scholarly journals Computertomography-Based Prediction of Complete Response Following Neoadjuvant Chemoradiotherapy of Locally Advanced Rectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Marina Maslova ◽  
Heinz Herden ◽  
Karin Schork ◽  
Michael Turewicz ◽  
Martin Eisenacher ◽  
...  

Therapeutic strategies for patients with locally advanced rectal cancer (LARC) who are achieving a pathological complete response (pCR) after neoadjuvant radio-chemotherapy (neoCRT) are being increasingly investigated. Recent trials challenge the current standard therapy of total mesorectal excision (TME). For some patients, the treatment strategy of “watch-and-wait” seems a preferable procedure. The key factor in determining individual treatment strategies following neoCRT is the precise evaluation of the tumor response. Contrast-enhanced computer tomography (ceCT) has proven its ability to discriminate benign and malign lesions in multiple cancers. In this study, we retrospectively analyzed the ceCT based density of LARC in 30 patients, undergoing neoCRT followed by TME. We compared the tumors´ pre- and post-neoCRT density and correlated the results to the amount of residual vital tumor cells in the resected tissue. Overall, the density decreased after neoCRT, with the highest decrease in patients achieving pCR. Densitometry demonstrated a specificity of 88% and sensitivity of 68% in predicting pCR. Thus, we claim that ceCT based densitometry is a useful tool in identifying patients with LARC who may benefit from a “watch-and-wait” strategy and suggest further prospective studies.

Author(s):  
J. F. Huisman ◽  
I. J. H. Schoenaker ◽  
R. M. Brohet ◽  
O. Reerink ◽  
H. van der Sluis ◽  
...  

Abstract Background Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is found in 15–20% of patients with locally advanced rectal cancer. A watch-and-wait (W&W) strategy has been introduced as an alternative strategy to avoid surgery for selected patients with a clinical complete response at multidisciplinary response evaluation. The primary aim of this study was to evaluate the efficacy of the multidisciplinary response evaluation by comparing the proportion of patients with pCR since the introduction of the structural response evaluation with the period before response evaluation. Methods This retrospective cohort study enrolled patients with locally advanced rectal cancer who underwent nCRT between January 2009 and May 2018, categorizing them into cohort A (period 2009–2015) and cohort B (period 2015–2018). The patients in cohort B underwent structural multidisciplinary response evaluation with the option of the W&W strategy. Proportion of pCR (ypT0N0), time-to-event (pCR) analysis, and stoma-free survival were evaluated in both cohorts. Results Of the 259 patients in the study, 21 (18.4%) in cohort A and in 8 (8.7%) in cohort B had pCR (p = 0.043). Time-to-event analysis demonstrated a significant pCR decline in cohort B (p < 0.001). The stoma-free patient rate was 24% higher in cohort B (p < 0.001). Conclusion Multidisciplinary clinical response evaluation after nCRT for locally advanced rectal cancer led to a significant decrease in unnecessary surgery for the patients with a complete response.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 681-681
Author(s):  
Ji Zhu ◽  
Jingwen Wang

681 Background: A watch-and-wait approach for patients with clinical complete response to neoadjuvant chemoradiation could avoid the morbidity of conventional surgery for rectal cancer. Here, we report the survival outcome of patients with this strategy in our center. Methods: We retrospectively analyzed the rectal cancer patients who received neoadjuvant chemoradiotherapy since 2015 in our center. Preoperative regimen included long-course radiotherapy (50 Gy / 25 Fx) combined fluoropyrimidin–based chemotherapy concurrently. MRI and endoscopic evaluation were performed after preoperative treatment. Patients with complete tumor response were referred to the “watch-and-wait” approach and omitted the surgery. Four to six cycles of consolidation chemotherapy were performed. Patients were followed up clinically, endoscopically, and radiologically to assess for local recurrence or disease progression. Results: From January 2015 to March 2018, a total of 47 patients with rectal cancer in our center received conservative treatment following neoadjuvant therapy. The median age of the patients is 58 (53-66). The proportions of stages I to IV are 4.3%, 12.8%, 70.2%, 8.5%, respectively. After a median follow-up of 20 month, tumor regrowth occurred in five out of 47 (10.6%) patients. All local regrowth was diagnosed in the first two years, and four out of five (80%) of local regrowth was located in the bowel wall. All patients underwent salvage surgery. Distant metastasis was diagnosed in four of 47 patients (8.5%). two-year overall survival was 89.9%, and two-year disease-free survival was 76.5%. Conclusions: Organ preservation for locally advanced rectal cancer is feasible for selected patients who achieve a complete response to individualized neoadjuvant CRT. The survival of patients is not impaired with “watch-and-wait” strategy.


2020 ◽  
Vol 27 (11) ◽  
pp. 4319-4336 ◽  
Author(s):  
S. Hoendervangers ◽  
J. P. M. Burbach ◽  
M. M. Lacle ◽  
M. Koopman ◽  
W. M. U. van Grevenstein ◽  
...  

Abstract Background Pathological complete response (pCR) following neoadjuvant treatment for locally advanced rectal cancer (LARC) is associated with better survival, less local recurrence, and less distant failure. Furthermore, pCR indicates that the rectum may have been preserved. This meta-analysis gives an overview of available neoadjuvant treatment strategies for LARC and analyzes how these perform in achieving pCR as compared with the standard of care. Methods Pubmed, Embase, and Cochrane Central bibliographic databases were searched. Randomized controlled trials in which patients received neoadjuvant treatment for MRI-staged nonmetastatic resectable LARC were included. The primary outcome was pCR, defined as ypT0N0. A meta-analysis of studies comparing an intervention with standard fluoropyrimidine-based chemoradiation (CRT) was performed. Results Of the 17 articles included in the systematic review, 11 were used for the meta-analysis. Addition of oxaliplatin to fluoropyrimidine-based CRT resulted in significantly more pCR compared with fluoropyrimidine-based CRT only (OR 1.46), but at the expense of more ≥ grade 3 toxicity. Other treatment strategies, including consolidation/induction chemotherapy and short-course radiotherapy (SCRT), did not improve pCR rates. None of the included trials reported a benefit in local control or OS. Five-year DFS was significantly worse after SCRT-delay compared with CRT (59% vs. 75.1%, HR 1.93). Conclusions All included trials fail to deliver high-level evidence to show an improvement in pCR compared with standard fluoropyrimidine-based CRT. The addition of oxaliplatin might result in more pCR but at the expense of more toxicity. Furthermore, this benefit does not translate into less local recurrence or improved survival.


2020 ◽  
pp. OP.20.00158
Author(s):  
Ashray Gunjur ◽  
Grace Chazan ◽  
Genni Newnham ◽  
Sue-Anne McLachlan

PURPOSE: In patients with rectal cancer who achieve a clinical complete response to neoadjuvant chemoradiation, it may be reasonable to adopt a watch-and-wait (W&W) strategy rather than proceed to immediate resection of the rectum. Patient preferences for this strategy are unknown. The primary aim of the current study was to determine the feasibility of assessing hypothetical recurrence and survival differences that relevant patients would tolerate to avoid immediate resection of the rectum. A secondary aim included estimating patients’ tolerance thresholds and the factors that might predict them. METHODS: We developed a study-specific written questionnaire based on a previously validated instrument. Hypothetical time tradeoff tasks were used to determine the recurrence rate patients would accept to adopt a W&W strategy and the survival benefit that would be needed to justify choosing immediate resection over W&W. Feasibility was measured on the basis of response rate, the stated ease of completion and the satisfaction of task, and time used. RESULTS: Twenty of 31 potentially eligible patients completed the study-specific questionnaire. The majority of respondents felt that questions were clear (70%) and not hard to understand (65%). The median acceptable recurrence risk to adopt a W&W strategy was 20% (interquartile range [IQR], 10%-35%). Patients required a median of 2.0 extra years of survival (IQR, 1.0-3.0 years) over a baseline 7.0 years, and they required a median extra 10% (IQR, 4%-19%) over baseline 70% survival rates to justify immediate resection. CONCLUSION: Measuring the preferences of patients with rectal cancer using time tradeoff methods seemed to be feasible. Larger studies are needed to confirm how acceptable a W&W strategy would be for relevant patients.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15144-e15144 ◽  
Author(s):  
Andrew Wang ◽  
Autumn Jackson McRee ◽  
A. William Blackstock ◽  
Bert H. O'Neil ◽  
Dominic T. Moore ◽  
...  

e15144 Background: There is strong interest in the development of novel agents to further improve the therapeutic ratio of neoadjuvant chemoradiotherapy for rectal cancer. CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. The purpose of this Phase Ib/II study is to assess toxicity and to evaluate whether the addition of CRLX101 to chemoradiotherapy can improve pathologic complete response (pCR) for rectal cancer. Methods: This is a single-arm multicenter Phase Ib/II study examining the addition of CRLX101 to a standard capecitabine-based chemoradiotherapy regimen. Phase Ib employs a 3+3 dose escalation design with starting dose of 12 mg/m2 every other week (QOW). Dose level +1 was 15 mg/m2 (MTD for CRLX101 single agent QOW). Upon reaching MTD for QOW dosing, protocol was modified to evaluate QW CRLX101 dosing starting at 12 mg/m2 and 15 mg/m2as +1 level. Secondary endpoints included pCR and clinical outcome. Results: A total of 32 patients were enrolled on the trial. 26/32 had T3-4, 9/32 had N2 and 16/32 had N1 disease. For QOW dosing, 9 patients completed treatment without DLT and MTD was identified as 15 mg/m2 QOW. 14 patients were treated on the Phase II portion of the study at 15 mg/m2 QOW prior to the initiation of weekly dosing Phase Ib cohorts. For QW dosing, 0/3 patients experienced DLT at 12 mg/m2 and 1/6 patients experienced DLT at 15 mg/m2. The DLT was skin desquamation requiring treatment delay. QW MTD was identified as 15 mg/m2. Toxicities (all grade 3 except lymphopenia) that could possibly be attributed to CRLX101 are in Table 1. Full clinical and pathologic staging were available for 29/32 patients. Mean neoadjuvant rectal (NAR) score was 19 with standard deviation of 15. At the weekly MTD, 3/6 patients had pCR. Conclusions: CRLX101 weekly at 15 mg/m2+ standard capecitabine-based chemoradiotherapy appears to be well tolerated, with promising pCR rates that warrants further evaluation. A larger PhII trial should be considered with this regimen. Clinical trial information: NCT02010567. [Table: see text]


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