Role of the Interval from Completion of Neoadjuvant Therapy to Surgery in Postoperative Morbidity in Patients with Locally Advanced Rectal Cancer.
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ABSTRACT:
SUBMITTER: Roxburgh CSD
PROVIDER: S-EPMC6579536 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Role of the Interval from Completion of Neoadjuvant Therapy to Surgery in Postoperative Morbidity in Patients with Locally Advanced Rectal Cancer.
Roxburgh Campbell S D CSD Strombom Paul P Lynn Patricio P Gonen Mithat M Paty Philip B PB Guillem Jose G JG Nash Garrett M GM Smith J Joshua JJ Wei Iris I Pappou Emmanouil E Garcia-Aguilar Julio J Weiser Martin R MR
Annals of surgical oncology 20190408 7
<h4>Background</h4>Increasing the interval from completion of neoadjuvant therapy to surgery beyond 8 weeks is associated with increased response of rectal cancer to neoadjuvant therapy. However, reports are conflicting on whether extending the time to surgery is associated with increased perioperative morbidity.<h4>Methods</h4>Patients who presented with a tumor within 15 cm of the anal verge in 2009-2015 were grouped according to the interval between completion of neoadjuvant therapy and surge ...[more]
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Project description:BackgroundNeoadjuvant (chemo) radiotherapy is used as a standard treatment for locally advanced rectal cancer (LARC), but there is no general consensus on either the efficacy of postoperative adjuvant chemotherapy in patients with LARC after neoadjuvant treatment and surgery, or whether the addition of oxaliplatin to adjuvant chemotherapy provides survival benefits.MethodsWe performed a meta-analysis of data from the PubMed and Embase databases. We included patients with LARC who received neoadjuvant (chemo) radiotherapy and curative surgery. Overall survival (OS), disease-free survival (DFS), toxicity, and compliance were analyzed in the oxaliplatin/fluorouracil- (OX/FU-) based group compared with the FU-based group, and in the chemotherapy group compared with the observation group.ResultsTwenty studies were included in the analysis. Our results indicated that adjuvant chemotherapy prolonged OS (hazard ratio [HR] = 0.78, 95%CI = 0.67-0.91) in patients with LARC treated with neoadjuvant (chemo) radiotherapy and surgery compared with those in the observation group. Subgroup analysis showed the same results in both the ypStage II and ypStage III groups. Compared with those in the observation group, patients in the chemotherapy group also showed an increase in DFS (HR = 0.75, 95%CI = 0.60-0.93). No significant increase was observed in OS (HR = 1.04, 95%CI = 0.87-1.24) or DFS (HR = 0.98, 95%CI = 0.76-1.27) when oxaliplatin was added to FU-based adjuvant chemotherapy, as compared with the FU-based treatment, and subgroup analysis also indicated no survival benefits in the clinical stage II, clinical stage III, ypStage II, and ypStage III groups.ConclusionsFor patients with LARC who have already received neoadjuvant (chemo) radiotherapy and curative surgery, adjuvant chemotherapy improves OS over that in the observation group. Adding oxaliplatin to FU-based adjuvant chemotherapy does not confer survival benefits beyond those from FU-based adjuvant chemotherapy.
| S-EPMC8319733 | biostudies-literature
Project description:ImportanceTreatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases.ObjectiveTo compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC.Design, setting, and participantsA retrospective cohort analysis using Memorial Sloan Kettering Cancer Center (MSK) records from 2009 to 2015 was carried out. A total of 811 patients who presented with LARC (T3/4 or node-positive) were identified.ExposuresOf the 811 patients, 320 received chemoRT with planned adjuvant chemotherapy and 308 received TNT (induction fluorouracil- and oxaliplatin-based chemotherapy followed by chemoRT).Main outcomes and measuresTreatment and outcome data for the 2 cohorts were compared. Dosing and completion of prescribed chemotherapy were assessed on the subset of patients who received all therapy at MSK.ResultsOf the 628 patients overall, 373 (59%) were men and 255 (41%) were women, with a mean (SD) age of 56.7 (12.9) years. Of the 308 patients in the TNT cohort, 181 (49%) were men and 127 (49%) were women. Of the 320 patients in the chemoRT with planned adjuvant chemotherapy cohort, 192 (60%) were men and 128 (40%) were women. Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose than those in the chemoRT with planned adjuvant chemotherapy cohort. The complete response (CR) rate, including both pathologic CR (pCR) in those who underwent surgery and sustained clinical CR (cCR) for at least 12 months posttreatment in those who did not undergo surgery, was 36% in the TNT cohort compared with 21% in the chemoRT with planned adjuvant chemotherapy cohort.Conclusions and relevanceOur findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines that categorize TNT as a viable treatment strategy for rectal cancer. Our data suggest that TNT facilitates delivery of planned systemic therapy. Long-term follow-up will determine if this finding translates into improved survival. In addition, given its high CR rate, TNT may facilitate nonoperative treatment strategies aimed at organ preservation.
| S-EPMC5885165 | biostudies-literature
Project description:Background: The addition of intensive preoperative chemotherapy and using of a longer waiting period between neoadjuvant radiotherapy and total mesorectal excision (TME) surgery lengthen the time interval from the initiation of neoadjuvant treatment to definitive surgery in patients with locally advanced rectal cancer (LARC). Here, we evaluated the prognostic value of different time intervals between the initiation of neoadjuvant treatment to TME surgery for LARC. Methods: A total of 2,267 patients with LARC, who received neoadjuvant radiochemotherapy and TME surgery, between January 2010 through December 2018 were recruited. The entire cohort was divided into 4 subgroups based on total-time-to surgery, defined as the time interval between initiation of neoadjuvant treatment and TME surgery (TTS): <13 weeks (TTS-1), 13 to <15 weeks (TTS-2), 15 to <17 weeks (TTS-3), ≥17 weeks (TTS-4). Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS) rates in different TTS subgroup patients were compared, and hazard ratios (HR) for different demographic and clinicopathological variables, including TTS, were calculated to determine their prognostic significance. Results: The median follow-up time was 42.0 (range, 5-162) months. The 3-year OS, DFS, DMFS, and LRFS rates were 87.0, 79.4, 80.9, and 93.8%, respectively. The varied OS, DFS, and DFMS rates were detected among these different TTS subgroups (P = 0.010, P < 0.001, and P < 0.001, respectively). Particularly, the lower survival outcome was mainly observed at patients in the shortest TTS group (TTS-1). Cox regression analysis confirmed that the only significant positive independent prognostic factor for 3-year DFS was a longer TTS (TTS 2-4 vs. TTS-1; HR 0.884, 95% CI 0.778-0.921, P < 0.001), while the significant negative independent prognosticfactors were moderate to poor tumor differentiation (vs. well-differentiated; HR 1.191, 95% CI 1.004-1.414, P = 0.045) and clinical N1-2 stage (vs. N0 stage; HR 1.190, 95% CI 1.052-1.347, P = 0.006). Conclusion: For patients with LARC, an interval between the initiation of neoadjuvant treatment and TME surgery of longer than 13 weeks is associated with favorable disease-free survival.
| S-EPMC7473386 | biostudies-literature
Project description:Background The treatment strategy for locally advanced rectal cancer (LARC) has recently expanded from total mesorectal excision to additional neoadjuvant chemoradiotherapy (nCRT) and/or systemic chemotherapy (NAC). Data on disease recurrence after each treatment strategy are limited. Methods Clinical stage II to III rectal cancer patients who underwent curative surgery between July 2005 and February 2021 were analyzed. The cumulative incidence and site of first recurrence were assessed. The median follow-up duration was 4.6 years. Results Among the 332 patients, we performed nCRT and NAC in 15.4% (N=51) and 14.8% (N=49), respectively. The overall recurrence rate was 23.5% (N=78). Although several differences in tumor stage or location were observed, there was no significant difference in the rate among the surgery alone (N=54, 23.3%), nCRT (N=11, 21.6%), and NAC (N=13, 26.5%) groups. In this cohort, the local recurrence rate (18.4%) was higher than the rate of distant metastasis in the NAC group (14.3%). All patients with recurrence in the nCRT group had distant metastases (N=11: one patient had distant and local recurrences simultaneously). For pathological stage 0-I, the recurrence rate was higher in the nCRT and NAC groups than in the surgery-alone group (nCRT, 10.0%; NAC, 15.4%; and surgery-alone, 2.0%). Curative-intent resection of distant-only recurrences significantly improved patients’ overall survival (hazard ratio [95% confidence interval], 0.34 [0.14–0.84]), which was consistent even when stratified according to neoadjuvant treatment. Regardless of neoadjuvant treatment, >80% of recurrences occurred in the first 2.2 years, and 98.7% within 5 years after surgery. Conclusion Regardless of neoadjuvant treatment, detecting distant metastases with intensive surveillance, particularly in the first 2 years after surgery, is important. Also, even if neoadjuvant treatment can downstage LARC to pathological stage 0-I, careful follow-up is needed. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-023-03136-0.
| S-EPMC10428603 | biostudies-literature
Project description:IntroductionPrognostic models can be used for predicting survival outcomes and guiding patient management. TNM staging alone is insufficient for predicting recurrence after chemoradiotherapy (CRT) and surgery for locally advanced rectal cancer. This study aimed to develop a nomogram to better predict cancer recurrence after CRT followed by total mesorectal excision (TME) and tailor postoperative management and follow-up.Materials and methodsBetween 2002 and 2019, data were retrospectively collected on patients with rectal adenocarcinoma. Data on sex, age, carcinoembryonic antigen (CEA) level, tumour location, induction chemotherapy, adjuvant chemotherapy, tumour downsizing, perineural invasion, lymphovascular invasion, pathological stage, resection margins (R0 versus R1), and pelvic septic complications were analysed. The variables significantly associated with cancer recurrence were used to build a nomogram that was validated in both the training and validation cohorts. Model performance was evaluated by receiver operating characteristic curve and area under the curve (AUC) analyses.ResultsAfter applying exclusion criteria, 634 patients with rectal adenocarcinoma were included in this study. Eight factors (CEA level, adjuvant chemotherapy, tumour downsizing, perineural invasion, lymphovascular invasion, pathological stage, resection margins (R0 versus R1), and pelvic septic complications) were identified as nomogram variables. Our nomogram showed good performance with an AUC of 0.74 and 0.75 in the training and validation cohorts respectively.ConclusionOur nomogram is a simple tool for predicting cancer recurrence in patients with locally advanced rectal cancer after neoadjuvant CRT followed by TME. It provides an individual risk prediction of recurrence to tailor surveillance.
| S-EPMC9749481 | biostudies-literature
Project description:For the past several decades, disease-related outcomes, particularly local recurrence rate, in patients with locally advanced rectal cancer have significantly improved as a result of advancement of surgical technique and implementation of neoadjuvant chemoradiation. However, distant metastasis remains unresolved, being a significant cause of cancer death. To focus on micrometastases early in the course of multimodal treatment, delivering systemic chemotherapy in the neoadjuvant setting is emerging. Also, driven by patient demand and interest in preserving quality of life, upfront chemotherapy prior to surgery serves as a strategy for organ preservation in the management of rectal cancer. Herein, currently available literature on different methods and strategies of the multimodal approach is critically appraised.
| S-EPMC6635691 | biostudies-literature
Project description:This study aimed to assess the clinical outcomes and predictive factors of neoadjuvant modified short-course radiotherapy (mSC-RT) for locally advanced rectal cancer (LARC). Data from 97 patients undergoing mSC-RT followed by radical surgery for LARC were retrospectively analyzed. A 2.5 Gy dose twice daily up to a total dose of 25 Gy in 10 fractions was administered through mSC-RT, and this was delivered with oral chemotherapy in 95 (97.9%) patients. Radical surgery was performed 6 (range, 3-13) weeks after mSC-RT. The median follow-up among surviving patients was 43 (8-86) months. All patients completed neoadjuvant radiotherapy with no acute toxicity grade ≥ 3. Three- and five-year local control rates were 96.3% and 96.3%, respectively. Three- and five-year overall survival (OS) rates were 92.7% and 79.8%, respectively. Univariate analyses revealed that poor OS was associated with no concurrent administration of capecitabine, C-reactive-protein-to-albumin ratio ≥ 0.053, carcinoembryonic antigen ≥ 3.4 ng/mL, and neutrophil-to-lymphocyte ratio (NLR) ≥ 1.83 (P = 0.045, 0.001, 0.041, and 0.001, respectively). Multivariate analyses indicated that NLR ≥ 1.83 was independently associated with poor OS (p = 0.018). mSC-RT followed by delayed surgery for LARC was deemed feasible and resulted in good clinical outcomes, whereas poor OS was associated with high NLR.
| S-EPMC8394890 | biostudies-literature
Project description:Background:There is recent interest in treating locally advanced rectal cancer (LARC) patients with total neoadjuvant therapy (TNT). However, whether TNT is associated with improved overall survival (OS) remains unknown. This study compares outcomes following TNT and following neoadjuvant chemoradiation therapy (nCRT) in patients with LARC, clinically defined cT3/4 or node positive disease, using the National Cancer Database. Methods:LARC patients diagnosed between 2004-2015 were included. TNT was defined as multi-agent chemotherapy given at least 2 months before RT followed by pre-operative chemoradiation therapy and definitive surgery without adjuvant chemotherapy. nCRT was defined as pre-operative RT and chemotherapy started within 2 weeks from each other followed by definitive surgery with or without adjuvant chemotherapy. Kaplan-Meier curve with logrank test and multivariable Cox proportional hazards regression modelling were used to analyse the primary endpoint of overall survival (OS). Multivariable logistic regression modelling was used for secondary outcomes to determine if TNT is associated with pathological complete response (pCR), defined as ypT0N0, and negative circumferential resection margin (CRM). Findings:Data from 372 TNT patients and 707 nCRT patients were analysed after a 2:1 propensity matching with replacement. Kaplan-Meier curve showed that OS with TNT was comparable to that with nCRT (p = 0•16). The 5-year OS rates for TNT and nCRT were 73•6% vs. 78•5% (p = 0•20). Multivariable Cox proportional hazards regression modelling confirmed no difference in OS between TNT and nCRT (HR = 1•21, p = 0•25). With TNT, 16•9% patients achieved pCR, whereas 13•1% patients achieved pCR with nCRT (p = 0•12). TNT was not found to be significantly associated with pCR (OR = 1•36, p = 0•13) or negative CRM (OR = 1•77, p = 0•19) in multivariable logistic regression modelling. Interpretation:With results from current clinical trials pending, our data suggested that TNT and nCRT resulted in similar survival, while TNT led to higher pCR and CRM negative rate, albeit not statistically significant.
| S-EPMC6890979 | biostudies-literature
Project description:There is variation in the responsiveness of locally advanced rectal cancer to neoadjuvant chemoradiation, from complete response to total resistance. This study compared genetic variation in rectal cancer patients who had a complete response to chemoradiation versus poor response, using tumor tissue samples sequenced with genomics analysis software. Rectal cancer patients treated with chemoradiation and proctectomy June 2006-March 2017 were grouped based on response to chemoradiation: those with no residual tumor after surgery (CR, complete responders, AJCC-CPR tumor grade 0, n = 8), and those with poor response (PR, AJCC-CPR tumor grade two or three on surgical resection, n = 8). We identified 195 variants in 83 genes in tissue specimens implicated in colorectal cancer biopathways. PR patients showed mutations in four genes not mutated in complete responders: KDM6A, ABL1, DAXX-ZBTB22, and KRAS. Ten genes were mutated only in the CR group, including ARID1A, PMS2, JAK1, CREBBP, MTOR, RB1, PRKAR1A, FBXW7, ATM C11orf65, and KMT2D, with specific discriminating variants noted in DMNT3A, KDM6A, MTOR, APC, and TP53. Although conclusions may be limited by small sample size in this pilot study, we identified multiple genetic variations in tumor DNA from rectal cancer patients who are poor responders to neoadjuvant chemoradiation, compared to complete responders.
| S-EPMC7199754 | biostudies-literature
Project description:PurposePatients with locally advanced rectal cancer (LARC) may experience a clinical complete response (cCR) to neoadjuvant chemoradiotherapy (NACRT) and opt for non-operative management. Pathological factors that relate to NACRT response have been well described. Host factors associated with response, however, are poorly defined. Calcification of the aortoiliac (AC) vessels supplying the rectum may influence treatment response.MethodsPatients with LARC having NACRT prior to curative surgery at Glasgow Royal Infirmary (GRI) and St Mark's hospital (SMH) between 2008 and 2016 were identified. AC was scored on pre-treatment CT imaging. NACRT response was assessed using pathologic complete response (pCR) rates, tumour regression grades (TRGs), the NeoAdjuvant Rectal score and T-/N-downstaging. Associations were assessed using Chi-squared, Mantel-Haenszel and Fisher's exact tests.ResultsOf 231 patients from GRI, 79 (34%) underwent NACRT for LARC. Most were male (58%), aged over 65 (51%) with mid- to upper rectal tumours (56%) and clinical T3/4 (95%), node-positive (77%) disease. pCR occurred in 10 patients (13%). Trends were noted between higher clinical T stage and poor response by Royal College of Pathologist's TRG (p = 0.021) and tumour height > 5 cm and poor response by Mandard TRG (0.068). In the SMH cohort, 49 of 333 (15%) patients underwent NACRT; 8 (16%) developed a pCR. AC was not associated with NACRT response in either cohort.ConclusionsAC was not associated with NACRT response in this cohort. Larger contemporary cohorts are required to better assess host determinants of NACRT response and develop predictive models to improve patient selection.
| S-EPMC8484095 | biostudies-literature