Chemotherapy In Rectal Cancer Patients Research Articles

Poor prognostic effects of lymphocytopenia induced by preoperative chemoradiotherapy in rectal cancer

Lymphocytopenia is a potential poor prognostic factor in various cancers. We evaluated the prognostic effect of lymphocytopenia caused by preoperative radiation therapy and chemotherapy in rectal cancer patients.

Comparison of clinical outcomes of stoma reversal during versus after chemotherapy for rectal cancer patients.

The optimal timing of stoma closure during or after adjuvant chemotherapy for rectal cancer patients undergoing sphincter-preserving surgery remains unknown. This study aimed to investigate the influence of clinical and oncological outcomes depending on the timing of stoma closure. Between January 2006 and December 2015, we enrolled 244 consecutive rectal cancer patients who underwent curative-intent sphincter-preserving surgery with diverting transverse colostomy and adjuvant chemotherapy. Patients with stoma closure during (During group) adjuvant chemotherapy were compared to those who had stoma closure after adjuvant chemotherapy (After group). Parastomal hernia occurred more frequently in the after group than in the during group. (10% vs. 2.9%,p = 0.028). Overall, no significant difference was observed in overall survival (OS) or disease-free survival (DFS) between the two groups (p = 0.911 for OS,p = 0.505 for DFS). However, an inferior OS occurred if reopen surgery was performed within 30days of stoma closure in the during group, as compared with the after group (p = 0.004). In addition, a marginally poor DFS was observed in the group of patients who received further operations due to 30-day stoma closure complications compared to the other patients (p = 0.07). For rectal cancer patients who underwent sphincter-preserving surgery, attention should be given to avoid 30-day major complications after stoma reversal because patients who require reoperation during adjuvant chemotherapy may have poor long-term survival.

The impact of adjuvant chemotherapy on survival in mucinous and non-mucinous rectal adenocarcinoma patients after TME surgery.

The value of adjuvant chemotherapy for rectal cancer patients is debated and varies in different subgroups. One such subgroup is mucinous adenocarcinoma (MAC), which is more treatment resistant compared to non-mucinous adenocarcinoma (NMAC). To date, mucinous histology is not taken into account when deciding on adjuvant treatment strategy. This is the first study to exclusively include patients with rectal cancer, then separate MAC and NMAC and compare the survival in patients that had or did not have adjuvant chemotherapy. The study included retrospective register data from 365 Swedish patients with stage II-IV rectal adenocarcinoma, 56 patients with MAC and 309 patients with NMAC. All patients were considered curative, had surgery with total mesorectal excision in 2004-2013, and were followed up until death or 2021. Patients with MAC that had adjuvant chemotherapy had better overall survival (OS, HR 0.42; CI 95%: 0.19-0.93; p = 0.032) and a trend towards better cancer-specific survival (CSS, HR 0.41 CI 95%: 0.17-1.03; p = 0.057) compared to patients without chemotherapy (HR 0.42; CI 95%: 0.19-0.93; p = 0.032). The difference in OS was still significant even after adjusting for sex, age, stage, differentiation, neoadjuvant chemotherapy and preoperative radiotherapy (HR 0.40; CI 95%: 0.17-0.92; p = 0.031). There was no such difference in the NMAC patients except in the stage-by-stage subgroup analyses where patients in stage IV had better survival after adjuvant chemotherapy. There may be a difference in treatment response to adjuvant chemotherapy between MAC and NMAC patients. Patients with MAC could possibly benefit from adjuvant chemotherapy in stages II-IV. Further studies are however needed to confirm these results.

Adjuvant chemotherapy and survival outcomes in rectal cancer patients with good response (ypT0-2N0) after neoadjuvant chemoradiotherapy and surgery: A retrospective nationwide analysis.

For rectal cancer, it remains unclear how to incorporate tumor response to neoadjuvant chemoradiotherapy (nCRT) when deciding whether to give adjuvant chemotherapy. In this study, we aim to determinate the survival benefit of adjuvant chemotherapy for rectal cancer patients with good response (ypT0-2N0) after nCRT and surgery. The study cohort included 720 rectal cancer patients who had good response (ypT0-2N0) after nCRT and surgery, who did or did not receive adjuvant chemotherapy between January 2007 and December 2017, from the Taiwan Cancer Registry and National Health Insurance Research database. The Kaplan-Meier method, log-rank tests, and Cox regression analysis were performed to investigate the effect of adjuvant chemotherapy on 5-year overall survival (OS) and disease-free survival (DFS). Of 720 patients, 368 (51.1%) received adjuvant chemotherapy and 352 (48.9%) did not. Patients who received adjuvant chemotherapy were more likely to be female, younger (≤ 65), with advanced clinical T (3-4)/N (1-2) classification and ypT2 classification. No significant difference in 5-year OS (p=0.681) or DFS (p=0.942) were observed by receipt of adjuvant chemotherapy or not. Multivariable analysis revealed adjuvant chemotherapy was not associated with better OS (adjusted hazard ratio [aHR], 1.03; 95% Confidence Interval [CI], 0.88-1.21) or DFS (aHR, 1.05; 95% CI, 0.89-1.24). Stratified analysis for OS and DFS found no significant protective effect in the use of adjuvant chemotherapy, even for those with advanced clinical T or N classification. Adjuvant chemotherapy may be omitted in rectal cancer patients with good response (ypT0-2N0) after nCRT and surgery.

Pathologic Implications of Radial Resection Margin and Perineural Invasion to Adjuvant Chemotherapy after Preoperative Chemoradiotherapy and Surgery for Rectal Cancer: A Multi-Institutional and Case-Matched Control Study.

Simple SummaryThe significance of the role of adjuvant chemotherapy in patients with rectal cancer treated with neoadjuvant chemoradiation and surgery has yet to be been determined. In this multi-center and case-matched analysis, we evaluated 1799 patients with rectal cancer who received adjuvant chemotherapy after neoadjuvant chemoradiation and total mesorectal excision. Positive surgical margin and perineural invasion were poor prognostic factors after neoadjuvant chemoradiotherapy and curative surgery. Adjuvant chemotherapy significantly decreased recurrences in patients with positive margin or perineural invasion. The role of adjuvant chemotherapy in rectal cancer patients without positive margin and perineural invasion after neoadjuvant chemoradiotherapy and surgery could be limited.We assessed the exact role of adjuvant chemotherapy after neoadjuvant chemoradiotherapy (CRT) and surgery in rectal cancer patients with positive surgical margin or perineural invasion (PNI). This multi-institutional study included 1799 patients with rectal cancer at cT3-4N0-2M0 stages. Patients were divided into two groups. The high-risk group had a positive margin and/or perineural invasion. The low-risk group showed no positive margin or PNI. Propensity-score matching analysis was performed, and a total of 928 patients, with 464 in each arm, were evaluated. The high-risk group showed significant differences in overall survival (OS, 73.4% vs. 53.9%, p < 0.01) and recurrence-free survival (RFS, 52.7% vs. 40.9%, p = 0.01) at five years between the adjuvant chemotherapy arm and observation arm. The low-risk group showed no significant differences in 5-year OS (p = 0.61) and RFS (p = 0.75) between the two arms. Multivariate analyses showed that age, pathologic N stage, and adjuvant chemotherapy were significantly correlated with OS and RFS in the high-risk group (all p < 0.05). Adjuvant chemotherapy improved OS and RFS more significantly in rectal cancer patients with positive surgical margin or PNI than in those with negative surgical margin and PNI.

P-216 Serum levels of HMGB1 might have a predictive role for neoadjuvant radiotherapy combined with chemotherapy in rectal cancer patients

The standard treatment for locally advanced rectal cancer (LARC), is neoadjuvant concurrent chemoradiation (nCCRT), after which total mesorectal excision is performed. The degree of response to combined therapy varies in patients. Tumor repopulation during radiotherapy is an important cause of treatment failure. High mobility group box 1 (HMGB1) is a nuclear protein released during the course of radiotherapy. It is essential for normal cellular function but also regulates the proliferation and migration of tumor cells.

Can Elevated Pretreatment Serum Carcinoembryonic Antigen Levels Serve as a Potential Biomarker Guiding Adjuvant Chemotherapy in Rectal Cancer Patients With ypTis-3N0 After Neoadjuvant Radiotherapy and Surgery?

Survival benefit of adjuvant chemotherapy (ACT) remained controversial in patients with stage II/III rectal cancer (RC) who received neoadjuvant therapy and surgery. This study aimed to investigate the guiding role of elevated pretreatment serum carcinoembryonic antigen (CEA) levels for receiving ACT in yield pathological Tis-3N0 (ypTis-3N0) RC patients after neoadjuvant radiotherapy and surgery. Between 2004 and 2015, 10,973 RC patients with ypTis-3N0 who received neoadjuvant radiotherapy and radical surgery were retrospectively analyzed using the Surveillance, Epidemiology, and End Results (SEER) database. Compared with CEA-normal group, elevated-CEA patients had worse 5-year CSS rate (90.1 vs 83.5%). The 5-year CSS rates were 86.3 and 87.4% for ypTis-3N0M0 patients with or without ACT, respectively. Patients receiving ACT had a comparable 5-year CSS rate compared to those who did not regardless of CEA levels in ypTis-3N0M0 RC patients (CEA elevation group: 76.4 vs. 83.5%, P = 0.305; CEA normal group: 90.0 vs. 90.1%, P = 0.943). Intriguingly, ypT3N0M0 RC patients with elevated CEA levels may benefit from ACT (5-year CSS: 69.1 vs. 82.9%, P = 0.045), while those with normal CEA levels did not (5-year CSS: 89.3 vs. 89.3%, P = 0.885). Multivariate Cox analysis demonstrated that ACT tended to be a protective factor in elevated-CEA ypT3N0M0 RC patients (HR = 0.633, 95% CI = 0.344–1.164, P = 0.141), while ACT was not associated with improved CSS in normal-CEA ypT3N0M0 RC patients (HR = 1.035, 95% CI = 0.487–2.202, P = 0.928). Elevated pretreatment serum CEA levels may serve as a promising biomarker guiding ACT in rectal cancer patients with ypT3N0M0.

Current evidence regarding the role of adjuvant chemotherapy in rectal cancer patients with pathologic complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.

The aim of this meta-analysis was to investigate the role of adjuvant chemotherapy (AC) in rectal cancer patients with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) and curative resection. This study was completed in accordance to the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The electronic scholar databases (Medline, Web of Science, Scopus) were screened for eligible articles. The level of evidence (LoE) was assessed using the GRADE methodology. Overall, 23 non-randomized studies and 17,406 patients were included in the present meta-analysis. Pooled comparisons confirmed that AC improved overall survival (HR: 0.68, p=0.0003), but not disease-free (p=0.22) and recurrence-free survival (p=0.39). However, the LoE for all outcomes was characterized as "very low," due to the absence of RCTs. Considering the study limitations and the lack of randomized studies, further high-quality RCTs are required to confirm the findings of our study.

Optimizing treatment sequencing of chemotherapy for patients with rectal cancer: The KIR randomized phase II trial

BackgroundRandomized studies have shown low compliance to adjuvant chemotherapy in rectal cancer patients receiving preoperative chemotherapy and external beam radiation (CT/EBRT) with total mesorectal excision. We hypothesize that giving neoadjuvant CT before local treatment would improve CT compliance. MethodsBetween 2010–2017, 180 patients were randomized (2:1) to either Arm A (AA) with FOLFOX x6 cycles prior to high dose rate brachytherapy (HDRBT) and surgery plus adjuvant FOLFOX x6 cycles, or Arm B (AB), with neoadjuvant HDRBT with surgery and adjuvant FOLFOX x12 cycles. The primary endpoint was CT compliance to ≥85% of full-dose CT for the first six cycles. Secondary endpoints were ypT0N0, five-year disease free survival (DFS), local control and overall survival (OS). ResultsPatients were randomized to either AA (n = 120, median age (MA) 62 years) or AB (n = 60, MA 63 years). 175/180 patients completed HDRBT as planned (97.2%). In AA, two patients expired during CT; three patients post-randomization received short course EBRT because of progression under CT (n = 2, AA) or personal preference (n = 1, AB). ypT0N0 was 31% in AA and 28% in AB (p = 0.7). CT Compliance was 80% in AA and 53% in AB (p = 0.0002). Acute G3/G4 toxicity was 35.8% in AA and 27.6% in AB (p = 0.23). With a median follow-up of 48.5 months (IQR 33–72), the five-year DFS was 72.3% with AA and 68.3% with AB (p = 0.74), the five-year OS 83.8% for AA and 82.2% for AB (p = 0.53), and the five-year local recurrence was 6.3% for AA and 5.8% for AB (p = 0.71). ConclusionWe confirmed improved compliance to neoadjuvant CT in this study. Although there is no statistical difference in ypT0N0 rate, local recurrence, and DFS between the two arms, a trend towards favourable oncological outcomes is observed.

Omission of Adjuvant Chemotherapy in Rectal Cancer Patients with Pathologic Complete Response: a National Analysis

BackgroundAn increasing number of patients achieve a pathologic complete response (pCR) after neoadjuvant chemoradiation for locally advanced rectal cancer. Consensus guidelines continue to recommend oncologic resection followed by adjuvant chemotherapy in these patients. We hypothesize that there is significant variability in compliance with this recommendation. MethodsThe National Cancer Database was queried from 2006 to 2015 for patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiation followed by oncologic resection with a pCR (ypT0N0). Hierarchical logistic regression models were used to generate risk and reliability-adjusted rates of adjuvant chemotherapy utilization in patients with pCR at each hospital. ResultsIn total, 2421 pCR patients were identified. Five-year overall survival was improved in pCR patients who received adjuvant chemotherapy compared with those who did not (92 vs. 85%, p < 0.01). Multivariate analysis indicated that improvement in overall survival remained associated with adjuvant chemotherapy (HR 0.60, 95% CI 0.44–0.82, p < 0.01). The mean adjuvant chemotherapy utilization rate among hospitals was 32%. There was an upward trend in use over the past decade, but two-thirds still do not receive the recommended therapy. High chemotherapy utilizer hospitals were more likely to be academic centers (54.9 vs. 45.9%, p < 0.01) when compared with low chemotherapy utilizers. ConclusionAdjuvant chemotherapy is associated with improved survival in rectal cancer patients with pCR following neoadjuvant chemoradiation and oncologic resection. However, utilization among centers in the USA was only 32% with significant variability across centers. National efforts are needed to standardize treatment patterns according to national guidelines.

Association between Preoperative Pelvic Irradiation and Toxicity of Subsequent Chemotherapy in Rectal Cancer

Background: Randomized trials have shown a lower efficacy of postoperative chemotherapy in rectal cancer patients having received preoperative radiotherapy than in nonirradiated colorectal cancer (CRC) patients. We hypothesized that preoperative radio(chemo)therapy impairs the relative dose intensity (RDI) of further chemotherapy because of long-term radiation damage. This retrospective study aimed to test this hypothesis. Methods: The analysis was conducted on 220 consecutive patients with CRC who received FOLFOX-4 postoperatively or because of cancer relapse. Of these, 41 patients with rectal cancer had preoperatively received radio(chemo)therapy (study group) and the remaining 179 with CRC had not (control group). The RDI of oxaliplatin at 8 and 16 weeks was calculated. Results: The median RDI of oxaliplatin at 8 weeks was 95.91% in the study group and 96.15% in the control group (p = 0.79). The corresponding percentages at 16 weeks were 87.6 and 86.5%, respectively (p = 0.55). It was found that within 0–8 weeks, 26.9% of the patients in the study group and 26.3% in the control group had grade 3+ toxicity, hypersensitivity reactions, or granulocyte colony-stimulating factor administration (p = 0.94). The corresponding percentages for 0–16 weeks were 44.8 and 43.9%, respectively (p = 0.92). Conclusions: We found no association between preoperative radio(chemo)therapy and the RDI of FOLFOX-4. We failed to explain the inferior efficacy of postoperative chemotherapy in patients with rectal cancer who had preoperatively received irradiation compared to those with CRC who had not.

Adjuvant chemotherapy in rectal cancer patients who achieved a pathological complete response after preoperative chemoradiotherapy: a systematic review and meta-analysis

This study evaluated the prognostic impact of ACT in patients who achieved a pathological complete response (pCR). Articles published from January 1990 to September 2018 were searched in EMBASE, PubMed, Ovid, Web of Science, and Cochrane Library. Hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS) were extracted. Thirteen observational studies were included. There were four National Cancer Database studies with overlapping study periods, thus individual pooled analyses of four different datasets were conducted (n = 3,182, 3,330, 3,575, and 4,739 for pooled analysis sets including Dossa et al., Polanco et al., Xu et al., and Shahab et al., respectively). Although a trend toward improved OS with ACT was observed, statistical significance was not proven (P = 0.09, P = 0.03, P = 0.12, and P = 0.10, respectively). When we performed a stratified analysis comparing the results from single institution and multicenter studies, there was no significant prognostic benefit of ACT. Publication bias was not observed. Routine use of ACT in patients with a pCR could not be warranted from the present meta-analysis. Further study of individual patient data from randomized trials is needed to clarify the role of ACT.

Phase II/III Study to Assess the Efficacy of Neoadjuvant Consolidation Chemotherapy in Rectal Cancer Patients.

Phase II/III Study to Assess the Efficacy of Neoadjuvant Consolidation Chemotherapy in Rectal Cancer Patients.

Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer after Preoperative Chemoradiotherapy (ADORE): Long-Term Results of an Open-Label, Multicentre, Phase 2, Randomised Controlled Trial

Background: Oxaliplatin-based adjuvant chemotherapy for rectal cancer patients after preoperative chemoradiotherapy (CRT) is currently based on extrapolated results from colon cancer patients. We evaluated the role of oxaliplatin as adjuvant chemotherapy in rectal cancer patients who received preoperative CRT with fluoropyrimidine monotherapy and total mesorectal excision (TME). Methods: The ADORE is a multicentre, randomised trial in patients with postoperative ypStage II (ypT3-4N0) or III (ypTanyN1-2) rectal cancer after fluoropyrimidine-based preoperative CRT and TME. Patients were randomly assigned (1:1) to receive adjuvant chemotherapy either with FL (5-fluorouracil 380 mg/m², leucovorin 20 mg/m²) or FOLFOX (oxaliplatin 85 mg/m², leucovorin 200 mg/m², 5-fluorouracil bolus 400 mg/m² on day 1, 5-fluorouracil infusion 2400 mg/m² for 46 hours). Stratification factors included ypStage and participating centre. Investigators were not blinded to the group assignment. Primary endpoint was disease-free survival (DFS), analysed according to the intention-to-treat principle (ClinicalTrials.gov registration number: NCT00807911). Findings: A total of 321 patients were enrolled between November 19, 2008, and June 12, 2012. The 6-year DFS rates were 68·2% in the FOLFOX arm vs 56·8% in the FL arm, with a stratified hazard ratio (HR) of 0·63 (95% CI, 0·43-0·93, p=0·018) by intention-to-treat analysis. In the subgroup analysis for DFS, FOLFOX was favourable to FL in patients with ypStage III, ypN1b, ypN2, high-grade histology, minimally regressed tumour, and absence of lymphovascular or perineural invasion. The 6-year overall survival (OS) rate was 78·1% in the FOLFOX arm vs 76·4% in the FL arm (HR 0·73 [0·45-1·19], p=0·21). In the subgroup analysis for OS, FOLFOX was favourable to FL in patients with ypN2 and minimally regressed tumour. Interpretation: Adjuvant FOLFOX improved DFS in rectal cancer patients with ypStage II/III after preoperative CRT. Adjuvant FOLFOX should be chosen based on the postoperative pathologic stage in those received preoperative CRT and TME. Trial Registration Number: ClinicalTrials.gov registration number: NCT00807911 Funding: Sanofi-Aventis, Republic of Korea Declaration of Interest: TWK received research funding from Sanofi-Aventis, Taiho, and Roche. YSH received research funding from Bayer. All other authors have no conflicts of interest to declare. Ethical Approval: All patients provided written informed consent, and the study protocol was approved by the institutional review boards of all participating institutions.

Adjuvant Chemotherapy in Rectal Cancer Patients Treated With Preoperative Chemoradiation and Total Mesorectal Excision: A Multicenter and Retrospective Propensity-Score Matching Study

The role of adjuvant chemotherapy after preoperative chemoradiation therapy (CRT) and curative surgery in rectal cancer has yet to be definitely determined. We performed a retrospective and multicenter study to evaluate whether adjuvant chemotherapy (AC) could reduce recurrence and improve survival in locally advanced rectal cancer. We analyzed data from 8 tertiary institutions for 1442 patients with rectal cancer who underwent preoperative CRT and total mesorectal excision. Patients were classified into 2 groups: the AC group (patients who received chemotherapy after surgery) and the observation group (those who did not receive chemotherapy after surgery). Propensity-score matching was used to assess the exact role of AC. The AC group was then subdivided to investigate the impact of adding oxaliplatin to 5-fluorouracil (5-FU). Group 1 was treated with 5-FU/folinic acid or capecitabine without oxaliplatin, and group 2 received 5-FU/folinic acid or capecitabine with oxaliplatin. The 3-year relapse-free survival rates in the AC and observation groups were 85.9% and 84.3%, respectively (P=.532). The 3-year overall survival rates in the AC and observation groups were 94.9% and 89.9%, respectively (P=.123). The rates of locoregional recurrence (2.2% vs 3.2%, P=.294) and distant metastasis(12.4% vs 12.9%, P=.927) at 3years were not significantly different between the two groups. The 3-year relapse-free survival rates of group 1 and group 2 were 71.5% and 74.8%, respectively (P=.426). The 3-year overall survivalrates of group 1 and group 2 were 89.9% and 96.5%, respectively (P=.102). This multicenter study found insufficient evidence to support the use of 5-FU-based AC after preoperative CRT and curative surgery in rectal cancer.

Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy

To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.

Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial

The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME). The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual. Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738.

96. Differences in adjuvant chemotherapy administration for rectal cancer patients - a EURECCA international comparison

Background: Considerable debate exists on the role of adjuvant chemotherapy for rectal cancer patients after preoperative (chemo)radiation and TME surgery, and trials did not give a definitive answer so far. The aim of this large population-based international comparison, using country as instrumental variable, is to compare treatment strategies and survival in rectal cancer patients among seven European countries. This could lead to new insights on the value of adjuvant chemotherapy for rectal cancer patients

Is there a role for adjuvant chemotherapy in pathological complete response rectal cancer tumors following neoadjuvant chemoradiotherapy?

To investigate the contribution of neoadjuvant chemotherapy in rectal cancer patients with pathological complete response (pCR). Data were collected on all consecutive locally advanced rectal cancer patients treated with neoadjuvant chemotherapy and later resected in our institution between 2001 and 2013. Surgery was performed by a single proctology team, and tumor specimens were evaluated by the hospital pathologists. The medical records of 260 patients were analyzed, and 54 patients of those patients were found to have achieved pCR (20.8%). Two of those patients were lost to follow-up. Thirty-five of the 54 pCR patients received adjuvant chemotherapy (Group A) and 17 did not (Group B). With the sole exception of the Group A patients being younger than the Group B patients (60.9±11.9 vs. 68.7±10.8years, respectively, p=0.0272), all other evaluated parameters were identical between the two groups. There was no advantage for the administration of adjuvant chemotherapy for disease-free survival (DFS) and overall survival (OS). Adjuvant chemotherapy played no part in disease-free survival and OS of patients with rectal cancer who had been treated with neoadjuvant chemotherapy and achieved pCR. Our findings indicate a tendency for adjuvant chemotherapy to be administered to younger rectal cancer patients. A randomized trial should be conducted to resolve the question of whether they derive any benefit from it.

Selective use of adjuvant chemotherapy for rectal cancer patients with ypN0

BackgroundThe administration of adjuvant chemotherapy for rectal cancer patients with ypN0 is controversial. The purposes of this study were to evaluate the role of adjuvant chemotherapy in ypN0 patients and to optimize its use for these patients.MethodsWe performed a retrospective study of 160 rectal cancer patients who had the final pathology of ypN0 between March 2003 and November 2010. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between patients who did and did not receive adjuvant chemotherapy. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, LRFS, and DMFS.ResultsFor ypT0–2N0 patients, the 5-year OS, DFS, LRFS, and DMFS were similar between patients who did and did not receive adjuvant chemotherapy (P > 0.05). For patients with ypT3–4N0, those who were given adjuvant chemotherapy exhibited a higher 5-year OS than those who were not (P = 0.026), with also an extended 5-year DFS (P = 0.050). Further analysis indicated that adjuvant chemotherapy could decrease the rates of distant metastases for ypT3–4N0 patients with no impact on local control. In multivariable analysis, both the final pathological stage and adjuvant chemotherapy were independent predictors of DMFS for the whole group. When stratified by pathological stage, adjuvant chemotherapy was still significantly associated with DMFS in the ypT3–4 stratum.ConclusionsAdjuvant chemotherapy may not improve survival for ypT0–2N0 patients. However, it may be clinically meaningful for ypT3–4N0 patients by decreasing rates of distant metastases. Further randomized controlled clinical trials are needed to address this problem.