Li Jen Kuo

Bio: Li Jen Kuo is an academic researcher from Taipei Medical University Hospital. The author has contributed to research in topics: Colorectal cancer & Medicine. The author has an hindex of 4, co-authored 5 publications receiving 1311 citations. Previous affiliations of Li Jen Kuo include Taipei Medical University.

Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data

Abstract: Summary Background Locally advanced rectal cancer is usually treated with preoperative chemoradiation. After chemoradiation and surgery, 15–27% of the patients have no residual viable tumour at pathological examination, a pathological complete response (pCR). This study established whether patients with pCR have better long-term outcome than do those without pCR. Methods In PubMed, Medline, and Embase we identified 27 articles, based on 17 different datasets, for long-term outcome of patients with and without pCR. 14 investigators agreed to provide individual patient data. All patients underwent chemoradiation and total mesorectal excision. Primary outcome was 5-year disease-free survival. Kaplan-Meier survival functions were computed and hazard ratios (HRs) calculated, with the Cox proportional hazards model. Subgroup analyses were done to test for effect modification by other predicting factors. Interstudy heterogeneity was assessed for disease-free survival and overall survival with forest plots and the Q test. Findings 484 of 3105 included patients had a pCR. Median follow-up for all patients was 48 months (range 0–277). 5-year crude disease-free survival was 83·3% (95% CI 78·8–87·0) for patients with pCR (61/419 patients had disease recurrence) and 65·6% (63·6–68·0) for those without pCR (747/2263; HR 0·44, 95% CI 0·34–0·57; p Q test and forest plots did not suggest significant interstudy variation. The adjusted HR for pCR for failure was 0·54 (95% CI 0·40–0·73), indicating that patients with pCR had a significantly increased probability of disease-free survival. The adjusted HR for disease-free survival for administration of adjuvant chemotherapy was 0·91 (95% CI 0·73–1·12). The effect of pCR on disease-free survival was not modified by other prognostic factors. Interpretation Patients with pCR after chemoradiation have better long-term outcome than do those without pCR. pCR might be indicative of a prognostically favourable biological tumour profile with less propensity for local or distant recurrence and improved survival. Funding None.

Adjuvant chemotherapy in rectal cancer: Defining subgroups who may benefit after neoadjuvant chemoradiation and resection: A pooled analysis of 3,313 patients

Abstract: Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorized into three groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios (HR) for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). One thousand seven hundred and twenty three (1723) (52%) of 3,313 included patients received aCT. Eight hundred and ninety eight (898) patients had a pCR, 966 had a ypT1-2 tumour and 1,302 had a ypT3-4 tumour. For 122 patients response, category was missing and 25 patients had ypT0N+. Median follow-up for all patients was 51 (0-219) months. HR for RFS with 95% CI for patients treated with aCT were 1.25(0.68-2.29), 0.58(0.37-0.89) and 0.83(0.66-1.10) for patients with pCR, ypT1-2 and ypT3-4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging.

Evaluation of response after chemoradiation for rectal cancer as a predictive factor for the benefit of adjuvant chemotherapy: A pooled analysis of 2,724 individual patients.

Abstract: 361 Background: Neoadjuvant chemoradiation (CRT) for rectal cancer increasingly results in pathologic response. It has been suggested that patients with different degrees of response might not have...

Prevalence of nodal involvement in rectal cancer after chemoradiotherapy

Abstract: BACKGROUND The purpose of this study was to investigate the prevalence of ypN+ status according to ypT category in patients with locally advanced rectal cancer treated with chemoradiotherapy and total mesorectal excision, and to assess the impact of ypN+ on disease recurrence and survival by pooled analysis of individual-patient data. METHODS Individual-patient data from 10 studies of chemoradiotherapy for rectal cancer were included. Pooled rates of ypN+ disease were calculated with 95 per cent confidence interval for each ypT category. Kaplan-Meier and Cox regression analyses were undertaken to assess influence of ypN status on 5-year disease-free survival (DFS) and overall survival (OS). RESULTS Data on 1898 patients were included in the study. Median follow-up was 50 (range 0-219) months. The pooled rate of ypN+ disease was 7 per cent for ypT0, 12 per cent for ypT1, 17 per cent for ypT2, 40 per cent for ypT3, and 46 per cent for ypT4 tumours. Patients with ypN+ disease had lower 5-year DFS and OS (46.2 and 63.4 per cent respectively) than patients with ypN0 tumours (74.5 and 83.2 per cent) (P < 0.001). Cox regression analyses showed ypN+ status to be an independent predictor of recurrence and death. CONCLUSION Risk of nodal metastases (ypN+) after chemoradiotherapy increases with advancing ypT category and needs to be considered if an organ-preserving strategy is contemplated.

A Scoping Review to Assess Adherence to and Clinical Outcomes of Wearable Devices in the Cancer Population

Abstract: Simple Summary The use of wearable devices in clinical care is gaining popularity among cancer patients. The COVID-19 pandemic highlighted the value of wearable devices for monitoring health. Wearable devices are used to record and monitor real-time data like physical activity, sleep metrics, and heart rate variables. The use of wearable devices can directly impact clinical decision-making. There are few pieces of evidence that prove that wearable could improve the quality of patient care while reducing the cost of care, such as remote health monitoring. The generated big data by the wearable device is both a challenge and an opportunity. Researchers can apply artificial intelligence and machine learning techniques to improve wearable devices and their usage among cancer patients. In this scoping review, we assessed the adherence to clinical outcomes of wrist-worn wearable devices in the cancer population. Abstract The use of wearable devices (WDs) in healthcare monitoring and management has attracted increasing attention. A major problem is patients’ adherence and acceptance of WDs given that they are already experiencing a disease burden and treatment side effects. This scoping review explored the use of wrist-worn devices in the cancer population, with a special focus on adherence and clinical outcomes. Relevant articles focusing on the use of WDs in cancer care management were retrieved from PubMed, Scopus, and Embase from 1 January 2017 to 3 March 2022. Studies were independently screened and relevant information was extracted. We identified 752 studies, of which 38 met our inclusion criteria. Studies focused on mixed, breast, colorectal, lung, gastric, urothelial, skin, liver, and blood cancers. Adherence to WDs varied from 60% to 100%. The highest adherence was reported in the 12-week studies. Most studies focused on physical activity, sleep analysis, and heart vital signs. Of the 10 studies that described patient-reported outcomes using questionnaires and personal interviews, 8 indicated a positive correlation between the patient-reported and wearable outcomes. The definitions of the outcome measures and adherence varied across the studies. A better understanding of the intervention standards in terms of the clinical outcomes could improve adherence to wearables.

Wait-and-See Policy for Clinical Complete Responders After Chemoradiation for Rectal Cancer

Abstract: Purpose Neoadjuvant chemoradiotherapy for rectal cancer can result in complete disappearance of tumor and involved nodes. In patients without residual tumor on imaging and endoscopy (clinical complete response [cCR]) a wait-and-see-policy (omission of surgery with follow-up) might be considered instead of surgery. The purpose of this prospective cohort study was to evaluate feasibility and safety of a wait-and-see policy with strict selection criteria and follow-up. Patients and Methods Patients with a cCR after chemoradiotherapy were prospectively selected for the wait-and-see policy with magnetic resonance imaging (MRI) and endoscopy plus biopsies. Follow-up was performed 3 to 6 monthly and consisted of MRI, endoscopy, and computed tomography scans. A control group of patients with a pathologic complete response (pCR) after surgery was identified from a prospective cohort study. Functional outcome was measured with the Memorial SloanKettering Cancer Center (MSKCC) bowel function questionnaire and Wexner incontinence score. Long-term outcome was estimated by using Kaplan-Meier curves. Results Twenty-one patients with cCR were included in the wait-and-see policy group. Mean follow-up was 25 19 months. One patient developed a local recurrence and had surgery as salvage treatment. The other 20 patients are alive without disease. The control group consisted of 20 patients with a pCR after surgery who had a mean follow-up of 35 23 months. For these patients with a pCR, cumulative probabilities of 2-year disease-free survival and overall survival were 93% and 91%, respectively. Conclusion A wait-and-see policy with strict selection criteria, up-to-date imaging techniques, and follow-up is feasible and results in promising outcome at least as good as that of patients with a pCR after surgery. The proposed selection criteria and follow-up could form the basis for future randomized studies. J Clin Oncol 29:4633-4640. © 2011 by American Society of Clinical Oncology

Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial.

Abstract: Summary Background Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. Methods In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 × 5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/m2 orally twice daily on days 1–14, oxaliplatin 130 mg/m2 intravenously on day 1, and a chemotherapy-free interval between days 15–21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin [folinic acid] 200 mg/m2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m2 intravenously and fluorouracil 600 mg/m2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3–14) followed by total mesorectal excision. Choice of CAPOX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1·8 Gy up to 50·4 Gy or 25 fractions of 2·0 Gy up to 50·0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m2 followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPOX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov , NCT01558921 , and is now complete. Findings Between June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5–5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8–27·6) in the experimental group versus 30·4% (26·1–34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60–0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression). Interpretation The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer. Funding Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network.

Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis

Abstract: Summary Background Induction of a clinical complete response with chemoradiotherapy, followed by observation via a watch-and-wait approach, has emerged as a management option for patients with rectal cancer. We aimed to address the shortage of evidence regarding the safety of the watch-and-wait approach by comparing oncological outcomes between patients managed by watch and wait who achieved a clinical complete response and those who had surgical resection (standard care). Methods Oncological Outcomes after Clinical Complete Response in Patients with Rectal Cancer (OnCoRe) was a propensity-score matched cohort analysis study, that included patients of all ages diagnosed with rectal adenocarcinoma without distant metastases who had received preoperative chemoradiotherapy (45 Gy in 25 daily fractions with concurrent fluoropyrimidine-based chemotherapy) at a tertiary cancer centre in Manchester, UK, between Jan 14, 2011, and April 15, 2013. Patients who had a clinical complete response were offered management with the watch-and-wait approach, and patients who did not have a complete clinical response were offered surgical resection if eligible. We also included patients with a clinical complete response managed by watch and wait between March 10, 2005, and Jan 21, 2015, across three neighbouring UK regional cancer centres, whose details were obtained through a registry. For comparative analyses, we derived one-to-one paired cohorts of watch and wait versus surgical resection using propensity-score matching (including T stage, age, and performance status). The primary endpoint was non-regrowth disease-free survival from the date that chemoradiotherapy was started, and secondary endpoints were overall survival, and colostomy-free survival. We used a conservative p value of less than 0·01 to indicate statistical significance in the comparative analyses. Findings 259 patients were included in our Manchester tertiary cancer centre cohort, 228 of whom underwent surgical resection at referring hospitals and 31 of whom had a clinical complete response, managed by watch and wait. A further 98 patients were added to the watch-and-wait group via the registry. Of the 129 patients managed by watch and wait (median follow-up 33 months [IQR 19–43]), 44 (34%) had local regrowths (3-year actuarial rate 38% [95% CI 30–48]); 36 (88%) of 41 patients with non-metastatic local regrowths were salvaged. In the matched analyses (109 patients in each treatment group), no differences in 3-year non-regrowth disease-free survival were noted between watch and wait and surgical resection (88% [95% CI 75–94] with watch and wait vs 78% [63–87] with surgical resection; time-varying p=0·043). Similarly, no difference in 3-year overall survival was noted (96% [88–98] vs 87% [77–93]; time-varying p=0·024). By contrast, patients managed by watch and wait had significantly better 3-year colostomy-free survival than did those who had surgical resection (74% [95% CI 64–82] vs 47% [37–57]; hazard ratio 0·445 [95% CI 0·31–0·63; p Interpretation A substantial proportion of patients with rectal cancer managed by watch and wait avoided major surgery and averted permanent colostomy without loss of oncological safety at 3 years. These findings should inform decision making at the outset of chemoradiotherapy. Funding Bowel Disease Research Foundation.

Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial

Abstract: Summary Background Preoperative chemoradiotherapy with infusional fluorouracil, total mesorectal excision surgery, and postoperative chemotherapy with fluorouracil was established by the German CAO/ARO/AIO-94 trial as a standard combined modality treatment for locally advanced rectal cancer. Here we compare the previously established regimen with an investigational regimen in which oxaliplatin was added to both preoperative chemoradiotherapy and postoperative chemotherapy. Methods In this multicentre, open-label, randomised, phase 3 study we randomly assigned patients with rectal adenocarcinoma, clinically staged as cT3–4 or any node-positive disease, to two groups: a control group receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy of 50·4 Gy in 28 fractions plus infusional fluorouracil (1000 mg/m 2 on days 1–5 and 29–33), followed by surgery and four cycles of bolus fluorouracil (500 mg/m 2 on days 1–5 and 29); or to an investigational group receiving preoperative radiotherapy of 50·4 Gy in 28 fractions plus infusional fluorouracil (250 mg/m 2 on days 1–14 and 22–35) and oxaliplatin (50 mg/m 2 on days 1, 8, 22, and 29), followed by surgery and eight cycles of oxaliplatin (100 mg/m 2 on days 1 and 15), leucovorin (400 mg/m 2 on days 1 and 15), and infusional fluorouracil (2400 mg/m 2 on days 1–2 and 15–16). Randomisation was done with computer-generated block-randomisation codes stratified by centre, clinical T category (cT1–3 vs cT4), and clinical N category (cN0 vs cN1–2) without masking. The primary endpoint was disease-free survival, defined as the time between randomisation and non-radical surgery of the primary tumour (R2 resection), locoregional recurrence after R0/1 resection, metastatic disease or progression, or death from any cause, whichever occurred first. Survival and cumulative incidence of recurrence analyses followed the intention-to-treat principle; toxicity analyses included all patients treated. Enrolment of patients in this trial is completed and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT00349076. Findings Of the 1265 patients initially enrolled, 1236 were assessable (613 in the investigational group and 623 in the control group). With a median follow-up of 50 months (IQR 38–61), disease-free survival at 3 years was 75·9% (95% CI 72·4–79·5) in the investigational group and 71·2% (95% CI 67·6–74·9) in the control group (hazard ratio [HR] 0·79, 95% CI 0·64–0·98; p=0·03). Preoperative grade 3–4 toxic effects occurred in 144 (24%) of 607 patients who actually received fluorouracil and oxaliplatin during chemoradiotherapy and in 128 (20%) of 625 patients who actually received fluorouracil chemoradiotherapy. Of 445 patients who actually received adjuvant fluorouracil and leucovorin and oxaliplatin, 158 (36%) had grade 3–4 toxic effects, as did 170 (36%) of 470 patients who actually received adjuvant fluorouracil. Late grade 3–4 adverse events in patients who received protocol-specified preoperative and postoperative treatment occurred in 112 (25%) of 445 patients in the investigational group, and in 100 (21%) of 470 patients in the control group. Interpretation Adding oxaliplatin to fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy (at the doses and intensities used in this trial) significantly improved disease-free survival of patients with clinically staged cT3–4 or cN1–2 rectal cancer compared with our former fluorouracil-based combined modality regimen (based on CAO/ARO/AIO-94). The regimen established by CAO/ARO/AIO-04 can be deemed a new treatment option for patients with locally advanced rectal cancer. Funding German Cancer Aid (Deutsche Krebshilfe).