scholarly journals Fusobacterium nucleatum persistence and risk of recurrence after preoperative treatment in locally advanced rectal cancer

2020 ◽  
Vol 31 (10) ◽  
pp. 1366-1375 ◽  
Author(s):  
G. Serna ◽  
F. Ruiz-Pace ◽  
J. Hernando ◽  
L. Alonso ◽  
R. Fasani ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Fusobacterium Nucleatum ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Preoperative Treatment ◽  
Risk Of Recurrence

scholarly journals Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer

2021 ◽  
Vol 9 (3) ◽  
pp. e001610
Author(s):  
Incheol Seo ◽  
Hye Won Lee ◽  
Sang Jun Byun ◽  
Jee Young Park ◽  
Hyeonji Min ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Enrichment Analysis ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Cytolytic Activity ◽  
Gene Set Enrichment Analysis ◽  
Preoperative Treatment ◽  
Rna Seq

BackgroundNeoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC.MethodsWe analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets.ResultsGene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature.ConclusionsTaken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.

Primary Tumor Response to Preoperative Chemoradiation With or Without Oxaliplatin in Locally Advanced Rectal Cancer: Pathologic Results of the STAR-01 Randomized Phase III Trial

2011 ◽  
Vol 29 (20) ◽  
pp. 2773-2780 ◽  
Author(s):  
Carlo Aschele ◽  
Luca Cionini ◽  
Sara Lonardi ◽  
Carmine Pinto ◽  
Stefano Cordio ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Primary Tumor ◽  
Tumor Response ◽  
Locally Advanced ◽  
Muscularis Propria ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Iii ◽  
Preoperative Treatment ◽  
The Impact

Purpose To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. Patients and Methods Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m2/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m2 weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here. Results Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P < .001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P < .001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014). Conclusion Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.

scholarly journals Phase II Study of Preoperative Treatment with External Radiotherapy Plus Panitumumab in Low‐Risk, Locally Advanced Rectal Cancer (RaP Study/STAR‐03)

2018 ◽  
Vol 23 (8) ◽  
pp. 912-918 ◽  
Author(s):  
Carmine Pinto ◽  
Maurizio Di Bisceglie ◽  
Francesca Di Fabio ◽  
Annamaria Bochicchio ◽  
Tiziana Latiano ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Low Risk ◽  
Preoperative Treatment ◽  
External Radiotherapy

scholarly journals Pathologic response after neoadjuvant chemoradiotherapy in Sudanese patients with locally advanced rectal adenocarcinoma

2015 ◽  
Vol 3 (2) ◽  
pp. 53
Author(s):  
Ahmed Abdalla ◽  
Awad Alawad ◽  
Hussein Abdalla M. Ali
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Pathologic Response ◽  
Response To Therapy ◽  
Clinical Staging ◽  
Preoperative Treatment ◽  
Surgical Specimen

<p><strong>Background:</strong> Locally advanced rectal cancer can be down staged by neoadjuvant therapy and the resultant tumor response can be quantified histologically.</p><p><strong>Objective:</strong> This study aimed to assess pathologic response of neoadjuvant chemoradiation in patients with locally advanced rectal cancers treated in Wad Medani Teaching Hospital (WMTH) and National Cancer Institute (NCI), Wad Medani, Sudan.</p><p><strong>Patients and Methods:</strong> A total of 36 consecutive patients with locally advanced rectal cancer that were managed in WMTH and NCI during the period from 2006-2011 were reviewed. Preoperative pelvic radiotherapy was delivered.  The total of 46 Grays were delivered concurrently with 5- fluorouracil (5-FU) on the first and last week of radiation. Total mesorectal excision of the rectal tumour either by anterior or abdominoperineal resections was planned at 6-8 weeks from completion of preoperative treatment. The pathological response to therapy was assessed by histopathology examination of the surgical specimen.</p><p><strong>Results:</strong> Initial clinical staging of patients revealed 58.3% of them were stage T3/T4N2M0 and 41.7% were stage T3N0M0. Down-staging to stage T1/T2N0M0 was found in 36.1% and stages T3N0M0 in 30.6%. No response was seen in 8.3% of cases with stage T3/T4N2M0 while a complete clinical response (no residual) was seen in 25.0%. Complete histological response was observed 13.8%. Positive lymph-nodes metastasis was confirmed in 8.3% of cases.</p><p><strong>Conclusion:</strong> Neoadjuvant chemoradiation is a reasonable option for cases of rectal cancer and deserves further evaluation.</p>

scholarly journals Cell-free DNA levels and correlation to stage and outcome following treatment of locally advanced rectal cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (11) ◽  
pp. 101042831773097 ◽  
Author(s):  
Anders Kindberg Boysen ◽  
Yvonne Wettergren ◽  
Boe Sandahl Sorensen ◽  
Helena Taflin ◽  
Bengt Gustavson ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Preoperative Chemoradiation ◽  
Cell Free Dna ◽  
Risk Of Recurrence ◽  
Pathologic Stage ◽  
Free Dna ◽  
Median Level

Accurate staging of rectal cancer remains essential for optimal patient selection for combined modality treatment, including radiotherapy, chemotherapy and surgery. We aimed at examining the correlation of cell free DNA with the pathologic stage and subsequent risk of recurrence for patients with locally advanced rectal cancer undergoing preoperative chemoradiation. We examined 75 patients with locally advanced rectal cancer receiving preoperative chemoradiation. Blood samples for translational use were drawn prior to rectal surgery. The level of cell free DNA was quantified by digital droplet PCR and expressed as copy number of beta 2 microglobulin. We found a median level of cell free DNA in the AJCC stages I-III of 3100, 8300, and 10,700 copies/mL respectively. For patients with 12 sampled lymph nodes or above, the median level of cell free DNA were 2400 copies/mL and 4400 copies/mL (p = 0.04) for node negative and node positive disease respectively. The median follow-up was 39 months and 11 recurrences were detected (15%). The median level for patients with recurrent disease was 13,000 copies/mL compared to 5200 copies/mL for non-recurrent patients (p = 0.08). We have demonstrated a correlation between the level of total cell free DNA and the pathologic stage and nodal involvement. Furthermore, we have found a trend towards a correlation with the risk of recurrence following resection of localized rectal cancer.

scholarly journals Fibrinogen and Albumin Score Changes during Preoperative Treatment Can Predict Prognosis in Patients with Locally Advanced Rectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Meng-Jun Tang ◽  
Shu-Bo Ding ◽  
Wang-Yuan Hu
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Preoperative Treatment ◽  
Prognostic Parameters ◽  
Group A ◽  
Group B

Background. Fibrinogen (Fib) and albumin (Alb) levels are indicators of systemic inflammatory responses. Elevated Fib and decreased Alb levels are considered negative prognostic factors in different types of cancer. Here, we explored the prognostic value of changes in pre- and post- neoadjuvant chemoradiotherapy (NCRT) plasma fibrinogen and serum albumin (FA) scores in patients with locally advanced rectal cancer (LARC). Methods. A total of 106 patients with LARC who underwent NCRT followed by surgical resection at Jinhua Municipal Central Hospital between 2011 and 2015 were analyzed. In addition, plasma Fib and serum Alb levels before and after NCRT were collected. FA scores were calculated based on the Fib and Alb levels dichotomized by clinical reference values. Patients were classified into two groups based on the changes in FA scores during NCRT: in group A, FA scores decreased or remained unchanged (n=84), and in group B, FA scores increased (n=22). Changes in FA scores were compared with patient outcomes. Results. Increased FA scores were associated with worse disease-free survival (DFS) and overall survival (OS) in patients with LARC. The occurrence of systemic failure was higher in group B than in group A (40.9% vs. 19%, P=0.032). In multivariate analysis, changes in FA scores, pretreatment carcinoembryonic antigen (CEA) levels, and pathologic differentiation were independent prognostic parameters for DFS and changes in FA scores and pretreatment CEA levels were independent prognostic parameters for OS. Conclusions. Increased FA score after NCRT was an independent negative prognostic factor for DFS and OS in patients with NCRT-treated LARC.

scholarly journals Assessing response to neo-adjuvant therapy in locally advanced rectal cancer using Intra-voxel Incoherent Motion modelling by DWI data and Standardized Index of Shape from DCE-MRI

2018 ◽  
Vol 10 ◽  
pp. 175883591880987 ◽  
Author(s):  
Antonella Petrillo ◽  
Roberta Fusco ◽  
Vincenza Granata ◽  
Salvatore Filice ◽  
Mario Sansone ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Nonparametric Tests ◽  
Preoperative Treatment ◽  
Tumour Regression Grade ◽  
Dce Mri ◽  
Standardized Index ◽  
Best Parameters

Background: Our aim was to investigate preoperative chemoradiation therapy (pCRT) response in locally advanced rectal cancer (LARC) comparing standardized index of shape (SIS) obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with intravoxel-incoherent-motion-modelling-derived parameters by diffusion-weighted imaging (DWI). Materials and methods: Eighty-eight patients with LARC were subjected to MRI before and after pCRT. Apparent diffusion coefficient (ADC), tissue diffusion (Dt), pseudodiffusion (Dp) and perfusion fraction (f) were calculated and percentage changes ∆ADC, ∆Dt, ∆Dp, ∆f were computed. SIS was derived comparing DCE-MRI pre- and post-pCRT. Nonparametric tests and receiver operating characteristic (ROC) curves were performed. Results: A total of 52 patients were classified as responders (tumour regression grade; TRG ⩽ 2) and 36 as not-responders (TRG > 3). Mann–Whitney U test showed statistically significant differences in SIS, ∆ADC and ∆Dt between responders and not-responders and between complete responders (19 patients with TRG = 1) versus incomplete responders. The best parameters to discriminate responders by nonresponders were SIS and ∆ADC, with an accuracy of 91% and 82% (cutoffs of −5.2% and 18.7%, respectively); the best parameters to detect pathological complete responders were SIS, ∆f and ∆Dp with an accuracy of 78% (cutoffs of 38.5%, 60.0% and 83.0%, respectively). No increase of performance was observed by combining linearly each possible couple of parameters or combining all parameters. Conclusion: SIS allows assessment of preoperative treatment response with high accuracy guiding the surgeon versus more or less conservative treatment. DWI-derived parameters reached less accuracy compared with SIS and combining linearly DCE- and DWI-derived parameters; no increase of accuracy was obtained.

Sign in / Sign up

Export Citation Format

Share Document