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Lung Cancer

Medically Inoperable Lung Cancer 
  Submitted By: Maria T. Vlachaki, MD, PhD, MBA, CPE

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MEDICALLY INOPERABLE LUNG CANCER


Ignacio Castellon, MD, Andrew T. Turrisi III, MD, and Maria T. Vlachaki, MD, PhD

Wayne State University School of Medicine, Department of Radiation Oncology



Surgery remains the treatment of choice for patients with stage I and II (early stage) non-small cell lung cancer (NSCLC).(1,2) However, a substantial number of patients are medically inoperable because of other medical conditions, which can lead to higher rates of complications and deaths after surgery. Definitive radiation therapy given with the intent of curing the cancer can be an excellent alternative to surgery for these patients.

What is "medically inoperable"?

In healthy patients, the incidence of complications is 2-5% following lung resection. However, complication rates are substantially greater in patients with pre-existing lung disease.(3) Most patients diagnosed with lung cancer are current or former cigarette smokers and have chronic obstructive pulmonary disease (COPD; emphysema) or heart disease. Once the diagnosis of a resectable, potentially curable NSCLC has been made, it is important to obtain pulmonary function tests to determine whether the patient will tolerate surgery without excessive risk for complications. Patients with poor pulmonary function are at higher risk for surgical complications including respiratory and heart failure, or even death.

How do we assess “pulmonary function”?

Pulmonary function tests assess the mechanical capacity of the lungs to breath in and out adequate volumes of air and effectively exchange oxygen and carbon dioxide. The capacity of the lung to breath in and out adequate volumes of air is measured using the forced expiratory volume in one second (FEV1). The ability of lung tissue to effectively exchange oxygen and carbon dioxide is measured using the carbon monoxide diffusion test (DLCO) as well as the arterial concentration of oxygen (pO2) and carbon dioxide (pCO2). These tests predict the risk for complications after surgery and are useful in either approving patients for surgery or identifying high-risk patients that require further evaluation.

Further evaluation with a quantitative ventilation and perfusion lung scan may also be indicated in patients with borderline pulmonary test results. This test uses a radioactive technique to map the lung regions that exchange air poorly. These lung regions will have minimal or no impact on the pulmonary function if removed along with the lung tumor with surgery. Exercise stress testing evaluates oxygen usage with exercise. Patients with maximum oxygen consumption values of < 15 mg/kg/min are not ideal surgical candidates as they have an increased risk of postoperative complications and death. (4)


Treatment Options

Medically inoperable patients with early stage lung cancer have various treatment options including radiation therapy, chemotherapy, targeted therapy, radiofrequency ablation and cryotherapy. For the purposes of this discussion, we will focus on treatment options utilizing conventional and novel radiation therapy techniques.

Radiofrequency Ablation

Radiofrequency ablation (RFA) is a procedure in which heat is used to kill a tumor. Initially, the tumor is localized using computed tomography (CT) or ultrasound and then a thin needle is inserted through the skin and into the tumor. Electrical energy delivered through this needle heats the tumor up to a temperature of 100 degrees C, thereby killing the cancer cells within the tumor. RFA is most suitable when the lung tumor is small in size and located away from vital organs in the chest such as the central airways, major blood vessels, and heart. Studies have shown that RFA is most effective when used for tumors of 3 cm or less, resulting in local tumor control in 57% of such selected patients at three years after treatment. Risks from this procedure include shortness of breath due to accumulation of air or fluid in the chest cavity and bleeding into the lung. (5,6).

Cryotherapy

Cryotherapy is a technique that kills cancer cells by freezing them with liquid nitrogen. During this procedure, steel probes are inserted into the tumor and deliver liquid nitrogen inside and around the tumor. This freezes the tumor by encasing it in a ball of ice. In patients with lung cancer, cryotherapy has been primarily used for the treatment of early stage disease within the main airways. A clinical trial in France reported complete disappearance of cancer in 91% of such patients at one year after treatment.(7) Another trial from China reported a survival rate of 86% at 18 months after cryotherapy. (8)

Conventional Radiation therapy Techniques

Three-dimensional conformal radiation therapy techniques have been traditionally used to treat patients with medically inoperable stage I and II non-small cell lung cancer. These techniques allow doctors to visualize the lung tumor and normal tissues in three dimensions and calculate radiation doses to the whole volume of tumor and to minimize damage to normal segments of the lungs. A relatively low dose of 2 Gy is applied to the tumor daily over the course of six to seven weeks to deliver a total dose of 60-70 Gy. Reviews of patient outcomes treated with this approach indicate overall survival rates up to 55% and 32% at 3 and 5 years. (9-13) Attempts to improve outcomes using higher radiation doses of 70-90 Gy in selected patients have increased local tumor control rates up to 78%. (14)

The potential benefit from increasing the radiation doses to the lung tumor must be balanced against the risk for injury to normal tissues, including the uninvolved normal lung, heart, esophagus and spinal cord. The risk for radiation side effects depends on the total dose of radiation, the dose per treatment session, and the volume of normal tissue exposed to radiation. (14,15) According to one study, fifteen percent of the patients treated with radiation doses of 70-90 Gy developed severe lung injury. (14) Radiation can cause pneumonitis (inflammation of the lung) or fibrosis (scarring of the lung) which present with shortness of breath and worsening of pulmonary function tests, and may require oxygen treatment on a temporary or permanent basis. Radiation injury to the esophagus (the food tube between the mouth and stomach) may result in painful swallowing and/or narrowing of the esophagus which may compromise nutrition. The risk for radiation injury with higher radiation doses underscores the need for new radiation therapy techniques that more accurately target the tumor while minimizing exposure of normal tissues.

Stereotactic Body Radiation Therapy

Stereotactic radiation therapy is an advanced technique in which numerous beam of radiation are aimed at the tumor from many different directions. Each of these beams delivers a relatively low dose of radiation, but the additive effect of these beams results in the delivery of a high dose of radiation to the target tumor. With this technique, high doses of radiation can be delivered to a small volume of tumor while delivering only low doses to the surrounding normal tissues. Stereotactic radiation therapy has been successfully used for the treatment of small brain tumors. It delivers large radiation doses in one to five sessions using rigid patient immobilization to ensure that the beam is directed to the target with only 1 mm or less of variation. Technological developments in the planning and delivery of radiation therapy have recently permitted the application of this technique to body sites other than the brain. This technique is called "stereotactic body radiation therapy" or SBRT. For lung tumors, SBRT is considered in selected patients with peripheral lung tumors less than 5 cm who are medically inoperable or refuse surgery. It involves radiation doses of 7 to 22 Gy delivered over the course of 1 to 2 weeks. Such higher doses per treatment have a theoretical advantage as they are expected to be more damaging to the tumor when compared to the lower doses of 1.8 to 2 Gy traditionally used to treat lung tumors. Since such treatment regimens shorten the overall duration of radiation therapy from 6-7 weeks to 1-2 weeks, they are also more convenient for the patient and may allow the earlier integration of other anti-cancer therapies whenever this is indicated. However, appropriate treatment planning and quality control measures must be undertaken to optimize tumor targeting while limiting radiation exposure of normal tissues while delivering such high radiation doses. Only specialized radiation treatment systems can provide such therapy safely. Table 1 demonstrates the results from clinical trials using SBRT in patients with early-stage non-small cell lung cancer with patient follow-up durations of 12 to 24 months. These studies reported that SBRT could shrink or keep the target tumor from growing in over 95% of patients. (16-19) Treatment-related side effects have been limited and are primarily observed when treating larger tumors or tumors located centrally within the lungs. (19,20)



Newer radiation therapy systems have the capability of delivering stereotactic body radiation therapy (Figure 1). They provide an innovative way of delivering radiation therapy because they combine the capabilities of imaging, computerized treatment planning and radiation treatment delivery into one system. Unlike conventional linear accelerators used to deliver standard radiation therapy these systems produce radiation beams that rotate while the patient is continuously moved through the device, therefore, creating a spiral beam pattern around the area of the body that needs treatment. With the aid of the radiation blocking devices, these systems produce thousands of beams of different intensities. This allow doctors to shape higher radiation doses around the tumor while minimizing the radiation exposure of the surrounding healthy tissues.(21) These advanced therapy devices allow Image Guided Radiation Therapy (IGRT) in which doctors obtain a CT scan right before the radiation is delivered and adjust the position of the patient in order to optimize targeting of the tumor by the radiation beam.



Figure 1. Radiation therapy device


For the treatment of lung cancer patients with IGRT, a custom molded cradle is made to immobilize them during radiation therapy. In addition, the pattern of tumor motion during breathing is tracked by obtaining a "Dimensional Gated Planning CT" that records the changes in tumor position and shape during the different phases of the respiratory cycle to ensure more accurate targeting of the tumor with radiation (Figure 2).




Case study

A sixty-nine year-old woman was referred with the diagnosis of early stage non-small cell lung cancer. Her imaging studies demonstrated a one centimeter tumor involving the right upper lobe of her lung. She has had a long standing history of chronic obstructive pulmonary disease and has been using oxygen at home. Pulmonary function tests confirmed that she was at high risk for surgical complications. Therefore, she was offered a short course of SBRT. She received five daily treatments of 10 Gy each for a total dose of 50 Gy. Figure 3 demonstrates the sharp decrease of the radiation doses beyond the tumor to minimize the exposure of normal lung to high radiation doses. Prior to each treatment, a CT scan was obtained to verify the position of the tumor (Figure 4). The patient tolerated the treatment very well and no radiation-related reactions were found at her first visit one month after completion of radiation therapy.










Summary

Patients with early-stage lung cancer who are not candidates for surgical resection of the cancer can be treated with radiotherapy alone. Technological advancements in radiation therapy enable radiation oncologists to precisely deliver higher, more effective radiation doses to tumors with minimal short-term toxicity. While preliminary clinical results are encouraging, longer patient follow-up will allow us to assess cancer control rates and the risk of long-term toxicity with this treatment approach.  


 


Additional Authors:  

Works Cited:  
  References

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