Correlation between Radiologic Tumor Regression Grading (ycMRI) and Pathological Tumor Regression Grading (ypTRG) in Rectal Cancer

Tumor regression grading in rectal cancer: is it time to move forward?

261 Background: High-dose-rate endorectal brachytherapy (Endo-HDR) is a promising technique using a short course of radiation therapy in the neoadjuvant setting for rectal cancer. While clinical exam and standard imaging (CT and MRI) suggest outstanding radiation response in these patients, they cannot reliably predict pathologic complete response (pCR) or high tumor regression grade (TRG). In this study, we investigate the utility of PERCIST criteria to predict pathologic change. Methods: We treated nine patients on a prospective clinical trial investigating Endo-HDR as a single agent neoadjuvant therapy (6.5 Gy x 4 fractions, total dose of 26 Gy) for stage II-III rectal cancer patients. A pre-radiation PET/CT scan was compared to a post-treatment PET/CT scan performed one month following the completion of radiation. All nine patients proceeded to surgical resection with the pathologic specimen analyzed for residual disease. TRG (Mandard et al.) was used to quantify response to treatment. A 50% decrease in SUVpeak by PERCIST criteria was correlated with a TRG 1 or 2 (none or minimal residual cancer cells on the final pathologic specimen). Results: As demonstrated in our table, 3/5 (60%) of patients achieving a TRG 1 or 2 had a SUVpeak that decreased by 50% or more; contrarily, zero of 4 (0%) of patients without a TRG 1 or 2 had a SUVpeak of 50% or more. Despite a trend, the small patient sample limited statistical significance (p=0.17). A minimum decrease of 50% in SUVpeak resulted in a positive predictive value of 100%, a negative predictive value of 67%, a specificity of 100%, and a sensitivity of 60% for predicting TRG 1 or 2. Conclusions: Our results demonstrate the first report of utilizing PERCIST criteria in rectal cancer treated with neoadjuvant Endo-HDR. Reliable clinical predictors following Endo-HDR for excellent pathologic response may identify patients in whom a non-operative rectal cancer treatment is possible. [Table: see text]

Tumor regression grading as prognostic factor in patients with locally advanced rectal cancer treated with preoperative radiochemotherapy

To determine whether the residual tumor volume measured using the Eclipse treatment planning system correlates with pathologic tumor regression grade after preoperative chemoradiotherpy for rectal cancer. The study included 30 patients with rectal cancer who had undergone preoperative chemoradiotherpy followed by surgery from June 2008 to April 2011 at the Korea University Guro Hospital. The tumor volume was measured using the Eclipse treatment planning system in the initial simulation computed tomography and boost planning computed tomography. The correlation between the residual tumor volume in boost planning computed tomography and the pathologic tumor regression grade was analyzed. Tumor regression grade defined in the American Joint Committee on Cancer 7th edition was used. The mean and median residual tumor volume was 57.34% ± 20.37% and 52.35% (range, 18.42%-95.79%), respectively. After surgery, pathologic complete response (tumor regression grade 0) occurred in 4 patients (13.33%), moderate response (tumor regression grade 1) in 18 patients (60%), minimal response (tumor regression grade 2) in 4 patients (13.33%), and poor response (tumor regression grade 3) in 4 patients (13.33%). When residual tumor volume was categorized into two groups (<50% and ≥50%), complete or moderate regression (tumor regression grade 0 or 1) was significantly greater for patients with a residual tumor volume <50% ( P <0.05). The mean residual tumor volume of tumor regression grade 0 or 1 was 49.07% ± 18.39% and that of tumor regression grade 2 or 3 was 76.31% ± 16.94% (P <0.05). Residual tumor volume measured using routine boost planning computed tomography during preoperative chemoradiotherpy correlated significantly with pathologic tumor regression grade after surgery.

To determine whether the residual tumor volume measured using the Eclipse treatment planning system correlates with pathologic tumor regression grade after preoperative chemoradiotherpy for rectal cancer. The study included 30 patients with rectal cancer who had undergone preoperative chemoradiotherpy followed by surgery from June 2008 to April 2011 at the Korea University Guro Hospital. The tumor volume was measured using the Eclipse treatment planning system in the initial simulation computed tomography and boost planning computed tomography. The correlation between the residual tumor volume in boost planning computed tomography and the pathologic tumor regression grade was analyzed. Tumor regression grade defined in the American Joint Committee on Cancer 7th edition was used. The mean and median residual tumor volume was 57.34% ± 20.37% and 52.35% (range, 18.42%-95.79%), respectively. After surgery, pathologic complete response (tumor regression grade 0) occurred in 4 patients (13.33%), moderate response (tumor regression grade 1) in 18 patients (60%), minimal response (tumor regression grade 2) in 4 patients (13.33%), and poor response (tumor regression grade 3) in 4 patients (13.33%). When residual tumor volume was categorized into two groups (<50% and ≥50%), complete or moderate regression (tumor regression grade 0 or 1) was significantly greater for patients with a residual tumor volume <50% ( P <0.05). The mean residual tumor volume of tumor regression grade 0 or 1 was 49.07% ± 18.39% and that of tumor regression grade 2 or 3 was 76.31% ± 16.94% (P <0.05). Residual tumor volume measured using routine boost planning computed tomography during preoperative chemoradiotherpy correlated significantly with pathologic tumor regression grade after surgery.

13524 Background: The main objective of this study is to clarify the correlation between pathological nodal status and Dworak tumor regression grade (TRG) (Dworak et al. Int Colorectal Dis 1997, 12:19–23) after pre-operative chemoradiotherapy. Methods: From May 1998 to February 2005, 112 patients with locally advanced rectal cancer were diagnosed at Centro Oncologico Modenese and treated with pre-operative concomitant pelvic irradiation (50 Gy in 25 fractions) and chemotherapy with 5-FU in continuous infusion (225 mg/msq/daily). We considered for our analysis only pathological stage III cases. Results: Clinical positive nodal status (by CT scan or ultrasonography) was present in 71 patients on 106 (66.9%) at diagnosis. Among all radically resected patients (106), pathologic assessment of lymph nodes in surgical specimens was performed; average number of nodes examined was 11 (range: 2–22). Thirty patients (28.3%) had a positive nodal status at pathological examination: 19 (63.3%) were pN1 (≤3 lymph nodes) and 11 (36.7%) were pN2 (&gt;3). The nodal status changed from 66.9% (clinical evaluation) to 28.3% (pathologic evaluation). Among stage III patients 5 (16.7%) had a TRG 3, 12 (40%) TRG 2, 11 (36.7%) TRG 1 and 2 (6.6%) TRG 0. At a median follow-up of 32,3 months, 20/106 patients relapsed (18.8%); of these 20, 10 (50%) had a positive pathologic nodal status. In this subset recurrence occurred in 5/10 (50%) pN1 patients (1 local and 4 with distant metastases) and 5/10 (50%) pN2 patients (2 local and 3 with distant metastases). The 3-y DFS was 63% (68% pN1 and 54% pN2) (p=0.32). The 3-y OS was 84% (94% pN1 and 68% pN2, p=0.72). The 3-y DFS in post-operative stage III patients according to tumor regression grade was 81% for TRG 2–3 and 38% TRG 0–1 (p&lt;0.026). Conclusions: In stage III patients, TRG is confirmed as a relevant prognostic factor in locally advanced rectal cancer treated with neo-adjuvant chemo-radiotherapy. In the same subset of patients the number of positive nodes seems to impact on the prognosis, even not reaching a significant relevance. No significant financial relationships to disclose.

21 Background: Patients with locally advanced rectal cancer (LARC) and a clinical complete response (cCR) or near-complete response (nCR) to total neoadjuvant therapy (TNT) can be offered watch-and-wait (WW) with the intention of achieving organ preservation. However, one third of patients on WW develop tumor regrowth and require total mesorectal excision (TME). Assessing the safety of WW in patients with a cCR or nCR is challenging due to the difficulty of finding an adequate control group. Here we compare the survival outcomes of patients with LARC treated with TNT and either mandatory TME or selective WW stratified by tumor response. Methods: This is a pooled analysis of two multicenter, phase II trials (CAO/ARO/AIO-12 [CAO] and OPRA) that randomized patients with stage II/III rectal cancer to either induction or consolidation TNT. All patients in the CAO trial underwent TME within 6 weeks of TNT. Pathologic tumor regression grade (TRG) was categorized as complete (TRG 4), intermediate (TRG 2,3) or poor (TRG 0,1). Patients in the OPRA trial were restaged by endoscopy and MRI 8±4 weeks after end of TNT. Clinical response was graded as cCR, nCR, or incomplete clinical response (iCR). Patients with a cCR or nCR were offered WW; patients with an iCR were recommended for TME. Survival curves were estimated using the Kaplan-Meier method and the log-rank test. Results: The study included 628 patients ( n =304 CAO; n =324 OPRA). Median follow-up was 3.6 (IQR 1.13) and 5.1 (IQR 2.2) years. Patients in the CAO trial were more likely to have cT3/4 and cN positive disease while patients in the OPRA trial had tumors closer to the anal verge. Compliance with TNT and rates of grade 3+ adverse events were similar between studies. A total of 144 (47%) patients in the OPRA trial achieved long term organ preservation. We found no differences in survival between trials. In addition, we found no differences in DFS between studies for patients with an excellent (TRG4 87% [95% CI, 79-97%], cCR 87% [95% CI, 81-93%]) or intermediate (TRG2-3 69% [95% CI, 62-76%], nCR 71% [95% CI, 68-80%]) response. Conclusions: This pooled analysis demonstrated that almost half of LARC patients treated with TNT can achieve organ preservation and that a selective WW strategy yields similar survival outcomes compared to mandatory TME. In addition, we found no differences in survival based on paired clinical and pathologic tumor response grades following TNT. This data provides further evidence supporting the safety of WW for patients with LARC and a cCR or nCR to TNT. Three-year survival outcomes in the CAO/ARO/AIO-12 and OPRA trials. CAO/ARO/AIO-12(95% CI) OPRA(95% CI) P 3y DFS 73 (71–81)% 76 (68–78)% 0.3 3y DRFS 82 (78–87)% 82 (78–87)% 0.7 3y LRFS 95 (92–98)% 95 (92–97)% 0.4 3y OS 92 (89–95)% 94 (89–95)% 0.5 DFS: disease-free survival, DRFS: distant recurrence-free survival, LRFS: local recurrence-free survival, OS: overall survival.

BackgroundWe investigated factors associated with pathologic complete response (pCR) and tumor regression grade (TRG) on the basis of clinical and pathological variables and their impact on cancer-free survival (CFS) after surgery for locally advanced rectal cancer (LARC).MethodsAll patients with LARC undergoing neoadjuvant treatment before curative total mesorectal excision surgery were included in a prospective institutional database connected to the National Mortality Registry. One-way analysis of variance and Pearson’s chi-squared test were utilized to compare TRG groups. The Kaplan–Meier method and regression models were used to evaluate CFS, radiation modality, and staging factors.ResultsOf 700 patients operated on for rectal cancer between 2014 and 2024, 159 (22.7%) had LARC without known systemic cancer. Twenty-seven patients had pCR (TRG 0, 17.0%), 46 TRG 1 (29.0%), 70 TRG 2 (44.0%), and 16 TRG 3 (10%). Poor tumor regression was associated with increasing age (p = 0.009), vascular (p < 0.001) and neural invasion (p = 0.005), less differentiated tumors (p < 0.001), short-course 5 Gy × 5 (p < 0.001) rather than long-course 2 Gy × 25 radiotherapy, and omission of neoadjuvant chemotherapy (p < 0.001). Older age was a predictor of short-course radiotherapy and omission of chemotherapy (p < 0.001). Follow-up time was 46.6 months (IQR 20–80.3 months). No differences were found in CFS between TRG groups 0–3 (p = 0.18), however pCR was associated with improved CFS (p = 0.047).ConclusionsDecreased tumor regression was associated with reduced radiotherapy and chemotherapy, neural and vascular invasion, poor differentiation, and increasing age. The latter may reflect reduced application of neoadjuvant treatment in older patients. Complete responders experienced increased cancer-free survival.

Neoadjuvant chemoradiotherapy for oesophageal cancer: Primary tumour/lymph node regression inconsistency and prognostic value analysis.

The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer

Background: Neoadjuvant therapy response correlates with survival in multiple gastrointestinal malignancies. To potentially augment neoadjuvant response for pancreas adenocarcinoma, we intensified treatment with stereotactic body radiotherapy (SBRT) following multi-agent chemotherapy. Using this regimen, we analyzed whether the College of American Pathology (CAP) tumor regression grade (TRG) at pancreatectomy correlated with established response biomarkers and survival.Materials and methods: We identified borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer patients treated according to our institutional clinical pathway who underwent surgical resection with reported TRG (n = 81, median follow-up after surgery 24.2 months). Patients had baseline CA19-9, computed tomography (CT), endoscopic ultrasound, and FDG positron emission tomography (PET)/CT then underwent multi-agent chemotherapy (79% with three cycles of gemcitabine, docetaxel and capecitabine) followed by 5-fraction SBRT. They then underwent restaging CT, PET/CT and CA19-9. Overall (OS) and progression-free (PFS) survival were estimated and compared by Kaplan–Meier and log-rank methods. Univariate ordinal logistic regression correlated TRG with baseline, restaging and change in CA19-9 and the PET maximum standardized uptake value (SUVmax).Results: Restaging level and decrease in CA19-9 correlated with improved TRG (p = .02 for both) as did restaging SUVmax (p < .01), yet there was no TRG correlation with decrease in SUVmax (p = .10) or CT response (p = .30). The TRG groups had similar OS and PFS except the TRG 0 (complete response) group. Compared to partial response levels (TRG 1-3, median OS 33.9 months, median PFS 13.0 months), the six (7%) patients with TRG 0 had no deaths (p = .05) and only one progression (p = .03). A group of 10 (12%) TRG 1 patients with only residual isolated tumor cells had similar outcomes to the other TRG 1-3 patients.Conclusion: Pre-operative PET-CT and CA19-9 response correlate with histopathologic tumor regression. Patients with complete pathologic response have superior outcomes, suggesting a rationale for intensification and personalization of neoadjuvant therapy in BRPC and LAPC.

High pathological response rates with a novel preoperative chemoradiaton regimen in locally advanced rectal cancer: Preliminary results and dynamic evaluation by PET

Importance of Tumor Regression Grade in ypStage III Rectal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy

Prognostic Significance of Tumor Regression Grade after Preoperative Chemoradiotherapy for Rectal Cancer

Aim. To determine relation between localization, grade of invasion and differentiation in rectal tumor and tumor regression grade after neoadjuvant chemoradiation therapy.&#x0D; Methods. 88 patients with local advanced rectal cancer (Т2-4N0-2М0) were analyzed: 46 females and 42 males. The average age was 52.4±1.4 years. All patients underwent neoadjuvant chemoradiotherapy. In all groups regardless of tumor localization patients with stage T3 and moderate differentiation grade predominated.&#x0D; Results. Complete pathological tumor response of grade 4 (TRG4) was revealed in 13 (14.7%) patients, grade 3 (TRG3) in 34 (38.6%) patients, low treatment effect (tumor response grade 2, TRG2) was registered in 26 (29.5%) patients, and lack of treatment effect (grade 1, TRG1) in 15 (17.2%) patients. Analysis of the data from patients with complete or nearly complete tumor regression (grade 3 and 4) demonstrated that such effect of neoadjuvant treatment was most often observed in patients with tumor localized in rectal lower ampulla (58.6%). Among patients with moderately differentiated adenocarcinomas, patients with tumor response of grade 3 and 4 predominated: 28 (56%) patients. According to invasion grade, in all groups patients with therapeutic response grade 3 and 4 prevailed, but most prominently - in groups of patients with stage T4a and T4b - 58.9%.&#x0D; Conclusion. The closer to anus tumor is located, the more significant effect neoadjuvant therapy has; moderate tumor differentiation grade can be considered as a relative predictive factor of tumor regression on preoperative chemoradiation therapy.