Mitomycin C and capecitabine: An additional option as an advanced line therapy in patients with metastatic colorectal cancer

BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treatment options are needed.Studies have shown that mitomycin C(MMC),an antitumor antibiotic,and capecitabine,a precursor of 5-fluorouracil,may act synergistically in combination.The efficacy of MMC/capecitabine has been demonstrated in the first-line setting,but only a few small studies have tested it in the advanced-line setting,with contradictory results.received a median of 2 MMC/capecitabine cycles(range 0.5-9.0).Thirty-four patients(28.6%)experienced grade≥3 toxicity,including 2(1.7%)with grade 4;there was no drug-related mortality.The objective response rate was 0.8%,and the disease control rate,24.4%.Median progression-free survival(PFS)was 2.1 mo(range 0.2-20.3),and median overall survival,4.8 mo(range 0.2-27.5).The 6-month overall survival rate was 44%;8.7%of patients remained progression-free.Factors associated with longer PFS were lower gamma-glutamyl transferase level(P=0.030)and primary tumor location in the left colon(P=0.017).Factors associated with longer overall survival were lower gamma-glutamyl transferase level(P=0.022),left-colon tumor location(P=0.044),low-to-moderate histological grade(P=0.012),Eastern Cooperative Oncology Group performance status 0-1(P=0.036),and normal bilirubin level(P=0.047).CONCLUSION MMC/capecitabine is an active,available,and relatively safe regimen for use beyond standard lines of therapy in mCRC.Several clinical and laboratory parameters can identify patients more likely to benefit.

Dynamic toxicity landscape of immunotherapy for solid tumors across treatment lines

Objective:Immune checkpoint inhibitors(ICIs)targeting programmed cell death-1/ligand-1(PD-1/PD-L1),cy-totoxic T lymphocyte antigen-4(CTLA-4),and lymphocyte-activation gene-3(LAG-3)have been widely studied and applied throughout the course of cancer treatment.This study aimed to provide a comprehensive profile of ICI-associated toxicity and elucidate the toxicity patterns of ICIs across different treatment lines.Methods:In total,155 cohorts comprising 24539 eligible patients were included in the safety analysis.Trial name,registration number,cancer type,trial phase,clinical setting,trial design,regimen,dosing schedule,age,sex and ethnicity distributions,number of patients,number of treatment-related adverse events(trAEs),and number of treatment-related death were extracted.We defined a timeline from the neoadjuvant setting to the third-line setting.We also introduced a synthesizing principle for adverse event rates(SPAER)of immunotherapy to ensure the comparability and reliability across different treatment lines.The study protocol was registered and approved by the PROSPERO protocol review committee(CRD42021242368).Results:After excluding the neoadjuvant setting group,we observed a distinct reduction in the incidence of treatment-related adverse events(trAEs)with an advancement of the line of ICI treatment.The incidence of trAEs was negatively correlated with the line of treatment,irrespective of whether monotherapy or dual-ICI combination therapy was administered.Sensitivity analyses also confirmed the coincident negative correlations.Conclusion:In summary,using a timeline-based concept centered around treatment lines,we revealed the dy-namic landscape of ICI-associated toxicity and found that patients treated with ICIs during later lines of therapy may have a lower risk of trAEs.

S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer: A meta-analysis

AIM: To assess the efficacy and tolerability of S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer (AGC).

Efficacy and safety of first‐line regimens for advanced HER2‐positive breast cancer:A Bayesian network meta‐analysis

Background:The current standard of care for advanced human epidermal growth factor receptor 2(HER2)‐positive breast cancer is pertuzumab plus trastuzumab and docetaxel as first‐line therapy.However,with the development of newer treatment regimens,there is a lack of evidence regarding which is the optimal treatment strategy.The aim of this network meta‐analysis was to evaluate the efficacy and safety of first‐line regimens for advanced HER2‐positive breast cancer by indirect comparisons.Methods:A systematic review and Bayesian network meta‐analysis were conducted.The PubMed,EMBASE,and Cochrane Library databases were searched for relevant articles published through to December 2023.The hazard ratio(HR)and 95%credible interval(CrI)were used to compare progressionfree survival(PFS)between treatments,and the odds ratio and 95%CrI were used to compare the objective response rate(ORR)and safety.Results:Twenty randomized clinical trials that included 15 regimens and 7094 patients were analyzed.Compared with the traditional trastuzumab and docetaxel regimen,PFS was longer on the pyrotinib and trastuzumab plus docetaxel regimen(HR:0.41,95%CrI:0.22–0.75)and the pertuzumab and trastuzumab plus docetaxel regimen(HR:0.65,95%CrI:0.43–0.98).Consistent with the results for PFS,the ORR was better on the pyrotinib and trastuzumab plus docetaxel regimen and the pertuzumab and trastuzumab plus docetaxel regimen than on the traditional trastuzumab and docetaxel regimen.The surface under the cumulative ranking curve indicated that the pyrotinib and trastuzumab plus docetaxel regimen was most likely to rank first in achieving the best PFS and ORR.Comparable results were found for grade≥3 AE rates of≥10%.Conclusions:Our results suggest that the pyrotinib and trastuzumab plus docetaxel regimen is most likely to be the optimal first‐line therapy for patients with HER2‐positive breast cancer.

Marker-Based,3-D Adaptive Cartesian Grid Method for Multiphase Flow Around Irregular Geometries

Computational simulations of multiphase flow are challenging because many practical applications require adequate resolution of not only interfacial physics associated with moving boundaries with possible topological changes,but also around three-dimensional,irregular solid geometries.In this paper,we highlight recent efforts made in simulating multiphase fluid dynamics around complex geometries,based on an Eulerian-Lagrangian framework.The approach uses two independent but related grid layouts to track the interfacial and solid boundary conditions,and is capable of capturing interfacial as well as multiphase dynamics.In particular,the stationary Cartesian grid with time dependent,local adaptive refinement is utilized to handle the computation of the transport equations,while the interface shape and movement are treated by marker-based triangulated surface meshes which freely move and interact with the Cartesian grid.The markers are also used to identify the location of solid boundaries and enforce the no-slip condition there.Issues related to the contact line treatment,topological changes of multiphase fronts during merger or breakup of objects,and necessary data structures and solution techniques are also highlighted.Selected test cases including spacecraft fuel tank flow management and liquid plug flow dynamics are presented.