1
Abstracts/Lung Cancer I2 (1995) 265-329 the disease can be reliably detected, (b) IPT sllows differentiation between SCLC and NSCLC and (c) IPT provides further information on mctaststic disease. AtIer giving their informed consent the patients were injected and imaged 4 and 24 h later using a planar whol&ody tcehniqw. In addition single-photon emission tomography of the thorax and, if necessary, other sress of the body wss performed at 24 h. In the 25 patients with SCLC 22 sites of primsly turnour were comctly identified (true-positive, TP); one wss falsenegative (FN) and two were true- negative (TN), the patients being in full remission. Metastascs were correctly identified in ten instances (lung, bone and brain), while the findings were FN in five cases. An additional six FN findings resulted in the sres of the upper abdomen due to the physiological uptake in the liver. spleen and kidneys. In the 13 patients with NSCLC, ten findings were TP and 3 FN with respect to the primary tumour. Two FNs were squamous cell carcinoma, and one, edcnocareinoma. Mcbxtsses were TP in nine csses and FN in one. We therefore conclude: (1) IPT is s highly sensitive method for the detection of primary bronchogcnic carcinoma, and in particular for SCLC, (2) different&ion between SCLC and NSCLC cannot be achieved and (3) the method is of limited use in the sesrch for metnstntic disessc. Compared with the conventional imaging modalities like X-my, CT and bone scintigrsphy, IPT provides only s small amount of additional diagnostic information. ‘l%erokofCTandMRIiostagingoftbemediaslinum Grover FL. Colorado Univ. Health Sciences Cti, Denver VA Medical Cenfer Derrwr CO. Ch&,1994:106:Supp1:391S-5S. Lung Cancer Study Group (LCSG) Protocol 883, the comparative study of the results of magnetic resonance imaging (MRI) and eomputexized tomography (CT) for staging of tumor, nodal, and selected mctsststic sights in patients with surgically staged lung cancer wss activated in August 1988 but wea not completed because of termination of LCSG funding. A literature review wss therefore undertaken to determine the nsults ofother studies that were performed to evaluate the relative efficacy of MRI and CT in the staging of patients with lung center. Thcsc studies detmnined that CT and MRI are approximately equal in the stsging of N2 disease with s sensitivity of 70 to 90%, s specificity of 60 to 90%. snd sn accuracy of66 to 90% depending on the criteria used for determining positive nodes and the compulsiveness of surgical staging. Magnetic resonance imsging is probably better in the assessment of superior suleus tumors, tumors involving the aorta-pulmonary window, hilsr nodes, in assessing chest wall or diaphragmstic invasion, end in evaluating patients whose CT findings sre equivocal Computed tomography and MRI reveal adrenal abnormalities in 10 to 20% of patients but only one third of these have metsstsses. Mediastinoscopy has s sensitivity of 85 to 90%, II specificity of 100%. and sn accuracy of about 95% and is therefore the gold standard forN2 stsging. Ifthc CT examination rwcals no N2 discesc, one can proceed directly to thorscotomy with approximately s 15% chance of finding N2 discasc. It wss concluded that because CT is much chesper, it should therefore be used for the noninvasive stsging of patients with lung cancer unless the abovanoted special circumstsnccs sre present that have teen shown to favor MRI. Because of the limited accuracy of CT and MRI however, positive findings must be eonfirmed by biopsy specimens and psthologic study. lEeearlydete&nofsecondphmaryhmgcancersbysputumimmuoo- staining To&man MS, Erozan YS, Gupts P, F’isntsdosi S, Mulshine JL, Ruckdeschel JC. JHSHPH, 61s N. War/c. Baltimo~ MD 21205-2179 Chest 1994$06:Suppl:385S- 90s. Srudy objective: To determine whether monoclonal antibody (Mab) detection of tumor-associsted antigen expressed on sputum epithclird cells precedes clinical p~ntstion of second primary lung cancer. Design SeftingParticiponLs: Eleven oncology centers collaborate in the accrual of I ,ooO patients with stage I non- small celllungcanccr(NSCLC) whohsd undergone resection. ThcMsbscxamined in this study (624H12, 703D4) detect two promising oncofe.taVdifferentiation markers (ie, II difucosylatcd Lewis X and s 31-Kd glycoprolein antigen). Interventions: Induced sputum specimens sre evaluated for quality, then sre Papsnicolaou and immunostaincd by independent central laboratories at enrollment and annually thcresftcr. The predictive value of Mab markers is compared with routine morphologic shady for detection of second primary lung cancer during sn anticipated 3 years of accrual and I year of follow-up. Meosurcnrenr~ and resulti Five hundred eighty of an anticipated 1,000 patients have ban accrued on schedule. Patients are primarily white (88.6%), former smokers (75.9%). men (55.6%), with s median age of 66.7, and joined the study at an 8~ragc of 3.7 years following resection of s stage I NSCLC (34.4% squamous, 43.6% adenocarcinoma). Central laboratories found less dysplasia end more unsstisfsctory specimens (27.3%) than do the accrual institution laboratories. Immunoslaining identifies more suspicious cells than does morphologic study. However, only two second primary lung cancers (eight total deaths) have occurred lo date. Conclusionx Halfway through the accrul, we describe the study design and preliminary observations. This study illustretes rations1 selection of carcinogenesis markers by linkage of marker expression on preneoplsstic specimens with subsequent expression on tumor tissue. ‘Ibe adverse effect of perioperative blood transfosioo ia lung cancer Piantadosi S, Moores DWO, MoKneally MF, Oncology Eiosfotisfics, 550 N Broadway. Baltimore. MD 21205. Chest 1994;106:Suppl:382S4S. Perioperstivc blood trsnsfusion appears to increase the risk of recurrence end death in patients with surgically resected lung cancer. This finding is consistent with that in other cancers and several studies in lung cancer report similar risk elevations. WC have reanalyzed the Lung Cancer Study Group data relevant to this question, assessing the potential confounding effects of some prognostic factors not examined previously. The results are nearly identical lo those reported esrlier. suggesting that increased risk is sttributsblc lo blood transfusion and not to confounding by known prognostic factors. pS3 Immunostaining positivity is associated with redoced survival and is imperfectly correlated with gene mutations in resected non-small cell long cancer: A preliminary report of LCSG 871 Carbone DP, Mitsudomi T, Chibs H, Piantsdosi S, Rusch V, Nowsk JA et al. VT Sarfhwes~em Med Ce 5323 Hany Hines, Do/Ins, TX 75235-8593. Chest 1994;106:Suppl:377S-81s. WC investigated the correlation of ~53 abnormalities with survival in 85 patients with non-small cell lung cancer (NSCLC) who had undergone resection with curative intent ss part of Lung Cancer Study Group (LCSG) 871. Our previous studies showed that only s subset of ~53 mutations in lung csncers result in overexpression. In addition, protein overexpression has been described in the absence of mutation. Therefore, we determined both ~53 protein overexpression (by irnmunostsining) and ~53 and rss gene mutations (by single- strand conformation polymorphism end DNA sequencing) in this set of resected tumor specimens. Clinicsl follow-up data were available for 75 cases. Of the studied patients, 64% showed p53 overexpression and 51% had mutant p53 sequences; however. the concordance rate wss only 67%. There was s negative survival correlation with positive ~53 immunostsining (p=O.OS), but not with the presence of gene mutations (6.62) in this group of patients. Overexpression of p53 protein determined by immunostaining may contribute to adverse outcome due to the ability of ~53 to ect ss s dominant oncogene, or alternatively, overexpression msy reflect ongoing DNA damage in the tumor as B marker for B moreaggressive behavior. Whenadjusted for stage,sge,and gendcrby multivariate analysis, however, there wss no independent impact of ~53 overexpression on survival. Role of mediastinal staging of long cancer Thomas PA Jr. Wesf Side Veterans Admin. Med. Ck, Chicago, IL. Chest 1994;106:Suppl:331S-3s. The Lung Cancer Study Group (LCSG) assured objective surgicaVpsthologic staging of clinical trial patients by requiring histologic examination of lymph nodes from anatomically idcnlified specific mcdiestinal locations. Therefore, within the larger population of heterogeneous patients with lung cancer, subsets of more homogeneous patients were identified. The addition of medisstinal exploration and removal of lymph nodes to the intmoperstivc procedure did not increase patient morbidity or mortality. The clinical trials designed using surgical pathologic medisstinsl lymph node staging provided definitive answers to severs1 important questions relative to sdjuvant and neosdjuvant treatment of patients with non-small cell lung cancer. The LCSG recommended that objective histopsthologic medisstinal lymph node staging be acc+pted 8s the standard of csre for patients with lung csncer.

The role of CT and MRI in staging of the mediastinum

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Abstracts/Lung Cancer I2 (1995) 265-329

the disease can be reliably detected, (b) IPT sllows differentiation between SCLC and NSCLC and (c) IPT provides further information on mctaststic disease. AtIer giving their informed consent the patients were injected and imaged 4 and 24 h later using a planar whol&ody tcehniqw. In addition single-photon emission tomography of the thorax and, if necessary, other sress of the body wss performed at 24 h. In the 25 patients with SCLC 22 sites of primsly turnour were comctly identified (true-positive, TP); one wss falsenegative (FN) and two were true- negative (TN), the patients being in full remission. Metastascs were correctly identified in ten instances (lung, bone and brain), while the findings were FN in five cases. An additional six FN findings resulted in the sres of the upper abdomen due to the physiological uptake in the liver. spleen and kidneys. In the 13 patients with NSCLC, ten findings were TP and 3 FN with respect to the primary tumour. Two FNs were squamous cell carcinoma, and one, edcnocareinoma. Mcbxtsses were TP in nine csses and FN in one. We therefore conclude: (1) IPT is s highly sensitive method for the detection of primary bronchogcnic carcinoma, and in particular for SCLC, (2) different&ion between SCLC and NSCLC cannot be achieved and (3) the method is of limited use in the sesrch for metnstntic disessc. Compared with the conventional imaging modalities like X-my, CT and bone scintigrsphy, IPT provides only s small amount of additional diagnostic information.

‘l%erokofCTandMRIiostagingoftbemediaslinum Grover FL. Colorado Univ. Health Sciences Cti, Denver VA Medical Cenfer Derrwr CO. Ch&,1994:106:Supp1:391S-5S.

Lung Cancer Study Group (LCSG) Protocol 883, the comparative study of the results of magnetic resonance imaging (MRI) and eomputexized tomography (CT) for staging of tumor, nodal, and selected mctsststic sights in patients with surgically staged lung cancer wss activated in August 1988 but wea not completed because of termination of LCSG funding. A literature review wss therefore undertaken to determine the nsults ofother studies that were performed to evaluate the relative efficacy of MRI and CT in the staging of patients with lung center. Thcsc studies detmnined that CT and MRI are approximately equal in the stsging of N2 disease with s sensitivity of 70 to 90%, s specificity of 60 to 90%. snd sn accuracy of66 to 90% depending on the criteria used for determining positive nodes and the compulsiveness of surgical staging. Magnetic resonance imsging is probably better in the assessment of superior suleus tumors, tumors involving the aorta-pulmonary window, hilsr nodes, in assessing chest wall or diaphragmstic invasion, end in evaluating patients whose CT findings sre equivocal Computed tomography and MRI reveal adrenal abnormalities in 10 to 20% of patients but only one third of these have metsstsses. Mediastinoscopy has s sensitivity of 85 to 90%, II specificity of 100%. and sn accuracy of about 95% and is therefore the gold standard forN2 stsging. Ifthc CT examination rwcals no N2 discesc, one can proceed directly to thorscotomy with approximately s 15% chance of finding N2 discasc. It wss concluded that because CT is much chesper, it should therefore be used for the noninvasive stsging of patients with lung cancer unless the abovanoted special circumstsnccs sre present that have teen shown to favor MRI. Because of the limited accuracy of CT and MRI however, positive findings must be eonfirmed by biopsy specimens and psthologic study.

lEeearlydete&nofsecondphmaryhmgcancersbysputumimmuoo- staining To&man MS, Erozan YS, Gupts P, F’isntsdosi S, Mulshine JL, Ruckdeschel JC. JHSHPH, 61s N. War/c. Baltimo~ MD 21205-2179 Chest 1994$06:Suppl:385S- 90s.

Srudy objective: To determine whether monoclonal antibody (Mab) detection of tumor-associsted antigen expressed on sputum epithclird cells precedes clinical p~ntstion of second primary lung cancer. Design SeftingParticiponLs: Eleven oncology centers collaborate in the accrual of I ,ooO patients with stage I non- small celllungcanccr(NSCLC) whohsd undergone resection. ThcMsbscxamined in this study (624H12, 703D4) detect two promising oncofe.taVdifferentiation markers (ie, II difucosylatcd Lewis X and s 31-Kd glycoprolein antigen). Interventions: Induced sputum specimens sre evaluated for quality, then sre Papsnicolaou and immunostaincd by independent central laboratories at enrollment and annually thcresftcr. The predictive value of Mab markers is compared with routine morphologic shady for detection of second primary lung cancer during sn anticipated 3 years of accrual and I year of follow-up. Meosurcnrenr~ and resulti Five hundred eighty of an anticipated 1,000 patients have ban accrued on schedule. Patients are primarily white (88.6%), former

smokers (75.9%). men (55.6%), with s median age of 66.7, and joined the study at an 8~ragc of 3.7 years following resection of s stage I NSCLC (34.4% squamous, 43.6% adenocarcinoma). Central laboratories found less dysplasia end more unsstisfsctory specimens (27.3%) than do the accrual institution laboratories. Immunoslaining identifies more suspicious cells than does morphologic study. However, only two second primary lung cancers (eight total deaths) have occurred lo date. Conclusionx Halfway through the accrul, we describe the study design and preliminary observations. This study illustretes rations1 selection of carcinogenesis markers by linkage of marker expression on preneoplsstic specimens with subsequent expression on tumor tissue.

‘Ibe adverse effect of perioperative blood transfosioo ia lung cancer Piantadosi S, Moores DWO, MoKneally MF, Oncology Eiosfotisfics, 550 N Broadway. Baltimore. MD 21205. Chest 1994;106:Suppl:382S4S.

Perioperstivc blood trsnsfusion appears to increase the risk of recurrence end death in patients with surgically resected lung cancer. This finding is consistent with that in other cancers and several studies in lung cancer report similar risk elevations. WC have reanalyzed the Lung Cancer Study Group data relevant to this question, assessing the potential confounding effects of some prognostic factors not examined previously. The results are nearly identical lo those reported esrlier. suggesting that increased risk is sttributsblc lo blood transfusion and not to confounding by known prognostic factors.

pS3 Immunostaining positivity is associated with redoced survival and is imperfectly correlated with gene mutations in resected non-small cell long cancer: A preliminary report of LCSG 871 Carbone DP, Mitsudomi T, Chibs H, Piantsdosi S, Rusch V, Nowsk JA et al. VT Sarfhwes~em Med Ce 5323 Hany Hines, Do/Ins, TX 75235-8593. Chest 1994;106:Suppl:377S-81s.

WC investigated the correlation of ~53 abnormalities with survival in 85 patients with non-small cell lung cancer (NSCLC) who had undergone resection with curative intent ss part of Lung Cancer Study Group (LCSG) 871. Our previous studies showed that only s subset of ~53 mutations in lung csncers result in overexpression. In addition, protein overexpression has been described in the absence of mutation. Therefore, we determined both ~53 protein overexpression (by irnmunostsining) and ~53 and rss gene mutations (by single- strand conformation polymorphism end DNA sequencing) in this set of resected tumor specimens. Clinicsl follow-up data were available for 75 cases. Of the studied patients, 64% showed p53 overexpression and 51% had mutant p53 sequences; however. the concordance rate wss only 67%. There was s negative survival correlation with positive ~53 immunostsining (p=O.OS), but not with the presence of gene mutations (6.62) in this group of patients. Overexpression of p53 protein determined by immunostaining may contribute to adverse outcome due to the ability of ~53 to ect ss s dominant oncogene, or alternatively, overexpression msy reflect ongoing DNA damage in the tumor as B marker for B moreaggressive behavior. Whenadjusted for stage,sge,and gendcrby multivariate analysis, however, there wss no independent impact of ~53 overexpression on survival.

Role of mediastinal staging of long cancer Thomas PA Jr. Wesf Side Veterans Admin. Med. Ck, Chicago, IL. Chest 1994;106:Suppl:331S-3s.

The Lung Cancer Study Group (LCSG) assured objective surgicaVpsthologic staging of clinical trial patients by requiring histologic examination of lymph nodes from anatomically idcnlified specific mcdiestinal locations. Therefore, within the larger population of heterogeneous patients with lung cancer, subsets of more homogeneous patients were identified. The addition of medisstinal exploration and removal of lymph nodes to the intmoperstivc procedure did not increase patient morbidity or mortality. The clinical trials designed using surgical pathologic medisstinsl lymph node staging provided definitive answers to severs1 important questions relative to sdjuvant and neosdjuvant treatment of patients with non-small cell lung cancer. The LCSG recommended that objective histopsthologic medisstinal lymph node staging be acc+pted 8s the standard of csre for patients with lung csncer.