The Impact Of Neoadjuvant Chemoradiotherapy On The Landscape Of Soluble Immune Checkpoint Molecules In Patients With Locally Advanced Rectal Cancer

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.

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Long-course neoadjuvant chemoradiotherapy with versus without a concomitant boost in locally advanced rectal cancer: a randomized, multicenter, phase II trial (FDRT-002)

Radiation Oncology ◽

10.1186/s13014-019-1420-z ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 4

Author(s):

Jingwen Wang ◽

Yun Guan ◽

Weilie Gu ◽

Senxiang Yan ◽

Juying Zhou ◽

...

Keyword(s):

Rectal Cancer ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Disease Free Survival ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Concomitant Boost ◽

The Impact ◽

To Receive ◽

Incision Healing

Abstract Background This study was designed to explore whether an intensified chemoradiotherapy (CRT) led to a better clinical outcome in locally advanced rectal cancer. Methods Patients with stage II/III rectal cancer were randomly allocated to receive either pelvic intensity-modulated radiation therapy (IMRT) of 50 Gy/25Fx concurrently with capecitabine and oxaliplatin (Arm A), or pelvic radiation of 50 Gy/25Fx with a concomitant boost of 5 Gy to the primary lesion, followed by a cycle of XELOX 2 weeks after the end of CRT (Arm B). All patients were planned to receive a definitive operation 8 weeks after the completion of CRT and a total of six perioperative chemotherapy cycles of capecitabine and oxaliplatin regardless of pathological result. Pathological complete response (ypCR) was the primary endpoint. Results From February 2010 to December 2011, 120 patients from three centers were enrolled in this study. Ninety-five percent patients completed a full-dose chemoradiotherapy as planning. Then 53 and 57 patients received a radical surgery, and 8 and 14 cases were confirmed as ypCR in two groups (P = 0.157). The other 10 patients failed to receive a definitive resection because of unresectable disease. Similar toxicities were observed between two groups and more incision healing delay were found in Arm B (3 vs.13, P = 0.011). No statistical differences were observed in local-regional control (P = 0.856), disease-free survival (P = 0.349) and overall survival (P = 0.553). Mesorectal fascia (MRF) involvement was an independent prognostic factor for survival in multivariate analysis. Conclusions A concomitant boost to oxalipatin-combined preoperative chemoradiotherapy demonstrated a slightly higher pCR rate but delayed incision healing after surgery. The impact of MRF involvement on survival merits further investigations. Trial registration NCT01064999 (ClinicalTrials.gov).

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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 ◽

10.3390/cells10061539 ◽

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.

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