the NSE score in the elderly, to verify the role of this tool as an easy help for decision making also for this class of patients. METHODS: All elderly patients (> 65 years) suffering from spinal metastases undergoing surgical or non-surgical treatment at the authors' Institutions between 2015 and 2022 were recruited. An agreement group (AG) and non-agreement group (NAG) were identified accordingly to the agreement between the NSE score indication and the performed treatment. Neurological status and axial pain were evaluated for both groups at follow-up (3 and 6 months). The same analysis was conducted specifically grouping patients older than 75 years. RESULTS: A strong association with improvement or preservation of clinical status (p < 0.001) at follow-up was obtained in AG. The association was not statistically significant in NAG at the 3-month follow-up (p 1.00 and 0.07 respectively) and at 6 months (p 0.293 and 0.09 respectively). The group of patients over 75 years old showed similar results in terms of statistical association between the agreement group and better outcomes. CONCLUSION: Far from the need or the aim to build dogmatic algorithms, the goal of preserving a proper performance status plays a key role in a modern oncological management: functional outcomes of the multicentric study group showed that the NSE score represents a reliable tool to establish the need for surgery also for elderly patients.

The impact of local control on widespread progression and survival in oligometastasis-directed SBRT: Results from a large international database.

PURPOSE: We investigated the impact of local control (LC) on widespread progression (WSP) and overall survival (OS) in patients treated to all extracranial oligometastases (OMs) at presentation to SBRT in this retrospective review across 6 international centers. MATERIALS/METHODS: Relationships between LC status of SBRT-directed OMs and OS and WSP (>5 new active/untreated lesions) were explored using Cox and Fine-Gray regression models, adjusting for radioresistant histology and pre-SBRT systemic therapy receipt. The association between LC and dosimetric predictors was analyzed with competing risk regression using death as a competing risk and across a wide range of simulated α/ßratios. RESULTS: In total, 1700 OMs in 1033 patients were analyzed, with 25.2% NSCLC, 22.7% colorectal, 12.8% prostate, and 8.1% breast histology. Patients who failed locally in any SBRT-directed OM within 6 mo were at 3.6-fold higher risk of death and 2.7-fold higher risk of WSP compared to those who remained locally-controlled (p < 0.001). Similar associations existed for each duration of LC investigated through 3 yrs post-SBRT. There was no significant difference in risk of WSP or death between patients who failed in a subset of SBRT-treated lesions vs. patients who failed in all lesions. Minimum dose (Dmin) to the GTV/ITV was most predictive of LC when compared to prescription dose, PTV Dmin, and PTV Dmax. Sensitivity analysis for achieving 1-yr LC > 95% found thresholds of 41.2 Gy and 55.2 Gy in 5 fractions for smaller (< 27.7 cc) and larger radioresistant lesions, respectively. CONCLUSION: This large multinational cohort suggests that the duration of LC following OM-directed SBRT strongly correlates with WSP and OS.

Helical tomotherapy and two types of volumetric modulated arc therapy: dosimetric and clinical comparison for several cancer sites.

Radiotherapy accelerators have undergone continuous technological developments. We investigated the differences between Radixact™ and VMAT treatment plans. Sixty patients were included in this study. Dosimetric comparison between the Radixact™ and VMAT plans was performed for six cancer sites: whole-brain, head and neck, lymphoma, lung, prostate, and rectum. The VMAT plans were generated with two Elekta linear accelerators (Synergy® and Versa HD™). The planning target volume (PTV) coverage, organs-at-risk dose constraints, and four dosimetric indexes were considered. The deliverability of the plans was assessed using quality assurance (gamma index evaluation) measurements; clinical judgment was included in the assessment. The mean AAPM TG218 (3%-2 mm, global normalization) gamma index values were 99.4%, 97.8%, and 96.6% for Radixact™, Versa HD™, and Synergy®, respectively. Radixact™ performed better than Versa HD™ in terms of dosimetric indexes, hippocampi D100%, spinal cord Dmax, rectum V38.4  Gy, bladder V30 Gy, and V40 Gy. Versa HD™ saved more of the (lungs-PTV) V5 Gy and (lungs-PTV) Dmean, heart Dmean, breasts V4 Gy, and bowel V45 Gy. Regarding Synergy®, the head and neck Radixact™ plan saved more of the parotid gland, oral cavity, and supraglottic larynx. From a clinical point of view, for the head and neck, prostate, and rectal sites, the Radixact™ and Versa HD™ plans were similar; Radixact™ plans were preferable for the head and neck and rectum to Synergy® plans. The quality of linac plans has improved, and differences with tomotherapy have decreased. However, tomotherapy continues to be an essential add-on in multi-machine departments.

The oligometastatic setting in HNSCC: A critical review by the Rete Oncologica Piemonte e Valle d'Aosta multidisciplinary team.

INTRODUCTION: The oligometastatic disease is a low burden metastatic disease that might still benefit from curable treatment. Squamous cell carcinoma of the head and neck (HNSCC) is a complex group of malignancies, with high rates of loco-regional recurrences. Distant metastases are less frequent, and a single or few deposits are often observed (oligometastatic disease). The optimal management of oligometastatic HNSCC remains to be defined. MATERIALS AND METHODS: Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. RESULTS: This paper contains a narrative report and a critical discussion of the available evidence on the management of oligometastatic HNSCC patients, with a focus on metastasis-directed therapy (MDT), particularly stereotactic ablative radiotherapy (SABR). CONCLUSIONS: in line with literature data, the multidisciplinary evaluation emerged as the key element in the management of oligometastatic HNSCC patients.

Conditional Survival of Patients With Extracranial Oligometastatic Treated With Stereotactic Body Radiation Therapy: An International Consortium Study.

PURPOSE: Prolonged survivorship is increasingly observed in patients with oligometastases (OM) treated with stereotactic body radiation therapy (SBRT). The purpose of this study was to study the conditional survival of patients with OM, which can provide more detailed prognostic information over time by considering time already survived. METHODS AND MATERIALS: A multi-institutional database consisting of 1033 patients with OM (≤5 metastases) treated with SBRT between 2006 and 2017 was analyzed. Conditional overall survival (OS) and progression-free survival (PFS) in 3 years were obtained at multiple time points for all patients and by primary cancer type. Cox regression was used to determine trends in conditional OS and PFS. Changes in the predictors of OS and PFS over time were also determined by multivariable Cox regression. RESULTS: The median follow-up was 24 months (0.3-105 months). Three-year OS and PFS at baseline were 56.7% and 23.2%, respectively. The OS in 3 years conditional on having survived for 3, 6, 12, and 24 months did not significantly change over time (56.7%, 55.4%, 55.8%, and 50.6%, respectively; P = .60). In contrast, the probability of PFS in 3 years conditional on having survived progression-free for 3, 6, 12, and 24 months significantly increased over time (23.6%, 27.3%, 35.1%, and 48.8%, respectively; P < .001). When stratified by primary site, conditional PFS significantly increased over time for patients with colorectal, breast, or kidney cancer. Conditional OS remained stable for patients with non-small cell lung cancer or kidney cancer but significantly decreased over time for patients with prostate, breast, or colorectal cancer. Changes in significant prognostic factors of OS and PFS over time were also observed. CONCLUSIONS: Analysis of conditional survival among patients with OM showed that as patients survived longer, their prognosis for further survival remained stable or decreased. However, patients who survived longer without disease progression had increased probability of PFS over time.

Stereotactic radiotherapy for lung oligometastases.

30-60% of cancer patients develop lung metastases, mostly from primary tumors in the colon-rectum, lung, head and neck area, breast and kidney. Nowadays, stereotactic radiotherapy (SRT ) is considered the ideal modality for treating pulmonary metastases. When lung metastases are suspected, complete disease staging includes a total body computed tomography (CT ) and/or positron emission tomography-computed tomography (PET -CT ) scan. PET -CT has higher specificity and sensitivity than a CT scan when investigating mediastinal lymph nodes, diagnosing a solitary lung lesion and detecting distant metastases. For treatment planning, a multi-detector planning CT scan of the entire chest is usually performed, with or without intravenous contrast media or esophageal lumen opacification, especially when central lesions have to be irradiated. Respiratory management is recommended in lung SRT, taking the breath cycle into account in planning and delivery. For contouring, co-registration and/or matching planning CT and diagnostic images (as provided by contrast enhanced CT or PET-CT ) are useful, particularly for central tumors. Doses and fractionation schedules are heterogeneous, ranging from 33 to 60 Gy in 3-6 fractions. Independently of fractionation schedule, a BED10 > 100 Gy is recommended for high local control rates. Single fraction SRT (ranges 15-30 Gy) is occasionally administered, particularly for small lesions. SRT provides tumor control rates of up to 91% at 3 years, with limited toxicities. The present overview focuses on technical and clinical aspects related to treatment planning, dose constraints, outcome and toxicity of SRT for lung metastases.

Role of Radiosurgery and Stereotactic Ablative Radiotherapy for Oligometastatic Non-Oncogene Addicted NSCLC.

Local ablative therapy (LAT), intended as stereotactic ablative radiotherapy or stereotactic radiosurgery, is a well-recognized effective treatment for selected patients with oligometastatic NSCLC. Current clinical evidence supports LAT alone or in combination with systemic therapies. Our retrospective mono-institutional study aims to assess the role of LAT with a peculiar focus on the largest series of non-oncogene addicted oligometastatic NSCLC patients to date. We included in this analysis all patients with the mentioned disease characteristics who underwent LAT for intracranial and/or extracranial metastases between 2011 and 2020. The main endpoints were local control (LC), progression free survival (PFS) and overall survival (OS) in the whole population and after stratification for prognostic factors. We identified a series of 245 consecutive patients (314 lesions), included in this analysis (median age 69 years). In 77% of patients, a single metastasis was treated with LAT and intracranial involvement was the most frequent indication (53% of patients) in our series. The overall response rate (ORR) after LAT was 95%. In case of disease progression, 66 patients underwent new local treatments with curative intent. With a median follow-up of 18 months, median PFS was 13 months (1-year PFS 50%) and median OS was 32 months (1-year OS 75%). The median LC was not reached (1-year LC 89%). The presence of brain metastases was the only factor that negatively affected all clinical endpoints, with a 1-year LC, PFS and OS of 82%, 29% and 62% respectively, compared to 95%, 73% and 91%, respectively, for patients without BMs (p < 0.001 for each endpoint). At the multivariate analysis, mediastinal nodal involvement at baseline (p = 0.049), ECOG PS = 1 (p = 0.011), intracranial disease involvement (p = 0.001), administration of chemotherapy in combination with LAT (p = 0.020), and no delivery of further local treatment for progression or delivery of focal treatment for intracranial progression (p < 0.001) were related to a poorer OS. In our retrospective series, which is to our knowledge the largest to date, LAT showed encouraging results and confirmed the safety and effectiveness of focal treatments in non-oncogene addicted oligometastatic NSCLC patients.

Development of a Prognostic Model for Overall Survival in Patients With Extracranial Oligometastatic Disease Treated With Stereotactic Body Radiation Therapy.

PURPOSE: Patients with oligometastatic disease (OMD) can experience durable disease control with ablative therapy to all sites of disease. Stereotactic body radiation therapy (SBRT) is an important modality in the management of OMD, although a validated prognostic model for OMD treated with SBRT is currently lacking. The purpose of this study was to develop a prognostic model for overall survival (OS) in patients with OMD treated with SBRT. METHODS AND MATERIALS: A multi-institutional database of patients with extracranial OMD treated with SBRT was used for model development. The final prognostic model was generated in a training set using recursive partitioning analysis representing 75% of the population. Model performance was evaluated in the reserved test set. RESULTS: The analysis included 1033 patients. The median OS for the entire cohort was 44.2 months (95% confidence interval [CI], 39.2-48.8 months). The variables used in the regression tree, in order of importance, were primary histology, lung-only OMD on presentation, the timing of OMD presentation, and age at the start of SBRT. A full 5-category risk stratification system based on the terminal nodes possessed fair to good discriminative power with a Harrell concordance statistic of 0.683 (95% CI, 0.634-0.731) and a time-dependent area under the receiver operating characteristic curve of 0.709 (95% CI, 0.706-0.711) in the test set, with good calibration. A simplified risk stratification system consisting of 3 risk categories was also proposed for greater ease of use with comparable performance. CONCLUSIONS: A clinical prognostic model for OS in patients with extracranial OMD treated with SBRT has been developed and validated.

An analysis of a large multi-institutional database reveals important associations between treatment parameters and clinical outcomes for stereotactic body radiotherapy (SBRT) of oligometastatic colorectal cancer.

PURPOSE: In recent years, stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for oligometastatic cancers. Here, we report radiation treatment parameters and clinical outcomes for patients with oligometastatic colorectal cancer (CRC) treated with SBRT using a large multi-institutional database. METHODS: Patients with extra-cranial oligometastatic CRC (≤5 lesions) treated with SBRT at six large academic cancer centers were included. The primary outcome was local recurrence while secondary outcomes included overall survival (OS) progression free survival, oligo-progression, and widespread progression. Survival outcomes were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were performed to determine the relationship between patient and treatment characteristics and clinical outcomes. RESULTS: We identified 235 patients with a total of 381 oligometastatic CRC lesions. The 1- and 5-year local recurrence rate was 13.6% and 44.3% respectively. The median OS was 49 months with a 2-and 5-year OS of 76.1% and 35.9%, respectively. On multivariable analysis, a BED10 of ≥120 Gy, and lung versus liver metastases were associated with a reduction in local recurrence. Larger total PTV size (≥17.5 cc) was associated with worse overall survival, progression free survival, and widespread progression. CONCLUSION: This large multi-institutional analysis found that the use of SBRT for oligometastatic colorectal cancer resulted in favorable overall survival. However, local recurrence is higher than expected for ablative radiation treatment. An increase in BED10 should be considered if feasible and safe.

Modern Radiation Therapy for the Management of Brain Metastases From Non-Small Cell Lung Cancer: Current Approaches and Future Directions.

Brain metastases (BMs) represent the most frequent event during the course of Non-Small Cell Lung Cancer (NSCLC) disease. Recent advancements in the diagnostic and therapeutic procedures result in increased incidence and earlier diagnosis of BMs, with an emerging need to optimize the prognosis of these patients through the adoption of tailored treatment solutions. Nowadays a personalized and multidisciplinary approach should rely on several clinical and molecular factors like patient's performance status, extent and location of brain involvement, extracranial disease control and the presence of any "druggable" molecular target. Radiation therapy (RT), in all its focal (radiosurgery and fractionated stereotactic radiotherapy) or extended (whole brain radiotherapy) declinations, is a cornerstone of BMs management, either alone or combined with surgery and systemic therapies. Our review aims to provide an overview of the many modern RT solutions available for the treatment of BMs from NSCLC in the different clinical scenarios (single lesion, oligo and poly-metastasis, leptomeningeal carcinomatosis). This includes a detailed review of the current standard of care in each setting, with a presentation of the literature data and of the possible technical solutions to offer a "state-of-art" treatment to these patients. In addition to the validated treatment options, we will also discuss the future perspectives on emerging RT technical strategies (e.g., hippocampal avoidance whole brain RT, simultaneous integrated boost, radiosurgery for multiple lesions), and present the innovative and promising findings regarding the combination of novel targeted agents such as tyrosine kinase inhibitors and immune checkpoint inhibitors with brain irradiation.

Volumetric burden of metastatic lesions drives outcomes in patients with extracranial oligometastatic disease.

BACKGROUND: We hypothesized that the total volume of metastases at initial oligometastatic (OM) presentation to stereotactic body radiation therapy (SBRT) is an important prognostic factor that can refine the definition of OM disease. METHODS: Patients with extracranial oligometastatic cancer (≤5 lesions) treated with SBRT were included in an international multi-institutional database. Multivariable Cox and competing risks regression models were used to determine the relationship between distant progression-free survival (DPFS), widespread progression (WSP), and overall survival (OS) with the total planning target volume (PTV) at initial OM presentation to SBRT. All models were adjusted for histology, pre-SBRT systemic therapy, osseous-only lesions, and number of metastases. RESULTS: In total, 961 patients were included. The median follow-up was 24.4 months (IQR: 13.8-37.5). Total PTV had a significant effect on DPFS in the first 18 months after SBRT and was most profound in the first 6 months, when each twofold increase in total PTV conferred a 40.6% increased risk of distant progression (p < 0.001). Each twofold increase in total PTV increased the risk of WSP by 45.4% in the first 6 months (p < 0.001). Total PTV had a significant effect on OS in the first 2 years after SBRT, with each twofold PTV change increasing the risk of death by 60.7% during the first 6 months (p < 0.001) and by 34% thereafter (p < 0.001). Exploratory gross tumor volume (GTV) analysis confirmed the PTV-based observations. CONCLUSION: The total volumetric burden of metastases at initial OM presentation to SBRT is strongly and independently prognostic for the risk of distant and widespread progression and survival. We propose that this metric should drive the definition of OM disease and guide treatment decision-making.

An international pooled analysis of SBRT outcomes to oligometastatic spine and non-spine bone metastases.

PURPOSE: There is a paucity of data on SBRT to non-spine bone (NSB) lesions compared to spine metastases. We report local recurrence (LR), widespread progression (WSP), and overall survival (OS) for oligometastatic patients treated to bone lesions with SBRT and investigate the hypothesis that outcomes are different between patients with spine and non-spine bone oligometastatic disease. METHODS: Patients with oligometastatic disease (≤5 cumulative extracranial metastases) treated with bone SBRT at 6 international institutions from 2007 to 2016 were reviewed. Fine and Gray competing risks and Cox regressions were used to analyze univariable and multivariable relationships between disease/treatment factors and outcomes. RESULTS: In total, 288 spine and 233 NSB lesions are reported in 356 patients. Cumulative incidence of LR across all bone lesions was 6.3%, 12.6% and 19.3% at 6 mo, 1 yr and 2 yrs. While univariable analysis suggested inferior LC and OS in spine patients, this did not hold true in multivariable analysis. The final regression model for LR in NSB lesions included PTV ≥ median of 31.8 cc (HR 5.02, p = 0.014) and primary histology, with RCC and NSCLC conferring a 10.8- and 6.5-fold increased risk of LR compared to prostate histology, respectively. The spine LR model included radioresistant histology (HR 2.11, p = 0.0051), PTV Dmin (BED10) ≥ median of 19.1 Gy (HR 0.46, p = 0.0085), and epidural disease (HR 1.99, p = 0.016). CONCLUSION: This large multi-institutional series reports comparably excellent response to SBRT for a balanced distribution of oligometastatic NSB and spine lesions. Dose escalation for large and/or radioresistant NSB lesions should be explored, given the typical lack of an immediately adjacent dose-limiting critical structure.

Late metastatic presentation is associated with improved survival and delayed wide-spread progression after ablative stereotactic body radiotherapy for oligometastasis.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is increasingly used to treat oligometastatic disease (OMD), but the effect of metastasis timing on patient outcomes remains uncertain. METHODS: An international database of patients with OMD treated with SBRT was assembled with rigorous quality assurance. Early versus late metastases were defined as those diagnosed ≤24 versus >24 months from the primary tumor. Overall survival (OS), progression-free survival (PFS), and incidences of wide-spread progression (WSP) were estimated using multivariable Cox proportional hazard models stratified by primary tumor types. RESULTS: The database consists of 1033 patients with median follow-up of 24.1 months (0.3-104.7). Late metastatic presentation (N = 427) was associated with improved OS compared to early metastasis (median survival 53.6 vs. 33.0 months, hazard ratio [HR] 0.59, 95% confidence interval [CI]: 0.47-0.72, p < 0.0001). Patients with non-small cell lung cancer (NSCLC, N = 255, HR 0.49, 95% CI: 0.33-0.74, p = 0.0005) and colorectal cancer (N = 235, HR 0.50, 95% CI: 0.30-0.84, p = 0.008) had better OS if presenting with late metastasis. Late metastasis correlated with longer PFS (median 17.1 vs. 9.0 months, HR 0.71, 95% CI: 0.61-0.83, p < 0.0001) and lower 2-year incidence of WSP (26.1% vs. 43.6%, HR 0.60, 95% CI: 0.49-0.74, p < 0.0001). Fewer WSP were observed in patients with NSCLC (HR 0.52, 95% CI: 0.33-0.83, p = 0.006) and kidney cancer (N = 63, HR 0.37, 95% CI: 0.14-0.97, p = 0.044) with late metastases. Across cancer types, greater SBRT target size was a significant predictor for worse OS. CONCLUSION: Late metastatic presentation is associated with improved survival and delayed progression in patients with OMD treated with SBRT.

Safety of lung stereotactic ablative radiotherapy for the functioning of cardiac implantable electronic devices.

BACKGROUND AND PURPOSE: The prevalence of patients with a cardiac implantable device (CIED) developing cancer and requiring a course of radiotherapy (RT) is increasing remarkably. Previously published reports agree that standard and conventionally fractionated RT is usually safe for CIEDs, but no "in-vivo" reports are available on the potential effects of thoracic stereotactic ablative radiotherapy (SABR) regimens to CIEDs functioning. The purpose of our study is therefore to evaluate the effects of SABR on CIEDs (pacemakers [PM] or implantable cardiac defibrillators [ICD]) in a cohort of patients affected by primary or metastatic lung lesions. MATERIALS AND METHODS: We retrospectively collected all CIED-bearing patients undergoing SABR between 2007 and 2019 at our Institution. All CIEDs were interrogated before and after the SABR course to check for any malfunction. Prescription dose, beam energy and maximum dose (Dmax) to CIEDs were retrieved for each patient. Electrical records of the CIEDs were reviewed by the medical records. RESULTS: Thirty-four consecutive patients (24 with a PM and 10 with an ICD), who underwent 38 separate SABR courses, were included in the study. Eight patients (24%) were PM-dependent. Prescription dose of SABR ranged 26-60 Gy in 1-8 fractions, with a photon energy ranging 6-to-10 MV (76.3% and 23.7%, respectively) and a median Dmax to CIEDs of 0.17 Gy (range 0.04-1.97 Gy). Electrical parameters were stable in post-treatment device programming visits and no transient or persistent alteration of the CIED function was recorded in any patient. No inappropriate interventions were recorded in the 10 ICD-bearing patients during the treatment fractions. CONCLUSIONS: Thoracic SABR proved to be safe for CIEDs when the dose is kept <2 Gy and the beam energy is ≤10 MV, irrespective of the pacing-dependency and of the CIED type.

Evaluation of Definitive Stereotactic Body Radiotherapy and Outcomes in Adults With Extracranial Oligometastasis.

Importance: The outcomes and factors that influence survival in patients with oligometastasis (OM) are not well understood and have not been well described in large-scale studies. Objective: To evaluate overall progression-free survival (PFS), widespread progression (WSP) outcomes, and survival factors from a pooled data set of 1033 patients with OM treated with stereotactic body radiotherapy (SBRT). Design, Setting, and Participants: Case series from January 1, 2008, to December 31, 2016. The dates of analysis were April 2019 to May 2020. The setting was multi-institutional tertiary care hospitals. Participants were consecutive patients with 5 or fewer extracranial OMs whose primary tumor was treated curatively. Exposure: Definitive SBRT. Main Outcomes and Measures: Overall survival (OS), progression-free survival, rate of WSP, patterns of failure, and factors altering OS. Results: In the largest international OM case series to date (1033 participants) (mean age, 68.0 years [range, 18.0-94.3 years]; 601 [58.2%] men), 1416 SBRT courses were delivered to patients with 1 OM (596 [57.7%]), 2 OMs (245 [23.7%]), 3 OMs (105 [10.2%]), 4 OMs (55 [5.3%]), and 5 OMs (32 [3.1%]). The median follow-up was 24.1 months (range, 0.3-104.7 months), and the median OS was 44.2 months (95% CI, 39.2-48.8 months). The median PFS was 12.9 months (95% CI, 11.6-14.2 months), and the median time to WSP was 42.5 months (95% CI, 36.8-53.5 months). The OS rates were 84.1% (95% CI, 81.7%-86.2%) at 1 year, 56.7% (95% CI, 53.0%-60.2%) at 3 years, and 35.2% (95% CI, 30.1%-40.3%) at 5 years. The 3-year OS, PFS, and WSP rates were 56.7% (95% CI, 53.0%-60.2%), 23.0% (95% CI, 20.2%-25.9%), and 45.2% (95% CI, 41.4%-48.9%), respectively. The 5-year OS, PFS, and WSP rates were 35.2% (95% CI, 30.1%-40.3%), 14.8% (95% CI, 11.9%-17.9%), and 54.5% (95% CI, 49.8%-59.2%), respectively. At the time of first progression, 342 patients (33.1%) had recurrence of OM disease, and 230 patients (22.3%) underwent subsequent ablative therapies to all known metastatic sites. Multivariable analyses identified primary tumor type (hazard ratio [HR], 3.73; 95% CI, 1.75-7.94; P < .001 for breast; 5.75; 95% CI, 2.88-11.46; P < .001 for colorectal; 4.67; 95% CI, 2.12-10.31; P < .001 for kidney; 10.61; 95% CI, 5.36-20.99; P < .001 for lung; and 12.00; 95% CI, 6.06-23.76; P < .001 for other [with prostate being the reference group]), metachronous OM presentation more than 24 months since initial diagnosis (HR, 0.63; 95% CI, 0.49-0.80; P < .001), metastases confined to the lung only (HR, 0.58; 95% CI, 0.48-0.72; P < .001), and nodal or soft-tissue metastases only (HR, 0.49; 95% CI, 0.26-0.90; P = .02) as survival factors. Sixty-six (6.4%) grade 3 or higher toxic effects were observed, including 1 (0.1%) grade 5 event. Conclusions and Relevance: This study found favorable long-term OS and WSP rates associated with extracranial OM ablated with SBRT; however, modest PFS rates were observed. A substantial proportion of patients with OM developed progressive disease and were treated with local ablation. Factors that can inform clinical decision-making and clinical trial design include primary tumor type, a metachronous presentation more than 24 months since diagnosis, and the site of OM presentation.

Separation surgery for metastatic epidural spinal cord compression: A qualitative review.

INTRODUCTION: The new concept of separation surgery has changed the surgical paradigms for the treatment of metastatic epidural spinal cord compression (MESCC), shifting from aggressive cytoreductive surgery towards less invasive surgery with the aim to achieve circumferential separation of the spinal cord and create a safe target for high dose Stereotactic Body Radiation Therapy (SBRT), which turned out to be the real game-changer for disease's local control. DISCUSSION: In this review a qualitative analysis of the English literature has been performed according to the rating of evidence, with the aim to underline the increasingly role of the concept of separation surgery in MESCC treatment. A review of the main steps in the evolution of both radiotherapy and surgery fields have been described, highlighting the important results deriving from their integration. CONCLUSION: Compared with more aggressive surgical approaches, the concept of separation surgery together with the advancements of radiotherapy and the use of SBRT for the treatment of MESCC showed promising results in order to achieve a valuable local control while reducing surgical related morbidities and complications.

Multimodal Treatment of Advanced Mucosal Melanoma in the Era of Modern Immunotherapy.

Mucosal melanoma is a rare disease epidemiologically and molecularly distinct from cutaneous melanoma developing from melanocytes located in mucosal membranes. Little is known about its therapy. In this paper, we aimed to evaluate the results of immunotherapy and radiotherapy in a group of patients with advanced mucosal melanoma, based on the experience of five high-volume centers in Poland and Italy. There were 82 patients (53 female, 29 male) included in this retrospective study. The median age in this group was 67.5 (IQR: 57.25-75.75). All patients received anti-PD1 or anti-CTLA4 antibodies in the first or second line of treatment. Twenty-three patients received radiotherapy during anti-PD1 treatment. In the first-line treatment, the median progression-free survival (PFS) reached six months in the anti-PD1 group, which was statistically better than 3.1 months in the other modalities group (p = 0.004). The median overall survival (OS) was 16.3 months (CI: 12.1-22.3) in the whole cohort. Patients who received radiotherapy (RT) during the anti-PD1 treatment had a median PFS of 8.9 months (CI: 7.4-NA), whereas patients treated with single-modality anti-PD1 therapy had a median PFS of 4.2 months (CI: 3.0-7.8); this difference was statistically significant (p = 0.047). Anti-PD1 antibodies are an effective treatment option in advanced mucosal melanoma (MM). The addition of RT may have been beneficial in the selected subgroup of mucosal melanoma patients.

What is the role of reirradiation in the management of locoregionally relapsed non small-cell lung cancer?

The prognosis of lung cancer patients has improved in the last few years. Despite definitive therapy, local recurrence or a second primary tumour can occur in many patients within previously irradiated areas. Recent developement of more accurate techniques in radiation oncology allows delivery of high radiation dose to the tumor with the aim of improving local control, delaying disease progression and in some cases even curing. Nevertheless, the use of high dose in the reirradiation setting is not without risks, especially when treatment volumes overlap with previously irradiated tissues. The risk of adverse effects must be balanced with the choice of an effective treatment by selecting suitable candidates and the best radiation technique. In this systemic review efficacy and toxicity of reirradiation in locoregionally recurrent non-small-cell lung cancer is extensively discussed. Results indicate that reirradiation might be beneficial in well-selected patients. Prospective and high quality studies are necessary in this field.