369 POOR CORRELATION BETWEEN FDG-PET AND PATHOLOGIC RESULTS AFTER EXPERIMENTAL NEOADJUVANT IMMUNOCHEMOTHERAPY FOR GASTROESOPHAGEAL ADENOCARCINOMA: RESULTS OF A CLINICAL TRIAL

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Thierry Alcindor ◽  
Touhid Opu ◽  
Carmen Mueller ◽  
Nicolas Ah-Son ◽  
Marc Hickeson ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Complete Response ◽  
Statistical Correlation ◽  
Poor Correlation ◽  
Rate Score ◽  
Pre Treatment ◽  
Gastroesophageal Adenocarcinoma ◽  
Ecog Ps

Abstract   A lack of FDG-PET response to neoadjuvant chemotherapy for gastroesophageal adenocarcinoma is considered as indicative of a poor prognosis, whereas pathologic complete or near-complete response (pCR/near-pCR) predicts a more favorable outcome. In a single-arm phase II trial of perioperative immunochemotherapy, we sought to establish a correlation between the results of an FDG-PET performed after the neoadjuvant part of the treatment and the pathologic results obtained after surgery. Methods Inclusion criteria: locally advanced gastroesophageal adenocarcinoma (T3 and/or N+); adequate organ function; ECOG PS 0–1; no contraindication to immunotherapy; Staging: CT, FDG-PET, EUS, diagnostic laparoscopy. Eligible patients receive docetaxel/cisplatin/5-FU (mDCF) on day 1 and avelumab on day 4 of each 2-week cycle and are restaged after 4 cycles. FDG-PET response is defined as reduction of >35% of pre-treatment SUV. Surgery is performed if no disease progression. Four cycles of mDCF/avelumab are administered after surgery. Tumor regression is scored from 0 (no tumor cells) to 3 (no tumor regression). The primary endpoint is the pCR/near-PCR rate (score 0–1). Results As of February 24, 2020, 28 patients have been enrolled and 22 have been operated. Paired FDG-PET response and pathologic response data are available for 21 patients. We observed 16/21 FDG-PET responses and 6/21 pCR/near-pCR. Of the latter, 4 were associated with an FDG-PET response and 2 with no FDG-PET response. Ten patients with score 3 tumor regression had had FDG-PET response. No statistical correlation could be found between FDG-PET response and likelihood of pCR/near-pCR. Conclusion Given the discrepancy observed between FDG-PET and pathologic results, the need for a repeat FDG-PET for gastroesophageal adenocarcinoma after neoadjuvant immunochemotherapy and before surgery should be questioned. Analysis of the tumor microenvironment could possibly explain these results. Future studies will look into correlation between the results presented and survival.

Phase II trial of perioperative chemotherapy + avelumab in locally advanced gastroesophageal adenocarcinoma: Preliminary results.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4046-4046
Author(s):  
Thierry Alcindor ◽  
Touhid Opu ◽  
Arielle Elkrief ◽  
Farzin Khosrow-Khavar ◽  
Carmen L. Mueller ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Regression ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Daily Intake ◽  
Disease Free Survival ◽  
Type I ◽  
Perioperative Chemotherapy ◽  
Preliminary Results ◽  
Gastroesophageal Adenocarcinoma

4046 Background: Perioperative chemotherapy improves cure rate in locally advanced gastroesophageal adenocarcinoma (GEA), and immune checkpoint inhibitors are active at the metastatic stage. This trial tests the hypothesis that the addition of avelumab to perioperative chemotherapy will increase the major pathologic response (MPR) rate in comparison with historical controls. Methods: Phase II study of avelumab + chemotherapy (docetaxel, cisplatin and 5-FU or mDCF) given every 2 weeks for 4 cycles before and after surgery. Main inclusion criteria: GEA, cT3 and/or cN+, M0, WHO PS 0-1. Main exclusion criteria: use of immunosuppressants, serious autoimmune disease, daily intake >10 mg prednisone. Staging studies: CT, PET-CT, endoscopic ultrasound, diagnostic laparoscopy. Surgical resection: D2 lymphadenectomy, en-bloc esophagectomy for type I/II gastroesophageal junction (GEJ) tumors. Aim of the study: MPR as defined as tumor regression grades 0-1 (modified Ryan scheme); as per hypothesis, this experimental regimen will result in a 20% rate of MPR, compared with 7% with chemotherapy alone. Simon 2-stage design: if less than 2 MPR are seen in the first 16 patients, the study will be closed. The study hypothesis cannot be rejected if at least 6 MPR are seen in the first 50 patients. All adverse effects are prospectively recorded per CTCAE guidelines in patients who have received at least one treatment cycle. Survival rates are calculated with Kaplan-Meier method. Preliminary results are presented since the study has met its primary endpoint. Results: Feb 2018-Feb 2020: 28 patients enrolled (25 M/3 F, age 45-78). Location: GEJ (23), stomach (5). Staging: cT3 (25), cT4 (1), cN+ (20). Biomarkers expression: mismatch repair (MMR) protein loss (3/28); PD-L1(clone 73-10) expression in 1% (TPS) or more of tumor cells seen in 12/28 samples, and >10% in 6 patients. Grade 3 toxicity: stomatitis (2/28); nausea (2/28); vomiting (1/28); diarrhea (1/28); hypothyroidism (1/28); arthralgia (3/28); neutropenia (1/28). Grade 4 toxicity: pneumonia (1/28); neutropenia (2/28). Postoperative 30-day mortality: 0%. One patient was excluded from efficacy analyses for M1 staging; 27 patients underwent surgery, 26 with R0 (96%). Six cases (22%) show MPR: 3 grade 0 (11%) and 3 grade 1 (11%) tumor regressions. No correlation was seen between MMR proteins or PD-L1 expression and tumor regression. With a median follow-up of 1.5 years (range 0.4-2.5), the disease-free survival rate is projected to be 0.92 (95% CI 0.83-1.00) at 12 months and 0.77 (95% CI 0.58-1.00) at 24 months. Conclusions: The combination of mDCF chemotherapy with Avelumab demonstrates a promising safety and activity profile. Ongoing laboratory investigations are underway to correlate our findings with tumor molecular features before exposure to treatment. Clinical trial information: NCT03288350.

scholarly journals Review of MR-Guided Radiotherapy for Esophageal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Sangjune Laurence Lee ◽  
Michael Bassetti ◽  
Gert J. Meijer ◽  
Stella Mook
Keyword(s):  
Esophageal Cancer ◽  
Tumor Regression ◽  
Imaging Modality ◽  
Locally Advanced ◽  
Respiratory Gating ◽  
Complete Response ◽  
Adaptive Planning ◽  
Dynamic Contrast Enhancement ◽  
Tumor Tracking ◽  
Esophageal Motion

In this review, we outline the potential benefits and the future role of MRI and MR-guided radiotherapy (MRgRT) in the management of esophageal cancer. Although not currently used in most clinical practice settings, MRI is a useful non-invasive imaging modality that provides excellent soft tissue contrast and the ability to visualize cancer physiology. Chemoradiation therapy with or without surgery is essential for the management of locally advanced esophageal cancer. MRI can help stage esophageal cancer, delineate the gross tumor volume (GTV), and assess the response to chemoradiotherapy. Integrated MRgRT systems can help overcome the challenge of esophageal motion due to respiratory motion by using real-time imaging and tumor tracking with respiratory gating. With daily on-table MRI, shifts in tumor position and tumor regression can be taken into account for online-adaptation. The combination of accurate GTV visualization, respiratory gating, and online adaptive planning, allows for tighter treatment volumes and improved sparing of the surrounding normal organs. This could lead to a reduction in radiotherapy induced cardiac toxicity, pneumonitis and post-operative complications. Tumor physiology as seen on diffusion weighted imaging or dynamic contrast enhancement can help individualize treatments based on the response to chemoradiotherapy. Patients with a complete response on MRI can be considered for organ preservation while patients with no response can be offered an earlier resection. In patients with a partial response to chemoradiotherapy, areas of residual cancer can be targeted for dose escalation. The tighter and more accurate targeting enabled with MRgRT may enable hypofractionated treatment schedules.

Phase II cisplatin, irinotecan, cetuximab and concurrent radiation therapy followed by surgery for locally advanced esophageal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4064-4064 ◽  
Author(s):  
P. C. Enzinger ◽  
T. Yock ◽  
W. Suh ◽  
P. Fidias ◽  
H. Mamon ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Radiation Therapy ◽  
Phase Ii ◽  
Locally Advanced ◽  
Complete Response ◽  
Tumor Location ◽  
Advanced Esophageal Cancer ◽  
Early Results ◽  
Ecog Ps ◽  
Locally Advanced Esophageal Cancer

4064 Background: Weekly irinotecan, cisplatin, and concurrent radiation therapy is a well-tolerated, active regimen in locally advanced esophageal cancer. (Ilson. JCO 2003) Cetuximab, an EGFR inhibitor, is a potent radiation sensitizer in head and neck cancer. (Bonner. Proc ASCO 2004) Methods: In this phase II trial, patients (pts) with T2–4N0–1M0–1A esophageal adenocarcinoma (A) or squamous cell carcinoma (S) receive 5040 cGy/28 fractions of radiation therapy (RT) and concurrent weekly cisplatin 30mg/m2 plus irinotecan 65 mg/m2 on weeks 1, 2, 4, and 5, followed by surgery 4–8 weeks after completion of RT. Additionally, pts receive weekly infusions of cetuximab 250 mg during RT, up to one week before surgery, and for 6 months following surgery. Results: Seventeen pts have been entered: male: female = 14:3, median age 54, ECOG PS 0:1 = 6:11, A:S = 17:0, stage IIA:IIB:III:IVA = 6:1:8:2, tumor location-esophagus-mid:lower:gastroesophageal junction = 1:4:12, >10% weight loss-yes:no = 8:9. Of 17 pts entered, 15 pts have proceeded to surgery, 1 pt died from Aspergillus infection resulting in respiratory failure and sepsis, and 1 pt is pending surgery. Of the 15 pts who underwent surgery, 2 (13%) had a complete pathologic response; pathologic stage for other pts: 0 = 1, I = 3, IIA = 3, IIB = 1, III = 4, IV = 1. Grade III/IV toxicity (17 pts) was: diarrhea 9 pts, neutropenia 9 pts, febrile neutropenia 5 pts, anorexia 5 pts, vomiting 4 pts, fatigue 3 pts, mucositis 1 pt. Chemotherapy dose attenuation was required for diarrhea in 5 pts, for neutropenia in 4 pts, and for folliculitis in 1 pt. One patient was removed from study during week 6 for prolonged diarrhea/ dehydration. Due to the 2-step design of the trial, accrual is on hold pending a 3rd required pathologic CR in the first 17 patients. Conclusions: Compared to other trials of irinotecan, cisplatin, radiation therapy, and surgery in similar groups of esophageal cancer patients, early results for this combination with cetuximab suggest a lower complete response rate and higher overall toxicity. Additional data will be available at ASCO. Supported by Bristol-Myers Squibb. No significant financial relationships to disclose.

Serial ctDNA analysis as a real-time indicator of neoadjuvant chemoradiotherapy in rectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3569-3569 ◽  
Author(s):  
Jiaolin Zhou ◽  
Guole Lin ◽  
Yuhua Gong ◽  
Yanyan Zhang ◽  
Yan-Fang Guan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Lymph Node ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Lymph Node Involvement ◽  
Tumor Regression Grade ◽  
Treatment Intensification

3569 Background: Neoadjuvant chemoradiotherapy (nCRT) is nowadays the standard of care for the locally advanced rectal cancer (LARC). However, there is no effective method to predict patients’ possible benefits from nCRT and monitor the response to it. Methods: Patients with locally advanced middle and low rectal cancer of stage cT3-4N0M0 or cTanyN+M0 were enrolled from August 2017 to July 2018. All patients received nCRT with long-term radiation plus fluorouracil based chemotherapy, followed by the radical surgery. Serial plasma samples were collected pre-nCRT, during nCRT, and preoperatively (8 weeks after the completion of nCRT). Somatic mutations were detected with next-generation sequencing using a 1021-gene panel with peripheral blood lymphocyte DNA as a germline control. Results: This prospective cohort study enrolled 61 patients with rectal cancer. The pathological complete response (pCR) rate and the downstage rate was 31% (19/61) and 80% (49/61), respectively. ctDNA was detectable in 77% (47/61), 18% (11/61) and 13% (8/61) of blood samples obtained pre-nCRT, during nCRT and preoperatively, respectively. No significant association was observed between pre-nCRT ctDNA status with any clinicopathological factors, including age, gender, differentiation or tumor circumferential extent. Among the 8 patients with detectable ctDNA preoperatively, pathological tumor regression grade (TRG) of CAP 2-3 were observed and hepatic metastasis was found in 4 patients within 2 months. For patients with undetectable pre-operative ctDNA, a higher proportion archived pathological downstaging (85% vs 50%). The correlation between preoperative ctDNA status and achievement of pathological downstage was independent of age, gender or differentiation (p = 0.02). In addition, preoperative ctDNA positivity was associated with the persistently involved lymph node (p = 0.02). However, neither pre-nCRT nor during-nCRT ctDNA status was associated with pathological downstaging or persistently lymph node involvement. Conclusions: Detectable ctDNA after the completion of nCRT is a predicator of unsatisfactory curative effect of patients with LARC, which might indicate novel treatment intensification studies. Clinical trial information: NCT03042000.

scholarly journals Induction Chemotherapy Followed by Concurrent Chemo-Radiotherapy for Locally Advanced Gastro-Esophageal and Gastric Carcinoma

2021 ◽  
pp. 35-44
Author(s):  
Nora Shaband ◽  
Niveen Abo-Touk ◽  
Mohamed Elawadi ◽  
Saleh Ta-Ema
Keyword(s):  
Induction Chemotherapy ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Esophageal Stenosis ◽  
University Hospital ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Gastroesophageal Adenocarcinoma

Aims: To assess the safety and efficacy of chemo-radiotherapy before radical surgery in locally advanced gastric and gastroesophageal adenocarcinoma. Study Design: This was a prospective phase Ⅱ single arm study. Place and Duration of Study: Department of Clinical Oncology and Nuclear Medicine, Mansoura University Hospital, Mansoura, Egypt, between May 2017 and June 2019. Methodology: Patients with pathologically proven gastric or gastroesophageal junction adenocarcinoma are included. They received one cycle of induction chemotherapy paclitaxel-carboplatin, [paclitaxel dose of 175 mg/m2, carboplatin dose of (AUC: 5)], followed by CCRT [RT 45 Gy over 25 fractions over 5 weeks concurrent with weekly paclitaxel at a dose of 50 mg/m2, carboplatin at a dose of (AUC: 2)], followed by surgery and 2 cycles of paclitaxel-carboplatin for responders. Results: The study included 24 patients. Most of the patients were diagnosed at stage III (83.3%). There were no major side effects of the induction chemotherapy cycle. There were no reported grade 3 or 4 toxicities for the CCRT. Only two patients suffered from late radiation toxicities (distal esophageal stenosis). Pathological complete response was achieved in seven patients (31.8%). Twenty-two patients had surgical resection with a 95% resection margin zero. The median follow-up time was 22.5 months. The median progression-free survival (PFS) and overall survival (OS) were 23, 23.5 months, respectively. Conclusion: The preliminary data suggested good efficacy of the studied treatment design with acceptable adverse-event rates, however a larger multicentric phase 3 trial with a longer follow-up duration is recommended.

scholarly journals Association of visual and quantitative heterogeneity of 18F-FDG PET images with treatment response in locally advanced rectal cancer: A feasibility study

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242597
Author(s):  
Paula Martin-Gonzalez ◽  
Estibaliz Gomez de Mariscal ◽  
M. Elena Martino ◽  
Pedro M. Gordaliza ◽  
Isabel Peligros ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Fdg Pet ◽  
Tumor Heterogeneity ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Metabolic Parameters ◽  
Response To Treatment ◽  
Tumor Regression Grade

Background and purpose Few tools are available to predict tumor response to treatment. This retrospective study assesses visual and automatic heterogeneity from 18F-FDG PET images as predictors of response in locally advanced rectal cancer. Methods This study included 37 LARC patients who underwent an 18F-FDG PET before their neoadjuvant therapy. One expert segmented the tumor from the PET images. Blinded to the patient´s outcome, two experts established by consensus a visual score for tumor heterogeneity. Metabolic and texture parameters were extracted from the tumor area. Multivariate binary logistic regression with cross-validation was used to estimate the clinical relevance of these features. Area under the ROC Curve (AUC) of each model was evaluated. Histopathological tumor regression grade was the ground-truth. Results Standard metabolic parameters could discriminate 50.1% of responders (AUC = 0.685). Visual heterogeneity classification showed correct assessment of the response in 75.4% of the sample (AUC = 0.759). Automatic quantitative evaluation of heterogeneity achieved a similar predictive capacity (73.1%, AUC = 0.815). Conclusion A response prediction model in LARC based on tumor heterogeneity (assessed either visually or with automatic texture measurement) shows that texture features may complement the information provided by the metabolic parameters and increase prediction accuracy.

5-fluorouracil (5-FU) plus cisplatin (CDDP) induction chemotherapy followed by combined external bean radiation therapy (XRT) and mitomycin-C (MMC) and 5-FU chemotherapy in locally advanced anal canal cancer (ACC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14016-14016
Author(s):  
J. J. Rodriguez-Riao ◽  
D. Figueira ◽  
E. Zarraga ◽  
L. Lion ◽  
M. B. Fuentes ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Complete Response ◽  
Sphincter Preservation ◽  
Combined Modality Treatment ◽  
Anal Canal Cancer ◽  
Grade 3 ◽  
Ecog Ps

14016 Background: Definitive chemoradiation therapy is the standard of care for squamous or cloacogenic cell ACC. The chemotherapy regimen comprising 5-FU and MMC is the most commonly used among patients with ACC, nearly 70% of patients can get complete response (CR), with the benefit of sphincter preservation, but patients with a large tumors (T3/T4) or nodal metastases have a response of 50%. Methods: To improve outcome, we conducted a phase II, study of 5-FU and CDDP followed by combined XRT plus 5-FU and MMC. Eligibility included patients withT3/T4 ACC with limited locoregional nodal involvement (N0/N1). Treatment: 5-FU 1000 mg/m2/days 1 to 5 in continuous i.v. infusion plus CDDP 100 mg/m2 i.v. day 1 q21d was administered for 2 cycles (weeks 1 and 4) followed by XRT (4.5 Gy) during 6 weeks (weeks 7 to12) with concurrent 5-FU 1000 mg/m2/days 1 to 4 in continuous i.v. infusion plus MMC 10 mg/m2 i.v. day 1 (weeks 9 and 17). RECIST criteria were used to assess tumor response Results: 59 patients were entered on this study from 8/2000 to 2/2005. Median age: 57 yrs (37–83), 49 F/10 M, median ECOG PS 0 (0–1), T3/T4 44/15, N0/N1 20/39. 54 patients were evaluable for clinical response: Induction chemotherapy led to 13 (24%) CR, 38 (70%) partial responses (PR) and 2 (6%) stable disease. After combined modality treatment, there were a total of 36 (67%) CR, 13 (24%) PR, 5 (9%) SD. Median follow up was 21.6 months (5–52).The median time to progression is 20.5 months (3–52). Toxicity grade 3/4: Neutropenia 20% (10/54), thrombocytopenia 13% (7/54), radiodermatitis 13% (7/54), nausea/vomiting 7% (4/54). Our previous experience with concurrent treatment without induction (n=27) resulted in a CR 59%, PR 37%, and 4% progressive disease Conclusions: We concluded that induction chemotherapy followed by combined XRT and chemotherapy could be an option in treatment of locally advanced ACC. No significant financial relationships to disclose.

Weekly cetuximab (CET) plus oxaliplatin (OX), infusional 5-fluorouracil (5-FU) and radiation therapy (RT) as neoadjuvant treatment for esophageal squamous cell carcinoma (ESCC): A phase I study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15507-e15507
Author(s):  
F. Lordick ◽  
C. Meyer zum Büschenfelde ◽  
P. Thuss-Patience ◽  
N. Röthling ◽  
H. Geinitz ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
R0 Resection ◽  
Moderate Anemia ◽  
Hand Foot Syndrome ◽  
Ecog Ps

e15507 Background: CET, a chimeric monoclonal IgG1 antibody that targets the epidermal growth factor receptor (EGFR), has proven activity in a variety of SCC models in vitro and in vivo and has also been shown to enhance the activity of both chemo- and radiotherapy. Methods: Patients (pts) with locally advanced ESCC received CET for 2 weeks at an initial dose of 400mg/m2 (d - 15) i.v. followed by 250mg/m2(d -8) before they started a neoadjuvant dose escalation regimen. Pts received weekly CET 250mg/m2 plus RT 25 x 1.8 Gy (cumulative dose 45 Gy) d1–33. Cohort 1–3 received escalating doses of OX 45–50 mg/m2 d1,8,22,29 plus 5-FU 180–200–225 mg/m2/d; d1–5,8–12,15–19,22–26,29–33). Surgery was scheduled 4–6 weeks after RT. Toxicity was assessed according to NCI-CTC. Response was categorized according to the histopathologic score. Results: 15 pts were enrolled (2 female, 13 male; mean age 62 years, ECOG-PS 0 or 1). All pts had locally advanced SCC (uT2–4, cNx, cM0–1a) of the cervical (n=1), the upper (n=5) or the distal (n=7) esophagus. 6 pts were treated in cohort 1 and 3 pts in cohort 2 without any dose limiting toxicity (DLT). Of 6 pts treated in cohort 3, 1 pt developed grade 3 diarrhea and mucositis. All other observed toxicities were mild or moderate: anemia n=12, neutropenia n=2, thrombocytopenia n=3, nausea/vomiting n=8, mucositis n=6, diarrhea n=4, neuropathy n=4, hand-foot-syndrome n=8, skin rash n=14, no infection and no infusion-related reactions were observed. 12 pts underwent abdomino-thoracic esophagectomy with no postop. mortality; 3 pts were not resected. 8/12 resected pts had an R0 resection (67%) and 4 pts (33%) achieved a histopathological complete response (score 1a). Conclusions: 2 weeks of CET (400mg/m2 and 250mg/m2) followed by weekly CET (250mg/m2) plus OX 50mg/m2 d1,8,22,29, 5-FU 225 mg/m2/d d1–5,8–12,15–19,22–26,29–33 and RT 45 Gy (1.8Gy/f) was shown to be safe as neoadjuvant treatment for locally advanced ESCC. The anti-tumor activity of this regimen is promising and is being further investigated in an ongoing phase II study. [Table: see text]

Locally advanced rectal cancer (LARC): A 12-year experience of multimodality approach.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 607-607
Author(s):  
F. Bertolini ◽  
L. Scarabelli ◽  
C. Del Giovane ◽  
S. Zironi ◽  
G. De Marco ◽  
...  
Keyword(s):  
Vascular Invasion ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Complete Response ◽  
Subsequent Treatment ◽  
University Hospital ◽  
Tumor Regression Grade ◽  
Histological Features

607 Background: Main objective of the report is to review retrospectively a 12 years experience of pre-operative chemo-radiotherapy (CRT) in patients (pts) with LARC at the University Hospital of Modena and to correlate clinical variables with outcome. Methods: Between 1998 and 2010, 275 consecutive pts with stage II, III and IV (oligometastatic in lung or liver) LARC who underwent neo-adjuvant CTR were identified from a single institution. All pts received fluoropyrimidine-based chemotherapy (alone or in combination) and RT (50-50.4 Gy). Results: On 275 pts, 166 were males (61%) and 109 females (39%); median age: 65.9 years (range: 26-84). Rectal primary site (on 260 pts): 112 low (43%), 91 medium (35%) and 57 high (22%). Stage at diagnosis (on 245): 2 cT2N0 (0.8%), 8 cT2N+ (3.3%), 68 cT3N0 (27.8%), 134 cT3N1 (54.7%), 11 cT4N0 (4.5%), 22 cT4N1 (8.9%). Pre-operative treatment (on 268 pts): 168 pts (62.6%) received 5fluorouracil (5FU) in continuous infusion, 37 (13.9%) capecitabine, 36 (13.5%) FU+oxaliplatin and 27 (10%) 5FU+cetuximab (clinical trial). On evaluable 177 pts, only 25 (14%) developed G3 toxicity and subsequent treatment interruption. No grade 4 toxicity was recorded. 252 pts underwent surgery (18 pts are still ongoing; 5 did not receive surgery for multiple distant metastases at pre-operative staging): 189 anterior resection (75%), 59 abdominal-perineal amputation (23.4%) and 4 endoscopic resection (1.6%). On 235 pts, 148 obtained a T and/or N downstaging (63%). Dworak tumor regression grade (TRG) was (on 209 pts): TRG4 (pathological complete response) 38 (18.3%), TRG3 37 (17.8%), TRG2 67 (32%), TRG1 63 (30%) and TRG0 4 (1.9%). 5 y-disease free survival (DFS) and overall survival (OS) are 75% and 73%, respectively. Down-staging, TRG 3-4 and histological features like the positivity for radial margins and vascular invasion correlate with both DFS and OS. Conclusions: Pre-operative CRT is well tolerated; downstaging, TRG and histological features such as radial margins and vascular invasion are the strongest predictors of survival. No significant financial relationships to disclose.

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