- Email: [email protected]
P-504 Malignant pleural mesothelioma in western Honshu, Japan
Poster Session 3/Pleural
WEDNESDAY, 13 AUGUST 2003
Pleural and Mediastinal Neoplasms ElP 500
lnterlobar Pleural Invasion in Lung Cancer
Makoto Nonaka’ , Shigeru Yamamoto’ , Daisuke Kataoka’, Mitsutaka Kadokura”, Naoya Horichi3, Toshiaki Kunimura4, Miki Kushimaa, Yoshimitsu Ohgiya6, Toshihiro Takaba’. ’ First Dept. of Surgery, Showa University School of Medicine, Tokyo, Japan; ‘Respiratory Center, Showa University Northern Yokohama Hospital, Yokohama, Japan; 3 First Dept. of Internal Medicine, Showa University School of Medicine, Tokyo, Japan; 4 First Dept. of Pathology Showa University School of Medicine, Tokyo, Japan; 5 Department of Hospital Pathology, Showa University Hospita/, Tokyo, Japan; 6 Department of Radiology, Showa University School of Medicine, Tokyo, Japan; 7 First Dept. of Surgery, Showa university School of Medicine, Tokyo, Japan To study whether the intralobar pleural invasion should be categorized as T3 or not, surgically treated primary non-small cell lung cancer was analyzed. The 5 year survival rate of the patients with intralobar pleural invasion was 62%. The 5-year survival rates of the patients without intralobar pleural invasion were 55% in Tl, 54% in T2, 24% in T3, and 20% in T4 diseases. The rate of the patients with interlobar pleural invasion was significantly higher than that of the T3 patients without interlobar pleural invasion. Additionally, the survival rate of the patients with intralobar pleural invasion was significantly higher than the patients with parietal pleural invasion. Similar results were observed in patients without lymph node metastasis. The rate of the lymph node metastases in the patients with interlobar pleural invasion was not higher than that in the patients without interlobar pleural invasion. In conclusion, interlobar pleural invasion should not be classified as T3. Lobectomy with partial resection of the invaded lobe is better selection to reserve the pulmonary function than bilobectomy but complete resection should be achieved.
pziq
Activity of Tomudex in Malignant Mesothelioma
Paul Baas’, Andrea Ardizzonia, Channa Debruynes, Catherina Legrand4, Giuseppe Giaccone5. ’ Thoracic Oncology NK//AVL, Amsterdam, Netherlands; 2 Department of Medical Oncology Genus, Italy; 3 EORTC, Brussels, Belgium; 4 EORTC, brussels, belgium; 5 Medical Oncology VUMC, Amsterdam, Netherlands Promising results have been obtained with anti-folates in the treatment of malignant pleural mesothelioma (MPM). The EORTC therefore decided to investigate the activity and toxicity of TomudexR (raltitrexed) as single agent treatment in patients with MPM in a multicenter phase II EORTC study. Patient and Methods: This study enrolled chemonaive patients with histologically confirmed measurable MPM. Raltitrexed was administered at the dose of 3 mg/m* i.v. bolus on an outpatient basis every 3 weeks. A maximum of 8 cycles was planned in case of absence of progression or unacceptable toxicity. Results: Twenty-four patients received a total of 104 courses. Five patients (20.&T%, 95% confidence interval 7.1-42.2%) had a partial response, which was confirmed by an independent radiology committee. Toxicity was mild, with diarrhea, nausea, vomiting, fatigue and neutropenia as major side effects, not exceeding grade 3 toxicity. Conclusion: raltitrexed has activity as single agent in the treatment of MPM. This response rate is the highest ever observed within the EORTC phase II single agent screening program for MPM. Further studies with this drug in MPM are warranted.
I.
P 502
Ttssue Polypeptide Antigen (TPA), Hyaluronan and CA 125 as Serum Markers in Malignant Mesothelioma
Mattias Hedman’, Johan Wernlunds, Henrik Riska3, Ola Brodin4. ‘Dept. of Oncology Huddinge University Hospital, Stockholm, Sweden; p Dept. of Radiology Uppsala University Hospital, Uppsala, Sweden; 3 Dept. Lung Medicine Central University Hospital Helsinki, Fin/and; 4 Dept. of Oncology Huddinge University Hospital, stockholm, Sweden Mesothelioma is a rare disease and the prognosis is poor. Monitoring the effect of treatment creates difficulties and a serum marker might be of use for this purpose. We have studied three serum markers TPA, Hyaluronan and CA 125 in a limited material with a total of 11 patients. The purpose was to find out if these three serum markers might reflect treatment effect and/or indicate prognosis. Correspondence between initial TPA levels and survival seems to be better than corresponding data regarding Hyaluronan and CA125 according to our study. The result in our material further shows five patients with increasing serum
and Mediastinal
Neoplasms
s211
levels of all three-serum markers from first to last sample as the mesothelioma progressed according to consecutive CT scans. In three of these patients stable disease was followed by a decrease in the serum marker levels. Our results indicate that these three serum markers and mainly TPA might be useful as markers of disease progression and TPA for prediction of survival.
I P 503
The management of malignant pleural mesothelioma due to environmental exposure to erionite and asbestos in Turkey
Hadi Akay’, Salih Emri”, Dalokay Kilics, Cem Kadila?, Serpil Dizbaye, Faruk ZorluG, lzzettin Baris7. ‘Ankara Medical Facult): Dept. of Chest Surgery, Ankara, Turkey;2 Hacettepe Medical Faculty, Deptof Chest Diseases, Ankara, Turkey; 3 Gfiven Hospital, Deptof Chest Surgery, Ankara, Turkey; ’ Hacettepe University, Dept. of Statistics, Ankara, Turkey; 5Ankara Medical Faculty, Dept.of Pathology, Ankara, Turkey; 6 Hacettepe Medical Faculty: Dept. of Radiation Oncology: Ankara, Turkey; ‘G&en Haspita/, Deptof Chest Diseases, Ankara, Turkey in Turkey malignant pleural mesothelioma (MPM) is mostly due to environmental asbestos or erionite related disease of pleura with a median survival of 10 months (95% Cl; 6-14). The objective of this study is to review our experience in the management of MPM patients for various modalities of treatment. Between 1994 and 2002, 154 patients with MPM have been evaluated for treatment decision. One hundred and five patients (68.2%) are male and 49 patients (31.8%) are female. The median age of the patients was 54 years (range:2880 yrs). Thirty-seven patients were treated by decortication/pleurectomy and 3 had an extra-pleural pneumonectomy (EPP). Five of 37 patients with decortication/pleurectomy also underwent chest wall resection. The rest of the patients (114/154; 74%) had undergone palliative minor surgery (PMS) for tissue diag nosis and pleurodesis. Sixty seven of them (43%) were diagnosed and treated for symptoms control by Video Assisted Thoracic Surgery (VATS), limited thorocotomy and biopsy were performed in 35 patients (23%), percutaneous pleural biopsy and drainage of effusion in 9 patients (6%) and lastly 3 patients (2%) were treated by pleuro-peritoneal shunt application. lntrapleural chemotherapy and systemic adjuvant chemotherapy was employed only in 66 patients following surgical procedures. Postoperative mortality and morbidity rates were 1,3% (2 of 154 patients) and 13% (21 of 154 patients) respectively. The overall median survival for all patients was 11 months (95% Cl; 9-13). The median survival was 20 months (95% Cl; 15-25) for those treated by debulking surgery (DS) and IO months (95% Cl; 8-12) for treated by palliative minor surgery (p=O.O013). The survival prevalence was 77 and 32% for patients treated by DS followed by adjuvant chemotherapy and 51 and 21% for patients treated by PMS followed by adjuvant chemotherapy at 1 and 2 years respectively (p=O.43). Eighteen of 40 patients in the DS group underwent trimodality therapy, including adjuvant chemotherapy and preventive radiation therapy. The median survivals were 21 months (95% Cl, 6-36), 20 months (95% Cl;13-27) and 16 months (95% Cl; O36) respectively for patients treated by trimodality, adjuvant chemotherapy and DS only (p=O.68). In conlusion our results show an increased survival benefit if the patients with MPM were treated with DS in combination with systemic adjuvant chemotherapy. Further trials are needed to improve the adjuvant treatment regimes.
P 504 Malignant pleural mesothelioma in western Honshu, Japan I Takumi Kishimoto’, Kenichi Gemba*. j Okayama Rousai Hospital, Okayama, Japan; * Okayama Rousai Hospital, Okatama, Japan One hundred and thirty-two cases of malignant pleural mesothelioma were found in the Seto Inland Sea area, Western Japan, during the period of 1991 to 2002. One hundred and eighteen cases were male and 14 were female. Their mean age was 65.3 years old with ages ranging from 37 to 92 years of age. Ninety-eight cases were accompanied with pleural effusion and 34 were found to be without effusion. As for diagnostic procedure, in 112 cases pleural biopsies were performed (25 at autopsy) with only five cases by cytological examination. Seventy-one cases were classified into epithelial type, 32 into biphasic type, 24 into sarcomatous type and 5 into desmoplastic type. One hundred and twenty-one cases had definite occupational histories of asbestos exposure. With 59 cases having been exposed in shipyards and 14 cases having been exposed in asbestos pipe manufacturing factories forming the two largest percentages by occupation. The duration of exposure to asbestos ranged from 0.5 to 57 years with a mean of 21.8f13.1 years and their latent period ranged from 15 to 72 years with a mean of 38.4&l 1.4 years. The number of asbestos bodies per lg dry lung tissue for 48 out of 49 cases exceeded 1000 bodies, which demonstrated occupational asbestos exposure according to our criteria. As for treatment procedure, 50 cases were treated with anti-cancer drugs. Seventeen cases were treated by pleural adhesion method and eight cases received pleuro-pneumonectomy. Twenty-one cases received only best supportive care. The survival rate of these 96 cases were 12.6f10.3 months. As for histolog-
S218
Poster Session 3/Pleural
and Mediastinal
ical types, epithelial type was 14.6f12.0 months, biphasic type was 8.2f2.8 months, sarcomatous type was 5.9h4.3 months and desmoplastic type was 11.8f3.3 months. In parts of Japan such as the Seto Inland Sea area, almost all patients exposed to asbestos, as well as survival rates after diagnosis, prove higher in comparison with data collected from other regions of Japan.
P 505 El
The North West Lung Centre Experience of Malignant Pleural Mesothelioma 1980-2000
Juliet Elizabeth King’, Rick Swindella, C.A.C. Pickerings, Nicholas J. Thatchers, Philip Hasleton3. ’ North West Lung Cenfre, Manchester, UK, Manchester, UK; * Christie Hospital NHS Trust, Manchester, UK; 3 North West Lung Cenfre, Manchester, UK
Introduction: The increase in incidence of malignant pleural mesothelioma has provoked renewed interest in its pathology and treatment. It is unclear as to which patient and tumour-related factors are of prognostic value, thereby hindering meaningful evaluation of treatment regimes. Method: We have identified a twenty year cohort of patients (n=553) with histologically confirmed malignant pleural mesothelioma that were diagnosed and/or treated at either of our institutions during the period 1980-2000. This cohort was then analysed to determine which patient and tumour-related factors were of prognostic significance. In particular the effect of clinical and demographic factors, histological subtype and asbestos exposure were evaluated for their effect on patient survival. Results: Our cohort consisted of 482 men (87%) and 71 women (12%). Survival, defined as the time elapsed from the date of histological diagnosis to death was known in 521 patients (95%). The mean survival of the cohort was 8 months (range 1 day - 11 years), with only 3 patients surviving longer than 5 years. The two most significant prognostic factors were age at diagnosis (p
El
P 507
Gemcitabine combined to Carboplatin in Malignant pleural mesothelioma: a multicentric phase II study
Adolf0 Gino Favaretto’, Savina M.L. Aversa*, Adrian0 Paccagnella3, Vincenzo De Pangher Manzini4, Francesco Oniga3, Micaela Stefanis, Federico Reas, Luigi Bortolottis, Lucia Loreggians, Silvio Monfardini”. ’Azienda Ospedaliera di Padova, Padova, ITALY; ” Azienda Ospedaliera di Padova, Padova, /ta/y; 3 Ospedale Civile di Venezia, Venezia, Italy; 4 Ospedale di Monfalcone, Monfalcone, Ifaly; 5Universit4 di Padova, Padova, Italy
Background: Malignant pleural mesothelioma is rapidly increasing worldwide. At present, pemetrexed plus cisplatin chemotherapy showed a survival advantage vs. cisplatin alone in a large trial; no impact on patient survival of surgery, radiotherapy or their combination has been demonstrated. Methods: a phase-11 multicenter study led by 8 centers in North-Eastern Italy. Chemotherapy consisted of Carboplatin AUC 5, on day 1, and Gemcitabine 1000 mgIm* on days 1, 8 and 15; recycle every 4 weeks. Results: Between July 1996 and September 2000 50 patients were treated. Their characteristics were: 68% males, 88% ECOG PS O-l; 56% stage Ill disease, 68% epithelioid histology, 62% had no previous treatments. The delivered Dose Intensity of gemcitabine was 617 mg/m*/week, 82% of the planned (750 mg/m”/week); for Carboplatin, the delivered Dose Intensity was 80 mglm’lweek. Overall, 44% of 15th day doses were omitted or reduced. Partial responses were 26% (95% confidence interval: 15-40%) disease progressions 24%. No complete responses were seen. The median response duration was 55 weeks (range 13-I 13 weeks). Patients had good clinical benefit: 46% improved dyspnoea, 40% improved in weight, 26% had reduced pain. In 18 cycles (11%) grade 3-4 leukopenia occurred. Thrombocytopenia grade 3-4 was more frequent: 24 episodes (15%) in 17 patients. Grade 3 anemia occurred in 8 cycles (5%). No patients developed grade 3-4 non-hematologic toxicity. Median survival was 66 weeks with 53%, 30% and 20% alive patients at 1, 2 and 3 years, respectively. The median progression-free survival was 40 weeks. Conclusion: the gemcitabine/carboplatin combination is a valid option in the treatment of MPM due to the acceptable toxicity profile, the good response rate and the ability to give clinical benefit. Probably minor adjustments in schedule (3-week instead of 4-week cycle) would permit a more optimal treatment administration.
Surgical management of malignant pleural mesothelioma
Dominique H. Grunenwald’, lsabelle Monnets, Pierre Bonnette3, Raffaele Caliandro’ , Denis Debrosse’ , Francoise Lepimpec-Barthes4, Pierre Magdeleina@, Maurice Perols, Jean-Francois Regnard5, Pierre Ruffie7. ’ lnstitut Mutualiste Montsouris, Paris, France; ’ Centre Hospitalier Intercommunal, Creteil, France; 3 Hopital Foch, Suresnes, France; 4 Hopital Europeen Georges Pompidou, Paris, France; 5 Hotel-Dieu, Paris, France; 6 Hopita/ de /a Croix Rousse, Lyon, France; 7 lnsfifut Gustave Roussy Villejuif, France Poor outcome of malignant pleural mesothelioma (MPM) led to attempting better local control using surgical resection. This multi-institutional study reports the results of extra-pleural pneumonectomy (EPP) in patients with MPM. Between july 1995 and february 2002, 44 patients were operated on for MPM by the surgeons of the “Groupe Mesotheliome Ile de France”, in five centers. Clinical and histological patterns, surgical findings and survival data were retrospectively recorded. Prognostic factors were analysed. Preoperative histological assessment was obtained by thoracoscopy in 31 patients, minimal thoracotomy in 11, and transcutaneous biopsy in 2. Histology was epithelial in 29 cases, sarcomatous in 2, combined in 11, and desmoplastic in 2. Preoperative treatments were given in 17 patients, cis-platine based chemotherapy in 5 (2 to 5 cycles), thoracic irradiation in 12 (mean dose 27 gy). Preoperative staging (IMIG) was respectively stage I in 16, stage II in 19, and stage Ill in 9 patients. Among the 44 EPP, 25 were right-sided. Pericardial resection was performed in 35 patients, diaphragmatic resection in 43. Complete surgical resection was achieved in 86% of the patients. Twenty-seven patients (61%) had postoperative complications, cardiac (27%), respiratory (14%) and surgical (27%). Three patients died postoperatively (6.8%). Seven patients received adjuvant chemotherapy, and 38 postoperative radiation therapy (45 gy). Late treatment-related morbidity was observed in 22% of the patients. Thirteen patients had disease recurrences (32%) distant in 7, distant and local in 5, and local only in 1. Prognostic factors of better survival were right side (p=O.O15), and Karnovsky index (p=O.O48). This retrospective multicentric study demonstrates that EPP is associated with a high rate of postoperative and late morbidity. Survival impact of EPP remains unknown. Performance status and side are independant prognostic factors. Multicentric prospective trials of multimodality strategies are needed to validate the role of EPP in limited MPM, in terms of both survival rates, and quality of life.
I I P 506
Neoplasm
P 508
Sarcomatoid Malignant Mesothelioma: A Clinicopathological Correlation of 330 Cases
Annabelle M. Mahar, Thomas A. Sporn, Victor L. Roggli. Duke University Medical Center, Durham VA Medical Center, Durham, USA The 1999 WHO classification of malignant mesothelioma recognizes three histological variants: epithelial, sarcomatoid and biphasic. The sarcomatoid variant is the least common. Highly aggressive, sarcomatoid mesotheliomas are also considered by most thoracic surgeons as an inoperable histology for radical surgery. These tumors must be distinguished from a variety of sarcomatoid malignancies that can involve the pleura as both primary and metastatic processes. This study reports the findings in 330 cases of the sarcomatoid variant from a database of 1954 cases of mesothelioma (17%). These included 314 men and 16 women, with a median age of 70 years (range 41-94). Tumor arose in the pleura in 323 cases, and in the peritoneum in 7. One hundred and eleven tumors (33%) were further categorized as desmoplastic (more than 50% of the tumor with a desmoplastic component) and 57 (17%) as sarcomatoid and desmoplastic (i.e. featuring a substantial desmoplastic component but less than 50%). Three cases were classified as having a lymphohistiocytoid pattern (1%). Seven cases (2%) showed osteosarcomatous or chondrosarcomatous differentiation. Most of the remaining 159 cases (48%) had a pattern that resembled fibrosarcoma. lmmunohistochemical staining for ‘cytokeratins was positive in 246/272 cases (90%), with one equivocal result. Fiber analysis was performed in 62 cases, with a median asbestos body count of 1400 as determined by light microscopy (range: 2- 436,000). Fiber type was analyzed by energy dispersive x-ray analysis, and the main fiber type was amosite. Two cases (3%) had asbestos fiber content within our normal range. Information regarding the presence or absence of pleural plaques was available in 181 cases and 146 had plaques. Information regarding the presence or absence of asbestosis was available in 125 cases and 32 had asbestosis. Sarcomatoid mesothelioma is the least common variant and frequently has a desmoplastic component. These tumors are typically keratin positive, which strongly aids in their distinction from true sarcomas and localized fibrous tumors, although the anti-cytokeratin phenotype is recognized. They are usually associated with asbestos exposure, may rarely show evidence of osteochondromatous differentiation, and are associated with an aggressive clinical course.
WEDNESDAY, 13 AUGUST 2003
Pleural and Mediastinal Neoplasms ElP 500
lnterlobar Pleural Invasion in Lung Cancer
Makoto Nonaka’ , Shigeru Yamamoto’ , Daisuke Kataoka’, Mitsutaka Kadokura”, Naoya Horichi3, Toshiaki Kunimura4, Miki Kushimaa, Yoshimitsu Ohgiya6, Toshihiro Takaba’. ’ First Dept. of Surgery, Showa University School of Medicine, Tokyo, Japan; ‘Respiratory Center, Showa University Northern Yokohama Hospital, Yokohama, Japan; 3 First Dept. of Internal Medicine, Showa University School of Medicine, Tokyo, Japan; 4 First Dept. of Pathology Showa University School of Medicine, Tokyo, Japan; 5 Department of Hospital Pathology, Showa University Hospita/, Tokyo, Japan; 6 Department of Radiology, Showa University School of Medicine, Tokyo, Japan; 7 First Dept. of Surgery, Showa university School of Medicine, Tokyo, Japan To study whether the intralobar pleural invasion should be categorized as T3 or not, surgically treated primary non-small cell lung cancer was analyzed. The 5 year survival rate of the patients with intralobar pleural invasion was 62%. The 5-year survival rates of the patients without intralobar pleural invasion were 55% in Tl, 54% in T2, 24% in T3, and 20% in T4 diseases. The rate of the patients with interlobar pleural invasion was significantly higher than that of the T3 patients without interlobar pleural invasion. Additionally, the survival rate of the patients with intralobar pleural invasion was significantly higher than the patients with parietal pleural invasion. Similar results were observed in patients without lymph node metastasis. The rate of the lymph node metastases in the patients with interlobar pleural invasion was not higher than that in the patients without interlobar pleural invasion. In conclusion, interlobar pleural invasion should not be classified as T3. Lobectomy with partial resection of the invaded lobe is better selection to reserve the pulmonary function than bilobectomy but complete resection should be achieved.
pziq
Activity of Tomudex in Malignant Mesothelioma
Paul Baas’, Andrea Ardizzonia, Channa Debruynes, Catherina Legrand4, Giuseppe Giaccone5. ’ Thoracic Oncology NK//AVL, Amsterdam, Netherlands; 2 Department of Medical Oncology Genus, Italy; 3 EORTC, Brussels, Belgium; 4 EORTC, brussels, belgium; 5 Medical Oncology VUMC, Amsterdam, Netherlands Promising results have been obtained with anti-folates in the treatment of malignant pleural mesothelioma (MPM). The EORTC therefore decided to investigate the activity and toxicity of TomudexR (raltitrexed) as single agent treatment in patients with MPM in a multicenter phase II EORTC study. Patient and Methods: This study enrolled chemonaive patients with histologically confirmed measurable MPM. Raltitrexed was administered at the dose of 3 mg/m* i.v. bolus on an outpatient basis every 3 weeks. A maximum of 8 cycles was planned in case of absence of progression or unacceptable toxicity. Results: Twenty-four patients received a total of 104 courses. Five patients (20.&T%, 95% confidence interval 7.1-42.2%) had a partial response, which was confirmed by an independent radiology committee. Toxicity was mild, with diarrhea, nausea, vomiting, fatigue and neutropenia as major side effects, not exceeding grade 3 toxicity. Conclusion: raltitrexed has activity as single agent in the treatment of MPM. This response rate is the highest ever observed within the EORTC phase II single agent screening program for MPM. Further studies with this drug in MPM are warranted.
I.
P 502
Ttssue Polypeptide Antigen (TPA), Hyaluronan and CA 125 as Serum Markers in Malignant Mesothelioma
Mattias Hedman’, Johan Wernlunds, Henrik Riska3, Ola Brodin4. ‘Dept. of Oncology Huddinge University Hospital, Stockholm, Sweden; p Dept. of Radiology Uppsala University Hospital, Uppsala, Sweden; 3 Dept. Lung Medicine Central University Hospital Helsinki, Fin/and; 4 Dept. of Oncology Huddinge University Hospital, stockholm, Sweden Mesothelioma is a rare disease and the prognosis is poor. Monitoring the effect of treatment creates difficulties and a serum marker might be of use for this purpose. We have studied three serum markers TPA, Hyaluronan and CA 125 in a limited material with a total of 11 patients. The purpose was to find out if these three serum markers might reflect treatment effect and/or indicate prognosis. Correspondence between initial TPA levels and survival seems to be better than corresponding data regarding Hyaluronan and CA125 according to our study. The result in our material further shows five patients with increasing serum
and Mediastinal
Neoplasms
s211
levels of all three-serum markers from first to last sample as the mesothelioma progressed according to consecutive CT scans. In three of these patients stable disease was followed by a decrease in the serum marker levels. Our results indicate that these three serum markers and mainly TPA might be useful as markers of disease progression and TPA for prediction of survival.
I P 503
The management of malignant pleural mesothelioma due to environmental exposure to erionite and asbestos in Turkey
Hadi Akay’, Salih Emri”, Dalokay Kilics, Cem Kadila?, Serpil Dizbaye, Faruk ZorluG, lzzettin Baris7. ‘Ankara Medical Facult): Dept. of Chest Surgery, Ankara, Turkey;2 Hacettepe Medical Faculty, Deptof Chest Diseases, Ankara, Turkey; 3 Gfiven Hospital, Deptof Chest Surgery, Ankara, Turkey; ’ Hacettepe University, Dept. of Statistics, Ankara, Turkey; 5Ankara Medical Faculty, Dept.of Pathology, Ankara, Turkey; 6 Hacettepe Medical Faculty: Dept. of Radiation Oncology: Ankara, Turkey; ‘G&en Haspita/, Deptof Chest Diseases, Ankara, Turkey in Turkey malignant pleural mesothelioma (MPM) is mostly due to environmental asbestos or erionite related disease of pleura with a median survival of 10 months (95% Cl; 6-14). The objective of this study is to review our experience in the management of MPM patients for various modalities of treatment. Between 1994 and 2002, 154 patients with MPM have been evaluated for treatment decision. One hundred and five patients (68.2%) are male and 49 patients (31.8%) are female. The median age of the patients was 54 years (range:2880 yrs). Thirty-seven patients were treated by decortication/pleurectomy and 3 had an extra-pleural pneumonectomy (EPP). Five of 37 patients with decortication/pleurectomy also underwent chest wall resection. The rest of the patients (114/154; 74%) had undergone palliative minor surgery (PMS) for tissue diag nosis and pleurodesis. Sixty seven of them (43%) were diagnosed and treated for symptoms control by Video Assisted Thoracic Surgery (VATS), limited thorocotomy and biopsy were performed in 35 patients (23%), percutaneous pleural biopsy and drainage of effusion in 9 patients (6%) and lastly 3 patients (2%) were treated by pleuro-peritoneal shunt application. lntrapleural chemotherapy and systemic adjuvant chemotherapy was employed only in 66 patients following surgical procedures. Postoperative mortality and morbidity rates were 1,3% (2 of 154 patients) and 13% (21 of 154 patients) respectively. The overall median survival for all patients was 11 months (95% Cl; 9-13). The median survival was 20 months (95% Cl; 15-25) for those treated by debulking surgery (DS) and IO months (95% Cl; 8-12) for treated by palliative minor surgery (p=O.O013). The survival prevalence was 77 and 32% for patients treated by DS followed by adjuvant chemotherapy and 51 and 21% for patients treated by PMS followed by adjuvant chemotherapy at 1 and 2 years respectively (p=O.43). Eighteen of 40 patients in the DS group underwent trimodality therapy, including adjuvant chemotherapy and preventive radiation therapy. The median survivals were 21 months (95% Cl, 6-36), 20 months (95% Cl;13-27) and 16 months (95% Cl; O36) respectively for patients treated by trimodality, adjuvant chemotherapy and DS only (p=O.68). In conlusion our results show an increased survival benefit if the patients with MPM were treated with DS in combination with systemic adjuvant chemotherapy. Further trials are needed to improve the adjuvant treatment regimes.
P 504 Malignant pleural mesothelioma in western Honshu, Japan I Takumi Kishimoto’, Kenichi Gemba*. j Okayama Rousai Hospital, Okayama, Japan; * Okayama Rousai Hospital, Okatama, Japan One hundred and thirty-two cases of malignant pleural mesothelioma were found in the Seto Inland Sea area, Western Japan, during the period of 1991 to 2002. One hundred and eighteen cases were male and 14 were female. Their mean age was 65.3 years old with ages ranging from 37 to 92 years of age. Ninety-eight cases were accompanied with pleural effusion and 34 were found to be without effusion. As for diagnostic procedure, in 112 cases pleural biopsies were performed (25 at autopsy) with only five cases by cytological examination. Seventy-one cases were classified into epithelial type, 32 into biphasic type, 24 into sarcomatous type and 5 into desmoplastic type. One hundred and twenty-one cases had definite occupational histories of asbestos exposure. With 59 cases having been exposed in shipyards and 14 cases having been exposed in asbestos pipe manufacturing factories forming the two largest percentages by occupation. The duration of exposure to asbestos ranged from 0.5 to 57 years with a mean of 21.8f13.1 years and their latent period ranged from 15 to 72 years with a mean of 38.4&l 1.4 years. The number of asbestos bodies per lg dry lung tissue for 48 out of 49 cases exceeded 1000 bodies, which demonstrated occupational asbestos exposure according to our criteria. As for treatment procedure, 50 cases were treated with anti-cancer drugs. Seventeen cases were treated by pleural adhesion method and eight cases received pleuro-pneumonectomy. Twenty-one cases received only best supportive care. The survival rate of these 96 cases were 12.6f10.3 months. As for histolog-
S218
Poster Session 3/Pleural
and Mediastinal
ical types, epithelial type was 14.6f12.0 months, biphasic type was 8.2f2.8 months, sarcomatous type was 5.9h4.3 months and desmoplastic type was 11.8f3.3 months. In parts of Japan such as the Seto Inland Sea area, almost all patients exposed to asbestos, as well as survival rates after diagnosis, prove higher in comparison with data collected from other regions of Japan.
P 505 El
The North West Lung Centre Experience of Malignant Pleural Mesothelioma 1980-2000
Juliet Elizabeth King’, Rick Swindella, C.A.C. Pickerings, Nicholas J. Thatchers, Philip Hasleton3. ’ North West Lung Cenfre, Manchester, UK, Manchester, UK; * Christie Hospital NHS Trust, Manchester, UK; 3 North West Lung Cenfre, Manchester, UK
Introduction: The increase in incidence of malignant pleural mesothelioma has provoked renewed interest in its pathology and treatment. It is unclear as to which patient and tumour-related factors are of prognostic value, thereby hindering meaningful evaluation of treatment regimes. Method: We have identified a twenty year cohort of patients (n=553) with histologically confirmed malignant pleural mesothelioma that were diagnosed and/or treated at either of our institutions during the period 1980-2000. This cohort was then analysed to determine which patient and tumour-related factors were of prognostic significance. In particular the effect of clinical and demographic factors, histological subtype and asbestos exposure were evaluated for their effect on patient survival. Results: Our cohort consisted of 482 men (87%) and 71 women (12%). Survival, defined as the time elapsed from the date of histological diagnosis to death was known in 521 patients (95%). The mean survival of the cohort was 8 months (range 1 day - 11 years), with only 3 patients surviving longer than 5 years. The two most significant prognostic factors were age at diagnosis (p
El
P 507
Gemcitabine combined to Carboplatin in Malignant pleural mesothelioma: a multicentric phase II study
Adolf0 Gino Favaretto’, Savina M.L. Aversa*, Adrian0 Paccagnella3, Vincenzo De Pangher Manzini4, Francesco Oniga3, Micaela Stefanis, Federico Reas, Luigi Bortolottis, Lucia Loreggians, Silvio Monfardini”. ’Azienda Ospedaliera di Padova, Padova, ITALY; ” Azienda Ospedaliera di Padova, Padova, /ta/y; 3 Ospedale Civile di Venezia, Venezia, Italy; 4 Ospedale di Monfalcone, Monfalcone, Ifaly; 5Universit4 di Padova, Padova, Italy
Background: Malignant pleural mesothelioma is rapidly increasing worldwide. At present, pemetrexed plus cisplatin chemotherapy showed a survival advantage vs. cisplatin alone in a large trial; no impact on patient survival of surgery, radiotherapy or their combination has been demonstrated. Methods: a phase-11 multicenter study led by 8 centers in North-Eastern Italy. Chemotherapy consisted of Carboplatin AUC 5, on day 1, and Gemcitabine 1000 mgIm* on days 1, 8 and 15; recycle every 4 weeks. Results: Between July 1996 and September 2000 50 patients were treated. Their characteristics were: 68% males, 88% ECOG PS O-l; 56% stage Ill disease, 68% epithelioid histology, 62% had no previous treatments. The delivered Dose Intensity of gemcitabine was 617 mg/m*/week, 82% of the planned (750 mg/m”/week); for Carboplatin, the delivered Dose Intensity was 80 mglm’lweek. Overall, 44% of 15th day doses were omitted or reduced. Partial responses were 26% (95% confidence interval: 15-40%) disease progressions 24%. No complete responses were seen. The median response duration was 55 weeks (range 13-I 13 weeks). Patients had good clinical benefit: 46% improved dyspnoea, 40% improved in weight, 26% had reduced pain. In 18 cycles (11%) grade 3-4 leukopenia occurred. Thrombocytopenia grade 3-4 was more frequent: 24 episodes (15%) in 17 patients. Grade 3 anemia occurred in 8 cycles (5%). No patients developed grade 3-4 non-hematologic toxicity. Median survival was 66 weeks with 53%, 30% and 20% alive patients at 1, 2 and 3 years, respectively. The median progression-free survival was 40 weeks. Conclusion: the gemcitabine/carboplatin combination is a valid option in the treatment of MPM due to the acceptable toxicity profile, the good response rate and the ability to give clinical benefit. Probably minor adjustments in schedule (3-week instead of 4-week cycle) would permit a more optimal treatment administration.
Surgical management of malignant pleural mesothelioma
Dominique H. Grunenwald’, lsabelle Monnets, Pierre Bonnette3, Raffaele Caliandro’ , Denis Debrosse’ , Francoise Lepimpec-Barthes4, Pierre Magdeleina@, Maurice Perols, Jean-Francois Regnard5, Pierre Ruffie7. ’ lnstitut Mutualiste Montsouris, Paris, France; ’ Centre Hospitalier Intercommunal, Creteil, France; 3 Hopital Foch, Suresnes, France; 4 Hopital Europeen Georges Pompidou, Paris, France; 5 Hotel-Dieu, Paris, France; 6 Hopita/ de /a Croix Rousse, Lyon, France; 7 lnsfifut Gustave Roussy Villejuif, France Poor outcome of malignant pleural mesothelioma (MPM) led to attempting better local control using surgical resection. This multi-institutional study reports the results of extra-pleural pneumonectomy (EPP) in patients with MPM. Between july 1995 and february 2002, 44 patients were operated on for MPM by the surgeons of the “Groupe Mesotheliome Ile de France”, in five centers. Clinical and histological patterns, surgical findings and survival data were retrospectively recorded. Prognostic factors were analysed. Preoperative histological assessment was obtained by thoracoscopy in 31 patients, minimal thoracotomy in 11, and transcutaneous biopsy in 2. Histology was epithelial in 29 cases, sarcomatous in 2, combined in 11, and desmoplastic in 2. Preoperative treatments were given in 17 patients, cis-platine based chemotherapy in 5 (2 to 5 cycles), thoracic irradiation in 12 (mean dose 27 gy). Preoperative staging (IMIG) was respectively stage I in 16, stage II in 19, and stage Ill in 9 patients. Among the 44 EPP, 25 were right-sided. Pericardial resection was performed in 35 patients, diaphragmatic resection in 43. Complete surgical resection was achieved in 86% of the patients. Twenty-seven patients (61%) had postoperative complications, cardiac (27%), respiratory (14%) and surgical (27%). Three patients died postoperatively (6.8%). Seven patients received adjuvant chemotherapy, and 38 postoperative radiation therapy (45 gy). Late treatment-related morbidity was observed in 22% of the patients. Thirteen patients had disease recurrences (32%) distant in 7, distant and local in 5, and local only in 1. Prognostic factors of better survival were right side (p=O.O15), and Karnovsky index (p=O.O48). This retrospective multicentric study demonstrates that EPP is associated with a high rate of postoperative and late morbidity. Survival impact of EPP remains unknown. Performance status and side are independant prognostic factors. Multicentric prospective trials of multimodality strategies are needed to validate the role of EPP in limited MPM, in terms of both survival rates, and quality of life.
I I P 506
Neoplasm
P 508
Sarcomatoid Malignant Mesothelioma: A Clinicopathological Correlation of 330 Cases
Annabelle M. Mahar, Thomas A. Sporn, Victor L. Roggli. Duke University Medical Center, Durham VA Medical Center, Durham, USA The 1999 WHO classification of malignant mesothelioma recognizes three histological variants: epithelial, sarcomatoid and biphasic. The sarcomatoid variant is the least common. Highly aggressive, sarcomatoid mesotheliomas are also considered by most thoracic surgeons as an inoperable histology for radical surgery. These tumors must be distinguished from a variety of sarcomatoid malignancies that can involve the pleura as both primary and metastatic processes. This study reports the findings in 330 cases of the sarcomatoid variant from a database of 1954 cases of mesothelioma (17%). These included 314 men and 16 women, with a median age of 70 years (range 41-94). Tumor arose in the pleura in 323 cases, and in the peritoneum in 7. One hundred and eleven tumors (33%) were further categorized as desmoplastic (more than 50% of the tumor with a desmoplastic component) and 57 (17%) as sarcomatoid and desmoplastic (i.e. featuring a substantial desmoplastic component but less than 50%). Three cases were classified as having a lymphohistiocytoid pattern (1%). Seven cases (2%) showed osteosarcomatous or chondrosarcomatous differentiation. Most of the remaining 159 cases (48%) had a pattern that resembled fibrosarcoma. lmmunohistochemical staining for ‘cytokeratins was positive in 246/272 cases (90%), with one equivocal result. Fiber analysis was performed in 62 cases, with a median asbestos body count of 1400 as determined by light microscopy (range: 2- 436,000). Fiber type was analyzed by energy dispersive x-ray analysis, and the main fiber type was amosite. Two cases (3%) had asbestos fiber content within our normal range. Information regarding the presence or absence of pleural plaques was available in 181 cases and 146 had plaques. Information regarding the presence or absence of asbestosis was available in 125 cases and 32 had asbestosis. Sarcomatoid mesothelioma is the least common variant and frequently has a desmoplastic component. These tumors are typically keratin positive, which strongly aids in their distinction from true sarcomas and localized fibrous tumors, although the anti-cytokeratin phenotype is recognized. They are usually associated with asbestos exposure, may rarely show evidence of osteochondromatous differentiation, and are associated with an aggressive clinical course.