Conebeam CT-based Online Adaptive Radio-Therapy for Esophageal Cancer (ARTEC) (ARTEC)

Despite multimodal therapy, patients with esophageal cancer have poor prognosis with 5-year overall survival around 25%. Considering tumor-related death as main reason for high mortality rate in those patients, treatment-related cardio-pulmonary toxicities could also play a role in this regard. Online adaptive radiotherapy offers the possibility for daily re-planning and therefore helps radiation oncologists to better spare the organs at risk and reduce radiation-induced toxicity. Tha aim of ARTEC is to assess the pulmonary toxicity in patients with esophageal cancer treated with online adaptive radiotherapy.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer

Detailed Description

Esophageal cancer (EC) is currently the tenth most common cancer and sixth leading cause of cancer-related mortality worldwide. Multimodal treatment strategy consisting of surgery with pre-/perioperative Radio-/chemotherapy (RCHT) regimens the standard of care for non-metastatic locally advanced EC. However, the treatment of EC is challenging and the risk of tumor recurrence remains high. Furthermore, toxicities of such combined treatments can be substantial and there is room for optimization of RT to reduce the radiation dose to heart and lungs. While 3D-conformal radiotherapy is traditionally used for treatment of EC, modern irradiation techniques, such as intensity-modulated radiotherapy (IMRT) or volumetric intensity modulated arc therapy (VMAT), are increasingly implemented in the management of EC. The investigators know from literature that esophageal motion could be a challenge and therefore bigger margins are needed to achieve an acceptable tumor coverage. In addition to positioning and motion uncertainties, there could be a substantial inter-fractional tumor size reduction during RCHT. Tumor shrinkage can consequently lead to OARs shifting into the target volumes, which results in excess radiation dose to OARs with increased toxicity. Adaptive radiotherapy (ART) is a treatment technique to do a re-planning during the course of treatment to adjust the delivery of radiation dose based on geometrical changes of tumor and OARs. Considering the uncertainties in OAR and tumor displacement positioning, as well as tumor size reduction during RCHT, makes EC a perfect candidate for ART. This single-arm prospective study aims to assess pulmonary toxicity and dosimetrical analysis of ART for EC.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Hossein Hemmatazad, MD; Phone Number: +41 31 632 26 32; Email: Hossein.Hemmatazad@insel.ch
• Study Contact Backup: Name: Timo Nannen; Phone Number: +41 31 632 90 74; Email: timo.nannen@insel.ch

Study Locations

• Switzerland
  • Berne, Switzerland, 3010
    • Recruiting
    • Inselspital, University of Berne, Deparftment of Radio-Oncology
    • Contact: Timo Nannen; Phone Number: +41 31 632 90 74; Email: timo.nannen@insel.ch
    • Contact: Hossein Hammatazad, MD; Phone Number: +41 31 632 26 32; Email: hossein.hemmatazad@insel.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Esophageal cancer (EC) is currently the tenth most common cancer and sixth leading cause of cancer-related mortality worldwide. Multimodal treatment strategy consisting of surgery with perioperative chemotherapy or preoperative radio-chemotherapy (RCHT) regimens the standard of care for locally advanced and potentially curable EC. For patients who decline surgery or patients in poor general condition and unfit for tumor resection, definitive RCHT alone could be considered as a reasonable treatment option.

Description

Inclusion Criteria:

• Written informed consent
• Histologically confirmed diagnosis of AC (Adenocarcinoma) or SCC (squamos cell carcinoma) of the thoracic esophagus or gastroesophageal junction (Siewert I-II)
• Patients with cT2-4b cN0 cM0 or cTany cN+ cM0 or any patient with early stage EC ineligible for upfront surgery
• Age >= 18 years old
• Karnofsky Performance Status (KPS) >= 70 or ECOG (Eastern Cooperative Oncology Group) 0 - 1
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with patients before registration in the trial

Exclusion Criteria:

• Cervical esophageal cancers (15-18 cm from the incisors)
• Definitive clinical or radiologic evidence of metastatic disease
• Any active malignancy within 2 years of study registration that may alter the course of esophageal cancer treatment
• Prior thoracic radiotherapy that would result in overlap of radiation therapy fields
• Induction chemotherapy for the current malignancy prior to RCHT is allowed if last dose is no more than 90 days and no less than 10 days prior to registration
• Pregnant and/or breast-feeding females

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with pulmonary toxicity	The primary endpoint of this prospective study is pulmonary toxicity after concurrent radio-chemotherapy for patients with esophageal cancer treated with ART. According to literature, around 10 - 25%- of EC patients experience radiation induced pulmonary complications (RIPC) after combined radio-chemotherapy. However, the high rates of toxicity (up to 25%) were seen in patients irradiated with old RT techniques, such as 3D-CRT (Conformal Radiotherapy). New data, using modern RT, show much less pulmonary toxicity (10%). RIPC includes mostly radiation pneumonitis, radiation pulmonary fibrosis and pleural effusion .	Up to 12 months after RCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with pathological complete response	A pathological complete response (pCR) is defined as the lack of all signs of cancer in tissue samples removed during surgery or biopsy after treatment with RCHT. To find out if there is a pCR, a pathologist checks the tissue samples to see if there are still cancer cells left after the anticancer treatment.	Directly after surgery up to two weeks
Dosimetrical analysis between scheduled and adaptive plans	Dosimetrical analysis between scheduled and adaptive plans. We set the dosimetric goals for target volumes and OARs as follows: CTV coverage: D95% >= 100.0%*; PTV coverage: D95% >= 100.0%; PTV Dminimum: D99% >= 99.0%; PTV Dmaximum: D1.0% <= 101.0%; Heart: Dmean < 18Gy°; Lung: V20Gy < 20% and mean lung dose (MLD) < 12Gy - Liver: Dmean < 18Gy"Dose that covers 95% of target volume is equal or more than 100% of prescribed dose. "Mean Dose to the heart should be less than 18Gy "Mean dose to the liver should be less than 18Gy All these values will be extracted from treatment planning system (TPS) for both adaptive and scheduled plans. Comparing these two data sets, we will demonstrate if patients profited from OART from dosimetrical point of view	Directly after radiotherapy up to two weeks

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Study Chair: Hossein Hemmatazad, MD, Inselspital Bern, Department of Radio-Oncology

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2024
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: March 25, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Esophageal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: 2023-01833

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No