Abstract
A 56-year-old male with stage IIIA (UICC 7th) non-small cell lung cancer (adenocarcinoma) received radiotherapy with 66 Gy/33 fractions concomitant with CBDCA and PTX. A partial response was achieved after chemoradiotherapy and the tumor continued to shrink over a period of 1 year; however, regrowth of the tumor attached to the aortic arch was observed without any other residual tumor or metastases. We diagnosed recurrence with slightly increased 18F-FDG uptake (maximum standardized uptake value: 12.2). Stereotactic radiotherapy was performed for the relapsed lesion with 60 Gy/10 fractions. The patient has survived for more than 5 years after stereotactic radiotherapy without recurrence or metastases, although he has been suffering from chest pain that has required treatment with a low dose of oxycodone.
Keywords: Non-small cell lung cancer, Salvage stereotactic radiotherapy, Definitive chemoradiotherapy
Introduction
Chemoradiotherapy is one of the definitive treatment methods for patients with stage III non-small cell lung cancer (NSCLC). However, local recurrence in the primary site is often seen after definitive chemoradiotherapy [1]. Even without metastases, it is still difficult to cure in-field recurrence after chemoradiotherapy.
The effectiveness of stereotactic radiotherapy for a small target has been reported; however, re-irradiation for recurrence after definitive radiotherapy is risky. Re-irradiation, even re-irradiation using stereotactic radiotherapy, should be performed carefully, especially for central regions of the lung, in order to prevent severe radiation-induced complication (e.g., fistula and bleeding) [2].
Case report
The patient was a 56-year-old Japanese male who was a heavy smoker with a 54-pack-year history. A tumor in the left upper lobe and left hilar swelling were revealed by a chest X-ray in a health examination. Results of a blood test showed a high serum carcinoembryonic antigen (CEA) level of 12.9 ng/ml. He had no significant historical disease. Adenocarcinoma was proved by biopsy through bronchoscopy. A diagnosis of clinical T3N2M0 (Union for International Cancer Control (UICC) 7th) NSCLC was made by CT and F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET). He was judged to be inoperable and concomitant chemoradiotherapy consisting of elective nodal irradiation and carboplatin (2 area under the blood concentration–time curve (AUC)) and paclitaxel (45 mg/m2) was performed. Elective nodal regions were irradiated by 3-dimensional conformal radiotherapy (3D-CRT) with 40 Gy/20 fractions (fr.) (Fig. 1a), and a sequential boost to the gross tumor for a total dose of 66 Gy was performed (Fig. 1b). Chemotherapy was performed for a total of 9 cycles. CT showed that partial regression was achieved 5 months after completion of chemoradiotherapy without severe complication. Serum CEA had fallen to within the normal range. At 18 months after chemoradiotherapy, CT showed regrowth of the tumor attached to the aortic arch with high FDG accumulation (maximum standardized uptake value (SUVmax): 12.2), but there was no other abnormal accumulation on FDG-PET (Fig. 2). He was asymptomatic; however, serum CEA level was increased again to 5.5 ng/ml. A diagnosis of in-field recurrence at the primary site was made. At that time, there was no effective and safe treatment method after definitive chemoradiotherapy, and salvage stereotactic radiotherapy was therefore performed. Stereotactic radiotherapy was performed with 7 non-coplanar static 6 MV X-ray beams to the site of relapse using daily cone-beam CT scan imaging before each fraction (Fig. 3). The patient was prescribed 60 Gy/10 fr. for the isocenter. No other treatment was performed. After salvage stereotactic radiotherapy for local recurrence, FDG-PET and CT showed that complete regression had been achieved (Fig. 4); however, grade 1 lung fibrosis and grade 2 chest pain were shown. The patient has survived and has been working for more than 5 years after salvage treatment, although he has been suffering from chest pain, which might be due to radiation neuritis of an intercostal nerve, that has required treatment with low-dose oxycodone.
Fig. 1.
a Dose distribution of radiotherapy with 40 Gy by anterior–posterior opposing fields. b Dose distribution of boost radiotherapy with 26 Gy by 4 fields
Fig. 2.
Local recurrence close to the aortic arch was shown by a CT and b FDG-PET/CT
Fig. 3.
Dose distribution of salvage stereotactic radiotherapy: a axial image and b coronal image
Fig. 4.
a CT and b FDG-PET/CT 5 years or more after salvage stereotactic radiotherapy showed complete regression
Discussion
Stereotactic radiotherapy for primary treatment of early-stage peripheral lung cancer has been established with some prospective trials. Local control rates for early-stage lung cancer using stereotactic radiotherapy have been reported to be higher than 90% [3, 4]. A systematic review including 563 central lung tumors by Senithi et al. showed that grade 3 or 4 toxicity occurred in 8.6% (36/418) of the central tumors treated with stereotactic radiotherapy [2] and they reported that treatment-related mortality was 1.0% when the biologically equivalent normal tissue dose (BED3) was ≤ 210 Gy and that no grade 3 or 4 toxicity occurred when using a BED3 ranging between 133 and 144 Gy. In the present case, although cumulative BED3 for the aortic arch attached to the recurrent tumor was 275.3 Gy, cumulative BED3 for the main bronchus within 2 cm of the proximal bronchial tree was 112.5 Gy, which was summed BED3 based on maximum irradiated doses in each radiotherapy, and cumulative BED3 for the esophagus was 143.6 Gy. Salvage stereotactic radiotherapy after definitive chemoradiotherapy could, therefore, be performed safely.
Amini et al. reported a literature review, including 140 patients, of re-irradiation using stereotactic radiotherapy for lung cancer previously treated with conventional radiotherapy. They showed relatively good local control with few severe complications [5]. On the other hand, Trovo et al. reported 17 patients who received stereotactic radiotherapy for centrally located recurrent NSCLC within the previously irradiated field [6]. Even though the prescription dose was limited up to the total 2-Gy-per-fraction cumulative dose to 87–100 Gy, 4 patients (23%) experienced grade 3 radiation pneumonitis and 1 patient developed fatal pneumonitis. One patient died of fatal hemoptysis 2 months after the completion of stereotactic radiotherapy. They reported that the high rate of severe toxicity is a concern in centrally located recurrent lung cancer. Re-irradiation for a centrally located tumor, especially a tumor located within 2 cm of the proximal bronchial tree, seems to require sufficient caution. When we treated this patient, those reviews had not been published yet. Even now, no one knows the appropriate irradiation dose in such a case. The reasons for selecting 60 Gy/10 fr. as a salvage treatment after definitive chemoradiotherapy were because we considered that we should use a higher biological effective dose for the tumor (BED10) than that used in the initial treatment for the tumor, which resisted the initial dose, and that we should irradiate with BED10 of 100 Gy or as close to it as possible due to past reports on SBRT for primary lung cancer [7, 8].
Recently, immune checkpoint inhibitors have been developed and have been shown to increase the overall survival of patients with previously treated metastatic or recurrent NSCLC [9]. Immune checkpoint inhibitors might be safer than re-irradiation; however, salvage stereotactic radiotherapy could be expected stronger local effect. Concurrent stereotactic radiotherapy with immune checkpoint inhibitors might be the most effective.
Conclusion
Salvage stereotactic radiotherapy for in-field recurrence after definitive chemoradiotherapy might be an effective treatment method for NSCLC; however, if in-field recurrence occurs in a central region, salvage stereotactic radiotherapy should be used with care.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee. For this type of study, formal consent is not required.
Informed consent
Informed consent was obtained from the patient.
Footnotes
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