Lung cancer induced from chemotherapy a 20 years old case.

Lung cancer is diagnosed at a late stage although we have novel diagnostic tools. The association of smoking and other environmental factors are well known. However; there are cases where a malignancy is associated with previous radiation treatment. There is an association between radiotherapy treatment and cancer incidence. We present a case where lung cancer and laryngeal cancer was induced 20 years after radiation therapy of a hogkin lymphoma.

Introduction

We have recent advances in the diagnosis and treatment of lung cancer with novel instruments and therapies. The convex-probe endobronchial ultrasound and the radial endobronchial ultrasound (EBUS) brought a revolution to the diagnosis of lung cancer, however; they are not tools that can be used in every pulmonary department [[1], [2], [3]]. On the other hand we have novel therapies for non-small cell lung cancer (NSCLC) such as; immunotherapy (nivolumab and pembrolizumab) and targeted therapies with tyrosine kinase inhibitors (TKIs) for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), murine sarcoma viral oncogene homolog B (BRAF) and proto-oncogene tyrosine-protein kinase (ROS-1) [4]. Radiotherapy can be used either as a primary therapy for NSCLC or palliative care [5]. In any case the medical history of the patient might reveal co-occurrence of multiple primary cancers. There is also the case where radiotherapy or chemotherapy pretreatment induced another type of cancer [6]. In the current case we will present a patient diagnosed with Hodgkin lymphoma in 1997 and presented in situ laryngeal cancer after 15 years and lung cancer after 20 years. Occurrence of a cancer after radiotherapy treatment has been previously reported and the association of radiotherapy treatment and cancer has been established [7].

Case presentation

A 57 year old patient (age today) was diagnosed with Hodgkin lymphoma in 1997 from a tracheal lymph-node. Smoking history when diagnosed with Hodgkin lymphoma with 15 p/y. He received in total 3000 rad of radiotherapy as primary therapy. The disease was stable until 2010 were the patient presented in the outpatient cabinet with enlarged lymph-nodes in the whole body. Again a biopsy from a tracheal lymph node revealed Hodgkin disease relapse. He received 6 cycles of Andriamycin 45mg Bleomycin 670mg Viblastine 10mg Detisene 680mg for 6 months. A positron emission tomography 3 months after the last chemotherapy was negative for active disease. The patient remained under observation as an outpatient for 4 years without disease relapse. However; early in 2016 he presented in the outpatient cabinet with hemoptysis and a in situ laryngeal cancer was diagnosed (Fig. 1). He received 6000 rad as radiotherapy treatment and platinum analog for six cycles carboplatin AUC 600mg. The patient remained under observation. In 2017 a CT thorax revealed a mass in the right lower lobe and enlarged mesothorax lymph-nodes positive with PET-CT (Fig. 2). Biopsy of the lymph-nodes with a convex probe endobronchial ultrasound revealed adenocarcinoma with EGFR and ALK negative expression(Fig. 3). He received 6 cycles of carboplatin AUC 600 and pemetrexed 1000mg. He was disease free for 4 months until a new staging with PET-CT revealed disease relapse and 4 cycles of carboplatin AUC 600 and taxane 370 derivative was administered. A further investigation in the first biopsy for BRAF, ROS-1 and PD-L1 expression revealed negative expression.

Fig. 1

Figure from microlaryngoscopy.

Fig. 2

CT of the thorax.

Fig. 3

Endoscopy with convex probe endobronchial ultrasound (EBUS) blue arrow indicating the block of lymph-nodes.

Discussion

It is known from the epidemiological study of survivors of atomic bomb irradiation [8,9] and it has been suggested and observed in clinical practice that irradiation of surrounding tissues can cause second cancers [10,11]. The benefits of radiotherapy outweigh the risks of developing subsequent cancers, therefore methods of minimizing the radiation dose delivered to surrounding tissues or the volume should be further investigated. However; there also other factors contributing to carcinogenesis like; environmental exposure to carcinogens, genetic predisposition, misdiagnosis of metastases as primary cancers, reproductive factors. Therefore increased medical surveillance should follow the first cancer for treatment-related effects. It has been observed that genetic and environmental predisposition may increase the incidence of a second cancer, while treatment related tumors are expected to develop some time after an iatrogenic effect. Previous clinical observations indicate that second cancers after an exposure to radiation would develop within a time window of 5 years for leukemia and 10 years for solid tumors [[12], [13], [14], [15], [16], [17]]. Previously it has been suggested that a certain latency period passes before a new tumor appears. There is a clear association between latency time and cancer type. Moreover; chemotherapy can induce second cancer development [18]. An excess incidence of acute myeloid leukemia and myelodysplastic syndrome has been associated with therapy in those patients who received doxorubicin when compared with those who received doxorubicin combined with cyclophosphamide therapy [16]. The incidence was higher in those patients that received intensified cyclophosphamide doses (requiring granulocyte colony-stimulating factor support). An excess incidence of lung cancer has been observed at 10 years or more after radiotherapy, in several studies [17,19]. In our case we have an association of radiotherapy, chemotherapy and secondary factors which we believe were smoking history and genetic predisposition. The patient is under close follow-up to date.

Disclosure

The authors declare no conflict of interest.