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The therapeutic landscape of metastatic prostate cancer has undergone a profound revolution in recent years. In addition to the introduction of novel molecules in the clinics, the field has witnessed a tremendous development of functional imaging modalities adding new biological insights which can ultimately inform tailored treatment strategies, including local therapies. The evolution and rise of Stereotactic Body Radiotherapy (SBRT) have been particularly notable in patients with oligometastatic disease, where it has been demonstrated to be a safe and effective treatment strategy yielding favorable results in terms of disease control and improved oncological outcomes. The possibility of debulking all sites of disease, matched with the ambition of potentially extending this treatment paradigm to polymetastatic patients in the not-too-distant future, makes Biology-guided Radiotherapy (BgRT) an attractive paradigm which can be used in conjunction with systemic therapy in the management of patients with metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Oligoprogression (OPD) is defined as a condition where limited progression (1–3 metastases) is observed in patients undergoing systemic cancer treatment. In this study we investigated the impact of stereotactic body radiotherapy (SBRT) in patients with OPD from metastatic lung cancer. Data from a cohort of consecutive patients with SBRT treated between June 2015 and August 2021 were collected. All extracranial metastatic sites of OPD from lung cancer were included. Dose regimens consisted of mainly 24 in 2 fractions, 30–51 Gy in 3 fractions, 30–55 Gy in 5 fractions, 52.5 Gy in 7 fractions and 44–56 Gy in 8 fractions. Kaplan–Meier method was used to calculate Overall Survival (OS), Local Control (LC), and Disease-Free Survival (DFS) from the start date of SBRT to the event. Sixty-three patients, 34 female and 29 males were included. Median age was 75 years (range 25–83). All patients received concurrent systemic treatment before the start of the SBRT: 19 chemotherapy (CT), 26 CT plus immunotherapy (IT) or Tyrosin kinase inhibitors (TKI) and 18 IT/TKI. SBRT was delivered to the lung (n = 29), mediastinal node (n = 9), bone (n = 7), adrenal gland (n = 19), other visceral metastases (1) and other node metastases (n = 4). After a median follow-up of 17 months, median OS was 23 months. LC was 93% at 1 year and 87% at 2 years. DFS was 7 months. According to our results, there was no statistically significant correlation between prognostic factors and OS after SBRT in OPD patients. Median DFS was 7 months, translating into the continuation of effective systemic treatment as other metastases grow slowly. In patients with oligoprogression disease, SBRT is a valid and efficient treatment that may enable postponing the switch of systemic line. [ABSTRACT FROM AUTHOR]

New metabolic tracers have improved sensitivity and specificity for the real extent of tumor burden in prostate cancer. This study aims to compare the impact of these tracers for metastasis-directed therapy. Gallium-68 prostate-specific membrane antigen-positron emission tomography-guided metastasis-directed therapy in castration-sensitive oligorecurrent prostate cancer patients resulted in higher rates of androgen deprivation therapy-free survival, when compared with 18F-fluorocholine positron emission tomography-guided treatments (P = .00). Background: The present analysis aims to compare the impact of 18F-fluorocholine (18F-choline) and gallium-68 prostatespecific membrane antigen (68Ga-PSMA) positron emission tomography (PET)-computed tomography (CT)eguided metastases-directed therapies (MDTs) in patients with castration-sensitive oligorecurrent prostate cancer (PC). Materials and Methods: Inclusion criteria were: (1) histologically proven prostate adenocarcinoma; (2) evidence of biochemical relapse after primary tumor treatment; (3) ≤ 3 hypermetabolic oligorecurrent lesions detected by 18F-choline or 68Ga-PSMA PET-CT; (4) PET-CT imaging performed in a single nuclear medicine department; (5) patients treated with upfront stereotactic body radiotherapy (SBRT) without hormone therapy; and (6) SBRT delivered with a dose per fraction ≥ 5 Gy. In the case of oligoprogression (≤ 3 lesions outside the previous RT field) after MTD, a further course of SBRT was proposed; otherwise, androgen deprivation therapy (ADT) was administered. Results: A total of 118 lesions in 88 patients were analyzed. Forty-four (50%) patients underwent 68Ga-PSMA PET-guided SBRT, and the remaining underwent choline PET-based SBRT. The median follow-up was 25 months (range, 5-87 months) for the entire cohort. Overall survival and local control were both 100%. Distant progression occurred in 48 (54.5%) patients, for a median distant progression-free survival of 22.8 months (range, 14.4-28.8 months). The median pre-SBRT prostate-specific antigen was 2.04 ng/mL in the choline PET cohort and 0.58 ng/mL in the PSMA-PET arm. Disease-free survival rates were 63.6% and 34%, respectively, in the 68Ga-PSMA and choline PET group (P = .06). The ADT administration rate was higher after choline-PETeguided SBRT (P = .00) owing to the higher incidence of polymetastatic disease after first-course SBRT compared with 68Ga-PSMA-based SBRT. Conclusion: In the setting of oligorecurrent castration-sensitive PC, PSMA-PET-guided SBRT produced a higher rate of ADT-free patients when compared with the 18F-choline-PET cohort. Randomized trials are advocated. [ABSTRACT FROM AUTHOR]

Authors review a series of 29 extra-skeletal Ewing Sarcoma (EES) They analyzed characteristics, prognostic factors and outcome of EES. Authors report 60% Overall Survival (OS) and 56% of Event Free Survival (EFS) at 5 years. Better 5 years EFS was found in patients with localized disease (68.8%) compared to metastatic EES (33.3%) (p = 0.042). Radiotherapy + surgery offered the best local treatment (p=0.017). Volume (p = 0.032), Surgical margins (p = 0.01), metastatic disease (p = 0.0013) were a significant prognostic factor for OS at 5-yrs. Adequate margins and surgery+radiotherapy improve Overall Survival. [ABSTRACT FROM AUTHOR]

The Authors reported a retrospective study of 100 Leiomyosarcoma (LMS), evaluating factors that may influence Overall Survival (OS), Local Recurrence Free Survival (LRFS), Metastasis Free Survival (MFS). Tumor Size (P=0,0009), Local Recurrence (P=0,0487), Distant relapse (P < 0,0001), Type of Presentation (P=0,0213) were significant risk factors affecting overall survival (OS). Tumor Size (P=0.024), age at diagnosis (P=0,0086), type of presentation (P < 0,0001) and Local Recurrence (P=0.0152) affected metastasis free survival (MFS). Type of presentation (P=0,001) was an independent prognostic factor of local recurrence-free survival (LRFS). [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]

This commentary addresses the need for novel endpoints in clinical research to assess the added value of local treatment of metastases in oligometastatic patients and in patients experiencing limited metastatic progression during systemic therapy (oligoprogressive). Novel metrics are proposed for future implementation in clinical trials. [ABSTRACT FROM AUTHOR]

Abstract: In a prospective study, we attempted to predict axillary metastases in 135 breast cancer patients by a preoperative multiparameter evaluation including axillary ultrasound scanning (US). After surgery, factors associated with lymph node metastases by univariate analysis were included in a multivariate model. By multivariate analysis, the stronger independent predictors of lymph node metastases were suspicious axillary US (p <0.001), tumor location in the outer quadrants (p =0.001) and high Ki-67 index (>10%) (p =0.002). A predictive model based on these variables, identified a high-risk group (20.0%) represented by women with suspicious axillary US, tumor in the outer quadrants and high Ki-67 index, with axillary metastases in 100%, whereas all patients with opposite features (8.1%) had uninvolved axillary lymph nodes. This multiparameter evaluation including axillary US may be used to optimize the selection of breast cancer patients candidate to sentinel lymph node biopsy or axillary lymph node dissection. The accuracy of this predictive model still requires prospective validation in a larger sample of women. [Copyright &y& Elsevier]

Purpose or objective: Oligoprogression (OPD) is defined as a condition where limited progression (1-3 metastases) is observed in patients undergoing systemic cancer treatment. Local treatment of OPD might delay systemic therapy line switch, which could be beneficial in patients experiencing prolonged global disease control with novel targeted or immune therapies. In this study we investigated the impact on outcome of stereotactic body radiotherapy (SBRT) in patients with OPD from metastatic lung cancer. Materials and methods: Data from a cohort of consecutive patients treated with Cyberknife and Linacbased SBRT between June 2015 and August 2021 were collected. All extracranial metastatic sites of OPD from lung cancer were included. Dose regimens consisted of 24 in 2 fractions, 30-51 Gy in 3 fractions, 30-55 Gy in 5 fractions, 52.5 Gy in 7 fractions and 44-56 Gy in 8 fractions. Dose was expressed as Biological Effective Dose for α/β=10 (BED10). Kaplan-Meyer method was used to calculate Overall Survival (OS), Local Control (LC) and Disease Progression-free Survival (DPFS) from the start date of SBRT to event. Results: Sixty-three patients, 34 female and 29 male were included. Median age was 75 years (range 25–83). All patients received concurrent systemic treatment before the start of the SBRT: 19 chemotherapy (CT) alone (30%), 26 CT plus immunotherapy (IT) or plus Tyrosin kinase inhibitors (TKI) (41%) and 18 IT/TKI alone (29%). SBRT was delivered to lung (n=29), mediastinal node (n=9), bone (n=7), adrenal gland (n=19), other visceral metastases (1) and other node metastases (n=4). A median BED10 of 104 (range 39-151) Gy10 was delivered. After a median follow up of 20 months (range 1-48), median overall survival was median OS was 23 months (figure 1). LC was 93% at 1 year and 87% at 2 years. DPFS was 7 months. At univariate analysis, age, type of systemic treatment, metastatic site receiving SBRT and BED were not significant prognostic factors for overall survival. Conclusion: SBRT in lung cancer patients for oligoprogression resulted in a long median OS of 23 months. One-year LC was 93%. Median DPFS was 7 months, translating into continuation of effective systemic treatment as other metastases grow slowly. SBRT could be useful to postpone the change of chemotherapy and/or immunotherapy. More research is needed to select OPD patients eligible for SBRT. [ABSTRACT FROM AUTHOR]

We present the case of a 52-year-old woman with a history of excised cutaneous malignant melanoma complaining of abnormal uterine bleeding 11 years after initial diagnosis. Hysteroscopic examination showed an endometrial lesion with polypoid shape and endometrial biopsy was suggestive for melanoma. After a complete clinical work-up ruling out other metastatic sites, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Final histopathological and immunohistochemical analysis confirmed the diagnosis of endometrial melanoma with initial myometrial invasion. After a 6-month follow-up period, the patient was disease free. Even after many years of negative follow up, gynecologists should be aware of the possibility that abnormal uterine bleeding could represent the clinical expression of metastatic melanoma in order to offer a prompt diagnosis and a personalized strategy of treatment. [ABSTRACT FROM AUTHOR]

After KEYNOTE 048, PDL1 CPS score has become essential in treatment choice for patients with squamous cell carcinoma of the head and neck (HNSCC) not eligible for curative treatment. This report aims to analyze efficacy and safety outcomes in a cohort of patients treated in our center with first line systemic therapy (FLST) from 2021. We collected retrospectively data about stadiation and treatment from patients with recurrent/metastatic HNSCC treated in our center with FLST according to CPS. The primary endpoints were overall survival (OS) and progression-free survival (PFS) (considered from the start of FLST). Toxicity data were reported according to CTCAEv4.0. [Display omitted] Thirty-nine patients who underwent FLST in our center between Jan 2021 and May 2023 were included in this retrospective study, with a median follow-up of 9 months [95%CI 1.2-16.8]. Median age was 63 years and PS ECOG mostly 0-1 (90%); CPS resulted negative in 8 (21%), >1 in 9 (23%) and >20 in 22 (56%) patients. 16 patients (41%) had distant metastases, the others locoregional disease not eligible for radical treatment. EXTREME schedule was chosen in the 8 CPS-negative patients; 20 of the CPS-positive cohort received Platinum+5FU+Pembrolizumab (PFP) and 11 Pembrolizumab alone. Considering all patients, median OS was 9 months [95%CI 3.1-14.8], 1-year OS 46%, 2-year OS 20%; median PFS was 5 months [95%CI 3.4-6.5] (Figure 1). One-year PFS 21%. Pembrolizumab group had a median OS of 9 months [95%CI 3.5-14.5] and 1-year OS of 38%; PFP group had median OS of 10 months [95%CI 0-23.9], 1-year OS 45% and 2-year OS 30%. At univariate analysis, younger age was associated with longer survival with a median OS of 17 months [95%CI 4.2-29.7] and 5 months [95%CI 1.7-8.3] for patients aged <70y and >70y respectively (p=0.01). Regarding toxicity, we reported 15 events > G3; the most frequent were mucositis (4) and neutropenia (4) in chemotherapy groups; only 3 occurred with Pembrolizumab alone. In our cohort, patients with recurrent/metastatic HNSCC had efficacy and safety outcomes in line with published chemo-immunotherapy data (KN048). Younger age was significantly associated with longer survival. [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]

Objectives. The authors reported a retrospective study on myxoid liposarcomas (MLs), evaluating factors that may influence overall survival (OS), local recurrence-free survival (LRFS), metastasis-free survival (MFS), and analyzing the metastatic pattern. Methods. 148 MLs were analyzed. The sites of metastases were investigated. Results. Margins (p = 0.002), grading (p = 0,0479), and metastasis (p < 0,0001) were significant risk factors affecting overall survival (OS). Type of presentation (p = 0.0243), grading (p = 0,0055), margin (p = 0.0001), and local recurrence (0.0437) were risk factors on metastasis-free survival (MFS). Authors did not observe statistically significant risk factors for local recurrence-free survival (LRFS) and reported 55% extrapulmonary metastases and 45% pulmonary metastases. Conclusion. Margins, grading, presentation, local recurrence, and metastasis were prognostic factors. Extrapulmonary metastases were more frequent in myxoid liposarcoma. [ABSTRACT FROM AUTHOR]

• Tyrosine Kinases Inhibitors were used in combination with SBRT in 93% of cases. • Radiotherapy schedules of single fraction doses were 10–20 Gy. • Radiotherapy schedules of hypofractionated doses were 35–60 Gy in 3–5 fractions. • Local control of irradiated lesions was achieved in 76–100% of the patients. • The 2-year overall survival was 71% after combined approach. To conduct a systematic review and meta-analysis of the role of SBRTdrug combination in patients affected by mRCC and associated oncologic outcomes and toxicity profiles. We performed a critical review of the Pubmed, Medline, and Embase databases from January 1, 2000 through April 30, 2020 according to the Preferred Reporting Items and Meta-Analyses statement. To assess the overall quality of the literature reviewed, we used a modified Delphi tool. A total of 6 studies were included, corresponding to a cohort of 216 patients. Tyrosine Kinases Inhibitors were the most widely used drugs in combination with SBRT, being administered in 93% patients. No study reported an increase of radiation-induced toxicity. SBRT resulted to be safe, without increase in terms of drugs-related adverse events in this setting. Moreover, this approach showed promising clinical outcomes in terms of LC and OS [ABSTRACT FROM AUTHOR]