Metastatic Heteroplasia of the Lung
70-year-old male underwent epileptic seizures. A brain CAT scan showed a space occupying lesion with surrounding edema in his left frontal lobe. A subsequent MRI examination enabled the demonstration of four separated lesions in his brain consistent with metastases. A total body CAT scan demonstrated a mass in the right lung. The diagnosis of poorly differentiated squamous cell carcinoma of the lung was established by bronchoscopy and transbronchial biopsy. The patient was treated by brain irradiation.
1) Suggested treatment?
2) Are there any experimental protocols?
male, 70 years old
Diagnosis: Metastatic heteroplasia of the lung
Hypertensive ischemic heart disease; Type II diabetes mellitus; hypercholesterolemia; Subclinical hyperthyroidism; Benign prostatic hypertrophy; Gallstones.
The patient was initially hospitalized at the Hospital of Cesena for the onset of epileptic seizures and was subsequently transferred to the neurology department of the Hospital of Baggiovara, as the emergency CAT scan of the brain performed on April 09 showed the presence of an expansive lesion located in the left frontal lobe and perifocal edema. In the NMR of the brain dated April 2009, at least four appreciable partially cystic-necrotic nodular lesions can be seen in the intraparenchymal area, with intense graphic contrast permeation of the solid portion, surrounded by extended perifocal edema, respectively in the vertex of the left frontal lobe (diameter of about 17 mm), in the back of the same side of the parietal lobe of 9 and 5 mm, and in the rolandic area of the frontal cortex to the right (7mm). Findings are suggestive of lesions of a secondary and metastatic nature. During the hospital stay in neurology at Baggiovara, the patient had both a radiation therapy consultation and an endocrinology consultation for the subclinical hyperthyroid findings. The patient then had a CAT scan of the chest and abdomen on April 2009, which showed a pulmonary mass of the posterior basal segment of the inferior lobe of the right lung without a good cleavage plane with the pleura, with other small 4 mm lesions in the anterior segment of the superior lobe on the same side.
The patient was therefore transferred to the respiratory diseases department of the Modena University Hospital, where he was hospitalized For 9 days in April 2009. During the hospital stay, a bronchoscopy with transbronchial biopsy was performed, with the following results: “fragments of bronchial mucosa with poorly differentiated squamous cell carcinoma.” A bone scan was performed for more complete diagnostic information. This total body scan did not show any focal areas of increased uptake of the radioisotope (99mTc-MDP at the dose of 740 MBq i.v.) attributable with certainty to acute recurrent lesions.
Following the results of the histological examination given above, the patient was advised to undergo radiation therapy, which he began on May 2009, for a course of ten sessions total.
Case interpretation and suggested treatment:
The presentation of brain metastases in an otherwise asymptomatic patient is well known within the population of patients with bronchogenic carcinoma, and I agree with this interpretation regarding the brain lesions in the case of the patient. The histological characterization of the lung tumor has been satisfactorily obtained by transbronchial biopsy. Based on the above described data I agree with the treating team, namely that we are dealing with a case of Grade 3 squamous cell carcinoma of Rt lung lower lobe, at Stage IV by metastases to brain (and possibly to Rt lung upper lobe as well). This is a condition that should be approached by a "conservative" policy, aimed at maximal prolongation of life with the best performance status.
Accordingly, I support the recent brain irradiation as first step in his treatment. I presume that he is on permanent anticonvulsant treatment aimed at prevention of additional convulsive events. Most probably he is still receiving dexamethasone for decreasing the peritumoral brain edema. I recognize that his Diabetes may represent a problem with steroidal treatment, possibly requiring adjustments of his antiglicemic treatment. Yet, I would recommend a repeated CAT scan of the brain along with the tapering down of steroids for confirming the regression of the edema.
At the same time a repeated CAT scan of the lungs should be conducted (two months since its last evaluation?) for determining the rate of progression of his disease. A trial of platinum-based chemotherapy (probably best with gemcitabine) should be considered as soon as the disease progresses. If at least an arrest of the disease is achieved following 3 cycles, and if no grade III-IV toxicity is caused, I would proceed with the same regime up to 5-6 cycles. If this is found to be effective it could contribute to the maximal prolongation of his best performance status.
In the event of further disease activity in the brain while with no progressive disease in any other organ, and with preserved good performance status (grade 0-1) I would suggest an additional consultation with radiotherapists that are experienced in the application of stereotactic brain irradiation ("radio-surgery"). This additional irradiation may contribute since: (a) brain metastases may represent THE limiting factor both for quality and for length of life; (b) brain irradiation has not yet reached the maximal tolerated dose in the current case; (c) this option should be discussed in due time considering the eventual course of both the disease and the chemotherapy treatment.
Experimental protocols and prognosis:
I am not aware of any practical experimental protocol for a non-operable poorly differentiated carcinoma of lung with multiple brain metastases.
Yet, there are first indications that "biological treatments" can improve he effect of chemotherapy for non small cell carcinoma of the lung (NSCLC). More specifically, Cetuximab has shown prolongation of survival in patients with NSCLC including those with squamous cell carcinoma, when administered in combination with platinum-based chemotherapy (FLEX study). However, this has not been proven in the presence of active brain metastases. Therefore, only if the brain condition of the patient is well controlled I would suggest considering the combination of Cetuximab and chemotherapy. Furthermore such a decision should be preceded by an immunohistochemical analysis of the biopsied material which demonstrates the presence of Epidermal Growth Factor Receptors. Another biological treatment with proven contribution includes Bevacizumab. However, this is CONTRAindicated for squamous cell carcinoma because of the proven risk of fatal hemorrhage in lung tumors of this histological type.
The patient has just initiated his treatment, and his precise prognosis is still uncertain. I very much hope that he will be one of those patients for whom treatment is effective such that he can enjoy an extended prognosis in good quality of life.