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ORIGINAL ARTICLE
Year : 2021  |  Volume : 17  |  Issue : 3  |  Page : 715-719

Efficacy comparison between microwave ablation combined with radiation therapy and radiation therapy alone for locally advanced nonsmall-cell lung cancer


1 Medical Oncology, School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, Jinan University; The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), Jinan, China
2 The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), Jinan, China

Date of Submission15-May-2020
Date of Decision13-Oct-2020
Date of Acceptance22-Mar-2021
Date of Web Publication9-Jul-2021

Correspondence Address:
Lijun Sheng
Shandong Academy of Medical Sciences, Affiliated Hospital Oncology, Jinan
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_633_20

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 > Abstract 


Purpose: Comparing the efficacy and complications of microwave ablation (MA) combined with intensity-modulated radiation therapy (IMRT) and IMRT alone for locally advanced peripheral nonsmall-cell lung cancer (NSCLC).
Methods: Retrospective analysis was conducted on 76 patients with locally advanced peripheral NSCLC undergoing chemotherapy and metastatic lymph node radiation therapy from June 2014 to June 2016. Either MA or IMRT was used to treat primary lesions. Thirty-four cases were treated with MA (MA group), 42 cases were treated with IMRT (IMRT group), and comparisons were made of the 1–3-year progression-free survival (PFS) and complications of the two groups.
Results: The PFS of the MA group at 1, 2, and 3 years were 70.59% (24/34), 47.06% (16/34), and 35.29% (12/34), and the PFS of the IMRT group at the same intervals were 71.43% (30/42), 52.38% (22/42), and 35.71% (15/42), with no significant difference (χ2 = 0.006, P = 0.936) (χ2 = 0.213, P = 0.645) (χ2 = 0.001, P = 0.970). Radiation-induced lung injury (RILI) occurred in 14.70% (5/34) of MA group patients, which was significantly lower than in the IMRT group 40.48% (17/42), but without grade II or above RILI.
Conclusion: MA combined with IMRT in the treatment of locally advanced peripheral NSCLC was not inferior to the clinical effect of radiation therapy alone, and radiation lung injury incidence was also lower.

Keywords: Chemoradiation therapy, computed tomography guidance, microwave ablation, nonsmall-cell lung cancer


How to cite this article:
Song P, Sun W, Pang M, He W, Zhang W, Sheng L. Efficacy comparison between microwave ablation combined with radiation therapy and radiation therapy alone for locally advanced nonsmall-cell lung cancer. J Can Res Ther 2021;17:715-9

How to cite this URL:
Song P, Sun W, Pang M, He W, Zhang W, Sheng L. Efficacy comparison between microwave ablation combined with radiation therapy and radiation therapy alone for locally advanced nonsmall-cell lung cancer. J Can Res Ther [serial online] 2021 [cited 2021 Jul 26];17:715-9. Available from: https://www.cancerjournal.net/text.asp?2021/17/3/715/321035




 > Introduction Top


Lung cancer is a malignant tumor with the highest morbidity and mortality rates worldwide, and nonsmall-cell lung cancer (NSCLC) accounts for 80%–85% of all lung cancers.[1] Moreover, locally advanced NSCLC accounts for nearly one-third of all NSCLC, with particular emphasis on stage III patients. Surgery is preferred for locally advanced resectable NSCLC patients, but most have lost the opportunity by the time of discovery. Radiation therapy combined with chemotherapy is often used in clinic for locally advanced NSCLC that is difficult to resect.[2],[3] Intensity-modulated radiation therapy (IMRT) has been widely used in clinic via dose and target area shape optimization, thereby helping better protect normal tissues in the nontarget area or patients. However, radiation-induced damage remains a challenge in current tumor disease treatment. Radiation-induced lung injury (RILI) is one of the most toxic and harmful side effects of chest tumor radiation therapy.[4] In turn, microwave ablation (MA) has become one of the new local therapies for lung cancer due to its local lesion destruction.[5] The independent factors for the incidence of RILI have been reported to be V5, PTV, and total radiation therapy dose.[6] A comprehensive treatment model was created to better reduce V5 and PTV which is composed of radiation therapy in mediastinal regional lymph node + MA in pulmonary lesions + systemic therapy, and it was performed on some locally advanced peripheral NSCLC. This study retrospectively analyzes the clinical data of locally advanced peripheral NSCLC patients treated with either MA or IMRT, thereby providing a reference for selecting reasonable treatment strategies for these patients.


 > Information and Methods Top


General information

Ninety-seven cases of locally advanced NSCLC were diagnosed via pulmonary puncture pathology and imaging in compliance with the following criteria: (1) primary lung tumor diameter ≤5 cm; (2) no invasion in the diaphragm or adjacent organs; (3) KPS score of 0–1, and no contraindication to radiation therapy or microwave therapy; (4) computed tomography (CT) scan showed complete lesion ablation in the MA group about 4 weeks postsurgery, and radical radiation therapy was implemented in the radiation therapy group as planned. Radiation therapy was not completed as planned for 21 patients with incomplete ablation and tumor diameter >5 cm. Chemotherapy, molecular-targeted therapy, or follow-up that were not performed in the hospital utilized by the study were excluded, and 76 patients were finally included in this study, including 34 patients receiving MA (MA group) and 42 patients receiving IMRT (IMRT group). The selection for MA patients was as follows: (1) elder age and (2) poor pulmonary function. No significant differences existed between the two groups regarding gender, KPS score, pathological type, gene mutation, tumor stage, tumor size, or smoking history (P > 0.05), but significant differences existed regarding age and pulmonary function grade (P < 0.05), as shown in [Table 1].
Table 1: Comparison in general information

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 > Methods Top


Equipment

Microwave Multifunctional Therapeutic Instrument (YZB/Guo0099-2006 Nanjing Kangyou) with a microwave frequency of 2450 MHz and output power of 10–100 W; 64-row spiral CT (Siemens, Germany); Big Bore 16-row Brilliance CT simulator (HILIPS); radiation therapy equipment (Varian23EX).

Preoperative preparation

Examinations were completed preoperatively to eliminate MA and radiation therapy contraindications. The patients and their families were told about the treatment purpose, possible risks, and complications. After obtaining their consent, radiation therapy and MA informed consent form was signed. An enhanced CT scan was utilized to evaluate the location, number, and size of the tumors. A body frame for radiation therapy was prepared, and the plans were made.

Treatment

Ablation treatment

The appropriate position was taken according to the planned puncture route. Electrocardiogram monitoring and oxygen inhalation were conducted, followed by the CT scan, then the puncture angle and route were selected again. Puncture points were marked on the chest wall surface, and the surgical area was disinfected. Local anesthesia was conducted with 2% lidocaine layer by layer. The MA needle was inserted layer by layer with CT guidance, the CT scan was repeated to confirm that the needle was located in the predetermined tumor position, then the needle was fixed. The water circulating cooling system was turned on, and the ablation power was selected. According to the tumor location and size, the power was generally 50–75 W, and the ablation time was 5–10 min. Single-needle ablation could be used for patients with a maximum tumor diameter of ≤3 cm, and multi-needle ablation could be used for those with a maximum tumor diameter of >3 cm. After treatment, the needle was slowly removed. CT scan was performed again to observe if there were any pneumothorax, hemorrhage, air embolism, or other-related complications.

Radiation therapy

Patients took a supine position, lying flat on the simulator bed. Cervical pleura or phantom was fixed according to the tumor location. The simulator was utilized for CT enhanced scanning. All patients were scanned in the supine position with head advanced, and the thickness and spacing were 3 mm. The CT scans were conducted and the images were uploaded to the Eclipse planning system, where maximum intensity projection (MIP) and average intensity projection (AIP) were established on the 4D-CT localization image. GTV was outlined under MIP and labeled GTV4D. CTV4Dt was generated by expanding 0.6 cm (squamous carcinoma)/0.8 cm (adenocarcinoma) of GTV4D, and 0.5–0.6 cm (positioning error) of CTV4Dt + involved mediastinal lymph node area to generate PTV4D. The involved organs, including the lung, spinal cord, and heart, were delineated on AIP. The dose was 60–70 Gy under conventional fractionated radiation therapy which was completed in 6–7 weeks.

Ablation group

Ablation was utilized in the lung lesions, and sequential IMRT was utilized for metastatic lymph nodes. Radiation therapy group: IMRT was utilized for lung lesions and metastatic lymph nodes. Both the ablation and radiation therapy groups were treated with platinum-based combination chemotherapy or molecular-targeted drugs post MA or radiotherapy.

Therapeutic evaluation

Follow-up observation

The follow-up period was 3–48 months. Enhanced CT scans were conducted every 3–6 months. Follow-up focused on the control of metastatic lymph nodes and primary lesions, progress-free survival (PFS), and related complications.

Complications

The main observation index was the radiation lung injury degree that was evaluated according to the revised acute radiation pneumonia criteria of the Radiation Therapy Oncology Group (RTOG).[7] Grade 0: No change; Grade 1: Mild symptoms of dry cough or dyspnea upon exertion; Grade 2: Persistent cough requiring narcotic, antitussive agents/dyspnea with minimal effort but not at rest; Grade 3: Severe cough that was unresponsive to narcotic antitussive agent or dyspnea at rest/clinical or radiological evidence of acute pneumonitis/intermittent oxygen or steroids; and Grade 4: Severe respiratory insufficiency/continuous oxygen or assisted ventilation.

Statistics

Data analysis was conducted with SPSS17.0 software (SPSS, Inc., Chicago, IL, USA). Measurement data with normal distribution were expressed as mean ± standard deviation, independent sample t-test was utilized, and enumeration data were tested by Chi-square test. The 1-, 2-, and 3-year PFS of the two groups were compared using the log-rank Chi-square test, and Kaplan–Meier curves were drawn. P < 0.05 was termed to be a significant difference.


 > Results Top


Local efficacy imaging evaluation

In the ablation group, complete ablation was achieved in 22 of the 34 cases with the first MA treatment, but 12 cases did not achieve complete ablation. Complete ablation was achieved in all 12 of these cases via supplementary ablation. The first complete ablation rate was 83.33% (15/18) in 18 cases with a tumor diameter of <3.0 cm, and 56.25% (9/16) in 16 cases with a tumor diameter of 3.0–5.0 cm. Five of the first incomplete ablation lesions failed to achieve the first complete ablation due to lesion area pain close to the chest wall, 4 failed due to irregular lesion shape, and 3 failed due to proximity of the legion to the large vessels. The radiation therapy plan was implemented in the radiation therapy group.

Complications

Five cases existed with the injury in the ablation group, which occurred in 14.70% (5/34), all of which were grade 1, according to RTOG classification criteria for RILI. Seventeen cases were in the radiation therapy group, which occurred in 40.48% (17/42), including 9 cases of grade 1, 4 cases of grade 2, 3 cases of grade 3, and 1 case of grade 4 [Figure 1].
Figure 1: Radiation-induced lung injury (grade 4)

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During ablation treatment, 28 cases had local pain, 18 cases had mild pain, and 10 cases had moderate pain, which lasted for 1–3 d post MA. Ten cases experienced a small amount of pneumothorax and 4 cases experienced a moderate amount of pneumothorax, which was improved after thoracic closed-chamber drainage. Two cases experienced a small amount of pleural effusion without special treatment and returning to normal after 1 w.

Comparison in postoperative progression-free survival and cumulative survival rate

The PFS of the ablation group at 1, 2, and 3 years were 70.59% (24/34), 47.06% (16/34), and 35.29% (12/34), and the PFS of the radiation therapy group at the same intervals were 71.43% (30/42), 52.38% (22/42), and 35.71% (15/42), with no significant difference (χ2 = 0.006, P = 0.936) (χ2 = 0.213, P = 0.645) (χ2 = 0.001, P = 0.970), as shown in [Figure 2].
Figure 2: Comparison in disease-free survival between the ablation group and the operation group

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 > Discussion Top


Locally advanced NSCLC refers to patients who have not developed distant metastasis but are no longer suitable for surgical treatment, and most of them (except some in stage III A and very little in stage III B) have lost the opportunity for surgery. Radiation therapy is an important treatment for locally advanced refractory NSCLC.[8] Increasing the dose of radiation therapy is often utilized to improve the survival rate of patients. However, the high-dose of radiation therapy greatly increases the risk of damage to surrounding normal tissue and death. The rapid development of percutaneous microwave coagulation therapy in- clinic has become one of the more important options for solid tumor treatment such as in the lung and the liver.

Studies have shown that tumor cells cannot tolerate high temperatures well, and many tumor cells will undergo coagulative necrosis at 54°C–60°C.[9] MA rapidly heats local tissues to kill tumor cells. Studies have proven that microwave coagulation reaches 60°C in the periphery and higher than 100°C in the center,[10] which completely inactivates the tumor. Meanwhile, MA could block the tumor blood supply vessels. The air close to the tumor of the lung is conducive to heat energy accumulation, which can cause a thermal insulation effect,[11] thereby providing thermal ablation efficiency for the lung tumor. The ablation range of ablation therapy is often beyond the treatment range. Park et al. found that after ablation, the tissue around the electrode would produce a protein degeneration series, and pathological changes such as collagen fiber thickening and scar fibrous tissue would replace the ablated lung tissue in 2 weeks.[12] Fibrous scarring plays a role in lesion encapsulation and the prevention of tumor metastasis.

This study analyzed MA and radiation therapy efficacy for locally advanced NSCLC. Results show no significant difference exists in PFS between the two groups over 1–3 years (P > 0.05), but the incidence of RILI was less in the ablation group, and MA is better for the patients with elder age and poor pulmonary function. Lesions selected in this study had a diameter of <5 cm considering that the tumor diameter of 5 cm is a widely accepted threshold for ablation therapy.

MA is minimally invasive, reproducible, easy to operate, and economical. However, the scope of MA is small and the conformal ability is insufficient. At present, when the tumor is slightly larger, or the shape is irregular, or there are large blood vessels in the periphery, the clinical application of MA is difficult to achieve. Whether or not radiation therapy combined with ablation is superior to radiation therapy alone for the treatment of locally advanced NSCLC differs with case selection, ablation equipment, and evaluation criteria. Therefore, studies report a wide variety of differing results. Moreover, the follow-up period is short, the number of clinical cases is small, the systematic data are insufficient, and the long-term curative effect requires further observation and study.


 > Conclusion Top


Above all, the development of the clinical treatment mode of tumors may cause a change in treatment concept and MA to become one of the most effective treatments. Limited cases were available and a low persuasion retrospective analysis was conducted. However, this study can be a valuable reference for future prospective randomized control studies.

Typical case: A male patient, 70-year-old, moderately differentiated adenocarcinoma in the right lung (stage IIIb). Arrow in [Figure 3]a indicates preoperative MA, and the arrow in [Figure 3]b indicates the intraoperative MA. The arrow in [Figure 3]c shows MA combined with IMRT. A 12-month CT scan shows tumor shrinkage and peripheral fibrous scar formation. The arrow in [Figure 3]d shows no tumor enhancement in the CT scan and complete ablation of the tumor.
Figure 3: Typical case: A male patient, 70-year-old, moderately differentiated adenocarcinoma in the right lung (stage IIIb). Arrow in Figure 3a indicates preoperative MA, and the arrow in Figure 3b indicates the intraoperative MA. The arrow in Figure 3c shows MA combined with IMRT. A 12-month CT scan shows tumor shrinkage and peripheral fibrous scar formation. The arrow in Figure 3d shows no tumor enhancement in the CT scan and complete ablation of the tumor.

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Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016;66:115-32.  Back to cited text no. 1
    
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Meijer TW, Peeters WJ, Dubois LJ, van Gisbergen MW, Biemans R, Venhuizen JH, et al. Targeting glucose and glutamine metabolism combined with radiation therapy in non-small cell lung cancer. Lung Cancer 2018;126:32-40.  Back to cited text no. 2
    
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Ren XC, Wang QY, Zhang R, Chen XJ, Wang N, Liu YE, et al. Accelerated hypofractionated three-dimensional conformal radiation therapy (3 Gy/fraction) combined with concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer: preliminary results of an early terminated phase II trial. BMC Cancer 2016;16:288.  Back to cited text no. 3
    
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Giuranno L, Ient J, De Ruysscher D, Vooijs MA. Radiation-induced lung injury (RILI). Front Oncol 2019;9:877.  Back to cited text no. 4
    
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Kodama H, Ueshima E, Gao S, Monette S, Paluch LR, Howk K, et al. High power microwave ablation of normal swine lung: Impact of duration of energy delivery on adverse event and heat sink effects. Int J Hyperthermia 2018;34:1186-93.  Back to cited text no. 5
    
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Knoll MA, Salvatore M, Sheu RD, Knoll AD, Kerns SL, Lo YC, et al. The use of isodose levels to interpret radiation induced lung injury: A quantitative analysis of computed tomography changes. Quant Imaging Med Surg 2016;6:35-41.  Back to cited text no. 6
    
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Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995;31:1341-6.  Back to cited text no. 7
    
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Bradley J, Hu C. Learning from trials on radiation dose in non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2016;96:748-50.  Back to cited text no. 8
    
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Stone HB, Dewey WC. Biologic basis and clinical potential of local-regional hyperthermia. Radiat Oncol 1987;2:1-2.  Back to cited text no. 9
    
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Murakami R, Yoshimatsu S, Yamashita Y, Matsukawa T, Takahashi M, Sagara K. Treatment of hepatocellular carcinoma: Value of percutaneous microwave coagulation. AJR Am J Roentgenol 1995;164:1159-64.  Back to cited text no. 10
    
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Shiono S, Yanagawa N. Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stage I lung adenocarcinoma. Interact Cardiovasc Thorac Surg 2016;23:567-72.  Back to cited text no. 11
    
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Park BJ, Louie O, Altorki N. Staging and the surgical management of lung cancer. Radiol Clin North Am 2000;38:545-61, ix.  Back to cited text no. 12
    


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