Simultaneous regression of non‐small cell lung cancer and orbital extranodal marginal zone lymphoma with chemoradiotherapy for lung cancer

Abstract This report describes the case of a 79‐year‐old Japanese man diagnosed with orbital extranodal marginal zone lymphoma (EMZL) and stage IIIA lung cancer. The patient received concurrent chemoradiation for lung cancer with carboplatin/paclitaxel treatment, resulting in regression of both the lymphoma and lung cancer. To our knowledge, this is the first reported case of concurrent orbital EMZL and lung cancer. In this case, a treatment strategy that prioritized lung cancer treatment was deemed appropriate. This case suggests that chemotherapy with carboplatin and paclitaxel may serve as an effective treatment for both lung cancer and lymphoma.


INTRODUCTION
Concurrent cancers are frequently observed, and treatment strategies should be individualized based on the prognosis of the overlapping diseases and their rate of progression. Herein, we present the case of a patient with an orbital extranodal marginal zone lymphoma (EMZL) of mucosaassociated lymphoid tissue, a low-grade lymphoma, and a stage IIIA lung squamous cell carcinoma. To our knowledge, this is the first reported case of concurrent orbital EMZL and lung cancer. Concurrent chemoradiation for lung cancer resulted in the regression of both lymphoma and lung cancer.

CASE REPORT
A 79-year-old Japanese man presented to the Department of Respiratory Medicine at our hospital because of a chest radiographic abnormality ( Figure 1A). He had no specific respiratory symptoms but complained of difficulty in opening his left eye. Computed tomography (CT) and fluorodeoxyglucose F18 positron emission tomography (FDG PET) scans revealed a 4.0 cm Â 2.4 cm mass in the left upper lobe and mediastinal lymphadenopathies; no distant metastases were observed ( Figure 1B-E). Additionally, an orbital mass was detected by FDG PET and contrast-enhanced magnetic resonance imaging (MRI) of the head ( Figure 1F, G). Histopathological examination of the transbronchial lung biopsy revealed squamous cell lung carcinoma at clinical stage cT3N2M0 (Figure 2A, B), and percutaneous biopsy of the orbital mass revealed EMZL ( Figure 2C-E). An additional bone marrow biopsy confirmed the EMZL, which was diagnosed as stage IE. The patient was initially treated with chemotherapy, carboplatin (area under the curve, 2) and paclitaxel (40 mg/m 2 ) weekly, and concurrent thoracic radiation 60 Gy/30 Fr for lung cancer. One month after chemotherapy, both the lung cancer and orbital EMZL regressed (Figure 3), and the patient was able to open his left eye. Radiotherapy was planned for the orbital EMZL.

DISCUSSION
We report a rare case of concurrent malignancies in which treatment for lung cancer was also effective for EMZL.
In Japan, lung cancer is the leading cause of cancer-related deaths in men, with 52,600 deaths reported in 2021. 1 Malignant lymphomas affect 19,200 men annually; 1 most are intranodal lymphomas, whereas extranodal lymphomas are rare. Lymphomas of the ocular adnexa account for approximately 5%-10% of extranodal lymphomas, 2 and 50%-63% of ocular adnexal lymphomas are orbital lymphomas. 2 EMZL is the most common type of orbital lymphoma, accounting for 57% of all cases. 3 To our knowledge, there are no reports of the simultaneous occurrence of lung cancer and orbital EMZL, and only one observational study has reported a case of lung cancer during a treatment-free follow-up of ocular adnexal EMZL. 4 EMZL is a low-grade lymphoma, and its prognosis is generally good, particularly for EMZL localized to the ocular adnexa. 4 A retrospective cohort study in Japan revealed that out of 36 patients with untreated ocular adnexal EMZL, six died, of which only two deaths were due to EMZL progression. 4 Notably, stage III lung cancer is the final opportunity for curative medical treatment. Therefore, prioritizing lung cancer treatment in our case was an appropriate strategy.
The treatment options for orbital EMZL include radiotherapy, surgery, and rituximab. In cases where radiotherapy is the preferred treatment, a common approach involves a 30 Gy/20 Fr regimen. However, if the patient has a history of extranodal marginal zone lymphoma (EMZL) and requires treatment prior to lung cancer therapy, there may be a potential delay of up to 4 weeks, which could remarkably reduce the likelihood of a successful medical cure for the lung cancer. When systemic chemotherapy is required for EMZL due to the stage, physicians typically choose treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; bendamustine plus rituximab; or rituximab plus cyclophosphamide, vincristine, and prednisone because the disease is classified as B-cell lymphoma. 3 In the present case, carboplatin plus paclitaxel was selected as the platinum-based and taxane-combined anticancer agent. Chemotherapy regimens, including platinum, are effective in treating patients with refractory non-Hodgkin's lymphoma, and both lung cancer and EMZL may also respond to carboplatin. However, apart from the effectiveness of carboplatin and paclitaxel in treating lymphoma, there are two other possible reasons for the reduced tumour size seen in our case. First, steroids can temporarily reduce the size of lymphomas, and the administration of dexamethasone to prevent side effects during chemotherapy for lung cancer may have affected tumour shrinkage. However, the effect persisted after chemotherapy despite the administration of steroids only on the first day of treatment, indicating that chemotherapy was effective. Second, in some cases, ocular adnexal lymphoma can spontaneously regress, 5 which may have occurred in the present case. However, the population studied in the previous report was distinct from our patient, and there have been no reports of the spontaneous regression of orbital EMZL. We believe that the chemotherapy for lung cancer was effective for EMZL, and therefore, treatment for lung cancer should be prioritized in cases where the two conditions occur simultaneously. The standard treatment for stage III non-small cell lung cancer is chemoradiotherapy, followed by durvalumab. However, in this case, radiation pneumonitis was observed immediately after chemoradiotherapy, and after consultation with the patient, we decided not to administer durvalumab.
In conclusion, in cases of concurrent orbital EMZL and lung cancer, the treatment of lung cancer should take precedence.