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In metastatic breast cancer (mBC), the change of human epidermal growth factor receptor 2 (HER2) status between primary and metastatic lesions is widely recognized, however clinical implications are unknown. Our study address the question if relevant differences exist between subjects who preserve the HER2 status and those who gain the HER2 positivity when relapsed. Data of patients affected by HER2-positive mBC, treated with pertuzumab and/or trastuzumab-emtansine (T-DM1) in a real-world setting at 45 Italian cancer centers were retrospectively collected and analyzed. From 2003 to 2017, 491 HER2-positive mBC patients were included. Of these, 102 (20.7%) had been initially diagnosed as HER2-negative early BC. Estrogen and/or progesterone receptor were more expressed in patients with HER2-discordance compared to patients with HER2-concordant status (p < 0.0001 and p = 0.006, respectively). HER2-discordant tumors were characterized also by a lower rate of brain metastases (p = 0.01) and a longer disease free interval (p < 0.0001). Median overall survival was longer, although not statistically significant, in the subgroup of patients with HER2-discordant cancer with respect to patients with HER2-concordant status (140 vs 78 months, p = 0.07). Our findings suggest that patients with HER2-positive mBC with discordant HER2 status in early BC may have different clinical, biological and prognostic behavior compared to HER2-concordant patients.

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]

The article explores on the health outcome of patients treated with breast-conserving surgery. It examines the safety and efficacy of postoperative radiation therapy (RT) and adjuvant endocrine treatments in treating the ductal carcinoma in situ (DCIS). It also cites the importance of knowledge about biologic features and response to treatment option.

• 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]

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]

Aim This analysis evaluated the efficacy and safety of nivolumab, an immune checkpoint inhibitor, in elderly patients with stage IIIB or IV squamous non–small-cell lung cancer (NSCLC) enrolled in the expanded access programme (EAP) in Italy. Methods Nivolumab was available on physician request. Safety data included adverse events (AEs). Efficacy data included investigator-assessed tumour response, progression date and survival information. Results were analysed for patients aged <65, 65–<75 and ≥75 years and for the overall population. Results A total of 371 patients with squamous NSCLC were enrolled at 96 centres between April 2015 and September 2015; 34% (n = 126), 47% (n = 175) and 19% (n = 70) were aged <65, 65–<75 and ≥75 years, respectively. Efficacy was similar among patients aged <65, 65–<75 and ≥75 years and the overall population (objective response rates: 18%, 18%, 19% and 18%, respectively; disease control rates: 49%, 47%, 43% and 47%, respectively). Median overall survival was reduced in patients aged ≥75 years (5.8 months) versus patients aged <65; years (8.6 months), patients aged 65–<75 years (8.0 months) and the overall population (7.9 months). The incidence of grade 3–4 treatment-related AEs was low in patients aged 65, 65–<75 and ≥75 years and the overall population (3%, 9%, 3%, 6%, respectively). Discontinuation rates due to treatment-related AEs were low irrespective of age (4–5%). Conclusions These EAP results suggest that elderly patients with advanced squamous NSCLC benefit from nivolumab, with tolerability similar to that in the overall population. [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]