CD8+ tumor-infiltrating lymphocyte infiltration prediction with radiomic signature in locally advanced rectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 123-123
Author(s):  
Eui Kyu Chie ◽  
Seung Hyuck Jeon ◽  
Yu Jin Lim ◽  
Jaemoon Koh ◽  
Sehui Kim ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Characteristic Curve ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Operator Method ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Pearson's R ◽  
Noninvasive Characterization ◽  
Pearson’S R

123 Background: Despite increasing use of cancer immunotherapies, no biomarker relevant to anti-tumor immunity has been developed in rectal cancer. The present study aims to develop a radiomic signature to predict the infiltration of CD8+ tumor-infiltrating lymphocytes (TILs). Methods: In total, 131 patients undergoing neoadjuvant chemoradiotherapy (CRT) from 2005 to 2012 were analyzed. The study included pre-CRT dataset A ( n = 113; n = 75 and 38 for training and validation) and post-CRT datasets B ( n = 32; predominance of tumor) and C ( n = 20; pure fibrosis). To build the radiomic signature, 38 features selected from pre-CRT T2-weighted MRI scans were incorporated into the least absolute shrinkage and selection operator method. Results: Higher CD8+ TIL infiltration was associated with better overall and progression-free survival ( P = 0.01 and 0.03, respectively). In pre-CRT dataset A, the area under the receiver operating characteristic curve values of radiomic score for predicting CD8+ TILs were 0.760 and 0.729 for training and validation subsets, respectively. A significant correlation was observed between the radiomic signature and CD8+ TIL density in the post-CRT dataset B (Pearson’s R = ‒0.372, P = 0.036), whereas no association was found within the dataset C accounting for pure fibrosis after CRT (Pearson’s R = ‒0.069, P = 0.77). Conclusions: We established the MRI-derived radiomic signature for predicting CD8+ TIL infiltration in the contemporary treatment era of rectal cancer. The noninvasive characterization of tumor immune status would provide insights into the role of radiomic-pathology modeling to predict the local immune phenotypes.

NSABP FR-2: Phase II study of durvalumab following neoadjuvant chemoRT in stage II-IV rectal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS264-TPS264
Author(s):  
Thomas J. George ◽  
Greg Yothers ◽  
Samuel A. Jacobs ◽  
Gene Grant Finley ◽  
Hiral D. Parekh ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Stage Iv ◽  
Tumor Infiltrating Lymphocytes ◽  
Sphincter Preservation ◽  
Stage Ii ◽  
Systemic Steroid

TPS264 Background: Clinical improvements for locally advanced rectal cancer have been relatively static over the past few decades. While immunotherapy shows no benefit in microsatellite stable (MSS) colorectal cancer, preclinical models suggest that radiotherapy (RT) can enhance neoantigen presentation, modulate the microenvironment, and improve the likelihood of anti-tumor activity with checkpoint inhibitor use. Using a “window-of-opportunity” study design, this prospective phase II trial will determine the safety and activity of this approach with the anti-PD-L1 agent durvalumab (MEDI4736). Methods: This multi-center phase II trial is currently enrolling patients (pts) with rectal cancer who are undergoing standard NCCN guideline-compliant neoadjuvant chemoradiotherapy (CRT). Eligibility includes pts with MSS stage II-IV rectal cancer with adequate organ function and pre-treatment diagnostic tumor available for profiling with intent to proceed to surgical resection after CRT. Stage IV disease must be limited such that the primary pelvic tumor requires definitive management. Standard ineligibility criteria include active infections, systemic steroid use, or other conditions making immunotherapy use unsafe. Treatment includes durvalumab (750mg IV infusion once every 2 wks) for 4 total doses beginning within 3-7 days after CRT completion. Surgery must be within 8-12 wks of the final CRT dose. Primary endpoint is a demonstrated improvement in Neoadjuvant Rectal Cancer (NAR) score compared to historical controls targeting a 20% relative risk reduction in DFS and 3-4% absolute OS improvement. Secondary endpoints include OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter preservation, off-target “abscopal” effects for the subset of stage IV pts, and exploratory assessments of tumor infiltrating lymphocytes, tumor Immunoscore, circulating immunologic profiles, and molecular predictors of response. A safety run-in phase has completed as a precedent to full enrollment. Enrollment now continues to 47 total pts to achieve 41 surgically evaluable pts. Support: AstraZeneca-Medimmune, NSABP Foundation. Clinical trial information: NCT03102047.

scholarly journals Neoadjuvant Chemoradiotherapy in the Downstaging of Locally Advanced Rectal Cancer and its Impact on Progression–Free Survival

2020 ◽  
Vol 18 (1) ◽  
pp. 39-44
Author(s):  
Tatjana Neško ◽  
Arvils Neško ◽  
Elīna Sīviņa ◽  
Gunta Purkalne
Keyword(s):  
Rectal Cancer ◽  
Vascular Invasion ◽  
Radical Surgery ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Progression Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Free Survival ◽  
The Impact

SummaryIntroductionThe standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (NACRT) followed by radical surgery, which allows to reduce local recurrence, downsize the tumor and facilitate its R0 resection.Aim of the studyThe aim of this study was to evaluate the downstaging of LARC after NACRT and to assess the impact of downstaging on progression–free survival (PFS).Materials and methods65 patients diagnosed with LARC from 2012 to 2018, who received NACRT with subsequent radical surgery were identified in the Pauls Stradins Clinical University Hospital in Riga and included in this retrospective study. Average follow–up period was 31 months. Data were analysed with SPSS Statistics 22.0, Wilcoxon signed–rank test and Kaplan–Meier survival analysis were performed.ResultsOverall, 66.7% (n=40) of patients experienced a downstaging in response to NACRT, of which 37.5% (n=24, p=0.004) had a downstaging of T and 63.3% (n=38, p=0.0001) of N.12–month PFS was 87.8%, 24–month PFS – 66.1% and 3–year PFS – 62.7%, median PFS (mPFS) was not met. 3–year PFS of those patients treated with intravenous 5FU/LV boluses was significantly higher (76.5%) than those who received oral tegafur (45.6%, mPFS 32 months), p=0.038. 3–year PFS of patients with downstaged T was 85.9%, compared to 52.1% without it; mPFS not met, p=0.04. Similarly, 3–year PFS of patients with downstaged N was 71.5%, compared to 43.3% without it (mPFS 24 months), p=0.112. Lymphatic and vascular invasion were associated with significantly lower PFS compared to the patients with absent lymphatic and vascular invasion (p=0.0001 and p=0.014, respectively), while perineural invasion did not show any impact on PFS. Age at diagnosis, tumor location, type of surgery and adjuvant chemotherapy did not have a significant impact on PFS.ConclusionsResults confirm the efficacy of NACRT in LARC in the downstaging of T and N. Downstaging of LARC, intravenous chemotherapy and absence of lymphovascular invasion are associated with significantly increased PFS.

scholarly journals Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1539
Author(s):  
Virgílio Souza e Silva ◽  
Emne Ali Abdallah ◽  
Bianca de Cássia Troncarelli Flores ◽  
Alexcia Camila Braun ◽  
Daniela de Jesus Ferreira Costa ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Transforming Growth Factor ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

Is Metformin Associated With Improved Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer?

2021 ◽  
Vol 268 ◽  
pp. 465-473
Author(s):  
Pere Planellas ◽  
Lidia Cornejo ◽  
Jose Ignacio Rodríguez-Hermosa ◽  
Eloy Maldonado ◽  
Ander Timoteo ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

651 A META-ANALYSIS OF SURVIVAL AFTER NEOADJUVANT CHEMORADIOTHERAPY VERSUS NEOADJUVANT CHEMOTHERAPY IN RESECTABLE LOCALLY ADVANCED ESOPHAGEAL CANCERS BASED ON HISTOLOGIC SUBTYPES

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Rawat Waratchanont ◽  
Jirat Leelapatanadit ◽  
Wichitra Asanprakit ◽  
Viriya Kaewkangsadan ◽  
Sukchai Sattaporn
Keyword(s):  
Overall Survival ◽  
Postoperative Complications ◽  
Neoadjuvant Chemotherapy ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Progression Free Survival ◽  
Comprehensive Search ◽  
Complications And Mortality ◽  
Histologic Subtypes

Abstract   Neoadjuvant treatments provided survival benefits over surgery alone in resectable locally advanced esophageal and esophagogastric junction (EGJ) cancer patients. Both neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) are shown to be effective treatments. However, the direct comparison between two methods based on histologic subtypes, squamous cell carcinoma (SCC) and adenocarcinoma (AC) is still limited. This study examined the hypothesis that nCRT could provide the better overall survival (OS) than nCT. Methods A comprehensive search of studies comparing nCRT and nCT in patients with esophageal and EGJ cancer based on histologic subtypes was conducted. A meta-analysis of randomized (8 articles) and non-randomized (15 articles) studies was performed using odds ratio (OR) and 95% confidence intervals (CI95%). The OS was the main objective, whereas the secondary objective were complete pathological response (pCR) rate, curative resection (R0) rate, locoregional progression free-survival (L-PFS) rate, postoperative complications and mortality. Results Twenty three articles included 1,671 SCC and 9,285 AC patients. Neither 3- nor 5-year OS was found to be different. However, SCC patients receiving nCRT showed the better 3-year OS (OR 1.67, CI95% 1.17–2.40, p = 0.005). Both pCR and R0 rates were superior in nCRT group (OR 3.30, CI95% 2.46–4.44 and 2.46, CI95% 1.66–3.65, p < 0.00001, respectively). The better 3-year L-PFS was observed in nCRT group (OR 1.47, CI95% 1.17–1.85, p = 0.008), but 5-year L-PFS was comparable. The 30-day mortality was comparable, while 90-day mortality was higher in nCRT group (OR 1.32, CI95% 1.01–1.72, p = 0.04). Conclusion The nCRT provided the better overall survival especially in SCC patients and also increased locoregional control. Meanwhile, postoperative complications and mortality were higher after nCRT. Due to clinical heterogeneity, the multidisciplinary team management for each patient is required before treatment.

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