|Year : 2008 | Volume
| Issue : 6 | Page : 89-96
|An overview of radiation therapy in the treatment of non-small-cell lung cancer
Adnan Al Hebshi1, Abdulrahman Al Hadab2
1 King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
2 King Abdulaziz Medical City for National Guards, Riyadh, Saudi Arabia
Adnan Al Hebshi
Consultant Radiation Oncology, King Faisal Cancer Centre, King Faisal Specialist Hospital and Research Centre, P.O. Box.3354, Riyadh 11211, MBC - 64
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Radiation therapy (RT) is an important treatment modality for non-small-cell lung cancer (NSCLC) and has a wide spectrum of applications and indications. Radiotherapy can be used with curative or palliative intent, alone or in combination with another modality-either in sequence or concurrently. In this manuscript, we review the utilization of RT in the treatment of NSCLC.
Keywords: Lung cancer, radiation therapy, combined therapy
|How to cite this article:|
Al Hebshi A, Al Hadab A. An overview of radiation therapy in the treatment of non-small-cell lung cancer. Ann Thorac Med 2008;3, Suppl S2:89-96
| Standard Therapeutic Approaches|| |
Radiotherapy for early-stage lung cancer
Patients with stage I and stage II disease who are medically fit can be treated surgically with good outcome. If such patients are medically unfit or refuse surgery, then definitive radiation therapy (RT) offers a potential curative alternative. Postoperative RT is used in selected patients (i.e., those patients who have positive margins after resection) with stage I and stage II disease.
Definitive RT for inoperable early-stage NSCLC
Some patients present with surgically resectable disease but have medical contraindications or refuse surgery. For such patients, primary RT offers an alternative and potentially curative approach.  The first published experience was from Hilton and Smart of University College Hospital of London, who gave 40-55 Gy using orthovoltage equipment to 38 patients.  Multiple retrospective series have reported survival rates ranging from 0-30%. ,,,,,,,,,, Surgery has the highest reported survival rates in stage I and stage II disease. The results from primary RT are inferior to surgery. The observed differences in results between surgery and radiation may be due in part to selection bias because, in many instances, patients referred for radiation have worse performance status, are less rigorously staged, and have poor pulmonary function combined with comorbid illnesses.  Surgical series have revealed that approximately 25-50% of clinical stage I patients are upstaged. The rate of occult Nl or N2 disease is as high as 56% if the patient has a positive preoperative bronchoscopy.  More modern series have examined the issues of dose and dose escalation in relation to tumor size, local control, and survival for stage I and II disease. The evidence suggests that radical radiotherapy is an effective treatment primarily for tumors less than 3 cm (Tl) when treated to doses of 65 Gy or higher. The highest reported survival was in a series that used the highest median dose.  Complete response and local control of larger tumors, however, appears less likely with standard radiation fraction schedules and doses despite availability of modern equipment and CT-based planning.
Elective nodal irradiation of the mediastinum is probably unnecessary for early-stage tumors. The inclusion of large volumes of lung within a radiation port, especially for peripheral T1 and T2 tumors, to prevent regional failure must be balanced against the potential for increased toxicity. The rationale for treating the local tumor volume alone appears justified when the patient's outcome is not negatively impacted if the regional lymph nodes are not included. The evidence appears to support the use of smaller target volumes to deliver higher doses without compromise of the regional outcome.  The regional failure rate is typically less than 10% in reported series where elective nodal areas were not treated. ,,,,, In one series, most patients did received elective nodal irradiation, but there was still a failure rate approaching 10%, which suggests that a typical elective dose of 40 Gy is not enough to control occult disease. 
Perhaps the most important issue yet to be elucidated in the treatment of early-stage NSCLC is that of the dose and fractionation to be used. The need for the traditional fractionation of 1.8-2 Gy is being challenged. The role of higher doses per fraction, such as 3-4 Gy or even as much as l0 Gy via stereotactic radiosurgery, is being investigated. A dose of 4 Gy per fraction has been investigated in a poor performance status population and found to yield adequate control. 
Marginally operable non-small-cell lung cancer
There is no standard definition of marginally operable NSCLC. However, the typical clinical situation is a patient with locally advanced disease that might be operable, or require a less morbid surgical procedure, if it responded to induction therapy. One major concern is that a patient might receive induction treatment with chemoradiotherapy up to 45 Gy and still be found to have unresectable disease when reassessed after the completion of chemoradiotherapy. In these situations, attempts are made to deliver more radiation to the tumor but, typically, only 15-20 Gy can be delivered. Thus, the patient would have been denied the opportunity for definitive treatment.
Intergroup trial 0139 investigated whether induction chemoradiotherapy up to 45 Gy followed by surgical resection was superior to chemoradiotherapy to 61 Gy alone in patients with Tl-3 N2 disease. Surgical resection of all tumors was considered technically feasible at the time of registration. Preliminary analysis of 392 eligible patients revealed a longer progression-free survival in patients who received surgery, but overall survival was not significantly improved due to the increased number of treatment-related deaths seen in the surgery arm. Of note, survival at 3 years in the trimodality arm was 38% vs. 33% in the bimodality arm. This data suggests that induction chemoradiotherapy followed by surgery will not be of value in patients who are not technically resectable at the time of presentation.
Superior sulcus tumor
The management of superior sulcus tumors (Pancoast tumors) is difficult. RT is an essential component of treatment either as sole therapy, preoperative therapy, postoperative therapy, or as intraoperative brachytherapy.
The current standard treatment of superior sulcus tumors generally consists of preoperative chemoradiotherapy to 45 Gy. This is followed, 4 weeks later, with surgical resection. This regimen was studied in a phase II Southwest Oncology Group (SWOG) protocol that enrolled 111 patients and reported a 65% rate of pathologic complete response or minimal microscopic disease and a 55% 2-year survival.  The 4-year survival exceeded 40%.
Patients with uncontrolled primary tumors in the superior sulcus often have severe, intractable pain. Therefore, palliative resection of the primary tumor could be offered even in the setting of metastatic disease.
Technique for the treatment of Pancoast tumors
The basic technique is the same, regardless of the setting in which RT is used. The usual technique is to use paired anterior and posterior fields. The dose administered to the spinal cord should be calculated upward and should not exceed 110% of the prescription dose. If necessary, a half-field wedge is used as a spinal cord dose compensator. It is important to use CT scans and / or MRI scans to determine field borders. In general, the field encompasses all areas of gross disease with a 2-cm margin. If part of a vertebral body is included in this field, then inclusion of the entire vertebral body should be considered in order to ensure a homogenous dose to the vertebral body.
The usual preoperative doses are well within the tolerance limit of the spinal cord, and the fields described here can be used for the entire treatment. If definitive RT alone is used, then the spinal cord dose has to be limited to 46-48 Gy, provided this does not underdose any portion of the tumor. If the tumor approximates the spinal cord, then an absolute maximum of 50 Gy can be given to the spinal cord. It is important to calculate the dose distribution throughout the entire spinal cord to make sure no portion receives a dose that exceeds this maximum. Simple anterior and posterior fields, as previously described, can be modified to exclude the spinal cord from the latter part of treatment. Alternatively, paired oblique fields may better cover the target, while excluding the spinal cord. When RT is used postoperatively, the total dose may be 50 Gy in conventional fractions of 1.8-2.0 Gy. Consequently, the cord dose has to be limited in a similar fashion.
| Preoperative RT|| |
RT may be delivered preoperatively or postoperatively. Theoretically, preoperative induction irradiation may improve resectability of larger tumors, sterilize cells beyond the margins of resection, and prevent dissemination by surgical manipulation; additionally, it uses lower doses of radiation than are required postoperatively, when surgical changes induce conditions of hypoxia and relative radioresistance. Compared with postoperative RT, the disadvantages of preoperative RT are that the precise surgical stage may not be known and some patients may be treated unnecessarily, the exact anatomical extent of tumor may not be appreciated, and the risks of postoperative complications are increased.
The initial report of preoperative RT for NSCLC was from Bromley and Szur in 1955. From a large population of patients with early- and intermediate-stage disease, they selected 66 patients who responded to a median of 4700 R and performed resection with lymph node dissection. Complete tumor eradication in the primary tumor and nodes was detected in 47% (29 of 62) of evaluable patients. However, survival was poor, with only approximately 17% alive at varying follow-up times. This was accounted for in part by the 17% incidence of bronchopleural fistula, which was fatal in all but one patient. 
Randomized trials with larger cohorts of patients were initiated to answer this question. The first such major randomized trial was performed by the Veterans Administration. With a minimum follow-up of 4 years in surviving patients, no increase in survival was noted in the pretreatment group. The overall survival rate was 12.5% in the pretreatment arm compared with 21% in the surgery-alone arm, although this was not statistically significant. 
In 1975, the National Cancer Institute published two separate but integrated multi-institutional randomized trials addressing the use of preoperative radiotherapy followed by surgery in both operable and inoperable NSCLC, but there was no evidence of an advantage with preoperative radiotherapy.  It is clear from both the nonrandomized and randomized data that preoperative irradiation alone does not improve long term survival and it has no role as a single modality in the induction treatment of marginally resectable or unresectable stage IlIA or IIIB disease. The use of RT as a single preoperative modality is no longer studied due to the advent of more effective chemotherapeutic agents. Most current trials investigate the use of preoperative concomitant chemoradiotherapy.
| Definitive RT for Locally Advanced NSCLC|| |
RT is the standard therapy for patients with unresectable NSCLC. Essentially, RT replaces surgery as the definitive treatment. Multiple series have shown that the median survival and long-term survival is low when RT alone is used. , Therefore, there have been investigations to establish whether there is any advantage in delivering thoracic radiotherapy in the setting of inoperable disease.
In a multi-institutional cooperative trial, Johnson and associates  reported the results of 319 patients with locally advanced unresectable NSCLC without evidence of distant metastases who were randomized prospectively to one of three arms: chemotherapy alone with vindesine, 3 mg / m 2 / wk; standard thoracic irradiation to a dose of 60 Gy in 6 weeks; or combined vindesine and thoracic radiotherapy. Although the overall response rate was superior in the radiotherapy arms (radiotherapy alone: 30%; radiotherapy plus vindesine: 34%; vindesine alone: 10%; P = 0.001), the intrathoracic progression rates were similar in the vindesine arm (60%) and in the radiotherapy arm (65%); both median survival and overall survival were also comparable in all three arms. This study has been criticized, however, for the large number of patients in the vindesine-alone arm who received RT after developing disease progression on vindesine, and the inadequate number of patients to detect a difference in survival. 
A retrospective study from British Columbia that controlled for tumor stage and other prognostic factors reported improved survival of 79 days in patients receiving high-dose palliative RT and improved survival of over a year in patients receiving radical RT. 
Although, it seems clear that thoracic RT does offer a survival advantage to patients with disease limited to the thorax, the poor results of these earlier studies led the RTOG and other groups to investigate methods of improving outcome with radiation alone by initially concentrating on dose intensification with conventional fractionation; the use of altered fractionation; identification of appropriate selection criteria, including prognostic factors for the various approaches; the use of innovative treatment planning and technology; and perhaps most importantly, the integration of chemotherapy with RT.
Selection of patients
Generally accepted eligibility criteria for definitive therapy for lung cancer are based on the extent of the tumor and the patient's physiologic status. The presence of distant metastases and pleural or pericardial effusions are contraindications. A performance status of 60% or more is preferable, as is adequate pulmonary function. Bleehen and Cox  have recommended that the FVC should be ≥ 45% of predicted; the FEV1 ≥ 40% of predicted; single-breath diffusing capacity for carbon monoxide, corrected for hemoglobin, should be 45% of predicted; and PaO 2 less that or equal to 49 mm Hg. However, these figures should be used as guidelines rather than as strict criteria, since the use of RT may improve performance status or relieve airway obstruction. In addition, for patients with poor pulmonary function, there is typically no adequate therapeutic option aside from RT, so it is probably still in the patient's best interest to proceed with treatment, with the patient being made aware of the increased risks.
Elective nodal irradiation
As described above, standard RT typically involves a dose of 40 Gy to the entire mediastinum, supraclavicular fossa, and ipsilateral hilum, even if there is no evidence of disease in these areas. It has been shown that this elective treatment can significantly add to the morbidity of radiation.  Many centers have made the decision to eliminate elective nodal irradiation in an effort to increase the dose to the tumor. When RTOG trials were reviewed to estimate the clinical impact of omitting nodal irradiation, it was found that when the ipsilateral hilum and mediastinum were incorrectly treated, there was an increased risk of progression.  Memorial Sloan-Kettering Cancer Center reported an elective nodal failure rate of 8% and a local failure rate of 65%,  which suggests that until regions of known disease can be better controlled there is probably no need to treat the whole mediastinum and supraclavicular region electively.
| Postoperative RT|| |
The Lung Cancer Study Group (LCSG) investigated the efficacy of postoperative mediastinal irradiation in completely resected stage II and III squamous cell carcinoma of the lung. This trial randomized 210 patients to receive 50 Gy in 25 fractions after surgery vs. observation alone. The locoregional failure rate (as first site of failure) was reduced from 41% to 3% with radiotherapy for all node-positive patients. Despite this improvement, the increase in locoregional control with radiotherapy did not translate into a survival benefit for stage II patients because more than two-thirds of first failures were distant.  The LCSG failed to separate patients with Nl and N2 disease but combined and analyzed them as a single group.  A trend toward improved survival was observed in N2 patients receiving radiotherapy.
The Medical Research Council of the United Kingdom also completed a randomized adjuvant trial in which 308 patients with stage II and III disease were treated with either 40 Gy or no further therapy. Although a trend toward improved survival was seen in the N2 subgroup, no overall survival benefit was observed. 
The meta-analysis performed by the Medical Research Council confirms these results. They reported local recurrences in 276 patients in the surgery-only arms of the trials. There were 195 local recurrences in patients receiving postoperative radiotherapy (PORT). In addition, there was a trend toward improved survival in stage III and N2 patients, although it did not reach significance; however, a survival decrement was observed in stage I and II patients. 
There have been criticisms of the meta-analysis due to its methodologic flaws. The trials studied had variable and unspecified staging, used cobalt-60 or other low-energy photons and had inadequate treatment planning. In addition, the interval between surgery and PORT was inconsistent and sometimes not reported.
Therefore, the role of PORT remains controversial. It has not been shown to produce a benefit in early-stage disease and should not be recommended in these patients except in the case of suspected residual microscopic or macroscopic residual disease. It has been shown to improve local control in patients with mediastinal nodal disease but has no proven survival benefit. It is likely that there is a subgroup of patients, such as those with micrometastatic disease, who will have improved survival with PORT; however, this patient population is yet to be identified.
Technique of postoperative RT
Postoperative RT for patients with microscopic residual disease or with resected hilar or mediastinal involvement is planned as follows: The area to be treated is determined by correlating preoperative imaging studies, intraoperative findings, surgical clips, and the pathologic review of the resected specimen. Generally, the objective is to treat the ipsilateral hilum, the mediastinal nodes bilaterally, and the ipsilateral supraclavicular area. Peripheral primary tumors which do not abut the mediastinum or hilum and are not adjacent to the chest wall are usually removed with generous margins. After surgery, their preoperative location is occupied by relocated and uninvolved lung parenchyma which does not need therapy unless there is clear evidence or strong suspicion of residual disease. The standard postoperative dose is 50.4 Gy in 1.8-Gy fractions or 50 Gy in 2-Gy fractions. Consequently, the majority of this dose can be given with energy greater than or equal to 6 MV, using opposed anterior and lateral fields and paying appropriate attention to the spinal cord dose. If there is a positive margin, this area is boosted with an additional 10-10.8 Gy to bring the total dose to 60-61.2 Gy. Half-field wedges can be used to decrease the dose to the spinal cord superiorly where the separation is less than at other levels. One approach is to deliver 41.4 Gy to the target volume with these fields, which will rarely deliver more than 45 Gy to any portion of the spinal cord, and to give the rest of the dose with oblique fields that completely exclude the spinal cord. The use of opposed lateral fields should be discouraged, even for these relatively small doses due to the excess amount of lung that would be treated.
| Chemoradiotherapy|| |
The RTOG investigated the effect of a variety of doses of RT on the outcome of 379 patients with locally advanced (TI-3 N0-2) NSCLC.  Patients were randomized to receive 40-Gy split-course or 40-Gy, 50-Gy, or 60-Gy continuous-course RT. Median survival was approximately 9 months and 5-year survival was 5%. Between 1 and 3 years, the curves diverged temporarily in favor of 60Gy but then converge. There was no clear effect of dose on survival. However, the in-field failure rate did decrease from 53-58% with 40 Gy to 35% with 60 Gy.
Sequential chemotherapy and radiation vs radiation alone
Because distant failure is common following RT for locally advanced NSCLC, attempts have been made to improve survival by adding chemotherapy to RT. Combination chemotherapy can produce higher response rates and potentially could be more efficacious in that setting. Initially the majority of randomized trials were negative, possibly because of failure to select healthier patients and because of the use of non-cisplatin regimens. The Cancer and Leukemia Group B (CALGB) randomized patients with locally advanced NSCLC to receive 60 Gy of thoracic irradiation with (n = 78) or without (n = 77) induction chemotherapy with vinblastine (5-weekly courses of 5 mg / m 2 ) and cisplatin (100 mg / m 2 two doses). The patients were selected on the basis of having a performance status of greater than or equal to 80, weight loss of less than or equal to 5%, and hematocrit greater than 30%. Median survival was 14 months with chemotherapy versus 10 months without (p = 0.006), and 3-year survival was 23% with chemotherapy vs. 11% without it.  At six and seven years, this survival advantage has persisted: 13% vs.16%.
A much larger Intergroup study confirmed in a preliminary manner that this chemotherapy regimen given before 60 Gy of RT improved survival compared to 60 Gy alone.  A large randomized study from France tested the value of vindesine, cyclophosphamide, cisplatin, and lomustine added to 65 Gy (split-course) of thoracic irradiation. Survival initially was not increased by the addition of chemotherapy but, later, follow-up confirmed a therapeutic advantage: 6% 5-year survival for the combined modality arm vs. 3% for the RT-only arm. Moreover, distant metastases were significantly reduced to 45% in the chemotherapy arm (n = 176) vs. 67% in the RT-alone arm (n = 177).  These data suggest a strong rationale for exploring the combined use of the most effective chemotherapy regimens with more effective thoracic radiation approaches.
Using a different study design, Kubota and coworkers randomized patients receiving induction chemotherapy to receive (n = 31) or not receive (n = 32) thoracic irradiation.  Thoracic irradiation significantly prolonged the time to progression and increased 2-year survival (P < 0.05). This trial shows that even in patients with an excellent response to induction chemotherapy, thoracic RT is still needed to prevent local recurrence.
Concurrent chemoradiation vs radiation alone
There have been three major trials comparing concurrent chemoradiotherapy and radiation alone. The EORTC reported that the addition of cisplatin 6 mg / m 2 daily to 55 Gy of radiation delivered via a split-course technique or cisplatin 30 mg / m 2 weekly with the radiation, or RT alone produced 3-year survival rates of 16%, 13%, and 2%, respectively.
Jeremic has reported two trials where carboplatin and etoposide delivered weekly or daily with hyperfractionated RT to 69.6 Gy were superior to the same radiation given alone. 
Sequential chemotherapy and RT vs concurrent chemoradiotherapy
There have been four trials comparing sequential chemotherapy and radiation and concurrent chemotherapy. Furuse compared definitive 56 Gy after induction mitomycin, vinblastine, and cisplatin (MVP) chemotherapy to the same chemotherapy regimen delivered concurrently with split-course RT. The 5-year survival increased significantly from 9% with the former to 16% with the latter regimen. There was also increased esophagitis.
RTOG 9410 compared 1) sequential cisplatin / vinblastine chemotherapy and radiation (63 Gy), 2) concurrent cisplatin / vinblastine chemotherapy and radiation (60 Gy), and 3) concurrent cisplatin / oral etoposide with hyperfractionated radiation to 69.6 Gy.  At the latest analysis, the concurrent once-daily arm treatment led to a significantly improved median survival (17.1 vs. 14.4 months) and 5-year survival rates (16% vs. 10%).
The Groupe Lyon-Saint-Etienne d'Oncologie Thoracique trial compared induction cisplatin / vinorelbine followed by 66 Gy with concurrent cisplatin / etoposide / 66 Gy followed by cisplatin / vinorelbine. There was no significant difference in survival between the groups, although trends favored the concurrent approach. 
Finally, a trial from the Czech Republic compared 60 Gy of RT delivered either during or after four cycles of cisplatin / vinorelbine. The investigators reported a significant increase in survival with concurrent treatment. 
Sequencing of chemoradiotherapy
The Locally Advanced Multimodality Protocol (LAMP) investigated three different schemes of delivering chemoradiotherapy and chemotherapy.  All arms used carboplatin and paclitaxel chemotherapy and radiotherapy does of 66 Gy. In one arm, the chemotherapy and radiation were given sequentially, similar to the CALBG trial. In the second arm, chemotherapy was given initially and then chemoradiotherapy was delivered. In the third arm, chemoradiotherapy was given initially, followed by consolidative chemotherapy with the same agent. Not surprisingly, esophagitis increased dramatically in the arms receiving concurrent chemotherapy. The median survival in the arms with induction chemotherapy was surprisingly low at 11-12.5 months. In the arm with early radiation and concurrent chemotherapy, median survival increased to 16.5 months.
SWOG 9019 employed consolidative cisplatin / etoposide after the use of concurrent cisplatin / etoposide / radiation in 50 stage IIIB patients.  Investigators reported a 3-year survival of 17%. A follow-up study, SWOG 9504, substituted docetaxel as the consolidative agent and obtained an encouraging increase in 3-year survival to 37%.  The use of consolidative chemotherapy is being further investigated by the Hoosier Oncology Group which did not confirm the role of docetaxel; however the study (the Hoosier Oncology Group Study which is not published yet but present) had multiple limitations.
Altered fractionated schemes
There are several theoretical advantages to split-course RT. It is postulated that the interval between the courses (usually 2-4 weeks) allows for maximal recovery from acute toxicity. Normal cells may repopulate more quickly than cancer cells during the interval and reoxygenation and redistribution of cancer cells may occur, rendering them more radiosensitive during the second course. However, an accelerated repopulation of malignant cells may occur during this interval.  In RTOG 73-01, the split-course treatment to 40 Gy had a lower in-field control rate than the continuous treatment.  Fowler and colleagues reported a significantly worse outcome in RTOG patients who received a 2-week or more treatment break during their radiation.  Split-course treatment as a single modality is generally out of fashion at present.
Hyperfractionated RT is a method of intensifying radiation effect by delivering smaller dose fractions (e.g., 1.2 Gy per fraction), given more than once per day, thus increasing the total daily dose to 2.4 Gy or more. Consequently, when given in a continuous course, 5 days per week, the treatment is also described as 'accelerated.' Theoretically, this approach has a greater effect against cancer cells and keeps chronic side effects at acceptable levels because of the low dose per fraction.
In a randomized phase I/II trial, Cox and coworkers used 69.6 Gy of hyperfractionated RT for locally advanced NSCLC and reported a median survival of 13 months in a subgroup of patients with good performance status and minimal weight loss.  However, a phase III trial addressing the value of the RTOG-type hyperfractionated radiation scheme compared with standard 60-Gy RT failed to show a survival benefit for hyperfractionation. 
Hyperfractionated accelerated RT
Continuous hyperfractionated RT (CHART) employs many radiobiologic principles in an effort to improve the therapeutic ratio. CHART delivers 54 Gy in three daily doses of 1.5 Gy over 12 continuous days, including weekends. With CHART, treatment is given every day to counteract rapidly proliferating cells. Hyperfractionation with many smaller doses of radiation may reduce long-term toxicity. Accelerating the treatment by reducing the treatment time from 6 weeks to 2 weeks also may counteract tumor repopulation.
CHART was first examined in a small prospective phase II trial.  Some degree of esophageal toxicity was present in all patients. Ten percent of patients developed acute radiation pneumonitis. Two-year survival was 34%.
A phase III randomized study was performed in 13 centers in the United Kingdom. Patients were assigned to either standard radiation of 60 Gy in 30 daily doses of 2 Gy over 6 weeks or to CHART. Approximately one half of the patients had stage III disease, the remainder had early-stage disease or NSCLC of unknown staging. No other modality of therapy was used. Two-year survival significantly increased from 20% to 29% in the CHART arm. In addition, local control significantly improved from 15% to 23%.  Severe esophageal toxicity also increased from 3% to 19%. Acute radiation pneumonitis was 19% in the conventional group and 10% in the CHART arm. However, late pulmonary toxicity and fibrosis, requiring treatment at 2 years, was present in 16% of living patients who received CHART as compared to 4% of those who received conventional RT. The physical and psychologic symptoms caused by this aggressive regimen have been shown to be tolerable as well. 
The use of CHART has been limited by the need to reorganize radiation departments to accommodate the demanding radiation treatment schedule. In addition, patients need to be hospitalized during their entire course of radiation, which significantly increases the cost of treatment. Therefore, trials have been conducted using CHART without treatment on weekends (CHARTWELL). 
An ECOG trial examined the feasibility of hyperfractionated accelerated radiation (HART).  Twenty-eight patients received 57.6 Gy over 15 days (12 treatment days) in three daily fractions of 1.5 Gy, 1.8 Gy, and 1.5 Gy, given 4 h apart. The need to wait 6 h was avoided by not treating fields containing spinal cord consecutively. Belani and Wagner found that this regimen was tolerable, with the main toxicity being esophagitis and moist desquamation of the skin. The HART schedule showed provocative efficacy, with the median survival improving from 13.7 months with standard 64 Gy RT in 2-Gy daily fractions to 22.2 months with HART.  All enrollees received induction chemotherapy with paclitaxel and carboplatin.
| Summary|| |
RT is used in the treatment of lung cancer in different clinical scenarios and as part of different approaches. The proper utilization of this modality should lead to improved outcomes for patients with NSCLC. Continuing improvement in the delivery of this treatment will lead to better outcomes for cancer patients.
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