Chou-Chen Chen’s research while affiliated with National Chung Hsing University and other places

Background and Objective: Colorectal cancer (CRC) is the third most common cancer worldwide, with colon cancer accounting for approximately 60% of all CRC cases. Surgery remains the primary and most effective treatment. Robotic-assisted surgery (RAS) has emerged as a promising approach for colon cancer resection. This retrospective study compares RAS and laparoscopic-assisted surgery (LSS) for stage I–III colon cancer resections at a single medical center in East Asia. Methods: Between 1 January 2018, and 29 February 2024, patients undergoing colectomy were classified into right-side and left-side colectomies. Propensity score matching was conducted based on age group, gender, ASA score, and BMI to ensure comparability between groups. After matching, there were 50 RAS and 200 LSS cases for right colectomy (RC), and 129 RAS and 258 LSS cases for left colectomy (LC). Perioperative outcomes were compared between the two surgical approaches. The primary outcomes were recovery milestones, while secondary outcomes included complications and postoperative pain scores. Results: RAS demonstrated faster recovery milestones compared to LSS (hospital stay: 6.5 vs. 10.2 days, p = 0.005 for RC; 5.5 vs. 8.2 days, p < 0.001 for LC). RAS also resulted in lower rates of ileus (14% vs. 26%, p = 0.064 for RC; 6.2% vs. 15.9%, p = 0.007 for LC) and higher lymph node yields (31.4 vs. 26.8, p = 0.028 for RC; 25.8 vs. 23.9, p = 0.066 for LC). Major complication rates showed no significant difference between RAS and LSS (4.0% vs. 7.0%, p = 0.746 for RC; 4.7% vs. 3.1%, p = 0.563 for LC). Patients in the RAS group experienced earlier diuretic phases and reported significantly lower postoperative pain scores (3.0 vs. 4.1, p = 0.011 for RC; 2.9 vs. 4.1, p < 0.001 for LC). Conclusions: Robotic-assisted surgery is associated with faster recovery, lower rates of ileus (LC), higher lymph node yield (RC) and reduced postoperative pain compared to laparoscopic-assisted surgery for colon cancer resection.

Aim: The tumor staging of colorectal cancer (CRC) plays a significant role in both treatment and prognosis, impacting surgical planning and adjuvant therapy decisions. Currently, the staging of CRC is based on the TNM system developed by the American Joint Committee on Cancer. Prior studies have suggested that survival rates and recurrent rates of T4a tumors appear to be worse than that of T4b tumors, although there is currently no consensus. Therefore, we collected patient data from Taichung Veterans General Hospital over the past decade in order to conduct further research. Method: Between 2010 and 2018, a total of 5760 newly diagnosed CRC patients were seen at the hospital. To eliminate the influence of any local lymph node involvement or distant organ metastasis on the research results, we focused on patients with pathologic Stage IIc disease (T4a-bN0M0). Patients with rectal cancer who had received neoadjuvant concurrent chemoradiotherapy were excluded. Ultimately, 132 patients were included in this study. A multivariate Cox regression analysis was conducted to identify independent risk factors for both 10-year cancer-specific survival (CSS) and overall survival (OS). Results: A total of 132 patients were included in the study, with 90 classified as T4a and 42 as T4b. The 10-year CSS for pT4a and pT4b was 72.5% and 56.5%, respectively, with a p-value of 0.011. The 10-year OS for pT4a and pT4b was 48.4% and 42.5%, respectively, with a p-value of 0.086. There was no significant difference in the site of first recurrence between the pT4a and pT4b groups (p-value = 0.936). Overall, patients who received adjuvant chemotherapy therapy had a significantly better prognosis (p-value < 0.05). However, there was no significant difference in prognosis between oral 5-FU and FOLFOX. Conclusion: Based on our data, patients diagnosed with pathologic T4aN0M0 CRC appeared to experience a trend toward better 10-year OS when compared to those with T4bN0M0 disease, but this trend lacks statistical significance. Patients with locally advanced Stage II colon cancer clearly benefited from adjuvant chemotherapy therapy; therefore, FOLFOX may not necessarily be required.

Background & aims: The QUASAR Phase 2b Induction Study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, or advanced therapy. Methods: In this double-blind, placebo-controlled, dose-ranging, induction study, patients were randomized (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0/4/8. The primary endpoint was clinical response (compared with baseline, modified Mayo score decrease ≥30% and ≥2 points, rectal bleeding subscore ≥1-point decrease or subscore of 0/1) at week 12. Guselkumab and placebo week-12 clinical nonresponders received subcutaneous or intravenous guselkumab 200 mg, respectively, at weeks 12/16/20 (uncontrolled study period). Results: The primary analysis population included patients with baseline modified Mayo scores ≥5 and ≤9 (intravenous guselkumab 200 mg, N=101; 400 mg, N=107; placebo, N=105). Week-12 clinical response percentage was greater with guselkumab 200 mg (61.4%) and 400 mg (60.7%) versus placebo (27.6%; both P<.001). Greater proportions of guselkumab-treated versus placebo-treated patients achieved all major secondary endpoints (clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization) at week 12. Among guselkumab week-12 clinical nonresponders, 54.3% and 50.0% of patients in the 200 and 400 mg groups, respectively, achieved clinical response at week 24. Safety was similar among guselkumab and placebo groups. Conclusions: Guselkumab intravenous induction was effective versus placebo in patients with moderately to severely active UC. Guselkumab was safe, and efficacy and safety were similar between guselkumab dose groups.

Malnutrition is a common problem in patients with metastatic colorectal cancer (mCRC) receiving targeted therapy plus chemotherapy, resulting in severe toxicity and decreased survival rates. This retrospective study employing propensity score matching (PSM) examined the efficacy and safety of a supplemental home parenteral nutrition (HPN) program for patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy. This retrospective nationwide registry study included data from 14 medical centers/hospitals across Taiwan, and the data period ranged from November 2016 to December 2020. Patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy as their first-line therapy were included and divided into HPN and non-HPN program groups. HPN was initiated based on patient-specific factors, such as baseline nutritional status, treatment-related toxicities, and comorbidities. Clinical outcomes were evaluated using response to therapy, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). This study recruited 758 patients, of whom 110 and 648 were included in the HPN and non-HPN program groups, respectively. After 1:3 PSM, the data of 109 and 327 patients from the HPN and non-HPN program groups were analyzed, respectively. The HPN program group had a higher metastasectomy rate (33.9% vs. 20.2%, p = 0.005), and longer duration of treatment and DoR than the non-HPN program group (13.6 vs. 10.3 and 13.6 vs. 9.9 months, p = 0.001 and < 0.001, respectively). The HPN program group tended to have a longer median PFS (18.2 vs. 13.9 months, p = 0.102). Moreover, we noted a significant improvement in the median OS in the same group (53.4 vs. 34.6 months, p = 0.002). Supplemental HPN programs may be recommended for select patients with mCRC receiving targeted therapy plus chemotherapy to improve oncological outcomes.

Background/aim: Metalloproteinase-7 (MMP-7) has been previously found to be up-regulated in hepatocellular carcinoma (HCC) specimens and cells, favoring epithelial-mesenchymal transition. However, the contribution of MMP-7 genotypes to HCC has not been revealed to date. The study aimed to evaluate the contribution of MMP-7 promoter A-181G (rs11568818) and C-153T (rs11568819) genotypes on the risk of HCC in Taiwan, where HCC incidence is extremely high compared to worldwide data. Materials and methods: In this case-control study, MMP-7 genotypes and their association with cigarette smoking and alcohol drinking habits were determined in 298 HCC patients and 889 healthy subjects by a typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Results: Ever smokers and alcohol drinkers were represented with higher percentages in the case group compared to the control group. MMP-7 rs11568818 genotypes were not found differentially distributed in case and control groups (p for trend=0.5246). People of the analyzed cohort of the present study were all of CC genotypes at their rs11568819 polymorphic sites, without any CT or TT genotypes. As for gene-lifestyle interactions, people with variant genotypes at MMP-7 rs11568818 had the same odds for HCC development compared to the wild-type AA genotype, no matter whether the subjects belonged to the smoker, non-smoker alcohol drinker, or non-drinker groups. Conclusion: MMP-7 variant genotypes did not present any significance towards being a marker for HCC risk in Taiwanese.

Background: Bevacizumab-awwb (MVASI®) is the first and the only bevacizumab biosimilar made available in Taiwan. However, its extrapolation of indication and the lack of available real-world clinical data has raised some concern. This article is aimed at presenting our real-world experience in the use of MVASI for treating patients with metastatic Colorectal Cancer (mCRC) for purposes of evaluating tumor response and safety. Materials & Methods: Adult patients from a single institution initiating MVASI use following an mCRC diagnosis during the period of May 2020 to August 2021 were included in the study. Each patient's demographics and tumor characteristics were collated retrospectively. We described treatment patterns and evaluated treatment efficacy stratified by initiating MVASI as either first line or later line therapy. Results: A total of 20 patients were identified, with 2 being excluded due to incomplete therapy and lost follow-up. The mean age of the subjects was 58.7 years. Most patients had a left-sided colorectal tumor (83.3%) and underwent a primary tumor resection (94%) prior to systemic antineoplastic therapy. Fourteen out of 18 patients initiated MVASI use as first line therapy, where the Disease-control Rate (DCR) was 85.7%. Alternatively, four out of 18 patients in later line therapy all experienced disease progression, with progression-free survival (PFS) ranging 4 to 10 months. Five patients had prior bevacizumab reference product utilization but switched to MVASI mostly due to economic issues, with three of these patients (60%) showing progression disease (PFS ranging 3-10 months). Only two patients (11%) encountered adverse events during MVASI therapy. Conclusion: Both the efficacy and safety of MVASI in the mCRC population are deemed comparable with the bevacizumab reference product, exclusively at first line therapy. The strategy of switching between the biosimilar and reference product is currently controversial, and therefore further studies are still required.

3603 Background: PEP503 (aka NBTXR3) is a novel radio-enhancer composed of functionalized hafnium oxide nanoparticles that increases the energy deposition of radiotherapy. A phase 3 study in soft tissue sarcoma patients has significantly increased pCR and R0 when PEP503 was added to preop radiotherapy. This phase 1b/2 study was conducted with the aim to identify a recommended phase 2 dose (RP2D), and evaluate the efficacy of PEP503 intratumoral injection in combination with concurrent chemoradiation (CCRT) in patients with locally advanced rectal cancer (LARC). Methods: Patients with stage T3-T4 LARC (or with unresectable disease) suitable for neoadjuvant CCRT were enrolled. An intratumoral single administration of PEP503 (multiple punctures) was done 24 to 72 hours prior to IMRT of 50 Gy in 25 fractions of 2 Gy per fraction over 5-6 weeks with concurrent capecitabine or 5-FU. Traditional 3 + 3 design with 4 levels, 5%, 10%, 15%, and 22%, of the baseline GTV as measured by MRI, of PEP503 were assessed in Phase Ib. PEP503 nanoparticles intratumoral dispersion was analyzed by CT-scan. Surgery was performed 8 to 12 weeks after the completion of CCRT for patients with resectable tumors. Body kinetics was evaluated in Phase Ib. (ClinicalTrials.gov, NCT02465593) Results: Thirty-two (32) patients (male/female: 20/12; median age 62 years, range 38 to 76) were enrolled (1 dropped out before starting CCRT). In Phase 1b, 20 patients were treated and dose was escalated to 22%. RP2D was then determined as 22% with 6 patients treated at this dose level without DLT. Twelve (12) patients were included in the Phase 2. One (1) (3.2%) and 19 (61.3%) of evaluable patients (n = 31) had CR and PR, respectively, as the best tumor response across dose levels. No patient progressed as all evaluable patients (n = 31) achieved disease control for a DCR of 100%. Furthermore, twenty-five patients underwent surgery, of which 24 (96%) had microscopically clear resection margins and 5 of them (20%) had pathological complete response (pCR). The G3 AEs were diarrhea, ileus, thrombocytopenia, urosepsis, procedural haemorrhage, wound complication, hypokalaemia, and myalgia (all in 3.1%). No G4 AE were observed. The results of CT scans for nanoparticles dispersion demonstrated PEP503 remained within the tumor without leakage to the surrounding healthy tissues, before and after CCRT. In most patients, hafnium was not detected or below the Lower Limit of Quantification (LLOQ) in the circulation 60 minutes after PEP503 injection and was not found in urine. Conclusions: A single intratumoral injection of PEP503 in locally advanced or unresectable rectal adenocarcinoma undergoing capecitabine or 5-FU based CCRT is feasible and safe. The preliminary observed efficacy results may warrant further examination in larger clinical studies. Clinical trial information: NCT02465593.