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NCI CANCERLIT® Search: Radiation, Surgery for Non-small Cell Lung Cancer - October 2001
National Cancer Institute®
Ultima Vez Modificado: 21 de noviembre del 2001
Table of Contents
1
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. chrkotoulas@hol.gr
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.
2
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. cdoddoli@mail.ap-hm.fr
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.
3
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. elia@unina.it
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.
4
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.
5
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. angelo.carretta@hsr.it
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.
6
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. ddougen@med.upatras.gr
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.
7
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.
mineo@med.uniroma2.it
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.
8
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. cdoddoli@mail.ap-hm.fr
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.
9
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.
10
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.
11
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.
12
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.
greg.videtic@lrcc.on.ca
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.
13
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.
bob.roberts@mcmail.vanderbilt.edu
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.
14
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.
socinski@med.unc.edu
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.
15
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.
16
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. lchycz@amb.ac.bialystok.pl
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.
17
UI - 21387836
AU - Macbeth F; Price A
TI -
Reviews should be more systematic.
SO - Radiother Oncol 2001 Aug;60(2):225-7
18
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. iweisman@aol.com
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
19
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.
20
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.
21
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. nuklearmedizin@medizin.uni-koeln.de
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.
22
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.
ka3s-hrt@asahi-net.or.jp
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.
23
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
24
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. machtay@xrt.upenn.edu
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
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