INDICATIONS FOR RADIATION THERAPY IN LUNG CANCER
Historical
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External beam radiation therapy (EBRT) has been used for several decades for definitive and palliative treatment of non-small cell lung cancer (NSCLC) patients.
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A dose of 60 Gy (1 Gray = 100 centiGray = 100 rad) in daily treatments over 6 to 6 1/2 weeks has been a standard dose for inoperable locally advanced cases based on a major randomized study in the 1970’s showing that dose to be superior to lower doses.
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More recently, numerous studies have shown that combined radiochemotherapy regimens are superior to EBRT alone in local control and survival for inoperable locally advanced NSCLC patients.
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EBRT is routinely used in patients with limited-stage small cell lung cancer.
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EBRT is highly effective in palliating lung cancer, which produces superior vena cava syndrome, obstruction of major airways, hemoptysis from endobronchial tumor involvement, and severe tumor pain. Palliative EBRT doses may range from 30 to 45 Gy in 2 to 5 weeks.
Adjuvant Radiation Therapy
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Postoperative radiation therapy (PORT) to hilar and mediastinal nodes can significantly reduce the frequency locoregional recurrence, but has not improved overall survival rates in stages I to III.
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PORT fell out of favor with publication of a major meta-analysis that revealed poorer survival rates with PORT due to cardiopulmonary complications.
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Modern EBRT techniques that use well-fractionated dose-schedules and better limit dose to heart and lungs do not appear to increase the risk of treatment-related mortality.
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PORT may have future indications in early-stage lung cancer if adjuvant chemotherapy decreases the frequency of distant metastases but not the frequency of locoregional recurrences.
Neoadjuvant Radiochemotherapy
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Preoperative EBRT alone has not been shown to be of benefit for NSCLC in downstaging, improved local control, or higher survival rates. In the past, the exception to this was for superior sulcus lung cancers (Pancoast tumors), in which preoperative RT and surgery appeared to produce superior results to either modality alone.
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Preoperative chemotherapy alone has demonstrated downstaging and improved survival in some studies.
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Preoperative radiochemotherapy using platinum-based regimens has also demonstrated downstaging, improved locoregional control, and in some studies, improved survival.
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The typical EBRT dose is 45 to 50 Gy over 5 weeks.
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Small studies have used EBRT doses of 59 to 66 Gy, particularly for patients with bulky primary or nodal disease.
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Treatment fields encompass the primary tumor and involved nodes.
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Major acute toxicities are myelosuppression and radiation esophagitis, both of which may be severe.
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Postoperative complications and mortality are mainly due to pulmonary toxicities, including pneumonia, pulmonary embolism, acute respiratory distress syndrome (ARDS), and bronchopleural fistula, particularly in patients who underwent pneumonectomy. Fatal pulmonary complications have been reported in 13% to 26% of patients who undergo pneumonectomy but only 1% to 3% who undergo lobectomy. Placement of an intercostal muscle flap to cover the bronchial stump has significantly reduced the frequency of bronchopleural fistulas.
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Pathologic complete responses occurred in 7% to 45% of cases.
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Overall survival has been reported to be 22% to 46% at 3 to 5 years.
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Preoperative radiochemotherapy combined with surgical resection is considered the standard optimal approach for superior sulcus tumors. The intergroup trial had a 2-year survival rate of 55% for eligible patients entered in the study. Of 111 patients entered in the study, there were only three (2.7%) treatment-related deaths. Complete pathologic responses were found in 28 (25%) of patients.
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ACUTE AND LATE TOXICITIES OF THORACIC RADIATION THERAPY
Acute Side Effects During Course of Thoracic Radiotherapy
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Radiation esophagitis is the most common acute toxicity and occurs to some degree in a large majority of patients. With concurrent chemotherapy, grade 3 or greater dysphagia may occur in 3% to 13% of patients. Treatment includes oral xylocaine-based medications, narcotics, intravenous fluids, and/or breaks from treatment. Radiation esophagitis quickly resolves, typically within 7 to 14 days, following discontinuation of EBRT to the esophagus. In some cases, esophageal candidiasis may aggravate the severity of the dysphagia.
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Myelosuppression is more frequent and more likely to be severe in patients who receive concurrent chemotherapy.
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Skin reaction is typically a mild erythema on chest or back.
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Acute pericarditis is extremely rare (<0.1%).
Acute Radiation Pneumonitis
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Acute radiation pneumonitis (ARP) is an inflammatory reaction that appears in the high-dose irradiated portion of the lungs after the completion of EBRT. Pathophysiology is incompletely understood but appears to involve a cascade of inflammatory cells and cytokine production.
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Symptomatic ARP may develop in up to 20% of lung cancer patients, with 5% to 10% of all lung cancer patients having moderate to severe symptoms. It is not understood why only a small minority of irradiated patients develop ARP.
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The relative risk or frequency of ARP can be estimated before the start of EBRT based on any of several EBRT treatment planning parameters. The V 20 , the percentage of total lung volume receiving at least 20 Gy, has been shown to be a very useful predictive parameter. It has been incorporated into many intergroup studies to put an upper limit to the volume of lung that may be irradiatied. The V 20 can be determined before the start of EBRT when CT simulation and computerized treatment planning are used by the radiation oncologist.
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Symptoms include any combination of dyspnea, dry hacking cough, low-grade fever up to 101.5°F, or ipsilateral chest aching discomfort. High-grade fevers or productive cough are more likely due to other etiologies such as infections.
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Symptoms may arise 3 weeks to 3 months after the last day of EBRT but may also arise up to a year after treatment. Typically symptoms gradually progress in severity. However, unrecognized cases may progress to respiratory failure requiring intubation.
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There are no laboratory tests or pathologic findings that are specific for ARP. Lung biopsies show inflammatory alveolar changes consistent with ARDS. Bronchoscopy with bronchoalveolar lavage shows nonspecific inflammatory findings.
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Chest computed tomography (CT) scans show a restricted zone of fluffy infiltrates, often with air bronchograms. The infiltrate does not have a lobar distribution.
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The diagnosis is established by the determination that the region of infiltrate corresponds to the zone of irradiated lung. This often requires the radiation oncologist to compare the diagnostic CT scan with the radiation therapy simulation or port films or the EBRT dosimetry planning CT scans ( Fig. 26-1 ).
Figure 26-1
Acute radiation pneumonitis (ARP) in a patient with right-sided lung cancer who underwent radiotherapy with standard anterior and posterior opposed fields encompassing the primary tumor and mediastinum. The interstitial infiltrate closely matched the irradiated region of the right lung and left paramediastinal lung tissue. Symptoms were promptly relieved with prednisone.
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If the zone of infiltrate does not closely correspond to the irradiated volume, other diagnoses should be entertained, such as infection or lymphangetic metastases. In some cases, pulmonary infiltrates may be due to multiple diagnoses (e.g., pneumocystis in a patient with simultaneous ARP). In such cases, bronchoscopy may be helpful to search for diagnoses other than ARP.
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The ARP infiltrate may be different when newer methods of EBRT are used. When multiple small EBRT fields are aimed from several directions toward a lung tumor, the high-dose volume will surround the tumor in a very restricted and irregular shape. In addition, intensity-modulated radiation therapy (IMRT) uses sophisticated computer-controlled delivery to each EBRT field so that the portion of a particular field that passes through the tumor receives a higher dose and the portion of the field that passes through a critical structure receives a lower dose. Compared with standard EBRT fields, this results in a very conformal treatment region in which a much smaller lung volume receives a high EBRT dose. This, in turn, can reduce the frequency and severity of ARP. However, when ARP does develop, its appearance will be a vague irregular cloud-like region surrounding the treated tumor ( Fig. 26-2 ).
