Importance of Tumor Regression Grading in Predicting the Outcome for Patients With Rectal Cancer After Preoperative Chemoradiation Therapy

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International Journal of Radiation Oncology  Biology  Physics

diagnostic cutoff point for EUS3/EUS1 was 52.2% (area under the curve (AUC) Z 0.710), and EUS3 was 8.1 mm (AUC Z 0.891). Conclusions: Repeated endorectal ultrasonographies before, during and after concurrent chemo-radiation therapy may predict therapeutic effect of preoperative chemoradiation therapy for rectal cancer. Author Disclosure: N. Li: None. J. Jin: None. Z. Yueming: None. Q. Xiao: None. Y. Li: None. H. Ren: None. W. Wang: None. S. Wang: None. H. Fang: None. W. Guiqi: None. Y. Zihao: None. L. Xinfan: None.

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2432 Randomized Clinical Trial on Hyperfractionated Versus Hypofractionated Preoperative Radiation Therapy for Rectal Cancer: Subset Analysis and Evaluation of the Prognostic Factors for Overall Survival and Loco regional Control R. Suwinski, I. Wzietek, M. Kryj, A. Idasiak, M. Bialas, A. Chmielarz, E. Stobiecka, E. Chmielik, L. Miszczyk, and J. Wydmanski; MSC Memorial Cancer Center, Gliwice, Poland Purpose/Objective(s): The aim of the study was to verify hypothesis that accelerated hyperfractionated preoperative radiation therapy for rectal cancer (HART) may provide a favorable long-term outcome compared to treatment given in higher fraction doses (HYPO). Evaluation of treatment tolerance was the primary endpoint of the study. Here we present the analysis of prognostic factor that influenced locoregional control and overall survival in the trial and the subset analysis focused on search of the potential predictive factors. The outcome of the trial with respect to adverse effects and quality of life is presented elsewhere. Materials/Methods: Between 2005 and 2012 338 patients with cT3-4 or cT2N+ resectable adenocarcinoma of the rectum were enrolled. The patients were randomly assigned to HART (n Z 168) or HYPO (n Z 170). The groups were well balanced with respect to age, gender, stage and interval radiation therapy-surgery. The pelvis was irradiated twice a day, with a minimal interfraction interval of 6h: the total dose of 42 Gy was given in 1.5 Gy per fractions over 18 days (HART). Patients in HYPO received 39 Gy in 3.0 Gy per fraction over 17 days. Surgery was performed 1-2 weeks after radiation therapy (median 11 days, Std18) Postoperative 5-Fu based chemotherapy was given to ypN positive patients. Multivariate Cox proportional hazard model was used in the analysis and optimized using stepwise backward regression. Results: Out of several variables studied age >63 years at the diagnosis (HR Z 2.49, p<0.001), male gender (HR Z 2.04, p Z 0.005), high platelets count at surgery (HR Z 1.74, p Z 0.011) and low hemoglobin concentration (HR Z 1.58,p Z 0.05) were among the factors that significantly and independently impaired the overall survival in a relatively homogeneous group of patients enrolled to the trial. Low hemoglobin concentration (HR Z 3.22, p Z 0.003) and low CEA concentration (HR Z 2.22, p Z 0.099) significantly and independently impaired loco-regional tumor control (note that the patients with high CEA concentration were at risk of distant failure and were more likely to die from metastases as locally controlled). Fractionation (HYPO vs HART) neither affected survival non loco-regional control. We were unable to find subsets of patients that would benefit from HART or HYPO with respect to loco-regional control or overall survival. Conclusions: The analysis did not reveal subsets that would benefit from HART or HYPO with respect to loco-regional control or overall survival. Platelets count appears as a readily available strong prognostic factor for overall survival that deserves more widespread recognition in combined treatment for rectal cancer. Author Disclosure: R. Suwinski: None. I. Wzietek: None. M. Kryj: None. A. Idasiak: None. M. Bialas: None. A. Chmielarz: None. E. Stobiecka: None. E. Chmielik: None. L. Miszczyk: None. J. Wydmanski: None.

The Role of Contact Brachytherapy X-Ray 50 kV (CBX) for Organ Preservation in Rectal Cancer: A Series of 61 Patients K. Benezery,1 A. Frin,1 F. Zhou,2 E. Francois,1 and J. Ge´rard1; 1Centre Antoine Lacassagne, Nice, France, 2Zhongnan Hospital, Wuhan, China Purpose/Objective(s): Randomized trials over past decade show that neoadjuvant chemoradiation therapy (nCRT) does not increase the rate of conservative treatment in T2-3-4 Nx M0 rectal tumors. To modify the surgical decision in favor of organ preservation it is necessary to achieve without excessive toxicity using nCRT a Clinical Complete Response (CCR). Contact Brachytherapy X Ray 50 kV (CBX) is a unique radiation therapy technique able to deliver accurately to the primary tumor high dose (30 Gy/3minutes) into a small volume. We report the results of 60 patients treated with CBX for cure and organ preservation in a single institution. Materials/Methods: 61 pts (all M0) with distal or middle rectal adenocarcinoma were treated between 2002 and 2012 in Nice. 2 groups of patients received CBX 50 kV as part of their treatment. A: 36 pts presenting T2 T3a-b (< ½ circumference; < 5cm diameter) received CBX (90 Gy/ 3 fr) with n(c)RT ( 45-50 Gy/ 5w  concurrent chemotherapy) followed by Local excision or close surveillance. 14 were operable pt (median age 65y) and 22 were inoperable or high surgical risk (median age 79y). B: 25 Pts presenting T1 tumors (median age 69 y) had Local Excision first, followed by CBX (50 Gy/3fr)  External Beam RT (EBRT in 3 Pts pT2). All these Pts were pT1 (22) or pT2.with R1 resection in 6Pts. Results: Group A : 35/ 36 Pts achieved CCR, 8 weeks after the end of treatment. Close follow-up only was done in 29 and LE in 7 (ypT0.2, ypT1 : 3, ypT2 : 2 1R1) none had further surgery and none had local recurrence. Median Follow-up: 42 months [3- 120]. Local control 32/36 achieved in 32/35 (89%). Distant metastases 7/36 (19%). Bowel function was good in all these patients with radiation rectal bleeding grade 1 in 75% of cases lasting for 3 years. Death 14/36 : 3 year DFS in operable pts : 85% vs 55% for inoperable Pt. None died from non-controlled pelvic disease. No perirectal lymph node failure was seen in any Pt. Group B : Median Follow-up : 52 months. One local recurrence salvaged using Anterior Resection. Distant metastases seen in 4/25 (16%). Overall survival at 4 years : 89%. Bowel function was good in all these Pts. Radiation rectal bleeding grade 2 was seen in 30%. No peri-rectal failure was seen in any PT. Conclusions: For T1N0 tumors which at present time are usually treated with LE first, abdomino-perineal Excision should be exceptional. CBX is a good alternative to TME surgery in most of cases. For T2 T3a-b, TME surgery ( nCRT) remains standard but the high rate of organ preservation achieved using CBX +nCRT justifies the upcoming European OPERA (Organ Preservation for Early Rectal Adenocarcinoma) randomized trial. The ultimate goal being to duplicate the Lyon R96-2 trial and achieve for such pts an organ preservation(either after LE or “Watch and Wait”) in 25% of cases with long term and good quality of life. Such CBX 50 kV treatment requires the routine clinical practice by the radiation oncologist of rigid proctoscopy. Author Disclosure: K. Benezery: None. A. Frin: None. F. Zhou: None. E. Francois: None. J. Ge´rard: G. Consultant; Ariane Medical Advisor.

2434 Importance of Tumor Regression Grading in Predicting the Outcome for Patients With Rectal Cancer After Preoperative Chemoradiation Therapy C. Yang,1,2 C. Li,3 M. Tai,2 and L. Lin1; 1Department of Radiation Oncology, Chi-Mei Foundation Medical Center, Tainan, Taiwan, 2Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, 3Department of Pathology, Chi-Mei Foundation Medical Center, Tainan, Taiwan Purpose/Objective(s): This retrospective 15-year study assessed whether the tumor regression grading (TRG) could be used to predict treatment outcome of rectal cancer patients after preoperative chemoradiation therapy.

Volume 90  Number 1S  Supplement 2014 Materials/Methods: Between January 1998 and December 2012, 257 patients treated at our hospital were enrolled. Preoperative chemoradiation therapy was given by 5-fuorouracil continuous infusion during the first and fifth week, delivered with concurrent pelvic radiation of 45-50 Gy, followed by curative resection at 4-6 weeks. TRG was evaluated on excised specimens and was divided into five grades based on the relative amount of fibrosis in the tumor embedding area. Clinicopathologic factors, stages, TRG and prognosis, were statistical analyzed. Results: Three groups were used: TRG 4 (complete response), TRG 2-3 (> 25% regression) and TRG 0-1 (< 25% response). TRG 4, 2-3, 0-1 were found in 9.7%, 68.5%, 21.5% of the resected specimens. Five-year overall survival (OS) after preoperative chemoradiation therapy and curative resection was 91% for TRG 4, 74% for grouped TRG 2-3, and 43% for grouped TRG 0-1 (P Z .037). Moreover, patients with better tumor regression (4 vs 2-3 vs 0-1) also have better results for 5-year local-free (LFS), disease-free (DFS), and metastases free survival (MFS) (P Z .004, P Z .002, and P Z .0001, respectively). On multivariate analysis, the vascular invasion on pathologic specimens and TRG after preoperative chemoradiation therapy were the most important independent prognostic factors for LFS and DFS, except MFS. Conclusions: TRG is considered to be a significant prognostic factor. Complete (TRG 4) and intermediate pathologic response (TRG 2-3) closely correlates with better survival and low local recurrence. However, in our results, TRG could not predict distant metastases. Author Disclosure: C. Yang: None. C. Li: None. M. Tai: None. L. Lin: None.

2435 Improvement of Rectal Boost Contouring by Comparing Colonoscopy (CL) and MRI With Planning CT (PCT) Findings E. Jimenez-Jimenez,1,2 P. Mateos,3 J. Pardo,1,2 J. Font,3 S. Montemuin˜o,1 A. Mena,1,2 and S. Sabater4; 1Radiation Oncology Department. Hospital Universitari Son Espases, Palma de Mallorca, Spain, 2Palma Health Research Institute (IdIsPa), Palma de Mallorca, Spain, 3Medical Physics Department. Hospital Universitari Son Espases, Palma de Mallorca, Spain, 4Radiation Oncology Department. Complejo Hospitalario Universitario de Albacete, Albacete, Spain Purpose/Objective(s): Despite the better soft tissue delineation provide by MRI which has a primary role in rectal cancer staging, modern radiation therapy contouring is based upon CT, because it includes geometric stability, electron density information, superior cortical bone information and lack of image distortion. The accuracy of boost volumes generated depends on precise GTV contouring in PCT. Our goal is to compare MRI and CL information with PCT in order to improve boost contouring. Materials/Methods: Imaging and planning data for 40 patients (30 in prone position and 10 in supine position) with locally advanced rectal cancer were reviewed. PCT slices were 0.5 cm thick, anal sphincter was marked and GTV was contoured according to the clinical-radiological information. All volumes were contoured by the same radiation oncologist. For each patient, tumor location in relation to anal verge and tumor length was compared between CL and pelvic MRI with respect to PCT. Data were analyzed using a commercial computer algorithm. The significant differences between these parameters were evaluated by the Wilcoxon signedrank test. Results: CL tumor location was more cranial, in 73.4% of cases, than in PCT, irrespective of the prone or supine position. In these cases, the mean difference was 2.93 cm (p < 0.001). A cranial location was also seen on MRI, in 79.3% of cases, compared with PCT. In these patients, the mean difference was 3.96 cm (p < 0.001). MRI reported distances from the anal verge were greater, in the 55.2% of cases, than distances reported on CL. A complete agreement was observed in ultra-low tumors that involve the anal verge. No clear pattern could be described with respect of the tumor length. This is likely because the tumor length is not reported by the radiologist or endoscopist, in many imaging tests. Conclusions: The location of a tumor or its length, assessed by different imaging modalities, may not be equivalent. Therefore, it is necessary to

S387 evaluate the different measures regarding to PCT. Tumor location defined distal from the anal sphincter was described more caudal on MRI and CL than PCT. This can result in a dose reduction to organs at risk and facilitate dose escalation. Multi-modality imaging with CL and MRI can assist GTV definition, but the measures reported may not be equivalent to our PCT. We believe that the occasional geographic misses could be avoided with more detailed reports. Author Disclosure: E. Jimenez-Jimenez: None. P. Mateos: None. J. Pardo: None. J. Font: None. S. Montemuin˜o: None. A. Mena: None. S. Sabater: None.

2436 The Role of Postoperative Adjuvant Radiation Therapy in Patients With Stage II and III Upper Rectal and Recto-Sigmoid Cancer: A Propensity-Score Matched Analysis J. Kim,1 C. Song,1 S. Song,2 and S. Kang1; 1Seoul National University Bundang Hospital, Seongnam, Korea, Republic of Korea, 2Seoul National University Hospital, Seoul, Korea, Republic of Korea Purpose/Objective(s): It is unclear whether postoperative adjuvant radiation therapy (PORT) is beneficial for tumors around and above peritoneal reflection. The aim of this study was to analyze the influence of PORT on recurrence and survival in patients with stage II and III upper rectal and recto-sigmoid cancer undergoing curative resection followed by adjuvant chemotherapy. Materials/Methods: A retrospective review was performed on the institutional databases of 209 patients with tumors located in upper rectum or recto-sigmoid junction, seventh American Joint Committee on Cancer (AJCC) stage II or III, no preoperative chemoradiation therapy, and primary curative resection between 2003 and 2010. Fifty-four patients received PORT. In all patients who received PORT, the pelvis received long-course radiation therapy, 45 Gy in 25 fractions, with a boost 5.4-10.8 Gy in 3-6 fractions. Propensity score matching was performed using several prognostic variables which included sex, T stage, N stage, and adjuvant chemotherapy. Results: Propensity score matching created a matched cohort of 108 patients (54 PORT/54 no PORT) with a median follow-up of 65 months. All patients in both groups received adjuvant chemotherapy. The PORT resulted in superior 5-year pelvic failure-free rate compared with no PORT (100% vs 92%, p Z 0.040). There were no differences in 5-year distant metastasis-free (75% vs 71%, p Z 0.646) and overall survival rates (83% vs 73%, p Z 0.495) between the PORT and no PORT groups. However, median survival after recurrence was significantly worse in patients with pelvic failure than in those with distant metastasis alone (11.9 vs 36.2 months, p Z 0.004). In specific, all patients who experienced pelvic failure died within 3 years after recurrence compared to 12 of 30 patients (40%) with distant metastasis alone have lived over 3 years after recurrence. Conclusions: Despite controversial benefits of PORT use in the upper rectal and recto-sigmoid cancer, we detected no differences in survival and improved pelvic control in propensity score-matched analyses. Due to the grave prognosis of pelvic failure, PORT needs to be considered in the stage II and III upper rectal and recto-sigmoid cancer. Author Disclosure: J. Kim: None. C. Song: None. S. Song: None. S. Kang: None.

2437 Validation of a Rectal Cancer Outcome Prediction Model in Routine Chinese Patients L. Shen,1 J. Van Soest,2 J. Yu,3 J. Wang,1 W. Hu,1 Y.U.T. Gong,3 V. Valentini,4 Y. Xiao,3 A. Dekker,2 and Z. Zhang1; 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China, 2Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands, 3Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, 4Unviersita Cattolica S. Cuore, Rome, Italy