Seok Byung Lim

Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial.

BACKGROUND The role of adjuvant chemotherapy for patients with rectal cancer is controversial, especially when used after preoperative chemoradiotherapy. Fluoropyrimidine-based adjuvant chemotherapy, including fluorouracil and leucovorin, has been widely used; however, the addition of oxaliplatin to fluorouracil and leucovorin (FOLFOX), a standard adjuvant regimen for colon cancer, has not been tested in rectal cancer. We aimed to compare the efficacy and safety of adjuvant fluorouracil and leucovorin with that of FOLFOX in patients with locally advanced rectal cancer after preoperative chemoradiotherapy. METHODS In this open-label, multicentre, phase 2, randomised trial, patients with postoperative pathological stage II (ypT3-4N0) or III (ypTanyN1-2) rectal cancer after preoperative fluoropyrimidine-based chemoradiotherapy and total mesorectal excision were recruited and randomly assigned (1:1) via a web-based software platform to receive adjuvant chemotherapy with either four cycles of fluorouracil and leucovorin (fluorouracil 380 mg/m(2) and leucovorin 20 mg/m(2) on days 1-5, every 4 weeks) or eight cycles of FOLFOX (oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), and fluorouracil bolus 400 mg/m(2) on day 1, and fluorouracil infusion 2400 mg/m(2) for 46 h, every 2 weeks). Stratification factors were pathological stage (II vs III) and centre. Neither patients nor investigators were masked to group assignment. The primary endpoint was 3-year disease-free survival, analysed by intention to treat. This study is fully enrolled, is in long-term follow-up, and is registered with ClinicalTrials.gov, number NCT00807911. FINDINGS Between Nov 19, 2008, and June 12, 2012, 321 patients were randomly assigned to fluorouracil and leucovorin (n=161) and FOLFOX (n=160). 141 (95%) of 149 patients in the fluorouracil plus leucovorin group and 141 (97%) of 146 in the FOLFOX group completed all planned cycles of adjuvant treatment. Median follow-up was 38·2 months (IQR 26·4-50·6). 3-year disease-free survival was 71·6% (95% CI 64·6-78·6) in the FOLFOX group and 62·9% (55·4-70·4) in the fluorouracil plus leucovorin group (hazard ratio 0·657, 95% CI 0·434-0·994; p=0·047). Any grade neutropenia, thrombocytopenia, fatigue, nausea, and sensory neuropathy were significantly more common in the FOLFOX group than in the fluorouracil plus leucovorin group; however, we noted no significant difference in the frequency of these events at grade 3 or 4. The most common grade 3 or worse adverse events were neutropenia (38 [26%] of 149 patients in the fluorouracil plus leucovorin group vs 52 [36%] of 146 patients in the FOLFOX group), leucopenia (eight [5%] vs 12 [8%]), febrile neutropenia (four [3%] vs one [<1%]), diarrhoea (four [3%] vs two [1%]), and nausea (one [<1%] vs two [1%]). INTERPRETATION Adjuvant FOLFOX improves disease-free survival compared with fluorouracil plus leucovorin in patients with locally advanced rectal cancer after preoperative chemoradiotherapy and total mesorectal excision, and warrants further investigation. FUNDING Korea Healthcare Technology R&D Project (South Korean Ministry of Health and Welfare).

Open versus robot‐assisted sphincter‐saving operations in rectal cancer patients: techniques and comparison of outcomes between groups of 100 matched patients

Although open resection using a sphincter‐saving operation (SSO) remains the standard of care for rectal cancer, few studies have compared open and robot‐assisted (RA) SSOs. This study aimed to compare the operative features, functional outcomes, and oncological validity of open and RA SSO for rectal cancer.

Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer.

OBJECTIVE To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. PATIENTS AND METHODS A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (-). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. RESULTS A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (-), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). CONCLUSIONS Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

Cefotetan versus Conventional Triple Antibiotic Prophylaxis in Elective Colorectal Cancer Surgery

This study examined infectious outcomes in elective colorectal cancer surgery between cefotetan alone or conventional triple antibiotics. From January to December 2007, 461 consecutive primary colorectal cancer patients underwent elective surgery. Group A contained 225 patients who received conventional triple antibiotics (cephalosporin, aminoglycoside and metronidazole) for prophylaxis, and group B contained 236 patients who received cefotetan alone for prophylaxis. Treatment failure was defined as the presence of postoperative infection including surgical-site infection (SSI), anastomotic leakage, and pneumonia or urinary tract infection. The two groups were similar in terms of demographics, American Society of Anesthesiologists (ASA) score, tumour location, stage, surgical approach (conventional open vs. laparoscopy-assisted), and type of operation. The treatment failure rates were 3.1% in Group A and 3.4% in Group B (absolute difference, -0.3%; 95% confidence interval [CI], 0.39 to 3.07, P=0.866), with SSI being the most common reason for failure in both groups (2.7% in Group A and 3.0% in Group B [absolute difference, -0.3%; 95% CI, 0.37 to 3.37, P=0.846]). Cefotetan alone is as effective as triple antibiotics for prophylaxis in primary colorectal cancer patients undergoing elective surgery.

Prognostic Factors in Terms of the Number of Metastatic Nodules in Patients With Colorectal Cancer Liver Metastases.

Purpose The hepatic resection is the gold-standard treatment for patients with colorectal-cancer liver metastases (CLM). This study aimed to identify prognostic factors in patients with synchronous CLM who underwent a surgical curative (R0) resection with respect to the number of metastatic nodules. Methods Of 1,261 CLM patients treated between January 1991 and December 2010, 339 who underwent a R0 resection for synchronous CLM were included in this retrospective analysis. Patients were grouped according to the number of CLM nodules: 1–2 CLM nodules, n = 272 (group 1) and 3–8 CLM nodules, n = 67 (group 2). Results The 5-year progression-free survival (PFS) rate in group 1was better than that in group 2 (P = 0.020). The multivariate analysis identified lymph-node metastasis (N2), lymphovascular invasion (LVI), and three or more CLM nodules as independent poor prognostic factors for PFS in all patients and lymph-node metastasis (N2) and LVI as independent poor prognostic factors for patients in group 1. No independent prognostic factors were identified for patients in group 2. CLM treatment method and neoadjuvant chemotherapy were not associated with survival. Conclusion Three or more metastatic nodules, lymph-node metastasis (N2), and LVI were independent poor prognostic factors for PFS in patients with synchronous CLM who underwent a R0 resection. The latter 2 factors were also independent prognostic factors for PFS in patients with less than 3 CLM nodules; however, in patients with three or more CLM nodules, the prognosis for PFS may be related only to liver metastasis.

Simple and Low-Cost Sampling of Cell-Free Nucleic Acids from Blood Plasma for Rapid and Sensitive Detection of Circulating Tumor DNA

Abstract Cell‐free nucleic acids (cfNAs) are emerging diagnostic biomarkers for monitoring the treatment and recurrence of cancers. In particular, the biological role and clinical usefulness of cfNAs obtained from the plasma of patients with various cancers are popular and still intensely explored, yet most studies are limited by technical problems during cfNA isolation. A dimethyl dithiobispropionimidate (DTBP)‐based microchannel platform that enables spontaneous cfNA capture in 15 min with minimal cellular background and no requirements for use of bulky instruments is reported first. This platform identified KRAS and BRAF hot‐spot mutations following cfDNA isolation from the blood plasma and tissues obtained from 30 colorectal cancer patients. The correlation of mutations between the primary tissues and plasma from the patients was high using this platform with whole genome sequencing compared to the spin‐column method. This platform can also be combined with various detection approaches (biooptical sensor, Sanger sequencing, and polymerase chain reaction (PCR)) for rapid, simple, low‐cost, and sensitive circulating tumor DNA detection in blood plasma. The efficiency and versatility of this platform in isolating cfNAs from liquid biopsies has applications in cancer treatment and precision medicine.

Peri-treatment change of anorectal function in patients with rectal cancer after preoperative chemoradiotherapy

Preoperative chemoradiotherapy (PCRT) is a standard treatment for locally advanced rectal cancer. The influence of PCRT on anorectal function has not been objectively assessed. We evaluated the short-term influence of PCRT on anorectal function in patients with locally advanced rectal cancer using anorectal manometry. We included 310 patients with locally advanced mid and lower rectal cancer who underwent PCRT from 2012 to 2015. We compared anorectal function based on anorectal manometry between before and after PCRT according to tumor location, clinical T (cT) stage, and tumor response after PCRT. Lower rectal cancer was common in the cohort of 310 patients (n = 228, 73.5%). Sphincter length (p = 0.003) and maximal resting pressure (p < 0.001) increased and maximal tolerated volume (p = 0.036) decreased after PCRT regardless of tumor location. Maximal squeezing pressure and rectal compliance slightly decreased, without statistical significance. Changes in manometric parameters after PCRT were not associated with changes of cT stage after PCRT. However, minimal sensory volume (p = 0.042) and maximal tolerated volume (p = 0.025) increased significantly in 143 patients (46.1%) with changes in the distance of the cancer from the anal verge after PCRT. PCRT did not impair the overall short-term anorectal manometric parameters in patients with locally advanced rectal cancer. Further study is required to investigate postoperative anorectal function after sphincter-preserving surgery to evaluate the long-term effects of PCRT on anorectal function.

Clinical Value of Whole Body F-18 FDG PET in The Management of Recurrent Colorectal Malignancy

PURPOSE The aim of this study was to evaluate the clinical value of whole body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the patient with a recurrence of a previously treated colorectal malignancy. MATERIALS AND METHODS Fifty-eight cases were scanned using PET at the PET Center of Seoul National University Hospital between May 1995 and Aug 2002. All the patients had had a previous operation for a colorectal malignancy. The PET scans were performed for the following reasons: - investigation of a recurrence (n=12), investigation of the operability (n=38) and clinical follow up (n=8). In these 58 cases, 47 of the CT scans and 55 of the CEA (Carcinoembryonic antigen) were checked prior to the FDG- PET. The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the PET scans were calculated, and compared with those of conventional CT scan and CEA, which were also compared with the previous reported data. Eight cases, whose managements were influenced by the PET findings, were analyzed. RESULTS Recurrences, or metastases, of colorectal cancer developed in 51 cases, with 49 of these being detected by the PET. The accuracy, sensitivity and specificity of the PET were 96.6 (56/58), 96.1 (49/51) and 100% (7/7), respectively. The PPV and NPV of the PET were 100 (49/49) and 77.8% (7/9), respectively. The accuracy and sensitivity of the PET were higher than those of the CT (85.1 and 88.1%), with the differences being statistically significant (p-value 0.001 and 0.003, respectively). CONCLUSION It is concluded that a FDG-PET scan is a more accurate and sensitive diagnostic tool than a CT scan for the detection of a recurrence or metastasis in a colorectal malignancy. In addition, a FDG-PET may alter the management of patients with recurrent colorectal cancer. Therefore, it is recommended that a PET should be considered when a tumor recurrence is suspected during conventional follow up.