Cancer Research and Treatment最新文献

Purpose: This study aimed to investigate the efficacy and safety of using metronomic S-1 adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC).

Materials and methods: We retrospectively collected data on patients diagnosed with LANPC between January 2016 and December 2021. All patients were treated with induction chemotherapy and concurrent chemoradiotherapy with or without metronomic chemotherapy (MC). Toxicities during MC were recorded. The chi-square test, Kaplan-Meier methods, propensity score matching (PSM), and Cox proportional hazards model were used for statistical analyses.

Results: A total of 474 patients were identified, including 64 (13.5%) and 410 (83.5%) patients with or without receiving MC, respectively. Patients who received metronomic S-1 had significantly better 3-year locoregional recurrence-free survival (LRFS) (100% vs. 90.9%, p=0.038), distant metastasis-free survival (DMFS) (98.5% vs. 84.1%, p=0.002), disease-free survival (DFS) (98.4% vs. 77.5%, p < 0.001), and overall survival (OS) (98.0% vs. 87.7%, p=0.008) compared to those without metronomic S-1. The multivariate prognostic analysis revealed that metronomic S-1 was identified as an independent prognostic factor associated with better DMFS (hazard ratio [HR], 0.074; p=0.010), DFS (HR, 0.103; p=0.002) and OS (HR, 0.127; p=0.042), but not in LRFS (p=0.071). Similar results were found using PSM. Common adverse events observed in the metronomic S-1 group included leukopenia, neutropenia, increased total bilirubin, anorexia, rash/desquamation, and hyperpigmentation. All patients with adverse events were grade 1-2.

Conclusion: It is worth conducting a randomized controlled trial to assess the effect of metronomic S-1 on survival outcomes and toxicities of LANPC.

Purpose: Clinical outcomes of surgery after neoadjuvant chemotherapy have not been investigated for locally advanced pancreatic cancer (LAPC), despite well-established outcomes in borderline resectable pancreatic cancer (BRPC). This study aimed to investigate the clinical outcomes of patients with LAPC who underwent curative resection following neoadjuvant chemotherapy.

Materials and methods: We retrospectively reviewed the records of patients diagnosed with pancreatic adenocarcinoma between January 2017 and December 2020.

Results: Among 1,358 patients, 260 underwent surgery following neoadjuvant chemotherapy. Among 356 LAPC patients, 98 (27.5%) and 147 (35.1%) of 418 BRPC patients underwent surgery after neoadjuvant chemotherapy. Compared to resectable pancreatic cancer (resectable PC) with upfront surgery, both LAPC and BRPC exhibited higher rates of venous resection (28.6% vs. 49.0% vs. 4.0%), arterial resection (30.6% vs. 6.8% vs. 0.5%) and greater estimated blood loss (260.5 vs. 213.1 vs. 70.4 mL). However, hospital stay, readmission rates, and postoperative pancreatic fistula rates (grade B or C) did not differ significantly between LAPC, BRPC, and resectable PC. Overall and relapse-free survival did not differ significantly between LAPC and BRPC patients. The median overall survival was 37.3 months for LAPC and 37.0 months for BRPC. The median relapse-free survival was 22.7 months for LAPC and 26.0 months for BRPC.

Conclusion: Overall survival time and postoperative complications in LAPC patients who underwent curative resection following neoadjuvant chemotherapy showed similar results to those of BRPC patients. Further research is needed to identify specific sub-populations of LAPC patients who benefit most from conversion surgery and to minimize postoperative complications.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC.

Materials and methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients.

Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052).

Conclusion: Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Purpose: Numerous patients experience long-term complications after hematopoietic stem cell transplantation (HSCT). This study aimed to identify the frequency and risk factors for psychiatric and endocrine complications following HSCT through big data analyses.

Materials and methods: We established a cohort of patients with hematologic disease who underwent HSCT in Korea between 2010 and 2012 using the Health Insurance Review & Assessment Service data. A total of 3,636 patients were identified, and insurance claims were tracked using psychiatric and endocrine diagnostic International Classification of Diseases, 10th Revision codes for the ensuing decade. We identified the incidence rates of long-term complications based on the baseline disease and HSCT type. Prognostic factors for each complication were scrutinized using logistic regression analysis.

Results: A total of 1,879 patients underwent allogeneic HSCT and 1,757 patients received autologous HSCT. Post-HSCT, 506 patients were diagnosed with depression, 465 with anxiety disorders, and 659 with diabetes. The highest incidence of long-term complications occurred within the first year post-HSCT (12.2%), subsequently decreasing over time. Risk factors for depressive disorders after allogeneic HSCT included female sex, a total body irradiation-based conditioning regimen, and cyclosporine. Identified risk factors for diabetes mellitus comprised old age, total body irradiation-based conditioning regimen, and non-antithymocyte globulin protocol. Regarding autologous HSCT, only female sex was identified as a risk factor for depressive disorders, whereas elderly patients and those with multiple myeloma were identified as poor prognostic factors for diabetes mellitus.

Conclusion: The incidence of long-term psychiatric and endocrine complications post-HSCT remains high, and patients with risk factors for these complications require vigilant follow-up.

Purpose: This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy.

Materials and methods: We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data.

Results: Among 208 consecutively enrolled patients, we selected 84 (41 males; median age, 59 years; range, 35 to 90 years) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, seven mutations in five patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival.

Conclusion: While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer's clonal evolution. Additionally, baseline-ctDNA's VAF values were prognostic after treatment.

Purpose: Delirium is a common neurocognitive disorder in patients with advanced cancer and is associated with poor clinical outcomes. As a potentially reversible phenomenon, early recognition of delirium by identifying the risk factors demands attention. We aimed to develop a model to predict the occurrence of delirium in hospitalized patients with advanced cancer.

Materials and methods: This retrospective study included patients with advanced cancer admitted to the oncology ward of four tertiary cancer centers in Korea for supportive cares and excluded those discharged due to death. The primary endpoint was occurrence of delirium. Sociodemographic characteristics, clinical characteristics, laboratory findings, and concomitant medication were investigated for associating variables. The predictive model developed using multivariate logistic regression was internally validated by bootstrapping.

Results: From January 2019 to December 2020, 2,152 patients were enrolled. The median age of patients was 64 years, and 58.4% were male. A total of 127 patients (5.9%) developed delirium during hospitalization. In multivariate logistic regression, age, body mass index, hearing impairment, previous delirium history, length of hospitalization, chemotherapy during hospitalization, blood urea nitrogen and calcium levels, and concomitant antidepressant use were significantly associated with the occurrence of delirium. The predictive model combining all four categorized variables showed the best performance among the developed models (area under the curve 0.831, sensitivity 80.3%, and specificity 72.0%). The calibration plot showed optimal agreement between predicted and actual probabilities through internal validation of the final model.

Conclusion: We proposed a successful predictive model for the risk of delirium in hospitalized patients with advanced cancer.

Accurate detection of homologous recombination deficiency (HRD) in cancer patients is paramount in clinical applications, as HRD confers sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. With the advances in genome sequencing technology, mutational profiling on a genome-wide scale has become readily accessible, and our knowledge of the genomic consequences of HRD has been greatly expanded and refined. Here, we review the recent advances in HRD detection methods. We examine the copy number and structural alterations that often accompany the genome instability that results from HRD, describe the advantages of mutational signature-based methods that do not rely on specific gene mutations, and review some of the existing algorithms used for HRD detection. We also discuss the choice of sequencing platforms (panel, exome, or whole-genome) and catalog the HRD detection assays used in key PARP inhibitor trials.

Purpose: BRAF mutations are detected in 30%-80% of papillary thyroid cancer (PTC) cases. DaBRAFenib and trametinib showed promising antitumor activity in patients with BRAFV600E-mutated metastatic melanoma and non-small cell lung cancer. This study aimed to evaluate the efficacy and safety of daBRAFenib and trametinib in patients with metastatic BRAFV600E-mutated thyroid cancer.

Materials and methods: This was a retrospective study to evaluate the efficacy of daBRAFenib and trametinib in patients with metastatic BRAFV600E-mutated PTC. The patients received daBRAFenib 150 mg twice daily and trametinib 2 mg once daily at the Samsung Medical Center. This study evaluated the progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) overall survival (OS), and safety of daBRAFenib and trametinib.

Results: Between December 2019 and January 2022, 27 PTC patients including eight patients with poorly differentiated or anaplastic transformation, received daBRAFenib and trametinib. The median age was 73.0 years, and the median follow-up period was 19.8 months. The majority (81.5%) had undergone thyroidectomy, while 8 patients had received prior systemic treatments. ORR was 73.1%, with 19 partial responses, and DCR was 92.3%. Median PFS was 21.7 months, and median OS was 21.7 months. Treatment-related adverse events included generalized weakness (29.6%), fever (25.9%), and gastrointestinal problems (22.2%). Dose reduction due to adverse events was required in 81.5% of the patients.

Conclusion: DaBRAFenib and trametinib demonstrated a high ORR with promising PFS; however, most patients with BRAFV600E-mutated metastatic PTC required a dose reduction.

Purpose: Hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR) are relatively common toxicities that interfere with the quality of life (QoL) of patients with cancer. Anti-inflammatory tripeptide cream (ATPC) is a complex formulation of anti-inflammatory tripeptides, the CD99-agonist Binterin and the Wnt-antagonist Winhibin. The present study aimed to assess the therapeutic effects of ATPC in HFS/HFSR associated with anticancer drugs.

Materials and methods: This was a single-center, randomized, double-blind, placebo-controlled trial. Patients who developed grade 1 HFS/HFSR after systemic anticancer treatments were enrolled, and randomly assigned to receive either ATPC or placebo cream (PC) and followed up at 3-week intervals for up to 9 weeks. Primary endpoint was the development of grade ≥ 2 HFS/HFSR.

Results: Between April 2019 and July 2022, 60 patients (31 in the ATPC and 29 in the PC group) completed the study. The incidence of grade ≥ 2 HFS/HFSR was significantly lower in the ATPC than in the PC group (25.8% vs. 51.7%, p=0.039). The ATPC showed trends towards a better QoL score, assessed by a HFSR and QoL questionnaire at 9 weeks (26.0 vs. 29.9, p=0.574), and a lower frequency of discontinuation, interruption, or dose reduction of anticancer drugs (51.6% vs. 58.6%, p=0.586) than the PC group over 9 weeks, though without statistical significance.

Conclusion: Our results showed that ATPC significantly decreased the development of grade ≥ 2 HFS/HFSR in patients already with HFS/HFSR. Therefore, ATPC may be an effective treatment for HFS/HFSR associated with anticancer drugs.

Purpose: Since 2020, atezolizumab plus bevacizumab (Ate/Bev) has been the standard first-line therapy for unresectable hepatocellular carcinoma (HCC), but long-term treatment studies are limited. This study evaluated the clinical characteristics and effects of Ate/Bev for over 1 year.

Materials and methods: This study included patients with unresectable HCC treated with first-line Ate/Bev between May 2020 and April 2022. Those receiving Ate/Bev for 1 year or more were classified as the long-term treatment group.

Results: Of 246 patients, 69 (28.0%) were in the long-term treatment group, which comprised more proportions of intrahepatic tumor burden < 25%, Eastern Cooperative Oncology Group 0, and a lower proportion of portal vein tumor thrombosis than the short-term treatment group. The long-term treatment group had a higher incidence of atezolizumab-related thyroid dysfunction (31.9% vs. 10.7%, p < 0.001; median time to onset [mTTO], 2.8 months), dermatologic toxicity (29.0% vs. 14.7%, p=0.017; mTTO, 3.3 months), bevacizumab-related hypertension (44.9% vs. 22.0%, p=0.001; mTTO, 4.2 months), and proteinuria (69.6% vs. 38.4%, p < 0.001; mTTO, 6.8 months), compared to the short-term treatment group. Regarding liver function in the long-term treatment group, patients initially classified as Child-Pugh class A decreased from 87.0% to 75.4%, and albumin-bilirubin grade 1 decreased from 68.1% to 50.7% after 1 year of treatment.

Conclusion: The Ate/Bev long-term treatment group had a lower intrahepatic tumor burden, less portal vein tumor thrombosis, and better performance status and liver function at baseline. Atezolizumab-related immunological adverse events emerged relatively early in treatment compared to the bevacizumab-related. Additionally, some patients demonstrated liver function deterioration during long-term Ate/Bev treatment.