Abstract
Background
ASCO and ESMO guidelines have identified inadequate sampling of lymph nodes, pT4 primary tumors, obstruction or perforation, lymphovascular and perineural invasion, and poorly ...differentiated tumors as negative prognostic factors supporting the clinicians in treating their patients with stage II colon cancer (CC). However, the influence of histological subtypes on the risk of death or disease recurrence remains controversial.
Methods
The phase III, multicenter, randomized TOSCA trial compared 3 vs. 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy in 3,759 patients with high-risk stage II or stage III CC. Objective of this sub-study was to investigate the role of the histological subtype (mucinous adenocarcinoma (MUC) or non-mucinous adenocarcinoma (NMUC) on the impact of the treatment duration in terms of relapse-free survival (RFS) and overall survival (OS) in the subgroup of patients with high-risk stage II, grade 3 CC.
Results
Out of 3,614 patients from 130 centres enrolled in the per-protocol population defined in the TOSCA trial, 85 MUC and 389 NMUC patients were included in this analysis. No statistical differences were found between 3 vs. 6 months groups in both histological subgroups in terms of baseline characteristics, except for tumor side. The proportion of patients with right-sided cancer was higher for patients with MUC than NMUC. A significant interaction between treatment duration and histology was observed on both RFS (p = 0.027) and OS (p = 0.017). In the subgroup of patients with MUC, worse RFS (adjusted hazard ratio HR, 3.95; 95% confidence interval CI, 1.03–15.17; p = 0.045) and OS (HR, 9.56; 95% CI, 1.14–79.98; p = 0.037) were detected for patients treated in the 3 months arm. No statistically significant differences were detected in the subgroup of patients with NMUC.
Conclusions
Both MUC and poorly differentiated subtypes have unfavorable clinical characteristics. Patients with MUC, grade 3, stage II CC require special attention and may need 6 months of oxaliplatin-based chemotherapy. Larger studies are required to clarify the possible negative effect of the histological subtype to improve the prognosis of these patients.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease with a poor 5-year overall survival rate (~10%). The revolution of immunotherapy in clinical oncology has not substantially changed ...clinical outcome for patients with PDAC. Despite outstanding efforts, neither immune checkpoint inhibitors (ICIs) alone, nor in combination with chemotherapy or targeted therapies have shown encouraging results. This failure mirrors the lack of knowledge about the real key players of immune system senescence and the complexity of the tumor microenvironment in PDAC. However, some hope can be derived from PARP-inhibitor combinations, vaccines, and CAR-T-cells therapy. In this review, we comprehensively summarize the latest updates about the use of ICIs in PDAC, focusing on clinical evidence and ongoing studies highlighting explanations for the failure of immunotherapy and possible solutions.
This paper deals with recognizing the public domain as a fundamental common heritage through a case study analysis. Public domain legal protection will be taken into account, too. In particular, the ...case study is referred to the universally known work of Antoine de Saint-Exupéry "Le Petit Prince", which in 2015 entered into public domain in all Europe apart France. In this Country, because of a number of measures, the works of Saint-Exupéry will be protected by copyright until 2032. In addition, the The Little Prince characters were registered by the aviator and writer's heirs as trademarks, which duration is potentially unlimited.
There are different cancers in the peri-ampullary region, including pancreatic ductal adenocarcinoma (PDAC), duodenum cancers (DCs), and ampullary adenocarcinoma (AAC). Here, significant ...morphological-molecular characterizations should be necessary for the distinction of primary tumours and classifications of their subtypes of cancers. The sub classification of AACs might include up to five different variants, according to different points of view, concerning the prevalence of the two more-cellular components found in the ampulla. In particular, regarding the AACs, the most important subtypes are represented by the intestinal (INT) and the pancreato-biliary (PB) ones. The subtyping of AACs is essential for diagnosis, and their identifications have been impacting clinical management responses to treatments and overall survival (os) after surgery. Pb is associated with a worse clinical outcome. Otherwise, the criteria, through which are possible to attribute its subtype classification, are not well established. A triage of immune markers represented by CK7, CK20, and CDX-2 seem to represent the best compromise in order to split the cohort of AAC patients in the INT and PB groups. The test of choice for the sub-classification of AACs is represented by the immuno-histochemical approach, in which its molecular classification acquires its diagnostic, predictive, and prognostic value for both the INT and PB patients.
Background & Aims Tumor shrinkage has been considered a fundamental surrogate efficacy measure for new cancer treatments. However, in patients treated with sorafenib for advanced hepatocellular ...carcinoma (HCC), tumor shrinkage rarely accompanies increased survival, thereby questioning the prognostic value of imaging-based Response Evaluation Criteria in Solid Tumors (RECIST). We investigated the prognostic usefulness of a decrease in serum alpha-fetoprotein (AFP) and compared it to RECIST. Methods In HCC patients treated with sorafenib with baseline AFP >20 ng/ml, AFP response was defined as a >20% decrease in AFP during 8 weeks of treatment. Patients were also assessed by RECIST and were categorized as having radiologically proven progressive disease or disease control (consisting of complete or partial responses and stable disease). Comparisons of survival by RECIST and AFP response were corrected for guarantee-time bias by the landmark method. Results We evaluated 85 patients for AFP response, among them, 82 were also evaluated by RECIST. In the analysis of AFP response, 32 out of 85 patients (37.6%) were responders, whereas 58 out of 82 patients (70.7%) achieved disease control. In landmark analysis, the hazard ratios (HR) for survival according to AFP response and disease control were 0.59 ( p = 0.040) and 1.03 ( p = 0.913), respectively. In multivariate analysis, only AFP response (HR = 0.52; p = 0.009) and Cancer of the Liver Italian Program dichotomized stage (HR = 0.42; p = 0.002) were prognostic factors of survival. Conclusions Assessment of AFP response may be considered as an alternative to RECIST to capture sorafenib activity in HCC.
To prevent damage from an immune response against autoantigens and toxins originating from the gut, the liver promotes an immune-tolerant milieu providing fertile ground for immune escape of cancer ...cells. Therefore, the use and evaluation of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) is a treatment rationale.
In this article, we discuss the role of the dual ICIs blockade in advanced HCC, covering the biological basis for their combination, their mechanism of action, and the results of the early-phase studies testing nivolumab plus ipilimumab and durvalumab plus tremelimumab. Furthermore, we provide the results of the phase III HIMALAYA trial and an overview of the ongoing trials investigating the dual ICIs in different disease stages.
The potential approval of the dual ICIs blockade strategies for advanced HCC will set the entry of antiangiogenic-free options, expanding the proportion of patients eligible for a first-line treatment. However, it will pose a series of clinical challenges with a sizable proportion of patients, namely Child-Pugh B, elderly, and immunocompromised patients, still marginalized. Also, given the rate of disease progression, identifying reliable predictive biomarkers is crucial to inform treatment choice and sequences. Finally, the compelling response rate of such combinations is paving the way for their evaluation in earlier stages.
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