Trial Outcomes & Findings for Proton Radiotherapy for Patients With Non-Small Cell Lung Cancer (NSCLC) (NCT NCT00495040)

NCT ID: NCT00495040

Last Updated: 2019-01-14

Results Overview

Chest CT with contrast (if possible) was used for evaluation of Local control. If is suspicious for recurrence by CT image, PET or PET/CT scan is required and biopsy is recommended to confirm the recurrence. Continuing CT or PET images follow up for un-confirmed recurrent disease. Timing of recurrence: at the time of first image (PET and/or CT) showing abnormalities. PET will use for progression free survival (PFS). Participants were followed up at 6 weeks after the completion of RT, every 3 months (±1 month) for 2 years, every 6 months (±1 month) for 3 years, and then annually. The Overall survival: time of registration to the last follow-up (f/u), or lost to f/u, or death. The PFS: time of registration to any local-regional recurrence or distant metastasis. Free local recurrence rate: time of registration to local recurrence. Free regional recurrence rate: time of registration to regional recurrence. Free distant metastasis rate: time of registration to distant metastasis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

38 participants

Primary outcome timeframe

The Overall survival (OS): time of registration to the last follow-up (f/u), or lost to f/u, or death up to 5 years. The progression free survival (PFS): time of registration to any local-regional recurrence or distant metastasis up to 5 years.

Results posted on

2019-01-14

Participant Flow

(1)Inoperable NSCLC;(2)T1N0M0 (stage IA) that was centrally or superiorly located ≤ 2 cm in all directions of any critical mediastinal structure; T2N0M0 in any location (stage IB, tumor size\>3 cm, with no upper size limit), or selected T3N0M0 (stage II,chest wall, mediastinal pleura, or parietal pericardium involvement) in any location (3)ECOG≤2

Participant milestones

Participant milestones
Measure
Dose-escalated Proton Therapy for Early-stage NSCLC
35 patients were treated with 87.5 Gy at 2.5 Gy/fraction of proton therapy, with fraction given once a day, 5 days per week. The biological effective dose was 109.4 Gy using α/β of 10
Overall Study
STARTED
38
Overall Study
COMPLETED
35
Overall Study
NOT COMPLETED
3

Reasons for withdrawal

Reasons for withdrawal
Measure
Dose-escalated Proton Therapy for Early-stage NSCLC
35 patients were treated with 87.5 Gy at 2.5 Gy/fraction of proton therapy, with fraction given once a day, 5 days per week. The biological effective dose was 109.4 Gy using α/β of 10
Overall Study
Withdrawal by Subject
3

Baseline Characteristics

There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Dose-escalated Proton Therapy for Early-stage Non-small Cell l
n=35 Participants
35 patients were treated with 87.5 Gy at 2.5 Gy/fraction of proton therapy, with fraction given once a day, 5 days per week. The biological effective dose was 109.4 Gy using α/β of 10
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
2 Participants
n=5 Participants
Age, Categorical
>=65 years
33 Participants
n=5 Participants
Sex: Female, Male
Female
18 Participants
n=5 Participants
Sex: Female, Male
Male
17 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
34 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
35 Participants
n=5 Participants
Age
73 years
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Karnofsky Performance Status (KPS) Score
80 units on a scale (%)
n=5 Participants • The Karnofsky Performance Score (KPS) ranking runs from 100 to 0, where 100 is "perfect" Normal health and 0 is death. Practitioners occasionally assign performance scores in between standard intervals of 10. The KPS was to allow physicians to evaluate a patient's survival. The higher KPS scores, the better treatment outcome.
Gross Tumor Volume (GTV)
42.9 cubic centimeters
n=5 Participants • In this study, Gross tumor volume is all known gross disease as demonstrated on end ventilation data set (30% phase as determined by Varian RPM or equivalent respiratory monitoring system) of the planning 4DCT using a lung window, and modified as deemed necessary based on PET/CT, diagnostic CT and other clinical studies.
iCTV (internal Clinical Target Volume)
123 cubic centimeters
n=5 Participants • iCTV (internal Clinical Target Volume): Volume encompassing the Clinical Target Volume (CTV) and Internal Margin (IM). (iCTV = CTV + IM). In this study, the iCTV is envelope of motion of the CTV estimated by an 8-mm isotropic expansion of the iGTV to encompase microextensions of the tumor (iCTV = iGTV+8mm);
Pre-Treatment Pulmonary Function - FEV1
48 percentage of predicted (%)
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Pre-Treatment Pulmonary Function - DLCO
49 percentage of predicted (%)
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Smoking History
Yes
31 Participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Smoking History
No
4 Participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Chronic Pulmonary Disease
COPD
16 Participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Chronic Pulmonary Disease
Emphysema
3 Participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Chronic Pulmonary Disease
Pulmonary Fibrosis
1 Participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Chronic Pulmonary Disease
Normal
15 Participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Tumor Histological Type
Squamous cell carcinoma
17 Participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Tumor Histological Type
Adenocarcinoma
11 Participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Tumor Histological Type
Squamous cell carcinoma + adenocarcinoma
1 Participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Tumor Histological Type
Neuroendocrine carcinoma
1 Participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Tumor Histological Type
Non-small cell carcinoma
5 Participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Number of Participants with Tumor Location
Central or Superior
25 Participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Number of Participants with Tumor Location
Peripheral
10 Participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Number of Participants with Tumor size
≤3 cm
13 participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Number of Participants with Tumor size
>3 cm ≤ 5 cm
16 participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Number of Participants with Tumor size
>5 cm
6 participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Number of Participants with Primary Tumor (T) Stage
T1:Tumor ≤3 cm in greatest dimension
12 participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Number of Participants with Primary Tumor (T) Stage
T2:tumor>3 cm; involve: main bronchus, the viscera
20 participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Number of Participants with Primary Tumor (T) Stage
T3
3 participants
n=5 Participants • There were 35 out of 38 patients treated under the protocol and evaluable for data analysis.
Number of Participants with Clinical Stage
IA
12 participants
n=5 Participants
Number of Participants with Clinical Stage
IB
16 participants
n=5 Participants
Number of Participants with Clinical Stage
IIA
4 participants
n=5 Participants
Number of Participants with Clinical Stage
IIB
3 participants
n=5 Participants

PRIMARY outcome

Timeframe: The Overall survival (OS): time of registration to the last follow-up (f/u), or lost to f/u, or death up to 5 years. The progression free survival (PFS): time of registration to any local-regional recurrence or distant metastasis up to 5 years.

Population: Kaplan-Meier curves used for overall survival, progression-free survival, local recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival. Differences between pairs of Kaplan-Meier curves were using the log-rank test. The Fisher's exact test was used to compare local, regional, and distant recurrence rates.

Chest CT with contrast (if possible) was used for evaluation of Local control. If is suspicious for recurrence by CT image, PET or PET/CT scan is required and biopsy is recommended to confirm the recurrence. Continuing CT or PET images follow up for un-confirmed recurrent disease. Timing of recurrence: at the time of first image (PET and/or CT) showing abnormalities. PET will use for progression free survival (PFS). Participants were followed up at 6 weeks after the completion of RT, every 3 months (±1 month) for 2 years, every 6 months (±1 month) for 3 years, and then annually. The Overall survival: time of registration to the last follow-up (f/u), or lost to f/u, or death. The PFS: time of registration to any local-regional recurrence or distant metastasis. Free local recurrence rate: time of registration to local recurrence. Free regional recurrence rate: time of registration to regional recurrence. Free distant metastasis rate: time of registration to distant metastasis.

Outcome measures

Outcome measures
Measure
Dose-escalated Proton Therapy for Early-stage Non-small Cell l
n=35 Participants
35 patients were treated with 87.5 Gy at 2.5 Gy/fraction of proton therapy, with fraction given once a day, 5 days per week. The biological effective dose was 109.4 Gy using α/β of 10
Overall Survival and Progression Free Survival
Overall Survival rate : 1 year
85.70 percentage of participants (%)
Overall Survival and Progression Free Survival
Overall Survival rate : 2 year
60 percentage of participants (%)
Overall Survival and Progression Free Survival
Overall Survival rate : 3 year
42.90 percentage of participants (%)
Overall Survival and Progression Free Survival
Overall Survival rate : 5 year
28.10 percentage of participants (%)
Overall Survival and Progression Free Survival
Progression Free Survival rate : 1 year
80 percentage of participants (%)
Overall Survival and Progression Free Survival
Progression Free Survival rate : 2 year
64.40 percentage of participants (%)
Overall Survival and Progression Free Survival
Progression Free Survival rate : 3 year
53.60 percentage of participants (%)
Overall Survival and Progression Free Survival
Progression Free Survival rate : 5 year
53.60 percentage of participants (%)
Overall Survival and Progression Free Survival
free local recurrence rate 5-year
85 percentage of participants (%)
Overall Survival and Progression Free Survival
free from regional recurrence rate: 5-year
89.20 percentage of participants (%)
Overall Survival and Progression Free Survival
free from distant metastasis rate: 5-year
56 percentage of participants (%)

Adverse Events

Dose-escalated Proton Therapy for Early-stage Non-small Cell l

Serious events: 2 serious events
Other events: 0 other events
Deaths: 30 deaths

Serious adverse events

Serious adverse events
Measure
Dose-escalated Proton Therapy for Early-stage Non-small Cell l
n=35 participants at risk
35 patients were treated with 87.5 Gy at 2.5 Gy/fraction of proton therapy, with fraction given once a day, 5 days per week. The biological effective dose was 109.4 Gy using α/β of 10
Skin and subcutaneous tissue disorders
Dermatitis
2.9%
1/35 • From the time of registration to the time of the adverse event start date, up to 5 years.
Grade \> 3 acute and chronic toxicities by Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE 3.0) will be analyzed.
Respiratory, thoracic and mediastinal disorders
Pneumonitis
2.9%
1/35 • From the time of registration to the time of the adverse event start date, up to 5 years.
Grade \> 3 acute and chronic toxicities by Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE 3.0) will be analyzed.
Gastrointestinal disorders
Esophagitis
0.00%
0/35 • From the time of registration to the time of the adverse event start date, up to 5 years.
Grade \> 3 acute and chronic toxicities by Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE 3.0) will be analyzed.
Cardiac disorders
Atrial fibrillation
0.00%
0/35 • From the time of registration to the time of the adverse event start date, up to 5 years.
Grade \> 3 acute and chronic toxicities by Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE 3.0) will be analyzed.
Musculoskeletal and connective tissue disorders
Rib fracture
0.00%
0/35 • From the time of registration to the time of the adverse event start date, up to 5 years.
Grade \> 3 acute and chronic toxicities by Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE 3.0) will be analyzed.
General disorders
Chest wall pain
0.00%
0/35 • From the time of registration to the time of the adverse event start date, up to 5 years.
Grade \> 3 acute and chronic toxicities by Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE 3.0) will be analyzed.

Other adverse events

Adverse event data not reported

Additional Information

Chang,Joe Y.,M.D. / Radiation Oncology

UT MD Anderson Cancer Center

Phone: 713-563-2337

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place