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Cuneo Lung Cancer Study Group First International Lung Cancer Conference: Non-small cell lung cancer: Open questions and controversies
LUNG CANCER Lung Cancer 12 (1995) 105-108
Meeting summary
Cuneo Lung Cancer Study Group First International Lung Cancer Conference: Non-small cell lung cancer: Open questions and controversies Sommariva Perno (Alba, Italy), 7-8 October, 1994
The First International Lung Cancer Conference organized by the Cuneo Lung Cancer Study Group (Cu.L.Ca.S.G.) was held on 7-8 October, 1994 in the vicinity of Alba, an ancient town in northwest Italy at the center of a prosperous area full of hills, renowned worldwide for its prestigious wines and truffles. The conference was held under the auspices of the International Association for the Study of Lung Cancer (IASLC) and the Italian Chapter of the American College of Chest Physicians and Surgeons. Participants from several regions of Italy, including the south, and from abroad, including Canada, attended the conference. The papers presented were not meant to cover all aspects of lung cancer, rather they focused on a few controversial and unsettled issues, which given in a contradictory sequence, stimulated discussions and debates between speakers and the audience. A total of 16 invited lectures from speakers from six European nations, and 12 oral presentations and four posters were presented. The conference was opened by the welcome address of Dr D. Ferrigno, on behalf of the entire Cu.L.Ca.S.G. Prof G. Motta, President-elect of the IASLC, brought the authority of the International Association he represents to the conference. Dr F. De Blasio, International Governor of the American College of Chest Physicians and Surgeons, expressed his appreciation for the stimulating program and his best wishes for the future research of the society. The first session of the conference was dedicated to staging, and to the underlying question about the optimal strategy of pre-surgical assessment and whether it can be improved. Dr G. Buecheri (Cuneo, Italy) presented a provocative paper on laboratory tests and tumor markers. Moving from the well documented correlation between tumor burden and some laboratory tests, he argued that it should be ever possible to identify threshold levels capable of recognising the stage of disease. He 0169-5002/95/$09.50 0 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0169-5002(94)00413-H
106
Meeting
Summary/Lung
Cancer
I2 (1995)
105-108
presented the results of an interesting analysis (to be published in Chest), which showed that a serum concentration of Tissue Polypeptide Antigen (TPA) below 110 or higher than 160 U/l should allow the differentiation between resectable and nonresectable tumors, with a diagnostic accuracy equal to that of a non-blind reading of a total body CT (69%). In the following discussion it was pointed out that, although a probability estimate of resectability will never replace an imaging technique (which remains paramount for the surgeon planning its intervention), it could be wise, given the very low cost, to add a TPA serum assay to the routine staging work-up of lung cancer (at least, in order to choose between a minimal strategy or a more aggressive and accurate strategy of investigation). Dr A. Biggi (Cuneo, Italy) summa&d the Cu.L.Ca.S.G. 6-year experience performed with a modem and sophisticated technique of anti-CEA immunoscintigraphy (more than 170 examinations, nearly half of them performed in patients with a pathological reference). He comprehensively reviewed the basic principles, the methodology, the theoretical reasons for successand failure of the immunodetection, the achievements from other groups working on the same subject, and the fairly high figures of sensitivity, specificity, and accuracy observed by his group in the diagnosis of the primary tumor, the nodal regional spread, and the presence of distant metastases. The discussion was focused on the chance that this technique could replace, in part or totally, computerised tomography (CT). Dr S. Spiro (London, England) gave an excellent lecture on the radiological imaging appearances of the primary tumor and the aging procedures of both the intrathoracic and the extrathoracic spread of lung cancer. His presentation provided information on state of the art techniques, from a more conservative point of view. In routine setting, he does not advocate replacing thoracic CT with any other noninvasive imaging technique (including magnetic resonance imaging). He recommended avoiding brain CT scanning or bone scanning in patients with no organ specific or non-organ specific abnormalities. Although ultrasound is probably the technique of choice for liver metastases, he said the upper abdomen CT is a more comprehensive and useful test. Dr M. Taviani (Genoa, Italy) concluded the session, outlining the role of the invasive staging technique, such as mediastinoscopy and anterior mediastinotomy. He stated that in spite of the new possibilities offered by transcarenal needle biopsy and videothoracoscopy, mediastinoscopy often remains the only way to confirm a positive CT scanning. Given the high false positive rate of any currently available imaging technique, it should be performed in any patient with abnormal thoracic CT. On the other side, it could be avoided if a correctly performed CT shows normal mediastinum. In the following debate, it was pointed out that the recourse to mediastinoscopy has changed in the last few years, and is still changing, given the more frequent extensive surgical removal of bulky diseases, in accordance with the newest super-radical surgical protocols (less mediastinoscopies) and the need of histologic documentation for neoadjuvant studies (more medistinoscopies). The second and third sessions were meant to debate the boundary of the SURGICAL TREATMENT and whether such boundaries could be enlarged by ADJUVANT and NEOADJWANT TREATMENTS. Prof G. Motta (Genoa, Italy) in his erudite dissertation, moved from the problem of identifying the small, but impor-
Meeting
Summary/Lung
Cancer
I2 (19951
105-108
107
tant, subgroup of patients with N2 disease that may benefit by surgical resection. These are patients, he said, with a favorable N2 disease (intact nodal capsule, no tixation and involvement of only one node in one of the following stations: low paratracheal, superior tracheobronchial, aortic window, and subcarinal nodes) found at thoracotomy, after a completely negative clinical staging, or at mediastinoscopy. He stressed the importance of the surgeon’s individual expertise in determining the final outcome. Prof P. Rocmans (Brussels, Belgium) presented a comprehensive and well documented overview on the technical possibilities of resection in bulky, locally advanced diseases. Prof G. Bonsignore (Palermo, Italy) presented clinical and experimental data to provide a rationale for the execution of clinical trials aimed at assessing the potential benefit of neoadjuvant chemotherapy and immunotherapy in patients with adenocarcinomas, including subjects with a limited stage I and II disease. The particular form of adjuvant treatment called chemopreventive, was highlighted by Dr U. Pastorino (London, England). Dr Pastorino presented the results of the pilot study on chemopreventive, which first started in Milan in 1985. Three hundred and seven Tl-2N0 NSCLC patients were random&d, after resection, to retinol pahnitate treatment or control (significantly reduced probability of tobacco-related new-primary tumors and improved total disease survival in the treatment arm). On the basis of that experience, in 1988 a joint venture of the E.O.R.T.C. Lung Cancer and Head and Neck Cancer Cooperative Groups was set up, called the EUROSCAN study. The speaker detailed selection criteria, study design, treatment arms, and major end-points of the study, updating on the current accrual (over 2,000 patients), compliance rate, side-effect of the treatment, and the number of neoplastic events already observed (372 recurrences and 90 s primaries). Patients enrolled in chemopreventive trials, Dr Pastorino said, offer a unique opportunity of investigating the role of prior and subsequent tobacco consumption and, in a distinct field of research, permit validation of several biologic markers, including ploidy and DNA content, squamous markers, cytogenetic abnormalities, amplification and/or overexpression of oncogenes and tumor suppressor genes. A general discussion on the overall value of neoadjuvant and adjuvant treatments followed, where it was decided that we have not yet enough evidence to consider that these alternative approaches are useful. The fourth session was based on the simple question: Do we suggest the palliation of CHEMOTHERAPY to any out-of-protocol patient with inoperable NSCLC and no specific contraindication? Dr P. Souquet’s (Lyon, France) answer was yes. In his lucid presentation, he argued that: 1, three meta-analysis studies of randomised trials of chemotherapy versus supportive care consistently showed a significant reduction of mortality, at least in the central part of the curve (at 3, and 6 months); 2, although no psychometric testing was successfully concluded, indirect evidence would suggest an improvement of quality of life after chemotherapy; and 3, the cost of chemotherapy for lung cancer is equal or inferior to other cancer treatments or medical intervention (e.g. liver transplantation, and coronary artery by-pass) and surprisingly, to the very supportive care. Dr R. Cellerlrto (Ancona, Italy) did not dispute survival data, but emphasized the fact that clinicians may now judge whether this survival advantage is of value in this patient, especially in the light of the scarcity of informa-
108
Meeting
Summary/Lung
Cancer
1.2 (1995)
105-108
tion concerning quality of life. He suggested treating patients with advanced NSCLC with 2-3 cycles of platinum-based chemotherapy and then stopping the treatment in non-responding patients. Dr M. Tamburini (Milan, Italy) gave the psychologist’s view. He argued that we need more information in terms of quality of life of patients in order to reach a sound treatment decision. He described the operational definition of quality of life, and the principal characteristics of the available instruments for evaluation (e.g. focused upon the patient, multidimensional, cancer-specific, simple and easily comprehensible by the patients, and possessing documented psychometric properties). The discussion that followed was concentrated on the need for additional studies of chemotherapy versus supportive care. Dr S. Spiro commented that we do need other random&d studies and he announced that he is trying to convince his colleagues at the British Medical Research Council to implement a very large scale study on this issue. The fifth and final session was focused on the question: what type of chemotherapy, if any, may be considered the standard for the mid-90s? The entire span of chemotherapies used in the past, currently in use today, and of possible future use were considered. Dr P. Marino (Milan, Italy) reviewed single agent chemotherapies; Dr F. De Blasio (Naples, Italy) illustrated non-platinum-based combination programs; Dr S. Sorenson (Vasteras, Sweden) analysed platinum-based combination regimens; and, finally, Dr U. Gatzemeier (Hamburg, Germany) gave an overview on new promising agents, including taxanes, gemcitabine, topoisomerase I-inhibitors, and vinarelbine. All speakers agreed that rates of objective response increased consistently from the oldest regimens to the current platinum-based regimens, as well as toxicity phenomena, which seemed to worsen with the increase of antitumor activity (with the possible exception of the latest new drugs). The net survival result of these two effects was the core of the following debate, where the participants assumed two distinct positions. Most participants agreed that there is already a body of evidence showing modem platinum-based chemotherapies doing better than older regimens; a few others, for the reason expressed in an editorial recently published in this journal (Lung Cancer 1994; 11: 115- 117), declared their scepticism. The conference was closed by Dr S. Spiro with a concise, and yet comprehensive round up, highlighting the main points of interest, and the agreements and disagreements encountered. The conference fulfilled the goal of providing a ‘forum’ for frank and friendly debates among experts who dedicate a great part of their professional life to the study and the treatment of lung cancer. Gianfranco
Buccheri
Post scriptum: A limited number of abstract books are available free of charge (postal expenses charged to the receiver), by writing to the Cu.L.Ca.S.G., Via Romita 15, I-12011 Borgo S. Dalmazzo (CN), Italy.
Meeting summary
Cuneo Lung Cancer Study Group First International Lung Cancer Conference: Non-small cell lung cancer: Open questions and controversies Sommariva Perno (Alba, Italy), 7-8 October, 1994
The First International Lung Cancer Conference organized by the Cuneo Lung Cancer Study Group (Cu.L.Ca.S.G.) was held on 7-8 October, 1994 in the vicinity of Alba, an ancient town in northwest Italy at the center of a prosperous area full of hills, renowned worldwide for its prestigious wines and truffles. The conference was held under the auspices of the International Association for the Study of Lung Cancer (IASLC) and the Italian Chapter of the American College of Chest Physicians and Surgeons. Participants from several regions of Italy, including the south, and from abroad, including Canada, attended the conference. The papers presented were not meant to cover all aspects of lung cancer, rather they focused on a few controversial and unsettled issues, which given in a contradictory sequence, stimulated discussions and debates between speakers and the audience. A total of 16 invited lectures from speakers from six European nations, and 12 oral presentations and four posters were presented. The conference was opened by the welcome address of Dr D. Ferrigno, on behalf of the entire Cu.L.Ca.S.G. Prof G. Motta, President-elect of the IASLC, brought the authority of the International Association he represents to the conference. Dr F. De Blasio, International Governor of the American College of Chest Physicians and Surgeons, expressed his appreciation for the stimulating program and his best wishes for the future research of the society. The first session of the conference was dedicated to staging, and to the underlying question about the optimal strategy of pre-surgical assessment and whether it can be improved. Dr G. Buecheri (Cuneo, Italy) presented a provocative paper on laboratory tests and tumor markers. Moving from the well documented correlation between tumor burden and some laboratory tests, he argued that it should be ever possible to identify threshold levels capable of recognising the stage of disease. He 0169-5002/95/$09.50 0 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0169-5002(94)00413-H
106
Meeting
Summary/Lung
Cancer
I2 (1995)
105-108
presented the results of an interesting analysis (to be published in Chest), which showed that a serum concentration of Tissue Polypeptide Antigen (TPA) below 110 or higher than 160 U/l should allow the differentiation between resectable and nonresectable tumors, with a diagnostic accuracy equal to that of a non-blind reading of a total body CT (69%). In the following discussion it was pointed out that, although a probability estimate of resectability will never replace an imaging technique (which remains paramount for the surgeon planning its intervention), it could be wise, given the very low cost, to add a TPA serum assay to the routine staging work-up of lung cancer (at least, in order to choose between a minimal strategy or a more aggressive and accurate strategy of investigation). Dr A. Biggi (Cuneo, Italy) summa&d the Cu.L.Ca.S.G. 6-year experience performed with a modem and sophisticated technique of anti-CEA immunoscintigraphy (more than 170 examinations, nearly half of them performed in patients with a pathological reference). He comprehensively reviewed the basic principles, the methodology, the theoretical reasons for successand failure of the immunodetection, the achievements from other groups working on the same subject, and the fairly high figures of sensitivity, specificity, and accuracy observed by his group in the diagnosis of the primary tumor, the nodal regional spread, and the presence of distant metastases. The discussion was focused on the chance that this technique could replace, in part or totally, computerised tomography (CT). Dr S. Spiro (London, England) gave an excellent lecture on the radiological imaging appearances of the primary tumor and the aging procedures of both the intrathoracic and the extrathoracic spread of lung cancer. His presentation provided information on state of the art techniques, from a more conservative point of view. In routine setting, he does not advocate replacing thoracic CT with any other noninvasive imaging technique (including magnetic resonance imaging). He recommended avoiding brain CT scanning or bone scanning in patients with no organ specific or non-organ specific abnormalities. Although ultrasound is probably the technique of choice for liver metastases, he said the upper abdomen CT is a more comprehensive and useful test. Dr M. Taviani (Genoa, Italy) concluded the session, outlining the role of the invasive staging technique, such as mediastinoscopy and anterior mediastinotomy. He stated that in spite of the new possibilities offered by transcarenal needle biopsy and videothoracoscopy, mediastinoscopy often remains the only way to confirm a positive CT scanning. Given the high false positive rate of any currently available imaging technique, it should be performed in any patient with abnormal thoracic CT. On the other side, it could be avoided if a correctly performed CT shows normal mediastinum. In the following debate, it was pointed out that the recourse to mediastinoscopy has changed in the last few years, and is still changing, given the more frequent extensive surgical removal of bulky diseases, in accordance with the newest super-radical surgical protocols (less mediastinoscopies) and the need of histologic documentation for neoadjuvant studies (more medistinoscopies). The second and third sessions were meant to debate the boundary of the SURGICAL TREATMENT and whether such boundaries could be enlarged by ADJUVANT and NEOADJWANT TREATMENTS. Prof G. Motta (Genoa, Italy) in his erudite dissertation, moved from the problem of identifying the small, but impor-
Meeting
Summary/Lung
Cancer
I2 (19951
105-108
107
tant, subgroup of patients with N2 disease that may benefit by surgical resection. These are patients, he said, with a favorable N2 disease (intact nodal capsule, no tixation and involvement of only one node in one of the following stations: low paratracheal, superior tracheobronchial, aortic window, and subcarinal nodes) found at thoracotomy, after a completely negative clinical staging, or at mediastinoscopy. He stressed the importance of the surgeon’s individual expertise in determining the final outcome. Prof P. Rocmans (Brussels, Belgium) presented a comprehensive and well documented overview on the technical possibilities of resection in bulky, locally advanced diseases. Prof G. Bonsignore (Palermo, Italy) presented clinical and experimental data to provide a rationale for the execution of clinical trials aimed at assessing the potential benefit of neoadjuvant chemotherapy and immunotherapy in patients with adenocarcinomas, including subjects with a limited stage I and II disease. The particular form of adjuvant treatment called chemopreventive, was highlighted by Dr U. Pastorino (London, England). Dr Pastorino presented the results of the pilot study on chemopreventive, which first started in Milan in 1985. Three hundred and seven Tl-2N0 NSCLC patients were random&d, after resection, to retinol pahnitate treatment or control (significantly reduced probability of tobacco-related new-primary tumors and improved total disease survival in the treatment arm). On the basis of that experience, in 1988 a joint venture of the E.O.R.T.C. Lung Cancer and Head and Neck Cancer Cooperative Groups was set up, called the EUROSCAN study. The speaker detailed selection criteria, study design, treatment arms, and major end-points of the study, updating on the current accrual (over 2,000 patients), compliance rate, side-effect of the treatment, and the number of neoplastic events already observed (372 recurrences and 90 s primaries). Patients enrolled in chemopreventive trials, Dr Pastorino said, offer a unique opportunity of investigating the role of prior and subsequent tobacco consumption and, in a distinct field of research, permit validation of several biologic markers, including ploidy and DNA content, squamous markers, cytogenetic abnormalities, amplification and/or overexpression of oncogenes and tumor suppressor genes. A general discussion on the overall value of neoadjuvant and adjuvant treatments followed, where it was decided that we have not yet enough evidence to consider that these alternative approaches are useful. The fourth session was based on the simple question: Do we suggest the palliation of CHEMOTHERAPY to any out-of-protocol patient with inoperable NSCLC and no specific contraindication? Dr P. Souquet’s (Lyon, France) answer was yes. In his lucid presentation, he argued that: 1, three meta-analysis studies of randomised trials of chemotherapy versus supportive care consistently showed a significant reduction of mortality, at least in the central part of the curve (at 3, and 6 months); 2, although no psychometric testing was successfully concluded, indirect evidence would suggest an improvement of quality of life after chemotherapy; and 3, the cost of chemotherapy for lung cancer is equal or inferior to other cancer treatments or medical intervention (e.g. liver transplantation, and coronary artery by-pass) and surprisingly, to the very supportive care. Dr R. Cellerlrto (Ancona, Italy) did not dispute survival data, but emphasized the fact that clinicians may now judge whether this survival advantage is of value in this patient, especially in the light of the scarcity of informa-
108
Meeting
Summary/Lung
Cancer
1.2 (1995)
105-108
tion concerning quality of life. He suggested treating patients with advanced NSCLC with 2-3 cycles of platinum-based chemotherapy and then stopping the treatment in non-responding patients. Dr M. Tamburini (Milan, Italy) gave the psychologist’s view. He argued that we need more information in terms of quality of life of patients in order to reach a sound treatment decision. He described the operational definition of quality of life, and the principal characteristics of the available instruments for evaluation (e.g. focused upon the patient, multidimensional, cancer-specific, simple and easily comprehensible by the patients, and possessing documented psychometric properties). The discussion that followed was concentrated on the need for additional studies of chemotherapy versus supportive care. Dr S. Spiro commented that we do need other random&d studies and he announced that he is trying to convince his colleagues at the British Medical Research Council to implement a very large scale study on this issue. The fifth and final session was focused on the question: what type of chemotherapy, if any, may be considered the standard for the mid-90s? The entire span of chemotherapies used in the past, currently in use today, and of possible future use were considered. Dr P. Marino (Milan, Italy) reviewed single agent chemotherapies; Dr F. De Blasio (Naples, Italy) illustrated non-platinum-based combination programs; Dr S. Sorenson (Vasteras, Sweden) analysed platinum-based combination regimens; and, finally, Dr U. Gatzemeier (Hamburg, Germany) gave an overview on new promising agents, including taxanes, gemcitabine, topoisomerase I-inhibitors, and vinarelbine. All speakers agreed that rates of objective response increased consistently from the oldest regimens to the current platinum-based regimens, as well as toxicity phenomena, which seemed to worsen with the increase of antitumor activity (with the possible exception of the latest new drugs). The net survival result of these two effects was the core of the following debate, where the participants assumed two distinct positions. Most participants agreed that there is already a body of evidence showing modem platinum-based chemotherapies doing better than older regimens; a few others, for the reason expressed in an editorial recently published in this journal (Lung Cancer 1994; 11: 115- 117), declared their scepticism. The conference was closed by Dr S. Spiro with a concise, and yet comprehensive round up, highlighting the main points of interest, and the agreements and disagreements encountered. The conference fulfilled the goal of providing a ‘forum’ for frank and friendly debates among experts who dedicate a great part of their professional life to the study and the treatment of lung cancer. Gianfranco
Buccheri
Post scriptum: A limited number of abstract books are available free of charge (postal expenses charged to the receiver), by writing to the Cu.L.Ca.S.G., Via Romita 15, I-12011 Borgo S. Dalmazzo (CN), Italy.