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Hepatic resection is the gold standard treatment for patients affected by liver-limited colorectal metastases. Reports addressing the impact of multidisciplinary team (MDT) evaluation on survival are controversial. The aim of this study was to evaluate the benefit of MDT management in these patients in our Institution experience. The objective of the analysis was to compare survivals of patients managed within our MDT (MDT cohort) to those of patients referred to surgery from other hospitals without MDT discussion (non-MDT cohort). Of the 523 patients, 229 were included in the MDT cohort and 294 in the non-MDT cohort. No difference between the two groups was found in terms of median overall survival (52.5 vs 53.6 months; HR 1.13; 95% CI, 0.88–1.45; p = 0.344). In the MDT cohort there was a higher number of metastases (4.5 vs 2.7; p p p

Background: Recently, CDK4/6i proved to improve the efficacy of HT of pts affected by luminal MBC. However, the best sequence of HT is still unclear and it is still uncertain if pts with lobular histology derive the same benefit of ductal when receiving second line CDK4/6i. Particularly in lobular MBC, the dysregulation of the AKTpathway with the overexpression of cyclin E potentially represents an important mechanism of acquired resistance to HT, finally providing an intrinsic resistance to subsequent CDK4/6i. Thus, a multicentric retrospective study was conducted to determine the efficacy of PALBO-FUL versus EVE-EXE as second line HT of MBC with Lobular histology.Methods: Pts affected by Lobular MBC receiving PALBO-FUL or EVE-EXE for second line HT from 2013 to 2018 in 6 Italian centers were considered eligible. The primary endpoint was progression free survival (PFS). A propensity score (PS) adjustment for baseline characteristics was further accomplished for survival analysis. Results: Seventy-four of 376 screened pts were diagnosed for Lobular MBC; 46pts received PALBO-FUL, whereas 28 were treated with EVE-EXE, without imbalance in clinical characteristics. PFS resulted to be significantly longer for pts receiving EVE-EXE in comparison with PALBO-FUL (6.1 vs. 4.5 months, HR 0.58, 95% CI 0.35-0.96; p=0.025). Previous chemotherapy exposure resulted to be significantly associated with PFS at the multivariate analysis (HR 0.41, 95% CI 0.24-0.72, p=0.002). At the PS analysis, adjusted for previous chemotherapy exposure and synchronous/metachronous metastatic status, PFS was confirmed to be significantly longer for pts receiving EVE-EXE in comparison with PALBO-FUL (6.0 vs. 4.6 months, p=0.04)Conclusion: This retrospective real-world analysis generates the hypothesis of a potential benefit of EVE-EXE in comparison with PALBO-FUL for second line HT of MBC with Lobular histology. Nevertheless, the small pts’ sample calls for a larger and adequately sized prospective validation. However, these data allow to speculate on the best hormonal therapeutic sequence in MLBC. Indeed, in this setting a late exposure to CDK4/6i might not allow to exploit its efficacy, while once hormonal resistance is acquired the inhibition of AKT/m-TOR pathway may represent the best option. Citation Format: Armando Orlandi, Elena Iattoni, Laura Pizzuti, Agnese Fabbri, Andrea Botticelli, Carmela Di Dio, Antonella Palazzo, Giovanna Garufi, Giulia Indellicati, Daniele Alesini, Luisa Carbognin, Ida Paris, Angela Vaccaro, Luca Moscetti, Alessandra Cassano, Patrizia Vici, Valentina Magri, Giuseppe Naso, Diana Giannarelli, Paolo Marchetti, Emilio Bria, Giampaolo Tortora. Palbociclib-fulvestrant (PALBO-FUL) and everolimus -exemestane (EVE-EXE) for second line hormonal treatment (HT) of metastatic breast cancer (MBC) with lobular histology: A propensity score matched analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-43.

Background: Organs at risk (OARs) delineation is a crucial step of radiotherapy (RT) treatment planning workflow. Time-consuming and inter-observer variability are main issues in manual OAR delineation, mainly in the head and neck (H & N) district. Deep-learning based auto-segmentation is a promising strategy to improve OARs contouring in radiotherapy departments. A comparison of deep-learning-generated auto-contours (AC) with manual contours (MC) was performed by three expert radiation oncologists from a single center. Methods: Planning computed tomography (CT) scans of patients undergoing RT treatments for H&N cancers were considered. CT scans were processed by Limbus Contour auto-segmentation software, a commercial deep-learning auto-segmentation based software to generate AC. H&N protocol was used to perform AC, with the structure set consisting of bilateral brachial plexus, brain, brainstem, bilateral cochlea, pharyngeal constrictors, eye globes, bilateral lens, mandible, optic chiasm, bilateral optic nerves, oral cavity, bilateral parotids, spinal cord, bilateral submandibular glands, lips and thyroid. Manual revision of OARs was performed according to international consensus guidelines. The AC and MC were compared using the Dice similarity coefficient (DSC) and 95% Hausdorff distance transform (DT). Results: A total of 274 contours obtained by processing CT scans were included in the analysis. The highest values of DSC were obtained for the brain (DSC 1.00), left and right eye globes and the mandible (DSC 0.98). The structures with greater MC editing were optic chiasm, optic nerves and cochleae. Conclusions: In this preliminary analysis, deep-learning auto-segmentation seems to provide acceptable H&N OAR delineations. For less accurate organs, AC could be considered a starting point for review and manual adjustment. Our results suggest that AC could become a useful time-saving tool to optimize workload and resources in RT departments.

Background: Previous locoregional treatment could affect the response to nivolumab in platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). The aim of this study is to evaluate the impact of the clinicopathological characteristics and previous treatment in predicting early progression to nivolumab in a real-world population. Methods: This is an observational, multicenter retrospective/prospective study including patients (pts) with platinum refractory R/M HNSCC who received nivolumab 240 mg every 2 weeks from October 2018 to October 2019. We analyzed the association between previous treatment, clinicopathological characteristics, and early progression (within 3 months). Results: Data from 61 pts were reviewed. Median age was 67 years (30&ndash, 82). Forty-two pts (69%) received previous locoregional treatment. Early progression to nivolumab occurred in 36 pts (59%), while clinical benefit (stable disease and partial response) was achieved in 25 pts (41%). Early progression to nivolumab was significantly associated to previous locoregional treatment both at univariate and multivariate analysis (p = 0.005 and p = 0.048, respectively). Conclusion: nivolumab in R/M HNSCC is burdened with a high early progression rate. Previous wide neck dissection and high dose radiotherapy may compromise the efficacy of nivolumab, distorting the anatomy of the local lymphatic system and hindering the priming of immune response.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) show meaningful efficacy and tolerability in patients with metastatic breast cancer (MBC), but the optimal sequence of ET has not been established. It is not clear if patients with lobular breast carcinomas (LBC) derive the same benefits when receiving second line CDK4/6i. This retrospective study compared the efficacy of palbociclib plus fulvestrant (PALBO&ndash, FUL) with everolimus plus exemestane (EVE&ndash, EXE) as second-line ET for hormone-resistant metastatic LBC. From 2013 to 2018, patients with metastatic LBC positivity for estrogen and/or progesterone receptors and HER2/neu negativity, who had relapsed during adjuvant hormonal therapy or first-line hormonal treatment, were enrolled from six centers in Italy in this retrospective study. A total of 74 out of 376 patients (48 treated with PALBO&ndash, FUL and 26 with EVE&ndash, EXE) with metastatic LBC were eligible for inclusion. Progression-free survival (PFS) was longer in patients receiving EVE&ndash, EXE compared with PALBO&ndash, FUL (6.1 vs. 4.5 months, univariate HR 0.58, 95% CI 0.35&ndash, 0.96, p = 0.025). On the propensity score (PS) analysis, PFS was confirmed to be significantly longer for patients treated with EVE&ndash, EXE compared to PALBO&ndash, FUL (6.0 vs. 4.6 months, p = 0.04). This retrospective analysis suggests that EVE&ndash, EXE is more effective than PALBO&ndash, FUL for second line ET of metastatic LBC, allowing us to speculate on the optimal therapeutic sequence.

L’utilizzo di lapatinib in combinazione con capecitabina è associato in alcune pazienti a tossicità gastrointestinale e cutanea, che ne compromette la regolare assunzione limitando l’utilizzo di un’efficace schedula terapeutica nel carcinoma metastatico della mammella HER2-positivo, refrattario al trattamento con trastuzumab. I due casi clinici presentati mostrano il buon profilo di tossicità e l’efficacia della combinazione lapatinib (1250 mg/die) + capecitabina metronomica (500 mg 3 volte/die) (Oncology).

Everolimus and exemestane represent a standard treatment for metastatic hormone receptor-positive/HER2-negative advanced breast cancer resistant to aromatase inhibitors. CA 15–3 serum levels detect soluble forms of MUC-1, a transmembrane oncoprotein aberrantly overexpressed in breast cancers. In clinical practice, CA 15–3 may be used to indicate treatment failure in the absence of readily measurable disease during cytotoxic therapy. In the targeted therapy era, it is important to note that the C-terminal subunit of MUC-1 interacts with PI3K/AKT pathway, inducting cell growth. Vice versa, the block of this pathway may influence MUC-1 expression and CA 15–3 serum levels. In this report, we emphasize the equivocal role of CA 15–3 serum levels in monitoring treatment with everolimus, suggesting a potential and intriguing role of a CA 15–3 increase as paradox predictive biomarker of response to everolimus.

e18508 Background: Immunotherapy is the standard of care in the treatment of platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC). Previous loco-regional treatment could have an impact on the immune system and response to Nivolumab. The aim of this study is to evaluate the efficacy and safety of Nivolumab in a real world population, identifying the impact of the clinic-pathological characteristics and previous treatment in prediction of early progression. Methods: This is a observational, multicenter retrospective/prospective study including patients (pts) with platinum refractory R/M HNSCC who received Nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity, from October 2018 to October 2019. We analyzed treatment outcomes in term of early progression (within 3 months), clinical benefit, progression free survival (PFS) and overall survival (OS). To determine the influence on outcomes, the following variables were investigated: primary tumor sub-site, age, gender, ECOG, previous loco-regional treatment, previous systemic therapy, metastatic site. Results: Data from 61 pts were reviewed: 15 oral cavity, 14 oropharynx, 7 hyphofarynx, 19 larynx, 6 paranasal sinus. Median age was 66 years (29-82), 48 pts were men. Forty-nine pts (80%) had performance status (ECOG) ≥ 1 at baseline evaluation. Eleven pts (18%) had only loco-regional recurrence, while 50 pts (82%) had one or more metastatic site. 32 (52%) and 17 pts (28%) had smoking and alcohol abuse history, respectively. 44 pts (72%) received surgery followed by adjuvant radiant treatment at standard dose (28, 46%) or concomitant definitive radiotherapy (16, 26%) as upfront treatment with curative intent. With a median follow up of 4 months (range 1-11), early progression occurred in 39 pts during Nivolumab treatment (64%), while clinical benefit (stable disease and partial response) was achieved in 22 pts (36%). No G3-G4 toxicities occurred. Early progression to Nivolumab was significantly associated to previous loco-regional treatment both at univariate and multivariate analysis (p=0.003 and p= 0.04, respectively). Conclusions: Nivolumab in R/M HNSCC is effective and safe even though burdened with a high early progression rate. Loco-regional treatment, including wide neck dissection and high dose radiotherapy, may compromise the efficacy of Nivolumab, distorting the anatomy of the local lymphatic system and hindering the priming of immune response.

The RAINBOW Phase III study established the efficacy of the combination of paclitaxel and ramucirumab, a monoclonal antibody targeting VEGF receptor-2 (VEGF-R2), as second-line therapy. We retrospectively analyzed the data of patients treated with ramucirumab plus paclitaxel at our Institution to evaluate the impact of clinical heterogeneous figures on the efficacy and safety of this combination paclitaxel/ramucirumab in a real- life cohort of patients. After a median follow-up of 10.74 months, the median progression-free survival (PFS) was 5.8 months (95% CI: 3.04 - 5,63). Disease control rate (DCR) was 61% and the median duration of response (DOR) was 5.8 months. Median overall survival (OS) was 8.3 months. A trend toward better outcome was observed in HER2 positive patients. In multivariate analysis, nutritional status (p = 0.0001) and number of metastatic sites (p = 0.0266) resulted significantly related with longer PFS. Our analysis confirmed the efficacy and safety of the combination of ramucirumab with paclitaxel also in the real-life practice and the median PFS is significantly longer than that reported for Western population in previous studies. Subgroup analysis confirms the key-role of nutritional status as prognostic factor and suggests a possible interaction between EGF and angiogenesis pathways that deserves further investigations.

Oesophageal gastrointestinal stromal tumors (GISTs) are rare neoplasms (about 2% of all GISTs); radical surgery is the standard treatment of all GISTs but in case of locally advanced and unresectable disease no clear treatment guide lines are available. Studies including neoadjuvant imatinib mesylate (IM) are relatively recent, includes small sample size of heterogeneous patients and do not report a standardized duration of neoadjuvant treatment. The main question still remains whether surgery after neoadjuvant IM gives a survival benefit in locally advanced disease. A 46-year-old man with locally advanced unresectable oesophageal GIST harboring KIT exon 11 mutation was treated in our institution for 12 months with neoadjuvant IM; a reduction of 83% of tumor volume was obtained in 9-month of neoadjuvant IM, but in the last 3 months no further response was seen. After neoadjuvant therapy, patient underwent radical surgery and adjuvant IM, which is still ongoing. Since no definitive data are available about survival benefit of surgery after neoadjuvant IM in locally advanced GISTs, a careful balance between morbidity and mortality derived from surgery should be considered and more studies are needed to better define the utility and the optimal duration of neoadjuvant treatment.

97 Background: Surgery is the only potentially curative treatment for LAGC. Evidences suggest that perioperative CT (pCT) plus surgery is superior to surgery alone, whereas studies on adjuvant CT (aCT) are controversial. Guidelines recommend a pCT approach in pts with stage II/III, nevertheless in real-life many pts receive immediate surgery followed by aCT. Histology influences both survival and pathological response with worse prognosis among diffuse LAGC. No trial has compared pCT and aCT or investigated the impact of histology on the outcome of these different approaches. We hypothesized that histology may predict a different benefit from CT administered in the two settings, allowing to define the optimal strategy. We performed a study comparing the two approaches according to histology. Methods: We retrospectively analyzed pts with stage II/III LAGCs treated at our Institution between Jan-09 and Jan-17. The objective of the study was to evaluate the impact of histology (intestinal and diffuse) on survival according to strategy approach (pCT vs aCT). Primary endpoints were DFS and OS. Results: 81 pts had diffuse LAGC (29 received pCT, 52 aCT) and 60 had intestinal LAGC (32 received pCT, 29 aCT). In the intestinal cohort both DFS and OS were significantly higher in pts treated with pCT compared to aCT (DFS: HR 0.3, p = 0.02; OS: HR 0.3, p = 0.03). On the contrary in the diffuse cohort both DFS and OS were significantly lower in pts receiving pCT compared to those receiving aCT (DFS: HR 2.4, p = 0.0014; OS: HR 2.6, p = 0.0012). Conclusions: Our study, although retrospective and small-sized, shows that the survival benefit of pCT is limited to intestinal LAGC, whereas in diffuse LAGC the administration of pCT appears detrimental. Indeed, diffuse LAGC is known to be chemoresistant and pCT might delay surgery allowing metastasization. Despite the arising of recent molecular classification, still far from modifying clinical practice, histotype might represent an easy factor to discriminate pts benefitting from pCT (intestinal) to those in whom upfront surgery might be recommended (diffuse). Our hypothesis needs to be confirmed in prospective trials.

671 Background: Hepatic resection is the gold standard treatment for pts with liver-limited mCRC with 5- and 10-yrs survival rates reaching up to 60% and 20%. Although multidisciplinary team (MDT) management might ensure a more accurate assessment of pts and a faster referral to surgeons, reports discussing the impact of MDTs on survival are controversial and to date there are no strong evidences supporting routinely MDT discussion. The aim of this study was to evaluate the benefit of MDT management in pts with liver-limited mCRC in our single institution experience. Methods: Clinical records of pts with liver-limited mCRC who underwent radical surgery at Fondazione Policlinico “A. Gemelli” - IRCCS from Jan-2006 to Dec-2016 were retrospectively analyzed. The objective of the analysis was to compare survivals of pts managed within our MDT (MDT cohort) to those of pts referred to surgery from other hospitals without MDT discussion (non-MDT cohort). Primary endpoints were DFS and OS. Differences in baseline characteristics and in post-operative morbidity were evaluated. Results: Of the 619 pts analyzed, 230 were included in the MDT cohort and 389 in the non-MDT cohort. No significant difference between the two groups was found in terms of DFS (12vs11 m; p 0.09) and OS (55vs51 m; p 0.68). Concerning baseline characteristics, in the MDT cohort compared to non-MDT cohort there was a statistically higher number of median metastases (4.5vs2.6; p < 0.0001) and a higher rate of synchronous metastases (61.7vs39.3%; p < 0.001). Despite pre-operative CT rate was higher in the MDT group (75.8vs70.7%), the median duration of CT before surgery was significantly lower in MDT pts (7 vs 8 cycle; p < 0.001). Moreover, post-operative morbidity was significantly lower in the MDT cohort (6.2vs19.2%; p < 0.00001). Conclusions: Our study does not demonstrate a survival benefit from MDT management of pts with liver limited mCRC. However, the analysis shows that MDT assessment allows to consider eligible for surgery pts with a more advanced disease. Moreover, MDT discussion seems to reduce the median duration of pre-operative CT with a consequent lower rate of post-operative morbidities. Our data warrant prospective validation.

669 Background: Nowadays the optimal treatment for mCRC beyond second line is still questioned. During last years, regorafenib and TAS-102 showed to improve survival compared to best supportive care in pts with refractory mCRC. Recently, some retrospective analyses compared the efficacy and safety of regorafenib and TAS-102 reporting no significant differences in survival and response outcomes. In real-world clinical practice, chemotherapy (CT) rechallenge is often considered for refractory mCRC. However, evidences regarding CT rechallenge is limited and no study has previously compared such approach with the recently approved antineoplastic agents in late lines. The aim of this study was to compare the efficacy between CT rechallenge and regorafenib in pts with refractory mCRC. Methods: This is a mono-institutional retrospective study. We compared the efficacy of FOLFOX rechallenge and regorafenib in pts with mCRC refractory to at least 2 lines of standard CT, treated at Fondazione Policlinico Universitario “A. Gemelli”-IRCCS between Jan-10 and Jan-18. The primary endpoint was OS. Secondary endpoints were RR and PFS. Results: One hundred thirty-one pts received regorafenib and 43 FOLFOX rechallenge. OS was significantly higher with FOLFOX rechallenge than it was with regorafenib (13 vs. 6 months; HR 0.67, 95% CI 0.33-0.66; p = 0.0002). PFS was significantly higher in the FOLFOX rechallenge group compared to the regorafenib group (5 vs. 3 months; HR 0.64, 95% CI 0.46-0.89; p = 0.0073). Accordingly, RR was better in pts receiving FOLFOX rechallenge compared to regorafenib (25 vs. 3%; Chi-square p < 0.0001). Conclusions: Our study, although retrospective and small-sized, compared for the first time to our knowledge the efficacy of CT rechallenge to regorafenib in refractory mCRC. In our analysis, CT rechallenge with FOLFOX proved to be superior compared to regorafenib, with a survival and response benefit in pretreated mCRC. The survival benefit observed for rechallenge might be explained by the significantly higher tumor shrinkage achieved with CT rechallenge compared to regorafenib. Our results warrant further confirmation in wider and/or prospective analyses.

e15295 Background: Human equilibrative nucleoside transporter 1 (hENT1) is a transmembrane protein which acts as a nucleoside transporter and represents the main mediator of gemcitabine (GEM) uptak...