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Background: Soft tissue sarcomas (STS) are a group of rare, heterogeneous tumors. Scarce terapeuthic options are currently available, given the limited efficacy of systemic chemotherapy. Patients with low-burden metastatic disease may benefit from adjunction of local ablative treatments. However, because of the presumed radioresistance of STS, stereotactic body radiotherapy (SBRT) has not been steadily considered as a viable treatment option. Methods: We retrospectively reviewed STS patients treated with SBRT in a single institution,, for oligometastatic and oligoprogressive metastatic disease. Local control (LC), disease-free survival (DFS), and overall survival (OS) were assessed. We also reported the incidence of early and late adverse events and their grade according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0. Univariate and multivariate statistical analysis were carried out to investigate variables correlated with outcome and toxicity. Results: Forty patients were treated between 2012 and 2019 to 77 metastases with SBRT to a median biologic effective dose (BED5, assuming an α/β=5) of 105 Gy (range 66 to 305 Gy). 63% of patients had received 2 or more chemotherapy lines at the time of SBRT. LC, DFS and OS at two years were 67%, 23% and 40% respectively. At multivariate analysis, LC only significantly improved in patients receving a BED5>150 Gy (hazard ratio [HR] 3.9. 95% confidence interval [CI], 1.6-9.7; p=0.028), while an interval>24 months between primary tumor diagnosis and metastatic disease relapse was correlated with improved DFS and OS (HR, 0.46; 95% CI, 0.22-0.96; P = 0.01 and HR, 0.48; 95% CI, 0.23- 0.99; P = 0.03, respectively). Early toxicity was observed in 4 patients, late toxicity in 1 patient. No toxicity grade>2 was observed. Conclusions: SBRT is an effective therapeutic option in metastatic STS. A BED5>150 Gy5 is required to obtain better tumor control rates. Metastatic relapse>24 months after diagnosis is correlated with improved overall survival. Adverse events are scarce and mostly transient, meaning SBRT is safe and could be an option even in heavily pretreated patients. [ABSTRACT FROM AUTHOR]

Purpose or objective: Stereotactic Body Radiotherapy (SBRT) is widely used for treatment of uncomplicated spine metastases to palliate symptoms and prolong disease control. However, criteria for patient selection are not available. The aim of this study is to identify determinants of local failure and progression-free interval in patients treated with SBRT to spinal metastases. Materials and methods: Data from consecutive patients treated with Cyberknife-based spine SBRT between January 2019 and March 2020 were retrospectively collected. Dose was expressed as Biological Effective Dose for α/β=10 (BED10). Kaplan-Meyer method was used to calculate Local Control (LC) and Disease Free Survival (DFS) from date of SBRT to event. Univariate (UVA) and Multivariate analysis (MVA) were performed using log-rank and Cox model, respectively. Results: Sixty-two patients accounting for 70 spinal metastases were included. Median age was 66 (range 32- 87) years. Disease was metastatic at diagnosis in 21 patients (34%) : an active primary tumor was present in 17 patients (27%). Among treated sites, most represented primary malignancies were prostate (n=28, 40%) and breast (n=21, 30%). Dose regimens consisted of 25-30 Gy in 5 fractions and 21-30 Gy in 3 fractions in respectively 61 (87%) and 9 (13%) cases, resulting in a median BED of 43.2 (range 37.5-60) Gy10. Concurrent chemotherapy (including cytotoxic or targeted agents) was administered in 43% of cases (n=30). After a median follow up of 10 months (range 1-24 months), 9 local relapses and 40 distant progressions were observed. One year LC was 87% (Fig.1): nonprostate primary tumor (p=0.003, Fig.2) and concurrent chemotherapy (p=0.006, Fig.3) were associated to poorer LC at UVA, and an independent correlation was confirmed at MVA (respectively p=0.017 and p=0.024). One-year DFS was 43% (Fig.4). UVA showed a correlation between impaired DFS and active primary tumor (p=0.003), metastatic dissemination at diagnosis (p=0.02) and nonprostate primary tumor (p=0.009), although only an active primary tumor site was independently associated to DFS at MVA (p=0.007, Fig.5). Only G2 acute pain or nausea were observed. No late toxicity, in particular vertebral fracture, was reported. Conclusion: Spine SBRT results in high LC rates and durable progression-free survival with low incidence of mild toxicity. Clinical nomograms based on patient-related characteristics may help to select candidates for this approach. [ABSTRACT FROM AUTHOR]

Aims: Brain metastases (BMs) represent a significant medical concern in cancer patients. A valuable treatment option in selected patients with BMs is radiosurgery (RS), in particular using dedicated platforms such as the GammaKnife (GK). However, the impact on treatment response of different technical solutions, in particular use of multiple or single isocenters (shots), has not been established. The aim of our study is to evaluate differences in dosimetric parameters and clinical outcome among patients receiving multiple or single shot GammaKnife radiosurgery (GKRS) for BMs measuring less than 1 cm. Methods: Demographic, disease- and treatment-related features of 86 consecutive patients treated with the Leksell Gamma Knife® Perfexion™ for a total of 282 BMs were retrospectively collected. Each lesion was irradiated using one or two shots with a diameter of 4 and/or 8 mm. Selectivity Coverage and Gradient Index (GI) were examined for each lesion. Radiological response to RS treatment was observed according to RANO (Response Assessment in Neuro Oncology) criteria with MRI at 1, 3, 6 and 9 months. Results: Mean volume of metastases was 103.1 mm3 (2.4-721 mm3). Among treated BMs, 210 (74%) and 72 (25%) BMs were treated with one or two shots, respectively. Mean coverage of the plans executed with one shot was 99.9% (range: 92-100%) while it was 99.7% (range: 95-100%) using two shots. Mean selectivity and mean gradient were respectively 0,25 (range: 0.001-0.63) and 3.2 (range: 0.85-8.10) in single shot plans, and 0.35 (range: 0.07-0.78) and 3.2 (range: 2.11-9.8) in two shots plans. A statistically significant improvement in coverage was found in one shot plans (0.9995 vs 0.9968, p=0.0001), while selectivity was significantly better using two shots (0.2494 vs 0.3546, p=0.0001). Considering patient and disease-related characteristics, breast histology correlated with a poorer local control (p=0.0001) at 3 and 6months MRI, while a GPA (Graded Prognostic Assessment) < 3 was predictive of local failure (p=0.018) at 9months MRI. Concerning local control, overall local control rate at 1 month was 96%: patients treated with one shot had an improved local control at 1 (1.0% vs 11.6% p=0.0001) and 6months (5.9% vs 20.7%, p=0.026) as to two shots. Conclusion: Our study suggested that, in BMs with a diameter inferior to 1 cm receiving GKRS, the use of a single shot resulted in a better coverage and a better local control at one and three months. However, GPA score and histology affect clinical outcome of patients with BMs. [ABSTRACT FROM AUTHOR]

Background: Brain metastasis (BM) occur in approximately 15% of patients affected by advanced breast cancer (BC). In the last two decades, overall prognosis of metastatic BC patients has improved with the introduction of new target therapies. Integration of systemic therapy of local ablative therapy may represent an effective, non-invasive approach to control intracranial metastasis, in particular in oligometastatic patients. This report analyzes clinical outcome of BM from BC treated with GammaKnifeRadiosurgery (GKRS). Materials and methods: Data of 58 consecutive BC patientstreated with GKRS from November 2012 to August 2020, accounting for 149 metastases, were retrospectively examined. We assessed the correlation between clinical-pathological factors and outcome. Overall survival (OS), local control (LC) and distant brain control (DBC) were calculated from the date of GKRS using the Kaplan-Meier method. Results: Medianage was 56 years (range: 31-80). RPA class was 1 in 28 out of 57 patients. Estrogen receptor positive, HER-2 positive and triple negative BC was found in 42%, 44% and 16% of patients. In 19 (34%) patients the brain was the only metastatic site. At the time of GKRS all patients had controlled extracranial disease. Ten patients (17%) had an history of surgical BM excission and 5 (9%) patients had a prior WBRT. Mean number of brain metastasis treated with GKRS was 2 (range:1-11). Mean prescription dose was 21 Gy (15-24): 9 patients underwent a second radiosurgery course. At the time of BM diagnosis 41 (72%) patients received GKRS and continuation of the same chemotherapy schedule. Fifteen radiological radio necrosis were reported: however, 3 patients had symptomatic radionecrosis, two treated with steroids and one with surgery. Local control was 95%, 92% and 86% at 6, 12 and 24 months, respectively. Median distant brain control after GKRS was 47months (95%CI:20-60 months), DBC was 85%, 72% and 63% at 6, 12 and 24months, respectively. Median overall survival was 24months (95% CI:15-45 months). Overall survival was 85% at 6months, 68% and 48% at 1 and 2 years. Patients with RPA class I had improved survival (median 45 versus 18 months, p=0.036, HR 2 C95% 1.1-3.9). Conclusions: Our study showed that GKRS is associated with high local control rates and rare severe side effects. Use of GKRS for progressive BMs allowed for continuation of the same chemotherapy line in the majority of patients. This may be of particular in RPA I patients that show longer survival and may draw the higher benefit from GKRS. [ABSTRACT FROM AUTHOR]

Introduction: Only 30% of patients with liver metastases (LM) may be suitable for surgery due to unfavourable location, comorbidities or extrahepatic disease burden. Patients treated with stereotactic radiotherapy (SBRT) reported excellent local control (LC) and low toxicity rate although data on global disease control are missing. The aim of this preliminary analysis was to assess patterns of failure in a cohort of patients treated with SBRT for LM. Method: Data from patients treated between 2018 and 2020 at our Institution with SBRT to LM receiving at least an EQD2 of 50 Gy (α/β=10) as per ESTRO consensus were collected. Failure patterns following SBRT and rates of local control (LC), intrahepatic relapse (excluding treated site, IHR), extrahepatic relapse (EHR), and overall survival (OS) were evaluated. Results: Forty-three patients received liver SBRT due to oligometastatic (20,46%) and oligoprogressive (23,54%) disease. Most common primary tumors were breast (n=18,42%) and colon (n=10,23%) cancer. SBRT was performed using Cyberknife real-time tumor tracking(n=30,70%) or abdominal compression-assisted VMAT (n=13,30%) delivering 35-60 Gy in 3-5 fractions, corresponding to median EQD2 of 94 (50-150) Gy. Twelve (28%) patients were chemotherapy-naïve, while the remaining patients received 1(20,46%), 2(5,12%) or ≥3(6,14%) chemotherapy lines. Median follow-up was 12 months. Patterns of failure are reported in Table 1. One-year LC, IHR, EHR and OS were 80%,51%,49% and 87% respectively. At multivariate analysis LC was significantly correlated with EQD2≥94Gy(p=0.009) and ≥3 chemotherapy lines(p=0.04). IHR and EHR were significantly associated with local failure (p=0.0013) and intrahepatic progression (p=0.03), respectively. A significant correlation between OS and local relapse was shown (p=0.026). Conclusion: In our experience, improved LC using high BED in non-heavily pretreated patients was correlated to reduced risk of IHR and to improved OS. IHR was the dominant mode of failure in patients treated with SBRT for LM,and was correlated to further progression at extrahepatic sites. Our findings suggest that IHR may result from uncontrolled macroscopic LM rather than ubiquitous micrometastatic dissemination, and preceed further systemic spread at distant sites. Our findings support the use of SBRT as an efficient tool to block stepwise metastatic spread from uncontrolled isolated LM to liver, and from liver to distant site, thus extending global disease control. [ABSTRACT FROM AUTHOR]

Major advances in the knowledge of cancer biology and its interactions with tumor immune environment led to the emergence, in the last five years of new immunotherapy-based treatment strategies in cancer patients. At the same time, improvement in radiation technique and progress in radiobiology allowed in the last decade to expand the applications of radiotherapy in a growing number of settings. At present, there are strong theoretical basis to propose immune-enhanced radiation therapy that may represent in the future a new paradigm of treatment, combining the intrinsic power of radiotherapy to elicit a specific, systemic, tumor-directed immune response with modern highly conformal and precise dose delivery, in order to maximize response at the major site of disease and obtain durable disease control. The aim of this review is to describe the principal mechanisms of immune modulation of response to radiation and investigational strategies to harness the potential of radiation-inducible immune response: radiation therapy is expected to be not just a local treatment but the cornerstone of a multimodal strategy that might achieve long-lasting tumor remission at the primary site and systemic efficacy metastatic lesions. [ABSTRACT FROM AUTHOR]

• SBRT is commonly used for the treatment of oligometastatic disease. • Few large prospective data are available regarding SBRT-realted toxicity. • The present is a toxicity analysis of OligoCare cohort on the first 1′600 patients. • Results documented only limited grade 3 or higher toxic events in eight cases. • Treatment-related deaths were limited to two cases. To evaluate acute toxicity at 6 months after stereotactic body radiotherapy (SBRT) in patients with oligometastatic cancer within the OligoCare cohort. OligoCare is a prospective, registry-based, single-arm, observational study that aims to report prospective real-world data of patients with oligometastases from solid cancer treated with SBRT (NCT03818503). Primary tumor included non-small cell lung cancer (NSCLC), breast cancer (BC), colorectal cancer (CRC), and prostate cancer (PC). This analysis addresses a secondary endpoint of the trial, acute toxicity within 6 months after SBRT. Out of 1,597registered patients, 1′468 patients were evaluated for acute toxicity. Globally, 290 (20 %) had NSCLC primary disease, 227 (16 %) had BC, 293 (20 %) had CRC, and 658 (45 %) had PC. Concomitant systemic treatment was administered in 527 (35.9 %) patients. According to the EORTC/ESTRO oligometastatic disease (OMD) classification, 828 (56 %) patients had de novo OMD, 464 (32 %) repeat OMD, and 176 (12 %) induced OMD. Acute grade ≥ 3 SBRT related adverse events were reported in 8 (0.5 %) patients, including 2 (0.1 %) fatal AEs. In particular, 6 (0.4 %) grade 3 events were: 1 empyema, 1 pneumonia, 1 radiation pneumonitis, 1 radiation skin injury, 1 decreased appetite, and 1 bone pain. Among those 2 occurred in NSCLC patients, 2 in BC patients, and 1 in CRC and PC patients each. The two (0.1 %) grade 5 toxicity were represented by: pneumonitis and cerebral hemorrhage. OligoCare is the largest prospective registry cohort on oligometastatic disease. Acute toxicity within 6 months was low, confirming the safety of SBRT in the treatment of oligometastases. [ABSTRACT FROM AUTHOR]

Purpose: Authors retrospectively analyzed possible prognostic factors in a series of patients affected by Ewing sarcoma of extremities (eEWS) and treated over a 20-year period at a single institution. Methods: Between 1997 and 2017, 88 bone eEWS were treated at our institution. Staging, age, gender, tumoral volume, local treatment, surgical margins, post-ChT necrosis were investigated for prognostic correlation with overall survival (OS) and event-free survival (EFS). Median follow-up was 74 months (1–236). Results: Staging of disease correlated with OS (81% vs 59%, p = 0.01) and not with EFS (68% vs 57%, p = 0.28) in localized vs metastatic eEWS at presentation. Age ≥ 14 years (p = 0.002) and volume ≥ 100 cm3 (p = 0.04) were significant negative prognostic factors. No difference was found in local treatment: OS was 76% vs 63% (p = 0.33), while EFS was 68% vs 49% (p = 0.06) after surgery alone or surgery + radiotherapy, respectively. Regarding surgical margins, OS was 76% vs 38% (p = 0.14), and EFS was 65% vs 33% (p = 0.14) in adequate vs not adequate, respectively. OS was 86% and 68% in good and poor responders, respectively (p = 0.13). Conclusion: In eEWS, metastatic disease at presentation, age > 14 years and tumoral volume > 100 cm3 are negative prognostic factors. Intensified adjuvant ChT can improve prognosis in poor responders and metastatic patients. [ABSTRACT FROM AUTHOR]

• Re-irradiation (re-RT) of intracranial recurrent meningiomas is still matter of debate and limited by radiation tolerance of the surrounding tissue and the increased risk of side effects. • Re-RT is increasingly considered in current clinical practice, but its efficacy and safety for brain tumors are still under investigation. The optimal choice of patient selection, RT modalities and dose for re-irradiation are not well established yet. • This retrospective analysis aims at providing data about clinical outcomes, toxicities and prognostic factors in a cohort of 181 intracranial recurrent meningioma patients treated in 8 different Italian centers with different RT modalities. Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities. A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/β = 2 for brain tissue and α/β = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan–Meier curves and Cox regression models were used for analysis. Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20–89) and median Karnofsky Performance Status (KPS) was 90 (range 60–100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7–6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19–0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21–0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27–0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48–5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80–5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21–0.64, p < 0.001; HR 0.38, 95 % CI 0.20–0.72, p = 0.003 and HR 0.31 95 % CI 0.13–0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively). In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice. [ABSTRACT FROM AUTHOR]

Introduction: The femur is the most frequent involved site by post-attinic fractures. The appropriate treatment of pathological fractures after radiotherapy is still controversial as they are associated with a high risk of delayed consolidation and non-union. Authors review a single Center series of pathological fractures after radiation therapy in patients affected by soft tissue sarcomas analyzing incidence, risk factors, failure rate and proposing a flow chart of treatment of postattinic fractures of the femur.Methods: Authors selected 570 patients treated by limb salvage surgery associated to radiation therapy from 1992 to 2018. A pathological fracture during follow up was observed in 28 cases (5%). The mean time between the onset of the fracture after the prior surgery + radiotherapy was 70 months (range 3-182). The mean follow-up from the fracture was 86 months (range 9-222).Results: The fracture treatment was performed with an intramedullary nail in 15 cases. Eight femoral fractures healed uneventfully (57%) and 6 required further surgical procedures. A total of eight patients underwent prosthetic replacement, 3 as a primary treatment and 5 as a salvage procedure after failure of internal fixation. Five patients developed a deep infection (62.5%).We observed 10 non-union (53%) in 19 patients treated with osteosynthesis. Overall amputation rate of the entire series was 18%. Authors propose a flowchart of treatment for femoral fractures.Conclusion: Intramedullary nailing is the treatment of choice in postradiation diaphyseal fractures of long bones, prosthetic replacement in meta-epiphyseal fracture site. Free vascularized grafts remain a valid salvage solution after failure of internal fixation. [ABSTRACT FROM AUTHOR]

Purpose: Severe bio-radiation dermatitis may develop in patients treated with concurrent radiotherapy and cetuximab for head and neck squamous cell carcinoma. The aim of our work was to report on the impact of a grade-specific management approach on treatment tolerability.Methods: Concomitant radiotherapy and cetuximab was prescribed for patients deemed ineligible for cisplatin-based chemoradiation. Since 2014, an advanced wound care nursing team was established in our clinic to implement a standardized policy for skin toxicity. A central role of calcium alginate dressings was defined in our management algorithm. The correlation between patient, disease, and treatment features with severe bio-radiation dermatitis and treatment tolerability was evaluated.Results: Between 2007 and 2018, 51 patients were treated at our center with radiotherapy and cetuximab. The incidence of G3/G4 bio-radiation dermatitis was 43.1%. Comparing two consecutive cohorts of 26 and 25 patients treated before and after January 2014, respectively, the adoption of a grade-specific dermatitis management allowed to improve treatment tolerability. A mean radiation treatment interruption of 8.42 days (SD, 6.73; 95% CI 5.7-11.1) was reduced to 0.86 days (SD, 2.66; 95% CI - 0.28-2.02) in the more recent group (p < 0.0001). Mean relative dose intensity of cetuximab was also significantly higher (86.3% vs 74.5%, p = 0.0226).Conclusions: Routine involvement of an advanced wound care management team and early consideration for calcium alginate dressings in case of moist desquamation should be warranted to ensure high compliance to radiotherapy and cetuximab in patients with head and neck cancer. [ABSTRACT FROM AUTHOR]

The so-called non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) account a very heterogeneous group of tumors. The rarity of each histotype prevents the performance of clinical trials on a single tumor type, and consequently, they have to be analyzed as a group. As definitive evidences about treatment are lacking, the aim of the study is to evaluate the prognosis of NRSTS after a multidisciplinary approach, and to test clinical outcomes of surgical reconstructions. It is performed a retrospective analysis of 33 consecutive pediatric-age patients affected by NRSTS seen at a single institution over a 15-year period. Patients were treated using the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) protocol, where surgery plays the main role and chemo- and radiotherapy are variable associated on the basis of the subtype of tumor, yet leaving wide gaps. Thirty-nine percent of patients received only surgical treatment, 33% patients received chemotherapy associated to surgery, only 3% had radiotherapy and surgery and the residual 24% underwent both chemo- and radiotherapy associated to surgery. The overall survival of our series was 91% at 1 year, 86% at 5 years, 81% at 10 years. The local free recurrence survival was 93% at 1 year, 85% at 5 years and 10 years. The metastasis free survival was 78% at 1 year, 75% at 5 years and 10 years. Limb-salvage surgery was possible in the majority of cases (97%) and functional outcomes were generally good, with only a 15% of patients complaining functional deficit. The results are generally satisfactory and in line with the poor literature available; they underline the primary importance of surgery and a multidisciplinary approach. Moreover, reconstructive procedures and functional outcomes must not be left out because life expectancy in these patients is steadily increasing. [ABSTRACT FROM AUTHOR]

Highlights • Bevacizumab in combination with RT increase the rates of complications in elderly patients. • In elderly patients the combination of primary RT with cetuximab seems feasible but with higher reported skin toxicities. • Patients' age should not be limited the association of trastuzumab and RT. • The concurrent administration of EGFR targeting TKIs and RT appears to be feasible and effective. • The tolerance of Immune Check Point inhibitors and RT seems good. RT plus vismodegib/sonidegib remains investigational. Abstract Purpose Aim of the present review is to assess present data about the use of the association of Radiotherapy (RT) and targeted therapy/immunotherapy (TT/IT) in elderly people. Design PubMed database was searched for English literature published up to December 2017 using the keywords "radiotherapy" combined with "bevacizumab", "cetuximab", "trastuzumab", "erlotinib", "gefitinib", "sorafenib", "sunitinib", "vismodegib", "sonidegib", "ipilimumab", "pembrolizumab", "nivolumab". Studies performing RT and TT/IT in people aged >65-years were evaluated focusing on safety, toxicity and efficacy. Studies eligible for inclusion were: case reports, retrospective/prospective studies in which RT and new drugs were used concomitantly or sequentially, focusing on elderly sub-group. Results The systematic search identified 626 records. After exclusion of duplicates, full-text review, cross-referencing and paper that did not respect the inclusion criteria, 81 studies were included in this review. In elderly patients the combination of RT with cetuximab or bevacizumab seems feasible but with higher reported side effects. Patients' age should not limit the association of trastuzumab and RT in HER2 positive breast cancer. The concurrent administration of TKIs and RT appears to be feasible and effective. Regarding the Immune Check Point inhibitors and RT, tolerance seems similar among older and younger people but definitive data are lacking. Instead, the association of RT and vismodegib/sonidegib remains investigational. Conclusion TT/IT in association of RT seems to be safe, but in elderly patients data concerning safety and toxicity are limited. Specific clinical trials on this population are encouraged. [ABSTRACT FROM AUTHOR]

Background and Objectives: Liposarcoma (LPS) is a malignant mesenchymal tumor and the most common soft tissue sarcoma. Four different subtypes are described: well differentiated (WD) LPS or atypical lipomatous tumor (ALT), dedifferentiated (DD) LPS, myxoid LPS, and pleomorphic LPS (PLS). The objective of the study was to investigate prognostic factors and clinical outcome of liposarcoma.Methods: We retrospectively examined the clinico-pathological features of a series of 307 patients affected by Liposarcoma at a mean follow-up of 69 months (range 6-257). ALT/WD LPS were analyzed separately. The influence of site, size, type of presentation, grading, histotype and local recurrence on local and systemic control and survival was assessed.Results: The statistical analysis indicated that only surgical margins represented a significant prognostic factor for local recurrence in ALT/WD LPS (P = 0.0007) and other subtypes of LPS (P = 0.0055). In myxoid, PLS and DD LPS, significant prognostic factors for metastasis free survival (MFS) were surgical margins (P = 0.0009), size of the tumor (P = 0.0358), histology (P = 0.0117) and local recurrence (P = 0.0015). In multivariate analysis, surgical margins (0.0180), size (0.0432) and local recurrence (0.0288) correlated independently with MFS. Margins (P = 0.0315), local recurrence (P = 0.0482) and metastases (P < 0.0001) were prognostic factors for overall survival (OS).Conclusion: Marginal surgery can be an accepted treatment for ALT/WD LPS. In other liposarcoma subtypes (Myxoid, DD, PLS) wide or radical surgery is recommended as the margins significantly influence local recurrence-free survival (LRFS), metastasis-free survival (MFS) and overall survival (OS). Local recurrence and metastases were significant prognostic factors for OS. [ABSTRACT FROM AUTHOR]

The primary aim of this review is to provide practical recommendations in terms of fractionation, dose, constraints and selection criteria to be used in the daily clinical routine. Based on the analysis of the literature reviewed, in order to keep the risk of severe side effects ≤3,5%, patients should be stratified according to the target volume. Thus, patients should be treated with different fractionation and total EQD2 (<12.5 ml: EQD2 < 65 Gy with radiosurgery; >12.5 ml and <35 ml: EQD2 < 50 Gy with hypofractionated stereotactic radiotherapy; >35 ml and <50 ml: EQD2 < 36 Gy with conventionally fractionated radiotherapy). Concurrent approaches with temozolomide or bevacizumab do not seem to improve the outcomes of reirradiation and may lead to a higher risk of toxicity but these findings need to be confirmed in prospective series. [ABSTRACT FROM AUTHOR]

Purpose Radiotherapy plus cetuximab is an effective combination therapy for locally advanced head and neck squamous cell carcinoma. The aim of our study was to determine the frequency of skin toxicity in patients receiving the combined treatment. Results Forty-eight studies were included in our analysis, for a total of 2152 patients. The mean rates of G3/G4 radiation dermatitis and acneiform rash were 32.5% (SD: 20.4; 95% CI: 28.5–36.5) and 13.4% (SD: 11.5; 95% CI: 11.2–15.6), respectively. The majority of studies referred to CTCAE scales for reporting both side effects (85.7% and 92.1%, respectively). Data on the management of skin toxicity were available in only 35.4% of the reviewed literature. Conclusions severe radiation dermatitis is a frequent side effect induced by the combination of radiotherapy and cetuximab in head and neck cancer. The lack of predictive biomarkers of toxicity hampers the possibilty to design preventive measures on a personalized basis. [ABSTRACT FROM AUTHOR]

Objectives: The aim of our work was to report on the clinical outcome of a moderately hyprofractionated radiotherapy regimen in elderly patients affected by head and neck squamous cell carcinoma (HNSCC).Material and Methods: HNSCC aged ≥65 deemed unsuitable for curatively-intended concurrent chemo-radiotherapy or high-dose radiotherapy by clinical judgement were further evaluated with the Geriatric 8 (G8) questionnaire and Charlson comorbidity index (CCI). In case of a G8 score ≤14, a de-intensified radiation schedule of 40 Gy delivered in 16 fractions was prescribed.Results: Thirty-six patients were treated between 2011 and 2016. The median age of the cohort was 77.5 (range: 65-91 years) with a combined ECOG PS of 2-3 in 77.8% and CCI of ≥8 in 25% patients, respectively. At a median follow-up of 13 months (range 2-62 months), the 6-month and 1-year rates of loco-regional control and progression-free survival were 42%, 28% and 36% and 20%, respectively. At univariate analysis, log-rank test showed that age >75 years (p=0.036), worse PS (ECOG≥2; p=0.027), lower G8 score (<9; p=0.027) and PTV volume greater than 200 cc (p=0.038) had a significant correlation with PFS. The negative impact of the PTV volume on PFS was the only parameter confirmed in the multivariate analysis (HR 2.68; 95% CI: 1.24-5.81, p=0.013). No grade 4-5 toxicity was observed, while 13/36 patients (36%) had G3 acute side effects.Conclusion: The hypofractionated radiation schedule evaluated provides clinical benefit with low toxicity in frail, elderly patients affected by locally advanced HNSCC. [ABSTRACT FROM AUTHOR]

Background: Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR gamma agonist rosiglitazone is of interest in prevention and therapy of radiation-induced toxicities. We aimed to evaluate the radioprotective effect of rosiglitazone in a mouse model of radiation-induced oral mucositis.Material and Methods: Oral mucositis was obtained by irradiation of the oral region of C57BL/6J mice, pretreated or not with rosiglitazone. Mucositis was assessed by macroscopic scoring, histology and molecular analysis. Tumor xenograft was obtained by s.c. injection of Hep-2 cells in CD1 mice. Tumor volume was measured twice a week to evaluate effect of rosiglitazone alone and combined with radiotherapy.Results: Irradiated mice showed typical features of oral mucositis, such as oedema and reddening, reaching the peak of damage after 12-15days. Rosiglitazone markedly reduced visible signs of mucositis and significantly reduced the peak. Histological analysis showed the presence of an inflammatory cell infiltrate after irradiation; the association with rosiglitazone noticeably reduced infiltration. Rosiglitazone significantly inhibited radiation-induced tnfα, Il-6 and Il-1β gene expression. Rosiglitazone controlled the increase of TGF-β and NF-kB p65 subunit proteins induced by irradiation, and enhanced the expression of catalase. Irradiation and rosiglitazone significantly reduced tumor volume as compared to control. Rosiglitazone did not protect tumor from the therapeutic effect of radiation.Conclusion: Rosiglitazone exerted a protective action on normal tissues in radiation-induced mucositis. Moreover, it showed antineoplastic properties on head-neck carcinoma xenograft model and selective protection of normal tissues. Thus, PPAR gamma agonists should be further investigated as radioprotective agents in head and neck cancer. [ABSTRACT FROM AUTHOR]

Aim of this analysis is to review the role of RT in the management of several rare tumors for adult patients. Collection data regarding RT and rare tumors was made by Pubmed. For mucosal melanomas, RT is prescribed, being associated with lower local recurrence rate. For trachea tumors, RT was used as adjuvant or salvage treatment for unresectable disease. For pNET, RT can be a suitable option for post-surgical or unresectable/borderline. For bronchopulmonary neuroendocrine tumors the role of adjuvant treatments is uncertain. For hepatobiliary and ovarian malignancy, stereotactic body RT (SBRT) is a promising approach. For soft tissue sarcoma, perioperative treatments are indicated, and a growing role of SBRT in oligometastatic disease is recognized. For endocrine tumors, adjuvant RT has demonstrated benefits through reducing recurrence risk. The radiotherapy is a frequent indication in adult rare cancers; thus the role of Radiation Oncologist must not be neglected. [ABSTRACT FROM AUTHOR]

• Localised recurrent glioblastoma (recGBM) should be considered for local treatment. • An overview on the use of reirradiation or second surgery in recGBM is herein provided. • A simple and practical algorithm to choose surgery versus RT for recGBM is proposed. • Estimation of life expectancy, prognostic score systems and predictive factors, and expected toxicity are its keypoints. In case of circumscribed recurrent glioblastoma (rec-GBM), a second surgery (Re-S) and reirradiation (Re-RT) are local strategies to consider. The aim is to provide an algorithm to use in the daily clinical practice. The first step is to consider the life expectancy in order to establish whether the patient should be a candidate for active treatment. In case of a relatively good life expectancy (>3 months) and a confirmed circumscribed disease(i.e. without multiple lesions that are in different lobes/hemispheres), the next step is the assessment of the prognostic factors for local treatments. Based on the existing prognostic score systems, patients who should be excluded from local treatments may be identified; based on the validated prognostic factors, one or the other local treatment may be preferred. The last point is the estimation of expected toxicity, considering patient-related, tumor-related and treatment-related factors impacting on side effects. Lastly, patients with very good prognostic factors may be considered for receiving a combined treatment. [ABSTRACT FROM AUTHOR]

• Stereotactic radiosurgery (SRS) is an option in patients with brain metastases (BM). • No consensus on optimal salvage modality for local failure in BM after SRS. • Stereotactic reirradiation (SRS2) is an option despite concern for Radionecrosis (RN). • A systematic review was carried out to test efficacy and safety of SRS2. • Eleven studies were included. • Pooled 1-year Local Failure rate was 24 % and median Overall Survival was 14 months. • A pooled crude RN rate of 13 % was reported. • SRS2 is an effective option in patients with recurrent BM following prior SRS. Local failure (LF) following stereotactic radiosurgery (SRS) of brain metastases (BM) may be treated with a second course of SRS (SRS2), though this procedure may increase the risk of symptomatic radionecrosis (RN). A literature search was conducted according to PRISMA to identify studies reporting LF, overall survival (OS) and RN rates following SRS2. Meta-analysis was performed to identify predictors of RN. Analysis included 11 studies (335 patients,389 metastases). Pooled 1-year LF was 24 %(CI95 % 19–30 %): heterogeneity was acceptable (I2 = 21.4 %). Median pooled OS was 14 months (Confidence Interval 95 %, CI95 % 8.8–22.0 months). Cumulative crude RN rate was 13 % (95 %CI 8 %–19 %), with acceptable heterogeneity (I2 = 40.3 %). Subgroup analysis showed higher RN incidence in studies with median patient age ≥59 years (13 % [95 %CI 8 %–19 %] vs 7 %[95 %CI 3 %–12 %], p = 0.004) and lower incidence following prior Whole Brain Radiotherapy (WBRT, 19 %[95 %CI 13 %–25 %] vs 7%[95 %CI 3 %–13 %], p = 0.004). SRS2 is an effective strategy for in-site recurrence of BM previously treated with SRS. [ABSTRACT FROM AUTHOR]

Purpose: Multiple inflammatory and nutritional biomarkers have been established as independent prognostic factors across various solid tumors, but their role in outcomes prediction for glioma is still under investigation. Aim of the present systematic review is to report the available evidence regarding the impact of nutritional assessment and intervention for glioma prognosis and patients' quality of life (QoL)., Materials and Methods: Our systematic review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The PubMed and EMBASE databases were searched to identify studies assessing the impact of nutritional status and intervention and hematological biomarkers on survival outcomes and quality of life in patients with newly diagnosed gliomas. In the search strategy Medical Subject Headings (MeSH) terms were used. Search terms included ("nutritional status" or "nutritional assessment" or "nutritional intervention") AND ("glioma" or "glioblastoma" or "high-grade glioma" or "low-grade glioma" or "anaplastic astrocytoma" or "anaplastic oligodendroglioma") AND ("prognosis" or "survival outcomes"). The quality of each study was investigated based on the Newcastle-Ottawa Scale (NOS) criteria. Selected papers were in English and included publications in humans. This study was registered on PROSPERO (Registration No. CRD42024555442)., Results: Our search retrieved 20 papers published between 2015 and 2023, all aiming at investigating correlations between hematological biomarkers (albumin, prealbumin, fibrinogen) and/or nutritional tools (Controlling Nutritional Score, CONUT; Prognostic Nutritional Index, PNI) and survival outcomes and quality of life of glioma patients. Nutritional intervention as well was evaluated for outcomes prediction. Overall, most papers contributed to the evidence of how nutritional assessment and inflammatory biomarkers could play an independent prognostic role also in the management of glioma patients., Conclusions: PNI, CONUT score and hematological biomarkers (e.g. albumin, globulin, neutrophils, lymphocytes) may serve as useful predictors in patients with gliomas, potentially influencing clinical decisions. Additional large-scale studies are required to validate these findings and determine the mechanisms by which nutritional status, systemic inflammation and immune status affect prognosis in glioma patients., (Copyright © 2025. Published by Elsevier Ltd.)

Metastatic spread to the central nervous system (CNS) is frequent in anaplastic lymphoma kinase ( ALK )-rearranged non-small cell lung cancer (NSCLC) and has an important impact on patient prognosis and quality of life. Leptomeningeal involvement may occur in up to 10% of cases of ALK-positive NSCLC. Lorlatinib is a third-generation ALK inhibitor that has excellent CNS penetrability and demonstrated its efficacy both in pretreated and treatment-naive patients. Herein, we present the case of a 34-year-old patient diagnosed with stage IV ALK-rearranged NSCLC who received two lines of ALK inhibitors (crizotinib followed by alectinib) and several courses of brain stereotactic ablative radiotherapy until leptomeningeal involvement was detected. Third-line lorlatinib was then administered, and 2 months later encephalic MRI documented complete regression of the leptomeningeal involvement that is still maintained after 36 months while treatment with lorlatinib is still ongoing with good tolerability. To the best of our knowledge, this is the longer intracranial response reported in the literature, underlining the importance of the most appropriate choice of systemic treatments and their integration with loco-regional approaches to improve outcomes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Texture analysis extracts many quantitative image features, offering a valuable, cost-effective, and non-invasive approach for individual medicine. Furthermore, multimodal machine learning could have a large impact for precision medicine, as texture biomarkers can underlie tissue microstructure. This study aims to investigate imaging-based biomarkers of radio-induced neurotoxicity in pediatric patients with metastatic medulloblastoma, using radiomic and dosiomic analysis., Methods: This single-center study retrospectively enrolled children diagnosed with metastatic medulloblastoma (MB) and treated with hyperfractionated craniospinal irradiation (CSI). Histological confirmation of medulloblastoma and baseline follow-up magnetic resonance imaging (MRI) were mandatory. Treatment involved helical tomotherapy (HT) delivering a dose of 39 Gray (Gy) to brain and spinal axis and a posterior fossa boost up to 60 Gy. Clinical outcomes, such as local and distant brain control and neurotoxicity, were recorded. Radiomic and dosiomic features were extracted from tumor regions on T1, T2, FLAIR (fluid-attenuated inversion recovery) MRI-maps, and radiotherapy dose distribution. Different machine learning feature selection and reduction approaches were performed for supervised and unsupervised clustering., Results: Forty-eight metastatic medulloblastoma patients (29 males and 19 females) with a mean age of 12 ± 6 years were enrolled. For each patient, 332 features were extracted. Greater level of abstraction of input data by combining selection of most performing features and dimensionality reduction returns the best performance. The resulting one-component radiomic signature yielded an accuracy of 0.73 with sensitivity, specificity, and precision of 0.83, 0.64, and 0.68, respectively., Conclusions: Machine learning radiomic-dosiomic approach effectively stratified pediatric medulloblastoma patients who experienced radio-induced neurotoxicity. Strategy needs further validation in external dataset for its potential clinical use in ab initio management paradigms of medulloblastoma., (© 2024. The Author(s).)