Proton Beam Therapy in the Treatment of Esophageal Cancer

Not Applicable

Active, not recruiting

Conditions: Cancer of the Esophagus
Esophageal Cancer
Esophagus Cancer

Interventions: Radiation: Proton beam therapy
Other: Patient-Reported Outcome Measures

Registration Number: NCT03482791

Lead Sponsor: Washington University School of Medicine

Brief Summary: The investigators plan to include both operable and inoperable patients with esophagus cancer in this prospective trial. Since both proton and photon treatments are biologically equivalent, the investigators do not expect a difference in tumor control compared to intensity modulated radiation therapy (IMRT). The investigators have a prospective experience of physician-reported toxicity and patient outcome using IMRT for patients with inoperable esophagus cancer that will serve as a comparison group. For the resectable patients receiving trimodality therapy (chemoradiation followed by surgery), the investigators will carefully track toxicity and patient outcomes prospectively. The central hypothesis is that the biologic efficacy for tumor control should be similar between protons and photons, and therefore survival measures should be similar between the two groups, but that the main difference lies in the total severe toxicities experienced by the patients undergoing therapy.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 22

Inclusion Criteria

Histologically or cytologically documented adenocarcinoma or squamous cell carcinoma of the cervical or thoracic esophagus or gastroesophageal junction or cardia of stomach.
Staged by PET/CT and esophagogastroduodenoscopy (EGD) or endoscopic ultrasound (EUS) OR CT w/contrast and EGD to have stage II or III disease per AJCC 7th edition guidelines
Prior endoscopic mucosal resection (EMR) with a diagnosis of stage II or III esophageal cancer (AJCC 7th edition) is eligible, irrespective of margin status.
Induction chemotherapy prior to concurrent chemoradiation is allowed.
Prior thoracic radiation is allowable if degree of overlap with the esophageal radiotherapy treatment is deemed to be safe by the treating radiation oncologist.
At least 18 years of age.
ECOG performance status < 2
Normal bone marrow and organ function as defined below:
- WBC > 2,500/mcL
- Platelets > 75,000/mcl
- Total bilirubin < 1.5 x institutional upper limit of normal (IULN)
- AST(SGOT)/ALT(SGPT) < 3.0 x IULN
- Creatinine < 1.5 x IULN OR Creatinine clearance > 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
Ability to understand and willingness to sign an IRB approved written informed consent document.
English speaker.
Financial coverage for proton therapy.

Exclusion Criteria

Planned treatment with radiation therapy alone without concurrent chemotherapy or chemotherapy alone.
Previous or concomitant cancers within the past 3 years other than curatively treated carcinoma in situ of the cervix, basal cell carcinoma of the skin, curative treatment for transitional cell carcinoma of the bladder, and low risk prostate cancer. Except for prostate cancer (which can be observed if low risk), other cancers listed must have been treated in the past 3 years without evidence of recurrence at the time of registration.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia not controlled by pacer device, myocardial infarction within 3 months of registration, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 7 days of the start of treatment.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Resectable (proton beam therapy)	Patient-Reported Outcome Measures	* Proton beam therapy: total dose of 50 or 50.4 Gy * Standard of care chemotherapy - the clinical trial doesn't dictate anything about the chemotherapy given, it is the treating physician's decision * Surgery should ideally be performed no later than 8 to 10 weeks after completing chemoradiation * Patient-reported outcome measures (PROs) performed at several time points
Arm 2: Unresectable (proton beam therapy)	Proton beam therapy	* Proton beam therapy: total dose of 59.4 or 60 Gy * Standard of care chemotherapy - the clinical trial doesn't dictate anything about the chemotherapy given, it is the treating physician's decision * Patient-reported outcome measures (PROs) performed at several time points
Arm 1: Resectable (proton beam therapy)	Proton beam therapy	* Proton beam therapy: total dose of 50 or 50.4 Gy * Standard of care chemotherapy - the clinical trial doesn't dictate anything about the chemotherapy given, it is the treating physician's decision * Surgery should ideally be performed no later than 8 to 10 weeks after completing chemoradiation * Patient-reported outcome measures (PROs) performed at several time points
Arm 2: Unresectable (proton beam therapy)	Patient-Reported Outcome Measures	* Proton beam therapy: total dose of 59.4 or 60 Gy * Standard of care chemotherapy - the clinical trial doesn't dictate anything about the chemotherapy given, it is the treating physician's decision * Patient-reported outcome measures (PROs) performed at several time points

Primary Outcome Measures

Name	Time	Method
Physician-reported Toxicity of PBT for Esophageal Cancer	Through 6 months following chemoradiation (estimated to be 9 months)	Number of participants with grade 3 or higher specific cardiac, metabolism/nutrition, gastrointestinal, respiratory/thoracic/mediastinal, and skin/subcutaneous toxicity using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 related to PBT
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the MD Anderson Symptom Inventory (MDASI)-Plus	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The MDASI-Plus is a reliable, validated tool for assessing cancer-related symptoms regardless of therapy or specific cancer diagnosis. Patients are asked to fill out a twenty-seven question inventory. 21 questions ask the patient about the severity of their symptoms with answers ranging from 0=not present to 10=as bad as you can imagine. 6 questions ask the patient about how their symptoms interfered with their life with answers ranging from 0=did not interfere to 10=interfered completely. The higher the score the more severe symptom experience the patient experienced.
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the EuroQol (EQ-5D) Questionnaire	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The EQ-5D is a standardized 2-part, patient-administered instrument used for direct and indirect assessment of health state utilities. The first part asks respondents to "check the ONE box \[next to the appropriate statement\] that best describes your health TODAY" for each of 5 health dimensions, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The second part of the EQ-5D is a visual analogue scale (VAS) valuing current health state. Both the 5-item index score and the VAS score are transformed into a utility score between 0 "Worst health state" and 1 "Best health state. The higher the score the better health a patient experienced.
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the Medical Outcomes Study (MOS) Social Support Survey	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The 19-item MOS Social Support Survey was designed for use with patients with chronic diseases and measures how often different kinds of support are available, if needed. Response choices range from "none of the time" (1) to "all of the time" (5). A mean social support score for all 19 items is computed to a 0-100 scale with higher scores indicating a greater availability of social support.
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the 4-Item Center for Epidemiological Studies Depression Scale (CES-D)	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The CES-D questionnaire is a 20-item measure which evaluates depressive symptoms. This trial will make use of the validated 4-item screening version in order to reduce participant burden. Possible range of scores is 0-60, with the higher scores indicating the presence of more symptomatology.
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Mental Component Score	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher scores indicate better quality of life. MCS scores from the SF-12 are recoded, weighted, and summed, and standardized by the SF-12 scoring procedure. SF-12 is a licensed product and this procedure is implemented in the QualityMetric PRO CoRE software package. MCS range is 40-65.
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Physical Component Score	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher scores indicate better quality of life. PCS scores from the SF-12 are recoded, weighted, and summed, and standardized by the SF-12 scoring procedure. SF-12 is a licensed product and this procedure is implemented in the QualityMetric PRO CoRE software package. PCS range is 30-55.
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - General Health Score	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Lower mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-5.
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Physical Function Score	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-3.
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Physical Role Score	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-2.
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Emotional Role Score	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-2.
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Bodily Pain Score	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Lower mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-5.
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Mental Health Score	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Lower mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-6.
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Vitality Health Score	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Lower mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-6.
Change in Patient-reported Outcomes of PBT for Esophageal Cancer as Measured by the SF-12 Questionnaire - Social Functioning Score	Baseline, post completion of chemoradiation, 2 months, 4 months, 6 months, 9 months, and 12 months	The SF-12 will be measured at each of 7 interviews, and mental and physical component scores will be calculated in addition to calculating the measure's eight individual subscales (physical functioning, social functioning, role limitations due to physical problems, body pain, general health, role limitations due to emotional problems general health, vitality, and mental health). Higher mean scores indicate better quality of life. The subscales are calculated by recoding and averaging the raw scores (Likert scales) the questions associated with the subscale. Range of 1-5.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) of Proton Beam Therapy (PBT) for Patients With Resectable	5 years following chemoradiation (estimated to be 5 years and 3 months)	-PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Overall Survival (OS)of PBT for Patients With Resectable Versus Unresectable Esophageal	5 years following chemoradiation (estimated to be 5 years and 3 months)