scholarly journals THUNDER 2: THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI guided radiotherapy

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Giuditta Chiloiro ◽  
Davide Cusumano ◽  
Luca Boldrini ◽  
Angela Romano ◽  
Lorenzo Placidi ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Dose Escalation ◽  
Treatment Plan ◽  
Locally Advanced ◽  
Residual Tumor ◽  
Complete Response ◽  
Tumour Regression ◽  
Patient Will ◽  
Mri Guided ◽  
The Impact

Abstract Background Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC). Since response to radiotherapy (RT) is dose dependent in rectal cancer, dose escalation may lead to higher complete response rates. The possibility to predict patients who will achieve complete response (CR) is fundamental. Recently, an early tumour regression index (ERI) was introduced to predict pathological CR (pCR) after nCRT in LARC patients. The primary endpoints will be the increase of CR rate and the evaluation of feasibility of delta radiomics-based predictive MRI guided Radiotherapy (MRgRT) model. Methods Patients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features will be enrolled in the trial. Neoadjuvant CRT will be administered using MRgRT. The initial RT treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45 Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine will be administered continuously. A 0.35 Tesla MRI will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated: if ERI will be inferior than 13.1, the patient will continue the original treatment; if ERI will be higher than 13.1 the treatment plan will be reoptimized, intensifying the dose to the residual tumor at the 11th fraction to reach 60.1 Gy. At the end of nCRT instrumental examinations are to be performed in order to restage patients. In case of stable disease or progression, the patient will undergo surgery. In case of major or complete clinical response, conservative approaches may be chosen. Patients will be followed up to evaluate toxicity and quality of life. The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. Discussion This clinical trial investigates the impact of RT dose escalation in poor responder LARC patients identified using ERI, with the aim of increasing the probability of CR and consequently an organ preservation benefit in this group of patients. Trial registration ClinicalTrials.gov Identifier: NCT04815694 (25/03/2021).

Circulating Biomarkers for Response Prediction of Rectal Cancer to Neoadjuvant Chemoradiotherapy

2020 ◽  
Vol 27 (25) ◽  
pp. 4274-4294 ◽  
Author(s):  
Chiara Bedin ◽  
Sara Crotti ◽  
Edoardo D’Angelo ◽  
Sara D’Aronco ◽  
Salvatore Pucciarelli ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Clinical Benefit ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Treatment Protocol ◽  
Predictive Biomarkers ◽  
Complete Response ◽  
Tumour Regression

: Rectal cancer response to neoadjuvant Chemoradiotherapy (pCRT) is highly variable. In fact, it has been estimated that only about 21 % of patients show pathologic Complete Response (pCR) after therapy, while in most of the patients a partial or incomplete tumour regression is observed. Consequently, patients with a priori chemoradioresistant tumour should not receive the treatment, which is associated with substantial adverse effects and does not guarantee any clinical benefit. For Locally Advanced Rectal Cancer Patients (LARC), a standardized neoadjuvant treatment protocol is applied, the identification and the usefulness of prognostic or predictive biomarkers can improve the antitumoural treatment strategy, modifying the sequence, dose, and combination of radiotherapy, chemotherapy and surgical resection. : For these reasons, a growing number of studies are actually focussed on the discovery and investigation of new predictive biomarkers of response to pCRT. In this review, we have selected the most recent literature (2012-2017) regarding the employment of blood-based biomarkers potentially predicting pCR in LARC patients and we have critically discussed them to highlight their real clinical benefit and the current limitations of the proposed methodological approaches.

scholarly journals Vascular calcification and response to neoadjuvant therapy in locally advanced rectal cancer: an exploratory study

2021 ◽  
Author(s):  
Katrina A. Knight ◽  
Ioanna Drami ◽  
Donald C. McMillan ◽  
Paul G. Horgan ◽  
James H. Park ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Poor Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumour Regression ◽  
Royal Infirmary

Abstract Purpose Patients 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. Methods Patients 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. Results Of 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. Conclusions AC 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.

scholarly journals Temporal determinants of tumour response to neoadjuvant rectal radiotherapy

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0254018
Author(s):  
Kendrick Koo ◽  
Rachel Ward ◽  
Ryan L. Smith ◽  
Jeremy Ruben ◽  
Peter W. G. Carne ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Tumour Response ◽  
Advanced Rectal Cancer ◽  
Tumour Regression ◽  
Neoadjuvant Radiotherapy ◽  
Time To Surgery ◽  
The Impact ◽  
Regression Grade

Introduction In locally advanced rectal cancer, longer delay to surgery after neoadjuvant radiotherapy increases the likelihood of histopathological tumour response. Chronomodulated radiotherapy in rectal cancer has recently been reported as a factor increasing tumour response to neoadjuvant treatment in patients having earlier surgery, with patients receiving a larger proportion of afternoon treatments showing improved response. This paper aims to replicate this work by exploring the impact of these two temporal factors, independently and in combination, on histopathological tumour response in rectal cancer patients. Methods A retrospective review of all patients with rectal adenocarcinoma who received long course (≥24 fractions) neoadjuvant radiotherapy with or without chemotherapy at a tertiary referral centre was conducted. Delay to surgery and radiotherapy treatment time were correlated to clinicopathologic characteristics with a particular focus on tumour regression grade. A review of the literature and meta-analysis were also conducted to ascertain the impact of time to surgery from preoperative radiotherapy on tumour regression. Results From a cohort of 367 patients, 197 patients met the inclusion criteria. Complete pathologic response (AJCC regression grade 0) was seen in 46 (23%) patients with a further 44 patients (22%) having at most small groups of residual cells (AJCC regression grade 1). Median time to surgery was 63 days, and no statistically significant difference was seen in tumour regression between patients having early or late surgery. There was a non-significant trend towards a larger proportion of morning treatments in patients with grade 0 or 1 regression (p = 0.077). There was no difference in tumour regression when composite groups of the two temporal variables were analysed. Visualisation of data from 39 reviewed papers (describing 27379 patients) demonstrated a plateau of response to neoadjuvant radiotherapy after approximately 60 days, and a meta-analysis found improved complete pathologic response in patients having later surgery. Conclusions There was no observed benefit of chronomodulated radiotherapy in our cohort of rectal cancer patients. Review of the literature and meta-analysis confirms the benefit of delayed surgery, with a plateau in complete response rates at approximately 60-days between completion of radiotherapy and surgery. In our cohort, time to surgery for the majority of our patients lay along this plateau and this may be a more dominant factor in determining response to neoadjuvant therapy, obscuring any effects of chronomodulation on tumour response. We would recommend surgery be performed between 8 and 11 weeks after completion of neoadjuvant radiotherapy in patients with locally advanced rectal cancer.

The impact of tumor regression grade on long-term survival in locally advanced rectal cancer treated with preoperative chemoradiotherapy

2020 ◽  
Vol 26 (7) ◽  
pp. 1611-1620
Author(s):  
Abdullah Sakin ◽  
Suleyman Sahin ◽  
Nilay Sengul Samanci ◽  
Nurgul Yasar ◽  
Cumhur Demir ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Residual Tumor ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Relapse Free Survival ◽  
Free Survival

Purpose The aim of this study is to investigate the prognostic effect of tumor regression grade (TRG) on long-term survival in locally advanced rectal cancer treated with preoperative chemoradiotherapy. Methods Medical records of 182 patients with locally advanced rectal cancer, who were treated with preoperative chemoradiotherapy followed by surgery between 2002 and 2016, were retrospectively reviewed. TRG was classified into five categories based on the pathological response as follows – TRG1: no viable cancer cell, TRG2: single cancer cell or small groups of cancer cells, TRG3: residual tumor outgrown by fibrosis, TRG4: residual tumor outgrowing fibrosis, TRG5: diffuse residual tumor without regression. TRG1, (TRG2+TRG3), and (TRG4+TRG5) were grouped as complete response, intermediate response, and no response, respectively. Results Of the 182 patients with locally advanced rectal cancer, 112 (61.5%) were male. The mean age was 54.4 (range, 25–87) years. The total number of patients in complete response, intermediate response, and no response group was 24 (13.2%), 105 (57.7%), and 53 (29.1%), respectively. The corresponding five-year relapse-free survival and overall survival rates were 79.8%–92.3%, 74.7%–79.4%, and 55.7%–55.8%, respectively (p < 0.05 for relapse-free survival, p < 0.05 for overall survival). According to ypTNM stage, there was no significant difference in relapse-free survival among TRG groups in ypStage I and II patients (p > 0.05). In ypStage III patients, relapse-free survival was 62 months in no response group vs. not reached in intermediate response group (p < 0.05). According to the ypTNM, there was no significant difference in overall survival among TRG groups in ypStage I, II, and III patients (p > 0.05). In the multivariate analysis, pathological complete response was found to be an independent variable for relapse-free survival and overall survival (hazard ratio (95% confidence interval), 0.34 (0.17–6.77), 0.39 (0.18–0.83), respectively). Conclusion This study showed that patients with pathological complete response to preoperative chemoradiotherapy had longer relapse-free survival and overall survival rates than those with residual disease.

scholarly journals The Impact of Surgical Diversion Before Neoadjuvant Therapy for Rectal Cancer

2015 ◽  
Vol 81 (5) ◽  
pp. 444-449
Author(s):  
Brandon J. Anderson ◽  
Elizabeth G. Hill ◽  
Robert E. Sweeney ◽  
Amy E. Wahlquist ◽  
David T. Marshall ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Treatment Plan ◽  
Locally Advanced ◽  
Patient Characteristics ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Fecal Diversion ◽  
Significant Difference ◽  
The Impact

Up-front fecal diversion can palliate emergent symptoms related to locally advanced rectal cancer (LARC) allowing patients to receive neoadjuvant chemoradiation therapy (nCRT). We analyzed outcomes of pretreatment-diverted LARC patients relative to nondiverted patients to define the impact of this management strategy. We retrospectively collected data on 103 LARC patients treated with nCRTand surgery. Medical records were reviewed for patient characteristics, staging, treatment plan, and outcomes. Thirteen LARC patients underwent pretreatment diversion for urgent symptoms and 90 LARC patients proceeded directly to nCRT. In all, 50 per cent of diverted patients presented with T4 tumor compared with 14 per cent in the nondiverted patients ( P = 0.003). Diverted patients experienced a delay in time-to-treatment initiation of 12 days, although this difference was not statistically significant. Similar rates of chemoradiation and surgical toxicities were observed. Even though diverted patients demonstrated less pathologic response to nCRT compared with nondiverted patients ( P = 0.04), there was no significant difference in overall survival. In conclusion, our study demonstrates the effectiveness of up-front fecal diversion at managing emergent obstructive symptoms related to advanced rectal cancer without additional complications, allowing patients to proceed with nCRT followed by radical surgery.

scholarly journals An expansion study of genotype-driven weekly irinotecan and capecitabine in combination with neoadjuvant radiotherapy for locally advanced rectal cancer with UGT1A1 *1*1 genotype

2019 ◽  
Vol 12 ◽  
pp. 175628481985229 ◽  
Author(s):  
Yun Guan ◽  
Yunzhu Shen ◽  
Ye Xu ◽  
Chao Li ◽  
Jingwen Wang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Treatment Compliance ◽  
Complete Response ◽  
Phase Iii ◽  
Tumour Regression

Background: In our previous dose-escalation study, we uncovered the maximum tolerated dose (MTD) of weekly irinotecan was escalated to 80 mg/m2 and 65 mg/m2 for UDP glucuronosyltransferase family 1 member A1 (UGT1A1) *1*1 and *1*28 rectal cancer patients in neoadjuvant chemoradiotherapy (nCRT). This is an expansion study for *1*1 patients. Methods: Patients with clinical stage T3–4, N0–2 rectal cancer eligible for preoperative chemoradiotherapy were screened for the UGT1A1*28 genotype. A total of 52 patients with the *1*1 genotype were enrolled. Whole-pelvic intensity-modulated radiation therapy was given in 50 Gy/25 fractions. Concurrently, irinotecan of 80 mg/m2 and capecitabine of 625 mg/m2 twice daily from Monday to Friday were administered weekly. Primary endpoint was toxicities; secondary endpoints included pathological complete response (pCR), tumour-regression grading, treatment compliance, overall survival, local recurrence and disease-free survival. Results: All patients completed capecitabine-based radiotherapy as scheduled, and 42 (81%) patients completed more than three cycles of weekly irinotecan. Overall, grade 3/4 toxicities were observed in 20 cases, including 11 leucopenia, 10 neutropenia and 12 diarrhoea. Forty-three patients (83%) underwent a radical surgery, and 12 were evaluated as pCR. Another four patients accepted a watch-and-wait strategy because of clinical complete response (CCR). Conclusions: Our data demonstrated manageable toxicities and an encouraging CCR rate for UGT1A1 *1*1 genotype in an enhanced neoadjuvant therapy. A phase III trial is ongoing to evaluate the value of irinotecan in neoadjuvant therapy (CinClare) [ClinicalTrials.gov identifier: NCT02605265].

Institutional variation in the thoroughness of pathologic assessment and pathologic complete response rates for locally advanced rectal cancers treated with neoadjuvant chemoradiation.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 696-696
Author(s):  
Oliver S Chow ◽  
Sujata Patil ◽  
Metin Keskin ◽  
Jesse Joshua Smith ◽  
Maria Widmar ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Size ◽  
Anal Verge ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Multivariable Analysis ◽  
Residual Tumor ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Pathologic Assessment

696 Background: A pathologic complete response (pCR) after neoadjuvant therapy and surgical excision is associated with a better prognosis and guides the management of patients with locally advanced rectal cancer. It is not known whether the thoroughness of pathologic assessment correlates with the finding of pCR. Methods: We introduce a surrogate measure for the thoroughness of pathologic assessment by taking the ratio of maximum residual tumor size and the number of cassettes prepared from the tumor: the Tumor Size to Cassette Ratio (TSCR). We retrospectively reviewed pathology reports from 259 patients with Stage II/III rectal cancer enrolled in a multicenter prospective clinical trial to determine whether TSCR is associated with pCR. Results: Of 247 included patients, 71 (29%) had a pCR. The pCR rate ranged from 0-45% and TSCR ranged from 0.0004 to 1.67 across the twelve trial sites. TSCR was significantly associated with pCR on univariable analysis. On multivariable analysis, TSCR remained significantly associated with pCR (odds ratio of 0.05; 95% CI 0.008-0.302) after adjusting for clinical stage, tumor size, distance from anal verge, radiation dose, and the number of neoadjuvant cycles of FOLFOX received. Conclusions: Pathologists tend to assess rectal cancer specimens with a pCR more thoroughly, but the thoroughness of pathologic assessment of residual tumor specimens varies between institutions. The thoroughness of pathologic assessment is associated with pCR. This raises the need for further standardization in the assessment of rectal cancer specimens after neoadjuvant chemoradiation.

Early outcomes in patients with locally advanced rectal cancer following total neoadjuvant therapy.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 848-848
Author(s):  
Tyler Friedrich ◽  
Karyn A. Goodman ◽  
Stephen Leong ◽  
Whitney Herter ◽  
Sarah Lindsey Davis ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Residual Tumor ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
University Of Colorado ◽  
Total Neoadjuvant Therapy ◽  
The University

848 Background: The current standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation followed by surgery, and then adjuvant chemotherapy. An alternative approach currently being offered to patients at University of Colorado is total neoadjuvant therapy (TNT), in which patients receive all of their planned treatment, including systemic chemotherapy, preoperatively. Methods: Records of patients from the University of Colorado multidisciplinary colorectal clinic between 2/2015 and 5/2017 were retrospectively reviewed. Treatment plans for included patients involved 8 cycles of preoperative chemotherapy with FOLFOX (5-fluoruracil, oxaliplatin, leucovorin), followed by chemoradiation with concurrent capecitabine, and then resection. Patient data collected includes demographic information, initial staging, chemotherapy and radiation received, adverse effects, surgical outcomes, and clinical and pathological response to treatment. Results: At the time of our analysis, 14 patients have completed TNT and undergone surgical resection, with either abdominoperineal resection or low anterior resection (LAR), at the University of Colorado. Patients ranged in age from 39 to 74 years (mean age 56) with 8 patients (57%) female sex. All 14 patients received 5-fluorouracil with all 8 cycles, though 4 (29%) required omission of oxaliplatin by cycle 8. Toxicities from preoperative treatment were as expected, without significant delays in surgery. Of the 14 patients, 4 (29%) showed a pathologic complete response (grade 0, no residual tumor) on their surgical pathology, with 8 (57%) having either grade 0 or 1 (minimal residual tumor) response. Of the 5 patients who underwent LAR with diverting loop ileostomies, mean time to ostomy reversal was 53.6 days (range 49-61). No patients developed clinically-apparent metastatic disease during preoperative therapy. Conclusions: The use of preoperative chemotherapy in addition to standard chemoradiation for locally advanced rectal cancer is well-tolerated, results in a high rate of pathologic complete response, and allows for early reversal of diverting ileostomies.

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