Naples 2000 - Relazioni



1. Lung cancer in the setting of multiple primary cancers

G. Massard

Department of Thoracic Surgery, Hôpitaux Universitaires de Strasbourg, F-67091 Strasbourg

2. LUNG METASTASES AND LASER TREATMENT

D. Branscheid

Zentrum fur Pneumologie und Thoraxchirurgie, Krankenhaus GroBhandsdorf, Hamburg, Germany

3. PRIMARY AND SECONDARY PLEURAL MALIGNANT DISEASES

M. Mezzetti

Department of Thoracic Surgery, San Paolo Hospital, University of Milan, Italy

4. THYMOMAS: EVALUATION AND TREATMENT OF ADVANCED DISEASE AND RECURRENCE.

G. Palmieri, L. Montella.

Department of Molecular and Clinical Endocrinology and Oncology, University “Federico II”, Naples.

5. INTRATHORACIC MALIGNANCIES IN CHILDHOOD

F. Casale

Pediatric Oncology, 2nd University of Naples, Italy

Lung cancer in the setting of multiple primary cancers

G. MASSARD

Department of Thoracic Surgery, Hôpitaux Universitaires de Strasbourg, F-67091 Strasbourg

The definition of lung cancer as a second primary cancer includes 2 categories of patients : patients with multiple primary lung cancers, and patients presenting with primary lung cancer following a previous extrathoracic malignancy. The legitimacy of surgical treatment is founded on an acceptable operative risk, and on fair 5-year survival rates as well.

1. Multiple primary lung cancer

Since the whole surface of the bronchial tree has been insulted by tobacco smoke, it is somehow surprising that most patients present with a single cancer ! However, the fact that most patients die from their first lung cancer in a relatively short delay may explain this paradox. About 11.7 % of long term survivors, i.e. patients with stage I disease having undergone curative resection, will develop a metachronous primary lung cancer1. Surgical treatment implicates an obvious increase of operative risk. In case of a homolateral second cancer, completion pneumonectomy is required. This operation carries an operative mortality close to 10 %2. In case of a contralateral second cancer, the operation concerning the functionally predominant lung is credited an increased morbidity, although this has not yet been reported as such. Long term results justify the operative risk : the estimated global 5-year survival rates range from 35 % to 45 % 2,3,4 ; rates for stage I vary from 40 % to 60 %.

Surprisingly, the incidence of simultaneous multiple lung cancers is low. Surgical treatment is limited by the extent of resection which is required. However, complete resection may yield fair survival rates, which are unequalled by nonsurgical oncologic treatments. Reported survival rates range from 20 % to 44 % at 5 years3,4,5. Paradoxically, the TNM classification reviewed in 1997 classifies simultaneous cancers in the non-operable categories, and is therefore hardly acceptable : satellite nodules located in the same lobe are staged T4, and nodules located in different lobes are staged M16,7.

Another challenging issue is the concept of multiple carcinoma in situ. Diffuse abnormalities of the upper aero-digestive mucosa, ranging from various degrees of dysplasia to carcinoma in situ, are seen in patients with multiple squamous cell carcinomas of the bronchus and head and neck. Recent investigations have shown that such lesions may regress spontaneously, but progression to invasive cancer is a realistic threat. Simple surveillance seems nonchalant, and extensive surgery seems excessive. There is a field for investigation of new technologies : autofluorescence endoscopy for screening of patients at risk, endoscopic photodynamic therapy for minimally invasive treatment. Alternatively, a good knowledge of bronchoplastic surgery may avoid extensive resections if such lesions are combined with invasive carcinoma.

2. Primary lung cancer following an extrathoracic primary malignancy.

In patients with a history of an extrathoracic primary cancer, the tissue diagnosis of a solitary lung mass may respond either to a primary lung cancer, or to a single metastasis. However, knowing that resection of single metastases may yield fair 5-year survival rates, aggressive surgical management is sound. The main question is whether life expectancy is reduced in patients with lung cancer as a second primary owing to the cumulated metastatic risk of 2 cancers.

Common risk factors explain the relatively high coincidence (7 %) of bronchial cancer and head and neck cancers8. Again, the central question is the balance between operative risk and long term benefit. Observed cumulative operative mortality rate was 3.5 % ; incidence of postoperative pneumonia was 25 %9. We have demonstrated an increased operative risk in patients with previous voice-sparing operations, because impairment of cough and swallowing favors aspiration pneumonia9. Liberal use of tube feeding and tracheostomy during the post-operative period are recommended. Long-term survival curves are skewed down by one stage: estimated survival rates have been 33.3 % for stage I and 19.2 % for stage II8,9. These figures challenge the concept of new primary cancer in favor of metastatic disease. However, there was no significant difference in survival of patients with squamous cell carcinoma compared to those with adenocarcinoma8. Therefore, the solitary lung nodule should be considered as a primary cancer ; the reduced survival may be explained by major comorbidities.

Lung cancer in patients with a history of extrathoracic and extracervical primary cancer has seldom been subjected to a dedicated evaluation. Two reports dealing with lung cancer surgery in the elderly failed to show any adverse effect on survival10,11. In a personal series12 of 55 patients operated on during a 10-year period, the previous malignancy was considered tobacco-induced in 15 patients, hormon-dependant in 18, and miscellaneous in 22. Following complete resection, 25 patients were classified stage I, 13 were stage II, and 17 were stage IIIA. There were 2 early perioperative deaths (3.6 %), and 3 others died during the second month because of cardiovascular complications. At the conclusion of the study, 32 further patients had died (58.2 %) : 25 had progression of lung cancer, 1 had progression of the previous malignancy, and 6 were without evidence of disease. Five-year survival (Kaplan-Meier) was estimated 47 ± 10.2 % in stage I (median 44 months), 30.8 ± 15.6 % in stage II (median 26 months), and 16.7 ± 9.9 % in stage IIIA (median 17 months). When excluding 5 early perioperative deaths, 5-year survival was 51.1 ± 10.6 % in stage I (median 93 months), 33.3 ± 16.7 % in stage II (median 36.5 months), and 19.0 ± 11.2 % in stage IIIA (median 20.5 months). Comparing the 3 groups defined according to location of previous malignancy, there was no significant difference neither for stage distribution, nor for 5-year survival estimates. We should underline that 7 patients (15 %) have developed a third primary cancer during follow-up. In opposition to data collected in patients with previous head and neck cancer, survival estimates according to stage were contained within the universally accepted range ; no high risk group has been identified. A relatively high age sustains an exaggerated cardiovascular comorbidity, which certainly has contributed to an increased mortality.

We conclude that surgery is the first-choice option for managing second primary lung cancer, regardless of the precise identity of the first primary cancer.

References.

1. Martini N, Bains MS, Burt ME, et al. Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg 1995;109:120-9

2. Massard G, Lyons G, Wihlm JM, et al. Early and long-term results after completion pneumonectomy. Ann Thorac Surg 1995 ;59 :196-200

3. Deschamps C, Pairolero PC, Trastek VF, Payne WS. Multiple primary lung cancers. Results of surgical treatment. J Thorac Cardiovasc Surg 1990 ;99 :769-77

4. Rosengart TK, Martini N, Ghosn P, Burt M. Multiple primary lung carcinomas : prognosis and treatment. Ann Thorac Surg 1991 ;52 :773-8

5. Deslauriers J, Brisson J, Cartier R, et al. Carcinoma of the lung. Evaluation of satellite nodules as a factor influencing prognosis after resection. J Thorac Cardiovasc Surg 1989 ;97 :504-12

6. Urschel JD, Urschel DM, Anderson TM, Antkowiak JG, Takita H. Prognostic implications of pulmonary satellite nodules : are the 1997 staging revisions appropriate ? Lung Cancer 1998 ;21 :83-7

7. Okada M, Tsubota N, Yoshimura M, Miyamoto Y, Nakai R. Evaluation of TNM classification for lung carcinoma with ipsilateral intrapulmonary metastasis. Ann Thorac Surg 1999 ;68 :326-30

8. Massard G, Roeslin N, Jung GM, Dumont P, Wihlm JM, Morand G. Bronchogenic cancer associated with head and neck tumors. Survival analysis of 194 patients. J Thorac Cardiovasc Surg 1993 ;106 :218-27

9. Massard G, Wihlm JM, Ameur S, et al. Association of bonchial and pharyngo-laryngeal malignancies. A reappraisal. Eur J Cardio-thorac Surg 1996 ;10 :397-402

10. Thomas P, Piraux M, Jacques LF, Grégoire J, Bedard P, Deslauriers J. Clinical patterns and trends of outcome of elderly patients with bronchogenic carcinoma. Eur J Cardiothorac Surg 1998 ;13 :266-74

11. Massard G, Moog R, Wihlm JM, et al. Bronchogenic cancer in the elderly : operative risk and long-term prognosis. Thorac Cardiovasc Surg 1996 ;44 :40-5

12. Massard G, Ducrocq X, Beaufigeau M, Herve JF, Wihlm JM. Prognosis of lung cancer in patients with a history of extrathoracic malignancy. Eur J Cardio-thorac Surg (submitted).

LUNG METASTASES AND LASER TREATMENT

D. BRANSCHEID

Zentrum fur Pneumologie und Thoraxchirurgie, Krankenhaus GroBhandsdorf, Hamburg, Germany

Surgery forms part of a combined oncological concept in the management of pulmonary metastases. The use of polychemotherapy to treat malignant neoplasms has certainly be able to reduce the incidence of lung metastases from specific primary tumors, but in general chemotherapy is still not a potentially curative therapeutic option for pulmonary metastases. Radiotherapy also appears to be of only minimal value in treating lung metastases. Consequent surgical resection represents the only mode of treatment with curative potential in patients in whom metastases are limited to the lungs. Although the number of patients who are completely cured by resection of pulmonary metastases is small, the majority of them owe a significantly prolonged survival to surgical therapy.

The continued improvement of techniques in laser surgery and specialised intraoperative ventilation methods seems to increase the potential for achieving complete surgical remission. In vivo and in vitro experiments with the non-contact neodymium aluminium garnet (Nd-YAG) laser have shown that it is possible to cut lung tissue while achieving reliable haemostasis and maintaining ventilation at the same time. Resection or vaporisation of metastatic tissues is nowadays established. Our analysis of the factors relevant for prognosis in relation to the type of primary tumour leads us to the conclusion that only complete surgical remission (radicality) can influence the survival rate. The attempt to achieve complete surgical remission is however limited by the clearly defined amount of parenchyma that may be sacrificed. Conventional resection methods therefore have their limits. Nd-YAG-Laser develops a technique that enables a great number of metastases to be removed while preserving the parenchyma. So even patients with a higher number of metastases can get the benefit of a complete surgical remission (radicality).

|Primary tumor |Radicality |N |Kind of |Localisation |Age |Metastasis-fre|

| | | |resection | | |e interval |

|Breast carcinoma |P60%); these results can be attributed to the multimodal therapeutic approach and refinements in chemotherapy, surgery and radiation therapy. Although a high proportion of children are being cured, there are still too many who fail to respond or who relapse after a good initial response; therefore a great effort must be still made for avancing in epidemiology, biology, immunology and molecular basis of childhood cancer.

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