National Cancer Institute®
Last Modified: November 21, 2001
UI - 21356543
AU - Kotoulas C; Lazopoulos G; Karaiskos T; Tomos P; Konstantinou M;
TI - Papamichalis G; Politi D; Lioulias A Prognostic significance of pleural lavage cytology after resection for non-small cell lung cancer.
SO - Eur J Cardiothorac Surg 2001 Aug;20(2):330-4
AD - Second Department of General Thoracic Surgery, Chest Diseases Hospital, Athens, Greece. email@example.com
OBJECTIVE: In the staging of lung cancer, pleural effusion that is malignant on cytologic examination is regarded as T4 disease, and curative resection cannot be performed. We conducted this study to determine whether cancer cells can be present in the pleural cavity with no pleural effusion, to investigate the factors contributing to that occurrence, and to evaluate its prognostic significance. METHODS: Eighty-five patients (77 males, eight females) with a median age 60.1-+/--7.9 years (31--74 years) underwent a major lung resection, due pneumonectomies, seven bilobectomies, 46 lobectomies and two wedge-resections were performed. Chest wall resection was performed in four patients. After performing a posterolateral thoracotomy and lung resection with extended mediastinal lymph node dissection, the pleural cavity was filled with 1 l physiologic saline solution (PSS) and the fluid was shaken. The lavage fluid was suctioned off (S1). Immediately after the lavage, the pleural cavity was refilled with 3 l PSS. The surgeon washed out the pleural cavity by hand for 1 min and the fluid was suctioned off. Finally, the pleural cavity was refilled with 1 l PSS and a new lavage fluid was suctioned off (S2). A cytologic examination was carried out for each sample. RESULTS: The pathology report showed 39 adenocarcinomas, 33 squamous-cell, two adenosquamous, four large-cell, two neuroendocrine and five undifferentiated carcinomas. S1 was positive in eight patients (9.4%), while S2 was positive in four patients (4.7%). The correlation of positive pleural lavage and infiltrated lymph nodes demonstrated a statistically significant relation between presence of N2 disease and positive S2 sample (P = 0.049). No significant correlation existed between positive lavage sample (S1 or S2) and TNM stage, level of T, extent of tumor invasion, kind of operation, histological type or differentiation of the cancer (Chi square test). The mean follow-up is 11.3 +/- 6.2 months (4--22 months). There are 78 patients alive. A significance difference in survival was identified in-patients with positive S1 (P = 0.0081), and positive S2 (P = 0.0251) (Kaplan--Meier). CONCLUSION: The cytologic results of lavage were positive for malignant cells in eight of 85 patients (9.4%). The existence of cancer cells in the pleural cavity can be the result of their exfoliation or surgical manipulations. The mechanical irrigation subdivides the percentage of positive samples. Our study supports that the positive findings on pleural lavage cytology is an essential prognostic factor.
UI - 21356545
AU - Doddoli C; Rollet G; Thomas P; Ghez O; Seree Y; Giudicelli R; Fuentes P
TI - Is lung cancer surgery justified in patients with direct mediastinal invasion?
SO - Eur J Cardiothorac Surg 2001 Aug;20(2):339-43
AD - Department of Thoracic Surgery, Sainte-Marguerite Hospital, Marseille, France. firstname.lastname@example.org
OBJECTIVE: To assess the results of the surgical treatment of patients with stage IIIB non-small cell lung carcinoma (NSCLC) invading the mediastinum (T4). METHODS: Twenty-nine patients were operated on from 1986 to 1999. Histology was squamous cell carcinoma in 17 patients, adenocarcinoma in eight, large cell carcinoma in two and neuroendocrinal carcinoma in two. Three patients received a preoperative chemotherapy (n = 2) or radiochemotherapy (n = 1). The lung resection consisted of a pneumonectomy in 25 patients and a lobectomy in four. The procedure was extended to one of the following structures: superior vena cava (SVC) (n = 17), aorta (n = 1), left atrium (n = 5) and carina (n = 6). Seventeen patients had a postoperative regimen including radiochemotherapy (n = 12), radiotherapy (n = 4), or chemotherapy (n = 1). RESULTS: Complete R0 resection was achieved in 25 patients, whereas four patients had a microscopically (n = 1) or macroscopically (n = 3) residual disease. The operative mortality rate was 7% (n = 2). Non-fatal major complications occurred in eight patients (28%). Overall 5-year survival rate was 28% (median 11 months), including the operative mortality. The median survival of the 18 patients with an N0 or N1 disease was 16 months whereas the median survival of the 11 patients with an N2 disease was 9 months. At completion of the study, 22 patients have died, two postoperatively and 10 from pulmonary causes without evidence of cancer. CONCLUSIONS: Surgical management of T4 NSC lung cancer invading the mediastinum should be considered, in the absence of N2 disease, when a complete resection is achievable.
UI - 21356548
AU - Elia S; Griffo S; Gentile M; Costabile R; Ferrante G
TI - Surgical treatment of lung cancer invading chest wall: a retrospective analysis of 110 patients.
SO - Eur J Cardiothorac Surg 2001 Aug;20(2):356-60
AD - Department of Thoracic Surgery, Medical Faculty, University Federico II, Naples, Italy. email@example.com
OBJECTIVE: To retrospectively assess the results of surgical treatment in a consecutive series of 110 patients with Stage IIb and IIIa non small cell lung cancer (NSCLC) invading chest wall. METHODS: A series of 110 patients underwent surgery for Stage IIb and IIIa NSCLC with involvement of chest wall. There were 101 male and 9 female patients, mean age was 61.4 (range 32--74), 52 (47.3%) of them complaining for chest pain. Surgical procedures were pneumonectomy in seven patients (6.4%), lobectomy in 73 (66.4%), bi-lobectomy in six (5.4%) and wedge resection in 24 (21.8%). In 63 patients (57.3%) an extrapleural resection was performed while in the other 47 (42.7%) an 'en bloc' resection of tumor with chest wall was required. In 22 patients (76.3%) repair was achieved by muscle flap while in 8 (26.7%) a prosthesis was required. Five-year survival was computed using the Kaplan--Meier method; P values correspond to the log-rank test. RESULTS: There were neither intraoperative nor postoperative deaths. Postoperative staging revealed 83 T3N0M0, 17 T3N1M0 and 10 T3N2M0. Mean postoperative hospital stay was 17.7 days (range 5--40). For N0 patients 5 year survival was 47% (39/83) and no significant difference was noted when extrapleural and 'en bloc' resection groups were compared (P = 0.08). In N1/N2 patients no survival was observed (0/27) and comparison between surgical procedures was not statistically significant (P = 0.41). Moreover when N0 patients were compared with N1 patients the difference in survival was significant for both extrapleural (P = 0.02) and 'en bloc' (P = 0.04) groups. No difference was noted when the two surgical procedures were compared independently form N status (P = 0.94).Within the group of patients undergone 'en bloc' resection survival was significantly better for N0 patients as in the group of extrapleural resection. CONCLUSION: Surgical treatment of Stage IIb and IIIa NSCLC invading chest wall by extrapleural or 'en bloc' resection is widely adopted and justified by the good results in terms of morbidity and relief of pain. Survival is always depending on the N status.
UI - 21356549
AU - Granone P; Margaritora S; D'Andrilli A; Cesario A; Kawamukai K; Meacci E
TI - Non-small cell lung cancer with single brain metastasis: the role of surgical treatment.
SO - Eur J Cardiothorac Surg 2001 Aug;20(2):361-6
AD - General Thoracic Surgery, Department of General Surgery, A. Gemelli Hospital-Catholic University of Rome, Rome, Italy.
OBJECTIVE: The prognosis of non-small cell lung cancer (NSCLC) with brain metastasis is very poor, with median survival rate below 6 months, even if treated with palliative radio and/or chemotherapy. To assess the effectiveness of surgical treatment for this kind of patients we patients (26 males and four females; mean age: 58.7 years) with NSCLC and single brain metastasis underwent surgical treatment of both primary lung cancer and secondary cerebral lesion. Patients (pts) were divided into two major groups. In group 1 (G1) 20 pts (18 males and two females) presented a synchronous brain metastasis. In group 2 (G2) 10 pts (eight males and two females) presented a metachronous brain metastasis during the follow-up period (range 3-24 months since the primary tumor). Patients selected in G1 had T1-2, N0-1 clinical staging, good 'performance status' (ECOG:0--1; Karnofsky index > 70%), age < 75 years. Craniotomy has always been the first approach. In G2 also patients with locally advanced tumors (T3 and/or N2) were included. Whole brain radiotherapy and/or chemotherapy was the post-operative choice treatment. RESULTS: Histologic findings have shown: adenocarcinoma in 17 cases (12 in G1; five in G2), squamous cell carcinoma in 10 cases (six in G1; four in G2), large cell carcinoma in 2 (one in G1; one in G2) and large cell neuroendocrine carcinoma in one (G1). Survival analysis (Kaplan--Meier method) has shown an overall value of 80% at 1 year (95% in G1; 50% in G2), 41% at 2 years (47% in G1; 30% in G2) and 17% at 3 years (14% in G1; 20% in G2). Overall median survival is 23 months (23 in G1; 11 in G2); mean survival 27.8 months (30.3 months in G1; 22.8 months in G2). According to univariate analysis prognosis is definitively better in N0 tumors compared to N1-2 tumors and in adenocarcinoma cases compared to other histotypes (P < 0.05). CONCLUSIONS: We can conclude that combined surgical therapy is, nowadays, the choice treatment for this kind of patients, even though restricted to selected cases. The knowledge of prognostic factors may optimize indications for surgery.
UI - 21356550
AU - Carretta A; Canneto B; Calori G; Ceresoli GL; Campagnoli E; Arrigoni G;
TI - Vagani A; Zannini P Evaluation of radiological and pathological prognostic factors in surgically-treated patients with bronchoalveolar carcinoma.
SO - Eur J Cardiothorac Surg 2001 Aug;20(2):367-71
AD - Department of Thoracic Surgery, Scientific Institute H San Raffaele, Milan, Italy. firstname.lastname@example.org
OBJECTIVE: The incidence of adenocarcinoma and bronchoalveolar carcinoma has increased in recent years. The aim of this study was to retrospectively evaluate radiological and pathological factors affecting survival in patients with bronchoalveolar carcinoma (BAC) or BAC associated with adenocarcinoma who underwent surgical treatment. and adenocarcinoma underwent surgical treatment. Complete resection was performed in 42 patients. In these patients the impact of the following factors on survival was evaluated: stage, TNM status, radiological and pathological findings (percentage of bronchoalveolar carcinoma in the tumour, presence or absence of sclerosing and mucinous patterns, vascular invasion and lymphocytic infiltration). RESULTS: Twenty-nine patients were male and 20 female. Mean age was 63 years. Five-year survival was 54%. Univariate analysis of the patients who underwent complete resection demonstrated a favourable impact on survival in stages Ia and Ib (P = 0.01) and in the absence of nodal involvement (P = 0.02) and mucinous patterns (P = 0.02). Mucinous pattern was also prognostically relevant at multivariate analysis (P = 0.02). In the 27 patients with stage Ia and Ib disease, univariate analysis demonstrated that the absence of mucinous pattern (P = 0.006) and a higher percentage of BAC (P = 0.01) favourably influenced survival. The latter data were also confirmed by multivariate analysis (P = 0.01). CONCLUSION: Surgical treatment of early-stage BAC and combined BAC and adenocarcinoma is associated with favourable results. However, the definition of prognostic factors is of utmost importance to improve the results of the treatment. In our series tumours of the mucinous subtype and with a lower percentage of BAC had a worse prognosis.
UI - 21356551
AU - Dougenis D; Patrinou V; Filos KS; Theodori E; Vagianos K; Maniati A
TI - Blood use in lung resection for carcinoma: perioperative elective anaemia does not compromise the early outcome.
SO - Eur J Cardiothorac Surg 2001 Aug;20(2):372-7
AD - Department of Cardiothoracic Surgery, Patras University School of Medicine, Patras 26500, Greece. email@example.com
OBJECTIVE: Blood transfusion may adversely affect the prognosis following surgery for non-small cell lung carcinoma (NSCLC). Conventionally by most thoracic surgeons, a perioperative haemoglobin (Hb) less than 10 g/dl has been considered a transfusion trigger. In this prospective trial we have (a) evaluated the overall blood transfusion requirements and factors associated with an increased need for transfusion and (b) in a subsequent subset of patients, tested the hypothesis that elective anaemia after major lung resection may be safely tolerated in the early postoperative period. METHODS: A total of 198 (M/F 179/10, mean age 61.2, range 32--85 years) patients suffering from NSCLC were submitted to pneumonectomy (n = 89), bilobectomy (n = 19) and lobectomy (n = 90). A rather strict protocol was used as a transfusion strategy. The transfusion requirements were analyzed and seven parameters (gender, age > 65, preoperative Hb < 11.5 g/dl, chest wall resection, history of previous thoracotomy, pneumonectomy and total blood loss) were statistically evaluated by univariate and logistic regression analysis. Subsequently, according to the perioperative Hb level during the first 48 h, patients were divided into group A (n = 49, Hb = 8.5--10) and group B (n = 149, Hb > 10) with a view to estimate the risks of elective perioperative anaemia. Groups were comparable in terms of age, sex, type of operation performed, preoperative Hb, creatinine level, FEV1, arterial blood gases and history of heart disease. RESULTS: The overall transfusion rate was 16%. Univariate analysis revealed that preoperative Hb < 11.5 g/dl (P < 0.01) and total blood loss (P < 0.0001) were associated with increased need for transfusion, but only the total blood loss was identified as an independent variable in multivariate analysis. Statistical analysis between groups A and B showed no significant difference regarding postoperative morbidity and mortality: atelectasis (3 vs. 6), chest infection (2 vs. 9), sputum retention requiring bronchoscopy (5 vs. 12), admission to intensive care unit (5 vs. 7), ARDS (0 vs. 3), postoperative hospital stay (7.7 +/- 2.6 vs. 9.1 +/- 3.8 days) and deaths (1 vs. 3). CONCLUSIONS: The use of a strict transfusion strategy could help in reducing overall blood transfusion. Furthermore, a perioperative Hb of 8.5--10 g/dl could be considered safe in elective lung resections for carcinoma.
UI - 21356552
AU - Mineo TC; Ambrogi V; Corsaro V; Roselli M
TI - Postoperative adjuvant therapy for stage IB non-small-cell lung cancer.
SO - Eur J Cardiothorac Surg 2001 Aug;20(2):378-84
AD - Department of Thoracic Surgery, Tor Vergata University, Rome, Italy. firstname.lastname@example.org
OBJECTIVE: Although surgical resection alone is considered adequate treatment in stage IB non-small-cell lung cancer (NSCLC), long-term survival is not satisfactory and the recurrence rate is quite high. The validity of postoperative chemotherapy at stage IB in terms of disease-free and overall survival was assessed in a randomised trial. METHODS: The trial was designed as a randomised, two-group study with postoperative adjuvant chemotherapy versus surgery alone as control group. All patients had stage IB disease (pT2N0) assessed after a radical surgical procedure. Chemotherapy consisted of treatment with cisplatin (100 mg/m(2) on day 1) and etoposide (120 mg/m(2) on days belonged to the adjuvant chemotherapy group and 33 to the control group. Groups were homogeneous for conventional risk factors. There was no clinical significant morbidity associated to chemotherapy. Patients were followed for a minimum period of 5 years. The rates of locoregional recurrence and distant metastases were 18 and 30%, respectively, in the adjuvant chemotherapy group and 24 and 43%, respectively, in the control group. The 5-year disease-free survival rates were 59% in the adjuvant group and 30% in the control group (P = 0.02). The difference in the Kaplan--Meier survival between the groups was significant as assessed using the log-rank test (P = 0.04). CONCLUSIONS: Our results suggest that adjuvant chemotherapy may reduce recurrences and prolong overall survival in patients at stage IB NSCLC deemed radically operated. Despite being difficult to accept, the use of adjuvant chemotherapy might have better long-term results.
UI - 21356553
AU - Doddoli C; Thomas P; Thirion X; Seree Y; Giudicelli R; Fuentes P
TI - Postoperative complications in relation with induction therapy for lung cancer.
SO - Eur J Cardiothorac Surg 2001 Aug;20(2):385-90
AD - Department of Thoracic Surgery, Sainte-Marguerite University Hospital, Marseilles, France. email@example.com
OBJECTIVES: The purpose of this study was to evaluate the risk of lung cancer surgery following induction chemotherapy and/or radiotherapy. METHODS: This retrospective study included 69 patients treated from had been performed after induction treatment. Surgery had not been considered initially for the following reasons: N2 disease (IIIA, n = 25); temporary functional impairment (two stages IB and two stages IIIA (N2), n = 4); and doubtful resectability (stage IIIB (T4), n = 40). The medical regimen resulted in combined radio-chemotherapy in 43 patients who received two to four cycles of chemotherapy (average 2.9 +/- 0.8 cycles) and 43 +/- 8 Gy (range 20--60 Gy), or chemotherapy alone in 26 patients (3 +/- 0.7 cycles). RESULTS: Exploratory thoracotomy was performed in four patients (6%). The in-hospital mortality was 9% (n = 6) from respiratory origin in all cases. There were four re-operations (6%): three for bronchial fistula and one for bleeding. Thirty-five patients (51%) required blood transfusion (4.5 +/- 3.8 cell packs). The incidence of early and delayed bronchial fistula after pneumonectomy was 15%. Thirteen patients had a postoperative pneumonia (19%). CONCLUSIONS: Surgery for lung cancer after induction chemotherapy and/or radiotherapy is associated with an increased risk. If the mortality seems 'acceptable', the morbidity rate, however, is high.
UI - 21356554
AU - Lewinski T; Zulawski M; Turski C; Pietraszek A
TI - Small cell lung cancer I--III A: cytoreductive chemotherapy followed by resection with continuation of chemotherapy.
SO - Eur J Cardiothorac Surg 2001 Aug;20(2):391-8
AD - Department of Lung and Thoracic Tumors, The Maria Sklodowska--Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
OBJECTIVES: To define the place for surgery in combined modality treatment of small cell lung cancer patients. The endpoint was: does complete resection reduce the risk of local failure? METHODS: Between with a bulky cN2 tumor at presentation, were exposed to VP-16 based cytoreductive chemotherapy. After three courses of induction treatment, 46 patients underwent thoracotomy and 35 of them had resection. RESULTS: There were two sudden deaths (pulmonary embolism). No other complications were observed. In six cases (6/35 = 16%), no residual tumor was found in the resected specimen. Four weeks after surgery, chemotherapy was resumed. Three patients experienced local relapse (3/33), among them, the single patient with incomplete resection, and two other patients developed local and distant failure (2/33). Thus, the local relapse rate was 15% (5/33). Eight patients, mainly with chemotherapy induced surgicopathological complete remission (pCR) and with lymph nodes free of tumor in surgical specimens (pN0), are alive, tumor-free, at a median of 136 + months. Two patients died tumor-free at 65 and 147 months. One patient died of unrelated causes at 21 months with no evidence of disease at autopsy. The median survival in the cN0 + N1 subsets was 25.09 months, whereas in cN2 disease, this was 13.75 months. There were no long-term survivors among the patients with persistent N2 disease. The median survival in all 35 patients using the Kaplan--Meier method was 18 months; the 5-year tumor-free survival rate was 29% and the 10-year tumor-free survival rate was 23%. CONCLUSIONS: Satisfactory local tumor control confirmed the assumption of the study. No residual tumor in the resected specimen (pCR) is the most favorable prognostic factor and determinant of long-term survival. Surgery should not be performed in the patients with persistent N2 disease.
UI - 21436102
AU - Liao M; Wang H; Lin Z; Feng J; Zhu D
TI - Vascular endothelial growth factor and other biological predictors related to the postoperative survival rate on non-small cell lung cancer.
SO - Lung Cancer 2001 Aug-Sep;33(2-3):125-32
AD - Chest Department, Shanghai Chest Hospital, Shanghai 20030, PR China.
OBJECTIVE: An analysis of postoperative 1-5 year-survival rates related to vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGF-r), microvascular density (MVD), P53, H-ras, CerbB2, proliferative index (PI), divisional index (DI) were carried out on 127 cases of non-small cell lung cancer (NSCLC) treated with curative resection and aim to find out more sensitive molecular prognostic predictors for the reference of medicine and molecular pathology. METHODS: All the cases were staged strictly using the UICC criteria of 1997 and regional lymphonodes seen by the naked eye should be dissected and sent to pathology with lung specimens. Immunohistochemical analyses were used for those biological predictors. Kaplan-Meier curve, Cox univariance and multivariance analysis were used for the survival and prognostic predictors. RESULTS: 52 cases (40.9%) with high expression of VEGF showed a worse postoperative year-survival rate than cases with low expression, but no statistical difference. The difference of survival on stage I case with high and low expression were closed to be significant value (P=0.0643). P53, PI and DI were related to postoperative survival, P=0.0341, 0.0005 and 0.0162, respectively. Co-expression of VEGF combined with P53, PI and DI was calculated for the difference of year-survival rate by Cox multivariance analysis. The survival rates of cases with both negative VEGF +P53 or VEGF+PI co-expression rate were better than those with both positive or either positive, P values were 0.0159 and 0.0154, respectively. CONCLUSION: The post-operative year-survival of NSCLC was of no statistical difference between with high expression and low expression of VEGF, but in stage I case it was closed to be significant difference, it speculated that the neoangiogenesis is more obviously in early stage NSCLC, but in the later stage of NSCLC, it may be covered by more complicated molecular-biological factors such as P53 and other oncogens. Co-expression of VEGF combined with p53 or PI was more meaningful than a single biological predicator on survival rate of NSCLC, it is worth to do further studies.
UI - 21436111
AU - Thomas CR Jr; Giroux DJ; Janaki LM; Turrisi AT 3rd; Crowley JJ; Taylor
TI - SA; McCracken JD; Shankir Giri PG; Gordon W Jr; Livingston RB; Gandara DR Ten-year follow-up of Southwest Oncology Group 8269: a phase II trial of concomitant cisplatin-etoposide and daily thoracic radiotherapy in limited small-cell lung cancer.
SO - Lung Cancer 2001 Aug-Sep;33(2-3):213-9
AD - Department of Radiation Oncology, San Antonio Cancer Institute, University of Texas Health Science Center, San Antonio, TX, USA
PURPOSE: To report the long-term follow-up of Southwest Oncology Group-8269, a phase II North American cooperative group trial of concurrent cisplatin, etoposide, vincristine (PEV), and thoracic radiotherapy (TRT) for limited small-cell lung cancer (L-SCLC). METHODS: 114 eligible patients from 47 institutions enrolled between April, 1985 consisted of three cycles of PEV. TRT was administered at 1.8 Gy/fraction in 25 daily fractions to a total dose of 45 Gy, to begin concomitantly. Consolidative chemotherapy included two cycles of vincristine, methotrexate, etoposide, doxorubicin and cyclophosphamide. Prophylactic cranial irradiation (PCI) was concurrent with the 3rd cycle of chemotherapy. The PCI dose was 30 Gy in 15 fractions of 2 progression-free with a minimum follow-up interval of 13.2 years, as of patients died of causes other than SCLC and five patients are still alive and progression-free. Of the remaining 71 patients dying of SCLC, local failure (LF) occurred in 24% (17 patients), distant metastasis (DM) occurred in 35% (25 patients), simultaneous LF and DM occurred in 25% (18 patients), and was indeterminate in 16% (11 patients). Thus, LF was a component of failure in 49%. Twenty patients had the CNS as the initial site of failure. Eleven patients (10%) developed fatal second primary cancers, including two with acute myelogenous leukemia, two with squamous cell lung cancer, one each with breast, pancreas, prostate, renal cell, and myelodysplasia. One patient developed both a melanoma and non-Hodgkin's lymphoma. CONCLUSION: There are long-term survivors with concomitant TRT and PEV. LF and DM are common. Pattern of failure suggests needs to improve local and systemic control.
UI - 21436115
AU - Videtic GM; Fung K; Tomiak AT; Stitt LW; Dar AR; Truong PT; Yu EW;
TI - Vincent MD; Kocha WI Using treatment interruptions to palliate the toxicity from concurrent chemoradiation for limited small cell lung cancer decreases survival and disease control.
SO - Lung Cancer 2001 Aug-Sep;33(2-3):249-58
AD - The Department of Radiation Oncology, London Regional Cancer Center, University of Western Ontario, London, Ontario, Canada. firstname.lastname@example.org
BACKGROUND AND PURPOSE: We analyzed the impact on survival outcomes of treatment interruptions due to toxicity arising during the concurrent phase of chemotherapy/radiotherapy (ChT/RT) for our limited-stage small-cell cancer (LSCLC) population over the past 10 years. MATERIALS AND METHODS: From 1989 to 1999, 215 patients received treatment for LSCLC, consisting of six cycles of alternating cyclophosphamide/doxorubicin or epirubicin/vincristine (CAV; CEV) and etoposide/cisplatin (EP). Thoracic RT was started with EP at either the second or third cycle (85% of patients). RT dose was either 40 Gy in 15 fractions over 3 weeks or 50 Gy in 25 fractions over 5 weeks, delivered to a target volume encompassing gross disease and suspected microscopic disease with a 2 cm margin. Treatment breaks arising during concurrent ChT+RT were used to manage severe symptomatic or hematologic toxicities. We used the interruptions in thoracic RT as the 'marker' for any concurrent break and measured 'break duration' by the total length of time (in days) RT was interrupted, since that also signaled that ChT could be re-initiated. Patient results were analyzed for the impact of interruptions/treatment prolongation on overall and disease-free survival. RESULTS: For all patients, 2-year and 5-year overall and disease-specific survivals were 22.7 and 7.2, 27.6 and 9.3%, respectively; overall and disease-specific median survivals were 14.7 months each. A total of 56 patients (26%) had treatment breaks due to toxicity. Hematologic depression caused the majority of breaks (88%). The median duration of breaks was 5 days (range 1-18). Patients with and without interruptions were compared for a range of prognostic factors and were not found to have any significant differences. Comparing interrupted/uninterrupted courses, median survivals were 13.8 versus 15.6 months, respectively, and 5-year overall survivals were 4.2 versus 8.3%, respectively. There was a statistical difference between overall survival curves which favored the uninterrupted group (P=0.01). When comparing a series of prognostic variables, multivariable analysis found that the most significant factor influencing survival in the present study was the presence of treatment breaks (P=0.006). There was a trend for development of any recurrence in the patients with breaks (P=0.08). When controlling for the use of prophylactic cranial irradiation (PCI) in the two groups, the rate of failure in the chest was higher in the patients with RT breaks (58 vs. 33%). The rate of failure in the brain was dependent on the use of PCI only. CONCLUSIONS: Interruptions in treatment to palliate the toxicity from concurrent chemoradiation result in poorer local control and decreased survival.
UI - 21449351
AU - Roberts JR; Eustis C; Devore R; Carbone D; Choy H; Johnson D
TI - Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung cancer.
SO - Ann Thorac Surg 2001 Sep;72(3):885-8
AD - Department of Cardiac and Thoracic Surgery, Vanderbilt University Hospital, Nashville, Tennessee 37232, USA. email@example.com
BACKGROUND: Neoadjuvant chemotherapy before resection is the standard of care for stage IIIA non-small cell lung cancer in many institutions. Further, neoadjuvant therapy is being studied in earlier stage lung cancer and may be applied more broadly in the future. There is little information about the effect of preoperative chemotherapy on the perioperative complications and mortality after lung resection. METHODS: All patients undergoing anatomic resection after neoadjuvant chemotherapy by a single surgeon at a single institution were compared with patients undergoing similar resections without preoperative chemotherapy. Complications were analyzed as life-threatening (pneumonia, emergency surgery, transfer to the intensive care unit, or intubation), major (prolonging hospital stay but not necessarily dangerous), and minor. The incidence of life-threatening complications, major complications, reintubation, tracheostomy, and mortality were analyzed to determine whether neoadjuvant chemotherapy might have an effect on these complications. Mortality was defined as hospital mortality. Two-tailed Student's t test was used to analyze differences in means and chi2 to determine differences in proportions. Differences less than 0.05 were considered significant. RESULTS: Thirty-four patients underwent resection after neoadjuvant chemotherapy, and 67 patients underwent resection without preoperative therapy. No differences between the two groups in age, pulmonary function, or comorbid diseases were found. The patients receiving chemotherapy did have a more advanced stage (2.52 versus 1.55, p < 0.0001). Striking increases were found in incidence of life-threatening complications (6.0% versus 26.5%, p = 0.0036), major complications (19.4% versus 47.1%, p = 0.0037), reintubation (3.0% versus 17.6%, p = 0.0093), and tracheostomy (0% versus 11.8%, p = 0.0042) in those patients who received preoperative chemotherapy. There was no hospital mortality. However, 2 (neoadjuvant) patients died within 90 days after discharge from the hospital of pneumonia and pulmonary embolus. This difference was also significant (0% versus 5.89%, p = 0.045). CONCLUSIONS: Neoadjuvant carboplatin and Taxol increased the perioperative life-threatening complications in this cohort of patients compared with a similar cohort undergoing operations by the same surgeon in the same institution. The most common life-threatening complication in patients receiving induction chemotherapy was the failure to respond to antibiotics given for pneumonia. Strategies to prevent these complications will be important, especially if chemotherapy before resection becomes the standard for earlier stages of non-small cell lung cancer.
UI - 21455248
AU - Socinski MA; Rosenman JG; Halle J; Schell MJ; Lin Y; Russo S; Rivera MP;
TI - Clark J; Limentani S; Fraser R; Mitchell W; Detterbeck FC Dose-escalating conformal thoracic radiation therapy with induction and concurrent carboplatin/paclitaxel in unresectable stage IIIA/B nonsmall cell lung carcinoma: a modified phase I/II trial.
SO - Cancer 2001 Sep 1;92(5):1213-23
AD - Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599, USA. firstname.lastname@example.org
BACKGROUND: A modified Phase I/II trial was conducted evaluating the incorporation of three-dimensional conformal radiation therapy into a strategy of sequential and concurrent carboplatin/paclitaxel in Stage III unresectable nonsmall cell lung carcinoma (NSCLC). The dose of thoracic conformal radiation therapy (TCRT) from 60 to 74 gray (Gy) was increased. Endpoints included response rate, toxicity, and survival. METHODS: Sixty-two patients with unresectable Stage III NSCLC were included. Patients received 2 cycles of induction carboplatin (area under the concentration curve [AUC], 6) and paclitaxel (225 mg/m(2) over 3 hours) every 21 days. On Day 43, concurrent TCRT and weekly (x 6) carboplatin (AUC, 2) and paclitaxel (45 mg/m(2)/3 hours) were initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy). RESULTS: The response rate to induction carboplatin/paclitaxel was 40%. Eight patients (13%) progressed on the induction phase. No dose-limiting toxicity was observed during the escalation of the TCRT dose from 60 to 74 Gy. The major toxicity was esophagitis, however, only 8% developed Grade 3/4 esophagitis using Radiation Therapy Oncology Group criteria. The overall response rate was 52%. Survival rates at 1, 2, 3, and 4 years were 71%, 52%, 40%, and 36%, respectively, with a median survival of 26 months. The 1-, 2-, and 3-year progression free survival probabilities were 47%, 35%, and 29%, respectively. CONCLUSIONS: Incorporation of TCRT with sequential and concurrent carboplatin/paclitaxel is feasible, and dose escalation of TCRT to 74 Gy is possible with acceptable toxicity. Overall response and survival rates are encouraging. Both locoregional and distant failure remain problematic in this population of patients. Copyright 2001 American Cancer Society.
UI - 21268046
AU - Niklinska W; Chyczewski L; Laudanski J; Sawicki B; Niklinski J
TI - Detection of P53 abnormalities in non-small cell lung cancer by yeast functional assay.
SO - Folia Histochem Cytobiol 2001;39(2):147-8
AD - Department of Histology and Embryology, Medical Academy, Bialystok, Poland.
We assessed the status of P53 in 32 surgically treated non-small cell lung cancers (NSCLC) by using yeast functional assay. For functional assay, total RNA extracted from fresh-frozen specimens was reverse transcribed and P53 cDNAs were PCR-amplified using Pfu DNA polymerase (Stratagene). The transcriptional competence of the P53 cDNA was then tested in a yeast reporter strain. 20 of the 32 (69%) NSCLC patients contained mutant P53 in the yeast functional assay with the higher frequency in squamous cell carcinoma (14/17, 82%) than in adenocarcinoma (5/10, 50%) and large cell carcinoma (3/5, 60%) (p<0.01, chi2 test). No significant difference was observed with respect to the TNM. Preliminary survival analysis showed that patients scoring positive for the yeast test had shorter disease-free survival (median = 10 months) than those that scored negative (median > 21 months). Our results suggest that yeast functional assay is not only an improved method to examine the status of P53, but might hopefully improve understanding of the role of mutant P53 in the clinical evaluation of NSCLC.
UI - 21268047
AU - Chyczewski L; Chyczewska E; Niklinski J; Niklinska W; Sulkowska M;
TI - Naumnik W; Kovalchuk O Morphological and molecular aspects of cancerogenesis in the lung.
SO - Folia Histochem Cytobiol 2001;39(2):149-52
AD - Department of Clinical Molecular Biology, Medical Academy, Bialystok, Poland. email@example.com
Morphology and some molecular aspects of hyperplastic (bronchial basal cell hyperplasia and alveolar cell hyperplasia), metaplastic (squamous metaplasia), preneoplastic and early neoplastic (dysplasia in squamous metaplasia, cancer in situ and atypical alveolar cell hyperplasia) changes were studied in 180 lungs resected due to non-small cell lung cancer: 106 cases (58.9%) of squamous cell carcinoma, 42 (23.3%) of adenocarcinoma and 32 (17.8%) of large cell carcinoma. P53 protein and PCNA expressions were detected immunohistochemically (using formalin-fixed, paraffin-embedded sections). DNA extracted from the microdissected P53-positive cells was analysed for point mutations in the P53 gene. No P53 immunostaining was observed in normal mucosa, hyperplasia of basal cells, squamous metaplasia without and with minor and moderate dysplasia of bronchial mucosa as well as alveolar cell hyperplasia. Overexpression of P53 protein occurred in 3 out of 12 (25%) cases of severe bronchial dysplasia, 5 out of 11 (45.5%) cases of intraepithelial carcinoma and 6 out of 45 (13.3%) cases of alveolar cell hyperplasia. Using direct sequencing, mutations in the P53 gene were detected in 11 out of 14 (87%) P53-immunopositive samples, including all severe dysplasias, all carcinomas in situ and 3 of 6 alveolar cell hyperplasias. A significant association was observed between PCNA expression and preinvasive as well as invasive lesions. The data clearly show that lung resected due to primary cancer ought to be treated as "field cancerization" in which one can find early morphologic events of multi-step cancerogenesis. P53 protein alterations and P53 gene mutations can occur before invasion and its frequency depends on the degree of dysplasia.
UI - 21385858
AU - Weisman IM
TI - Cardiopulmonary exercise testing in the preoperative assessment for lung resection surgery.
SO - Semin Thorac Cardiovasc Surg 2001 Apr;13(2):116-25
AD - Department of Clinical Investigation, Human Performance Laboratory and Pulmonary/Critical Care Services, William Beaumont Army Medical Center, El Paso, TX 79920-5001, USA. firstname.lastname@example.org
Whereas pulmonary function tests (PFTs) initially identify high-risk pulmonary patients being evaluated for lung resection surgery, other diagnostic modalities, including cardiopulmonary exercise testing (CPET) and/or split function studies, are then necessary for a more accurate assessment. CPET including VO2max have emerged as integral components of a step approach for the physiologic assessment for lung resection surgery. Increasingly, CPET is being used because it provides the best index of functional capacity and global O2 transport (VO2max) as well as estimating both cardiac and pulmonary reserves not available from other modalities. CPET permits the detection of clinically occult heart disease and provides a more reliable estimate of functional capacity postoperatively compared with PFTs, which routinely overestimate functional loss after lung resection. Currently, though split function studies are clearly established and have traditionally been used before CPET in preoperative decision analysis, recent work favors using CPET including VO2max before split function studies because VO2max % predicted is a good independent predictor of risk. Importantly, both studies are complementary and optimize assessment of surgical risk; this is particularly valuable for borderline patients, so that opportunity for curative resection is not denied. Copyright 2001 by W.B. Saunders Company
UI - 21424851
AU - Knippel SL
TI - Surgical therapies for lung carcinomas.
SO - Nurs Clin North Am 2001 Sep;36(3):517-25, x-xi
AD - Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4095, USA.
Lung cancer is the leading cause of cancer-related death for men and women in the world today. Surgical resection of early stage non-small cell lung cancer is the recommended treatment option and offers the patient the best chance for survival. Nurses are instrumental in lung cancer prevention, early detection, delivery of quality perioperative care, and maximizing long-term patient survival.
UI - 21431853
AU - Billing PS; Miller DL; Allen MS; Deschamps C; Trastek VF; Pairolero PC
TI - Surgical treatment of primary lung cancer with synchronous brain metastases.
SO - J Thorac Cardiovasc Surg 2001 Sep;122(3):548-53
AD - Division of General Thoracic Surgery, Mayo Clinic and Foundation, Rochester, Minn 55905, USA.
OBJECTIVES: The role of surgical resection for brain metastases from non-small cell lung cancer is evolving. Although resection of primary lung cancer and metachronous brain metastases is superior to other treatment modalities in prolonging survival and disease-free interval, resection of the primary non-small cell lung cancer and synchronous metastases from non-small cell lung cancer at our institution. Twenty-eight (12.7%) of these patients underwent surgical resection of synchronous brain metastases and the primary non-small cell lung cancer. RESULTS: The group comprised 18 men and 10 women. Median age was 57 years (range 35-71 years). Twenty-two (78.6%) patients had neurologic symptoms. Craniotomy was performed first in all 28 patients. Median time between craniotomy and thoracotomy was 14 days (range 4-840 days). Pneumonectomy was performed in 4 patients, bilobectomy in 4, lobectomy in 18, and wedge excision in 2. Postoperative complications developed in 6 (21.4%) patients. Cell type was adenocarcinoma in 11 patients, squamous cell carcinoma in 9, and large cell carcinoma in 8. After pulmonary resection, 17 patients had no evidence of lymph node metastases (N0), 5 had hilar metastases (N1), and 6 had mediastinal metastases (N2). Twenty-four (85.7%) patients received postoperative adjuvant therapy. Follow-up was complete in all patients for a median of 24 months (range 2-104 months). Median survival was 24 months (range 2-104). Survival at 1, 2, and 5 years was 64.3%, 54.0%, and 21.4%, respectively. The presence of thoracic lymph node metastases (N1 or N2) significantly affected 5-year survival (P =.001). CONCLUSION: Although the overall survival for patients who have brain metastases from non-small cell lung cancer is poor, surgical resection may prove beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.
UI - 21440838
AU - Dietlein M; Moka D; Weber K; Theissen P; Schicha H
TI - [Cost-effectiveness of PET in the management algorithms of lung tumors: comparison of health economic data]
SO - Nuklearmedizin 2001 Aug;40(4):122-8
AD - Klinik und Poliklinik fur Nuklearmedizin der Universitat zu Koln, Deutschland. email@example.com
Modelling is an accepted, valid and often necessary method for assessing economic effectiveness in terms of cost per life year gained. Comparing an alternative strategy (a) with a baseline strategy (bl), the incremental cost (COSTa-COSTbl) divided by the incremental life expectancy (LEa-LEbl) defines the incremental cost-effectiveness ratio (ICER). Taking watchful waiting as the low-cost baseline strategy for the management of solitary pulmonary nodules, the ICER of positron emission tomography (PET) [3218 euros (EUR) per life year saved (LYS)] was more favourable than that of exploratory surgery (4210 EUR/LYS) or that of transthoracic needle biopsy (6120 EUR/LYS). Changing the baseline strategy to exploratory surgery, the use of PET led to cost savings and additional life expectancy in case of an intermediate pretest probability of malignancy. For management of potentially operable non-small cell lung cancer the use of PET in patients with normalisized mediastinal lymph nodes on CT was most cost-effective (143 EUR/LYS), and the costs of PET were almost balanced by a better selection of patients for beneficial cancer resection. Using PET in patients with enlarged lymph nodes on CT, the ICER raised to 36,667 EUR/LYS. When PET or CT were positive for mediastinal lymph nodes, the exclusion from biopsy confirmation led to cost savings that did not justify the expected reduction in life expectancy. Economic data from the USA and Japan also demonstrated the cost-effectiveness of PET-based algorithms for the management of lung tumours.
UI - 21453152
AU - Hirota S; Tsujino K; Endo M; Kotani Y; Satouchi M; Kado T; Hishikawa Y;
TI - Obayashi K; Takada Y; Kono M; Abe M Dosimetric predictors of radiation esophagitis in patients treated for non-small-cell lung cancer with carboplatin/paclitaxel/radiotherapy.
SO - Int J Radiat Oncol Biol Phys 2001 Oct 1;51(2):291-5
AD - Department of Radiology, Hyogo Medical Center for Adults, Akashi, Japan. firstname.lastname@example.org
PURPOSE: To establish dosimetric predictors of radiation esophagitis (RE) in patients treated with a combination of carboplatin, paclitaxel, and radiotherapy. METHODS AND MATERIALS: Three-dimensional radiotherapy plans of 26 patients with non-small-cell lung cancer who received 50-60 Gy of radiotherapy concurrently with weekly administration of carboplatin (AUC 2) and paclitaxel (40-45 mg/m(2)) were reviewed in conjunction with RE. The factors analyzed included the following: percentages of organ volumes receiving >40 Gy (V40), >45 Gy (V45), >50 Gy (V50), and >55 Gy (V55); the length of esophagus (total circumference) treated with >40 Gy (LETT40), >45 Gy (LETT45), >50 Gy (LETT50), and >55 Gy (LETT55); the maximum dose in the esophagus (Dmax); and the mean dose in the esophagus (Dmean). Data were obtained on the basis of superposition algorithm. RESULTS: All factors except Dmax showed statistical correlation with RE. Good correlations were shown between RE and LETT45 (rho = 0.714) and V45 (rho = 0.686). CONCLUSIONS: LETT45 and V45 appear to be useful dosimetric predictors of RE. It is also suggested that Dmax does not predict RE.
UI - 21463144
AU - Bonner JA; Tincher SA; Fiveash JB
TI - Balancing the possible effectiveness of postoperative radiotherapy for non-small-cell lung cancer against the possible detriment of radiation-induced toxicity.
SO - J Clin Oncol 2001 Oct 1;19(19):3905-7
UI - 21463146
AU - Machtay M; Lee JH; Shrager JB; Kaiser LR; Glatstein E
TI - Risk of death from intercurrent disease is not excessively increased by modern postoperative radiotherapy for high-risk resected non-small-cell lung carcinoma.
SO - J Clin Oncol 2001 Oct 1;19(19):3912-7
AD - Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA. email@example.com
PURPOSE: Some studies report a high risk of death from intercurrent disease (DID) after postoperative radiotherapy (XRT) for non-small-cell lung cancer (NSCLC). This study determines the risk of DID after modern-technique postoperative XRT. PATIENTS AND METHODS: A total of 202 patients were treated with surgery and postoperative XRT for NSCLC. Most patients (97%) had pathologic stage II or III disease. Many patients (41%) had positive/close/uncertain resection margins. The median XRT dose was 55 Gy with fraction size of 1.8 to 2 Gy. The risk of DID was calculated actuarially and included patients who died of unknown/uncertain causes. Median follow-up was 24 months for all patients and 62 months for survivors. RESULTS: A total of 25 patients (12.5%) died from intercurrent disease, 16 from confirmed noncancer causes and nine from unknown causes. The 4-year actuarial rate of DID was 13.5%. This is minimally increased compared with the expected rate for a matched population (approximately 10% at 4 years). On multivariate analy