Tracheobronchial Adenoid Cystic Carcinoma Treated Successfully With Chemoradiotherapy Followed by Durvalumab: A Case Report

Discussion

The standard therapy for ACC has, so far, not yet been established. While radiotherapy and chemoradiotherapy have been administered to unresectable ACC patients, no randomized phase III trials on these therapies have been conducted to date. It is also not clear whether chemotherapy significantly extends the survival of advanced tracheobronchial ACC (4), although some reports have shown survival benefits in ACC patients who received radiotherapy (5). Thus, we chose chemoradiotherapy for this patient. Due to the proximity of the trachea to the lungs and esophagus, both radiation pneumonitis and esophagitis are potential problems associated with increasing radiation intensity. Prevention of radiation pneumonitis is important because it is sometimes severe and fatal. Hence, we used IMRT to reduce pneumonitis without compromising its efficacy. IMRT allows focusing of the radiation on the tumor and reduces the amount of radiation to the surrounding normal tissues, allowing the tumor to receive a stronger radiation dose without an increase in side effects (6). The percentage of total lung volume irradiated by a radiation intensity of >20 Gy (V20) is an important predictor of radiation pneumonitis. Reportedly, in lung cancer cases receiving chemoradiotherapy, the risk of developing symptomatic radiation pneumonitis is low if V20 is less than 25-30% (7). In our patient, V20 was maintained at 30%, and although the patient developed radiation pneumonitis, it was only grade 1. These results suggest that IMRT was effective in reducing side-effects for ACC treatment.

Although standard chemotherapy regimens for advanced tracheal ACC have not been established, tracheobronchial carcinoma is treated as a part of lung cancer. Currently, the standard therapy for patients with a good performance status and unresectable stage III NSCLC, regardless of PD-L1 status, is platinum doublet chemotherapy concurrent with radiotherapy, followed by durvalumab, as recommended in the PACIFIC trial (8). Various chemotherapy regimens are used in combination with radiation therapy. Weekly carboplatin plus paclitaxel is one potential option because it is widely used and easy to interrupt if bone marrow suppression develops during treatment. Since ACC is a rare type of NSCLC, chemoradiotherapy followed by durvalumab, the so-called PACIFIC regimen, might be a standard therapy for stage III ACC. However, the PACIFIC trial report did not describe whether or not ACC was included in the trial (8). Recently, a tracheal ACC case that had been successfully treated with chemoradiotherapy and durvalumab was reported (9). In that study, the authors used cisplatin and S-1 (tegafur/gimeracil/uracil) as the chemotherapy regimen (9), while we successfully used weekly carboplatin and paclitaxel, suggesting that both regimens are effective for ACC. To the best of our knowledge, our case is the second reported tracheobronchial ACC case successfully treated with chemoradiotherapy followed by maintenance ICI therapy.

Study limitations. Due to the limited biopsy sample volumes, driver oncogene mutations and expression levels of PD-L1 could not be explored. Some driver oncogenes, including EGFR, KRAS, ALK, PDGFR, and DDR2, have been identified as potential therapeutic targets for ACC (10). Several reports have shown favorable effects of molecular-targeted agents, such as EGFR-TKI, and multi-targeted TKI (11, 12) in selected ACC patients, suggesting that these might be potential treatment options. Additionally, we cannot comment on the duration of progression-free survival and overall survival with this treatment due to the short observation period in our case. Continuous follow-up is needed in the future.