Adjuvant treatment in biliary tract cancer

Biliary tract cancers (BTCs) are a heterogeneous group of malignancies with a dismal prognosis. Despite radical surgery, the five-year overall survival (OS) does not exceed 40% in the best series. Adjuvant treatments are widely used even though they have mainly been investigated in small retrospective series until recently. Available data suggest that chemotherapy with 5-fluorouracil (and relative prodrugs) or gemcitabine can reduce the risk of relapse and potentially improve patients\u2019 long-term outcome. The role of adjuvant radiotherapy seems to be confined to patients with positive surgical margins. In addition, patients with highrisk factors for relapse (nodal involvement and non-radical resection) benefit most from chemotherapy. Recent results from large randomized trials have clarified the benefit of adjuvant treatments and probably defined a new standard of care

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

Immunotherapy in Pancreatic Cancer: Why Do We Keep Failing? A Focus on Tumour 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

Postsorafenib systemic treatments for hepatocellular carcinoma: questions and opportunities after the regorafenib trial.

The search for systemic therapies for hepatocellular carcinoma has been characterized by difficulties and failures. Despite recent progresses, many issues are still to be settled. In particular, the development of drugs inhibiting different neoplastic pathways remains a priority for patients intolerant or resistant to antiangiogenic drugs. This task may be daunting, as previous failures extensively demonstrated. We aimed to identify the future perspective of postsorafenib trials analyzing the strengths and the critical points of past and currently undergoing studies, in the light of the most recent evidences in the field. We identified various points (including stratification, biomarkers, end points, radiologic criteria of response, treatment beyond radiologic progression) that should be considered by future trials to reduce the risks of failure

Metronomic capecitabine vs. best supportive care in Child-Pugh B hepatocellular carcinoma: A proof of concept

There is a relative lack of evidence about systemic treatments in patients with hepatocellular carcinoma (HCC) and moderate liver dysfunction (Child-Pugh B). In this multicenter study we retrospectively analyzed data from Child-Pugh B-HCC patients na\uefve to systemic therapies, treated with MC or best supportive care (BSC). To reduce the risk of selection bias, an inverse probability of treatment weighting approach was adopted. Propensity score was generated including: extrahepatic spread; macrovascular invasion; performance status, alphafetoprotein > 400 ng/ml, Child- Pugh score [B7 vs. B8-9]. We identified 35 MC-treated patients and 70 controls. Median overall survival was 7.5 [95% CI: 3.733-11.267]in MC-patients and 5.1 months [95% CI: 4.098-6.102] in the BSC group (p = 0.013). In patients treated with MC, median progression-free survival was 4.5 months (95% CI: 2.5-6.5). The univariate unweighted Cox regression showed a 42% reduction in death risk for patients on MC (95%CI: 0.370-0.906; p = 0.017). After weighting for potential confounders, death risk remained essentially unaltered. In the MC group, 12 patients (34.3%) experienced at least one adverse event, the most common of which were: fatigue (17.1%), hand-foot syndrome (8.5%), thrombocytopenia (8.5%), and neutropenia (5.7%). MC seems a safe option for Child-Pugh B-HCC patients. Its potential antitumour activity warrants prospective evaluations

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

Clinical Features of the Intrahepatic and Extrahepatic Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a very heterogeneous cancer in many aspects including epidemiology, risk factors, clinical presentation and genetics. Medical literature reflects this feature especially in terms of differences of clinical presentation among the intrahepatic/extrahepatic subtypes and according to related risk factors and geographic areas. Consequently these tumors are often challenging to diagnose and treat and the prognosis is poor.This manuscript deals with the clinical presentation and epidemiology of cholangiocarcinoma

Percutaneous radiofrequency ablation in intrahepatic cholangiocarcinoma: a retrospective single-center experience

Background & aims: Very few data are available in literature about the role of radiofrequency ablation (RFA) in intrahepatic cholangiocarcinoma (ICC) and previous studies are mainly case reports and case series on a very small number of patients and nodules. In this study, we aimed to evaluate effectiveness and safety of RFA for the treatment of unresectable ICC. Methods: This is a retrospective observational cohort study comprising all consecutive patients treated with RFA for unresectable ICC at Policlinico Sant'Orsola Malpighi Hospital, Bologna, Italy. Primary endpoint was Local Tumor Progression-Free Survival (LTPFS) while Overall Survival (OS) was also assessed as secondary endpoint. Results: From January 2014 to June 2019, 29 patients with 117 nodules underwent RFA. Technique effectiveness 1 month after RFA was 92.3%; median LTPFS was 9.27 months. Univariate analysis and multivariate analysis showed that LTPFS was significantly related to tumor size ≥20 mm. At a median follow up of 39.9 months, median OS from the date of RFA was 27.5 months, with an OS of 89%, 45% and 11% at 1, 2 and 4 years, respectively. Number of overall lesions and the sum of their diameter at the moment of the first RFA significantly affected OS in multivariate analysis. Minor and major complication rates were 14% and 7%, respectively. Conclusion: Tumor size ≥20 mm was associated with lower LTPFS, representing a potential useful threshold value. A careful evaluation of tumor burden appears as a crucial element in choosing the best therapeutic strategy in unresectable ICC

The Best Management of Portal Neoplastic Thrombosis in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fifth commonest cancer worldwide. Vascular invasion of the portal vein is one of the most important prognostic factors for survival in HCC patients and the prognosis is generally poor. The optimal treatment for patients with HCC and portal vein tumour thrombus (PVTT) remains controversial. Although many therapeutic options have been proposed, surgical resection is the only hope of cure for such patients.We present the case of a 74-year-old man diagnosed with a single HCC nodule with portal thrombosis in the right hepatic lobe in the setting of HCV-related liver cirrhosis. After a first approach with a loco-regional treatment not tolerated by the patient, a right hepatectomy proved the best option. One year later the patient is still free from disease

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