Impact on survival benefits of asymptomatic primary tumor resection after bevacizumab plus FOLFIRI as first-line therapy for patients with metastatic colorectal cancer with synchronous unresectable metastasis.

BACKGROUND: Metastatic colorectal cancer (mCRC) poses a clinical challenge and requires a combination of systemic therapy and conversion surgery. Although first-line chemotherapy and targeted therapy are considered the standard treatments for mCRC, the role of primary tumor resection (PTR) in asymptomatic synchronous mCRC with unresectable metastatic lesion after initial therapy remains relatively underexplored. MATERIALS: A retrospective review was conducted from January 2015 to January 2021, involving 74 patients with synchronous mCRC who received bevacizumab plus FOFIRI as first-line systemic therapy. All 74 patients had unresectable metastatic lesions confirmed through multidisciplinary team discussion. Patient characteristics, PTR data, and radiotherapy (RT) and overall survival (OS) outcomes were analyzed. The patients were categorized into a "PTR" group and a "No PTR" group and then further stratified into "4A," "4B," and "4C" subgroups based on the initial mCRC stage. Additionally, four subgroups-namely "PTR( +)/RT( +)," "PTR( +)/RT( -)," "PTR( -)/RT( +)," and "PTR( -)/RT( -)"-were formed to assess the combined effects of PTR and RT. RESULTS: The median OS for all the patients was 23.8 months (20.5-27.1 months). The "PTR" group exhibited a significantly higher median OS of 25.9 months (21.3-30.5 months) compared with 21.4 months (15.8-27.1 months) in the "No PTR" group (p = 0.048). Subgroup analyses revealed a trend of improved survival with PTR in patients with stage IVA and IVB; however, the results were not statistically significant (p = 0.116 and 0.493, respectively). A subgroup analysis of PTR and RT combinations revealed no significant difference in median OS rates. CONCLUSION: For asymptomatic mCRC with synchronous unresectable distant metastasis, PTR following first-line therapy with bevacizumab plus FOLFIRI may provide a potential survival benefit, particularly in stage IVA/IVB patients compared with stage IVC patients. Additionally, RT for primary tumor did not provide an additional OS benefit in mCRC with unresectable metastasis. A prospective randomized trial with a larger sample size is essential to further elucidate the role of PTR in this context.

Innovative needle-assisted technique for intracorporeal anastomosis: Simplifying closure of common enterotomy in laparoscopic gastrointestinal surgery.

BACKGROUND: Intracorporeal anastomosis offers notable advantages over extracorporeal techniques, including reduced tissue manipulation leading to faster recovery and potentially lower risks of surgical site infections and complications. However, it also involves several challenges, such as increased operative time and the need for experienced assistants and multiple trocars. Our novel technique addresses these problems. METHODS: We present a novel approach for closing common enterotomies during intracorporeal anastomosis by using a linear stapler. This technique involves the use of a 6-cm straight needle, which facilitates closure of the common enterotomy. The technique can be performed independently by a single surgeon without the need for additional trocars or assistants. RESULTS: This technique was applied for 20 patients undergoing laparoscopic gastrointestinal surgery between June 2023 and February 2024. The median age of the enrolled patients was 65 years, with laparoscopic right hemicolectomy with intracorporeal ileocolostomy being the most common procedure (60% of cases). The median anastomosis time was 22.5 min. No occurrence of anastomotic leakage was reported, and only one patient (5%) developed temporary postoperative bowel obstruction, which was managed conservatively. CONCLUSIONS: Our technique enables efficient and safe closure of common enterotomies during intracorporeal anastomosis, minimizing reliance on additional trocars and experienced assistants. It simplifies the procedure and ensures fullthickness stapling, potentially reducing the likelihood of complications. Because of its broad applicability across various laparoscopic surgeries, this technique offers substantial benefits and is worth recommending for intracorporeal anastomosis.

Efficacy of transarterial chemoembolization with drug-eluting beads combined with systemic chemotherapy and targeted therapy in colorectal cancer liver metastasis.

BACKGROUND: Systemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy. MATERIALS: We retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups. RESULTS: In total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed. CONCLUSION: The combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.

Real-World Outcomes of First-Line FOLFIRI Plus Bevacizumab with Irinotecan Dose Escalation versus FOLFOXIRI Plus Bevacizumab in BRAFV600E-Mutant Metastatic Colorectal Cancer: The Preliminary Data from a Single-Center Observational Study.

Background and Objectives: Approximately 5-10% of all patients with metastatic colorectal cancer (mCRC) harbor a BRAFV600E mutation. These patients exhibit distinct metastatic patterns, poor prognosis, and heterogenous survival outcomes. The findings from the TRIBE study indicated that the administration of FOLFOXIRI plus bevacizumab as first-line treatment extended the median duration of overall survival (OS). In this study, we explored the effects of UGT1A1 polymorphism on the outcomes of irinotecan dose escalation versus FOLFOXIRI plus bevacizumab in patients with BRAFV600E-mutant mCRC. Materials and Methods: We retrospectively reviewed the medical records of 25 patients who had received a diagnosis of BRAFV600E-mutant mCRC between October 2015 and August 2022. All patients underwent UGT1A1 genotyping before receiving bevacizumab plus FOLFIRI. The primary end point was progression-free survival (PFS), and secondary endpoints were OS and adverse events (AEs). The two treatment arms were compared in terms of 6-month PFS and 12-month OS. Results: Over a median follow-up duration of 15.0 (interquartile range, 10.0-30.5) months, no significant differences were noted between the treatment arms in severe AEs (SAEs), 6-month PFS, or 12-month OS (all p < 0.05). Regarding AEs, the FOLFIRI plus bevacizumab regimen was associated with a lower incidence of anorexia than was the FOLFOXIRI plus bevacizumab regimen (p = 0.042). Conclusions: Our findings indicate that FOLFIRI plus bevacizumab with irinotecan dose escalation is an effective first-line treatment regimen for patients with BRAFV600E-mutant mCRC. This regimen leads to acceptable clinical outcomes with manageable AEs. However, the effects on survival and safety outcomes could only be speculated, and further studies are needed because of the sample size, the follow-up for the OS evaluation, and the non-uniformity in all the variables considered in the two groups.

Comparison of Next-Generation Sequencing and Polymerase Chain Reaction for Personalized Treatment-Related Genomic Status in Patients with Metastatic Colorectal Cancer.

Personalized treatments based on the genetic profiles of tumors can simultaneously optimize efficacy and minimize toxicity, which is beneficial for improving patient outcomes. This study aimed to integrate gene alterations associated with predictive and prognostic outcomes in patients with metastatic colorectal cancer (mCRC) with polymerase chain reaction (PCR) and in-house next-generation sequencing (NGS) to detect KRAS, NRAS, and BRAF mutations. In the present study, 41 patients with mCRC were assessed between August 2017 and June 2019 at a single institution. The overall concordance between NGS and PCR results for detecting KRAS, NRAS, and BRAF mutations was considerably high (87.8-92.7%), with only 15 discrepant results between PCR and NGS. Our companion diagnostic test analyzes KRAS, NRAS, and BRAF as a panel of CRC molecular targets; therefore, it has the advantages of requiring fewer specimens and being more time and cost efficient than conventional testing for separate analyses, allowing for the simultaneous analysis of multiple genes.

Effects of Good Pain Management (GPM) ward program on patterns of care and pain control in patients with cancer pain in Taiwan.

BACKGROUND: The undertreatment of cancer pain is a global issue although many international guidelines and various studies bloom to explore the approaches in pain management. However, there is no standard care for cancer pain in routine practices. To set up a standardized procedure for improving cancer pain management in Taiwan, the Good Pain Management (GPM) program is explored to provide treatments following the US National Cancer Care Network (NCCN) Adult Cancer Pain Guideline. METHOD: Patients diagnosed with moderate-to-severe cancer pain were eligible and randomized into the GPM or control arm and observed the first 48 h to evaluate the effects of pain management between 2 arms. Pain control, adequacy of treatments, patient satisfaction, and quality of life (QoL) of eligible patients were analyzed. Ad hoc analyses based on the pain medication category were also conducted. RESULT: Fifty-one patients were enrolled, with 26 and 25 assigned to the GPM and control arms, respectively. Significant differences among the GPM and control arms were found including a greater decrease in the mean numerical rating scale (NRS) score in the GPM arm (- 4.6 vs. - 2.8), a lower proportion of moderate-to-severe pain in the GPM arm (23.2% vs. 39.8%), and a higher pain management index (PMI) score in the GPM arm (0.64 points vs. 0.33 points) (all p < 0.05). Ad hoc analyses revealed that the patient subgroups using strong opioids showed better patient satisfaction in GPM arm when compared with the same subgroup in the control arm. CONCLUSION: In summary, our study demonstrated that the implementation of a standardized pain assessment and management approach (GPM ward program) showed significant improvements on pain relief, decreased the portion of moderate-to-severe cancer pain, and increased patient satisfaction in the 1st 48 h after admission. The implementation of the GPM approach in the cancer ward may provide sooner and better improvement of cancer pain management for patients who suffered moderate-to-severe cancer pain. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT03155516).

Supplemental home parenteral nutrition improved nutrition status with comparable quality of life in malnourished unresectable/metastatic gastric cancer receiving salvage chemotherapy.

BACKGROUND: Even with significant advances in surgical techniques and treatment, salvage chemotherapy remains the major treatment strategy for patients with unresectable or metastatic gastric cancer (GC). Practical and technical advances have simplified safe and convenient use of supplemental home parenteral nutrition (HPN). We aimed to clarify the role of HPN in patients with incurable GC undergoing salvage chemotherapy. METHODS: We enrolled 25 patients with GC with a nutritional risk index (NRI) of ≦ 97.5 undergoing HPN. Their nutritional status, laboratory data, and quality of life (QoL) were analyzed using the Research and Treatment of Cancer quality of life questionnaire-C30 before and after HPN administration at 0.5, 1, 2, and 3 months. We enrolled 25 patients with an NRI of > 97.5 not undergoing HPN as the control group. RESULTS: Total protein (P = 0.008), prealbumin (P < 0.001), and total cholesterol (P = 0.023) levels improved significantly after 0.5 months of HPN administration. The study group also demonstrated a marked improvement in nitrogen balance (P = 0.004) and prealbumin levels (P < 0.012) after 1 month. Gains in body weight after 1 month and body mass index after 2 months of HPN administration remained comparable with those of the control group. Global QoL scores were maintained and comparable with those of the control group. CONCLUSIONS: Supplemental HPN therapy for malnourished patients with unresectable or metastatic GC undergoing salvage chemotherapy is feasible and revealed marked improvement in nutritional status. Early HPN intervention should be considered an important part of palliative treatment for advanced GC.

Low-Molecular-Weight Fucoidan as Complementary Therapy of Fluoropyrimidine-Based Chemotherapy in Colorectal Cancer.

This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF--5FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the (1) induction of cell cycle arrest in the S phase and (2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both the c-mesenchymal-epithelial transition (MET)/Kirsten rat sarcoma virus (KRAS)/extracellular signal-regulated kinase (ERK) and the c-MET/phosphatidyl-inositol 3-kinases (PI3K)/protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required in order to validate the results of the present study.

BRAF, MEK, and EGFR Triplet Inhibitors as Salvage Therapy in BRAF-Mutated Metastatic Colorectal Cancer-A Case Series Study Target Therapy of BRAF-Mutated mCRC.

Backgroundand objectives: Patients with BRAF-mutated metastatic colorectal cancer have considerably poorer responses to conventional systemic treatment. The real-world effects of triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in Asia have not been well-reported. Materials and Methods: This single-center case series included patients with BRAF-mutated metastatic colorectal cancer undergoing triplet therapy after failure of prior systemic treatment from 2016 to 2020. The primary outcome was progression-free survival, and secondary outcomes were overall survival, response rate, disease control rate, and adverse events. Results: Nine eligible patients with BRAF-mutated metastatic colorectal cancer receiving triplet therapy were enrolled, with a median follow-up time of 14.5 months (range, 1-26). Most patients (88.8%) had two or more prior systemic treatments, and the triplet regimen was mainly dabrafenib, trametinib, and panitumumab. The overall response rate and disease control rate were 11.1% and 33.3%, respectively. Median progression-free survival and overall survival were 2.9 and 7.4 months, respectively, and a trend toward better overall survival was found with left-sided metastatic colorectal cancer compared with right-sided disease (9.2 vs. 6.9 months, p = 0.093). Adverse events were mostly Grade 1-2, including nausea, hypertension, gastrointestinal symptoms, and skin disorders. Conclusions: In this single-center case series, triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in BRAF-mutated metastatic colorectal cancer had an acceptable safety profile and reasonable efficacy.

Feasibility of robot-assisted surgery in elderly patients with rectal cancer.

BACKGROUND: Although surgical resection is the main treatment for rectal cancer, the optimal surgical protocol for elderly patients with rectal cancer remains controversial. This study evaluated the feasibility of robot-assisted surgery in elderly patients with rectal cancer. PATIENTS AND METHODS: This retrospective study enrolled 156 patients aged 28-93 years diagnosed with Stage I-III rectal cancer, who underwent robot-assisted surgery between May 2013 and December 2018 at a single institution. RESULTS: In total, 156 patients with rectal cancer, including 126 non-elderly (aged < 70 years) and 30 elderly (aged ≥70 years) patients, who underwent robot-assisted surgery were recruited. Between the patient groups, the post-operative length of hospital stay did not differ statistically significantly (P = 0.084). The incidence of overall post-operative complications was statistically significantly lower in the elderly group (P = 0.002). The disease-free and overall survival did not differ statistically significantly between the two groups (P = 0.719 and 0.390, respectively). CONCLUSIONS: Robot-assisted surgery for rectal cancer was well tolerated by elderly patients, with similar results to the non-elderly patients. Oncological outcomes and survival did not depend on patient age, suggesting that robot-assisted surgery is a feasible surgical modality for treating operable rectal cancer and leads to age-independent post-operative outcomes in elderly patients.

Impact of previous abdominal surgery on robotic-assisted rectal surgery in patients with locally advanced rectal adenocarcinoma: a propensity score matching study.

BACKGROUND: The application of minimally invasive surgery in patients with colorectal cancer (CRC) and a history of previous abdominal surgery (PAS) remains controversial. This retrospective study with propensity score matching (PSM) investigated the impact of PAS on robotic-assisted rectal surgery outcomes in patients with locally advanced rectal adenocarcinoma undergoing preoperative concurrent chemoradiotherapy (CCRT). METHODS: In total, 203 patients with locally advanced rectal adenocarcinoma who underwent preoperative CCRT and robotic-assisted rectal surgery between May 2013 and December 2019 were enrolled. Patients were categorized into PAS and non-PAS groups based on the PAS history. The PSM caliper matching method with 1-to-3 matches was used to match PAS patients with non-PAS. RESULTS: Of the 203 enrolled patients, 35 were PAS patients and 168 were non-PAS patients. After PSM, 32 PAS patients and 96 non-PAS patients were included for analysis. No significant between-group differences were noted in the perioperative outcomes, including median console time (165 min (PAS) vs. 175 min (non-PAS), P = 0.4542) and median operation time (275 min (PAS) vs. 290 min (non-PAS), P = 0.5943) after PSM. Postoperative recovery and overall complication rates were also similar (all P > 0.05). Moreover, the between-group differences in pathological or short-term oncological outcomes were also nonsignificant (all P > 0.05). No 30-day postoperative deaths were observed in either group. CONCLUSION: The current results indicate that robotic-assisted surgery is safe and feasible for PAS patients with locally advanced rectal adenocarcinoma undergoing preoperative CCRT. However, future prospective randomized clinical trials are required to verify these findings.

Ectopic pancreas mimicking gastric submucosal tumour treated using robotic surgery.

Gastric ectopic pancreas presenting as a submucosal tumour accounts for approximately 11% of all endoscopic ultrasonography (EUS) examinations. Definitive diagnosis through endoscopy is difficult, even with EUS-guided fine-needle aspiration biopsy for histological examination. For symptomatic patients or those with uncertain diagnosis, complete surgical resection is the primary strategy for treatment and diagnosis. Herein, we report a case of gastric ectopic pancreas treated using robotic surgery.

Impact of a Dual-Ring Wound Protector on Outcome After Elective Surgery for Colorectal Cancer.

BACKGROUND: The impact of dual-ring wound protectors (DRWPs) on the long-term outcomes of patients with colorectal cancer (CRC) undergoing elective surgery remains unclear. The aim of this cohort study was to compare short- and long-term outcomes after CRC resection with or without use of a DRWP. METHODS: This study enrolled 625 patients with stage I-III CRC undergoing curative resection and divided them into DRWP (n = 348) and control (n = 277) groups. Primary endpoints were postoperative short- and long-term complications. Secondary endpoints were oncological outcomes including wound recurrence, disease-free survival, and overall survival. RESULTS: Rates of postoperative complications (P = 0.004) and laparotomy wound infection (LWI) (P < 0.001) were markedly lower in the DRWP group. Operation quality, as per the number of lymph nodes harvested and rate of R0 resection, did not differ between the groups (all P > 0.05). The DRWP group exhibited significantly lower rates of incisional hernia occurrence (5.3% versus 9.5%, P = 0.045) compared with the control group. Multivariable analyses demonstrated an increased risk of LWI with no wound protector in colorectal surgery (odds ratio, 3.778; P = 0.001), and patients who developed LWI after surgery were more than 4 times more likely to develop an incisional hernia during outpatient follow-up (odds ratio, 4.333; P = 0.001). One patient in the control group (0.36%) had isolated wound recurrence at 12 mo postoperatively. CONCLUSIONS: Fewer postoperative and late complications, comparable oncological safety, and similar long-term clinical outcomes confirmed the benefits of DRWP use for patients with CRC undergoing elective surgery. Therefore, the use of DRWP may be considered in curative CRC resection.

Is ypTNM staging a comparable predictor as pTNM staging for survival in non-metastatic rectal cancer after preoperative chemoradiation therapy?

Background: The pTNM staging system is widely recognized as the most effective prognostic indicator for cancer. The latest update of this staging system introduced a new pathological staging system (ypTNM) for patients receiving neoadjuvant chemoradiotherapy (NACRT). However, whether the prognostic value of the ypTNM staging system for rectal cancer is similar to that of the pTNM staging system remains unclear. This study was conducted to compare the ypTNM and pTNM staging systems in terms of their prognostic value for patients with nonmetastatic rectal cancer undergoing proctectomy. Material and Methods: This study was conducted at a large teaching hospital. Between January 2014 and December 2022, 542 patients with rectal cancer were analyzed (median follow-up period, 60 months; range, 6-105 months). Of them, 258 and 284 were included in the pTNM and ypTNM groups, respectively. Inverse probability of treatment weighting (IPTW) was performed to account for the effects of confounders. Cox proportional-hazards regression was performed for the between-group comparison of overall survival (OS). Results: The crude model revealed that OS was similar between the two groups (p = 0.607). After performing IPTW, we found that patients with the same ypTNM- and pTNM-classified stages had similar overall survival (hazard ratio = 1.15; 95% CI = 0.76-1.73; p = 0.5074). Conclusions: For patients with rectal cancer who have received preoperative NACRT, the prognostic value of ypTNM staging appears to be similar to that of pTNM staging, mostly because of the downstaging effect of neoadjuvant chemoradiotherapy.

Identifying and clinically validating biomarkers for immunotherapy in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is a leading cause of death. For three decades, chemotherapy with or without targeted therapy (provided before or after tumor resection surgery) has been the standard treatment for patients with CRC. Biomarkers are key tools for performing early detection, prognostication, and survival and treatment response predictions. Notably, immune checkpoint inhibitors (ICIs) have transformed prognoses for solid tumors (including CRC). AREA COVERED: Although immunotherapy has developed considerably, it is only effective for a small number of microsatellite instability-high (MSIH) cancer cases; such cases represent only 5% of metastatic CRC (mCRC) cases, which are characterized by an immune-inflamed microenvironment that can be rewired against cancer cells through ICI administration. Immunotherapy research is gradually uncovering the mechanism underlying immune resistance in patients with CRC and discovering new biomarkers. For example, studies have clinically validated the associations of deficient mismatch repair system/microsatellite instability, tumor mutation burden, programmed death ligand 1 expression, and polymerase epsilon with CRC in patients undergoing immunotherapy. EXPERT OPINIONS: Clinical trials documenting the effect of immune checkpoints were performed to produce long-lasting effects for patients with mCRC. Consequently, therapeutic decision-making models are further refined by the inclusion of powerful molecular biomarkers in patients with CRC.

Clinical and cost-effectiveness analysis of mFOLOFX6 with or without a targeted drug among patients with metastatic colorectal cancer: inverse probability of treatment weighting.

This study investigated the cost-effectiveness and quality of life (QoL) within 1 year of receiving mFOLOFX6 with or without a targeted drug (bevacizumab or ramucirumab) as second-line treatment among patients with metastatic colorectal cancer (mCRC) following the failure of FOLFIRI + bevacizumab as first-line treatment. This prospective cohort study included patients who received a diagnosis of mCRC between March 2015 and May 2020. QoL was evaluated before treatment and at 6 months and 1 year posttreatment. All related variables were controlled using the inverse probability of treatment weighting method. Generalized estimating equations with the difference-in-difference method was used to explore changes in QoL. The incremental cost-utility ratio (ICUR) of the two groups was simulated using the annual-cycle Markov decision tree model. Finally, 39 and 76 patients were included in the targeted and nontargeted agent groups, respectively. At 6 months after treatment, QoL of the two groups improved significantly, but the targeted agent group had significantly better QoL than did the nontargeted agent group at 1 year posttreatment (P < 0.05). When the time frame was set to 20 years, the ICUR of the targeted agent group compared with the nontargeted agent group was US$32,052 per quality-adjusted life years. Addition of a targeted drug to the second-line mFOLOFX6 regimen not only improved the patients' QoL but was also more cost effective when the willingness-to-pay threshold was set at US$33,004 (the per capita gross domestic product of Taiwan). These patients should be reimbursed for these targeted agents by the National Health Insurance scheme in Taiwan.

The Auxiliary Effects of Low-Molecular-Weight Fucoidan in Locally Advanced Rectal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy Before Surgery: A Double-Blind, Randomized, Placebo-Controlled Study.

Patients with cancer use low-molecular-weight fucoidan (LMF) as a supplement to therapy. However, most studies of LMF are in vitro or conducted using animals. Concurrent chemoradiotherapy (CCRT) is the gold standard for locally advanced rectal cancer (LARC). This study investigated the quality of life (QoL) and clinical outcomes of patients with LARC taking LMF as a supplement to neoadjuvant CCRT. This was a double-blind, randomized, placebo-controlled study. The sample comprised 87 patients, of whom 44 were included in a fucoidan group and 43 were included in a placebo group. We compared their QoL scores and clinical outcomes before treatment, and at 1 month, 2 months, and 3 months posttreatment. Pretreatment and posttreatment gut microbiota differences were also compared. Although enhanced physical well-being (PWB) at 2 months and 3 months posttreatment in the fucoidan group were observed (both P < .0125), the improvements of the Functional Assessment of Cancer Therapy for Patients with Colorectal Cancer (FACT-C) were nonsignificant (all P > .0125). Skin rash and itching and fatigue were less common in the fucoidan group (both P < .05). Posttreatment, the genus Parabacteroides was significantly more common in the gut microbiota of the fucoidan group. LMF administration improved the QoL, skin rash and itching, fatigue, and gut microbiota composition of the patients with LARC receiving CCRT.Clinical Trial Registration: NCT04342949.

Clinicopathological Features and Oncological Outcomes of Early and Late Recurrence in Stage III Colorectal Cancer Patients after Adjuvant Oxaliplatin-Based Therapy.

Aims: An adjuvant oxaliplatin-based regimen is the standard of care for patients with stage III colorectal cancer (CRC). Few reports have compared the clinicopathological features and oncological outcomes of such treatment between patients with early (≤1 year) and late recurrence (>1 year). Methods: Between January 2012 and December 2019, CRC recurred in 128 (24.1%) of 531 patients with consecutive stage III CRC after they received curative resection and an adjuvant oxaliplatin-based regimen. The clinicopathological features and oncological outcomes of the 128 patients were analyzed retrospectively. Results: The median follow-up period after the first chemotherapy cycle was 35.0 months (range, 7-100.9), and the median recurrence time was 16.1 months. Forty-seven patients (36.7%) had an early recurrence and eighty-one patients (63.3%) had a late recurrence. Compared with patients with late recurrence, those with early recurrence were mostly younger (median: 58 vs. 64 years, p=0.009), had less oxaliplatin-based therapy cycles (median: 8 vs. 12 cycles, p < 0.001), and had a shorter overall survival time (median: 23.3 vs. 39.7 months, p < 0.001). The area under the curve of patient age and chemotherapy cycles for predicting early recurrence was 0.629 and 0.705 (p=0.015 and p < 0.001), respectively. The receiver operating characteristic curve analysis demonstrated that the cutoff level for patient age was 57 years and the number of chemotherapy cycles was 8. A multivariate analysis revealed that patient age ≤57 years and oxaliplatin-based therapy ≤8 cycles were independent risk factors for early recurrence (odds ratio (OR) = 3.049, p=0.022; OR = 4.995, p=0.002). These factors were associated with an approximately 77.8% risk of recurrence within 1 year, compared with the 21.5% risk associated with patient age >57 years and oxaliplatin-based therapy >8 cycles (p = 0.003). Conclusion: Patients with early recurrence had poorer survival than those with late recurrence. If >8 cycles of oxaliplatin-based therapy can be administered without disease progression, then patients with stage III CRC would have a lower risk of early recurrence.

Efficacy of concurrent radiotherapy in patients with locally advanced rectal cancer and synchronous metastasis receiving systemic therapy.

Background: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is the standard treatment for patients with nonmetastatic locally advanced rectal cancer (LARC). However, for patients with LARC and synchronous metastasis, the optimal treatment strategy and sequence remain inconclusive. In the present study, we evaluated the efficacy and safety of concurrent radiotherapy in patients with de novo metastatic rectal cancer who received chemotherapy and targeted therapy. Methods: We retrospectively reviewed the data of 63 patients with LARC and synchronous metastasis who received intensive therapy at the study hospital between April 2015 and November 2018. The included patients were divided into two groups: RT-CT, those who received systemic chemotherapy with targeted therapy and concurrent radiotherapy (for primary rectal cancer), and CT, those who received only systemic chemotherapy with targeted therapy. Results: Treatment response was better in the RT-CT group than in the CT group. The rate of primary tumor resection (PTR) was higher in the RT-CT group than in the CT group (71.4% and 42.9%, respectively; P = .0286). The RT-CT group exhibited considerably longer local recurrence-free survival (P = .0453) and progression-free survival (PFS; from 13.3 to 22.5 months) than did the CT group (P = .0091); however, the groups did not differ in terms of overall survival (OS; P = .49). Adverse events were almost similar between the groups, except frequent diarrhea, the prevalence of which was higher in the RT-CT group than in the CT group (59.5% and 23.8%, respectively; P = .0075). Conclusions: In the era of biologics, radiotherapy may increase the resectability of primary rectal tumors, reducing the risk of locoregional failure and prolonging PFS. Concurrent pelvic radiotherapy may not substantially improve OS, which is indicated by metastasis. Hence, the resection of the distant metastases may be essential for improving long-term OS. To further determine the efficacy of concurrent radiotherapy, additional prospective, randomized studies must combine preoperative pelvic radiotherapy with PTR and metastectomy to treat patients with stage IV LARC.

Unknown­primary neuroendocrine neoplasms diagnosed by short­acting somatostatin test: Case series in one institution.

Neuroendocrine neoplasms (NENs) are a rare heterogeneous group of neoplasms that arise from neuroendocrine cells. Unknown-primary NENs (UP-NENs) are particularly challenging to diagnose and treat. Techniques such as immunohistochemical stains, functional imaging studies, and molecular cancer classifier assays may help clinicians identify the origin of a tumor. However, numerous medical facilities lack the necessary medical equipment, such as functional imaging scanning, to provide patients with a complete primary tumor survey. Even these tests are not enough to determine the original tumor in some cases. The present case series described the diagnosis and treatment outcomes of patients with UP-NEN in a single institution. The medical records of four patients treated between November 2012 and January 2022 were retrospectively reviewed and clinical symptoms, diagnostic methods, image findings and treatment modalities were considered. All patients were diagnosed having functional UP-NENs by using a short-acting somatostatin test. These patients were treated with long-acting release somatostatin analogs along with a positive result. Short-acting somatostatin is an alternatively simple method to determine if a patient has UP-NENs that are functional or expresses somatostatin receptors in the absence of imaging scanning.