Distance to the anal verge is associated with pathologic complete response to neoadjuvant therapy in locally advanced rectal cancer

The aim of the study: to increase the frequency of achieving pathologic complete response and increase disease-free survival in the investigational group of patients with locally advanced rectal cancer T3(MRF+)–4N0–2M0 by developing a new strategy for neoadjuvant therapy.Materials and methods. In total, 414 patients were assigned to treatment. Control group I included 89 patients who underwent radiotherapy (RT) 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week. Control group II included 160 patients who underwent RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and oxaliplatin once a week, during the course of RT. Study group III consisted of 165 patients. This group combined RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and additional consecutive CapOx cycles. This group was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating chemotherapy (after CRT); subgroup IIIb included 59 patients who underwent “sandwich” treatment. Therapy consisted of conducting from 1 to 2 cycles of induction CapOx (up to CRT) and from 1 to 2 cycles of consolidating CapOx with an interval of 7 days. In the interval between the courses of drug therapy, RT 52–56 Gy/26–28 fractions was performed. According to the results of the control examination, further treatment tactics were determined. The primary end points were 5-year disease-free survival and the achievement of a pathologic complete response.Results. Pathologic complete response was significantly more often recorded in patients in the investigational group III (17.48 %; p = 0.021) compared with control groups (7.95 % in the I group and 8.28 % in the II group). 5-year disease-free survival in patients in the study groups was: 71.5 % in the III group, 65.6 % in the II group and 56.9 % in the I group.Conclusion. The shift in emphasis on strengthening the neoadjuvant effect on the tumor and improving approaches to drug therapy regimens have significantly improved disease-free survival of patients with locally advanced rectal cancer.

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Clinical predictive factors of pathologic complete response in locally advanced rectal cancer

Oncotarget ◽

10.18632/oncotarget.8133 ◽

2016 ◽

Vol 7 (22) ◽

pp. 33374-33380 ◽

Cited By ~ 24

Author(s):

Francesca De Felice ◽

Luciano Izzo ◽

Daniela Musio ◽

Anna Lisa Magnante ◽

Nadia Bulzonetti ◽

...

Keyword(s):

Rectal Cancer ◽

Predictive Factors ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer

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Analysis of Clinical characteristics to predict pathologic complete response for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy

Journal of Cancer ◽

10.7150/jca.25493 ◽

2018 ◽

Vol 9 (15) ◽

pp. 2687-2692 ◽

Cited By ~ 3

Author(s):

Haihua Peng ◽

Chengtao Wang ◽

Weiwei Xiao ◽

Xiaodan Lin ◽

Kaiyun You ◽

...

Keyword(s):

Rectal Cancer ◽

Clinical Characteristics ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Neoadjuvant Chemoradiotherapy ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer

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Molecular and Kinetic Analyses of Circulating Tumor Cells as Predictive Markers of Treatment Response in Locally Advanced Rectal Cancer Patients

Cells ◽

10.3390/cells8070641 ◽

2019 ◽

Vol 8 (7) ◽

pp. 641 ◽

Cited By ~ 8

Author(s):

Bianca C. Troncarelli Flores ◽

Virgilio Souza e Silva ◽

Emne Ali Abdallah ◽

Celso A.L. Mello ◽

Maria Letícia Gobo Silva ◽

...

Keyword(s):

Rectal Cancer ◽

Protein Expression ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Excision Repair ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer

Neoadjuvant chemoradiation (NCRT) followed by total mesorectal excision is the standard treatment for locally advanced rectal cancer (LARC). To justify a non-surgical approach, identification of pathologic complete response (pCR) is required. Analysis of circulating tumor cells (CTCs) can be used to evaluate pCR. We hypothesize that monitoring of thymidylate synthase (TYMS) and excision repair protein, RAD23 homolog B (RAD23B), can be used to predict resistance to chemotherapy/radiotherapy. Therefore, the aims of this study were to analyze CTCs from patients with LARC who underwent NCRT plus surgery for expression of TYMS/RAD23B and to evaluate their predictive value. Blood samples from 30 patients were collected prior to NCRT (S1) and prior to surgery (S2). CTCs were isolated and quantified by ISET®, proteins were analyzed by immunocytochemistry, and TYMS mRNA was detected by chromogenic in situ hybridization. CTC counts decreased between S1 and S2 in patients exhibiting pCR (p = 0.02) or partial response (p = 0.01). Regarding protein expression, TYMS was absent in 100% of CTCs from patients with pCR (p = 0.001) yet was expressed in 83% of non-responders at S2 (p < 0.001). Meanwhile, RAD23B was expressed in CTCs from 75% of non-responders at S1 (p = 0.01) and in 100% of non-responders at S2 (p = 0.001). Surprisingly, 100% of non-responders expressed TYMS mRNA at both timepoints (p = 0.001). In addition, TYMS/RAD23B was not detected in the CTCs of patients exhibiting pCR (p = 0.001). We found 83.3% of sensitivity for TYMS mRNA at S1 (p = 0.001) and 100% for TYMS (p = 0.064) and RAD23B (p = 0.01) protein expression at S2. Thus, TYMS mRNA and/or TYMS/RAD23B expression in CTCs, as well as CTC kinetics, have the potential to predict non-response to NCRT and avoid unnecessary radical surgery for LARC patients with pCR.

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Tumor size as a predictor of pathologic complete response (pCR) and survival in a prospective trial of chemoradiation for locally advanced rectal cancer

Journal of Clinical Oncology ◽

10.1200/jco.2005.23.16_suppl.3672 ◽

2005 ◽

Vol 23 (16_suppl) ◽

pp. 3672-3672

Author(s):

C. S. Kim ◽

P. R. Anne ◽

E. P. Mitchell ◽

J. Palazzo ◽

E. Pequignot ◽

...

Keyword(s):

Rectal Cancer ◽

Tumor Size ◽

Locally Advanced ◽

Prospective Trial ◽

Pathologic Complete Response ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer

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The prognostic value of an early response in chemoradiation of locally advanced rectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14134 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14134-e14134

Author(s):

John Ploeen ◽

Jan Lindebjerg ◽

Jens Christian Riis Joergensen ◽

Anders Kristian Moeller Jakobsen

Keyword(s):

Rectal Cancer ◽

Clinical Examination ◽

Anal Verge ◽

Locally Advanced ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Clinical Value ◽

Cancer Specific Survival ◽

End Of Treatment

e14134 Background: Preoperative chemoradiation is standard treatment of locally advanced rectal cancer, and there is an obvious need for new methods of assessing the effect. Evaluation by clinical examination with endoscopy is controversial. In most papers the assessment of effect has been performed after the end of treatment. The aim of the present study was to investigate the clinical value of an examination during chemoradiation. Methods: The study included 128 patients with histopathologically verified rectal cancer. Further inclusion criteria were a T3 tumor with a circumferential margin ≤ 5 mm by MRI or a T4 tumor, a distance of < 10 cm from the anal verge and localized diseased only by abdominal and chest CT scan. The treatment was 50.4 Gy/28 fractions or the same treatment with the addition of endorectal brachytherapy 10 Gy/2 fractions in a randomized trial. The concomitant chemotherapy was UFT 300 mg/m2 and L-leucovorin 22.5 mg daily. Both drugs were given five days a week. Clinical examination with endoscopy was performed week 4 during treatment. The clinical effect was classified into complete response (CR) or not complete response with clinical residual tumor (NCR). The patients were operated eight weeks after end of treatment and the pathological tumor response was classified according to Mandard (TRG). Results: CR was found in 14% of the patients. Comparison with TRG showed that 82% with CR had TRG1 as compared to the NCR group where only 9% had TRG1 (p<10-4). The risk of lymph node metastasis was also different with 94% pN0 in the group with CR compared to 57% in the NCR group (p=0.02). The rate of CR translated to a major difference in the risk of recurrence (local and distant). No patients with CR experienced recurrence as compared to 19% in the NCR group (p<0.05). The CR also correlated with cancer specific survival. None of the patients with CR died from rectal cancer with a median observation time of 36 months compared to 30% in the NCR group. Conclusions: CR is a major prognostic parameter in locally advanced rectal cancer treated with chemoradiation. Early CR should be considered in the selection of patients for Watchful Waiting.

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