Biomarkers of immunotherapy response in rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy.

593 Background: Immunotherapy (IO) in combination with chemoradiotherapy (CRT) in the neoadjuvant treatment for locally advanced rectal adenocarcinoma (RAC) is an area of active clinical research. There are no well-defined biomarkers in RAC predicting response to neoadjuvant therapy. Increase in tumor PD-L1 expression and tumor infiltrating lymphocytes (TIL) has been observed after neoadjuvant CRT which potentially enhances response to IO. We report herein expression of PD-L1 and CD8+ TIL and other biomarkers of immune activation including CXCL9, TIM3 (HAVCR2), IDO1, IFNG, IL17RE, LAG3 and OX40 (TNFRSF4) pre and post neoadjuvant CRT in RAC. Methods: We retrospectively evaluated 38 RAC patients from 2007-2016 treated with neoadjuvant CRT using 5FU based therapy. Pre and post CRT tissue samples were stained with VENTANA PD-L1 (SP263) rabbit monoclonal antibody to quantify PD-L1 expression. CD8+ TIL were recorded over one high power field (hpf) (40x objective) in the area of densest infiltrate. Additional biomarkers CXCL9, TIM3 (HAVCR2), IDO1, IFNG, IL17RE, LAG3 and OX40 (TNFRSF4) were assayed with RT-PCR. Independent sample and paired sample t-tests were used for statistical analysis of difference in biomarker expression. Relevant clinical endpoints including local relapse, distant metastases and survival were collected. Results: Median age was 60 years (range 32–87). Median follow up was 16.7 months (range 2.6-120.1). Median duration from completion of CRT to resection was 73 days (range 44–315). PD-L1 expression increased from 10% to 23% in pre-CRT versus post-CRT patients. CD8+ TIL increased in 30/39 (83%) patients with an average increase from 66.48 to 129.20 CD8+ TIL/hpf in the pre-CRT versus post-CRT setting. Using RT-PCR, a statistically significant increase in the expression of CXCL9, IFNG and OX40 (TNFRSF4) was found pre-CRT versus post-CRT using paired samples t-test. Conclusions: Neoadjuvant CRT for RAC increased PD-L1 expression and CD8+ TIL along with an increased expression of CXCL9, IFNG and OX40 (TNFRSF4). These data suggest a novel role for IO in neoadjuvant treatment of rectal cancer. Clinical outcome data on these patients will be presented.

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Adding Three Cycles of CAPOX after Neoadjuvant Chemoradiotherapy Increases the Rates of Complete Response for Locally Advanced Rectal Cancer

Current Oncology ◽

10.3390/curroncol28010033 ◽

2021 ◽

Vol 28 (1) ◽

pp. 283-293

Author(s):

Zhiwei Zhai ◽

Kunning Zhang ◽

Chen Wang ◽

Tian Zhang ◽

Lixia Wang ◽

...

Keyword(s):

Rectal Cancer ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Neoadjuvant Chemoradiotherapy ◽

Distant Metastases ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Consolidation Chemotherapy ◽

Significant Difference

Background and Objectives: the total neoadjuvant chemoradiotherapy (TNT) includes different strategies, but the most appropriate model remains uncertain. The purpose of this retrospectively study was to evaluate the safety and pathological response in the consolidation chemotherapy model. Methods: patients with cT3/T4 or TxN + M0 rectal cancer that were receiving neoadjuvant chemoradiotherapy (CRT) (50 Gy with oral capecitabine)/TNT (CRT followed by three cycles of CAPOX) during September 2017 to September 2019 in our department were included. All of the patients were recommended to receive radical surgery. Results: a total of 197 patients were included. Eighty-one patients received CRT, while one hundred and sixteen patients received TNT. Nine patients did not undergo surgery because of the distant metastases (one patient (1.2%) in CRT group, two patients (1.7%) in TNT group) or a refusal of resection (two patients in CRT group, four patients in TNT group). The pathological complete response (pCR) rate was 32.7% in TNT compared with 12.8% in CRT (p = 0.002). There was no statistically significant difference in grade 3 acute toxicities of neoadjuvant treatment and surgical complications between the two groups. Conclusions: the consolidation chemotherapy model is safe for patients with locally advanced rectal cancer and it has a high pCR rate. The long-term follow-up is necessary to be evaluated in a future prospective, randomized trial.

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Neoadjuvant treatment for rectal cancer in fit and vulnerable patients older than 70 years

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.13586 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 13586-13586

Author(s):

M. L. Friso ◽

L. M. Pasetto ◽

U. Basso ◽

S. Pucciarelli ◽

M. Rugge ◽

...

Keyword(s):

Rectal Cancer ◽

Elderly Patients ◽

Rating Scale ◽

Anal Verge ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Rectal Adenocarcinoma ◽

Neoadjuvant Chemoradiotherapy ◽

Vulnerable Patients ◽

Lost To Follow Up

13586 Background: To evaluate the toxicity and feasibility of neoadjuvant 5FU continuous infusion or bolus in combination with pelvic radiotherapy (RT) in rectal cancer patients older than 70 years. Methods: From June 2000 to June 2005, 36 patients older than 70 years out of a total of 300 consecutive cases with histologically proven locally advanced rectal adenocarcinoma (≤ 12 cm from the anal verge) classified as either T3 or T4, N0 or N1–2 M0 disease, were examined. Comorbidities were evaluated according to Cumulative Illness Rating Scale-Geriatric (CIRS-G) and patients were deemed “fit” if they were otherwise healthy or had one or more comorbidities of only grade 1; “vulnerable” if had one or more comorbidities of grade 2. Results: Median age was 74 years (range, 70–82). 14 patients (5 healthy, 13.8%, and 9 with slight comorbidities, 25%) were fit and 22 (61.2%) were vulnerable. All the patients received the full course of RT, with a total dose of 50.4 Gy. The mean number of chemotherapy weeks was 5.34 (range, 2–6). 4 out 14 (28.6%) fit patients and 9 out 22 (40.9%) vulnerable patients had to interrupt chemotherapy prematurely because of toxicity (p=0.26). Vulnerable patients did not experience superior toxicity compared to fit patients (8/22 vulnerable and 6/14 fit patients developed toxicities of grade ≥ 2, p=0.69). With the exception of 2 fit and 2 vulnerable patients who were lost to follow up before surgery, 32 patients (88.9%) were operated. Thirty cases (12/14 fit patients, 85.7%, and 18/22 vulnerable patients, 81.8%) were radically resected without relevant postoperative complications. 13/20 vulnerable and 10/12 fit patients had a pathological downstaging of disease (p=0.24). Conclusions: Selected vulnerable elderly patients with rectal cancer can receive the same neoadjuvant chemoradiotherapy and undergo surgery as well as fit elderly patients since tolerability and response rate seem to be similar in both categories of patients. No significant financial relationships to disclose.

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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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A multicenter phase Ib/II study of DNA-PK inhibitor peposertib (M3814) in combination with capecitabine and radiotherapy in patients with locally advanced rectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.tps144 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. TPS144-TPS144

Author(s):

Paul Bernard Romesser ◽

Emma B. Holliday ◽

Tony Philip ◽

Rocio Garcia-Carbonero ◽

Jaume Capdevila ◽

...

Keyword(s):

Rectal Cancer ◽

Colon Cancer ◽

Phase Ii ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Rectal Adenocarcinoma ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Phase Ib

TPS144 Background: Perioperative radiotherapy and chemotherapy, followed by total mesorectal excision, is the standard of care for patients with locally advanced rectal cancer (LARC). However, 1/3 of these patients still develop distant metastases, indicating the need for more effective therapies. In addition, strategies that increase pathological complete response rates are needed to enable non-surgical management of LARC. DNA-dependent protein kinase (DNA-PK) regulates a key DNA damage repair pathway for double-strand break repair. Peposertib (M3814), a potent, selective, orally administered DNA-PK inhibitor, has been shown to potentiate the effect of ionizing radiation in a human colon cancer xenograft model and several colon cancer cell lines. Peposertib is being investigated in several different trials across multiple indications. This Phase Ib/II study (NCT03770689) aims to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of the neoadjuvant treatment combination of peposertib, capecitabine, and radiotherapy (RT) in patients with LARC. Methods: Patients aged ≥18 years with histologically confirmed and resectable Stage II/III rectal adenocarcinoma are eligible. Induction chemotherapy is permitted, but residual disease must first be documented by MRI, digital rectal examination and endoscopy. Patients who received other anticancer therapies or those with prior pelvic RT are excluded. At open-label Phase Ib (open), 18–30 patients (n = 3 per cohort) will receive peposertib + capecitabine (orally, 825 mg/m2 twice daily [BID]) + RT (45–50.4 Gy), 5 days/week. Peposertib 50 mg once daily (QD) was the starting dose. Additional dose levels will range between 100─800 mg QD. Dose escalation is determined by the safety monitoring committee and guided by a Bayesian 2-parameter logistic regression model. At Phase II (planned), 150 patients will be randomized (1:1) to receive oral capecitabine (825 mg/m2 BID) + RT (45–50 Gy), with either oral peposertib (recommended phase II dose [RP2D] or placebo, QD for 5 days/week. Primary objectives are to define a maximum tolerated dose and RP2D (Phase Ib), and to evaluate the efficacy of peposertib + capecitabine + RT in terms of pathological/clinical complete response (Phase II). Secondary objectives include assessment of antitumor activity (Phase Ib), quality of life outcomes (Phase II), and PK of peposertib, and the safety and tolerability of the combination therapy (both phases). To date, one patient has received peposertib 50 mg QD, six patients peposertib 100 mg QD, three patients peposertib 150 mg QD, and three patients peposertib 250 mg QD. Clinical trial information: NCT03770689.

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Effect of bevacizumab (BV) and chemotherapy (CT) on serum levels of vascular endothelial growth factor receptor-2 (sVEGFR-2) in patients with inflammatory and locally advanced breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.13003 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 13003-13003

Author(s):

J. M. Walshe ◽

N. Denduluri ◽

A. W. Berman ◽

D. Nguyen ◽

S. Y. Yang ◽

...

Keyword(s):

Breast Cancer ◽

Wound Healing ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Statistical Testing ◽

Reference Sequence ◽

Tissue Samples ◽

Significant Difference ◽

Wound Healing Problems

13003 Background: VEGFR-2 is a principal mediator of angiogenesis. The effects on sVEGFR-2 after anti-angiogenesis therapy are unknown. Methods: Twenty-one patients (pts) with breast cancer underwent neoadjuvant treatment with BV for 1 cycle (C1) followed by 6 cycles of BV, CT and filgrastim. Blood was collected at baseline (BL), post-cycles 1, 4 and 7. Objectives were to correlate sVEGFR-2 changes after treatment with response, assess wound healing complications, and evaluate for tumor VEGFR-2 mutations. sVEGFR-2 levels were measured by ELISA. Exons 17–26 were sequenced on tissue samples from 20 pts at BL and post C1 to evaluate for VEGFR-2 mutations. Statistical testing is non-parametric. All p-values are two-tailed, with a p < 0.01 interpreted as a statistically significant difference. Results: Thirteen pts had a partial response (PR), 1 unconfirmed PR, 5 stable disease (SD), and 2 progressive disease (PD). Median sVEGFR-2 levels increased by 16% from BL to post C1 (p = 0.0003) and decreased by 19% post C1 to post C4 (p = 0.048). sVEGFR-2 levels were not associated with clinical response. sVEGFR-2 levels at BL did not correlate with other BL parameters: Ki67, microvessel density, VEGF-A, pVEGFR-2, VEGFR-2 or TUNEL (apoptosis). A moderate-weak correlation was seen between post C1 levels of sVEGFR-2 and pVEGFR-2 (r = 0.43). A moderate inverse correlation was seen in the relative difference of sVEGFR-2 and TUNEL from BL to post C1 (r = −0.59). Comparing pts with (n = 5) and without (n = 16) wound healing problems, median sVEGFR-2 levels were 11322 ng/ml and 7524 ng/ml at BL (p = 0.019), 13928 ng/ml and 10148 ng/ml post C1 (p = 0.029), and 10965 ng/ml and 7932 ng/ml post C4 (p = 0.042). In 40 samples where tumor VEGFR-2 sequencing was obtained, no mutations were seen compared to the reference sequence. Conclusion: sVEGFR-2 levels rose significantly following BV alone but were not associated with response. There is a suggestion that sVEGFR-2 may correlate with activated VEGFR2 and a decrease in apoptosis. sVEGFR-2 levels were higher in pts with wound healing problems and may predict pts at higher risk of this complication. There were no mutations of VEGFR2. [Table: see text]

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Impact of biomarker dynamic profile and pathological response induced by neoadjuvant chemoradiotherapy in rectal cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.3614 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 3614-3614

Author(s):

A. L. Gentile ◽

C. Pinto ◽

C. Ceccarelli ◽

F. Di Fabio ◽

C. Funaioli ◽

...

Keyword(s):

Rectal Cancer ◽

Neoadjuvant Therapy ◽

Neoadjuvant Treatment ◽

Rectal Adenocarcinoma ◽

Neoadjuvant Chemoradiotherapy ◽

Rectal Surgery ◽

Pathological Response ◽

Resection Margins ◽

Tumor Regression Grade ◽

Operative Specimen

3614 Background: The aim of this study was to evaluate the correlation among biomarkers, pathological response and clinical outcomes in patients (pts) with rectal cancer submitted to neoadjuvant chemoradiotherapy. Methods: Pts entering the study had rectal adenocarcinoma, uT3/4N-/+ or uT2N-/+ with inferior location. Chemotherapy consisted of oxaliplatin 60 mg/m2 weekly infusion IV for 6 times and 5-fluorouracil 225 mg/m2/die continuous infusion IV d 1–38. Radiotherapy was delivered up to a dose of 50.4 Gy in daily fractions of 1.8 Gy d 1–38. Rectal surgery with TME was performed 6–8 weeks after neoadjuvant treatment. Immunohistochemical determination of Ki67, p53, bcl2, TS, EGFR, MLH1 and MSH2 was performed in pretreatment biopsy and operative specimen. Results: Between March 2002 and May 2005, 32 pts had completed neoadjuvant therapy and surgery. Pt characteristics: 24 (75%) men and 8 (25%) women; median age 64 (33–80) years; stage uT2N-M0 3 (9.4%) pts, uT3N-M0 14 (43.8%), uT3N+M0 10 (31.2%), uT3NXM0 2 (6.2%), uT4N+M0 3 (9.4%). Surgery consisted of abdominal-perineal amputation in 12 (37.5%) and low-anterior resection in 17 (53.1%) pts, with negative circumferential resection margins in 86.2%. Laparoscopic local excision was performed in 3 (9.4%) pts. Pathological down-staging occurred in 18 (56.2%) pts, including 7 (21.9%) pT0N0, with sphincter preservation in 40%. Tumor Regression Grade (TRG) (according to Mandard) evaluation of operative specimen was: 7 TRG1, 11 TRG2, 11 TRG3 and 3 TRG4. Expression mean value in pretreatment biopsy and operative specimen was: Ki67 88.8% and 31.7%; p53 49.7% and 40.7%; TS 12.6% and 10.0%; MLH1 89.7% and 76.4%; MSH2 84.3% and 72.2%. The evaluation of biomarker profile in operative specimen of TRG2 pts vs TRG3–4 showed: Ki67 16.6% vs 46.2% (p=0.03); TS 4.5% vs 12.9% (ns); MSH2 82.3% vs 65.6% (ns); p53 52.3% vs 34.8% (ns). Median DFS was 19 (3–35) months. At a median follow-up of 22 (5–41) months, 100.0% of TRG1 pts, 90.9% of TRG2, 73.3% of TRG3–4 had no-evidence of disease relapse. Conclusions: These preliminary results suggest a correlation between Ki67 and pathological response in rectal cancer pts treated with neoadjuvant therapy. Moreover, DFS appears to be related to TRG. No significant financial relationships to disclose.

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Neoadjuvant chemoradiotherapy in rectal cancer patients (pt) with oxaliplatin (Ox) and capecitabine (Cp): Results of a phase II trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15101 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15101-e15101

Author(s):

J. Gasent Blesa ◽

V. Alberola Candel ◽

O. Juan ◽

M. Provencio Pulla ◽

V. Giner Marco ◽

...

Keyword(s):

Neoadjuvant Treatment ◽

Rectal Adenocarcinoma ◽

Neoadjuvant Chemoradiotherapy ◽

Preoperative Chemoradiotherapy ◽

Sphincter Preservation ◽

Pathological Result ◽

Complete Treatment ◽

Tumor Downstaging ◽

The Mean

e15101 Background: Between April 2006 and May 2008, 27 rectal adenocarcinoma pt were included (cT3: 25 pt, T4: 2 pt, N0: 11 Pt, N+: 16 pt), stages II-III, RMN staged, 14 male and 13 female. Mehtod: Neoadjuvant treatment was: Ox: 50 mg/m2 weekly, oral Cp: 825 mg/m2 tid the days of the Rt, and a Rt of 50.4 Gy. 9 pt had a lower third tumor, 9 middle, 9 upper. Surgery was planned 6–8 weeks after treatment´s end. 4 adjuvant chemotherapy cycles with Xelox were planned. Results: 7 pt had pCR (26%), 2 pt progression disease 18 pt tumor downstaging(dwst). Percentages of dwst were: T 85%, N 37%. Sphincter preservation (sp) was 81.9%, for tumors of the lower third sp was 44.4%. Presurgical (prsrg) RMN did not predict the pathological result in 21 pt. Main side effects: Dermatitis G1 in 21 pt, and G2 in 4 pt. Diarrhea 12 pt G1, 11 pt G2, and 4 pt G3. Hand and foot G1 5 Pt and G2 4 pt. Paresthesias G1 10 pt, G2 7 pt. Leucopenia 6 pt G1. 4 Pt did not complete treatment because of toxicity. Median Rt dose was 49.7 Gy (47.5–50.4 Gy).At a mean follow up of 22.5 months (7–31) 4 pt presented metastatic disease (15% ), none in the pCR group. Mean pre-neoadjuvant (preneo) CEA was 6.8 ng/ml (2.1–17.0). There was difference statistically significant when compared preneo CEA vs prsrg CEA: 2.72 ng/ml inferior with the second outcome (p<0.001). Mean prsurg CEA was 4.1 (0.1–12.0). In the subgroup with pCR the mean prsrg CEA was 1.1 (0.5–1.5), and in non-pCR it was 5.1 (0.1–12.0). Comparing the prsrg CEA between pCR and the non-pCR subgroups, the mean difference was 4.0 ng/ml greater in the non pCR. This difference was statistically significant (p=0.002, 95% CI: 1.68–6.3).We found a nadir of <5ng/ml as significantly associated with pCR (p=0.036). Conclusions: Preoperative chemoradiotherapy with Ox and Cp, is safe and well tolerated. Offers an interesting ratio of pCR, and of tumor downstaging. Prsrg CEA level and CEA nadir should be studied as predictors of pCR. It is possible that with more patients, the significant nadir level could be lower. We consider this combination and the CEA nadir interesting to be included in further studies. No significant financial relationships to disclose.

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Randomized multicenter phase III trial comparing two neoadjuvant chemoradiotherapy (CT-RT) regimens (RT45-Cap versus RT50-Capox) in patients (pts) with locally advanced rectal cancer (LARC): Results of the ACCORD 12/0405 PRODIGE 2

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.18_suppl.lba4007 ◽

2009 ◽

Vol 27 (18_suppl) ◽

pp. LBA4007-LBA4007 ◽

Cited By ~ 15

Author(s):

J. Gerard ◽

D. Azria ◽

S. Gourgou-Bourgade ◽

I. Martel-Laffay ◽

C. Hennequin ◽

...

Keyword(s):

Locally Advanced ◽

Rectal Adenocarcinoma ◽

Neoadjuvant Chemoradiotherapy ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Concurrent Chemotherapy ◽

Phase Iii ◽

Phase Iii Trial ◽

Total Mesorectum Excision

LBA4007 Background: Following the results of randomized trials FFCD 9203 and EORTC 2291, neoadjuvant CT-RT is considered standard treatment for LARC. The ACCORD 12/0405 PRODIGE 2 trial was initiated to optimize this regimen. Methods: Pts with T3 or resectable T4 N0–1-2 M0, rectal adenocarcinoma were randomized to arm A: concurrent RT 45Gy/25f/5 weeks (w) + capecitabine (800mg/m2/bid) or arm B: concurrent RT 50Gy/25f/5w + capecitabine (800mg/m2/bid/5/7days) + oxaliplatine 50mg/m2/w. Resection with Total Mesorectum Excision was scheduled 6 weeks after the end of CT-RT. Adjuvant chemotherapy was optional. 590 patients were needed to show an increase in the pathological complete response (Dworak) rate from 11% (arm A) to 20% (arm B). Circumferential positive rectal margin (CRM R1) was defined as the presence of residual cancer cells within 0 to 1 mm from the perirectal surface. Results: This trial closed in 07/2008 after randomization of 598 pts since 11/2005. Patients characteristics of 586 eligible pts were well balanced: male 66%, median age 61 years, 66% low rectum, 87% T3 stage. Data base was locked in March 2009. Results are reported in Table . Conclusions: The RT 50 capox regimen is compatible with surgery in 98% of cases with no increase in postoperative complication. In the RT 50 arm, there is a trend in favour of a higher rate of pathological complete sterilization and lower rate of positive CRM. These data could contribute to design a new standard preoperative regimen for LARC. 50 Gy/25 F/5 weeks combined with concurrent chemotherapy could be proposed as an efficient schedule. [Table: see text] No significant financial relationships to disclose.

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Positron emission tomography-computed tomography (PET-CT) for the assessment of pathologic response to neoadjuvant chemoradiotherapy in rectal adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.537 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 537-537

Author(s):

Noman Ashraf ◽

Saqib Razzaque ◽

Ben C. Creelan ◽

Julio C. Chavez ◽

David Shibata ◽

...

Keyword(s):

Overall Survival ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Rectal Adenocarcinoma ◽

Neoadjuvant Chemoradiotherapy ◽

Standardized Uptake Value ◽

Neoadjuvant Chemoradiation ◽

Significant Trend ◽

Pet Ct

537 Background: Preoperative 5-fluorouracil and radiation (FU-XRT) has been demonstrated to improve recurrence-free survival in locally advanced rectal adenocarcinoma, however the role of interval PET-CT remains unclear. We performed a retrospective study with the primary objective of examining the association of change in standardized uptake value (SUV) by PET-CT after neoadjuvant chemoradiation and pathologic complete response (path CR) to survival. Methods: Data was extracted for cases at our institution between August 2006–August 2009, with last follow-up performed July 2012. Patients were included if (i) they had completed a full course of preoperative FU-XRT, followed by surgery with intent for R0 resection, and (ii) pre- and post- therapy PET-CT as well as pathologic reports were available for review. Data was compared by Fischer's exact and Wilcoxon rank-sum, and survival was analyzed using Kaplan-Meier method. Clinicopathologic data was compared by log-rank test and univariate Cox proportional hazards for relationship to overall survival (OS). Results: Of 128 total rectal cancer cases reviewed, 25 (19%) met inclusion criteria. Characteristics of 25 patients included: 13 female, age 57± 14 years (median ± SD). After 116 patient-years of follow-up, median OS was not reached; mean OS was 4.6 ± 0.9 years. Mean baseline pre-treatment PET SUV (18.5 ± 9.1) decreased after neoadjuvant FU-XRT (5.0 ± 4.3, p < 0.0001). Five achieved path CR. Presence of earlier stage was associated with non-significant trend towards improved chance of pathologic CR (RR 3.1, p = 0.07). A decrease in PET SUV by 80% or more was associated with improved odds of path CR (OR 25, 95% CI 1.2 - 513, p = 0.009), and was also associated with a non-significant trend towards improved OS (HR 0.19, 95% CI 0.01 - 2.7). Path CR was associated with a non-statistically significant trend to improved overall survival (HR 0.28, 95% CI 0.01 - 8.4). Conclusions: Reduction in PET-CT SUV after neoadjuvant chemoradiation may be a useful predictor of pathologic CR in rectal adenocarcinoma. These exploratory findings need to be validated in larger prospective studies.

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Neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Predicting long-term outcomes based on response to treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.621 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 621-621

Author(s):

Kirsten Elizabeth Jean Laws ◽

Christina Wilson ◽

David McIntosh ◽

Stephen Harrow

Keyword(s):

Rectal Cancer ◽

Locally Advanced ◽

Preoperative Staging ◽

Neoadjuvant Treatment ◽

Neoadjuvant Chemoradiotherapy ◽

Combined Modality Treatment ◽

Long Term Outcomes ◽

Node Positive ◽

Long Course

621 Background: Neoadjuvant long course chemoradiotherapy is well recognised as a standard treatment in locally advanced, margin threatening rectal cancer, in order to downstage and reduce local recurrence. We investigated retrospectively whether long term outcomes could be predicted by response to neoadjuvant treatment, and which factors specifically seemed to predict a risk of poorer outcome. Methods: All patients treated with long course chemoradiotherapy between January 2008 and December 2009 were identified retrospectively. Patients were excluded if the treatment indication was for inoperable disease, postoperative, recurrence, or palliative intent. A total of 231 patients were analysed with retrospective analysis of all electronic records and case notes. The following information was collated: preoperative staging, chemoradiotherapy treatment planned and received, operation performed, postoperative pathology (including nodal status, margins, presence of LVSI, and evidence of response to neoadjuvant treatment), disease free survival, and overall survival. Results: Kaplan Meier curves are presented showing patients with either a complete or partial response to neoadjuvant treatment appear to have a statistically significant improvement in long term outcomes, compared to those with no response (Mean survival 55 months, 56 months and 43months respectively, p<0.01). Furthermore, those who remain node positive or have evidence of LVSI following neoadjuvant treatment appear to have a statistically significant poorer outcome. Conclusions: Our study further develops on previous work looking at the prediction of outcomes following response to neoadjuvant treatment in rectal cancer. It appears that those who respond to initial treatment will have a better outcome than those who do not, including those who remain node positive or with LVSI following treatment. This study is limited because it is retrospective. Randomised controlled trial data is required to enable identification of poor risk imaging and pathology features that might suggest the need for adjuvant therapy following combined modality treatment with neoadjuvant chemoradiotherapy and surgery.

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