scholarly journals Fractal-Based Radiomic Approach to Tailor the Chemotherapy Treatment in Rectal Cancer: A Generating Hypothesis Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Carmela Di Dio ◽  
Giuditta Chiloiro ◽  
Davide Cusumano ◽  
Francesco Catucci ◽  
Luca Boldrini ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Staging ◽  
Univariate Analysis ◽  
External Validation ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Logistic Models ◽  
Advanced Rectal Cancer ◽  
Image Features

IntroductionThe aim of this study was to create a radiomic model able to calculate the probability of 5-year disease-free survival (5yDFS) when oxaliplatin (OXA) is or not administered in patients with locally advanced rectal cancer (LARC) and treated with neoadjuvant chemoradiotherapy (nCRT), allowing physicians to choose the best chemotherapy (CT) regimen.MethodsLARC patients with cT3–4 cN0 or cT1–4 cN1–2 were treated according to an nCRT protocol that included concomitant CT schedules with or without OXA and radiotherapy dose of 55 Gy in 25 fractions. Radiomic analysis was performed on the T2-weighted (T2-w) MR images acquired during the initial tumor staging. Statistical analysis was performed separately for the cohort of patients treated with and without OXA. The ability of every single radiomic feature in predicting 5yDFS as a univariate analysis was assessed using the Wilcoxon–Mann–Whitney (WMW) test or t-test. Two logistic models (one for each cohort) were calculated, and their performance was assessed using the area under the receiver operating characteristic (ROC) curve (AUC).ResultsA total of 176 image features belonging to four families (morphological, statistical, textural, and fractal) were calculated for each patient. At the univariate analysis, the only feature showing significance in predicting 5yDFS was the maximum fractal dimension of the subpopulation identified considering 30% and 50% as threshold levels (maxFD30–50). Once the models were developed using this feature, an AUC of 0.67 (0.57–0.77) and 0.75 (0.56–0.95) was obtained for patients treated with and without OXA, respectively. A maxFD30–50 >1.6 was correlated to a higher 5yDFS probability in patients treated with OXA.ConclusionThis study suggests that radiomic analysis of MR T2-w images can be used to define the optimal concomitant CT regimen for stage III LARC cancer patients. In particular, by providing an indication of the gross tumor volume (GTV) spatial heterogeneity at initial staging, maxFD30–50 seems to be able to predict the probability of 5yDFS. New studies including a larger cohort of patients and external validation sets are recommended to verify the results of this hypothesis-generating study.

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.

Polymorphisms of thymidylate synthase as prognostic factor in rectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 433-433
Author(s):  
V. Arrazubi ◽  
J. Suarez ◽  
D. Guerrero ◽  
K. Cambra ◽  
M. L. Gomez Dorronsoro ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Thymidylate Synthase ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumour Regression ◽  
The Difference

433 Background: Neoadjuvant fluoropyrimidine-based chemotherapy (ChT) plus radiotherapy (Rt) is a standard approach for locally advanced rectal cancer. Polymorphisms of thymidylate synthase (TS), the target for fluoropyrimidines, are recognized prognostic factors in colon cancer. The aim of this study was to evaluate the prognostic value of the polymorphisms of TS in rectal cancer after neoadjuvant ChT plus Rt. Methods: We studied one-hundred consecutive patients with stage II/III rectal cancer between November 2001 and March 2009. Patients underwent surgery 6-8 weeks after neoadjuvant Rt (5,040 cGy) plus fluoropyrimidine-based ChT. DNA was extracted from paraffin embedded biopsies. TS1494del6 and 5′-28bp repeat +G/C SNP polymorphisms were determined. Results: Sixty-seven percent were men and median age was 67 years. ypT stage was: T0 9%, T1 2%, T2 27%, T3 60% and T4 2%; 32% had locoregional adenopathies. The median follow-up was 45 months and relapse occurred in 20% of patients. Polimorphisms could be determined in 98% of pt: -6bp/-6bp 10%, - 6bp/+6bp 39%, +6bp/+6bp 51% and 2R/2R 72%, 2R/3R 21%, 3R/3R 6%. The grade of pathological tumour regression was not associated with polymorphisms. Relapses occurred in 40% of patients -6bp/-6bp, 22% of patients -6bp/+6bp and 21% of patients +6bp/+6bp. The difference in disease- free survival (DFS) between the first and the third groups was stadistically significative (p=0.049). No relation between 5′-28bp repeat +G/C SNP polymorphism and DFS was found. Conclusions: Our data suggest that the TS1494del6 polimorphism may be an important prognosis factor in rectal cancer receiving neoadjuvant chemoradiotherapy. No significant financial relationships to disclose.

Predicting pathologic response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer using FDG PET/CT.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 505-505
Author(s):  
S. Shanmugan ◽  
R. Arrangoiz ◽  
J. R. Nitzkorski ◽  
J. Q. Yu ◽  
T. Li ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Fdg Pet ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Pet Ct ◽  
Fdg Pet Ct

505 Background: Pathologic complete response (pCR) after neoadjuvant chemoradiation has been observed in 15% to 30% of patients with locally advanced rectal cancer. The utility of FDG PET/CT scans in the management of patients with stage II or III rectal cancer is not well defined. The objective of this study is to determine if FDG PET/CT can be used to predict pCR and disease-free survival in patients receiving neoadjuvant chemoradiation with locally advanced rectal cancer. Methods: A retrospective chart review was conducted in patients with endorectal ultrasound-staged T3 to T4 rectal tumors who underwent preoperative and postoperative FGD PET/CT imaging. All patients were treated with neoadjuvant chemoradiotherapy (CRT). Maximum standardized uptake value (SUV) of each tumor was recorded. Logistic regression was used to analyze the association of pre-CRT SUV, post-CRT SUV, % SUV change, and time between therapy and surgery in comparison to pathological complete response. Kaplan-Meier estimation was used to look for significant predictors of survival. Results: Seventy patients (mean age 62; 42M:28F) with preoperative stage T3Nx (n = 60) and T4Nx (n = 10) underwent pre-CRT and post-CRT FDG PET/CT scans between November 2002 and March 2009. All patients underwent definitive surgery after therapy with standard pathologic evaluation.The pCR rate was 26%. Median pre-CRT SUV was 10.5 while the median post-CRT SUV was 4.05. Patients with pCR had a lower mean post-CRT SUV compared to those without pCR (2.7 vs. 4.5, p = 0.02). Median SUV decrease was 61% (range 6% to 95%) and was significant in predicting pCR (p = 0.004). Patients with a pCR had a greater time interval between neoadjuvant therapy and surgery (median 57 days vs. 50 days) than those without (p = 0.05). Furthermore, patients with post-CRT SUV < 4 had a lower local recurrence rate compared to those with post-CRT SUV > 4 (p = 0.03). Patients with SUV decrease > 61% had improved overall survival at mean follow-up of 39 months than those without (p = 0.01). Conclusions: PET/CT can predict response to neoadjuvant chemoradiation in patients with locally advanced rectal cancer. Pre-CRT SUV was the only predictor of disease-free survival. No significant financial relationships to disclose.

A novel preoperative protocol for locally advanced rectal cancer: Hyperfractionated short-course radiotherapy combined with chemotherapy.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 577-577
Author(s):  
Hiroshi Doi ◽  
Naohito Beppu ◽  
Yasuhiro Takada ◽  
Yasue Niwa ◽  
Masayuki Fujiwara ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Radical Surgery ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Short Term ◽  
Term Outcome ◽  
Short Course ◽  
Short Course Radiotherapy

577 Background: Neoadjuvant chemoradiotherapy (NACRT) has become a widely accepted strategy for rectal cancer (RC). The purpose of this study is to examine the safety and efficacy of a novel protocol of neoadjuvant hyperfractionated short-course radiotherapy (NAHSRT) combined with chemotherapy for locally advanced RC. Methods: 82 patients (pts) with RC were treated with NACRT followed by radical surgery between March 2008 and May 2012. 50 pts with RC of cT3N1M0 were analyzed in the present study. NAHSRT was performed with a dose of 2.5 Gy twice daily, with an interval of at least 6 hours between fractions, up to a total dose of 25 Gy (25 Gy in 10 fractions for 5 days) with chemotherapy. Radical surgery was performed within 3 week following the end of the NAHSRT. Results: 50 pts included 37 men and 13 women. The median age was 65.0 (range: 39-85) years. The median follow-up term was 12.0 (2-36) months. S-1, oxaliplatin with capecitabine, and fluorouracil, leucovorin plus irinotecan (FOLFIRI) was administered with NAHSRT in 48 pts, 1 pt, and 1 pt, respectively. 48 pts (96%) had no apparent adverse events before surgery. 49 pts (98%) completed NACRT except for 1 pt stopped chemotherapy (S-1) because of grade 3 gastrointestinal toxicity (CTCAE v.3). In addition, no pts showed grade 4 toxicities. Postoperative complications were found in 30 pts (60.0%). 33 pts (66.0%) received adjuvant chemotherapy. S-1, capecitabine, oxaliplatin with capecitabine, uracil/tegafur (UFT) and oral leucovorin, and oxaliplatin combined with S-1 (SOX) was delivered after surgery in 20 pts, 4 pts, 4 pts, 4 pts, and 1 pt, respectively. No pts. developed local failure, although distant failures were found in 3 pts. The median disease free survival and overall survival was 11.6 (2-36) months and 12.0 (2-36) months, respectively. In addition, disease-specific survival rate was 100.0%. Conclusions: We presented a novel protocol of NAHSRT for locally advanced RC and the short-term outcome. NAHSRT was well tolerated and produced excellent short-term outcomes in pts with locally advanced RC.

Predicting the pathologic complete regression with hematologic markers during neoadjuvant chemoradiotherapy in the locally advanced rectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 583-583
Author(s):  
Jae-Sung Kim ◽  
Joo Ho Lee ◽  
Changhoon Song
Keyword(s):  
Rectal Cancer ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
P Value ◽  
Complete Regression ◽  
Operating Characteristics ◽  
Predictive Values

583 Background: The present study aimed to evaluate the hematologic markers for predicting the pathologic complete regression during and after neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. Methods: Total 297 patients with rectal cancer underwent neoadjuvant CRT followed by surgical resection and performed complete blood counts (CBC) serially during and after CRT. The timepoints of CBC were before CRT (pre-), three weeks after the day of starting CRT (intra-), and four weeks after CRT (post-). We calculated the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte (NLR), derived neutrophil-to-lymphocyte (dNLR) using the serial CBC test. The ratio of change in PLR (cPLR), NLR (cNLR), and dNLR (cdNLR) was calculated as the change of value/pre-value. Chi-square and T-test for univariate analysis and multivariate logistic regression were performed to identify the significant predictor for pCR. Receiver operating characteristics (ROC) analysis was used to compare the predictive values. Results: The overall rate of pCR was 15.9%. The Pre-Hb, pre-NLR, intra-PLR, intra-NLR, intra-cPLR, intra-cNLR, post-WBC, post-Hb, and post-cPLR were significantly different between patients with pCR and no pCR. In the multivariate logstic regression, pre-Hb (OR 1.456 p-value .026), intra-cPLR (OR 4.949, p-value < .001), post-WBC (OR 0.664, p-value .008), and post-PLR (OR 1.011 p-value .001) were significant predictors for pCR. In the comparison of ROCs, intra-cPLR was the most accurate predictor for pCR among the hematologic variables (AUC = 0.74, p ≤ .001). Conclusions: Change of PLR during neoadjuvant CRT is the clinically applicable and significant predictor for pCR with high negative predictive value in the patients with LRC.

scholarly journals Factors Predicting Pathological Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer: The Experience of a Single Institution with 269 Patients (STONE-01)

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6074
Author(s):  
Michele Fiore ◽  
Pasquale Trecca ◽  
Luca E. Trodella ◽  
Roberto Coppola ◽  
Marco Caricato ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Female Gender ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Time Interval ◽  
Interval Time ◽  
Time To Surgery

Aims: The aim of this study was to define a potential benefit of pathological complete response rate (pCR) and downstaging rate after neoadjuvant chemoradiotherapy (CRT) in relation to treatment and patient factors in locally advanced rectal cancer. Methods: We performed a retrospective cohort study. Patients were divided according to chemotherapy regimens concurrent to radiotherapy (1-drug vs. 2-drug) and according to the time interval between the end of CRT and surgery (≤8 weeks vs. >8 weeks), as well as in relation to specific relevant clinical factors. Logistic regression was used to estimate the independent factors for pCR and downstaging. Results: 269 patients were eligible for this study. Overall, pCR and downstaging rates were 26% and 75.4%, respectively. Univariate analysis showed that female gender (p = 0.01) and time to surgery >8 weeks (p = 0.04) were associated with pCR; age > 70 years (p = 0.05) and time to surgery >8 weeks (p = 0.002) were correlated to downstaging. At multivariate analysis, interval time to surgery of >8 weeks was the only independent factor for both pCR and downstaging (p = 0.02; OR: 0.5, CI: 0.27–0.93 and p = 0.003; OR: 0.42, CI: 0.24–0.75, respectively). Conclusions: This study indicates that, in our population, an interval time to surgery of >8 weeks is an independent significant factor for pCR and downstaging. Further prospective studies are needed to define the best interval time.

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.

Watch and wait approach following neoadjuvant chemoradiotherapy for rectal cancer patients: A single-centre experience.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 681-681
Author(s):  
Ji Zhu ◽  
Jingwen Wang
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Preoperative Treatment ◽  
Watch And Wait

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.

scholarly journals Elevated Platelet Count as Predictor of Recurrence in Rectal Cancer Patients Undergoing Preoperative Chemoradiotherapy Followed by Surgery

2015 ◽  
Vol 100 (2) ◽  
pp. 199-207 ◽  
Author(s):  
Yuji Toiyama ◽  
Yasuhiro Inoue ◽  
Mikio Kawamura ◽  
Aya Kawamoto ◽  
Yoshinaga Okugawa ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Poor Overall Survival ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
The Impact

The impact of systemic inflammatory response (SIR) on prognostic and predictive outcome in rectal cancer after neoadjuvant chemoradiotherapy (CRT) has not been fully investigated. This retrospective study enrolled 89 patients with locally advanced rectal cancer who underwent neoadjuvant CRT and for whom platelet (PLT) counts and SIR status [neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR)] were available. Both clinical values of PLT and SIR status in rectal cancer patients were investigated. Elevated PLT, NLR, PLR, and pathologic TNM stage III [ypN(+)] were associated with significantly poor overall survival (OS). Elevated PLT, NLR, and ypN(+) were shown to independently predict OS. Elevated PLT and ypN(+) significantly predicted poor disease-free survival (DFS). Elevated PLT was identified as the only independent predictor of DFS. PLT counts are a promising pre-CRT biomarker for predicting recurrence and poor prognosis in rectal cancer.

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