DECREASING ALBUMIN mRNA EXPRESSION IN CHOLANGIOCARCINOMAS ALONG THE BILE DUCT TREE.

INTRODUCTION: The progressive technologies in Albumin in situ hybridization (ISH) changed the routine application and the differential diagnosis of hepatic malignancies in the last years. The aim of the present work was to assess the diagnostic utility of albumin ISH on different cholangiocarcinoma (CCA) subtypes, as well as to assess how albumin production changes along the biliary tree. METHODS: Forty-five CCAs were retrospectively selected: 29 intrahepatic (15 small-duct and 14 large-duct subtypes), 7 peri-hilar and 9 extrahepatic. Histology was revised in all cases, and Albumin ISH was automatically performed by the RNAscope®. RESULTS: ISH was always negative in extrahepatic CCAs, only 1 peri-hilar case was positive, and any positivity was observed in 25/29 (86.2%) intrahepatic CCAs (p<0.001). Concerning CCA subtypes, mean cell positivity was 38.8±29.8% in small-duct CCAs and 11.4±21.9 in large-duct CCAs respectively (p=0.003); 12/15 (80.0%) small-duct and 3/14 (21.4%) large-duct CCAs showed >5% positive cells (p=0.002; odd-ratio 14.7). CONCLUSIONS: The introduction of more sensitive techniques changed the indications for ISH, since most small-duct intrahepatic CCAs show diffuse positivity. Albumin positivity decreases from liver periphery to the large ducts, suggesting that ISH can be helpful in the differential diagnosis between small-duct and large-duct CCAs, as well as between intrahepatic large-duct CCAs and metastases.

Pemigatinib for patients with previously treated, locally advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements: A joint analysis of the French PEMI-BIL and Italian PEMI-REAL cohort studies.

BACKGROUND: Pemigatinib is approved for patients with pretreated, locally advanced or metastatic CCA harboring FGFR2 rearrangements or fusions. We aim to assess the effectiveness and safety of pemigatinib in real-world setting. MATERIAL AND METHODS: A joint analysis of two multicentre observational retrospective cohort studies independently conducted in France and Italy was performed. All consecutive FGFR2-positive patients affected by CCA and treated with pemigatinib as second- or further line of systemic treatment in clinical practice, within or outside the European Expanded Access Program, were included. RESULTS: Between July 2020 and September 2022, 72 patients were treated with pemigatinib in 14 Italian and 25 French Centres. Patients had a median age of 57 years, 76% were female, 81% had ECOG-PS 0-1, 99% had intrahepatic CCA, 74% had ≥ 2 metastatic sites, 67% had metastatic disease at diagnosis, while 38.8% received ≥ 2 previous lines of systemic treatment. At data cut-off analysis (April 2023), ORR and DCR were 45.8% and 84.7%, respectively. Median DoR was 7 months (IQR: 5.8-9.3). Over a median follow-up time of 19.5 months, median PFS and 1-year PFS rate were 8.7 months and 32.8%. Median OS and 1-year OS rate were 17.1 months and 60.6%. Fatigue (69.4%), ocular toxicity (68%), nail toxicities (61.1%), dermatologic toxicity (41.6%) hyperphosphataemia (55.6%), stomatitis (48.6%), and diarrhea (36.1%) were the most frequent, mainly G1-G2 AEs. Overall incidence of G3 AEs was 22.2%, while no patient experienced G4 AE. Dose reduction and temporary discontinuation were needed in 33.3% and 40.3% of cases, with 1 permanent discontinuation due to AEs. CONCLUSIONS: These results confirm the effectiveness and safety of pemigatinib in a real-world setting.

Activated FGFR2 signalling as a biomarker for selection of intrahepatic cholangiocarcinoma patients candidate to FGFR targeted therapies.

FGFR inhibitors have been developed to inhibit FGFR activation and signal transduction; notwithstanding, currently the selection of intrahepatic cholangiocarcinoma (iCCA) patients for these drugs only relies on the detection of FGFR2 genetic alterations (GAs) in tumor tissues or circulating tumor DNAs, without concomitant assessment of FGFR2 signalling status. Accordingly, we performed multi-omic analyses of FGFR2 genes and FGFR2 signalling molecules in the tissue samples from 36 iCCA naïve patients. Gain-of-function FGFR2 GAs were detected in 7 patients, including missense mutations (n = 3; p.F276C, p.C382R and p.Y375C), translocations (n = 1) and copy number gain (n = 4; CNV ≥ 4). In contrast, among 29 patients with wild-type FGFR2, 4 cases showed activation of FGFR2 signalling, as they expressed the FGFR2 ligand FGF10 and phosphorylated FGFR2/FRS2α proteins; the remaining 25 cases resulted negative for activated FGFR2 signalling, as they lacked FGFR2 (n = 8) or phosphorylated FRS2α (n = 17) expression. Overall, we found that activation of FGFR2 signalling occurs not only in iCCA naïve patients with FGFR2 GAs, but also in a subgroup carrying wild-type FGFR2. This last finding entails that also this setting of patients could benefit from FGFR targeted therapies, widening indication of these drugs for iCCA patients beyond current approval. Future clinical studies are therefore encouraged to confirm this hypothesis.

Immune-Based Combination Therapies for Advanced Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fourth most frequent cause of cancer-related death worldwide. HCC frequently presents as advanced disease at diagnosis, and disease relapse following radical surgery is frequent. In recent years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced HCC, particularly with the introduction of atezolizumab/bevacizumab as the new standard of care for first-line treatment. Recently, dual immune checkpoint blockade with durvalumab plus tremelimumab has also emerged as an effective first-line treatment for advanced HCC and most of the research is currently focused on developing combination treatments based mainly on ICIs. In this review, we will discuss the rationale and ongoing clinical trials of immune-based combination therapies for the treatment of advanced HCC, also focusing on new immunotherapy strategies such as chimeric antigen receptor T cells (CAR-T) and anti-cancer vaccines.

Prognostic value of integrated morphofunctional imaging methods in inoperable intrahepatic cholangiocarcinoma.

Introduction and aim: Intrahepatic cholangiocarcinoma (iCCA) is a disease characterized by rarity, heterogeneity, and high mortality, where surgical resection is often not possible. Nowadays, due to the recent introduction of new therapeutic options such as trans-arterial radioembolization (TARE), it is increasingly important to define the role of morphofunctional imaging methods for the prognostic stratification of patients affected by iCCA. The aim of the study was to verify the prognostic value of morphofunctional imaging methods at the baseline in patients with inoperable iCCA. Methods: In total, 45 patients with iCCA were sent to our center between January 2016 and March 2021 for being evaluated to be treated with TARE. All of them underwent both [18F]-FDG-PET/CT and contrast-enhanced CT (ceCT) in a single procedure and were included in our study. The inclusion criteria were as follows: a diagnosis of inoperable iCCA; both [18F]-FDG-PET/CT and ceCT scans; and washout from therapy for at least 2 months before baseline [18F]-FDG-PET/CT and ceCT scans. Both clinical and laboratory data and baseline imaging data (ceCT and [18F]-FDG-PET/CT) were collected. In particular, regarding clinical and laboratory data, we collected overall survival (OS), gender, age, prior therapies, liver function indices, and tumor markers. Regarding ceCT, we collected TNM staging, lesion diameter, volume, vascularization, and presence of intravascular necrosis. Regarding [18F]-FDG-PET/CT, we collected TNM staging, Standard-Uptake-Value max (SUVmax), Metabolic-Tumor-Volume (MTV), and Total-Lesion-Glycolysis (TLG=MTV*lesions SUVmean). Philips-Vue-PACS software was used, setting hepatic SUVmean as TLG threshold. Results: A statistically significant correlation was found between some examined parameters at morphofunctional investigations at the baseline and OS. [18F]-FDG-PET/CT parameters statistically correlated with OS were the stage of disease greater than M0 (p = 0.037), major lesion SUVmax (p = 0.010), MTV (p ≤ 0.001), and TLG (p < 0.001). Other parameters at ceCT correlated with OS were the stage of disease greater than T2 (p = 0.038), maximum lesion diameter (p = 0.07), volume of the major lesion (p = 0.016), and total volume of lesions (p = 0. 009). Biochemical parameters correlated with OS were gamma glutamyl transferase (GGT, p = 0.014), alkaline phosphatase (ALP, p = 0.019), carcinoembryonic antigen (CEA, p = 0.004), and carbohydrate antigen 19-9 (CA 19-9, p < 0.001). From the parameters estimated by the multivariate model, we derived a four-variable score for OS combining nodal involvement and SUVmax at [18F]-FDG-PET/CT, GGT, and CA 19-9 levels. Conclusion: Considering our data, performing integrated pre-therapy imaging is critical for the prognostic stratification of patients with iCCA.

Improvements in Systemic Therapies for Advanced Malignant Mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy associated with poor prognosis and a 5-year survival rate of 12%. Many drugs have been tested over the years with conflicting results. The aim of this review is to provide an overview of current therapies in MPM and how to best interpret the data available on these drugs. Furthermore, we focused on promising treatments under investigation, such as immunotherapy with targets different from anti-PD-1/PD-L1 inhibitors, vaccines, target therapies, and metabolism-based strategies.

The Potential Role of Adjuvant Chemoradiotherapy in Patients with Microscopically Positive (R1) Surgical Margins after Resection of Cholangiocarcinoma.

(1) Background: Biliary tract cancers (BTCs) are a heterogeneous group of neoplasms with dismal prognosis and the role of adjuvant chemoradiotherapy in high-risk resected patients is unclear. (2) Methods: We retrospectively analyzed the outcomes of BTC patients who received curative intent surgery with microscopically positive resection margins (R1) and adjuvant chemoradioradiotherapy (CCRT) or chemotherapy (CHT) from January 2001 to December 201. (3) Results: Out of 65 patients who underwent R1 resection, 26 received adjuvant CHT and 39 adjuvant CCRT. The median recurrence-free survival (RFS) in the CHT and CHRT groups was 13.2 and 26.8 months, respectively (p = 0.41). Median overall survival (OS) was higher in the CHRT group (41.9 months) as compared to the CHT group (32.2 months), but the difference was not statistically significant (HR 0.88; p = 0.7). A promising trend in favor of CHRT was observed in N0 patients. Finally, no statistically significant differences were observed between patients undergoing adjuvant CHRT after R1 resection and patients treated with chemotherapy alone after R0 surgery. (4) Conclusions: Our study did not show a significant survival benefit with adjuvant CHRT over CHT alone in BTC patients with positive resection margins, while a promising trend was observed.

Are FGFR and IDH1-2 alterations a positive prognostic factor in intrahepatic cholangiocarcinoma? An unresolved issue.

Despite representing some of the most common and investigated molecular changes in intrahepatic cholangiocarcinoma (iCCA), the prognostic role of FGFR and IDH1/2 alterations still remains an open question. In this review we provide a critical analysis of available literature data regarding this topic, underlining the strengths and pitfalls of each study reported. Despite the overall poor quality of current available studies, a general trend toward a better overall survival for FGFR2 rearrangements and, possibly, for FGFR2-3 alterations can be inferred. On the other hand, the positive prognostic role of IDH1/2 mutation seems much more uncertain. In this scenario, better designed clinical trials in these subsets of iCCA patients are needed in order to get definitive conclusions on this issue.

Can repeated surgical resection offer a chance of cure for recurrent cholangiocarcinoma?

INTRODUCTION: The incidence of cholangiocarinoma (CCA), as well as the related mortality rate, has progressively increased over the last decades. Nevertheless improvement in patient management, diagnosis and therapies, recurrence rate remains high (50-70%) with a low 5-year survival (7-20%). Palliative chemotherapy and best supportive care are the treatment of choice in case of recurrence. In recent years, some reports have been published on repeated resection suggesting a survival benefit. The aim of this study was to evaluate the long-term outcome of all repeated resections for recurrent CCA in our institution. MATERIALS AND METHODS: We performed a retrospective analysis of all data recorded in our prospective maintained database of all patients who underwent repeated resection for recurrence of any type of CCA (intrahepatic, perihilar, distal, and gallbladder) with curative intent in our institution. RESULTS: Between 1997 and 2017, twenty-six patients underwent repeated surgical resection for recurrent CCA. Median time to first recurrence was 20 months. Site of recurrence was liver in 18 patients (70%), lymph nodes in 6 (23%), and lungs in 2 (7%). Twenty-five patients (96%) underwent upfront surgical resection of the recurrence, while one received preoperative chemotherapy. Median overall and disease-free survival from repeated surgical resection was 21 and 18 months with a 1-, 3-, and 5-year survival of 87, 41, 29% and 75%, 27%, and 17% respectively. Five patients (21%) did not experience recurrence after repeated surgical resection after a median follow-up of 73 months. CONCLUSIONS: Repeated surgical resection of recurrent CCAs is feasible with good postoperative results and can lead to an increase in survival.

Asbestos exposure as an additional risk factor for small duct intrahepatic cholangiocarcinoma: a pilot study.

Intrahepatic cholangiocarcinoma (iCCA) is a rare malignancy, recently classified in small duct and large duct morphological subtypes. Growing evidence suggests asbestos as a putative risk factor for iCCA, albeit no correlation between asbestos and iCCA morphology has been investigated so far. The aim of the present study was to assess the relationship between asbestos exposure and iCCA morphological subtype. Forty patients with surgically removed iCCA were prospectively enrolled: asbestos exposure was assessed according to the Italian National Mesothelioma Register questionnaire. From the surgical iCCA specimens the main histopathological variables were collected, including the small duct (sd-iCCA, 32 patients) and large duct subtypes (ld-iCCA, 8 patients). Five sd-iCCA cases had a definite/probable occupational exposure to asbestos, while no cases of ld-iCCA were classified as being occupationally exposed (definite/probable). Other kind of asbestos exposure (i.e. possible occupational, familial, environmental) were recorded in 16 sd-iCCA and 3 ld-iCCA. Cases with unlikely exposure to asbestos were 11 sd-iCCA (35.5%) and 5 ld-iCCA (62.5%). In conclusion, these findings seem to indicate that sd-iCCA might be more frequently associated to asbestos exposure rather than ld-iCCA, suggesting that asbestos fibres might represent a parenchymal, rather than a ductal risk factor for iCCA. This pilot study must be confirmed by further case-control studies or large independent cohorts.

Second-Line Chemotherapy in Elderly Patients with Advanced Biliary Tract Cancer: A Multicenter Real-World Study.

Objectives: The ABC-06 and the NIFTY trials recently established the role of second-line chemotherapy (2L) in patients with advanced biliary tract cancer (BTC). Our real-world study aimed to explore 2L in BTC patients aged ≥ 70 years old and to compare their outcomes with younger subjects. Methods: Institutional registries across three academic medical centers were retrospectively reviewed. The Kaplan−Meier methods were used to estimate survival, and the log-rank test was used to make comparisons. Results: A total of 190 BTC patients treated with 2L were identified and included in the analysis. Among them, 52 (27.3%) were aged ≥ 70 years (range 70−87 years). No statistically significant differences in both median overall survival (mOS) and median progression-free survival (mPFS) were recorded between the elderly and younger patients. Absolute lymphocyte count < 1000/mmc (p < 0.001) and albumin level < 3 g/dL (p < 0.001) were independently associated with worse prognoses. Conclusions: The results of this real-world study suggest that for patients aged ≥ 70 years, 2L could be equally effective for younger patients with survival outcomes aligned to those from the ABC-06 and NIFTY trials. The delivery of 2L should be carefully evaluated and monitored in this patient subset.

Advances in novel systemic therapies for advanced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents the most frequent type of primary liver tumor. Most HCC patients present with advanced disease at diagnosis and the recurrence rate after surgery remains high. Treatment options for advanced HCC are limited, with sorafenib representing the only systemic agent approved for treatment of advanced HCC in more than a decade. However, in recent years new molecular targeted therapies and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced HCC. In particular, combinations of ICIs with antiangiogenic drugs, or with other ICIs, represent one of the most promising strategies. Herein we provide a comprehensive overview of the main therapeutic advances in the systemic treatment of HCC, focusing on the most relevant ongoing clinical trials.

Intensive Follow-Up Program and Oncological Outcomes of Biliary Tract Cancer Patients after Curative-Intent Surgery: A Twenty-Year Experience in a Single Tertiary Medical Center.

AIM: The aim of this research was to assess the impact of an intensive follow-up program on BTC patients who had received surgery with curative intent at a tertiary referral hospital. METHODS: BTC patients were followed-up every three months during the first two years after their first surgery and every six months from the third to the fifth post-operative year. RESULTS: A total of 278 BTC patients who received R0/R1 surgery were included. A total of 17.7% of patients underwent a second surgery following disease relapse, and none of these patients experienced additional disease relapse. CONCLUSIONS: An intensive follow-up after surgical resection may help in the early identification of disease relapse, leading to early treatment and prolonged survival in selected cases.

Immunotherapy in Pancreatic Cancer: Why Do We Keep Failing? A Focus on Tumor Immune Microenvironment, Predictive Biomarkers and Treatment Outcomes.

The advent of immunotherapy and targeted therapies has dramatically changed the outcomes of patients affected by many malignancies. Pancreatic cancer (PC) remains one the few tumors that is not treated with new generation therapies, as chemotherapy still represents the only effective therapeutic strategy in advanced-stage disease. Agents aiming to reactivate the host immune system against cancer cells, such as those targeting immune checkpoints, failed to demonstrate significant activity, despite the success of these treatments in other tumors. In many cases, the proportion of patients who derived benefits in early-phase trials was too small and unpredictable to justify larger studies. The population of PC patients with high microsatellite instability/mismatch repair deficiency is currently the only population that may benefit from immunotherapy; nevertheless, the prevalence of these alterations is too low to determine a real change in the treatment scenario of this tumor. The reasons for the unsuccess of immunotherapy may lie in the extremely peculiar tumor microenvironment, including distinctive immune composition and cross talk between different cells. These unique features may also explain why the biomarkers commonly used to predict immunotherapy efficacy in other tumors seem to be useless in PC. In the current paper, we provide a comprehensive and up-to-date review of immunotherapy in PC, from the analysis of the tumor immune microenvironment to immune biomarkers and treatment outcomes, with the aim to highlight that simply transferring the knowledge acquired on immunotherapy in other tumors might not be a successful strategy in patients affected by PC.

Dual immune checkpoint blockade in hepatocellular carcinoma: where do we stand?

Hepatocellular carcinoma (HCC) represents the fourth most common cause of cancer-related death. Surgery, local ablative therapies and liver transplantation are the only potentially curative strategies, but the majority of patients present with advanced disease at diagnosis or develop recurrence after surgery. In recent years, immunotherapy for HCC has received growing interest, and one of the most promising strategies is the association of two immune checkpoint inhibitors (ICIs), which has already demonstrated its potential in other solid tumors such as melanoma and renal cell carcinoma. Herein, we discuss the role and the biologic rationale of dual immune checkpoint blockade in HCC patients, focusing on the two ICI combinations: nivolumab plus ipilimumab and durvalumab plus tremelimumab.

Risk-adjusted analysis of survival variability among hospitals treating biliary malignancy.

Biliary tract cancer's (BTC) treatment main stone for advanced stages is constituted by chemotherapy. Surgical centralization and physicians' confidence in the use of new technologies and molecular analysis turned out to be of interest and potentially influencing survival. After applying a random-effect model, the relationship between each clinical variable on the main outcome was investigated through multilevel mixed-effects logistic regression. The risk-standardized outcomes were calculated for each centre involved. In the unadjusted cohort the median survival was 8.6 months (95%C.I.: 7.8-9.3) with a 9-month survival rate of 48.3% (95%C.I.: 45.0-51.5). A substantial heterogeneity across hospitals was found (I2: 70.3%). In multilevel mixed effect logistic regression, male, being treated for gallbladder cancer, higher ECOG, increased NLR, CEA and Ca 19.9 and low value of haemoglobin showed to increase the odds for 9-month mortality. The model estimated that the residual variance observed in 9-month mortality was attributable for the 2.6% to the treating hospital. Through a multilevel mixed effect model, average risk-standardized mortality within 9 months was 50.1%. As noticeable, all hospital's risk-standardized mortality falls within 95%C.I., thus all participating centres provided similar outcomes when adjusted for patient case-mix. Heterogenicity between hospital did not affect the outcome in term of overall survival.

The power of kindness: curative treatment with metronomic combination in advanced hepatocellular carcinoma.

The administration of approved systemic treatments for advanced hepatocellular carcinoma (HCC) is limited to patients with preserved liver function (Child-Pugh A/B7) and performance status. Conversely, metronomic chemotherapy can be safely administered to patients with poor clinical conditions and severe liver impairment. The metronomic schedule demonstrated to exert different anticancer mechanisms compared to that of the same agent administered at its standard schedule, including immune stimulation and the inhibition of angiogenesis and vasculogenesis. Nevertheless, metronomic chemotherapy is a nearly neglected option for the treatment of advanced HCC patients, even among those who cannot afford standard treatments. Herein, we report the case of a 40-year-old patient affected by HBV-HDV-related cirrhosis who was diagnosed with advanced HCC. The severe liver impairment (Child-Pugh B9) did not allow to administer first-line treatment with tyrosine kinase inhibitors so that the patient received metronomic capecitabine as upfront therapy. Due to the suspect of progressive disease at the first radiologic assessment, metronomic cyclophosphamide was added to capecitabine aiming to enhance its efficacy. After 4 months of treatment, complete tumor response, alpha-fetoprotein (AFP) normalization and the recovery of a Child-Pugh A were achieved. The patient was then able to undergo liver transplantation, and, after 18 months from the diagnosis, he is still free of disease recurrence. This experience emphasizes the reliability of metronomic capecitabine as a well-tolerated and effective treatment when patient's conditions prevent the administration of standard first-line treatments. In fact, metronomic capecitabine demonstrated its effectiveness in advanced HCC in retrospective and prospective analyses, leading to median progression-free survival and overall survival of, respectively, 6.03 and 14.47 months in phase II single-arm trial. Moreover, in consideration of the raising interest in immune-checkpoint inhibition in HCC, we believe that the immunomodulating effects of metronomic chemotherapy, either capecitabine or cyclophosphamide, warrant future trials exploring its combination with immunotherapy.

Prognostic Role of a New Index Tested in European and Korean Advanced Biliary Tract Cancer Patients: the PECS Index.

BACKGROUND AND AIM: The aim of the present study is to evaluate a new index (PECS (PsECogSii)index) influenced by PS ECOG and systemic immune-inflammation index (SII) in unresectable locally advanced or metastatic BTC patients treated with first-line chemotherapy. METHODS: This multicenter, international, study was conducted on a training cohort of 130 patients and in three European and Korean validation cohorts The PECS index was calculated as ECOG × SII index (neutrophil count × platelet count/lymphocyte count). Event-time distributions were estimated using the Kaplan-Meier method and survival curves were compared using the log-rank test. RESULTS: In the training cohort, the median overall survival (mOS) was 13.2 months, 8.7 months, and 3.8 months for patients with PECS-0, PECS-1, and PECS-2, respectively (PECS-0: HR = 1; PECS-1: HR 1.41; PECS-2: HR 3.23) (p < 0.0001). In the first validation cohort, the mOS was 12.8 months, 10.1 months, and 5.3 months for patients with PECS-0, PECS-1, and PECS-2, respectively (PECS-0: HR = 1; PECS-1: HR 1.29; PECS-2: HR 2.40) (p < 0.0001). In the second validation cohort, the mOS was 21.2 months, 10.2 months, and 3.0 months for patients with PECS-0, PECS-1, and PECS-2, respectively (PECS-0: HR = 1; PECS-1: HR 2.25; PECS-2: HR 9.00) (p < 0.0001). In the third validation cohort, the median OS was 15.5 months, 7.5 months, and 3.7 months for patients with PECS-0, PECS-1, and PECS-2, respectively (PECS-0: ref HR = 1; PECS-1: HR 2.14; PECS-2: HR 5.00) (p < 0.0001). Multivariate analysis in all cohorts confirmed the PECS index as an independent prognostic factor for OS. CONCLUSIONS: The easy assessment, low cost, and reproducibility make PECS index a promising tool to assess the prognosis of BTC patients in future clinical practice.

A Novel Prognostic Tool in Western and Eastern Biliary Tract Cancer Patients Treated in First-line Setting: the ECSIPOT Index.

BACKGROUND AND AIM: The need to estimate prognosis of advanced BTC (aBTC) patients treated with first-line chemotherapy is compelling. The aim of the study is to evaluate the ECSIPOT (psECogSIiPnigOT) index, influenced by PECS (PsECogSii) index, prognostic nutritional index (PNI), and GOT. METHODS: This international study was conducted on a training cohort of 126 patients and in three validation cohorts, both European and Korean. ECSIPOT index formula: (PECS:0 = 1 point; PECS:1 = 1.4 points; PECS:2 = 3.2 points) + (PNI > 36.7 = 1 point; PNI < 36.7 = 2 points) + (GOT < 100 = 1 point; GOT > 100 = 2 points). Event-time distributions were estimated using the Kaplan-Meier method, and survival curves were compared using the log-rank test. RESULTS: In the training cohort, mOS was 12.9, 6.3, and 2.8 months for patients with ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR 1; ECSIPOT-1: HR 2.11; ECSIPOT-2: HR 4.93; p < 0.0001). In the first validation cohort, mOS was 11.5, 7.3, and 3.3 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR 1; ECSIPOT-1: HR 1.74; ECSIPOT-2: HR 3.41; p < 0.0001). In the second validation cohort, mOS was 25.2, 12.5, and 3.0 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR = 1; ECSIPOT-1: HR 2.33; ECSIPOT-2: HR 8.46; p < 0.0001). In the third validation cohort, mOS was 11.8, 8.1, and 4.6 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR = 1; ECSIPOT-1: HR 1.47; ECSIPOT-2: HR 3.17; p < 0.0001). Multivariate analysis in all cohorts confirmed the ECSIPOT index as an independent prognostic factor for OS. CONCLUSION: The easy assessment and good risk-stratification performance make the ECSIPOT index a promising tool to comprehensively estimate the prognosis of aBTC patients.

Clinical insights and prognostic factors from an advanced biliary tract cancer case series: a real-world analysis.

Advanced biliary tract cancer (aBTC) comprises a heterogeneous group of rare malignancies with dismal prognosis. Given the scarcity of prospective evidence, the aim of this study was to derive clinically useful insights and prognostic factors from a large, real-world series of aBTC. Clinicopathologic variables and treatment outcomes were retrospectively collected involving 940 patients diagnosed with aBTC between 2001 and 2017, and treated with first-line chemotherapy (CT1) at 14 Italian medical oncology institutions. Median overall survival (OS) was 10.3 months (CI95% 9.5-11.1). CT1 with gemcitabine-Platinum salts doublets achieved OS of 11.7 months vs 7.5 with gemcitabine alone (HR 0.67, p < 0.001). However, a clear temporal trend towards improved OS could not be demonstrated. Radical surgery of recurrent disease achieved a relapse-free survival of 5.9 months. A substantial minority (44.5%) of patients were able to receive a second-line chemotherapy, which achieved a response rate of 7.6%, and disease control in 30% of patients with no significant differences between combination regimens and monotherapies. In a large retrospective series of real-world aBTC, outcomes of standard CT1 closely resembled those of the registrational trials. A limited set of easily retrievable independent prognostic factors was defined. Further research is needed on second-line regimens.