Predictive Factors of Esophageal Stenosis after Radiation Therapy for 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.

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Concurrent cisplatin, 5-FU, paclitaxel, and radiation therapy in patients with locally advanced esophageal cancer

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2006.02.013 ◽

2006 ◽

Vol 65 (4) ◽

pp. 1120-1128 ◽

Cited By ~ 25

Author(s):

Kevin S. Roof ◽

John Coen ◽

Thomas J. Lynch ◽

Cameron Wright ◽

Panos Fidias ◽

...

Keyword(s):

Esophageal Cancer ◽

Radiation Therapy ◽

Locally Advanced ◽

Advanced Esophageal Cancer ◽

Locally Advanced Esophageal Cancer

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Preoperative induction chemotherapy with docetaxel-cisplatin followed by concurrent docetaxel-cisplatin and radiation therapy in patients with locally advanced esophageal cancer: A prospective, multicenter phase ll trial of the Swiss Group for Clinical Cancer Research

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4562 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4562-4562

Author(s):

T. Ruhstaller ◽

L. Widmer ◽

S. Balmer Majno ◽

W. Mingrone ◽

V. Hess ◽

...

Keyword(s):

Esophageal Cancer ◽

Radiation Therapy ◽

Gastroesophageal Junction ◽

Locally Advanced ◽

Preoperative Therapy ◽

Tumor Regression Grade ◽

Thoracic Esophagus ◽

Advanced Esophageal Cancer ◽

Community Based ◽

Locally Advanced Esophageal Cancer

4562 Background: The role of preoperative therapy in patients (pts) with locally advanced esophageal cancer remains unclear. Non-randomized and randomized studies were often performed in single and highly specialized centers. The purpose of this study was to investigate 1) the efficacy and toxicity of preoperative docetaxel-cisplatin together with radiation therapy (RT) 2) the feasibility of a complex preoperative strategy in a community-based multicenter setting. Methods: Eligibility criteria: resectable, locally advanced (uT3 or uN1, T4 if deemed resectable) squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the thoracic esophagus or gastroesophageal junction (Siewert type l); staged by EUS, CT and PET scan; age 18–70y; PS <2; normal organ functions. Treatment: 2 cycles of docetaxel 75mg/m2 and cisplatin 75mg/m2 q3w, followed by weekly x5 docetaxel 20mg/m2 and cisplatin 25mg/m2 with concomitant 45 Gy RT in 25 fractions; surgery 3- 8 weeks after RT. A two stage-design was used with two primary endpoints: 1) efficacy (TRG : tumor regression grade ); 2) feasibility (successful completion of entire therapy and being alive 30 days after surgery). Results: 66 pts, 56 males, were included from 11 institutions; median age 61y (35–70y); AC 53%; SCC 46%; 53 pts (80%) completed the preoperative therapy, underwent resection and were alive 30 days after surgery; 10 pts (15%) had no resection (4 progressive disease, 4 medical reasons, 2 patient’s refusal). Of 56 (85%) pts who had surgery, 51 pts had RO-resection (91%), 5 pts (9%) died due to complications after surgery (3 after > 30 days). Conclusion: Our trimodality treatment shows encouraging antineoplastic activity with 57% histopathological responders (TRG1 and 2) and acceptable feasibility in a community-based multicenter setting. [Table: see text] No significant financial relationships to disclose.

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Preoperative induction chemotherapy with docetaxel-cisplatin followed by concurrent docetaxel-cisplatin and radiation therapy (RT) in patients with locally advanced esophageal cancer: Final results of the multicenter phase ll trial SAKK 75/02

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.4550 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 4550-4550 ◽

Cited By ~ 3

Author(s):

J. C. Schuller ◽

S. Balmer-Majno ◽

W. Mingrone ◽

V. Hess ◽

R. von Moos ◽

...

Keyword(s):

Esophageal Cancer ◽

Radiation Therapy ◽

Induction Chemotherapy ◽

Locally Advanced ◽

Advanced Esophageal Cancer ◽

Multicenter Phase ◽

Locally Advanced Esophageal Cancer

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Randomized Phase IIB Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced Esophageal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.19.02503 ◽

2020 ◽

Vol 38 (14) ◽

pp. 1569-1579 ◽

Cited By ~ 26

Author(s):

Steven H. Lin ◽

Brian P. Hobbs ◽

Vivek Verma ◽

Rebecca S. Tidwell ◽

Grace L. Smith ◽

...

Keyword(s):

Esophageal Cancer ◽

Radiation Therapy ◽

Interim Analysis ◽

Locally Advanced ◽

Intensity Modulated Radiation Therapy ◽

Proton Beam Therapy ◽

Advanced Esophageal Cancer ◽

Intensity Modulated ◽

Locally Advanced Esophageal Cancer

PURPOSE Whether dosimetric advantages of proton beam therapy (PBT) translate to improved clinical outcomes compared with intensity-modulated radiation therapy (IMRT) remains unclear. This randomized trial compared total toxicity burden (TTB) and progression-free survival (PFS) between these modalities for esophageal cancer. METHODS This phase IIB trial randomly assigned patients to PBT or IMRT (50.4 Gy), stratified for histology, resectability, induction chemotherapy, and stage. The prespecified coprimary end points were TTB and PFS. TTB, a composite score of 11 distinct adverse events (AEs), including common toxicities as well as postoperative complications (POCs) in operated patients, quantified the extent of AE severity experienced over the duration of 1 year following treatment. The trial was conducted using Bayesian group sequential design with three planned interim analyses at 33%, 50%, and 67% of expected accrual (adjusted for follow-up). RESULTS This trial (commenced April 2012) was approved for closure and analysis upon activation of NRG-GI006 in March 2019, which occurred immediately prior to the planned 67% interim analysis. Altogether, 145 patients were randomly assigned (72 IMRT, 73 PBT), and 107 patients (61 IMRT, 46 PBT) were evaluable. Median follow-up was 44.1 months. Fifty-one patients (30 IMRT, 21 PBT) underwent esophagectomy; 80% of PBT was passive scattering. The posterior mean TTB was 2.3 times higher for IMRT (39.9; 95% highest posterior density interval, 26.2-54.9) than PBT (17.4; 10.5-25.0). The mean POC score was 7.6 times higher for IMRT (19.1; 7.3-32.3) versus PBT (2.5; 0.3-5.2). The posterior probability that mean TTB was lower for PBT compared with IMRT was 0.9989, which exceeded the trial’s stopping boundary of 0.9942 at the 67% interim analysis. The 3-year PFS rate (50.8% v 51.2%) and 3-year overall survival rates (44.5% v 44.5%) were similar. CONCLUSION For locally advanced esophageal cancer, PBT reduced the risk and severity of AEs compared with IMRT while maintaining similar PFS.

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