Clinical and Translational Oncology最新文献

Purpose

Progression after first-line immunochemotherapy (ICT) for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) is a clinical concern due to subsequent limited treatment options. This study firstly predicted the progress outcome.

Methods

A cohort of 186 R/M NPC cases that received first-line ICT was included for developing a Cox regression model for progression-free survival (PFS) and risk stratification, which was verified by cross-validation. Discrimination and calibration were evaluated. Progression sites in risk groups was shown with a Sankey diagram.

Results

Baseline predictors including liver metastasis, trend of plasma Epstein–Barr virus DNA copies, lymphocyte-to-monocyte ratio, and level of platelet and lactate dehydrogenase were identified for model construction, which stratify the cohort into low, middle, and high-risk groups. The overall concordance index (C-index) was 0.67 (95% CI 0.62–0.73). The area under the curve (AUC) was 0.68 (95% CI 0.60–0.76), 0.74 (95% CI 0.66–0.82), 0.75 (95% CI 0.65–0.84) at predicting 12, 18, and 24 months PFS, indicating a moderate accuracy. Cross-validation showed the model performance was robust. Compared with the low-risk group (median PFS: 24.4 months, 95% CI 18.4 months to not reached), the high-risk group (median PFS: 7.1 months, 95% CI 6.4–10.1 months; hazard risk: 7.4, 95% CI 4.4–12.4, p < 0.001) progressed with more liver metastasis after ICT resistance.

Conclusion

It was the first study that described the risk factors and progression characteristics in R/M NPC patients who received first-line ICT, investigating the progression patterns, which was helpful to identify patients with different risks and help guide personalized interventions.

Appendiceal mucinous lesions’ classification and nomenclature has been modified several times along the last decades, reflecting their great heterogeneity and making difficult to compare results and draw conclusions. Despite its nearby origin, appendiceal mucinous lesions have a distinctive behaviour compared to colorectal cancer, including their molecular and genetic markers. Due to their low frequency, their management is not well standardised. However, surgery is considered the cornerstone of treatment. Their indolent behaviour has encouraged surgeons to apply more aggressive treatments, such as cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), that may extend overall survival. Chemotherapy is reserved for unresectable and/or disseminated disease and could play a role in the adjuvant and neoadjuvant setting. Pressurised intraperitoneal aerosol chemotherapy (PIPAC) is recently emerging as a possible alternative for treatment in advanced disease although its results in long-term survival are lacking Hereby, we review the available evidence in the management of appendiceal mucinous lesions, including localised and disseminated disease, with a special emphasis on the oncological perspective, focusing on the lights and shadows of the systemic treatments.

Purpose

This study aimed to validate the classification of breast cancer (BC) patients in progression risk groups based on total tumor load (TTL) value to predict lymph node (LN) affectation after neo-adjuvant systemic therapy (NAST) obtained in the NEOVATTL study.

Methods/patients

This was an observational, retrospective, international, multicenter study including patients with infiltrating BC who received NAST followed by sentinel lymph node biopsy (SLNB) analyzed with one-step nucleic acid amplification (OSNA) from nine Spanish and two Italian hospitals. Patients were classified into three groups according to the progression risk, measured as disease-free survival (DFS), based on TTL values (> 250, 250–25,000, and > 25,000 copies/μL). The previous (NEOVATTL study) Cox regression model for prognosis was validated using prognostic index (PI) and Log ratio test (LRT) analyses; the value of TTL for axillary non-SLN affectation was assessed using receiver operating characteristic (ROC) curves.

Results

We included 263 patients with a mean age of 51.4 (± SD 10.5) years. Patients with TTL > 25,000 copies/μL had a shorter DFS (HR 3.561 [95% CI 1.693−7.489], p = 0.0008 vs. TTL ≤ 25,000). PI and LRT analyses showed no differences between the two cohorts (p = 0.2553 and p = 0.226, respectively). ROC analysis showed concordance between TTL and non-SLN involvement (area under the curve 0.828), with 95.7% sensitivity and 92.9% specificity at a TTL cut-off of > 15,000 copies/μL.

Conclusions

In BC patients who had received NAST and underwent SLNB analysis using OSNA, a TTL value of > 25,000 copies/μL was associated with a higher progression risk and > 15,000 copies/μL was predictive of non-SLN involvement.

Drug repurposing of widely prescribed patent-off and cheap drugs may provide affordable drugs for cancer treatment. Nevertheless, many preclinical studies of cancer drug repurposing candidates use in vitro drug concentrations too high to have clinical relevance. Hence, preclinical studies must use clinically achievable drug concentrations. In this work, several FDA-approved cancer drugs are analyzed regarding the correlation between the drug inhibitory concentrations 50% (IC₅₀) tested in cancer cell lines and their corresponding peak serum concentration (C_max) and area under the curve (AUC) reported in clinical studies of these drugs. We found that for most targeted cancer drugs, the AUC and not the C_max is closest to the IC₅₀; therefore, we suggest that the initial testing of candidate drugs for repurposing could select the AUC pharmacokinetic parameter and not the C_max as the translated drug concentration for in vitro testing. Nevertheless, this is a suggestion only as experimental evidence does not exist to prove this concept. Studies on this issue are required to advance in cancer drug repurposing.