Hotspot Stereotactic Ablative Radiotherapy Versus Traditional Stereotactic Ablative Radiotherapy for the Treatment of Early-Stage Non-Small Cell Lung Cancer

(PRESTO) A Randomized Phase II Trial Evaluating Hotspots in Stereotactic Ablative Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

This clinical trial compares stereotactic ablative radiotherapy (SBRT) with hot spots to standard of care SBRT for the treatment of patients with early-stage non-small cell lung cancer. SBRT with hot spots intentionally makes sure the tumor gets a higher radiation dose during treatment. This potentially may result in better control of the tumor, but also more side effects. SBRT with or without hot spots may be more effective in treating patients with early-stage non-small cell lung cancer, compared to standard of care SBRT.

Study Overview

• Status: Not yet recruiting
• Conditions: Stage II Lung Cancer AJCC v8; Stage I Lung Cancer AJCC v8; Early Stage Lung Non-Small Cell Carcinoma
• Intervention / Treatment: Procedure: Biospecimen Collection; Other: Survey Administration; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Procedure: Lymph Node Biopsy; Radiation: Stereotactic Body Radiation Therapy; Radiation: Stereotactic Body Radiation Therapy

Detailed Description

PRIMARY OBJECTIVE:

I. Evaluate the impact of incorporating high isodoses termed "hot spots" in radiation therapy planning on local control.

SECONDARY OBJECTIVES:

I. Evaluate the impact of "hot spots" in radiation therapy planning on progression-free survival (PFS).

II. Evaluate the impact of "hot spots" in radiation therapy planning on overall survival (OS).

III. Evaluate the impact of tumor size on local control and if hotspot grouping impacts local control in a size-dependent manner.

IV. To prospectively evaluate the PFS in early stage-non small cell lung cancer (ES-NSCLC) patients undergoing SABR who are already taking a beta-blocker as well as a potential interaction between beta-blocker usage and the perceived stress scale.

V. Will evaluate for any potential interactions between quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer [EORTC QLQ-LC13]) and hotspot grouping.

VI. Evaluate the impact of "hot spots" in radiation therapy planning on toxicity by total number of grade 3+ adverse effects.

EXPLORATORY OBJECTIVE:

I. Change in immune cell marker levels at week 12 post-SBRT (± 1 week) versus baseline, such as mediators of tumor antigen presentation, costimulatory molecules, immune effector cell populations, including CD4+ and CD+8 T-cells, T regulatory cells (CD4+CD25+FoxP3+), natural killer (NK) cells, monocytes, macrophages, dendritic cells (DCs) and myeloid derived suppressor cells (MDSCs).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive standard of care (SOC) SBRT for 1-5 fractions over 1-11 days, in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan with or without positron emission tomography (PET) scan and blood sample collection throughout the study. Patients may undergo lymph node sampling throughout the study.

ARM II: Patients receive hot spot SBRT for 1-5 fractions over 1-11 days, in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan with or without PET scan and blood sample collection throughout the study. Patients may undergo lymph node sampling throughout the study.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 3-6 months up to month 36.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
      • Contact: Mark Farrugia; Phone Number: 716-845-1179; Email: Mark.Farrugia@RoswellPark.org
      • Principal Investigator: Mark Farrugia

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Diagnosed with T1-3N0 biopsy-proven NSCLC of the lung. Multiple primary lung tumors are allowed; however, each lesion requires histologic confirmation
• Metachronous lung tumors as defined as a new lung lesion in the setting of a historically treated lung cancer are allowed under certain conditions. The previous lung cancer must have been treated greater than 6 months prior to protocol therapy and this cancer must be considered controlled
• Eligible for SABR
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Patients with a history of a prior lung cancer will be excluded only if the previous treatment is within 6 months of the protocol therapy
• Mixed small cell and non-small cell lung cancer
• History of allogeneic organ transplantation
• History of primary immunodeficiency
• Patients must not have undergone prior radiation to overlapping regions of the chest that, in the opinion of the treatment physician, will interfere with protocol treatment
• Active autoimmune disease that has required systemic treatment in the last 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
• Known EGFR or ALK mutation
• Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
• Pregnant or nursing female participant
• Unwilling or unable to follow protocol requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aim II (hot spot SBRT); Patients receive hot spot SBRT for 1-5 fractions over 1-11 days, in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan with or without PET scan and blood sample collection throughout the study. Patients may undergo lymph node sampling throughout the study.	Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Other: Survey Administration; Ancillary studies; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Procedure: Lymph Node Biopsy; Undergo lymph node sampling; Other Names: Biopsy of Lymph Node; Radiation: Stereotactic Body Radiation Therapy; Receive SOC SBRT; Other Names: SBRT; SABR; Stereotactic Ablative Body Radiation Therapy; Radiation: Stereotactic Body Radiation Therapy; Receive hot spot SBRT; Other Names: SBRT; SABR; Stereotactic Ablative Body Radiation Therapy
Experimental: Arm I (SOC SBRT); Patients receive SOC SBRT for 1-5 fractions over 1-11 days, in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan with or without PET scan and blood sample collection throughout the study. Patients may undergo lymph node sampling throughout the study.	Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Other: Survey Administration; Ancillary studies; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Procedure: Lymph Node Biopsy; Undergo lymph node sampling; Other Names: Biopsy of Lymph Node; Radiation: Stereotactic Body Radiation Therapy; Receive SOC SBRT; Other Names: SBRT; SABR; Stereotactic Ablative Body Radiation Therapy; Radiation: Stereotactic Body Radiation Therapy; Receive hot spot SBRT; Other Names: SBRT; SABR; Stereotactic Ablative Body Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression (local control)	Defined as no failure within the radiotherapy planning target volume (PTV), based on the international consensus on assessing local failure after stereotactic ablative radiotherapy (SBRT) will be utilized. The 2-year local control rates will be summarized by treatment arms using 90% Clopper-Pearson confidence intervals. The local control rates between arms will be compared using one-sided Cochrane-Mantel-Haenszel test (alpha=0.1), stratified by performance status, surgery candidacy, and beta-blocker usage.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Will be summarized by treatment arms using the Kaplan-Meier product limit estimator.	From the start of treatment to first documented disease progression, or death due to any cause, up to 3 years
Overall survival (OS)	Will be summarized by treatment arms using the Kaplan-Meier product limit estimator. One-sided log-rank test stratified by tumor size, performance status, and surgery candidacy will be used to compare the OS between treatment arms (alpha=0.1).	From the start of treatment to patient death due to any cause, up to 3 years
Time to progression (local control) in a size-dependent manner	Defined as no failure within the radiotherapy PTV, based on the international consensus on assessing local failure after SBRT will be utilized.	Up to 3 years
PFS for patients who are already taking a beta blocker		Up to 3 years
Perception of Stress using Perceived Stress Scale	Will be measured by The Perceived Stress Scale (PSS) which assesses the perception of stress. The scale is constituted by 10 items that are self-rated by the subject on a 0-4 Likert scale. The scale minimum total score is 0, the maximum is 40. Higher total scores indicate a worse outcome	Up to 3 years
Change in Quality of life	Assessed via European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer.	Up to 3 years
Incidence of grade 3+ adverse events	Toxicities and adverse events (as per Common Terminology for Adverse Events version 5.0) will be summarized by the treatment arms, type, incidence, severity, seriousness, and relatedness. The rate of grade ≥ 3 AEs will be summarized as proportions with 90% Clopper Pearson confidence intervals.	Up to 3 years

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: Mark Farrugia, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 25, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: July 14, 2026
• First Submitted That Met QC Criteria: July 17, 2026
• First Posted (Actual): July 22, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 17, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Biopsy; Cytodiagnosis; Diagnostic Techniques, Surgical; Chemistry Techniques, Analytical; Spectrum Analysis; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Lymph Node Excision; Specimen Handling; Magnetic Resonance Spectroscopy; Radiosurgery; Sentinel Lymph Node Biopsy
• Other Study ID Numbers: I-4050824 (Other Identifier: Roswell Park Cancer Institute); NCI-2026-04889 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes