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.

Cetuximab, paclitaxel, carboplatin and radiation for esophageal and gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4029-4029 ◽  
Author(s):  
M. Suntharalingam ◽  
T. Dipetrillo ◽  
P. Akerman ◽  
H. Wanebo ◽  
B. Daly ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Esophageal Cancer ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Complete Response ◽  
Grade 3

4029 Background: Cetuximab is an IgG1, chimerized, monoclonal antibody that binds specifically to the epidermal growth factor receptor. Cetuximab improves survival when combined with radiation for patients with locally advanced head and neck cancer. We evaluated the safety and efficacy of the addition of cetuximab to concurrent chemoradiation for patients with esophageal and gastric cancer. Methods: Patients with adenocarcinoma or squamous cell cancer of the esophagus or stomach without distant organ metastases were eligible. Patients with locally advanced disease from mediastinal, celiac, portal and gastric lymphadenopathy were eligible. Surgical resection was not required. Clinical complete response was defined as no tumor on postreatment endoscopic biopsy. Patients received cetuximab, 400mg/m2 week #1 then 250 mg/m2/week for 5 weeks, paclitaxel, 50 mg/m2/week, and carboplatin, AUC =2 weekly for 6 weeks, with concurrent 50.4 Gy radiation. Results: Thirty-seven patients have been entered. The median age was 61 (range of 30–87). Thirty-four have esophageal cancer and 3 have gastric cancer. Of the patients with esophageal cancer, twenty-five have adenocarcinoma and nine have squamous cell cancer. Thus far, 30 patients have completed treatment and are evaluable for toxicity. There have been no grade 4 non-hematologic toxicities and 1 pt had grade 4 neutropenia (3%). Six patients (20%) had grade 3 esophagitis. Other grade 3 toxicities included dehydration (n=5), rash (n=9), and paclitaxel/cetuximab hypersensitivity reactions (n=2). Eighteen of 27 patients (67%) have had clinical complete response. Seven pts out of 16 (43%) who have gone to surgery have had a pathologic CR. Conclusions: Cetuximab can be safely administered with chemoradiation for patients with esophageal cancer. Consistent with the data in head and neck cancer, cetuximab increases cutaneous toxicity but does not increase mucositis/esophagitis when combined with chemoradiation. Further evaluation is ongoing. [Table: see text]

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.

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.

Outcomes of recurrence after complete response to definitive chemoradiotherapy for stage II/III (non–T4) esophageal squamous cell carcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 179-179
Author(s):  
Hiroki Kuwabara ◽  
Ken Kato ◽  
Yusuke Sasaki ◽  
Naoki Takahashi ◽  
Hirokazu Shoji ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Survival Time ◽  
Cox Regression ◽  
Performance Status ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Esophageal Cancer ◽  
Locoregional Failure ◽  
Distant Failure ◽  
Locally Advanced Esophageal Cancer

179 Background: Recurrence after definitive chemoradiotherapy (dCRT) for locally advanced esophageal cancer is associated with poor outcome. We examined patterns of recurrence and clinical outcomes in patients with recurrence after complete response (CR) to dCRT. Methods: We retrospectively investigated 238 patients who had achieved initial CR after dCRT for locally advanced esophageal cancer between January 2000 and December 2010. From among these patients we selected 95 who had developed disease recurrence after CR. Overall survival was defined as survival time from recurrence to death and was calculated by using the Kaplan-Meier method. Univariate and multivariate analyses were performed with the Cox regression model to determine prognostic factors for survival. Results: The characteristics of the 95 patients were as follows: male: female = 84:11; median age = 64 years (range 46 to 80); clinical stage at diagnosis (UICC 6th edition) IIA/IIB/III = 20/31/44; and performance status at recurrence (0/1) = (51/44). Primary CRT consisted of 5-FU+cisplatin (n = 87), 5-FU+nedaplatin (n = 3), S-1+cisplatin (n = 3), 5-FU+cisplatin+ nimotuzumab (n = 1), or docetaxel (n = 1). The pattern of recurrence was locoregional failure (n = 53) or any distant failure (n = 42). Median time from the start of dCRT to recurrence was 13.0 months, and median survival time from recurrence to death was 19.6 months. Median survival time according to the pattern of failure was 34.7 months (locoregional failure) or 17.0 months (any distant failure). Application of the Cox regression model, including the additional prognostic variables of age, ECOG performance status, number of organs in which metastases were present, and LDH, revealed that any distant failure (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.2 to 4.1; P = 0.01) and recurrence before 13.0 months (HR 2.1; 95% CI 1.2 to 3.6; P = 0.01) were predictors of poor overall survival. Conclusions: Early recurrence and any distant failure were associated with poor prognosis after CR to dCRT for locally advanced esophageal cancer.

Changes in neutrophil-to-lympocyte and platelet-to-lymphocyte ratios to predict survival and pathologic complete response in esophageal cancer patients who receive trimodality therapy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 170-170
Author(s):  
Jalal Hyder ◽  
Drexell Boggs ◽  
Andrew Hanna ◽  
Mohan Suntharalingam ◽  
Michael David Chuong
Keyword(s):  
Esophageal Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Complete Response ◽  
Trimodality Therapy ◽  
Lymphocyte Ratio

170 Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict for survival in cancer patients. In patients receiving multi-modality therapy, the effect of each specific therapy on the NLR and PLR is not well understood. We therefore evaluated changes in NLR and PLR among locally advanced esophageal cancer patients who received trimodality therapy. Methods: We performed a retrospective analysis of non-metastatic patients with esophageal cancer who received neoadjuvant chemoradiation (CRT) followed by esophagectomy at our institution between March 2000 and April 2012. NLR and PLR values were obtained the following time points (TP): 1) at diagnosis before CRT, 2) after CRT prior to surgery, and 3) after surgery. We also evaluated change in NLR and PLR using the difference and ratio between TPs. Overall survival (OS) was evaluated by Kaplan-Meier analysis. Univariate and multivariate Cox regression models were applied to evaluate the independent prognostic significance of NLR and PLR. Results: 83 patients with stage II-IV esophageal cancer and median age 60 years were included. Median follow up was 29.3 months. Median dose of 50.4 Gy (50.4-59.4) in 28 fractions (28-33) was used. Median NLR and PLR at the each TP: 1) 3.3 and 157.2, 2) 12 and 645, and 11.5 and 391.7, respectively. On multivariate analysis, inferior OS was associated with PLR ≥250 at TP 3 (p=.03), PLR decrease ≥609.2 from TP 2-3 (p=.02), and PLR ratio (TP 1/TP3) ≥1.08 (p=.03). Inferior progression free survival (PFS) was associated with NLR at TP 2 ≥36 (p=.0008), NLR increase ≥28.3 from TP 1-2 (p=.0005), PLR increase from TP 1-3 ≥19 (p=.01), and PLR ratio (TP 2/TP 3) ≥0.34 (p=0.1). Pathologic complete response (pCR) was less likely for adenocarcinoma histology (p=.03), NLR at TP 2 ≥10.6 (p=.04), and NLR increase from TP 1 to TP 2 ≥4.6 (p=.03). Conclusions: This is the first study to demonstrate that changes in NLR and PLR throughout trimodality therapy for esophageal cancer correlate with OS, PFS, and pCR. Further evaluation is warranted to better define which of the identified cut-off values are most clinically significant.

Phase I/II Trial of Capecitabine, Oxaliplatin, and Radiation for Rectal Cancer

2003 ◽  
Vol 21 (16) ◽  
pp. 3098-3104 ◽  
Author(s):  
Claus Rödel ◽  
Gerhard. G. Grabenbauer ◽  
Thomas Papadopoulos ◽  
Werner Hohenberger ◽  
Hans-Joachim Schmoll ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Sphincter Preservation ◽  
Phase Iii ◽  
Grade 3

Purpose: The purpose of this study was to establish the feasibility and efficacy of preoperative radiotherapy (RT) with concurrent capecitabine and oxaliplatin (XELOX-RT) in patients with rectal cancer. Patients and Methods: Thirty-two patients with locally advanced (T3/T4) or low-lying rectal cancer received preoperative RT (total dose, 50.4 Gy). Capecitabine was administered concurrently at 825 mg/m2 bid on days 1 to 14 and 22 to 35, with oxaliplatin starting at 50 mg/m2 on days 1, 8, 22, and 29 with planned escalation steps of 10 mg/m2. End points of the phase II study included downstaging, histopathologic tumor regression, resectability of T4 disease, and sphincter preservation in patients with low-lying tumors. Results: Dose-limiting grade 3 gastrointestinal toxicity was observed in two of six patients treated with 60 mg/m2 of oxaliplatin. Thus, 50 mg/m2 was the recommended dose for the phase II study. Toxicities observed at this dose level were generally mild, with only two cases of short-lived grade 3 diarrhea. Myelosuppression, mainly leukopenia, was restricted to grade 2 in 19% of patients. T-category downstaging was achieved in 17 (55%) of 31 operated patients, and 68% of patients had negative lymph nodes. Pathologic complete response was found in 19% of the resected specimens. Radical surgery with free margins could be performed in 79% of patients with T4 disease, and 36% of patients with tumors ≤ 2 cm from the dentate line had sphincter-saving surgery. Conclusion: Preoperative XELOX-RT is a feasible and well tolerated treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based therapy with XELOX chemoradiotherapy.

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