scholarly journals Chances, risks and limitations of neoadjuvant therapy in surgical oncology

2016 ◽  
Vol 1 (1) ◽  
pp. 3-11 ◽  
Author(s):  
Florian Lordick ◽  
Ines Gockel
Keyword(s):  
Neoadjuvant Therapy ◽  
Systemic Disease ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Rare Event ◽  
Surgical Oncology ◽  
Clinical Staging ◽  
Tumor Control ◽  
Tumor Types

AbstractOver the last decades, neoadjuvant treatment has been established as a standard of care for a variety of tumor types in visceral oncology. Neoadjuvant treatment is recommended in locally advanced esophageal and gastric cancer as well as in rectal cancer. In borderline resectable pancreatic cancer, neoadjuvant therapy is an emerging treatment concept, whereas in resectable colorectal liver metastases, neoadjuvant treatment is often used, although the evidence for improvement of survival outcomes is rather weak. What makes neoadjuvant treatment attractive from a surgical oncology viewpoint is its ability to shrink tumors to a smaller size and to increase the chances for complete resection with clear surgical margins, which is a prerequisite for cure. Studies suggest that local tumor control is increased in some visceral tumor types, especially with neoadjuvant chemoradiotherapy. In some other studies, a better control of systemic disease has contributed to significantly improved survival rates. Additionally, delaying surgery offers the chance to bring the patient into a better general condition for major surgery, but it also confers the risk of progression. Although it is a relatively rare event, cancers may progress locally during neoadjuvant treatment or distant metastases may occur, jeopardizing a curative surgical treatment approach. Although this is seen as risk of neoadjuvant treatment, it can also be seen as a chance to select only those patients for surgery who have a better control of systemic disease. Some studies showed increased perioperative morbidity in patients who underwent neoadjuvant treatment, which is another potential disadvantage. Optimal multidisciplinary teamwork is key to controlling that risk. Meanwhile, the neoadjuvant treatment period is also used as a “window of opportunity” for studying the activity of novel drugs and for investigating predictive and prognostic biomarkers of chemoradiotherapy and radiochemotherapy. Although the benefits of neoadjuvant treatment have been clearly established, the risk of overtreatment of cancers with an unfavorable prognosis remains an issue. All indications for neoadjuvant treatment are based on clinical staging. Even if staging is done meticulously, making use of all recommended diagnostic modalities, the risk of overstaging and understaging remains considerable and may lead to false indications for neoadjuvant treatment. Finally, despite all developments and emerging concepts in medical oncology, many cancers remain resistant to the currently available drugs and radiation. This may in part be due to specific molecular resistance mechanisms that are marginally understood thus far. Neoadjuvant treatment has been one of the major advances in multidisciplinary oncology in the last decades, requiring a dedicated treatment team and an optimal infrastructure for complex oncology care. This article discusses the goals and novel directions as well as limitations in neoadjuvant treatment of visceral cancers.

Deferral of rectal surgery following a continued response to preoperative chemoradiotherapy (Watch and Wait) study: A phase II multicenter study in the United Kingdom.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 489-489 ◽  
Author(s):  
S. K. Yu ◽  
G. Brown ◽  
R. J. Heald ◽  
S. Chua ◽  
G. Cook ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Clinical Staging ◽  
Pet Ct

489 Background: Neoadjuvant chemoradiotherapy (CRT) and surgical resection are standard components of therapy for patients locally advanced rectal cancer (T3,T4 or N+) in UK. In 15%-30% of patients treated pre-operatively with CRT will develop pathological complete response (CR). The time from completion of CRT to maximal tumour response is as yet unknown. This study is the first prospective study to attempt to identify the percentage of patients who can safely omit surgery and the safety of deferred surgery in patients who achieve clinical complete response post CRT. Of the 59 patients required for the study, this provides an update on 19 patients entered. Methods: Patients with locally advanced rectal cancer requiring neoadjuvant treatment are identified in the multidisciplinary meet (MDT). Patients undergo CRT using a minimum of 50.4Gy in 28 # daily conformal CT planned CRT with concomitant Capecitabine at 825mg/m2 BD. MRI pelvis and body CT are repeated 4 weeks post CRT and rediscussed at MDT. If there is a good partial response or CR, patients are considered for Deferral of Surgery Study. Based on the pre treatment clinical staging, patients are considered for adjuvant chemotherapy as per NICE guidance. At any point of the study, if there is histology proven tumour regrowth or progression, patient undergo surgery. Results: 10 (53%) patients remain in CR. 6 (32%) patients underwent surgical resection with clear margin after detection of tumour regrowth at from 2-23 months post CRT. 5 out of 6 of the patients with tumour regrowth underwent PET CT as per protocol, and all tumour regrowth in those 5 patients were detected by PET CT, i.e. FDG avid disease. The pathological stages on these 6 patients were ypT2N0 CRM negative in 5 and ypT3N0 CRM negative in 1. 3 (15%) patients with tumour regrowth refused surgery. Conclusions: In the 19 recruited patients, all the patients with tumour regrowth underwent surgical resection with clear margins. PET CT appears a useful tool for detecting tumour regrowth. The median time for tumour regrowth is 17.5 months post CRT. The trial will be successful if at least 11/59 patients are able to safely omit surgery. Accrual of patients continues. No significant financial relationships to disclose.

Accuracy of clinical staging with EUS for early stage esophageal cancer: Are we denying patients beneficial neoadjuvant chemo-radiation?

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 163-163
Author(s):  
Carrie Luu ◽  
Norbert Garcia-Henriquez ◽  
Jason Klapman ◽  
Cynthia L. Harris ◽  
Khaldoun Almhanna ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Neoadjuvant Therapy ◽  
Early Stage ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Significant Proportion ◽  
Surgical Pathology ◽  
Clinical Staging ◽  
Cancer Center

163 Background: Esophagectomy alone has been considered the standard of care for early stage esophageal cancer (EC) while neoadjuvant therapy is now standard for locally advanced disease. The choice of treatment therefore hinges on accurate locoregional staging by endoscopic ultrasound (EUS). Our objective is to evaluate the accuracy of EUS performed in a high-volume tertiary cancer center in clinical stage T1N0 (cT1N0) and T2N0 (cT2N0) esophageal cancer patients undergoing esophagectomy without neoadjuvant therapy. Methods: A retrospective review of the esophageal cancer database at a single institution was performed. Patients with cT1N0 and cT2N0 esophageal cancer based on EUS undergoing esophagectomy without neoadjuvant treatment were evaluated. Patient demographics, tumor characteristics, and treatment were reviewed. Surgical pathology was compared to EUS staging. Results: Between 2000 and 2015, 139 patients were identified. There were 25 (18%) female and 114 (82%) male patients. The tumor location included the middle 1/3 of the esophagus in 11 (8%) and lower 1/3 and gastroesophageal junction in 128 (92%) patients. Eighty-one percent of patients had adenocarcinoma, 9% had squamous cell carcinoma, 9% had Barrett’s dysplasia, and 1% had mixed histology. Clinical staging were as follows: 110 (79%) patients had cT1N0 and 29 (21%) patients had cT2N0 tumors. For the entire cohort, preoperative EUS matched the final surgical pathology in 76/139 patients for an accuracy rate of 53%. Twenty-nine patients (21%) were under-staged by EUS; of those, 19 (14%) had unrecognized nodal disease. This included 12/109 (11%) of cT1N0 and 7/29 (24%) of cT2N0 patients. Conclusions: The accuracy of preoperative EUS staging in early esophageal cancer remains sub-optimal. Interestingly, a significant proportion (24%) of cT2N0 EC patients were found to have positive lymph nodes on surgical pathology, and perhaps these patients could have benefitted from neoadjuvant therapy. In light of these findings, the current management of cT2N0 esophageal cancer should be reconsidered.

scholarly journals Recent Progress in the Neoadjuvant Treatment Strategy for Locally Advanced Esophageal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5162
Author(s):  
Sicong Hou ◽  
Ziyin Pan ◽  
Xin Hao ◽  
Qinglei Hang ◽  
Yanbing Ding
Keyword(s):  
Esophageal Cancer ◽  
Neoadjuvant Therapy ◽  
Randomized Clinical Trials ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Preoperative Chemoradiotherapy ◽  
Research Progress ◽  
Preoperative Radiation ◽  
Treatment Protocols

Neoadjuvant therapies, primarily chemotherapy and chemoradiotherapy, are able to improve the overall survival (OS) in patients with locally advanced resectable esophageal cancer (EC) based on the results of several randomized clinical trials. The advantage of neoadjuvant therapy is chiefly attributed to the decreased risk of local–regional recurrence and distant metastasis. Thus, it has been recommended as standard treatment for patients with resectable EC. However, several fundamental problems remain. First, the combination of neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), and surgery for EC patients with different histological types remains controversial. Furthermore, to reduce the toxicity of preoperative chemotherapy and the risk of complications caused by preoperative radiation therapy, the treatment protocols of nCT and nCRT still need to be investigated and optimized by prospective trials. Moreover, for patients with complete clinical response following neoadjuvant therapy, it is worth ascertaining whether a “watch and wait” surveillance plus surgery-as-needed policy is more favorable, as well as, in addition to preoperative chemoradiotherapy, whether immunotherapy, especially when combined with the traditional neoadjuvant therapy regimens, brings new prospects for EC treatment. In this review, we summarize the recent insights into the research progress and existing problems of neoadjuvant therapy for locally advanced resectable EC.

PS02.117: OUTCOMES FOR SQUAMOUS CELL CARCINOMA OF THE OESOPHAGUS IN A WESTERN POPULATION

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 154-154
Author(s):  
Anantha Madhavan ◽  
Alex Phillips ◽  
Nicola Wyatt ◽  
Maziar Navidi ◽  
S Michael Griffin
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Median Survival ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Clinical Staging ◽  
Treatment Modalities ◽  
Significant Difference

Abstract Background Squamous cell carcinoma of the oesophagus comprises approximately 30% of oesophageal malignancies in the ‘west’. Different approaches in management have been advocated. In the UK patients may receive conventional neoadjuvant chemotherapy (OEO2) or neoadjuvant chemoradiotherapy (CROSS). The aim of this study was to evaluate outcomes of patients receiving potentially curative surgical treatment for squamous cell carcinoma of the oesophagus. Methods A retrospective review of patients who underwent treatment with curative intent for oesophageal squamous cell carcinoma between 2006 to 2016 at a single institution was performed. Patients underwent a standardised staging protocol and were assigned to the treatment modality based on the stage of the disease by a multi-disciplinary team. Outcomes were evaluated according to the treatment received. Results Overall 199 patients underwent curative treatment in the 10 year period. This comprised 26% of the oesophagectomies for carcinoma. Of these, 168 patients had disease which was staged T3 and above or had evidence of nodal disease. 81% of these patients received neo-adjuvant treatment, 108 receiving chemotherapy alone and 29 receiving chemoradiotherapy. The remaining 31 patients underwent surgery alone. There was no significant difference in the clinical staging between the three treatment modalities, (P = 0.25). There were 31 patients with early (T1/2 N0) cancer that underwent unimodality treatment in the form of surgery. Estimated median survival was 85 months for those that received chemotherapy and 53 months chemoradiotherapy (P = 0.45). Within the surgical group those patients with locally advanced disease (T3 + or N + ) median survival was 19 months; median survival was not reached for early cancers. Conclusion Both chemoradiotherapy and chemotherapy in the neoadjuvant setting combined with radical surgery enable excellent long-term outcomes to be achieved. Data from the Neo-aegis trial will hopefully inform which neoadjuvant treatment confers the greatest survival advantage. Disclosure All authors have declared no conflicts of interest.

scholarly journals 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 ◽  
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.

Rectal cancer – current treatment strategy and the tumor regression grade evaluation after neoadjuvant therapy in patients who underwent surgery at the I. Department of Surgery, General University Hospital in Prague between 2012 and 2016

2021 ◽  
Vol 100 (2) ◽  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Tumor Regression ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Current Treatment ◽  
University Hospital ◽  
Tumor Regression Grade ◽  
Oncological Treatment ◽  
Regression Grade

Introduction: The article contains a summary of the issues of staging and therapy with an emphasis on the neoadjuvant treatment and associated tumor regression grade with the analysis of our own group of patients. Methods: Retrospective analysis of patients with rectal cancer who underwent a surgery at the 1st Department of Surgery – Thoratic, Abdominal and Injury Surgery; First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic, focusing on those who underwent neoadjuvant chemoradiotherapy and their pathologists evaluated tumor regression grade after the resection. Results: The group consists of 161 patients operated on between 2012 and 2016. 47 patients underwent neoadjuvant oncological treatment with further evaluation of the tumor regression grade by a pathologist, a scoring system according to Ryan was used. A complete pathological response was elicited in 10.4% of patients, no response in 35.4% of patients, and partial tumor regression in 54.2%. Conclusion: Although there is a difference in our results compared to foreign publications, the proportion of patients remains comparable. Studies evaluating the advantages versus disadvantages of neoadjuvant therapy will certainly follow, and the question of the suitability of surgical treatment as the only curative solution is partially raised.

Phase-II study of toripalimab combined with neoadjuvant chemotherapy for the treatment of resectable esophageal squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16029-e16029
Author(s):  
Delin Liu ◽  
Qin Zhang ◽  
Jinghua Zhu ◽  
Ting Qian ◽  
Rong Yin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Radiochemotherapy ◽  
Grade 3

e16029 Background: Compared with neoadjuvant chemotherapy alone，Neoadjuvant radiochemotherapy can significantly increase pCR rate in esophageal squamous cell carcinoma and improve patient overall survival. However, the addition of radiotherapy increases the risk of adverse reactions and surgery. Neoadjuvant radiochemotherapy is currently used in < 5% of Chinese patients.The purpose of this phase II study is to assess the efficacy and safety of toripalimab combined with paclitaxel and cisplatin as neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma(clinical trial registration number: ChiCTR1900025318). Methods: Patients 18–75 years old with esophageal squamous cell carcinoma confirmed by endoscopic biopsy, assessed to be locally advanced esophageal squamous cell carcinoma (cT1–cT2, N+; cT3–cT4 a, any N), and expected to be resectable were given toripalimab (240 mg d1 + PTX 175 mg/m2 + PDD 75 mg/m2 q3w) before surgery for two treatment cycles, followed by efficacy assessment. A consultation meeting with thoracic surgeons was held to assess radical surgery for patients with resectable lesions 4–6 weeks after neoadjuvant therapy was completed. pCR and postoperative-stage statistical analysis were conducted based on postoperative pathology test results. These results were used to determine the efficacy and safety of PD-1 monoclonal antibody combined with chemotherapy as neoadjuvant therapy for locally advanced esophageal cancer. Results: By December 2020, 23 subjects were enrolled. Of the subjects, five withdrew without undergoing surgery (three subjects refused surgery and switched to radical radiochemotherapy, one subject progressed to PD after two cycles of neoadjuvant therapy and switched to palliative treatment, and one subject could not undergo surgery after neoadjuvant treatment and gave up the treatment) and 18 evaluable patients underwent surgery. The R0 resection rate was 100%, and T0–Tis 33.3% (6/18) achieved pCR. Among these patients, 61.1% (11/18) achieved T0–T1 after surgery, and 72.2% (13/18) achieved N0. Moreover, stage reduction effects were significant compared with preoperative TN staging. Common side-effects include nausea, vomiting, neutropenia, thrombocytopenia, rash, asthenia, constipation, and muscle soreness. Most adverse events were grades 1–2, and grades 3/4 adverse events include one case of grade 3 neutropenia and one case of grade 3 diarrhea (suspected immune-related colitis), which improved after symptomatic treatment. Conclusions: Toripalimab combined with the TP scheme showed preliminary efficacy and controllable safety in the treatment of resectable locally advanced esophageal squamous cell carcinoma and is worthy of further exploration. Clinical trial information: ChiCTR1900025318.

Camrelizumab combined with paclitaxel and nedaplatin as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESPRIT): A phase Ⅱ, single-arm, exploratory research.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16033-e16033
Author(s):  
Jianqun Ma ◽  
Jinfeng Zhang ◽  
Yingnan Yang ◽  
Dayong Zheng ◽  
Xiaoyuan Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Radical Surgery ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Therapeutic Effects

e16033 Background: Camrelizumab has been approved as a standard therapy in the second-line treatment of esophageal squamous cell carcinoma (ESCC). This study aimed to explore the efficacy and safety of camrelizumab combined with commonly used neoadjuvant chemotherapy (paclitaxel and platinum) in neoadjuvant treatment of ESCC. Methods: In this single-arm, phase Ⅱ study, patients with advanced ESCC who were expected to receive neoadjuvant therapy followed by radical surgery were recruited. The patients received 2-4 cycles of camrelizumab (200mg, iv, q3w) in combination with paclitaxel (155mg/m2, iv, q3w) and nedaplatin (80mg/m2, iv, q3w) as neoadjuvant therapy, and the therapeutic effects were determined every 2 cycles. The radical surgery was performed on patients whose tumors were evaluated as resectable. The primary endpoint was pCR, and the secondary endpoints were objective response rate (ORR) and disease control rate (DCR). Results: From May 2020 to January 2021, 24 patients with a median age of 60.5 years (50-73) were enrolled. Among them, 21 patients were available for efficacy analysis, of which 1 achieved complete response (CR), 7 achieved partial response (PR), and 13 had stable disease (SD). The ORR was 38.1% and DCR was 100%. The tumor in 10 patients shrank significantly after neoadjuvant therapy and these patients preferred radiotherapy instead of surgery as the radical therapeutic method. 2 patients abandoned surgery because of personal reasons. 2 patients were in the process of neoadjuvant therapy and had not undergone surgery yet. The remaining 7 patients underwent radical surgery and 4 patients (57.14%) achieved pCR (pT0N0M0). The main treatment-related grade 3/4 adverse event (AE) was neutropenia (1/21). All the AEs were manageable. The average intraoperative blood loss was 221mL and the average hospitalization time after operation was 12.7 days (range 8-19 days). No anastomotic leakage and treatment-related death occurred. Conclusions: Camrelizumab in combination with paclitaxel and platinum as a neoadjuvant therapy was well tolerated. The pCR rate of 57.14% was higher than the expected 40%. This encouraging result promoted us to continue this phase Ⅱ study. Clinical trial information: ChiCTR2000033761.

Adjuvant and Neoadjuvant Therapy for Pancreatic Adenocarcinoma

2017 ◽  
Author(s):  
Gregory C Wilson ◽  
Brent T Xia ◽  
Syed A Ahmed
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Borderline Resectable

Despite decades of advancement and research into the multimodal care of pancreatic cancer, mortality after the diagnosis of pancreatic ductal adenocarcinoma remains grim. The role of adjuvant therapy following surgical resection has been well established in the literature. However, adjuvant therapy is imperfect, and outside of a clinical trial, there are high rates of omission or delayed initiation of therapy. Neoadjuvant treatment strategies continue to be explored in the management of resectable, borderline-resectable, and locally advanced unresectable pancreatic adenocarcinoma. With improved resection rates and the possibility for tumor downstaging, neoadjuvant therapy has become standard for patients with borderline-resectable and locally advanced unresectable tumors. Additional benefits of neoadjuvant therapy in the treatment of resectable tumors include improved completion rates of systemic therapy and R0 resection rates. Future clinical trials, including the use of novel treatment agents and combination treatment strategies in both neoadjuvant and adjuvant regimens, will add value to the treatment of pancreatic adenocarcinoma. Key words: adjuvant therapy, borderline-resectable pancreatic cancer, locally advanced pancreatic cancer, neoadjuvant therapy, pancreatic adenocarcinoma, resectable disease 

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

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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