Redetermination of PD-L1 expression after chemio-radiation in locally advanced PDL1 negative NSCLC patients: retrospective multicentric analysis.

Background: Chemoradiation therapy (CRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CRT on tumor cells programmed cell death ligand-1 (PD-L1) expression is unknown. Methods: In this multicentric retrospective study, we analyzed paired NSCLC specimens that had been obtained pre- and post-CRT. PD-L1 expression on tumor cells was studied by immunohistochemistry. The purpose of this study was to evaluate the feasibility, risk of complications, and clinical relevance of performing re-biopsy after CRT in patients with PD-L1 negative LA-NSCLC. Results: Overall, 31 patients from 6 centers with PD-L1 negative LA-NSCLC were analyzed. The percentage of tumor cells with PD-L1 expression significantly increased between pre- and post-CRT specimens in 14 patients (45%). Nine patients had unchanged PD-L1 expression after CRT, in five patients the rebiopsy material was insufficient for PD-L1 analysis and in two patients no tumor cells at rebiopsy were found. The post-rebiopsy complication rate was very low (6%). All patients with positive PD-L1 re-biopsy received Durvalumab maintenance after CRT, except one patient who had a long hospitalization for tuberculosis reactivation. Median PFS of patients with unchanged or increased PD-L1 expression was 10 and 16.9 months, respectively. Conclusion: CRT administration can induce PD-L1 expression in a considerable fraction of PD-L1 negative patients at baseline, allowing them receiving the maintenance Durvalumab in Europe. Hence, after a definitive CRT, PD-L1 redetermination should be considered in patients with LA-NSCLC PD-L1 negative, to have a better selection of maintenance Durvalumab candidates.

Refining critical structure contouring in STereotactic Arrhythmia Radioablation (STAR): Benchmark results and consensus guidelines from the STOPSTORM.eu consortium.

BACKGROUND AND PURPOSE: In patients with recurrent ventricular tachycardia (VT), STereotactic Arrhythmia Radioablation (STAR) shows promising results. The STOPSTORM.eu consortium was established to investigate and harmonise STAR treatment in Europe. The primary goals of this benchmark study were to standardise contouring of organs at risk (OAR) for STAR, including detailed substructures of the heart, and accredit each participating centre. MATERIALS AND METHODS: Centres within the STOPSTORM.eu consortium were asked to delineate 31 OAR in three STAR cases. Delineation was reviewed by the consortium expert panel and after a dedicated workshop feedback and accreditation was provided to all participants. Further quantitative analysis was performed by calculating DICE similarity coefficients (DSC), median distance to agreement (MDA), and 95th percentile distance to agreement (HD95). RESULTS: Twenty centres participated in this study. Based on DSC, MDA and HD95, the delineations of well-known OAR in radiotherapy were similar, such as lungs (median DSC = 0.96, median MDA = 0.1 mm and median HD95 = 1.1 mm) and aorta (median DSC = 0.90, median MDA = 0.1 mm and median HD95 = 1.5 mm). Some centres did not include the gastro-oesophageal junction, leading to differences in stomach and oesophagus delineations. For cardiac substructures, such as chambers (median DSC = 0.83, median MDA = 0.2 mm and median HD95 = 0.5 mm), valves (median DSC = 0.16, median MDA = 4.6 mm and median HD95 = 16.0 mm), coronary arteries (median DSC = 0.4, median MDA = 0.7 mm and median HD95 = 8.3 mm) and the sinoatrial and atrioventricular nodes (median DSC = 0.29, median MDA = 4.4 mm and median HD95 = 11.4 mm), deviations between centres occurred more frequently. After the dedicated workshop all centres were accredited and contouring consensus guidelines for STAR were established. CONCLUSION: This STOPSTORM multi-centre critical structure contouring benchmark study showed high agreement for standard radiotherapy OAR. However, for cardiac substructures larger disagreement in contouring occurred, which may have significant impact on STAR treatment planning and dosimetry evaluation. To standardize OAR contouring, consensus guidelines for critical structure contouring in STAR were established.

Good clinical practice and the use of hypofractionation radiation schedules as weapons to reduce the risk of COVID-19 infections in radiation oncology unit: A mono-institutional experience.

BACKGROUND: After coronavirus disease outbreak emerged in 2019, radiotherapy departments had to adapt quickly their health system and establish new organizations and priorities. The purpose of this work is to report our experience in dealing with COVID-19 emergency, how we have reorganized our clinical activity, changed our priorities, and stressed the use of hypofractionation in the treatment of oncological diseases. MATERIALS AND METHODS: The patients' circuit of first medical examinations and follow-up was reorganized; a more extensive use of hypofractionated schedules was applied; a daily triage of the patients and staff, use of personal protective equipment, hand washing, environment sanitization, social distancing and limitations for the patients' caregivers in the department, unless absolutely essential, were performed; patients with suspected or confirmed COVID-19 were treated at the end of the day. In addition, the total number of radiotherapy treatment courses, patients and sessions, in the period from February 15 to April 30, 2020, comparing the same time period in 2018 were retrospectively investigated. In particular, changes in hypofractionated schedules adopted for the treatment of breast and prostate cancer and palliative bone metastasis were analyzed. RESULTS: Between February 15, and April 30, 2020, an increased number of treatments was carried out: Patients treated were overall 299 compared to 284 of the same period of 2018. Stressing the use of hypofractionation, 2036 RT sessions were performed, with a mean number of fractions per course of 6.8, compared to 3566 and 12.6, respectively, in 2018. For breast cancer, the schedule in 18 fractions has been abandoned and treatment course of 13 fractions has been introduced; a 27% reduction in the use of 40.5 Gy in 15 fractions, (67 treatments in 2018-49 in 2020) was reported. An increase of 13% of stereotactic body radiation therapy for prostate cancer was showed. The use of the 20 Gy in 4 or 5 sessions for the treatment of symptomatic bone metastasis decreased of 17.5% in favor of 8 Gy-single fraction. Three patients results COVID-19 positive swab: 1 during, 2 after treatment. Only one staff member developed an asymptomatic infection. CONCLUSIONS: The careful application of triage, anti-contagion and protective measures, a more extensive use of hypofractionation allowed us to maintain an effective and continuous RT service with no delayed/deferred treatment as evidenced by the very low number of patients developing COVID-19 infection during or in the short period after radiotherapy. Our experience has shown how the reorganization of the ward priority, the identification of risk factors with the relative containment measures can guarantee the care of oncological patients, who are potentially at greater risk of contracting the infection.

Moderately Hypofractionated Helical Tomotherapy for Prostate Cancer: Ten-year Experience of a Mono-institutional Series of 415 Patients.

BACKGROUND/AIM: Radiotherapy represents an important therapeutic option in the management of prostate cancer (PCa). As helical tomotherapy may improve toxicity outcomes, we aimed to evaluate and report the toxicity and clinical outcomes of localized PCa patients treated with moderately hypofractionated helical tomotherapy. PATIENTS AND METHODS: We retrospectively analyzed 415 patients affected by localized PCa and treated with moderately hypofractionated helical tomotherapy in our department from January 2008 to December 2020. All patients were stratified according to the D'Amico risk classification: low-risk 21%, favorable intermediate-risk 16%, unfavorable intermediate-risk 30.4%, and high-risk 32.6%. The dose prescription for high-risk patients was 72.8 Gy to the prostate (planning tumor volume-PTV1), 61.6 Gy to the seminal vesicles (PTV2), and 50.4 Gy to the pelvic lymph nodes (PTV3) in 28 fractions; for low- and intermediate-risk patients 70 Gy for PTV1, 56 Gy for PTV2, and 50.4 Gy for PTV3 in 28 fractions. Image-guided radiation therapy was performed daily in all patients by mega-voltage computed tomography. Forty-one percent of patients received androgen deprivation therapy (ADT). Acute and late toxicity was assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v.5.0 (CTCAE). RESULTS: Median follow-up was 82.7 months (range=12-157 months) and the median age of patients at diagnosis was 72.5 years (range=49-84 years). The 3, 5, and 7 yr overall survival (OS) rates were 95%, 90%, and 84%, respectively, while 3, 5, and 7 yr disease-free survival (DFS) were 96%, 90%, and 87%, respectively. Acute toxicity was as follows: genitourinary (GU) G1 and G2 in 35.9% and 24%; gastrointestinal (GI) in 13.7% and 8%, with G3 or more acute toxicities less than 1%. The late GI toxicity G2 and G3 were 5.3% and 1%, respectively, and the late GU toxicity G2 and G3 were 4.8% and 2.1%, respectively, and only three patients had a G4 toxicity. CONCLUSION: Hypofractionated helical tomotherapy for PCa treatment appeared to be safe and reliable, with favorable acute and late toxicity rates and encouraging results in terms of disease control.

Efficacy and Tolerability of Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review.

(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of glutamatergic activity in the tumor microenvironment may favor epileptogenesis, but also tumor growth and invasiveness. The selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel (PER) was demonstrated to be efficacious and well-tolerated in patients with focal seizures. Moreover, preclinical in vitro studies suggested a potential anti-tumor activity of this drug. In this systematic review, the clinical evidence on the efficacy and tolerability of PER in brain tumor-related epilepsy (BTRE) is summarized. (2) Methods: Five databases and two clinical trial registries were searched from inception to December 2022. (3) Results: Seven studies and six clinical trials were included. Sample size ranged from 8 to 36 patients, who received add-on PER (mean dosage from 4 to 7 mg/day) for BTRE. After a 6-12 month follow-up, the responder rate (% of patients achieving seizure freedom or reduction ≥ 50% of seizure frequency) ranged from 75% to 95%, with a seizure freedom rate of up to 94%. Regarding tolerability, 11-52% of patients experienced non-severe adverse effects (most frequent: dizziness, vertigo, anxiety, irritability). The retention rate ranged from 56% to 83%. However, only up to 12.5% of patients discontinued the drug because of the adverse events. (4) Conclusions: PER seems to be efficacious, safe, and well-tolerated in patients with BTRE. Further randomized studies should be conducted in more homogeneous and larger populations, also evaluating the effect of PER on tumor progression, overall survival, and progression-free survival.

Clinical Effects of Immuno-Oncology Therapy on Glioblastoma Patients: A Systematic Review.

The most prevalent and deadly primary malignant glioma in adults is glioblastoma (GBM), which has a median survival time of about 15 months. Despite the standard of care for glioblastoma, which includes gross total resection, high-dose radiation, and temozolomide chemotherapy, this tumor is still one of the most aggressive and difficult to treat. So, it is critical to find more potent therapies that can help glioblastoma patients have better clinical outcomes. Additionally, the prognosis for recurring malignant gliomas is poor, necessitating the need for innovative therapeutics. Immunotherapy is a rather new treatment for glioblastoma and its effects are not well studied when it is combined with standard chemoradiation therapy. We conducted this study to evaluate different glioblastoma immunotherapy approaches in terms of feasibility, efficacy, and safety. We conducted a computer-assisted literature search of electronic databases for essays that are unique, involve either prospective or retrospective research, and are entirely written and published in English. We examined both observational data and randomized clinical trials. Eighteen studies met the criteria for inclusion. In conclusion, combining immunotherapy with radiochemotherapy and tumor removal is generally possible and safe, and rather effective in the prolongation of survival measures.

Linac-based stereotactic salvage reirradiation for intraprostatic prostate cancer recurrence: toxicity and outcomes.

BACKGROUND: The rates of local failure after curative radiotherapy for prostate cancer (PC) remain high despite more accurate locoregional treatments available, with one third of patients experiencing biochemical failure and clinical relapse occurring in 30-47% of cases. Today, androgen deprivation therapy (ADT) is the treatment of choice in this setting, but with not negligible toxicity and low effects on local disease. Therefore, the treatment of intraprostatic PC recurrence represents a challenge for radiation oncologists. Prostate reirradiation (Re-I) might be a therapeutic possibility. We present our series of patients treated with salvage stereotactic Re­I for intraprostatic recurrence of PC after radical radiotherapy, with the aim of evaluating feasibility and safety of linac-based prostate Re­I. MATERIALS AND METHODS: We retrospectively evaluated toxicities and outcomes of patients who underwent salvage reirradiation using volumetric modulated arc therapy (VMAT) for intraprostatic PC recurrence. Inclusion criteria were age ≥ 18 years, histologically proven diagnosis of PC, salvage Re­I for intraprostatic recurrence after primary radiotherapy for PC with curative intent, concurrent/adjuvant ADT with stereotactic body radiation therapy (SBRT) allowed, performance status ECOG 0-2, restaging choline/PSMA-PET/TC and prostate MRI after biochemical recurrence, and signed informed consent. RESULTS: From January 2019 to April 2022, 20 patients were recruited. Median follow-up was 26.7 months (range 7-50). After SBRT, no patients were lost at follow-up and all are still alive. One- and 2­year progression free survival (PFS) was 100% and 81.5%, respectively, while 2­year biochemical progression-free survival (bFFS) was 88.9%. Four patients (20%) experienced locoregional lymph node progression and were treated with a further course of SBRT. Prostate reirradiation allowed the ADT start to be postponed for 12-39 months. Re­I was well tolerated by all patients and none discontinued the treatment. No cases of ≥ G3 genitourinary (GU) or gastrointestinal (GI) toxicity were reported. Seven (35%) and 2 (10%) patients experienced acute G1 and G2 GU toxicity, respectively. Late GU toxicity was recorded in 10 (50%) patients, including 8 (40%) G1 and 2 (10%) G2. ADT-related side effects were found in 7 patients (hot flashes and asthenia). CONCLUSION: Linac-based SBRT is a safe technique for performing Re­I for intraprostatic recurrence after primary curative radiotherapy for PC. Future prospective, randomized studies are desirable to better understand the effectiveness of reirradiation and the still open questions in this field.

Thoracic Radiotherapy in Extensive Disease Small Cell Lung Cancer: Multicenter Prospective Observational TRENDS Study.

(1) Introduction: Small cell lung cancer (SCLC) is an aggressive tumor type, accounting for about 15% of all lung cancers. Radiotherapy (RT) plays a fundamental role in both early and advanced stages. Currently, in advanced disease, the use of consolidative chest RT should be recommended for patients with good response to platinum-based first-line chemotherapy, but its use has not yet been standardized. The present prospective study aims to evaluate the pattern of care of consolidative chest RT in patients with advanced stage SCLC, and its effectiveness in terms of disease control and tolerability. (2) Materials and methods: This study was a multicenter prospective observational trial, proposed and conducted within the AIRO lung study group to evaluate the pattern of care of consolidative chest RT after first-line chemotherapy in patients with advanced SCLC. The patient and tumor characteristics, doses, fractionation and volumes of thoracic RT and prophylactic cranial irradiation (PCI), as well as the thoracic and extrathoracic response to the treatment, toxicity and clinical outcomes, were collected and analyzed. (3) Results: From January 2017 to December 2019, sixty-four patients were enrolled. Median follow-up was 33 months. The median age was 68 years (range 42-81); 38 patients (59%) were male and 26 (41%) female. Carboplatin + etoposide for 6 cycles was the most commonly used first-line therapeutic scheme (42%). With regard to consolidative chest RT, 56% of patients (35) received 30 Gy in 10 factions and 16 patients (26%) received 45 Gy in 15 sessions. The modulated intensity technique was used in 84.5% of cases, and post-chemotherapy macroscopic residual disease was the target volume in 87.5% of patients. Forty-four patients (69%) also underwent PCI. At the last follow-up, over 60% of patients did not experience chest disease progression, while 67% showed extrathoracic progression. At the first radiological evaluation after RT, complete response and stable disease were recorded in 6% and 46% of the cases, respectively. Two patients had a long-term complete response to the combined treatment. The brain was the first site of extrathoracic progression in 28%. 1y and 2y OS and PFS were 67%, 19%, 28% and 6%, respectively. Consolidative chest RT was well-tolerated in the majority of patients; it was interrupted in three cases (due to G2 pulmonary toxicity, disease progression and clinical decay, respectively). Only 1 patient developed G3 asthenia. (4) Conclusions: Consolidative chest RT has been shown to be useful in reducing the risk of thoracic disease progression and is absolutely well-tolerated in patients with advanced stage SCLC with good response after first-line chemotherapy. Among the Italian centers that participated in this study, there is still variability in the choice of fractionation and target volumes, although the guidelines contain clear recommendations. The aim of future research should be to clarify the role and modalities of chest RT in the era of immunotherapy in advanced-stage SCLC.

Lattice Radiation Therapy in clinical practice: A systematic review.

Purpose: Lattice radiation therapy (LRT) is an innovative type of spatially fractionated radiation therapy. It aims to increase large tumors control probability by administering ablative doses without an increased toxicity. Considering the rising number of positive clinical experiences, the objective of this work is to evaluate LRT safety and efficacy. Method: Reports about LRT clinical experience were identified with a systematic review conducted on four different databases (namely, Medline, Embase, Scopus, and Cochrane Library) through the August 2022. Only LRT clinical reports published in English and with the access to the full manuscript text were considered as eligible. The 2020 update version PRISMA statement was followed. Results: Data extraction was performed from 12 eligible records encompassing 7 case reports, 1 case series, and 4 clinical studies. 81 patients (84 lesions) with a large lesion ranging from 63.2 cc to 3713.5 cc were subjected to exclusive, hybrid, and metabolism guided LRT. Excluding two very severe toxicity with a questionable relation with LRT, available clinical experience seem to confirm LRT safety. When a complete response was not achieved 3-6 months after LRT, a median lesion reduction approximately ≥50 % was registered. Conclusion: This systematic review appear to suggest LRT safety, especially for exclusive LRT. The very low level of evidence and the studies heterogeneity preclude drawing definitive conclusions on LRT efficacy, even though an interesting trend in terms of lesions reduction has been described.

Impact of low skeletal muscle mass and quality on clinical outcomes in patients with head and neck cancer undergoing (chemo)radiation.

The study aimed to explore the impact of low skeletal muscle mass and quality on survival outcomes and treatment tolerance in patients undergoing radical chemo-radiation therapy for head and neck cancer (HNC). This is significant given the growing interest in sarcopenia as a possible negative predictive/prognostic factor of disease progression and survival. From 2010 to 2017, 225 patients were included in the study. Pre-treatment computed tomography (CT) scans of HNC patients undergoing (chemo)radiation therapy were retrospectively reviewed. The skeletal muscle area, normalized for height to obtain the skeletal muscle index (SMI), the skeletal muscle density (SMD) and the intramuscular adipose tissue area (IMAT) were measured at the level of the L3 vertebra. Low SMD and low SMI were defined according to previously reported thresholds, while high IMAT was defined using population-specific cut-point analysis. SMI, SMD, and IMAT were also measured at the proximal thigh (PT) level and tested as continuous variables. Clinical morpho-functional parameters, baseline nutritional markers with a known or suspected impact on HNC treatment, clinical outcomes and sarcopenia were also collected. In multivariate analyses, adjusted by age, sex, stage, diabetes, body mass index (BMI), and weight loss, L3-SMI was not significantly associated with survival, while poor muscle quality was negatively associated with overall survival (OS) (HR = 1.88, 95% CI = 1.09-3.23, p = 0.022 and HR = 2.04, 95% CI = 1.27-3.27, p = 0.003, for low L3-SMD and high L3-IMAT, respectively), progression-free survival (PFS) (HR = 2.26, 95% CI = 1.39-3.66, p = 0.001 and HR = 1.97, 95% CI = 1.30-2.97, p = 0.001, for low L3-SMD and high L3-IMAT, respectively) and cancer-specific survival (CSS) (HR = 2.40, 95% CI = 1.28-4.51, p = 0.006 and HR = 1.81, 95% CI = 1.04-3.13, p = 0.034, for low L3-SMD and high L3-IMAT, respectively). Indices at the PT level, tested as continuous variables, showed that increasing PT-SMI and PT-SMD were significant protective factors for all survival outcomes (for OS: HR for one cm2/m2 increase in PT-SMI 0.96; 95% CI = 0.94-0.98; p = 0.001 and HR for one HU increase in PT-SMD 0.90; 95% CI = 0.85-0.94; p < 0.001, respectively). PT-IMAT was a significant risk factor only in the case of CSS (HR for one cm2 increase 1.02; 95% CI = 1.00-1.03; p = 0.046). In conclusion, pre-treatment low muscle quality is a strong prognostic indicator of death risk in patients affected by HNC and undergoing (chemo)radiotherapy with curative intent.

The Use of Cardiac Stereotactic Radiation Therapy (SBRT) to Manage Ventricular Tachycardia: A Case Report, Review of the Literature and Technical Notes.

BACKGROUND: among cardiac arrhythmias, ventricular tachycardia (VT) is one that can lead to cardiac death, although significant progress has been made in its treatment, including the use of implantable cardioverter-defibrillators (ICD) and radiofrequency catheter ablation. Nevertheless, long-term recurrence rates remain in about half of patients and drastically impact the patient's quality of life. Moreover, recurrent ICD shocks are painful and are associated with higher mortality and worsening of heart failure. Recently, more and more experiences are demonstrating potential efficacy in the use of stereotactic body radiotherapy (SBRT) (also called cardiac radio-ablation) to treat this condition. In this paper, we report our experience in the use of cardiac radio-ablation for the treatment of refractory ventricular tachycardia with a focus on the technique used, along with a review of the literature and technical notes. CASE PRESENTATION: an 81-year-old male patient with a long history of non-ischemic dilated cardiomyopathy and mechanical mitral prosthesis underwent a biventricular cardioverter defibrillator implant after atrial ventricular node ablation. At the end of 2021, the number of tachycardias increased significantly to about 10 episodes per day. After failure of medical treatment and conventional RT catheter ablation, the patient was treated with SBRT for a total dose of 25 Gy in a single session at the site of the ectopic focus. No acute toxicity was recorded. After SBRT (follow-up 7 months) no other VT episodes were recorded. CONCLUSION: SBRT appears to be safe and leads to a rapid reduction in arrhythmic storms as treatment for VT without acute toxicity, representing one of the most promising methods for treating VT storms.

Epileptogenesis and Tumorigenesis in Glioblastoma: Which Relationship?

Epilepsy is reported in 29-52% of patients with glioblastoma (GBM) and has an important role in the natural history of this tumor and patients' life quality. Although GBM is less epileptogenic than lower-grade gliomas, seizures are usually more difficult to control with common antiseizure medications; drug resistance is found in 20% of cases. Recent studies suggest that seizures at the onset of GBM could be a possible favorable independent prognostic factor in patients. Moreover, a growing body of evidence shows that many molecular mechanisms that influence epileptogenesis often regulate GBM growth and invasiveness, sometimes favoring or counteracting the tumor, respectively. The better-characterized players include glutamate, γ-aminobutyric acid, aquaporin-4, and hypoxia-activated molecules. However, currently available data on the molecular basis of epileptogenesis, tumorigenesis, and their relationship is incomplete or discordant and further research is urgently needed on this topic.

Safety of Inhomogeneous Dose Distribution IMRT for High-Grade Glioma Reirradiation: A Prospective Phase I/II Trial (GLIORAD TRIAL).

Glioblastoma multiforme (GBM) is the most aggressive astrocytic primary brain tumor, and concurrent temozolomide (TMZ) and radiotherapy (RT) followed by maintenance of adjuvant TMZ is the current standard of care. Despite advances in imaging techniques and multi-modal treatment options, the median overall survival (OS) remains poor. As an alternative to surgery, re-irradiation (re-RT) can be a therapeutic option in recurrent GBM. Re-irradiation for brain tumors is increasingly used today, and several studies have demonstrated its feasibility. Besides differing techniques, the published data include a wide range of doses, emphasizing that no standard approach exists. The current study aimed to investigate the safety of moderate-high-voxel-based dose escalation in recurrent GBM. From 2016 to 2019, 12 patients met the inclusion criteria and were enrolled in this prospective single-center study. Retreatment consisted of re-irradiation with a total dose of 30 Gy (up to 50 Gy) over 5 days using the IMRT (arc VMAT) technique. A dose painting by numbers (DPBN)/dose escalation plan were performed, and a continuous relation between the voxel intensity of the functional image set and the risk of recurrence in that voxel were used to define target and dose distribution. Re-irradiation was well tolerated in all treated patients. No toxicities greater than G3 were recorded; only one patient had severe G3 acute toxicity, characterized by muscle weakness and fatigue. Median overall survival (OS2) and progression-free survival (PFS2) from the time of re-irradiation were 10.4 months and 5.7 months, respectively; 3-, 6-, and 12-month OS2 were 92%, 75%, and 42%, respectively; and 3-, 6-, and 12-month PFS2 were 83%, 42%, and 8%, respectively. Our work demonstrated a tolerable tolerance profile of this approach, and the future prospective phase II study will analyze the efficacy in terms of PFS and OS.

Sixteen-Year Follow-Up in a Cavernous Sinus Hemangiopericytoma: Improved Outcomes over Radiotherapy Advances.

Intracranial hemangiopericytomas are rare tumors, accounting for 1% of all central nervous system malignancies. This tumor is considered at high risk of local and also distant metastases. Surgical excision is the gold standard for treatment, but it is seldom curative by itself. Adjuvant radiotherapy is often recommended. We report an overview and update of the available literature on one such rare but aggressive mesenchymal tumor, using the case of a 46-year-old woman affected by hemangiopericytoma of the cavernous sinus surgically removed and treated with adjuvant radiotherapy at our institution. After seven years, the patient underwent a local recurrence and was treated with exeresis and Gamma Knife radiotherapy. Sixteen years after the initial diagnosis, she is still well with stable disease.

Histiocytic Sarcoma Involving Cervical Vertebra: A Case Report and Review of the Literature.

Histiocytic sarcoma (HS) is a rare neoplasm composed of cells with immunohistochemical characteristics of mature histiocytes. It can be disseminated or localized and usually involves the skin, spleen, and gastrointestinal tract. Primary involvement of the vertebral column is extremely rare. We report a 29-year-old female who presented with neck pain and had a destructive 35*43*48 mm lesion in C2 with a paravertebral extension. The initial biopsy did not lead to the correct diagnosis. She later developed dysphagia, and the anterior approach was used for tumor decompression. The diagnosis of cervical histiocytic sarcoma was made, and she underwent radiotherapy. The follow-up MRI showed a marked response to radiotherapy. Here, we report the first case of cervical HS, review all cases of vertebral HS, compare patients' characteristics and clinical courses, and discuss diagnostic nuances and treatment options.

Novel Harmonization Method for Multi-Centric Radiomic Studies in Non-Small Cell Lung Cancer.

The purpose of this multi-centric work was to investigate the relationship between radiomic features extracted from pre-treatment computed tomography (CT), positron emission tomography (PET) imaging, and clinical outcomes for stereotactic body radiation therapy (SBRT) in early-stage non-small cell lung cancer (NSCLC). One-hundred and seventeen patients who received SBRT for early-stage NSCLC were retrospectively identified from seven Italian centers. The tumor was identified on pre-treatment free-breathing CT and PET images, from which we extracted 3004 quantitative radiomic features. The primary outcome was 24-month progression-free-survival (PFS) based on cancer recurrence (local/non-local) following SBRT. A harmonization technique was proposed for CT features considering lesion and contralateral healthy lung tissues using the LASSO algorithm as a feature selector. Models with harmonized CT features (B models) demonstrated better performances compared to the ones using only original CT features (C models). A linear support vector machine (SVM) with harmonized CT and PET features (A1 model) showed an area under the curve (AUC) of 0.77 (0.63-0.85) for predicting the primary outcome in an external validation cohort. The addition of clinical features did not enhance the model performance. This study provided the basis for validating our novel CT data harmonization strategy, involving delta radiomics. The harmonized radiomic models demonstrated the capability to properly predict patient prognosis.

Can Radiotherapy Empower the Host Immune System to Counterattack Neoplastic Cells? A Systematic Review on Tumor Microenvironment Radiomodulation.

Despite the rising evidence in favor of immunotherapy (IT), the treatment of oncological patients affected by so-called "cold tumors" still represents an open issue. Cold tumors are characterized by an immunosuppressive (so-called cold) tumor microenvironment (TME), which favors host immune system suppression, cancer immune-escape, and a worse response to IT. However, the TME is not a static element, but dynamically mutates and can be changed. Radiotherapy (RT) can modulate a cold microenvironment, rendering it better at tumor killing by priming the quiescent host immune system, with a consequent increase in immunotherapy response. The combination of TME radiomodulation and IT could therefore be a strategy for those patients affected by cold tumors, with limited or no response to IT. Thus, this review aims to provide an easy, rapid, and practical overview of how RT could convert the cold TME and why cold tumor radiomodulation could represent an interesting strategy in combination with IT.

How a very large sarcomatoid lung cancer was efficiently managed with lattice radiation therapy: a case report.

BACKGROUND: The management of large tumors represent a concerning issue in the palliative setting. Since a surgical approach is excluded and systemic therapy has reported limited efficacy, the patients are commonly referred for radiation therapy as last resort. However, to improve quality of life and to avoid excessive toxicity, low doses of palliative radiotherapy (RT) are delivered. In these cases, with limited and short response. Lattice radiation therapy (LRT) represents an innovative technique aiming to increase tumor response without enhancing adjacent organs at risk (OAR) toxicity, by administering inhomogeneous doses with ablative high dose areas inside the tumor and low doses near the OAR. CASE DESCRIPTION: A 69-year-old male patient was admitted to our hospital complaining of sacral pain and mild dyspnea. After a suspicious opacity on X-ray, the chest computed tomography (CT), the positron emission tomography/CT (PET/CT) and the endobronchial ultra sound-guided transbronchial needle aspiration confirmed the diagnosis of a bulky sarcomatoid lung cancer (stage IV: cT4N3M1c). After an effective antalgic RT on the sacral metastasis and three lines of systemic therapy without response, the patient started to have a disabling dyspnea. Thus, we administered LRT on the bulky lesion. The patients experienced no significant toxicity, with a marked lesion response on the 3 month-follow CT and a significant improvement in symptoms and in his daily life. CONCLUSIONS: This is the first LRT treatment done in our Center and it provides another evidence in the efficacy of LRT planning. It shows how LRT could represent an innovative technique to provide durable response in large tumors, without increasing treatment-related toxicity.

Stereotactic Body Radiation Therapy (SBRT) for Oligorecurrent/Oligoprogressive Mediastinal and Hilar Lymph Node Metastasis: A Systematic Review.

INTRODUCTION: Mediastinal or hilar lymph node metastases are a challenging condition in patients affected by solid tumors. Stereotactic body radiation therapy (SBRT) could play a crucial role in the therapeutic management and in the so-called "no-fly zone", delivering high doses of radiation in relatively few treatment fractions with excellent sparing of healthy surrounding tissues and low toxicity. The aim of this systematic review is to evaluate the feasibility and tolerability of SBRT in the treatment of mediastinal and hilar lesions with particular regard to the radiotherapy doses, dose constraints for organs at risk, and clinical outcomes. MATERIALS AND METHODS: Two blinded investigators performed a critical review of the Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA), starting from a specific question: What is the clinical impact of SBRT for the treatment of oligorecurrent/oligoprogressive mediastinal and hilar metastasis? All retrospective and prospective clinical trials published in English up to February 2022 were analyzed. RESULTS: A total of 552 articles were identified and 12 of them were selected with a total number of 478 patients treated with SBRT for mediastinal or hilar node recurrence. All the studies are retrospective, published between 2015 and 2021 with a median follow-up ranging from 12 to 42.2 months. Studies following SBRT for lung lesions or retreatments after thorax radiotherapy for stage III lung cancer were also included. The studies showed extensive heterogeneity in terms of patient and treatment characteristics. Non-small cell lung cancer was the most frequently reported histology. Different dose schemes were used, with a higher prevalence of 4-8 Gy in 5 or 6 fractions, but dose escalation was also used up to 52 Gy in 4 fractions with dose constraints mainly derived from RTOG 0813 trial. The radiotherapy technique most frequently used was volumetric modulated arc therapy (VMAT) with a median PTV volume ranging from 7 to 25.7 cc. The clinical outcome seems to be very encouraging with 1-year local control (LC), overall survival (OS) and progression-free survival (PFS) rates ranging from 84 to 94%, 53 to 88% and 23 to 53.9%, respectively. Half of the studies did not report toxicity greater than G3 and only five cases of fatal toxicity were reported. CONCLUSIONS: From the present review, it is not possible to draw definitive conclusions because of the heterogeneity of the studies analyzed. However, SBRT appears to be a safe and effective option in the treatment of mediastinal and hilar lymph node recurrence, with a good toxicity profile. Its use in clinical practice is still limited, and there is extensive heterogeneity in patient selection and fractionation schedules. Good performance status, small PTV volume, absence of previous thoracic irradiation, and administration of a high biologically effective dose (BED) seem to be factors that correlate with greater local control and better survival rates. In the presence of symptoms related to the thoracic lymph nodes, SBRT determines a rapid control that lasts over time. We look forward to the prospective studies that are underway for definitive conclusions.

State of the Art in Combination Immuno/Radiotherapy for Brain Metastases: Systematic Review and Meta-Analysis.

OBJECTIVES: Common origins for brain metastases (BMs) are melanoma, lung, breast, and renal cell cancers. BMs account for a large share of morbidity and mortality caused by these cancers. The advent of new immunotherapeutic treatments has made a revolution in the treatment of cancer patients and particularly, as a new concept, if it is combined with radiotherapy, may lead to considerably longer survival. This systematic review and meta-analysis aimed to evaluate the survival rate and toxicities of such a combination in brain metastases. METHODS: To perform a systematic review of the literature until January 2021 using electronic databases such as PubMed, Cochrane Library, and Embase; the Newcastle-Ottawa Scale was used to evaluate the quality of cohort studies. For data extraction, two reviewers extracted the data blindly and independently. Hazard ratio with 95% confidence interval (CI), fixed-effect model, and inverse-variance method was calculated. The meta-analysis has been evaluated with the statistical software Stata/MP v.16 (The fastest version of Stata). RESULTS: In the first step, 494 studies were selected to review the abstracts, in the second step, the full texts of 86 studies were reviewed. Finally, 28 studies were selected consisting of 1465 patients. The addition of IT to RT in the treatment of brain metastasis from melanoma and non-small-cell lung carcinoma was associated with a 39% reduction in mortality rate and has prolonged overall survival, with an acceptable toxicity profile. The addition of IT to RT compared with RT alone has a hazard ratio of 0.39(95% CI 0.34-0.44). CONCLUSIONS: A combination of immuno/radiotherapy (IR) for the treatment of patients with BMs from melanoma and non-small-cell lung carcinoma has prolonged overall survival and reduced mortality rate, with acceptable toxicity. In terms of timing, RT seems to have the best effect on the result when performed before or simultaneously with immunotherapy.