Stereotactic Body Radiation Therapy in Treating Patients With Inoperable Stage I or Stage II Non-Small Cell Lung Cancer

A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients With Medically Inoperable Stage I/II Non-Small Cell Lung Cancer

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Stereotactic body radiation therapy may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue.

PURPOSE: This phase II trial is studying how well stereotactic body radiation therapy works in treating patients with inoperable stage I or stage II non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Radiation: stereotactic body radiation therapy

Detailed Description

OBJECTIVES:

Primary

• Determine whether treatment with stereotactic body radiotherapy results in acceptable local control (i.e., ≥ 80%) in patients with medically inoperable stage I or II non-small cell lung cancer.

Secondary

• Determine treatment-related toxicity in patients treated with this therapy.
• Determine disease-free survival, overall survival, and patterns of failure in patients treated with this therapy.

OUTLINE: This is a multicenter study.

Patients receive 3 fractions of stereotactic body radiotherapy over 8-14 days in the absence of disease progression or unacceptable toxicity.

Patients are followed up at 6 and 12 weeks, every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study within 26 months.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M.D. Anderson Cancer Center at University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

  • The following primary cancer subtypes are eligible:

    • Squamous cell carcinoma
    • Adenocarcinoma
    • Large cell carcinoma
    • Bronchoalveolar cell carcinoma
    • Non-small cell carcinoma not otherwise specified

• Stage I or II disease based on 1 of the following tumor node metastasis (TNM) stage criteria:

  • T1, N0, M0
  • T2 (≤ 5 cm), N0, M0
  • T3 (≤ 5 cm), N0, M0 (chest wall primary tumors only)
• No primary tumor of any T-stage within or touching the zone of the proximal bronchial tree* NOTE: *Defined as a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, and right and left lower lobe bronchi)
• No primary T3 tumors involving the central chest (≤ 2 cm toward carina invasion) or structures of the mediastinum
• Any hilar or mediastinal lymph nodes > 1 cm on CT scan OR demonstrating suspicious uptake on positron-emission tomography scan must be biopsied and confirmed negative for NSCLC
• The primary tumor must be deemed technically resectable with a reasonable possibility of obtaining a gross total resection with negative margins (defined as a potentially curative resection (PCR))

• Deemed medically inoperable based on pulmonary function for surgical resection of NSCLC secondary to an underlying physiological problem, including any of the following medical conditions*:

  • Baseline forced expiratory volume (FEV)_1< 40% of predicted
  • Postoperative predicted FEV_1 < 30% of predicted
  • Severely reduced diffusion capacity
  • Baseline hypoxemia and/or hypercapnia
  • Exercise oxygen consumption < 50% of predicted
  • Severe pulmonary hypertension
  • Diabetes mellitus with severe end organ damage
  • Severe cerebral, cardiac, or peripheral vascular disease
  • Severe chronic heart disease NOTE: *Patients who refuse a PCR due to preference, ideology, emotional or psychological issues, mental illness, or inability to give informed consent are not eligible
• No evidence of regional or distant metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• See Disease Characteristics
• No active pericardial infection

Pulmonary

• See Disease Characteristics
• No active pulmonary infection

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active systemic infection
• No other concurrent illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent biologic therapy
• No concurrent vaccine therapy

Chemotherapy

• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior lung or mediastinal radiotherapy
• No concurrent standard fractionated radiotherapy
• No concurrent intensity modulated radiotherapy
• No concurrent cobalt-60 or charged particle beams (including electrons, protons, or heavier ions)

Surgery

• See Disease Characteristics
• No concurrent surgery

Other

• No other concurrent antineoplastic therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Stereotactic body radiation therapy (SBRT); 20 Gy per fraction for 3 fractions over 1.5-2 weeks, for a total of 60 Gy	Radiation: stereotactic body radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Control at 2 Years	Local control is defined as absence of local failure, which is defined as the combination of primary tumor failure (PTF) or involved lobe failure (ILF). PTF was defined based on meeting two criteria: 1. Local enlargement defined as ≥ 20% increase in the longest diameter of the gross tumor volume (GTV) per computerized tomography (CT), and 2. Evidence of tumor viability. Tumor viability could be affirmed by either demonstrating positron emission tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, or by repeat biopsy confirming carcinoma. PTF included marginal failures occurring within 1 cm of the planning target volume (PTV). ILF is defined as failure beyond the primary tumor but within the involved lobe. Local control time is defined as time from start of treatment to the the date of local recurrence, last known follow-up (censored), or death without local failure (censored). Rates are estimated using the Kaplan-Meier method.	From the start of treatment to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects With Specified Adverse Events	Specified adverse events are defined as any treatment-related adverse events that are grade 4, grade 5, or any of the following treatment-related grade 3 adverse events: Gastrointestinal: dysphagia, esophagitis, esophageal stricture, esophageal ulceration;; Cardiac: pericarditis, pericardial effusion, cardiomyopathy, ventricular dysfunction;; Neurologic: myelitis, neuropathy (cranial and motor); Hemorrhage: pulmonary or upper respiratory; Pulmonary: decline in pulmonary function as measured by pulmonary function tests, pneumonitis, pulmonary fibrosis, hypoxemia, pleural effusion. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The Common Terminology Criteria for Adverse Events (CTCAE) v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.	From randomization to last follow-up. Analysis occurred after all patients had been on study for at least 2 years. Maximum follow-up at time of analysis was 4.2 years.
Rate of Local Recurrence at 2 Years	Local failure is defined as the combination of primary tumor failure (PTF) or involved lobe failure (ILF). PTF was defined based on meeting two criteria: 1. Local enlargement defined as ≥ 20% increase in the longest diameter of the gross tumor volume (GTV) per computerized tomography (CT), and 2. Evidence of tumor viability. Tumor viability could be affirmed by either demonstrating positron emission tomography (PET) imaging with uptake of a similar intensity as the pretreatment staging PET, or by repeat biopsy confirming carcinoma. PTF included marginal failures occurring within 1 cm of the planning target volume (PTV). ILF is defined as failure beyond the primary tumor but within the involved lobe. Time to local recurrence is defined as time from start of treatment to the the date of local recurrence, last known follow-up (censored), or death without local recurrence (censored).	From the start of treatment to 2 years
Rate of Regional Recurrence at 2 Years	Regional recurrence is defined as hilar, mediastinal, and supraclavicular nodal failure.Time to regional recurrence is defined as time from start of treatment to the date of first regional recurrence, last known follow-up (censored), or death without regional recurrence (competing risk). Rates are estimated using the cumulative incidence method.	From the start of treatment to 2 years
Rate of Disseminated Recurrence at 2 Years	Disseminated recurrence is defined as uninvolved lobe failures and failures beyond the lungs and regional lymph nodes. Time to disseminated recurrence is defined as time from start of treatment to the the date of disseminated recurrence, last known follow-up (censored), or death without disseminated recurrence (competing risk). Rates are estimated using the cumulative incidence method.	From the start of treatment to 2 years
Rate of Disease-free Survival at 2 Years	Disease is defined as local or regional progression or development of distant metastases. Disease-free survival time is defined as time from start of treatment to the date of disease, death, or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method.	From the start of treatment to 2 years
Rate of Overall Survival at 2 Years	Overall survival time is defined as time from start of treatment to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.	From the start of treatment to 2 years

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Hurkmans CW, Cuijpers JP, Lagerwaard FJ, Widder J, van der Heide UA, Schuring D, Senan S. Dosimetric evaluation of heterogeneity corrections for RTOG 0236: stereotactic body radiotherapy of inoperable Stage I-II non-small-cell lung cancer. In reply to Dr. Xiao et al. Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):318; author reply 318. doi: 10.1016/j.ijrobp.2009.05.050. No abstract available.
• Timmerman R, Galvin J, Michalski J, Straube W, Ibbott G, Martin E, Abdulrahman R, Swann S, Fowler J, Choy H. Accreditation and quality assurance for Radiation Therapy Oncology Group: Multicenter clinical trials using Stereotactic Body Radiation Therapy in lung cancer. Acta Oncol. 2006;45(7):779-86. doi: 10.1080/02841860600902213.
• Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, Fakiris A, Bezjak A, Videtic G, Johnstone D, Fowler J, Gore E, Choy H. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 2010 Mar 17;303(11):1070-6. doi: 10.1001/jama.2010.261.
• Xiao Y, Papiez L, Paulus R, Timmerman R, Straube WL, Bosch WR, Michalski J, Galvin JM. Dosimetric evaluation of heterogeneity corrections for RTOG 0236: stereotactic body radiotherapy of inoperable stage I-II non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2009 Mar 15;73(4):1235-42. doi: 10.1016/j.ijrobp.2008.11.019.
• Timmerman RD, Paulus R, Galvin J, et al.: Toxicity analysis of RTOG 0236 using stereotactic body radiation therapy to treat medically inoperable early stage lung cancer patients. [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-151, S86, 2007.

Study record dates

Study Major Dates

• Study Start: May 1, 2004
• Primary Completion (ACTUAL): March 1, 2010
• Study Completion (ACTUAL): December 1, 2016

Study Registration Dates

• First Submitted: July 8, 2004
• First Submitted That Met QC Criteria: July 9, 2004
• First Posted (ESTIMATE): July 12, 2004

Study Record Updates

• Last Update Posted (ACTUAL): January 16, 2019
• Last Update Submitted That Met QC Criteria: December 21, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: squamous cell lung cancer; large cell lung cancer; adenocarcinoma of the lung; stage I non-small cell lung cancer; stage II non-small cell lung cancer; bronchoalveolar cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: RTOG-0236; CDR0000371578