The patient is a 60 year-old male diagnosed with non-small cell lung cancer. The patient’s father was a smoker, had hypertension and diabetes, and died at the age of 57 as a result of lung cancer. The patient’s mother is 84 and apparently in good health. The patient does not have any siblings. He has two sons who are apparently in good health.

 

The patient has been smoking 20-25 cigarettes a day for 35 years. He was in apparent good health until about 10 months before this review, when he began experiencing a pain in his shoulder that was resistant to various analgesic therapies. After a short time, the patient experienced the onset of palpebral ptosis and paresthesia in his left hand in the region of innervation of the ulnar nerve.

 

The patient turned to medical services for a chest x-ray that showed an abnormality in the left lung apex. He was admitted for a broad range of tests: ECG, blood tests, echo color Doppler of the epiaortic vessels, abdomen and thyroid echotomography, total body skeletal scintigraphy, chest CAT scan, total abdomen CAT scan, cranial CAT scan, guided CT biopsy, cytopathology consultation. The diagnosis was (Pancoast) non-small cell apical carcinoma and Claude Bernard–Horner Syndrome. A cycle of chemotherapy and adjuvant radiotherapy was advised after a possible surgical procedure. Therefore, the patient began his first chemotherapy cycle with Taxotere 75 mg/m2/iv (150 mg/tot/iv) and Cisplatin 75 mg/m2/iv (150/tot/iv) following cortisone and antiemetic premedication. The patient was required to repeat this therapy every 21 days. He was prescribed the relevant domiciliary therapy for his symptoms. Subsequently, the patient had three cycles of chemotherapy, which he tolerated fairly well. Given the reduction in the tumor mass, the patient was admitted for the surgical procedure. This involved a left upper en-bloc lobectomy with ribs 1 and 2, vertebral biopsy and lymphadenectomy via widened thoracotomy. The procedure was successful and the patient was discharged with a diagnosis of left lung squamous carcinoma infiltrating the chest wall with metastases in the mediastinal lymph nodes, stage T4N2. The histology results were as follows: Moderately undifferentiated squamous cell carcinoma (G2) infiltrating the muscle tissue of the chest wall (T1-4) and vertebral body tissue. Collateral pulmonary parenchyma with slight emphysema. Mediastinal lymph node packet with squamous cell carcinoma metastases (NM1). A further 4 ilo-mediastinal lymph nodes with reactive hyperplasia. pT4N2Mx.

 

Following discharge, the patient began and completed the adjuvant radiotherapy protocol, which included the left apex region, the supraclavicular region, the mediastinum to the bifurcation. Radiation was carried out with a linear accelerator, power 15 MeV, with multifield technique, fractioning 200 cGY/session to a total dose of 5000 cGy. The treatment was tolerated fairly well. The patient subsequently had a bone scintigraphy that showed the presence of “repetitive lesions in the left coxofemoral articulation, right sacroilial synchondrosis with a central lacunar area, vertebral bodies D10 and D9, the posterior region of rib 6 (probably as a result of surgery), anterolateral region of right rib 2.” The results of the patient’s full abdomen CAT scan were as follows: “Parenchymal tissue lamellae that obliterate the left apical region, causing partial infiltration of the left hemisoma of D2. The abnormality has developed since the previous follow-up. Repetitive nodular lesion of approximately 20 mm in diameter in the left costal area in the upper lateral region. The formation is adhered to the pleura and there is significant homolateral pleural effusion. Repetitive lesion in soma D8. Voluminous repetitive lesion with large necrotic areas affecting the right ilial ala at full depth, interrupting the cortical both anteriorly and posteriorly. The lesion infiltrates the contiguous soft tissue and has a diameter of 8x4 cm. The pulmonary parenchyma presents a small nodular area of approximately 10 mm in the apical segment of the right inferior lobe. No significant mediastinal lymphoadenomegalies. Newly developed small focal area of 12 mm in segment VIII of the hepatic region. The cyst in segment I has remained unchanged. No significant dilation of the intra and extra hepatic biliary duct. The patient’s pancreas, spleen and kidneys are within normal limits. No adrenal abnormalities. No abdominopelvic lymphoadenomegalies. No free effusion in abdominal cavity.”

 

Cranial CAT scan within normal limits.

 

 

 

A) Reconstruction of the case history:

The patient is a 60 year old male, who has been smoking 20-25 cigarettes a day for 35 years. About 10 months before this review he began experiencing symptoms of Horner´s syndrome, and was consequently diagnosed to suffer from pancoast tumour (squamous cell carcinoma) of left lung. The patient received three cycles of neo-adjuvant chemotherapy with Taxotere (75 mg/m2) and Cisplatin (75 mg/m2). Given the reduction in the tumour mass, the patient was admitted for a radical surgical procedure, which apparently achieved complete gross resection of a tumour that infiltrated the chest wall (T1-4) and vertebral body tissue (left hemisoma of D2), and metastases in the mediastinal lymph nodes (stage T4N2). By that time there were no demonstrable distant metastases (Mx). His treatment was then complemented by adjuvant radiotherapy to the tumor bed and to the areas of its lymphatic drainage. The patient later had a skeletal scintigraphy that showed the presence of several bone metastases. In addition a CAT scan revealed a newly developed focal area consistent with metastatic spread to the liver, and a small nodular area in the parenchyma of the right lung (was this a new finding, consistent with metastatic spread to the lung as well?).

 

B) Comments:

The presence of new metastatic findings (in bones and in liver and possibly in lung as well), represent a totally new kind of situation, thus requiring a different approach for medical treatment from now on.

 

It is eventually apparent that the intensive therapeutic measures successfully undertaken for the control of the pancoast tumor (T4N2), while there was a possibility of curing the patient, were applied too late for that purpose. In retrospect, they failed to prevent the spread of distant metastases, although they did contribute to saving the patient from the significant morbidity and suffering correlated with uncontrolled pancoast tumors.

 

At the current stage of the disease (M+), treatment should consist of systemic therapy. However, since this does not have curative potential at this point, the preference of types and sequence of agents in this situation is usually at the discretion of the attending physician.

 

The initial response to Docetaxel and Cisplatin is encouraging. However, the appearance of distant metastases within less than 6 months should suggest some different component of treatment.

 

Question A. What would be the most useful therapeutic indications in this stage of the patient’s condition? The rate of response to any doublet is higher than to any single drug, but this is expected to be more toxic as well. Therefore, if the attending physician chooses a doublet, such as Carboplatin and Gemcitabine, or Carboplatin and Pemetrexed, this should be applied very carefully considering previous treatment with chemotherapy and irradiation.

 

If the patient has already shown significant toxicity consequent to previous treatment, future treatment should be initiated/ tested at adequately reduced doses.

 

Alternatively, if the patient is not in a condition requiring a rapid palliation, I would offer to expose him to single drugs, carefully testing the clinical benefit from each one. In view of the inevitable prognosis the practical aim of treatment should not be that of achieving response but that of preserving quality of life and prolonging survival, as can be achieved by arresting tumor progression. The main drugs for these purposes are pemetrexed, vinorelbine and gemcitabine. The presence of various bone metastases, justify the addition of bisphosphonates along with chemotherapy. This could improve the outcome, at least from the palliative point of view.

 

Question B. Are there any new experimental medications that could be used? A) An additional treatment option is that of Erlotinib. Although the patient is not in the most promising category for this treatment, namely that of a non-smoker/female patient with Adenocarcinoma of lung, he still might benefit from this drug. According to the experience of the "National Cancer Institute of Canada Clinical Trials Group" [Clin Lung Cancer. 2006 May;7(6):389-94] "Subset analyses of ever-smokers revealed significant survival advantages for men and patients with squamous cell histology. Male ever-smokers with squamous cell non-small-cell lung cancer derived a significant survival benefit from erlotinib (HR, 0.66; P = 0.015) despite a very low tumor response rate." The chances for clinical benefit from erlotinib could be better predicted if his tumor is analyzed for expression of EGFR, although for practical purposes this is not mandatory in the present case.

 

B) Bevacizumab is recognized as a means of increasing the effect of chemotherapy in various cancer diseases, including in non-small cell lung cancer [N Engl J Med. 2006 Dec 14; 355(24):2542-50]. However, due to an increased risk for hemorrhage correlated with the subtype of squamous cell histology, [Clin Lung Cancer. 2006 Dec;8 Suppl 1:S23-30] this is not recommended in the case of this patient.