Istituto Oncologico Veneto Research Articles

High pre-treatment NLR and PLR predict poor prognosis of patients with recurrent/metastatic head and neck squamous cell carcinoma treated with immune checkpoint inhibitors.

e18001 Background: The treatment landscape of unresectable recurrent and/or metastatic (R/M) Head and Neck Squamous cell Carcinoma (HNSCC) has profoundly changed with the introduction of Immune checkpoint inhibitors (ICIs). High neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been associated with poor outcome in several tumor types. The aim of the present study was to investigate the role of pre-treatment NLR and PLR in predicting overall survival (OS) of patients treated with ICIs. Materials and Methods: We retrospectively reviewed the clinical records of 106 consecutive patients with R/M-HNSCC who received ICIs (single-agent or ICIs-based treatment) between January 2018 and June 2023 at the Istituto Oncologico Veneto of Padua. Patients were grouped into platinum-refractory (patients progressed within 6 months from the last platinum dose) and platinum-sensitive. The cut-off values of pre-treatment NLR and PLR were determined based on percentile distribution (75th percentile). OS was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used to compare survival outcomes. Results: A total of 102 patients were analyzed. Four patients were excluded because of incomplete data. Primary tumor sites were oropharynx (37%), oral cavity (24%), hypopharynx (19%), larynx (15%), nasopharynx (5%) and nasal cavity (1%). 63 patients (62%) with platinum-refractory disease received nivolumab single-agent. All 39 patients (38%) with platinum-sensitive disease were PD-L1 positive (CPS≥1) and received pembrolizumab-based treatment. Median OS was 8.0 months (95% CI 5.8-10.1) in the platinum-refractory cohort and 13.3 months (95% CI 7.3-19.3) in the platinum-sensitive cohort. At the univariate analysis high NLR (≥7) and PLR (≥345) correlated with poor OS in the overall population and in both the platinum-refractory and the platinum-sensitive cohorts (Table1). At the multivariate analysis PLR was an independent predictor of OS. Conclusions: The efficacy results reported in this retrospective series were in line with the literature data. High PLR was an independent predictor of poor outcome regardless of the platinum sensitivity. Prospective studies are needed to better explore the predictive role of easily obtainable blood biomarkers in this poor prognostic population. Univariate analysis for OS [Table: see text]

Correlation between irAEs and treatment efficacy of anti-PD-1 single agent in patients with recurrent/metastatic head and neck squamous cell carcinoma: A monocentric real-world observational study.

6029 Background: Immune-related adverse events (irAEs) are associated with efficacy of ICIs-based treatment in various cancer types. The aim of this retrospective study was to assess the relationship between irAEs and outcomes in patients with recurrent/metastatic Head and Neck squamous cell carcinoma (R/M-HNSCC) treated with immune checkpoint inhibitors (ICIs) monotherapy. Methods: We retrospectively reviewed data from patients with R/M HNSCC treated with ICIs single-agent between January 2018 and June 2023 at the Istituto Oncologico Veneto of Padua. Common Terminology Criteria for Adverse Events v.5.0 was used to assess irAEs evaluation. Patients were stratified into irAEs (any grade) and non-irAEs groups. Overall survival (OS) and progression free survival (PFS) were assessed using the Kaplan-Meier method. Univariate and multivariate Cox-regression were used to compare survival outcomes. The chi-square test was used to assess the association between irAEs and objective responses (ORR). Results: A total of 89 patients were eligible for the analysis. Patients with platinum-refractory disease received nivolumab (64 patients, 72%). All the 25 patients (28%) with platinum-sensitive disease were PD-L1 positive (CPS≥1) and received pembrolizumab as first line treatment for R/M disease. Median follow-up was 8.7 months. IrAEs (any grade) were observed in 60 patients (67%), including 9 patients (10%) with grade ≥3 AEs. The most common irAEs were endocrinopathies (35%), skin events (15%), hepatic events (13%), diarrhea/colitis (10%) and lipase/amylase elevation (10%). The ORR was higher in the irAEs group than in the non-irAEs group (19.5% vs 2%, p=0.017). PFS and OS were also significantly longer in the irAEs group: median PFS was 3.9 months vs 2.1 months (HR 0.48 95% CI 0.30-0.77; p=0.003) and median OS was 12.5 months vs 4.3 months (HR 0.36 95% CI 0.21-0.60; p=0.000). The statistically significant benefit for both PFS and OS was confirmed at the multivariate analysis (Table1). Patients who experienced endocrine-related irAEs (p=0.004), diarrhea/colitis (p=0.040) and lipase/amylase increase (p=0.005) had significantly longer OS than those without the corresponding toxicity. A positive trend was observed for skin toxicity (p=0.051). Conclusions: The occurrence of irAEs was a predictor of response and survival outcomes in patients with R/M HNSCC treated with ICIs single-agent.[Table: see text]

Abstract PO3-13-06: TILs are an independent prognostic factor in early-stage TNBC patients achieving pathologic complete response after neoadjuvant chemotherapy

Abstract Introduction: In patients with triple negative breast cancer (TNBC) the achievement of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with better long-term clinical outcomes. However, the attainment of pCR does not guarantee cure, since ~ 10% of patients undergo disease relapse. Higher levels of tumor infiltrating lymphocytes (TILs) are associated with better prognosis in TNBC patients undergoing upfront surgery and in patients with residual disease after NACT. However, the prognostic role of TILs among TNBC patients undergoing pCR during NACT has not been investigated so far. Methods: We included 134 TNBC patients (ER cutoff< 10%) who achieved pCR after NACT. These cases were identified from a cohort of 348 TNBC patients who received NACT at Istituto Oncologico Veneto (Padova) and Istituto Nazionale Tumori (Milano) from April 2004 to April 2021. TILs were quantified in pre-NACT tumor biopsy according to International guidelines. We assessed the association between TILs and relapse-free survival (RFS) or overall survival (OS). Results: Main patients characteristics were: median age 48 years; ductal histotype 92.8%; histologic grade 3 95.2%; stage I 9.7%, stage II 71.6%, stage III 18.7%. Almost all patients received anthracyclines (98.5%) and taxanes (99.3%) as part of NACT for a median number of 4 cycles each; 55.2% of patients received carboplatin. At a median FU of 4.6 years, the 5-yr RFS and OS rates were 90.4% and 94.4%, respectively. As a continuous variable (1% increment), TILs were independently associated with better RFS and OS after adjusting for patient age and tumor stage: HR 0.90 (95%CI 0.83-0.98), p=0.015 and HR 0.89 (95%CI 0.80-1.00), p=0.041, respectively. The best prognostic TILs cut-off in this cohort was 20%. Patients with TILs>20% showed a 100% 5-yr RFS rate (0/63 events) vs 82.6% (12/71 events) for patients with TILs< 20% (log-rank p< 0.001). OS rates at 5 years were 100% and 90.1% for high vs low TILs (log-rank p=0.007). Conclusions: This is the first demonstration of an independent prognostic role of baseline TILs in TNBC patients achieving pCR after NACT. Baseline TILs may discriminate patients who are cured after achieving pCR from patients at risk of disease relapse despite the achievement of pCR. These latter may be candidate to treatment escalation in the context of clinical trials. Our work provides relevant data in the ongoing debate on the role of adjuvant therapy (primarily pembrolizumab) following pCR. Citation Format: Maria Vittoria Dieci, Claudio Vernieri, Davide Massa, Lorenzo Nicolè, Gaia Griguolo, Federica Miglietta, Andrea Vingiani, Riccardo Lobefaro, Fabio Girardi, Grazia Vernaci, Tommaso Giarratano, Carlo Alberto Giorgi, Giancarlo Pruneri, Matteo Fassan, Filippo De Braud, Valentina Guarneri. TILs are an independent prognostic factor in early-stage TNBC patients achieving pathologic complete response after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-13-06.

Advanced Non-Clear Cell Renal Cell Carcinoma Treatments and Survival: A Real-World Single-Centre Experience.

Non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous group of cancer. Treatment recommendations are extrapolated from ccRCC and lack solid evidence. Here, we review advanced nccRCC patients treated at our institute. We collected retrospective data on all advanced nccRCC pts treated at the Istituto Oncologico Veneto from January 2008. We compared overall response rate (ORR), progression free survival (PFS) and overall survival (OS) according to histological subtypes and type of systemic treatments. Kaplan-Meier method, log-rank test and Cox regression were used to estimate and compare PFS and OS. Of 1370 RCC patients, 289 had a diagnosis of nccRCC and 121 were eligible for the analysis. Fifty-three pts showed papillary histology (pRCC), 15 chromophobe; 37 unclassified RCC (NOS-RCC), 16 other histologies. Pts with chromophobe and other hystologies showed poorer survival rates compared to pRCC and NOS-RCC (mOS 10.7 vs. 20.7 vs. 30.7, p = 0.34). Pts treated with combination regimens achieved a better OS (30.7 vs. 13.7, p = 0.10), PFS (12.7 vs. 6.4, p = 0.10) and ORR (42.4% vs. 13.9%, p = 0.002) than those treated with monotherapy. IMDC and Meet-URO score retained their prognostic value. Our retrospective real-life cohort of advanced nccRCC patients shows that immunotherapy-based combinations could improve ORR, PFS and OS compared to TKI monotherapy. Prospective trials for nccRCC patients utilizing novel therapies are ongoing and their results eagerly awaited.

Abstract P2-11-12: Pattern of distant relapse according to intrinsic molecular subtype in patients with HER2-positive breast cancer: a combined analysis of ShortHER, CherLOB, and two institutional cohorts

Abstract Background: All intrinsic molecular subtypes are represented among HER2-positive breast cancer, with implications on clinical outcome and treatment sensitivity. The impact of molecular subtypes on the pattern and site of relapse is largely unexplored. Methods: 677 patients with HER2-positive early breast cancer from the Shorther trial (n=437), the CherLOB trial (n=84) and two Institutional cohorts (Istituto Oncologico Veneto IRCCS Padova n=39 and Hospital Clinic Barcelona n=117) were included. Only patients with available PAM50 intrinsic molecular subtyping were considered. We analyzed the incidence of distant relapse (at any site and at specific sites) as the first event. Cumulative incidence was estimated according to competing risk analysis (Fine and Gray’s method). Competing risk regression was used to calculate the subdistribution Hazard Ratios (subHR) and their 95% Confidence Interval (CI). Results: The distribution of molecular subtypes was: 130 LumA (19%), 75 LumB (11%), 347 HER2-e (51%), 46 Basal (7%), 79 Normal (12%). Median follow up was 8.4 years (95%CI 8.2-8.6). The 10-yr cumulative incidence rates of distant relapse as first event were: LumA 7.9%, LumB 14.8%, HER2-e 14.7%, Basal 15.5%, Normal 10.4% (HER2-e vs LumA: SubHR 2.21, 95%CI 1.05-4.64, p=0.037). Table 1 shows the 5-yr and 10-yr cumulative incidence rates of distant metastases at specific sites (as first event) according to intrinsic subtype. HER2-e enriched and Basal tumors were more prone as compared to other subtypes to develop brain and lung metastasis as first event, respectively. Isolated brain metastases without extracranial disease occurred only in patients with HER2-e tumors. All brain metastases as first event occurred within 5 years from diagnosis. Bone-only disease as first event was less frequent in HER2-e and Basal subtype (subHR HER2-e vs LumA: 0.32, 95%CI 0.10-10.4. p=0.058). Next, we analyzed the frequency of site-specific first metastasis among patients who experienced a distant metastasis as first event (n=77). Lung metastases were more frequent in Basal tumors (LumA 25.0%, LumB 20.0%, HER2-e 24.4%, Basal 71.4%, Normal 0.0%, p=0.037) and bone metastases were more frequent in Luminal tumors (LumA 100.0%, LumB 60.0%, HER2-e 31.1%, Basal 42.9%, Normal 57.1%, p=0.006). Among 45 HER2-e patients with a first distant relapse, 25.6% were diagnosed with a brain metastasis and 15.6% had brain-only disease. Conclusions: Molecular subtypes influence the metastatic behaviour of clinically HER2-positive breast cancer. These results, if further validated, may have implication in planning personalized monitoring strategies. Table 1. 5-yr and 10-yr cumulative incidence rates of distant metastasis at specific sites (as first event) according to intrinsic subtype. Citation Format: Maria Vittoria Dieci, Giancarlo Bisagni, Stefania Bartolini, Antonio Frassoldati, Daniele Giulio Generali, Federico Piacentini, Gaia Griguolo, Enrico Tagliafico, Fara Brasó-Maristany, Nuria Chic, Francesca Porra, Roberto Vicini, Roberto D’Amico, Sara Balduzzi, Aleix Prat, PierFranco Conte, Valentina Guarneri. Pattern of distant relapse according to intrinsic molecular subtype in patients with HER2-positive breast cancer: a combined analysis of ShortHER, CherLOB, and two institutional cohorts. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-12.

Multi-institutional prostate cancer unit of Padova: Review of activity and performance indicators of the first 18 months after ISO9001 certification.

337 Background: The development of Prostate Cancer Units (PCUs) determined a paradigm shift in the treatment of this disease based on multidisciplinary management and shared clinical pathways among several specialists, but activities of PCUs are rarely reported. The Multi-Institutional PCU of Padova was decreed on Nov 2020 and involves Istituto Oncologico Veneto (IOV IRCCS), Azienda Ospedaliera-University of Padova (AOPD UNIPD) and Casa di Cura of Abano Terme. Padova PCU achieved the ISO 9001 certification on Dec 2020 and performance indicators were identified. Methods: We assessed clinical indicators of coordination, process and outcome of our PCU from 1st Jan 2021 to 30 Jun 2022. Data were extracted from the Electronic Medical Record ONCOSYS and from HEALTHMEETING, the software dedicated to register clinical information of patients, shared therapeutic decisions and participation of specialists to the PCU meetings. Results: A total of 739 consecutive pts were managed by the PCU in 18 months, generating a total of 1002 case discussions in 76 meetings, for a mean of 12,8 case discussions per week. Three Urology units performed 500 prostatectomies per year. Presence of at least one specialist for each core team specialty (either in presence of teleconference) was almost 100% with the exception of the pathologists, who were consulted mainly on demand. Waiting time for case discussion was always less than 2 weeks. Pts were presented by urologist, oncologist, radiation oncologist or other specialist in 46,3, 39,8, 10,5 and 3,4% of cases, respectively. They had localized/locally advanced, biochemically recurrent, metastatic castration-sensitive or castration-resistant disease in 43.3, 8, 28.2 and 20.5% of cases, respectively. Decision by the PCU was eventually carried out in 75,5% of cases, was changed due to pt’s preference of other reasons in 6.5%, or was still pending or not assessable in 18% of cases. Median time to completion of pathology report of prostatic biopsies was 8 days, median time from surgery to adjuvant radiotherapy was 5 months. Clinical trials with investigational drugs were proposed to 17% of pts with metastatic disease. Several process and outcome indicators (e.g., rate of active surveillance, rate of combined systemic therapy in men with metastatic castration sensitive cancer, survival of patients with metastatic castration resistant disease, etc.) could not be verified yet because they could not be extracted as aggregate data from institutional software and administrative databases. Conclusions: The volumes of Padova PCU and participation rate of core team specialists fulfill international requirements. Institutional software should be implemented in order to allow for aggregate data collection for the assessment of pre-defined performance indicators of PCU instead of reviewing the clinical chart of each prostate cancer pt.

Management and Outcomes of Older Patients (Age ≥ 70 Years) with Advanced Soft Tissue Sarcoma and Role of Geriatric Assessment and Oncological Multidimensional Prognostic Index (Onco-MPI) in a Real-World Setting.

Background: Incidences of soft tissue sarcomas (STS) steadily increase with age. Yet, despite the high prevalence in advanced age, older patients (pts) are underrepresented in sarcoma clinical trials and evidence-based guidelines for chemotherapy are lacking. International oncological societies suggest using geriatric tools to evaluate older patients with cancer to optimise treatment indication. Comprehensive geriatric assessment (CGA) is a multidimensional assessment of older subjects, based on which pts can be classified as fit, vulnerable or frail. Onco-MPI (multidimensional prognostic index) is a CGA-based score which also considers tumour characteristics, classifying pts into three risk groups of death at one year: high-risk, intermediate-risk and low-risk. Methods: This is a single-centre retrospective study which aims at describing real-word management and outcomes of older pts with advanced stage STS and at assessing the ability of CGA and onco-MPI to predict survival in these pts. Consecutive pts with advanced stage STS aged 70 years or older and treated at the Istituto Oncologico Veneto from January 2009 to June 2020 were retrieved from a prospectively maintained database. Pts' demographics, CGA assessments and tumour characteristics were analysed. Statistical analysis was performed with R version 3.4.3 Results: Out of 101 pts, with a median age of 77 years, 76 received chemotherapy (75.3%), which was anthracycline-based for 46 pts (60.5%). Anthracyclines were used in a higher proportion in fit pts (58.9% fit vs. 45.1% vulnerable vs. 12.5% frail pts). Frail pts and pts in the onco-MPI high-risk group experienced a higher rate of chemotherapy-related toxicities. Median OS was 13.8 months (95% CI 11.3-17.7 months). According to CGA, the median OS was 19.53 months (95% CI 15.23-36.8) for fit pts, 12.83 months (95% CI 9.7-17.5) for vulnerable and 7.75 months (95% CI 2.73-30) for frail pts (p = 0.005). Onco-MPI confirmed a predictive value for 1-year survival with intermediate risk pts not reaching a median OS at 1 year, and high-risk pts having a median one-year OS of 11.5 months (95%CI 9.7-NA), p = 0.02. In multivariate analysis, onco-MPI and CGA were associated with survival (high risk onco-MPI: HR 5.5, 95%CI 1.25-24.7 p = 0.02; fitness at CGA HR 0.552 95% 0.314-0.973; p = 0.040) as well as chemotherapy use (HR 0.24, 95% CI 0.11-0.51, p < 0.005). Conclusions: Both CGA and onco-MPI retain prognostic value for survival in pts with metastatic STS. Pts frail/vulnerable at CGA and pts within the onco-MPI high risk category should be offered an oncogeriatric management approach in order to optimise treatment-related survival and reduce toxicity.

P566 Colitis due to immunotherapy with anti-PD-1: a case series

Abstract Background Anti-programmed death-1 (PD-1) drugs have been associated with immune-mediated gastrointestinal adverse events in 0.5-9% of the cases. The aim of this study was to investigate the characteristics of colitis occurring in oncological patients treated with anti-PD-1 drugs. Methods This is a prospective cohort study including patients referred for new onset colitis at Azienda Ospedaliera of Padua between 2020 and 2022. All patients were treated with anti-PD-1 drugs at Istituto Oncologico Veneto due to oncological disease [n=2 melanoma, n=1 colorectal cancer, n=1 pleural mesothelioma, n=14 non-small-cell lung cancer (NSCLC)]. Median duration of follow up was 10 months. Results Eighteen patients who developed diarrhea (≥G2, CTCAE) following treatment with anti-PD-1 were included (n=12 males, median age 70 years). The diarrhea began after a mean of seven months of therapy and after two to six months its discontinuation in 3/18 patients. The mean fecal calprotectin values at diarrhea onset was 1063 ug/g. Most of the patients (14/18) had their immunotherapy suspended, among them four required hospitalization. All patients were initially treated with systemic steroids (1 mg/kg). Seven patients had ulcerative colitis (UC)-like colitis (n=5 pancolitis, n=2 left colitis) while the others (60%) had microscopic colitis (MC, n=9 collagenous, n=1 lymphocytic) with unspecific inflammatory mucosal abnormalities in half of the cases. Among patients with UC-like colitis, two were hospitalized and treated with anti-TNFα because of steroid refractoriness; all remaining patients with UC-like colitis are maintaining remission with oral mesalamine or with budesonide non-MMX or low-dose systemic steroid (0.1 mg/kg). Two patients restarted anti-PD-1 drugs with no colitis relapse in the following three months, with mesalamine as maintenance therapy. Among patients who developed a MC, one required Vedolizumab as maintenance therapy, while 8/10 achieved partial or complete remission with oral budesonide non-MMX or low-dose systemic steroid. Three patients restarted anti-PD-1 drugs with no colitis relapse in the following three months, taking budesonide non-MMX as maintenance therapy. In our cohort of study all patients with MC were previously treated with anti-PD-1 drugs for NSCLC, while those with UC-like colitis were treated for NSCLC (n=4), melanoma (n=2) and colorectal cancer (n=1). Conclusion We observed a significant proportion of microscopic colitis in patients with NSCLC, while UC-like colitis was equally distributed in the other forms of neoplasia. Men are at higher risk to develop anti-PD-1 induced MC in NSCLC, rather than women. Anti-PD-1 induced microscopic colitis presents more frequently endoscopic signs of inflammation.

SIOG2022-0138 - The Mini-COG as Cognitive Screening Tool in Elderly Cancer Patients: A Monoistitutional, Prospective Experience at Istituto Oncologico Veneto (IOV)

SIOG2022-0138 - The Mini-COG as Cognitive Screening Tool in Elderly Cancer Patients: A Monoistitutional, Prospective Experience at Istituto Oncologico Veneto (IOV)

Newly Diagnosed Multifocal GBM: A Monocentric Experience and Literature Review.

Simple SummaryGlioblastoma is an aggressive brain tumor with a dismal prognosis. In a minority of cases, it presents with multiple lesions already at the time of diagnosis, affecting patients’ survival and treatment. Our retrospective study aims to increase the current understanding and define a treatment for this sub-entity, to improve patient survival. Chemoradiotherapy is a also safe and efficacy treatment in patients with multiple lesions. Survival advantages from extensive resection remain unclear.Glioblastomas with multiple foci at presentation (mGBMs) account for 2–35% of all GBMs. mGBMs have limited existing data and no standardized treatment. This study aims to determine their incidence, demographic and clinical features, outcome, and prognostic factors in terms of overall survival. We performed a monocentric retrospective study, reviewing patients treated at the Istituto Oncologico Veneto. Inclusion criteria were: new diagnosis of GBM and presence of multiple lesions on pre-treatment MRI. ECOG PS was used to evaluate clinical condition, RANO criteria for radiological assessment, and CTCAE v5.0 for treatment-related adverse events. The incidence of newly diagnosed mGBM was 7.2% and the study population consisted of 98 patients. Median age was 63 years, M:F ratio of 1.8:1, and a surgical approach was undertaken in 73 patients (mostly partial resection). MGMT was methylated in 47.5%, and 82 patients received active oncological treatment (65.9% radiotherapy plus temozolomide (RT + TMZ)). The disease control rate with RT + TMZ was 63%. Median OS of the entire study population was 10.2 months (95% CI 6.6–13.8), and median PFS was 4.2 months (95% CI 3.2–5.2). The ECOG PS, the extent of resection, and the RT + TMZ were significant prognostic factors in the univariate analysis for OS, but only the RT + TMZ was a significant independent OS predictor in the multivariate analysis (HR = 3.1, 95% IC 1.3–7.7, p = 0.014). The incidence of mGBM is not rare. RT + TMZ is confirmed to be an independent prognostic factor for survival and a safe and effective treatment. When feasible, RT + TMZ should be considered as a possible first-line treatment. The role of the extent of resection is still unclear.

Abstract PD4-01: Response according to revised RANO criteria is associated with overall survival in breast cancer patients with leptomeningeal metastasis

Abstract Introduction: Leptomeningeal metastasis (LM) is a severe complication of many solid tumors generally associated with dismal prognosis. Limited therapeutic options are available in this setting and assessment of response to treatment currently lacks validated tools. In 2017, the Response Assessment in Neuro-Oncology (RANO) LM Working Group proposed a standardized scorecard to aid in the evaluation of MRI findings in LM, which was revised and simplified in a subsequent 2019 version. To date, the prognostic impact of response to treatment evaluated according to these criteria has not been assessed in breast cancer (BC). In this study, we aim to validate this tool in a multicentric cohort of BC patients (pts) diagnosed with LM.Methods: Pts with LM from BC diagnosed at Istituto Oncologico Veneto (Padova, Italy) and Montpellier Regional Cancer Institute (Montpellier, France) between December 2005 and June 2018 were identified. Clinicopathological characteristics were collected from medical charts. Baseline and follow-up MRI scans were centrally reviewed by a dedicated radiologist and response assessment was evaluated according to the 2019 revised RANO LM response criteria (Le Rhun E. et al., Neuro-Oncology 2019).Results: A total of 225 pts diagnosed with BC-related LM were identified; among these, 142 had an available baseline brain MRI imaging and were included in the present study. Among these 142 pts, 78 had a positive cerebrospinal fluid (CSF) cytology and were classified as type I according to EANO-ESMO classification (41 type IA, 9 type IB, 28 type IC); for 64 pts CSF cytology was negative (N=25) or not performed (N=39), and were classified as type II (28 type IIA, 4 type IIB, 32 type IIC). At the time of last follow-up, 138 out of 142 pts had died and median overall survival (OS) from baseline MRI was 5.0 months (95% CI 3.4-6.7). Presence/absence of positive CSF cytology did not impact OS (median OS 5.3 versus 5.2 months, log-rank p=0.406). A total of 60 pts (positive/negative/not done CSF cytology: N=36/9/15) had an evaluable follow-up MRI imaging, with drop-off mainly due to deteriorating performance status or death. In this selected subgroup of pts, a longer OS was observed (median OS 15.2 months; 95% CI 9.5-21.0). Treatment administered for BC-related LM was heterogeneous and several pts received more than one treatment modality: systemic chemotherapy (N=44), endocrine therapy (N=27), HER2-targeted treatment (N=16), intrathecal chemotherapy (N=37) and radiotherapy (N=24). Response to treatment at time of first disease re-evaluation by brain MRI imaging was as follows: complete response for 2 pts, partial response for 12 pts, stable disease for 33 pts, and progression of disease for 13 pts. Response according to 2019 RANO criteria was significantly associated with OS (p=0.029, Table 1). Conclusions: Response assessment in pts with LM is challenging. In our study, the 2019 RANO revised response score was associated with OS in patients with LM from BC, thus validating these criteria in a real-world cohort. Response according to 2019 RANO LM criteriaMedian OS (months)OS 95% CI (months)Univariate Cox Hazard RatioUnivariate Cox Hazard Ratio 95% CIp-valueComplete Response31.1NE-NE0.100.01-0.780.028Partial Response16.10.0-37.40.410.17-0.970.043Stable Disease17.98.3-27.50.450.22-0.910.026Progression of Disease9.55.9-13.1Ref.Ref.Ref. Citation Format: Gaia Griguolo, Vittoria Aldegheri, Michele Bottosso, Francesca Caumo, Stéphane Pouderoux, Federica Miglietta, William Jacot, Maria Vittoria Dieci, Amélie Darlix, Valentina Guarneri. Response according to revised RANO criteria is associated with overall survival in breast cancer patients with leptomeningeal metastasis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD4-01.

Paternity, relationship, sexual activity and fertility in testicular cancer (TC) survivors (TCS): Results from a single institution observational prospective study.

380 Background: TC represents 1% of male neoplasms but it is the most common in young adults. Interdisciplinary management with chemotherapy, radiotherapy and surgery has led to a 10-year relative survival rate of up to 95%. These treatments (Tx) have short- and long-term side effects. While sexual dysfunction can reduce fertility, psychosocial distress can create relationship problems and finally affect the ability to procreate. Methods: From February 2020, we submitted a series of questionnaires to all the patients (pts) currently followed-up at the Istituto Oncologico Veneto free from TC recurrence for at least 2 years from the last Tx. International Index of Erectile Function (IIEF-15) and Premature Ejaculation Diagnostic Tool (PEDT) were used. We also set up a questionnaire to investigate paternity and family status. Data about disease and treatments were collected from medical records. Results: 84 TCS completed the questionnaires, clinical data are reported in the table below. 29,8% of pts fathered children before diagnosis with a strong correlation with older age at diagnosis (45,4 vs 30,8 years, p&lt;0,001). After Tx, 14 pts had children: 9 of which naturally, 2 out 6 were successful via assisted reproductive technology (ART) (including one patient that received high-dose chemotherapy and stem cell transplantation), 3 via adoption. 89,3% of pts had stable relationships. Of pts who did not have children: 13,1% claimed to be due to lack of a partner, 39,3% claimed to be unready, while 14,3% had tried unsuccessfully to conceive. While 28,6% pts claim to currently have fertility issues, only 8,3% of pts reported to have these issues before diagnosis. 70,2% of pts performed a spermiogram after Tx, 10 pts had spermatogenic impairment. Higher rate of sexual dysfunction after Tx was detected by questionnaires while only 4 pts claimed to have had a pre-existing issue prior to TC diagnosis. PEDT shows that 38,1% had premature ejaculation and that in 22,6% this issue is highly probable. IIEF confirms a high rate of erectile dysfunction (14,3% severe and 10,7% mild or moderate). No correlations were identified between sexual dysfuntion and previous Tx. Conclusions: Most TCS had not planned fatherhood while 16,7% had children after Tx and 14.3% tried unsuccessfully to conceive. ART and adoption is possible but challenging and little used. PEDT and IIEF found high rates of sexual dysfunction but no association with previous Tx were found. [Table: see text]

Extraskeletal Myxoid Chondrosarcoma: Clinical and Molecular Characteristics and Outcomes of Patients Treated at Two Institutions.

Background: Extraskeletal myxoid chondrosarcoma (EMC) is a rare subtype of STS, which usually arises in extremities. It carries reciprocal translocations involving the NR4A3 gene. It displays an indolent behavior, but studies with long follow-up showed a high proportion of local and distant recurrences. For patients with progressing metastatic disease anthracycline-based chemotherapy is the standard front-line regimen, though has limited activity. There is some evidence on possible activity of antiangiogenetics.Methods: This is a retrospective study conducted at Istituto Oncologico Veneto and at Institut Gustave Roussy. All patients with a confirmed diagnosis of EMC from January 1980 to December 2018 were extracted from a prospectively maintained database.Results: 59 patients were identified, 37 male (62.7%) and 22 female (37.3%) with a M/F ratio of 1.7/1. We performed molecular analysis in 23 cases, all carried a EWSR1-NR4A3. Out of 49 patients treated with curative intent, 28.6% developed local recurrence and 40.8% patients developed metastases. In patients who had been radically resected (R0) local recurrence occurred in 7.6% of cases and metastases occurred in 15.4% of cases; in patients treated with R1 surgery, rates of relapse were higher. Twenty patients received chemotherapy for metastatic disease; best response was partial response with clinical benefit in 50% of patients. Fourteen patients received a second line of chemotherapy, with 46.1% disease control rate. A drug holiday was proposed to 8 patients with a mean duration of 22.8 months. Median overall survival was 180 months for the study population and 76 months for metastatic patients. No significant prognostic role was found for all studied variables, yet a trend of better survival for complete surgery, location in extremities of primary tumor and solitary lung metastases was observed. Chemotherapy for metastatic disease was negatively associated with survival.Conclusion: In this large retrospective cohort of patients with ECM, location of primary tumor and solitary lung metastases seem to be associated with better survival. Chemotherapy did not impact survival in unselected patients. Further research is necessary in order to identify more active regimens and to provide clinical and molecular factors to select patients that could delay systemic treatment for metastatic disease.

Breast cancer in neurofibromatosis 1: survival and risk of contralateral breast cancer in a five country cohort study

PurposeIn the original version of this Article, the affiliation details for Medical Oncology 1 Unit, Department of Oncology, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy were incorrectly given as IOV, Oncology, Padova, Italy. This has now been corrected in both the PDF and HTML versions of the Article. MethodsWe included 142 women with NF1 and breast cancer from five cohorts in Europe and 335 women without NF1 screened for other familial breast cancers. Risk of contralateral breast cancer and death were assessed by Kaplan–Meier analysis with delayed entry. ResultsOne hundred forty-two women with NF1 were diagnosed for breast cancer at a median age of 46.9 years (range 27.0–84.3 years) and then followed up for 1235 person-years (mean = 8.70 years). Twelve women had contralateral breast cancer with a rate of 10.5 per 1000 years. Cumulative risk for contralateral breast cancer was 26.5% in 20 years. Five and 10-year all-cause survival was 64.9% (95% confidence interval [CI] = 54.8–76.8) and 49.8% (95%CI = 39.3–63.0). Breast cancer–specific 10-year survival was 64.2% (95% CI = 53.5–77.0%) compared with 91.2% (95% CI = 87.3–95.2%) in the non-NF1 age-matched population at increased risk of breast cancer. ConclusionWomen with NF1 have a substantial contralateral breast cancer incidence and poor survival. Early start of breast cancer screening may be a way to improve the survival.

Use of scalp cooling device to prevent alopecia for early breast cancer patients receiving chemotherapy: A prospective study.

Chemotherapy-induced alopecia (CIA) affects the majority of patients receiving chemotherapy (CT) for early breast cancer. It is a highly distressing side effect of CT, with psychological and social impact. Primary aim of the present analysis was to assess the efficacy of scalp cooling with DigniCap® in preventing CIA. Success rate was defined as patients' self-reported hair loss <50% according to Dean scale. In this analysis, we reported success rate at 3weeks after the first CT course and at 3weeks after the last CT course. Secondary endpoints included self-reported tolerability and patients' judgment on scalp cooling performance. Consecutive early breast cancer patients admitted to Istituto Oncologico Veneto who were recommended to receive neoadjuvant or adjuvant CT, were eligible to undergo scalp cooling during the CT administration within this study. 135 patients were included: 74% received adjuvant CT and 26% neoadjuvant CT (P<.001). The type of CT was: docetaxel-cyclophosphamide (26%), paclitaxel (23%), epirubicin-cyclophosphamide followed by paclitaxel (32%), and paclitaxel followed by epirubicincyclophosphamide (19%). The rate of success in preventing alopecia was 77% (104/135) at 3weeks from the start of CT and 60% (81/135) at 3weeks from the end of treatment. Higher success rates were reported in non-anthracycline (71%) compared to anthracycline-containing CT regimens (54%; P<0.001). Premature discontinuation of scalp cooling was reported in 29/135 patients (21.5%), including withdrawal for alopecia (16/29), for low scalp cooling tolerability (8/29) or both (5/29). Scalp cooling was generally well tolerated. These results overall suggest that the use of scalp cooling is effective in preventing alopecia in the majority of early breast cancer patients receiving neoadjuvant or adjuvant CT, especially for patients undergoing a taxane-based non-anthracycline regimen.

144P - Circulating biomarkers and risk of immune-related adverse events (irAEs) in patients (pts) with advanced non-small cell lung cancer (aNSCLC) and metastatic melanoma (mMel)

BackgroundImmune checkpoint inhibitors (ICIs) have changed the treatment of pts with aNSCLC and mMel. No predictive markers of development of irAEs are available. Aim of the study is to evaluate the role of circulating markers in predicting irAE onset. MethodsWe reviewed clinical data of aNSCLC and mMel pts treated with ICIs at Istituto Oncologico Veneto (Padova, Italy) and San Bortolo Hospital (Vicenza, Italy) between January 2012 and January 2019. We collected data on type and grading (G) of irAEs and calculated neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) before first ICI administration and at irAE onset. Values were dichotomized in: high (H) and low (L) NLR and H- and L-PLR, using pre-identified cut-offs of 3 and 180 for aNSCLC, 3 and 120 for mMel. ResultsAnalysis included 377 pts (252 aNSCLC and 125 mMel). In aNSCLC cohort, median PFS and OS were 4.9 months (m) (95% CI: 3.6-6.1) and 8.6m (95% CI: 6.3-10.8). Ninety-seven pts (38%) developed irAEs, mainly G1-2 (72%), with permanent ICI discontinuation in 29 (29.9%) cases; 26 pts (26.8%) experienced more than one irAE. Pts with baseline L-NLR or L-PLR had a higher risk of irAE (OR=2.3, 95% CI: 1.3-3.9, p=0.002 | OR=2.4, 95% CI: 1.3-4.1, p=0.02). Multivariate analysis confirmed NLR and PLR as independent predictive markers (OR=1.8, 95%CI: 1.0-3.2, p=0.04 | OR=1.9, 95%CI: 1.0-3.4, p=0.03). L-PLR at irAE onset was associated with risk of irAE recurrence or second irAE development (OR=4.2, 95% CI: 1.4-12.9, p=0.01). In mMel pts, median PFS and OS were 5.1m (95% CI: 3.6-6.5) and 18.1m (95% CI: 11-25.2). Fifty-four pts (43%) developed irAEs, mainly G1-2 (76%), with permanent ICI discontinuation in 10 (18.5%) cases; 14 pts (25.9%) had multiple irAEs. Pts with baseline L-NLR had higher risk of irAE (OR=2.2, 95% CI: 1.1-4.6, p=0.04). NLR and PLR at time of irAE onset were not associated with the risk of irAE recurrence or second irAE development. ConclusionsBaseline NLR and PLR may be reliable and inexpensive predictive tools of irAE risk. For aNSCLC pts L-PLR at irAE onset correlates with risk of further toxicity. If validated, these biomarkers may help pts’ management during ICIs and treatment handling after a first irAE. Legal entity responsible for the studyIRCCS Istituto Oncologico Veneto - IOV - Padua – Italy. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

BMI is an independent prognostic factor for late outcome in patients diagnosed with early breast cancer: A landmark survival analysis

BMI is an independent prognostic factor for late outcome in patients diagnosed with early breast cancer: A landmark survival analysis

Androgen Receptor Expression and Association With Distant Disease-Free Survival in Triple Negative Breast Cancer: Analysis of 263 Patients Treated With Standard Therapy for Stage I-III Disease.

Background: We evaluated immunohistochemical AR expression and correlation with prognosis in a large series of homogeneously treated patients with primary TNBC.Material and Methods: Patients diagnosed with stage I-III TNBC between 2000 and 2015 at Istituto Oncologico Veneto who received treatment with surgery and neoadjuvant and/or adjuvant chemotherapy were included. Whole tissue slides were stained for AR. AR-positive expression was defined as >1% of positively stained tumor cells. Distant-disease-free survival (DDFS) was calculated from diagnosis to distant relapse or death. Late-DDFS was calculated from the landmark of 3 years after diagnosis until distant relapse or death.Results: We included 263 primary TNBC patients. Mean AR expression was 14% (range 0–100%), and 29.7% (n = 78) of patients were AR+. AR+ vs. AR- cases presented more frequently older age (p < 0.001), non-ductal histology (p < 0.001), G1-G2 (p = 0.003), lower Ki67 (p < 0.001) and lower TILs (p = 0.008). At a median follow up of 81 months, 23.6% of patients experienced a DDFS event: 33.3% of AR+ and 19.5% of AR- patients (p = 0.015). 5 years DDFS rates were 67.2% and 80.6% for AR+ and AR- patients (HR = 1.82 95%CI 1.10–3.02, p = 0.020). AR maintained an independent prognostic role beyond stage, but when TILs were added to the model only stage and TILs were independent prognostic factors. AR was the only factor significantly associated with late-DDFS: 16.4% of AR+ and 3.4% of AR- patients experienced a DDFS after the landmark of 3 years after diagnosis (p = 0.001). Late-DDFS rates at 5 years from the 3-year landmark were 75.8% for AR+ and 95.2% for AR- patients (log-rank p < 0.001; HR = 5.67, 95%CI 1.90–16.94, p = 0.002).Conclusions: AR expression is associated with worse outcome for patients with TNBC. In particular, AR+ TNBC patients are at increased risk of late DDFS events. These results reinforce the rationale of AR targeting in AR+ TNBC.

Abstract P4-08-04: PD-L1 expression and prognosis in triple negative breast cancer (TNBC): An analysis of 265 patients (pts) treated with standard therapy for stage I-III disease

Abstract Background: Targeting the PD-L1/PD-1 axis has proved to be effective in various cancers, including promising data for metastatic TNBC pts. The evaluation of PD-L1 expression is limited by the lack of standardized methods. Here we sought to evaluate the prognostic role of PD-L1 expression in a large cohort of patients with non-metastatic TNBC treated with standard therapy. Methods: Consecutive patients diagnosed with stage I-III TNBC (ER and PgR &amp;lt;10%, HER2 0/1+ or ISH non amplified) between May 2012 and December 2015 and treated at the Istituto Oncologico Veneto of Padova were included. All patients received treatment with surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (when indicated). For each case, one FFPE tumor slide was stained for PD-L1 with the PD-L1 IHC 73-10 Research Use Only assay developed by Agilent Technologies and one slide was stained for cytokeratins with MNF116 (to distinguish MNF116+ tumor cells from MNF116- stromal cells). Digital slides were evaluated by a specifically-developed Visiopharm® software application. Following alignment of the PD-L1 and MNF116 digital slides, the software analyzed PD-L1 expression on tumor cells (% of positively stained tumor cells/total tumor cells) and stromal cells (% of positively stained stromal cells/total stromal cells). Disease-free survival (DFS) was calculated from diagnosis to relapse or death. In survival analyses, PD-L1 was evaluated as continuous and categorical variable. Results: 265 TNBC pts were evaluated. Median PD-L1 was 2.6% (Q1-Q3 0%-18.6%) on tumor cells and 5.2% (Q1-Q3 0.2%-25.4%) on stromal cells. PD-L1 levels on tumor and stromal cells were positively correlated (spearman's 0.938, p&amp;lt;0.001). For further analyses, PD-L1 on stromal cells was considered. Higher PD-L1 was associated with age &amp;lt;50 yrs (p=0.011), Grade 3 (p=0.003) and Ki67 &amp;gt;30% (p=0.005). Lower PD-L1 was observed in lobular and apocrine tumors (p=0.001).Cox model for DFS showed HR=0.99 (95%CI 0.97-1.00, p=0.059) for every 1% PD-L1 increment. 3-yrs DFS was 86% for pts with PD-L1&amp;gt;20% (n=88, 29%) vs 75% for pts with PD-L1&amp;lt;20% (n=177, 71%): HR 0.52, 95%CI 0.28-0.97, p=0.039. PD-L1 at 20% cut-off maintained prognostic value in multivariate model including stage (HR 0.48, 95%CI 0.25-0.89, p=0.021). Of the 265 pts included, 108 received neoadjuvant chemotherapy (NACT). Of the 78 pts with residual disease after NACT, 61 had pre- and post-NACT samples evaluable for PD-L1. PD-L1 increased from pre- to post-NACT: median 2.7% (Q1-Q3 0%-26.9%) vs 20.1% (Q1-Q3 5.9%-41.4%), p&amp;lt;0.001. Pts with PD-L1&amp;gt;20% post-NACT showed improved DFS: 3-yrs DFS 68% vs 43% (HR 0.44, 95%CI 0.20-0.96, p=0.039), whereas PD-L1 pre-NACT did not show significant association with DFS in this subgroup (HR 0.47, 95%CI 0.23-1.40, p=0.218). Conclusions: PD-L1 expression evaluated with a software-assisted method was prognostic for stage I-III TNBC pts treated with standard therapy. The significant increase of PD-L1 on residual disease post-NACT supports the rationale to evaluate the efficacy of anti-PD-L1 drugs in this high-risk population. Citation Format: Dieci MV, Orvieto E, Tsvetkova V, Griguolo G, Miglietta F, Bonaguro S, Tasca G, Giorgi CA, Cumerlato E, Guarneri V, Conte P. PD-L1 expression and prognosis in triple negative breast cancer (TNBC): An analysis of 265 patients (pts) treated with standard therapy for stage I-III disease [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-04.

Prevalence of pain in patients with cancer aged 70 years or older: A prospective observational study.

Pain is a common symptom among patients with cancer, yet pain prevalence and management in older cancer pts. are poorly known. Patients aged ≥70 years referred to Istituto Oncologico Veneto IRCCS from January 2011 to December 2013 were evaluated with Comprehensive Geriatric Assessment (CGA). Pain was assessed by means of short form of McGill Pain Questionnaire (MPQ-sf), Brief Pain Inventory (BPI-sf), and numerical rating scale (NRS). Pts with completed CGA, no severe cognitive impairment and completed pain assessment were enrolled. Enrolled patients were 745; 51% male, median age 76 years, median ECOG Performance Status (PS) 1. Frail patients at CGA were 45.2%. Patients with pain were 266 (35.7%). Mean Average Pain Intensity (API) was significantly higher among females, patients fit at CGA, with advanced disease, poorer PS and more comorbidity. Pain was detected by the oncologist in 20.4% of cases and deemed cancer-related in 54.8%. Gender, PS, status of disease, stage, function disability, mood, cognitive functioning and frailty were significantly associated with reporting of pain. At BPI, moderate-severe pain was found in 81 patients. The degree of agreement between API and pain intensity evaluated by physician was minimal. Patients on pain medications were 184, with 113 patients reporting rates of pain relief ≥50%. About one third of older patients with cancer report pain, which is not cancer-related in about half of cases. Female gender, fitness at CGA, advanced stage, poorer PS, higher number of comorbidities and primary site were associated with significant differences in pain reporting.