While anatomical resection is the standard treatment for early stage lung cancer, some patients cannot tolerate surgery due to comorbidities such as emphysema and heart disease. These patients are deemed medically inoperable and are generally offered conventional radiotherapy (most commonly given during 20-30 outpatient treatments) or observed without specific cancer therapy. Outcomes are not ideal with either approach. Conventional radiotherapy fails to durably control the primary lung tumor in 60% to 70% of patients.^1-3 More than half of patients ultimately die specifically from progressive lung cancer with observation^4,5 and 2-year survival is less than 40% with either approach.

Purpose Surgical resection is standard therapy in stage I non–small-cell lung cancer (NSCLC); however, many patients are inoperable due to comorbid diseases. Building on a previously reported phase I trial, we carried out a prospective phase II trial using stereotactic body radiation therapy (SBRT) in this population. Patients and Methods Eligible patients included clinically staged T1 or T2 (≤ 7 cm), N0, M0, biopsy-confirmed NSCLC. All patients had comorbid medical problems that precluded lobectomy. SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks. Results All 70 patients enrolled completed therapy as planned and median follow-up was 17.5 months. The 3-month major response rate was 60%. Kaplan-Meier local control at 2 years was 95%. Altogether, 28 patients have died as a result of cancer (n = 5), treatment (n = 6), or comorbid illnesses (n = 17). Median overall survival was 32.6 months and 2-year overall survival was 54.7%. Grade 3 to 5 toxicity occurred in a total of 14 patients. Among patients experiencing toxicity, the median time to observation was 10.5 months. Patients treated for tumors in the peripheral lung had 2-year freedom from severe toxicity of 83% compared with only 54% for patients with central tumors. Conclusion High rates of local control are achieved with this SBRT regimen in medically inoperable patients with stage I NSCLC. Both local recurrence and toxicity occur late after this treatment. This regimen should not be used for patients with tumors near the central airways due to excessive toxicity.

Introduction: Stereotactic body radiation therapy (SBRT) uses advanced technology to deliver a potent ablative dose to deep-seated tumors in the lung, liver, spine, pancreas, kidney, and prostate. Methods: SBRT involves constructing very compact high-dose volumes in and about the tumor. Tumor position must be accurately assessed throughout treatment, especially for tumors that move with respiration. Sophisticated image guidance and related treatment delivery technologies have developed to account for such motion and efficiently deliver high daily dose. All this serves to allow the delivery of ablative dose fractionation to the target capable of both disrupting tumor mitosis and cellular function. Results: Prospective phase I dose-escalation trials have been carried out to reach potent tumoricidal dose levels capable of eradicating tumors with high likelihood. These studies indicate a clear dose-response relationship for tumor control with escalating dose of SBRT. Prospective phase II studies have been reported from several continents consistently showing very high levels of local tumor control. Although late toxicity requires further careful assessment, acute and subacute toxicities are generally acceptable. Patterns of toxicity, both clinical and radiographic, are distinct from those observed with conventionally fractionated radiotherapy as a result of the unique biologic response to ablative fractionation. Conclusion: Prospective trials using SBRT have confirmed the efficacy of treatment in a variety of patient populations. Although mechanisms of ablative-dose injury remain elusive, ongoing prospective trials offer the hope of finding the ideal application for SBRT in the treatment arsenal.

Purpose: Patients with stage IV non–small-cell lung cancer (NSCLC) who progress through first-line therapy have poor progression-free survival (PFS) and overall survival (OS), most commonly failing in original sites of gross disease. Cytoreduction with stereotactic body radiation therapy (SBRT) may help systemic agents delay relapse. Patients and Methods: Patients in our single arm phase II study had stage IV NSCLC with no more than six sites of extracranial disease who failed early systemic chemotherapy and were able to receive SBRT and concurrent erlotinib until disease progression. After erlotinib commencement, SBRT with equipotent fractionation was delivered to all sites of disease. PFS, OS, and other end points were evaluated. Results: Twenty-four patients (13 men and 11 women) with a median age of 67 years (range, 56-86 years) were enrolled with median follow-up of 11.6 months. All patients had progressed through platinum-based chemotherapy. A total of 52 sites were treated with 16 of 24 patients receiving SBRT to more than one site. Lung parenchyma was most often irradiated. Median PFS was 14.7 months, and median OS was 20.4 months. Most patients progressed in new distant sites with only three of 47 measurable lesions recurring within the SBRT field. Two grade 3 toxicities were radiation related. Zero of 13 patients tested were positive for an EGFR mutation. Conclusion: Use of SBRT with erlotinib for unselected patients with stage IV NSCLC as a second- or subsequent line therapy resulted in dramatic changes in patterns of failure, was well tolerated, and resulted in high PFS and OS, substantially greater than historical values for patients who only received systemic agents.

Stereotactic body radiation therapy (SBRT) is generally a tumor-ablative radiation modality using essential technologies capable of accurately and precisely damaging the target with a high dose while geometrically sparing innocent normal tissues. The intent, conduct, and tissue biology are all dramatically distinct from conventionally fractionated radiotherapy such that new understanding is required for its optimization. It is most practical, tolerable, and tumoricidal in its most potent form treating tumors in the lung and liver. However, it is increasingly being used for tumors adjacent to bowels and nervous tissue, albeit with somewhat less ablative potency. Its strengths include high rates of tumor eradication via a noninvasive, convenient outpatient treatment. Its weakness relates to the possibility of causing difficult-to-manage toxicity (eg, ulceration, stenosis, fibrosis, and even necrosis) that may occur considerably later after treatment, particularly in the vicinity of the body's many tubular structures (eg, organ hila, bowel). However, clinical trials in a variety of organs and sites have shown SBRT to result in good outcomes in properly selected patients. Given its short course, lack of need for recovery, and favorable overall toxicity profile, there is great hope that SBRT will find a prominent place in the treatment of metastatic cancer as a consolidative partner with systemic therapy. With considerable published experience, available required technologies and training, and many patients in need of local therapy, SBRT has found a place in the routine cancer-fighting arsenal.