Stereotactic Body Radiotherapy (SBRT) for Early-Stage Non-small Cell Lung Cancer (NSCLC)(beta)
Medically Operable Patients
Patients with stage I NSCLC should be evaluated by a thoracic surgeon, preferably within a multidisciplinary cancer care team, to determine operability. The decision to undergo an operation should be made by the surgeon and patient, in collaboration with family members.
For patients with standard operative risk and stage I NSCLC, SBRT is not recommended as an alternative to surgery outside of a clinical trial. Discussions about SBRT among members of the multidisciplinary cancer care team may be appropriate. For this population, lobectomy with systematic mediastinal/hilar lymph node evaluation remains the recommended treatment, though a sublobar resection may be considered in select clinical scenarios.
For patients with high operative risk stage I NSCLC, discussions about SBRT as a potential alternative to surgery are encouraged within the multidisciplinary cancer care team. In cases where SBRT is offered, patients should be informed that while SBRT may have decreased risks from treatment in the short term, the longer-term outcomes >3 years are not well established.
Where multidisciplinary consultation and patient preference result in a decision to perform resection in high operative risk patients, limited resection (segmentectomy or wedge resection), rather than lobectomy, is more commonly selected. At this time, there have been no prospective randomized trials completed that directly compare limited resection with SBRT [ASCO qualifying statement].
Longer-term data from the RTOG 0236 phase II trial of inoperable T1-T2N0M0 tumors ≤5 cm showed that rates of 5-year primary tumor, in-lobe, and locoregional failure were 7%, 20%, and 38%, respectively. Overall survival at 5 years was 40%. Treatment-related grade 3, grade 4, and grade 5 adverse events were reported in 27%, 4%, and 0% of patients, respectively [ASCO qualifying statement].
While there is no universally accepted definition, high operative risk has been defined by various studies as “Forced expiratory volume in one second (FEV1) <50% predicted, diffusing capacity of the lungs for carbon monoxide <50% predicted, or a combination of advanced age, impaired pulmonary function, pulmonary hypertension, and poor left ventricular function. A thoracic surgeon who specializes in lung resections remains the best person to assess operative risk” (Videtic 2017) [ASTRO qualifying statement].
Medically Inoperable Patients
SBRT directed toward centrally located lung tumors carries unique and significant risks when compared with treatment directed at peripherally located tumors. The use of 3 fraction regimens is not recommended in this setting.
There is a significant rate of nodal disease in this population; therefore, pretreatment staging with PET/CT and invasive mediastinal/hilar staging with endobronchial ultrasound/mediastinoscopy is recommended [ASCO qualifying statement].
Providers should use caution when considering SBRT for central tumors. Delivery of SBRT in more than 3 (i.e., 4 or 5) fractions may reduce the risk of severe toxicity. Adherence to volumetric and maximum dose constraints may optimize the safety profile of this treatment. For central tumors for which SBRT is deemed too high-risk (e.g. tumors directly abutting or invading the esophagus or proximal bronchial tree), hypofractionated radiotherapy utilizing 6-15 fractions or conventionally fractionated radiotherapy may be considered.
Caution is recommended due to the potential for serious toxicity to normal centrally located tissues. “In this setting, adequate informed consent to patients—including a discussion of patient risk tolerance and goals of care—is a necessary part of communication between radiation oncologists and patients” (Videtic 2017) [ASTRO qualifying statement].
The RTOG 0813 phase I/II study aimed to evaluate escalating radiation doses ranging from 50 to 60 Gy in five fractions delivered every other day to central tumors ≤5 cm (including tumors within 2 cm of the tracheobronchial tree, and abutting the pericardium, mediastinum, or spine). Four patients, including one treated to 10.5 Gy × 5, two treated to 11.5 Gy × 5, and one treated to 12 Gy × 5, experienced grade 5 or fatal adverse events, while those treated at the lowest dose level did not experience any grade ≥3 events. We are currently awaiting mature, long-term efficacy results presented in full manuscript form from this trial. These results will be used to determine whether there is a dose that results in an acceptable balance of tumor control and toxicity [ASCO qualifying statement].
SBRT may be an appropriate option for select tumors >5 cm in diameter with an acceptable therapeutic ratio. Therapeutic ratio refers to a treatment schedule that balances maximizing tumor cell kill while minimizing radiation-induced acute and late morbidity to surrounding critical structures. Adherence to volumetric and maximum dose constraints may optimize the safety profile of this treatment.
There is a significant rate of nodal disease in this population; therefore, accurate pretreatment invasive mediastinal/hilar staging with endobronchial ultrasound/mediastinoscopy is recommended [ASCO qualifying statement].
Whenever possible, obtain a biopsy prior to treatment with SBRT to confirm a histologic diagnosis of a malignant lung nodule.
SBRT may be delivered in patients who refuse a biopsy, have undergone nondiagnostic biopsy, or who are thought to be at prohibitive risks of biopsy. Prior to SBRT in patients lacking tissue confirmation of malignancy, treatment options should be discussed within a multidisciplinary cancer care team with a consensus that the lesion is radiographically and clinically consistent with a malignant lung lesion based on tumor, patient, and environmental factors.
Tumor-specific factors to consider include lesion size, growth over time, presence of spiculations or lack of benign-appearing calcifications, PET avidity, and lesion location. Other patient-specific factors, such as smoking history or history of prior lung cancers, should also be considered. Regional environmental factors, such as the incidence of histoplasmosis, may affect the probability that a lesion is malignant and should also be considered in the calculation of obtaining histologic confirmation [ASTRO qualifying statement].
Patients should be staged with PET/CT and mediastinal/hilar nodal sampling when feasible [ASCO qualifying statement].
For patients deemed to be at prohibitive risk of biopsy, a multidisciplinary discussion should occur to ensure that safe means of obtaining tissue are not feasible (e.g. transbronchial biopsy, etc). In addition, consideration should also be given as to whether SBRT would pose prohibitive risks. The goals, expectations, and potential increased risks of SBRT should be carefully weighed and discussed with the patient and family in the context of shared decision making [ASCO qualifying statement].
Multiple primary lung cancers can be difficult to differentiate from intrathoracic metastatic lung cancer and pose unique issues for parenchymal preservation; therefore, it is recommended that they are evaluated by a multidisciplinary cancer care team.
PET/CT and brain MRI are recommended in patients suspected of having multiple primary lung cancer to help differentiate from intrathoracic metastatic lung cancer. Invasive mediastinal/hilar staging with endobronchial ultrasound/mediastinoscopy should be strongly considered.
SBRT may be considered by the multidisciplinary cancer care team as a potentially curative treatment option for patients with synchronous multiple primary lung cancer.
SBRT for synchronous multiple primary lung cancer has equivalent rates of local control and may have comparable toxicity but decreased rates of overall survival compared with SBRT for single tumors. The decision to treat multiple lesions with SBRT is an individualized process that should be discussed by a multidisciplinary cancer care team, as this approach may increase radiation doses to normal tissues and increase the risk of toxicity in some cases [ASTRO qualifying statement].
SBRT may be considered by the multidisciplinary cancer care team as a potentially curative treatment option for patients with metachronous multiple primary lung cancer.
SBRT may be considered by the multidisciplinary cancer care team as a potentially curative treatment option for patients with metachronous multiple primary lung cancer in a postpneumonectomy setting.
“While SBRT for metachronous multiple primary lung cancer appears to have equivalent rates of local control and acceptable toxicity compared to single tumors, SBRT in the postpneumonectomy setting might have a higher rate of toxicity than in patients with higher baseline lung capacity" (Videtic 2017). Delivery of SBRT would depend on tumor location, size, and patient comorbidities, and patients should be thoroughly evaluated by a multidisciplinary cancer care team [ASTRO qualifying statement].
“Generally, great caution should be taken to minimize the dose to the single lung, as high grade radiation pneumonitis in a single lung may be a serious and potentially life-threatening toxicity” (Videtic 2017). The potential for radiation pneumonitis should be discussed with patients, and a pulmonary evaluation should be obtained, including pulmonary function tests and consideration of a pulmonary evaluation by a dedicated pulmonologist [ASTRO qualifying statement].
Medically Inoperable Patients in High-risk Clinical Scenarios
Providers should use caution when considering SBRT for tumors in close proximity to the proximal bronchial tree. Delivery of SBRT in 4-5 fractions may reduce the risks of severe toxicity. Physicians should endeavor to meet the constraints that have been used in prospective studies, given the severe toxicities that have been reported
There are a limited number of retrospective studies that report the use of SBRT in patients with tumors abutting the proximal bronchial tree. Patients with tumors abutting the proximal airways should be counseled about the potential for fatal treatment complications, even when dose constraints and highly conformal SBRT techniques are used [ASTRO qualifying statement].
Appropriate staging, including PET/CT and invasive mediastinal/hilar staging with endobronchial ultrasound/mediastinoscopy, are recommended due to the high risk of nodal disease in this patient population [ASCO qualifying statement].
Where a discussion within the multidisciplinary cancer care team results in a recommendation for SBRT for tumors in close proximity to the esophagus, physicians should endeavor to meet the constraints that have been used in prospective studies or otherwise reported in the literature, given the severe esophageal toxicities that have been reported.
Severe, life-threatening esophageal toxicity is possible after SBRT. Despite limited data to support firm recommendations, dose to the esophagus should be carefully assessed and minimized. Highly conformal techniques can be used to facilitate esophageal avoidance with central tumors [ASTRO qualifying statement].
For tumors in close proximity to the heart and pericardium, SBRT should be delivered in 4-5 fractions with low incidence of serious toxicities to the heart, pericardium, and large vessels observed. Adherence to volumetric and maximum dose constraints used in prospective trials or reported in the literature may optimize the safety profile of this treatment.
SBRT is an appropriate option for treatment and may be offered for T1-2 tumors that abut the chest wall. Grade 1 and 2 chest wall toxicity, presenting most commonly as pain due to rib fracture or irritation of the intercostal nerves, is a common occurrence post SBRT that usually resolves with conservative management. Patients with peripheral tumors approximating the chest wall should be counseled on the possibility of this common toxicity.
The volume of chest wall receiving SBRT has been identified as a predictor of chest wall toxicity; however, the use of highly conformal techniques to reduce this volume may increase dose to the ipsilateral lung. Thus “compromising coverage of the planning target volume (PTV) or PTV trimming away from the chest wall are not favored as techniques to meet chest wall constraints” (Videtic 2017) [ASTRO qualifying statement].
The use of salvage SBRT after primary conventionally fractionated radiation may be offered to selected patients who are identified as appropriate candidates following a discussion among members of the multidisciplinary cancer care team.
Patients should be informed of the risk of significant (including fatal) toxicities associated with SBRT as salvage therapy after conventionally fractionated radiation [ASTRO qualifying statement].
“For centrally located salvage SBRT after an in-field recurrence, … severe toxicities were more common than some other retrospective reports and included a 23% grade 3 pneumonitis risk, 6% grade 5 pneumonitis risk, and 6% grade 5 hemoptysis risk. The authors conclude that local control can be achieved but that the high-risk nature of these central in-field recurrences warrants caution due to significant risk of grade 5 fatal events" (Videtic 2017) [ASTRO qualifying statement].
Patient selection for salvage SBRT after prior treatment, including primary conventionally fractionated radiation, SBRT, or sublobar resection, is a highly individualized process. Radiation oncologists should assess evidence-based patient, tumor, and treatment factors prior to treatment initiation.
“Salvage SBRT treatment plans should ideally be reviewed with medical physics and other radiation oncologists (in a peer review quality assurance setting) to ensure high-quality results to optimize patient selection, maximize local control and survival, and minimize treatment toxicities" (Videtic 2017) [ASTRO qualifying statement].
Toxicities vary on an individual basis depending on patient’s health, prior treatment, comorbidities, etc and should be discussed within the multidisciplinary cancer care team. “Predictors of toxicity for SBRT salvage include central tumor location, in-field recurrence, larger treatment volumes, bilateral mediastinal primary planning target volume targets, composite lung V20 (the percentage of the lung volume [with subtraction of the volume involved by lung cancer] that receives radiation doses of 20 Gy or more) ≥ 30%, FEV1 ≤ 65%, and poor baseline performance status” (Videtic 2017).
How strong is the ASTRO's recommendation?