Synchronous Metastases Research Articles

Renal Tumor Size and Presence of Synchronous Lung Metastasis at Time of Diagnosis: Implications for Chest Imaging

ObjectiveTo quantify synchronous lung metastasis risk based on renal tumor size and determine a renal tumor size threshold to determine when chest imaging is warranted. MethodsWe assessed 253,838 patients diagnosed with a renal tumor who underwent staging chest imaging between 2010 and 2016 within the National Cancer Database. Patients were stratified by renal tumor size in 10 mm increments, and synchronous lung metastasis risk was calculated for each category. Logistic regression analyses were used to test the relationship between renal tumor size and presence of synchronous lung metastasis after adjusting to all available covariables. ResultsOverall, 14,524 out of 253,838 (5.7%) patients had evidence of synchronous lung metastasis. Median (IQR) tumor size for patients with vs without sLM was 90 mm (65-115) vs 40 mm (25-60), respectively. The incidence of synchronous lung metastasis was low for renal tumors <40 mm, without significant change, based on tumor size. Conversely, synchronous lung metastasis increased proportionally to renal tumor size for lesions ≥40 mm. In our cohort, 47% of patients (120,386/253,838) had a renal tumor <40 mm, and 0.9% (1,135/120,386) of these had patients had synchronous lung metastasis. Only 8% (1,135/14,524) of patients with synchronous lung metastasis had a renal tumor <40 mm. ConclusionThe risk of synchronous lung metastasis increased proportionally to renal tumor size; however, the risk was low for tumors <40 mm. These findings suggest that there may be minimal utility of performing screening chest imaging for patients with renal tumors <40 mm.

The incidence, risk factors and predictive nomograms for early death of lung cancer with synchronous brain metastasis: a retrospective study in the SEER database

BackgroundThe prognosis of lung cancer with synchronous brain metastasis (LCBM) is very poor, and patients often die within a short time. However, little is known about the early mortality and related factors in patients with LCBM.MethodsPatients diagnosed with LCBM between 2010 and 2016 were enrolled from the Surveillance, Epidemiology, and End Result (SEER) database. Univariate and multivariate logistic regression analysis were used to identify significant independent prognostic factors, which were used to construct nomograms of overall and cancer-specific early death. Then, the prediction ability of the model was verified by receiver operating characteristic (ROC) curve. At last, the clinical application value of the model was tested through decision curve analysis (DCA).ResultsA total of 29,902 patients with LCBM were enrolled in this study. Among them, 13,275 (44.4%) patients had early death, and 11,425 (38.2%) cases died of lung cancer. The significant independent risk factors for overall and cancer-specific early death included age, race, gender, Gleason grade, histological type, T stage, N stage, bone metastasis, liver metastasis and marital status, which were used to construct the nomogram. The ROC curve demonstrated good predictive ability and clinical application value. The areas under the curve (AUC) of the training group was 0.793 (95% CI: 0.788–0.799) and 0.794 (95% CI: 0.788–0.799), in the model of overall and cancer-specific early death respectively. And the AUC of the validation group were 0.803 (95% CI: 0.788–0.818) and 0.806 (95% CI: 0.791–0.821), respectively. The calibration plots of the model showed that the predicted early death is consistent with the actual value. The DCA analysis indicated a good clinical application value of this model.ConclusionsWe established a comprehensive nomogram to predict early death in lung cancer patients with synchronous brain metastases. Nomograms may help oncologists develop better treatment strategies, such as clinical trials and hospice care.

P-171 Does metastasectomy really improve survival in gastric cancer?

Previous observational studies suggest that metastasectomy improves overall survival (OS) for patients with metastatic gastric/gastroesophageal junction cancer (mG/GEJC). However, most conclusions were based on comparisons of distinct populations, with surgery groups having favorable characteristics that could have influenced the results. All consecutive patients with mG/GEJC who underwent metastasectomy in our institution were retrospectively recruited. After, a non-metastasectomy control group, with a single site of metastasis and ECOG 0-1, was paired in a 1:1 ratio by the nearest neighbor propensity score matching method, using the following pairing categories: age at diagnosis < 60 years vs ≥ 60 years; intestinal vs diffuse subtype; synchronous vs metachronous metastasis; peritoneal vs other site of metastasis. The primary objective was to compare the overall survival (from the metastasis diagnosis to death by any cause) between the groups. Secondarily, prognostic factors associated with OS were evaluated. Time-to-event variables were analyzed by Kaplan-Meier curves and compared by Log-rank test. Cox regression was used for multivariable analysis. Between September 2007 to January 2020, 138 mG/GEJC patients were included (69 in each group). The median follow-up was 37 months. The median age at diagnosis was 54 years (31% were ≥ 60 years old); most were men (57.2%), with comorbidities (55.1%) and without malnutrition (only 8.7%). Gastric cancer (88.4%), diffuse subtype (65.2%), synchronous (77.5%) and peritoneal metastasis (65.2%) were predominant. The characteristics between the metastasectomy and the control group were well balanced, with a non-significant increased proportion of GEJC in the control group (17.4% vs 5.8%, p=0.06). Patients who underwent metastasectomy were more exposed to FLOT and less exposed to FOLFOX regimens (16.4% vs 3.0% and 37.3% vs 52.2%, respectively; p=0.048); and tended to receive triplet regimens more often (41.8% vs 29.9%; p=0.207). The median OS was superior in the metastasectomy group (26.0 vs 14.0 months; HR 0.52, 95%CI 0.35-0.78; p=0.001), as it was the median progression-free survival in first-line (12.0 vs 6.0 months; HR 0.56, 95%CI 0.39-0.80; p=0.001). The median time between the metastasectomy to death was 17.0 months (95%CI 11.4-22.6) and this was not influenced by triplet vs doublet schemes or by the metastasectomy site (peritoneal vs others, linfonodal vs others, or visceral vs non-visceral). Data were immature to evaluate the influence of type of perioperative chemotherapy on these results. Metastasectomy, FLOT regimen and ECOG 0 were independent prognostic factors for improved overall survival in multivariate analysis. Metastasectomy in gastric/gastroesophageal junction cancer was associated with improved overall survival, even when compared to a matched-paired population of metastatic patients with a favorable prognostic profile. This study reinforces the importance of considering this approach, when reasonable, for mG/GEJC patients.

The clinicopathological characteristics, prognosis, and CT features of ovary metastasis from colorectal carcinoma.

BackgroundThe aim of this study was to study patients diagnosed with ovary metastasis from colorectal carcinoma (OM-CRC) regarding their clinical manifestations, pathological characteristics and developments based on the results of computed tomography (CT).MethodsResearch was conducted with OM-CRC admissions to our facility during the period of January, 2000 to January, 2020, with examinations of both patients and imaging statistics.ResultsA group of 21 female participants with a median age of 54-year-old, ranging from 48 to 68 years old, were investigated. In the univariate analyses, synchronous metastasis and R2 resection (macroscopic residual lesions) during cytoreductive surgery (CRS) were shown to be negatively associated with the OM-CRC prognosis. Results of the multivariate analysis showed that R2 resection during CRS was the only independent predictor of the overall survival (OS) rate as well as the progression-free survival (PFS) rate. OM-CRC cases frequently exhibited a well-defined borderline (90.9%), predominantly cystic ovarian mass (90.9%), heterogeneous enhancement (72.3%), moderate enhancement (63.6%), peritoneal implantation (81.8%) and an absence of lymphadenopathy (90.9%).ConclusionsIt is important to develop a thorough comprehension of the pathological characteristics as well as developments of OM-CRC, in order to understand its diagnosis, develop useful therapeutic interventions, and predict accurate prognosis. Nevertheless, OM-CRC is an uncommon malignant ovarian tumor and a good prognosis requires a CRS without macroscopic residual lesions, as a significant finding of our study.

Abstract 2174: The genomic and anti-tumor immune evolution of breast cancer

Abstract Background: Immunotherapy has changed the paradigm for a fraction of cancer patients. However, the evolution of tumor and immune microenvironment may uncover therapy resistance and immune evasion and its impact on clinical outcome. Here, in order to analyze the genomic and anti-tumor immune evolution, we performed extensive characterization of a dataset of a triple negative breast cancer patient including longitudinal and synchronous metastases (mets) and blood samples, collected over 2,039 days (d) of clinical follow-up. Methods: Multi-platform profiling included whole exome seq, RNAseq, targeted multiplex gene expression, immunohistochemistry, and ELISpot T-cell assay of longitudinal chest wall biopsies (n=17 samples) and peripheral blood (n=14 samples), synchronous multi-regional mets at research autopsy (n=20 mets) and primary tumor analysis. State-of-the-art bioinformatics was applied to the data. Results: Tumor mutation burden (TMB) estimates from the immunotherapy naïve chest wall lesion (M1) (d799) and 20 multi-regional mets (immunotherapy experienced, IE-mets) (d2,033) were 1.5 mut/mb and had median of 3.9 mut/mb, respectively (delta TMB 1.6 mut/mb). There were 73 neoantigens in M1 (subclonal/clonal ratio=0.4), and a median of 226 neoantigens per IE-mets (subclonal/clonal ratio=1.1). TP53 T256fs was validated as a T-cell specific clonal neoantigen and was targeted as liquid biopsy cell-free tumor DNA since cancer diagnosis. Clonal ordering and clonal evolution models for M1 and IE-mets evidenced that clustered mutations shared the same evolutionary history but with a mixed pattern of seeding: metastatic clones were shed by polyclonal and monoclonal seeding. Distinct seeding events occurred from early M1 to late IE-mets, and among late IE-mets (CI 0.95, p&amp;lt; 0.0001). Longitudinal tumor inflammation (IFNy signaling) and antigen presenting machinery (APM) signatures defined immunophenotype statuses (i-inflamed, i-desert, i-excluded). They were modulated over clinical responses towards immune evasion and higher tumor cell proliferation. Immunophenotype statuses were also assigned to IE-mets that showed an overall heterogeneity and significant positive correlation to TMB (p=0.012), but not with the number of predicted neoantigens. M1 had HLA machinery status intact at the genomic level. IE-mets immunophenotyped as i-desert displayed statistically significant HLALOH (p&amp;lt;0.05), indicating APM failure. However, an i-inflamed monoclonal IE-met evolving from M1 kept HLA status intact. This suggested APM machinery failure in IE-mets likely went through clonal evolution as a result of an immunoediting process. Conclusion: By analysis of metastases genomes, we show that the immune tumor microenvironment shapes triple negative breast cancer progression by promoting and activating immune evasion mechanisms, culminating in heterogeneous lethal cancer. Citation Format: Juan Blanco-Heredia, Carla Anjos Souza, Samuel Gonçalves-Ribeiro, Maria Gonzalez-Cao, Maurizio Callari, Francesc Tresserra, Rafael Rossell, Carlos Caldas, Leticia De Mattos-Arruda. The genomic and anti-tumor immune evolution of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2174.

P-208 Pancreatic neuroendocrine neoplasia: Experience of a comprehensive cancer center

Pancreatic neuroendocrine neoplasia (Pan-NEN) are rare tumors in which therapeutic options have been increasing over the last decade. However, the effect of implementing these therapies in the real world is poorly understood. We aim to characterize the clinical features and therapeutic strategies of patients with Pan-NEN within a 12-year period in a cohort of patients followed at IPOFG-Porto. We performed a retrospective cohort study of patients diagnosed with Pan-NEN between 2006 and 2017 at the largest NEN reference Portuguese Center. Progression-free (PFS) and overall survival (OS) time estimates were calculated by Kaplan-Meier method. To assess the impact of baseline clinicopathological characteristics on survival, we used univariate and multivariate Cox proportional hazard models. Ninety-seven patients were included. Mean patient age was 59.5±13.55 years-old, with 55 (56.7%) being male. Forty-five patients (48.5%) had an Adjusted Charlson Comorbidity Index >3. Most patients were symptomatic at diagnosis, mainly due to tumor location-related symptoms (n=55, 69.6%), and 12 (15.0%) hormone secretion-related symptoms. Most tumors were well differentiated neuroendocrine tumors (NET) (n=77, 79.9%) according with WHO 2010 classification. NET G1 and NET G2 constituted the majority of cases (n=72, 75.8%). Predominant pancreatic topography was body and tail (n=43, 44.3%) followed by head (n=28, 28.9%). Fifty-two (53.6%) had localized/locoregional disease while 46.4% (n=45) had metastatic disease. Liver was the most frequent site of synchronous metastasis at diagnosis (n=42, 93.3%), followed by non-regional nodal (n=11, 24.4%) and bone (n=11, 24.4%). Globally, 60 (61.9%) surgical procedures were performed, 22 (22.9%) transarterial embolization, 5 (5.2%) other locoregional therapies, 56 (57.7%) somatostatin analogues, 23 (23.7%) Peptide Receptor Radionuclide Therapy, 11 (11.3%) everolimus and 32 (33.0%) chemotherapy. Forty-six patients (47.4%) had potentially curative disease, of which 43 (93.5%) had surgery as primary treatment. Eighteen patients (45.0%) had disease recurrence after surgery. Five-year Disease-free Survival was 61.9%. Seventy-two patients received antineoplastic palliative treatments (51 patients with metastatic/irresectable disease at diagnosis, 18 with disease recurrence and 3 refused curative intention therapy). Of those, twenty-six (36.1%) received 2 lines and 20 (27.8%) ≥3 lines of treatment. Median PFS after first line treatment was 25.0 months (95%CI 18.0-32.0) and median OS was 58 months (95%CI 30.0-86.0). Patients with localized/locoregional disease had a median OS of 160 months and patients with metastatic disease of 29 months, HR 4.55 (95%CI 2.58-8.02), p On univariate analysis, the risk of death was increased in those patients with NEC, metastatic disease at diagnosis, and primary location of the tumor not in the pancreatic body or tail. On multivariate analysis, NEC (HR 2.46 95%CI 1.28-4.73) and metastatic disease (HR 3.44 95%CI 1.85-6.37) were independent prognostic factors. Patients with PAN-NENs analyzed in this study present similar characteristics to other cohorts described in the literature. Therapeutic strategies in PAN-NENs are highly diversified and adapted to histological differentiation, stage, hormone hypersecretory-related symptoms and patients characteristics and preferences. NEC and metastatic disease were associated with a significant increase risk of death.

Prognostic Implications of MRI-Detected EMVI and Tumor Deposits and Their Response to Neoadjuvant Therapy in cT3 and cT4 Rectal Cancer

Magnetic resonance imaging-detected extramural venous invasion (mrEMVI) and tumor deposits (TDs) are risk factors for the development of local recurrence and distant metastases (DMs) in rectal cancer. However, little is known about their response to neoadjuvant treatment and its relation to oncologic outcomes. This study evaluated the incidence and features of mrEMVI and TDs before and after neoadjuvant treatment in relation to the development of local recurrence and DMs. Patients with cT3/4 rectal cancer without synchronous metastases who underwent surgery in a tertiary referral hospital were retrospectively analyzed. MRI scans were re-evaluated for the presence of mrEMVI, the occurrence of TDs, and response to neoadjuvant therapy (mr-vTRG). In total, 277 patients were included, of whom 163 (58.8%) presented with mrEMVI. TDs were present in 56.4% of mrEMVI-positive and 9.6% of mrEMVI-negative patients (P < .001). The 5-year DM rate was significantly higher in mrEMVI-positive patients with and without TDs (45.2% and 35.9%, respectively) compared with mrEMVI-negative patients (25.7%; P=.012). After neoadjuvant treatment, the 5-year DM rate of patients with mr-vTRG 3-5 was 46.1%, whereas good responders (mr-vTRG 1-2) had a DM rate similar to mrEMVI-negative patients (25.7% and 25.7%, respectively; P=.002). The occurrence of TDs and larger mrEMVI size resulted in a lower likelihood of regression of mrEMVI. The prevalence of mrEMVI and TDs in cT3-4 rectal cancer is high and is associated with worsened oncologic outcomes. mrEMVI regression (mr-vTRG 1-2), which occured in 25% of the cases, leads to oncologic outcomes similar to those in patients without mrEMVI on baseline MRI.

Association between PD‐L1 expression and initial brain metastasis in patients with non‐small cell lung cancer and its clinical implications

BackgroundBrain metastases frequently occur in patients with non‐small cell lung cancer (NSCLC) resulting in a poor prognosis. Here, we investigated the association between PD‐L1 expression and brain metastasis in patients with NSCLC and its clinical significance.MethodsA total of 270 patients diagnosed with metastatic NSCLC who underwent PD‐L1 testing on their tumor tissue between January 2017 and March 2019 were retrospectively reviewed. The VENTANA PD‐L1 (SP263) assay was used, and positive PD‐L1 expression was defined as staining in ≥1% of tumor cells.ResultsPositive PD‐L1 expression was observed in 181 (67.0%) patients, and 74 (27.4%) patients had brain metastasis at diagnosis. Synchronous brain metastases were more frequently observed in PD‐L1‐positive compared with PD‐L1‐negative patients (31.5% vs. 19.1%, p = 0.045). Multiple logistic regression analysis identified positive PD‐L1 expression (odds ratio [OR]: 2.24, p = 0.012) as an independent factor associated with synchronous brain metastasis, along with the histological subtype of nonsquamous cell carcinoma (OR: 2.84, p = 0.003). However, the incidence of central nervous system (CNS) progression was not associated with PD‐L1 positivity, with a two‐year cumulative CNS progression rate of 26.3% and 28.4% in PD‐L1‐positive and PD‐L1‐negative patients, respectively (log rank p = 0.944). Furthermore, positive PD‐L1 expression did not affect CNS progression or overall survival in patients with synchronous brain metastasis (long rank p = 0.513 and 0.592, respectively).ConclusionsInitial brain metastases are common in NSCLC patients with positive PD‐L1 expression. Further studies are necessary to understand the relationship between early brain metastasis and cancer immunity.

The Italian Consensus on minimally invasive simultaneous resections for synchronous liver metastasis and primary colorectal cancer: A Delphi methodology.

At the time of diagnosis synchronous colorectal cancer, liver metastases (SCRLM) account for 15-25% of patients. If primary tumour and synchronous liver metastases are resectable, good results may be achieved performing surgical treatment incorporated into the chemotherapy regimen. So far, the possibility of simultaneous minimally invasive (MI) surgery for SCRLM has not been extensively investigated. The Italian surgical community has captured the need and undertaken the effort to establish a National Consensus on this topic. Four main areas of interest have been analysed: patients' selection, procedures, techniques, and implementations. To establish consensus, an adapted Delphi method was used through as many reiterative rounds were needed. Systematic literature reviews were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses instructions. The Consensus took place between February 2019 and July 2020. Twenty-six Italian centres participated. Eighteen clinically relevant items were identified. After a total of three Delphi rounds, 30-tree recommendations reached expert consensus establishing the herein presented guidelines. The Italian Consensus on MI surgery for SCRLM indicates possible pathways to optimise the treatment for these patients as consensus papers express a trend that is likely to become shortly a standard procedure for clinical pictures still on debate. As matter of fact, no RCT or relevant case series on simultaneous treatment of SCRLM are available in the literature to suggest guidelines. It remains to be investigated whether the MI technique for the simultaneous treatment of SCRLM maintain the already documented benefit of the two separate surgeries.

The Pan-Immune-Inflammation Value in Patients with Metastatic Melanoma Receiving First-Line Therapy.

Since a non-negligible fraction of patients with metastatic melanoma does not experience long-term disease control, even with immunotherapy and targeted therapy, new biomarkers for patient stratification and treatment tailoring are needed in this setting. We investigated the association of a novel immune-inflammatory blood-based biomarker, the Pan-Immune-Inflammation Value (PIV), with clinical outcomes of patients with metastatic melanoma receiving first-line therapy. We retrospectively included patients treated at the Fondazione IRCCS Istituto Nazionale dei Tumori of Milan and having an available baseline complete blood cell count (CBC). PIV was calculated as: [neutrophil count (103/mm3) × platelet count (103/mm3) × monocyte count (103/mm3)]/lymphocyte count (103/mm3). A total of 228 patients were included: 119 (52%) had been treated with immunotherapy and 109 (48%) with targeted therapy. PIV was significantly higher in patients with ECOG PS ≥ 1, high disease burden, synchronous metastases, and elevated baseline LDH level. High baseline PIV was independently associated with poor overall survival (adjusted hazard ratio [HR]: 2.06; 95% confidence interval [CI]: 1.30-3.29; adjusted P=0.002) and progression-free survival (adjusted HR 1.56; 95% CI 1.01-2.41; adjusted P=0.044). High PIV was also associated with primary resistance to both immunotherapy (odds ratio [OR]: 3.98; 95% CI 1.45-12.32; P=0.005) and targeted therapy (OR: 8.42; 95% CI 2.50-34.5; P < 0.001). PIV showed a promising discrimination ability in terms of AIC and c-index when compared with other CBC-based biomarkers. PIV may guide the treatment decision process and the development of novel first-line treatment strategies in melanoma, but warrants further study and validation.

Involvement of Neutrophils in Metastatic Evolution of Pancreatic Neuroendocrine Tumors.

Simple SummaryThe neutrophil-to-lymphocytes (NLR) reflects the systemic inflammation. Based on a cohort of 144 patients treated for localized or metastatic well-differentiated pancreatic neuroendocrine tumors (pNET), we identified the NLR ≥ 4 to be associated with worse overall survival. Using MCP-Counter on a publicly available pNET RNA-sequencing dataset, we inferred the tumor microenvironment composition of 83 primary pNET and 30 liver metastasis. The neutrophils scores were statistically higher in liver metastasis relative to primary pancreatic tumors (p = 0.005). Gene set enrichment analysis further revealed activation of complement pathway signature in liver metastasis. Through combination of the neutrophil and complement pathway genes, we found that pNET can be classified into two clusters: Neu-Comp1 and Neu-Comp2. Notably, the Neu-Compt1 cluster was enriched in neutrophils and complement pathway signatures and was associated with liver metastasis. These data offer new insights into the role of inflammatory factors in the metastatic progression of the pNET.Well-differentiated pancreatic neuroendocrine tumors (pNET) have an unpredictable natural history. The identification of both blood and tumor immune features associated with patients’ outcomes remains limited. Herein, we evaluated the best prognostic value of the neutrophils-to-lymphocyte ratio (NLR) in a cohort of 144 pNETs. The NLR ≥ 4 was associated with worse overall survival in both univariate analysis (HR = 3.53, CI95% = 1.50–8.31, p = 0.004) and multivariate analysis (HR = 2.57, CI95% = 1.061–6.216, p = 0.036). The presence of synchronous liver metastasis was identified as a prognostic factor in multivariate analysis (HR = 3.35, CI95% = 1.411–7.973, p = 0.006). Interestingly, the absolute tumor-associated neutrophils count was higher in liver metastasis as compared to their paired primary tumor (p = 0.048). Deconvolution of immune cells from the transcriptome of 83 primary tumors and 30 liver metastases reveals enrichment for neutrophils in metastasis relative to primary tumors (p = 0.005), and this was associated with upregulation of the complement pathway (NES = 1.84, p < 0.0001). Combining neutrophils signature and complement pathway genes, unsupervised clustering identified two pNETs subgroups, namely Neu-Comp1 and Neu-Comp2. Characterized by neutrophils infiltration and activation of the complement pathway, Neu-Comp1 was highly enriched for metastatic liver samples as compared to Neu-Comp2 (p < 0.0001). These data suggest the possible link between liver metastasis, complement pathway activation, and neutrophils infiltration in well-differentiated pNET and open avenues for targeting complement pathways in these tumors.

The impact of synchronous liver resection on the risk of anastomotic leakage following elective colorectal resection. A propensity score match analysis on behalf of the iCral study group

Introductionhow best to manage patients with colorectal cancer and synchronous liver metastasis is still controversial, with specific concerns of increased risk of postoperative complications following combined resection. We aimed at analyzing the influence of combined liver resection on the risk of anastomotic leak (AL) following colorectal resection. Methodswe reviewed the iCral prospectively maintained database to compare the relative risk of AL of patients undergoing colorectal resection for cancer to that of patients receiving simultaneous liver and colorectal resection for cancer with isolated hepatic metastases. The incidence of AL was the primary outcome of the analysis. Perioperative details and postoperative complications were also appraised. Resultsout of a total of 996 patients who underwent colorectal resection for cancer, 206 receiving isolated colorectal resection were compared with a matched group of 53 patients undergoing simultaneous liver and colorectal resection. Combined surgery had greater operative time and resulted in longer postoperative hospitalization compared to colorectal resection alone. The proportion of overall morbidity following combined resection was significantly higher than after isolated colorectal resection (56.6% vs. 37.9%, p = 0.021). Overall, the two groups of patients did not differ neither on the rate of major postoperative complications, nor in terms of AL (9.4% vs. 6.3%, p = 0.381). At specific multivariate analysis, the duration of surgery was the only risk factor independently associated with the likelihood of AL. Conclusionscombining hepatic with colorectal resection for the treatment of synchronous liver metastasis from colorectal cancer does not increase significantly the incidence of AL.

P0640 - Renal mass size and presence of synchronous lung metastasis at time of diagnosis: Implications for chest imaging

P0640 - Renal mass size and presence of synchronous lung metastasis at time of diagnosis: Implications for chest imaging

Risk scoring system for recurrence after simultaneous resection of colorectal cancer liver metastasis.

BackgroundThe simultaneous resection of synchronous colorectal cancer liver metastasis (SCRLM) has been widely applied. It is necessary to establish a risk scoring system to predict post-operative recurrence, especially in patients with neoadjuvant treatment.MethodsThe medical records of 221 patients undergoing simultaneous resection of CRLM were assessed in this study with a further 128 patients allocated to a validation group. All patients in the study group were classified according to their history of neoadjuvant treatment and univariate and multivariate analyses were applied to study independent risk factors. A score model was then generated according to the factors included. Our data set were also applied to validate three other existing scoring models [Fong clinical recurrence score (CRS), Konopke, and Zakaria disease-free survival (DFS) score], and the concordance index was calculated for comparison among these models.ResultsCRLM involving more than three nodes positive for a primary tumor was considered an independent risk factor for progression in patients without neoadjuvant treatment and all score models could discretely stratify patients according to disease free survival. In patients receiving neoadjuvant treatment, CRLM involving more than one node and transfusion invasion were major determinants in patients after treatment. However, only our scoring system and Fong’s CRS score could discretely discriminate patients. In the validation group, patients were significantly classified with the score system.ConclusionsExisting score models had better values for determining prognosis in patients with SCRLM, especially in those undertaking neoadjuvant treatment. Larger cohorts, along with more detailed clinical features and multicenter validation should be undertaken before utilization.

Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays.

Simple SummaryImmunome in Sporadic Colorectal Cancer as source for biomarkers. Hence, a self-assembled protein array has been designed and developed to perform a serum screening to determined specific immune response against tumor antigens proteins as potential diagnostics biomarker panel.Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.

Hepatectomy Followed by Adjuvant Chemotherapy with 3-Month Capecitabine Plus Oxaliplatin for Colorectal Cancer Liver Metastases.

Lessons Learned Three‐month adjuvant capecitabine plus oxaliplatin in combination (CAPOX) appeared to reduce recurrence, with mild toxicity in postcurative resection of colorectal cancer liver metastases (CLM).Recurrence in patients who underwent the 3‐month adjuvant CAPOX after resection of CLM was most commonly at extrahepatic sites. BackgroundThe role of neoadjuvant and adjuvant chemotherapy in the management of initially resectable colorectal cancer liver metastases (CLM) is still unclear. We evaluated the feasibility of 3‐month adjuvant treatment with capecitabine plus oxaliplatin in combination (CAPOX) for postcurative resection of CLM.MethodsPatients received one cycle of capecitabine followed by four cycles of CAPOX as adjuvant chemotherapy after curative resection of CLM. Oral capecitabine was given as 1,000 mg/m2 twice daily for 2 weeks in a 3‐week cycle, and CAPOX consisted of oral capecitabine plus oxaliplatin 130 mg/m2 on day 1 in a 3‐week cycle. Primary endpoint was the completion rate of adjuvant chemotherapy. Secondary endpoints included recurrence‐free survival (RFS), overall survival (OS), dose intensity, and safety.ResultsTwenty‐eight patients were enrolled. Median age was 69.5 years, 54% of patients had synchronous metastases, and 29% were bilobar. Mean number of lesions resected was two, and mean size of the largest lesion was 31 mm. Among patients, 20 (71.4%; 95% confidence interval, 53.6%–89.3%) completed the protocol treatment and met its primary endpoint. The most common grade 3 or higher toxicity was neutropenia (29%). Five‐year recurrence‐free survival and overall survival were 65.2% and 87.2%, respectively.ConclusionThree‐month adjuvant treatment with CAPOX is tolerable and might be a promising strategy for postcurative resection of CLM.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer with Synchronous Peritoneal Metastases: Multicenter Study of \u2018Italian Peritoneal Surface Malignancies Oncoteam\u2014S.I.C.O.\u2019

BackgroundThe development of multimodality treatment, including cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC), has led to promising results in selected patients with peritoneal disease of gastric origin. The aim of this study was to investigate the short- and long-term outcomes of CRS/HIPEC in the treatment of synchronous peritoneal metastasis in gastric cancer.MethodsThe Italian Peritoneal Surface Malignancies Oncoteam—S.I.C.O. retrospective registry included patients with synchronous peritoneal malignancy from gastric cancer submitted to gastrectomy with CRS and HIPEC between 2005 and 2018 from 11 high-volume, specialized centers.ResultsA total of 91 patients with a median age of 58 years (range 26–75) were enrolled. The median overall survival (OS) time for the whole group of patients was 20.2 months (95% confidence interval [CI] 11.8–28.5] and the median recurrence-free survival (RFS) was 7.3 months (95% CI 4–10.6). The completeness of cytoreduction score (CCS) of 0 and Peritoneal Cancer Index (PCI) score of ≤ 6 groups showed a significantly better long-term survival (median OS 40.7 and 44.3 months, respectively) compared with the incomplete resected groups (median OS 10.7 months, p = 0.003) and PCI score of > 6 group (median OS 13.4 months, p = 0.005). A significant difference was observed in the survival rate according to neoadjuvant treatment (untreated patients: 10.7 months, 95% CI 5.1–16.2; treated patients: 35.3 months, 95% CI 2.8–67.8; p = 0.022).ConclusionsIn referral centers, CRS and HIPEC after neoadjuvant treatment significantly improved survival in selected patients. Patients with a PCI score ≤ 6, complete cytoreduction, negative nodal involvements, and negative cytology had encouraging results, showing a clinically meaningful survival.

Synchronous bone metastasis in lung cancer: retrospective study of a single center of 15,716 patients from Tianjin, China

BackgroundThis study aimed to describe the incidence, clinical characteristics, and prognosis of lung cancer patients with synchronous bone metastasis (SBM) and to analyze the prognostic factors of the lung cancer patients with SBM.MethodsA total of 15,716 lung cancer patients who were diagnosed between 2009 to 2018 in the Tianjin Medical University Cancer Institute and Hospital were retrospectively reviewed. Among them, patients with SBM were checked. Both the demographic and clinical characteristics were included as follows: age, gender, marital status, history of smoking, alcohol consumption, family history of tumor, Karnofsky score, lymph node metastasis, histological type. Besides, laboratory data such as alkaline phosphatase, lactate dehydrogenase, carcinoembryonic antigen, squamous cell carcinoma antigen, cytokeratin-19 fragment, and neuron specific enolase were also included. The log-rank test and multivariate Cox regression analysis were employed to reveal the potential prognostic predictors. A further analysis using the Kaplan–Meier was employed to demonstrate the difference on the prognosis of LC patients between adenocarcinoma and non-adenocarcinoma.ResultsAmong the included patients, 2738 patients (17.42%) were diagnosed with SBM. A total of 938 patients (34.3%) with SBM were successfully followed and the median survival was 11.53 months (95%CI: 10.57–12.49 months), and the 1-, 2-, and 5-year overall survival rate was 51, 17, and 8%, respectively. Multivariable Cox regression results showed history of smoking and high level of NSE were associated with the poor prognosis, while adenocarcinoma histological type was associated with better survival.ConclusionThe prevalence of SBM in lung cancer is relatively high with poor survival. The lung cancer patients with SBM showed diverse prognosis. Among all the pathological types, the division of adenocarcinoma suggested different prognosis of the lung cancer patients with SBM. The present study emphasized the importance of pathological diagnosis on prognostic determinants in lung cancer patients with SBM.

Dissemination patterns and chronology of distant metastasis affect survival of patients with head and neck squamous cell carcinoma

ObjectivesTo define metastatic categories based on their prognostic significance. We hypothesized that oligometastasis in patients with head and neck squamous cell carcinoma (HNSCC) is associated with better post-distant metastasis disease specific survival (post-DM DSS) compared to patients with polymetastasis. Furthermore, the impact on survival of synchronous versus metachronous distant metastasis (DM) occurrence was assessed. Materials and methodsRetrospective cohort study in which patients with DM were stratified into three groups: oligometastasis (maximum of 3 metastatic foci in ≤2 anatomic sites), explosive metastasis (≥4 metastatic foci at one anatomic site) and explosive-disseminating metastasis (spread to ≥3 anatomic sites or >3 metastatic foci in 2 anatomic sites). In addition, patients were divided into synchronous versus metachronous DM. ResultsBetween January 1, 2006 and December 31, 2013, a total of 2687 patients with HNSCC were identified, of which 324 patients developed DM. In this group, 115 (35.5%) patients had oligometastasis, 64 (19.8%) patients had explosive metastasis and 145 (44.8%) patients had explosive-disseminating metastasis. Their median post-DM DSS were 4.7 months, 4.1 months and 1.7 months respectively (p < .001). Synchronous DM was associated with more favorable survival rates in univariable and multivariable analyses than metachronous DM with recurrence of the index tumor (6-month post-DM DSS probability of 0.51 vs 0.17, p < .001). ConclusionOligometastasis in HNSCC signifies a better prognosis than a polymetastatic pattern. Metachronous DM occurrence with recurrence of the primary index tumor is associated with an unfavorable prognosis.

Induction Chemotherapy Combined With Intensity-Modulated Radiotherapy for 129 Nasopharyngeal Carcinoma Patients With Synchronous Metastases: A Retrospective Study.

ObjectiveTo analyze the therapeutic effect and prognostic factors of nasopharyngeal carcinoma (NPC) patients with distant metastases at initial diagnosis receiving induction chemotherapy with intensity-modulated radiotherapy (IMRT).MethodsA total of 129 patients who underwent platinum-based induction chemotherapy followed by definitive IMRT with or without concurrent or adjuvant chemotherapy for newly diagnosed distant metastatic NPC in our center between March 2008 and November 2018 were retrospectively analyzed. 41 patients underwent local therapy for metastatic sites. Kaplan-Meier method was used to estimate survival rates, Log-rank test and Cox proportional hazards model were used to figure out independent prognostic factors of overall survival (OS).ResultsA total of 66 patients had been dead (median follow-up time, 51.5 months). The median overall survival (OS) time was 54.2 months (range, 7-136 months), and the 1-year, 2-year, 3-year, 5-year overall survival rates were 88.0%,71.0%,58.0%, and 47.0%. Multivariate analysis found that the factors correlated with poor overall survival were pre-treatment serum lactate dehydrogenase (SLDH) >180U/L, chemotherapy cycles<4, and M1 stage subdivision (M1b, single hepatic metastasis and/or multiple metastases excluding the liver; and M1c, multiple hepatic metastases). The 5-year OS rates for M1a, M1b and M1c were 62.6%,40.4% and 0%, respectively.ConclusionPlatinum-containing induction chemotherapy combined with IMRT seemed to be advantageous to prolong survival for some NPC patients with synchronous metastases at initial diagnosis. The independent factors to prognosticate OS were pre-treatment SLDH, number of chemotherapy cycles, and M1 subcategories. Prospective clinical trials are needed to confirm the result.