Trial Information

Role of SPECT in Radiotherapy Treatment Planning and Toxicity Evaluation for the Patients With Stage I-III NSCLC: a Randomized Phase II Trial

Primary objective:

-To compare the rate of grade 2 or higher pneumonitis amongst patients with stage III NSCLC
treated with radiotherapy using SPECT in radiotherapy treatment planning versus standard
CT-based radiotherapy planning;

Secondary Objectives:

- To evaluate SPECT as a tool to predict lung toxicity;

- To establish estimates for the incidence and severity of pulmonary tissue effects
observed in stage III NSCLC patients treated with radiotherapy;

- To generate hypotheses for subsequent use of SPECT-CT-based treatment planning as a
method for minimization of toxicity risks

- To generate hypotheses for modeling studies of SPECT-CT-based treatment planning for
dose-escalation;

- To compare the loco-regional control, time to progression and overall survival of
patients treated with SPECT-based plan versus standard CT-based plan

- To compare the quality of life in patients randomized to the two study arms.

This trial is a single center, randomized phase II study. All patients will irrespective of
their registration in the trial receive radiotherapy according to the standard treatment
regimen at the Department of Oncology, Aarhus University Hospital. Participation implies
baseline and follow-up procedures. In the treatment planning phase patients will be
randomized to one of the following arms: Arm 1 SPECT/CT-based treatment plan with functional
dose-volume parameters and Arrm 2 Standard CT-based plan with conventional dose-volume
parameters.

The trial will consist of two parts. To initiate the trial a pilot study (part 1) will be
performed to determine the feasibility in our setting at Aarhus University Hospital as it is
described in the literature. Consecutive patients will be enrolled in the pilot study during
1-year period. The interim analysis after one year of enrollment will be performed to
determine what patients are most likely to benefit from functional radiotherapy planning
based on SPECT. The main objective of this part is to determine whether V/Q-SPECT data are
valid and usable in the radiotherapy planning. The timing for acute and late follow-up SPECT
will be determined. Randomized trial (part 2) will be performed thereafter.

Statistical analysis. The randomization by permitted blocks method will be used to allocate
patients to treatment arm. Stratification factors will be age, gender, disease stage,
histology, concurrent chemotherapy and irradiated volumes.

The chi-squire test (α=0.10) with the continuity correction will be used for analysis of the
primary analysis. For all other comparisons, two-sided analyses will be performed and a
p-value of 0.05 or less will be considered statistically significant. 95% confidence
intervals will be constructed for outcomes of interest. Descriptive statistics will be used
to summarize patient characteristics and outcomes by intervention arm. Differences in
outcomes between intervention arms will be compared by using paired t-tests, Wilcoxon rank
sum tests or McNemar tests as appropriate. Adjusting for stratification factors will be
performed using logistic regression or linear regression. Time-to-event analyses will be
estimated using the Kaplan-Meier method, and compared using Cox proportional hazards
regression.

Estimation of the relationship between dose-volume parameters and toxicity will be evaluated
using logistic regression analyses. Within patients who were planned using SPECT, the
association between dose-volume parameters calculated using SPECT and those calculated under
a CT-plan will be evaluated using correlation coefficients.

All patients who are randomized will be included in the analysis of safety and efficacy
outcomes. Secondary analyses may be performed on those patients only on those who received
radiotherapy as per the treatment plan based on SPECT or CT as per the intervention arm. Any
patient who is randomized but does not receive radiotherapy based on the intervention
allocated treatment plan will be described in detail along with the reason for not receiving
the prescribed plan.