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Abramson Cancer CenterNCI CANCERLIT® Search: Radiation, Surgery for Non-small Cell Lung Cancer - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
UI - 11740990
AU - Waller DA
TI -
Neoadjuvant chemotherapy in non small cell lung cancer-the UK
experience.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S31-3
AD - Glenfield Hospital, Leicester LE3 9QP, UK. debra.grew@uhl-tr.nhs.uk
2
UI - 11740992
AU - Zierhut D; Bettscheider C; Schubert K; van Kampen M; Wannenmacher M
TI -
Radiation therapy of stage I and II non-small cell lung cancer (NSCLC).
SO - Lung Cancer 2001 Dec;34 Suppl 3():S39-43
AD - Department of Clinical Radiology, University of Heidelberg, Im
Neuenheimer Feld 400, D-69120 Heidelberg, Germany.
dietmar_zierhut@med.uni-heidelberg.de
Surgery is the preferred and standard treatment for patients with
resectable stage I and II non-small cell lung cancer (NSCLC). Survival
rates of local surgery are unbeaten by other treatment modalities. Up to
70% of these patients survive 5 years or longer. However, there is a
subset of patients who either are inoperable due to the presence of
severe associated diseases, or who refuse surgery. In these patients
radical radiotherapy with curative intent is an effective alternative.
In our department we retrospectively analysed survival and freedom from
treatment failure in those patients treated in our hospital with primary
irradiation for stage I and II NSCLC (T1-2 N0-1 M0) during the last 20
years. In total 60 patients with a median age of 69 years could be
evaluated. 35% had stage I and 65% had stage II NSCLC. All patients
received 2- or 3-dimensionally planned megavoltage radiotherapy with a
median dose of 60 Gy with normally fractionated single doses of 2.0 Gy
five times a week. Pneumonitis WHO Grade III was found in 5 out of the
60 patients (8.3%). Locoregional recurrence was observed in 53% of the
patients resulting in a median progression-free survival of 18 months
and a median overall survival of 20.5 months. However, there is a need
for further improvement of treatment outcome of radiotherapy for
medically inoperable patients with early-stage NSCLC. One possibility
might be radiation dose escalation or alteration in fractionation of
radiotherapy, such as continuous hyperfractionated accelerated
radiotherapy CHART or a modification thereof CHARTWEL. These new
fractionation schemes might be beneficial for a subset of patients in
terms of improved local control, reduced incidence of metastasis and
improved long term survival. The combination of chemotherapy and
radiotherapy might be another option for treatment of early-stage NSCLC.
In advanced disease combined modality treatment turned out to be
superior to radiotherapy alone, concerning local control and survival.
If this is true also for early-stage NSCLC, it has to be shown in
further investigations.
3
UI - 11740993
AU - Crino L; Cappuzzo F
TI -
Multimodality therapy for non-small cell lung cancer (NSCLC): ongoing
Italian experiences in the adjuvant and neoadjuvant settings.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S45-7
AD - Division of Medical Oncology, Bellaria Hospital, Via Altura 3, 40039
Bologna, Italy. lucio.crino@ausl.bologna.it
4
UI - 11740994
AU - Kris MG; Azzoli CG
TI -
Chemotherapy for early stage non-small cell lung cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S49-52
AD - Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275
York Avenue, New York, NY 10021, USA. krism@mskcc.org
For patients with locally advanced non-small cell lung cancer (NSCLC)
undergoing surgery, both induction and adjuvant chemotherapy improve
survival and curability. Induction chemotherapy is also feasible for
patients with early stage NSCLC. Randomized trials of induction
treatment for early stage NSCLC, as well as induction and adjuvant
treatment for Stage IIIA patients, are in progress. These trials should
build on current successes, and add new approaches such as targeted
therapies and vaccines, in an attempt to prevent metastases, recurrence,
and second primary malignancies.
5
UI - 11740995
AU - Manegold C
TI -
Chemotherapy in Stage I/II NSCLC and projects of the EORTC-Lung Cancer
Group for Early Stage Lung Cancer.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S53-8
AD - Thoraxklinik-Heidelberg gGmbH, Amalienstrasse 5, 69126 Heidelberg,
Germany. prof.manegold@t-online.de
The utilization of systemic chemotherapy within multi-modality treatment
concepts in early stage NSCLC would seem to be a very promising concept,
which potentially could lead to increased survival rates. It must be
noted, however, that application of multi-modality treatment strategies
in Stage I and II NSCLC is still experimental and should only be applied
within clinical trials. Caution is thus advisable because the existing
data are not conclusive and there still are a great number of questions
to be answered concerning at least: (1) the regimen, the intensity, the
duration of therapy and the most appropriate schedule to be used for
chemotherapy, (2) the most appropriate time for surgery and its
extensiveness, and (3) the time, dose, and best application modus for
radiotherapy. The Lung Cancer Group of the EORTC has been active in the
clinical development of multi-modality treatment strategies to improve
treatment results for patients with localized, early NSCLC and presently
offers its members several attractive studies dealing with induction
preoperative chemotherapy, induction preoperative chemo-radiotherapy,
and sequential/concomitant chemo-radiotherapy.
6
UI - 11740996
AU - Novello S; Le Chevalier T
TI -
Ongoing/planned studies in France Stage I-II NSCLC.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S59-61
AD - Department of Medicine, Institut Gustave-Roussy, Rue Camille-Desmoulins,
94805 Villejuif Cedex, France.
7
UI - 11740997
AU - Rosell R; Felip E; Maestre J; Sanchez JM; Sanchez JJ; Manzano JL;
TI -
Astudillo J; Taron M; Monzo M
The role of chemotherapy in early non-small-cell lung cancer management.
SO - Lung Cancer 2001 Dec;34 Suppl 3():S63-74
AD - Medical Oncology Service, Hospital Germans Trias i Pujol, Ctra Canyet,
s/n, 08916 Badalona (Barcelona), Spain. rrosell@ns.hugtip.sc.es
Great advances have been made in chemotherapy in advanced and metastatic
non-small-cell lung cancer (NSCLC), and a major milestone was reached
with the administration of neoadjuvant chemotherapy in stage IIIA N2
disease. The systemic nature of lung cancer has been confirmed by many
genetic analyses documenting micrometastases in negative lymph nodes and
bone marrow, and mRNA gene overexpression as a surrogate of cancer cells
has been identified in peripheral blood. Furthermore, serum or plasma
cell-free tumor DNA has been observed even in tumors with a diameter of
less than 2 cm. Pharmacogenetic screening can lead to tailored
chemotherapy even in patients with early disease through the use of a
genetic tool kit that will allow us to optimize the use of chemotherapy
by using serial measurements of serum DNA that can help to detect
residual disease and re-assess the chemosensitivity of sub-clinical
micrometastatic disease. The ongoing (neo)adjuvant taxol/carboplatin
hope (NATCH) trial is testing the value of three cycles of chemotherapy
given pre- or post-operatively compared with surgery alone and will
analyze genetic abnormalities in serum DNA at three different points
during patient follow-up. Our major concern in this review is to analyze
the pros and cons of chemotherapy in NSCLC. Although this review is not
a formal meta-analysis, we have discussed the most relevant published
studies in this field. We conclude that not only is there no evidence of
detrimental effects of chemotherapy, in fact, there are many indications
that chemotherapy induces response in up to 80% of patients and
downgrades N2 disease in up to 50% of patients. This translates into
significantly better survival when accompanied by complete resection.
Since at least 50% of patients with stage IB disease develop distant
metastases, it seems logical to explore the role of chemotherapy in
early disease.
8
UI - 11803144
AU - Turrisi AT; Sherman CA
TI -
The treatment of limited small cell lung cancer: a report of the
progress made and future prospects.
SO - Eur J Cancer 2002 Jan;38(2):279-91
AD - Department of Radiation Oncology, Medical University of South Carolina,
169 Ashley Avenue, POB 250318, Charleston, SC 29425, USA.
turrisi@radonc.musc.edu
The improvements in the treatment of small cell lung cancer over the
last 30 years have been realised by understanding that it is a systemic
disease, but that areas of bulk and sanctuary require a complementary
therapy. Despite successful strategies using combinations and thoracic
radiotherapy, there remains uncertainty about what the best regimens
are, their timing and their intensity. However, earlier concurrent
therapy and rather brief intense chemotherapy and radiotherapy seem to
produce the best results in moderately fit patients of all ages. How to
select the fit patients and what to do about the less fit ones remains
controversial and have economic consequences for governments and payers.
Despite a meta-analysis demonstrating the success of prophylactic
cranial irradiation (PCI), doubts linger about its safety, despite
nothing more than anecdotal evidence from a previous era. The role of
surgery continues to be explored, more in Europe than North America or
Asia. Strategies for treatment of minimum residual disease seem a focus.
New drugs, molecular targeted therapy, immunotherapy and other molecular
therapies offer promise and theory, but there is little evidence about
their place in the treatment protocols of today.
9
UI - 11803145
AU - Novello S; Le Chevalier T
TI -
Use of chemo-radiotherapy in locally advanced non-small cell lung
cancer.
SO - Eur J Cancer 2002 Jan;38(2):292-9
AD - Department of Medicine, Institut Gustave-Roussy, Rue Camille-Desmoulins,
94805 Villejuif Cedex, France.
Lung cancer is the leading cause of cancer mortality in the Western
countries for both men and women. Approximately 40% of patients present
with locally advanced and/or unresectable disease. While small
improvements in outcome have occurred for this group of patients in the
last decade, 5-year survival remains low, ranging from 5 to 20%. Distant
metastases and loco-regional progression remain significant patterns of
failure. Up to the late 1980s, the standard management for locally
advanced non-small cell lung cancer (NSCLC) was conventional thoracic
radiotherapy, but when treated with radiotherapy alone, less than 10% of
patients survived for 5 years or more. 60-70% failed at distant sites
and less than 20% achieved durable local control. The addition of
chemotherapy reduces the rate of distant failure, improves survival and
the combination of chemotherapy and radiotherapy has become the standard
of care of patients with locally advanced NSCLC. Current developments
aim to optimise individual components of combined modality schedules,
increase their synergism and minimise toxicity.
10
UI - 11905734
AU - Saunders M I
TI -
Programming of radiotherapy in the treatment of non-small-cell lung
cancer--a way to advance care.
SO - Lancet Oncol 2001 Jul;2(7):401-8
AD - Centre for Cancer Treatment, Mount Vernon Hospital, Northwood,
Middlesex, UK. mcrw@mtvern.co.uk
Radical radiotherapy, the mainstay of treatment for early inoperable
non-small-cell lung cancer, is most commonly given in daily fractions,
Monday to Friday, to a total dose of 60-70 Gy over 6-8 weeks. Since the
1980s, novel fractionation schedules have been explored with the aim of
improving local tumour control and survival without increasing late
morbidity. There have been two main approaches. In hyperfractionated
radiotherapy the dose per fraction is reduced and the total dose
increased to give improved tumour control without increased late
morbidity. Hyperfractionation schedules, with more than one fraction per
day have been successfully evaluated, but so far significant benefit has
not been achieved when compared with conventional radiotherapy plus
chemotherapy. In accelerated radiotherapy the overall duration of
radiotherapy is reduced to overcome repopulation of tumour cells during
the course of treatment. In all the different regimens of accelerated
radiotherapy a common feature is giving two or more fractions on some or
all treatment days and, in some cases, a lower dose per fraction is also
incorporated. CHART (continuous hyperfractionated accelerated
radiotherapy) is the most novel and accelerated schedule tested, and a
randomised controlled trial showed a significant survival advantage from
CHART compared with conventional radiotherapy. Changes in the
fractionation of radiotherapy must be combined with other approaches
such as neoadjuvant and concomitant chemotherapy, hypoxic-cell
modifiers, and conformal radiotherapy, so that care of patients with
non-small-cell lung cancer can be further advanced.
11
UI - 11891611
AU - Shiau YC; Tsai SC; Wang JJ; Ho YJ; Ho ST; Kao CH
TI -
Technetium-99m tetrofosmin chest imaging related to p-glycoprotein
expression for predicting the response with paclitaxel-based
chemotherapy for non-small cell lung cancer.
SO - Lung 2001;179(4):197-207
AD - Department of Nuclear Medicine, Far Eastern Memorial Hospital, Institute
of Biomedical Engineering, College of Electrical Engineering, National
Taiwan University, Taipei, Taiwan.
Our aim was to use technetium-99m tetrofosmin (Tc-TF) uptake in
non-small cell lung cancer (NSCLC) for predicting the chemotherapeutic
response of NSCLC to paclitaxel and to compare the results with the
expression of multidrug resistance (MDR) - P-glycoprotein (Pgp). Twenty
patients with advanced NSCLC were enrolled in this study before
chemotherapy with paclitaxel. Tc-TF chest imaging was performed to
calculate early and delayed tumor-to-normal lung (T/NL) count-density
ratios, as well as washout indexes (WIs). Immunohistochemical analyses
were performed on multiple nonconsecutive sections of the biopsy
specimens to detect Pgp expression. The response to chemotherapy was
evaluated by clinical and radiological methods in the third month after
completion of treatment. The early and delayed T/NL count-density ratios
of patients with good response were significantly higher than those of
patients with poor response (p <0.05). However, no significant
difference in WI between the two groups of patients was found (p >
0.05). A significantly higher incidence of good response was found in
patients with negative Pgp expression (100%) than in patients with
positive Pgp expression (40%) (p <0.05). Significantly higher early and
delayed T/NL count-density ratios as well as decreased WIs were found in
patients with negative Pgp expression than in patients with positive Pgp
expression. However, other prognostic factors (age, sex, body weight
loss, performance status, tumor stage, and tumor cell type) were not
significantly different between the patients with good response and
those with poor response. Because Tc-TF chest images can correctly
represent the expression of Pgp in NSCLC, it can accurately predict the
chemotherapeutic response to paclitaxel.
12
UI - 11579109
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
13
UI - 11579111
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
analysis, age and radiotherapy dose were borderline significant factors
associated with a higher risk of DID (P =.06). The crude risk of DID for
patients receiving less than 54 Gy was 2% (4-year actuarial risk 0%)
versus 17% for XRT dose > or = 54 Gy. The 4-year actuarial overall
survival was 34%; local control was 84%; and freedom from distant
metastases was 37%. CONCLUSION: Modern postoperative XRT for NSCLC does
not excessively increase the risk of intercurrent deaths. Further study
of postoperative XRT, particularly when using more sophisticated
treatment planning and reasonable total doses, for carefully selected
high-risk resected NSCLC is warranted.
14
UI - 11924237
AU - Moro D
TI -
[Neoadjuvant treatment for early stages of non-small-cell lung carcinoma
(NSCLC)]
SO - Rev Pneumol Clin 2001 Nov;57(5 Pt 2):S22-4
AD - Unite d'oncologie thoracique, CHU, Grenoble.
15
UI - 11924238
AU - Papadakis E
TI -
[Adjuvant treatment for early stages of non-small-cell lung carcinoma
(NSCLC)]
SO - Rev Pneumol Clin 2001 Nov;57(5 Pt 2):S25-8
AD - Service de pneumologie, Hopital Sotiria, Athenes.
16
UI - 11924239
AU - Mornex F
TI -
[Therapeutic management of non-small-cell lung carcinoma (NSCLC) of
stage III A]
SO - Rev Pneumol Clin 2001 Nov;57(5 Pt 2):S29-32
AD - Service d'oncologie, Hopital Jules Courmot, Lyon.
17
UI - 11924245
AU - Bonnette P
TI -
[Lymph node excision in the surgical treatment of bronchopulmonary
cancer]
SO - Rev Pneumol Clin 2001 Nov;57(5 Pt 2):S7-12
AD - Service de chirurgie thoracique, Hopital Foch, Suresnes.
18
UI - 11780699
AU - Movsas B
TI -
Role of adjuvant therapy in resected stage II/IIIA non-small-cell lung
cancer.
SO - Oncology (Huntingt) 2001 Dec;15(12):1549-58
AD - Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia,
Pennsylvania 19111, USA. B_Movsas@FCCC.edu
The role of adjuvant therapy following complete resection of
node-positive (stage II/IIIA) non-small-cell lung cancer remains
controversial. Five-year survival rates in pathologic stage II disease
range from 30% to 50% and in resected stage IIIA disease from 10% to
30%. The majority of recurrences following surgery are distant
metastases. This two-part review, which will conclude in the January
2002 issue, analyzes the role of adjuvant therapy in this setting, using
an evidence-based approach and focusing primarily on randomized trials
and meta-analyses. The key variables in evaluating these studies are
elucidated, ranging from the extent of mediastinal, systemic, and
"molecular" staging to the quality of the adjuvant treatments
administered. Some of the potential flaws inherent in meta-analyses are
reviewed. To date, there is no convincing evidence that any therapy
consistently improves survival in the adjuvant setting. Postoperative
radiotherapy has been associated with a significant improvement in local
control, particularly in patients with pathologic N2 disease.
Chemotherapy should be offered to patients in appropriate clinical
trials, and active phase III trials are reviewed. Future strategies
include novel chemotherapy, methods to reduce toxicity, the emerging
role of neoadjuvant therapy, and the promise of new biologic agents.
19
UI - 11882767
AU - Brabender J; Park J; Metzger R; Schneider PM; Lord RV; Holscher AH;
TI -
Danenberg KD; Danenberg PV
Prognostic significance of cyclooxygenase 2 mRNA expression in non-small
cell lung cancer.
SO - Ann Surg 2002 Mar;235(3):440-3
AD - Department of Molecular Biology, University of Southern California Keck
School of Medicine, Los Angeles, California, USA. drbrabender@cs.com
OBJECTIVE: To investigate cyclooxygenase-2 (COX-2) mRNA expression in
curatively resected non-small cell lung cancer (NSCLC) and to determine
its association with prognosis. SUMMARY BACKGROUND DATA: Lung cancer is
one of the most common malignancies in the world. Despite improvements
in the diagnosis and treatment of NSCLC, the 5-year survival rate
remains less than 15%. Identification of prognostic predictors based on
molecular alterations could lead to additional diagnostic tools and
eventually to more effective therapeutic options. Overexpression of
COX-2 has been reported in several human malignancies, including lung
cancer, but the prognostic importance of this overexpression has not
been elucidated. METHODS: COX-2 mRNA expression was analyzed using a
quantitative real-time polymerase chain reaction (Taqman) method in
surgically resected tumor specimens from 89 patients with curatively
resected NSCLC. RESULTS: COX-2 mRNA was detectable in all 89 (100%)
tumor tissues. High COX-2 expression in tumors was significantly
associated with inferior survival. Multivariate analysis showed that
high COX-2 expression is an independent predictor of worse survival in
patients with NSCLC. CONCLUSIONS: High COX-2 mRNA expression is an
important biomarker for biologically aggressive disease in NSCLC and
might be helpful in identifying patients who would benefit from
additional therapies for controlling their disease.
20
UI - 11939670
AU - Wang CY; Hsie CC; Hsu HS; Wu YC; Hsu WH; Huang BS; Lin TC; Huang MH
TI -
Pulmonary resection for metastases from colorectal adenocarcinomas.
SO - Zhonghua Yi Xue Za Zhi (Taipei) 2002 Jan;65(1):15-22
AD - Department of Surgery, Taipei Veterans General Hospital, Taiwan, ROC.
BACKGROUND: Colorectal cancer is one of the most common cancers in
Taiwan, as in the other part of the world. Surgical intervention is the
best treatment of choice, yet some patients still developed distant
metastasis after primary lesions were controlled. Metastasectomy is
reported to improve the survival. This retrospective study was carried
out to evaluate the relationship between the prognostic factors of lung
metastasectomy and patient survival. METHODS: From 1981 to 2000, 68
patients undergoing complete lung metastasectomy in our section were
studied. The prognostic factors influencing survival were analyzed, and
the survival analysis was made with Kaplan-Meier method and compared by
log-rank test. RESULTS: There was no surgical mortality in our series.
The 5-year survival was 36.1%. None of parameters such as age, sex,
stage of primary colorectal cancer, surgical method, size, number of
metastatic deposits and disease free interval showed to relate with the
survival. CONCLUSIONS: We concluded that lung metastasectomy for
colorectal cancer is safe and effective to improve the survival. Since
there were no significant factors influencing the survival, there should
be no absolute contraindication against resectable pulmonary metastasis
after primary lesions were adequately controlled.
21
UI - 11804694
AU - Plataniotis GA; Kouvaris JR; Dardoufas C; Kouloulias V; Theofanopoulou
TI -
MA; Vlahos L
A short radiotherapy course for locally advanced non-small cell lung
cancer (NSCLC): effective palliation and patients' convenience.
SO - Lung Cancer 2002 Feb;35(2):203-7
AD - Department of Radiation Oncology, Aristoteles University of
Thessaloniki, AHEPA Hospital, 1 St. Kyriakidi str., Thessaloniki, 54636
Greece. gplatan3@otenet.gr
In order to facilitate patients with symptomatic locally advanced NSCLC,
especially those coming from remote areas we have employed two
palliative RT schedules. The first (S1) is the well known from Medical
Research Council (MRC) randomized studies 2 x 8.5 Gy one week apart and
the second (S2) is a two-day RT schedule: three fractions of 4.25 Gy are
given on the first day and two fractions of 4.25 Gy on the second day.
The records of 92 patients were reviewed (48 for S1 and 44 for S2).
Patients, disease characteristics and results were similar for both
groups; rates of symptom disappearance were for S1 and S2, respectively:
cough 24 and 20%, hemoptysis 60 and 67%, chest pain 57 and 64% and
dyspnoea 55 and 45% The overall condition improved in 39 and 36%,
respectively. The median palliation time in days was in S1 and S2,
respectively: cough 70 and 66, haemoptysis 133 and 139, chest pain 68
and 62 and dyspnoea 74 and 69 days. The median survival was 25 weeks in
both S1 and S2 groups (P=0.89 log-rank test). At 52 weeks (one year),
ten (21%) and seven (16%) of the patients were alive in S1 and S2
groups, respectively. At 104 weeks, the corresponding figures were two
(4%) and two (4.7%) for S1 and S2. Our results are in accordance to
those reported in literature regarding the safety and efficacy of
palliative hypofractionated radiotherapy schemes. Their use in selected
patients could be cost-effective and convenient for patients especially
those coming from remote areas.
22
UI - 11888009
AU - Van Houtte P
TI -
The role of radiotherapy and the value of combined treatment in lung
cancer.
SO - Eur J Cancer 2001 Oct;37 Suppl 7():S91-8
AD - Institut J. Bordet, Department of Radiotherapy, Brussels, Belgium.
23
UI - 11917282
AU - Werner-Wasik M; Axelrod RS; Friedland DP; Hauck W; Rose LJ; Chapman AE;
TI -
Grubbs S; Deshields M; Curran WJ
Phase II: trial of twice weekly amifostine in patients with non-small
cell lung cancer treated with chemoradiotherapy.
SO - Semin Radiat Oncol 2002 Jan;12(1 Suppl 1):34-9
AD - Kimmel Cancer Center of Jefferson Medical College, Philadelphia, PA,
USA.
Twenty-four patients with non-small cell lung cancer received induction
chemotherapy (paclitaxel, carboplatin) followed by concurrent thoracic
irradiation (RT) and weekly paclitaxel. Acute esophagitis was scored
weekly. Amifostine (AMI), 500 mg intravenously twice weekly, was added
to the regimen in the second cohort of 12 patients. AMI was well
tolerated. The incidence of grade 3 esophagitis was 18% in the initial
11 patients versus 9% in the AMI-treated patients. Mean esophagitis
index (EI) was numerically lower in the AMI-treated patients than in the
initial group (5.1 v 11.6, P =.14). The length of esophagus in the RT
field was similar in both groups. Median survival time for all patients
was 12.4 months. The EI, a novel measure of the severity and duration of
acute esophagitis, may be reduced in lung cancer patients receiving AMI
twice weekly with thoracic RT and paclitaxel. The effect of AMI was not
caused by the shorter irradiated esophageal length. A phase III
randomized trial is now open to assess the effect of AMI on esophagitis.
Copyright 2002, Elsevier Science (USA). All rights reserved.
24
UI - 11917283
AU - Movsas B
TI -
Exploring the role of the radioprotector amifostine in locally advanced
non-small cell lung cancer: Radiation Therapy Oncology Group trial
98-01.
SO - Semin Radiat Oncol 2002 Jan;12(1 Suppl 1):40-5
AD - Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia,
PA 19111, USA.
The ultimate goal of any strategy in oncology is to enhance the
therapeutic ratio, defined as tumor cell kill divided by normal tissue
injury. Whereas most trials focus on intensifying therapy, this often
increases toxicity so that there is no overall gain in the therapeutic
ratio. Radiation Therapy Oncology Group (RTOG) trial 98-01, a phase III
study testing the ability of a radioprotector (Amifostine [Ethyol,
WR-2721]) to reduce the toxicity of an intensive chemoradiation regimen
for locally advanced non-small cell lung cancer (NSCLC), is unique in
that it addresses both "sides" of this equation. During the 1990s,
thoracic radiotherapy (RT) combined with chemotherapy was accepted as a
"new" gold standard for patients with good performance status locally
advanced/inoperable NSCLC. This paradigm shift away from RT alone has
raised several key questions: What is the optimal method of integrating
chemotherapy and RT? Equally importantly, how can the toxicity of
combined modality strategies be reduced? This article will review the
background underlying RTOG 98-01, a trial exploring the potential role
of amifostine in NSCLC. Copyright 2002, Elsevier Science (USA). All
rights reserved.
25
UI - 11917284
AU - Komaki R; Lee JS; Kaplan B; Allen P; Kelly JF; Liao Z; Stevens CW;
TI -
Fossella FV; Zinner R; Papadimitrakopoulou V; Khuri F; Glisson B;
Pisters K; Kurie J; Herbst R; Milas L; Ro J; Thames HD; Hong WK; Cox JD
Randomized phase III study of chemoradiation with or without amifostine
for patients with favorable performance status inoperable stage II-III
non-small cell lung cancer: preliminary results.
SO - Semin Radiat Oncol 2002 Jan;12(1 Suppl 1):46-9
AD - Department of Radiation Oncology, The University of Texas M.D. Anderson
Cancer Center, Houston, TX 77030, USA.
A prospective randomized study was conducted to determine whether
amifostine (Ethyol) reduces the rate of severe esophagitis and
hematologic and pulmonary toxicity associated with chemoradiation or
improves control of non-small cell lung cancer (NSCLC). Sixty patients
with inoperable stage II or III NSCLC were treated with concurrent
chemoradiotherapy. Both groups received thoracic radiation therapy (TRT)
with 1.2 Gy/fraction, 2 fraction per day, 5 days per week for a total
dose 69.6 Gy. All patients received oral etoposide (VP-16), 50 mg Bid,
30 minutes before TRT beginning day 1 for 10 days, repeated on day 29,
and cisplatin 50 mg/m(2) intravenously on days 1, 8, 29, and 36.
Patients in the study group received amifostine, 500 mg intravenously,
twice weekly before chemoradiation (arm 1); patients in the control
group received chemoradiation without amifostine (arm 2). Patient and
tumor characteristics were distributed equally in both groups. Of the 60
patients enrolled, 53 were evaluable (27 in arm 1, 26 in arm 2) with a
median follow-up of 6 months. Median survival times were 26 months for
arm 1 and 15 months for arm 2, not statistically significantly
different. Morphine intake to reduce severe esophagitis was
significantly lower in arm 1 (2 of 27, 7.4%) than arm 2 (8 of 26, 31%; P
=.03). Acute pneumonitis was significantly lower in arm 1 (1 of 27,
3.7%) than in arm 2 (6 of 26, 23%; P =.037). Hypotension (20 mm Hg
decrease from baseline blood pressure) was significantly more frequent
in arm 1 (19 of 27, 70%) than arm 2 (1 of 26, 3.8%; P =.0001). Only 1
patient discontinued treatment because of hypotension. These preliminary
results showed that amifostine significantly reduced acute severe
esophagitis and pneumonitis. Further observation is required to assess
long-term efficacy. Copyright 2002, Elsevier Science (USA). All rights
reserved.
26
UI - 11917285
AU - Antonadou D
TI -
Radiotherapy or chemotherapy followed by radiotherapy with or without
amifostine in locally advanced lung cancer.
SO - Semin Radiat Oncol 2002 Jan;12(1 Suppl 1):50-8
AD - Metaxas Cancer Hospital, Greece.
Radiotherapy (RT) or radiochemotherapy is the treatment of choice for
patients with medically or technically inoperable non-small cell lung
cancer (NSCLC) localized to the primary site and regional lymph nodes.
Radiation-induced damage has been recognized as a major complication in
thoracic RT. The use of concurrent chemoradiation has been associated
with an increase in acute and late toxicity. Amifostine (Ethyol) is an
effective cytoprotective agent and also may have a role in protecting
healthy lung tissue during radiation treatment. The purpose of these 2
clinical trials was to investigate whether daily pretreatment with
amifostine could reduce the incidence of esophagitis, and acute and late
lung toxicity without affecting the antitumor efficacy of the treatment.
The first was a phase III randomized trial of 146 patients with locally
advanced lung cancer. All patients received conventional RT to a total
of 55 to 60 Gy, and they were assigned randomly to pretreatment with 340
mg/m(2) of amifostine (A). Acute and late toxicities were graded
according to the Radiation Therapy Oncology Group (RTOG) grading system
from grades 0 to 4. Ninety-seven patients were evaluated 2 months
post-RT for the incidence of pneumonitis; 43% (23 of 53) of patients in
the RT arm and 9% (9 of 44) in the A plus RT arm experienced grade > or
= 2 pneumonitis (P <.001). Forty-nine percent (26 of 53) of patients in
the RT arm and 16% (7/44) in the A plus RT arm showed changes that were
representative of grade > or = 2 lung damage in the computed tomography
(CT) scan. Fibrosis was present in 53% (19 of 36) of patients receiving
RT versus 28% (9 of 32) in the A plus RT arm at 6 months (P < 0.05). The
incidence of esophagitis grade > or = 2 during week 4 was 42% (31 of 73)
in the RT arm versus 4% (3 of 73) in the A plus RT arm (P <.001). Among
97 patients evaluable for response 2 months after RT, complete or
partial responses were present in 76% (40 of 53) of patients in the RT
arm and 75% (33 of 44) in the A plus RT arm (P = 1.0). The second trial
was a phase II randomized study of 45 patients with NSCLC. All patients
had received platinum-based induction chemotherapy before being referred
for conventional radiation treatment with or without A; a total dose of
55 to 60 Gy was administered at the primary site. Acute and late
toxicities were evaluated and graded according the RTOG criteria from
grades 0 to 4. Forty-five patients were evaluable for response 2 months
after RT. Complete or partial responses were achieved in 78% (18 of 23)
of patients in the RT arm and 82% (18 of 22) in the A plus RT arm (P
=.278). By week 5, 74% (17 of 23) of patients in the RT group versus 36%
(8 of 22) in the A plus RT group experienced grade > or = 2 esophagitis.
(During the follow-up period, pulmonary toxicity was evaluated by CT
scan.) Three months after RT, 65% (15/23) of patients in the RT group
and 32% (7 of 22) in the A plus RT group presented with grade > or = 2
pneumonitis (P =.038). Amifostine reduces the incidence of acute and
late radiation-induced toxicities. Copyright 2002, Elsevier Science
(USA). All rights reserved.
27
UI - 11917286
AU - Arquette M; Wasserman T; Govindan R; Garfield D; Senzer N; Gillenwater
TI -
H; Socinski M
Phase II evaluation of amifostine as an esophageal mucosal protectant in
the treatment of limited-stage small cell lung cancer with chemotherapy
and twice-daily radiation.
SO - Semin Radiat Oncol 2002 Jan;12(1 Suppl 1):59-61
AD - Washington University, St Louis, MO 63110, USA.
For limited-stage small cell lung cancer, twice-daily radiation with
concurrent chemotherapy improves survival rate, but has dose-limiting
esophageal toxicity. The authors studied 34 patients treated with
amifostine in an attempt to decrease the incidence and grade of
esophagitis. The results indicate that there was no reduction in
toxicity, but the authors were able to maintain the high complete
response rate that had been reported previously. These results differ
from the use of amifostine in non-small cell lung cancer in which there
is the observation of esophageal protection. Copyright 2002, Elsevier
Science (USA). All rights reserved.
28
UI - 11920642
AU - Chen JT; Chen YC; Wang YC; Tseng RC; Chen CY; Wang YC
TI -
Alterations of the p16(ink4a) gene in resected nonsmall cell lung tumors
and exfoliated cells within sputum.
SO - Int J Cancer 2002 Apr 10;98(5):724-31
AD - Department of Pathology, Taichung Veterans General Hospital, Republic of
China.
Recently, we reported that p16 protein expression was nondetectable in
49.5% of 107 resected nonsmall cell lung cancers (NSCLCs), suggesting
that the p16(INK4a) gene is frequently inactivated in primary NSCLC. To
identify the molecular basis for this p16 immunohistochemical negativity
further, we performed a genetic and epigenetic study of p16(INK4a)
status in a series of 115 NSCLC samples parallel to the
clinicopathologic and prognostic analyses. Microdissected tumor DNA
samples were screened for homozygous deletion using comparative
multiplex-polymerase chain reaction (PCR), for intragenic mutation using
direct sequencing and for loss of heterozygosity (LOH) using an
intragenic microsatellite marker, D9S942. Of these samples, 67 were
further analyzed by SmaI-based PCR methylation assay to evaluate
aberrant methylation at the gene. To examine the correlation of aberrant
methylation in tumor and sputum samples, sputum samples from 12 matched
patients were assessed for this change. We found that methylation of the
p16(INK4a) gene was present in 38 of the 67 (56.7%) tumors and was
significantly associated with negative p16 protein expression (p =
0.029). A 92% (11/12) concordance of sputum samples with matched
resected tumors was found. The survival rates among adenocarcinoma
patients with p16(INK4a) methylation were lower, but at a level of
borderline significance compared with those patients without methylation
(p = 0.071). In addition, 29.4% of the informative cases were found to
harbor LOH at D9S942. None of the 115 microdissected tumors exhibited
homozygous deletion in the p16(INK4a) gene. Only 1 patient exhibited a
complex mutation at the fourth ankyrin repeat consensus sequence and
concordantly demonstrated p16 immunohistochemical negativity. Overall,
69% (79/115) of NSCLC tumors had at least 1 type of p16(INK4a)
alteration. Our data provide compelling evidence that p16(INK4a)
alterations are involved in NSCLC tumorigenesis and that promoter
methylation is the predominant mechanism in p16(INK4a) deregulation.
Copyright 2002 Wiley-Liss, Inc.
29
UI - 9053852
AU - Wolf G; Elez R; Doermer A; Holtrich U; Ackermann H; Stutte HJ;
TI -
Altmannsberger HM; Rubsamen-Waigmann H; Strebhardt K
Prognostic significance of polo-like kinase (PLK) expression in
non-small cell lung cancer.
SO - Oncogene 1997 Feb 6;14(5):543-9
AD - Chemotherapeutisches Forschungsinstitut, Georg-Speyer-Haus, Frankfurt,
Germany.
Our previous data indicate that the expression of the PLK gene which
codes for a serine/threonine kinase is restricted to proliferating
cells. In Northern blot experiments PLK mRNA expression was at the limit
of detection in normal lung tissue but elevated in most samples of
non-small cell lung cancer (NSCLC). A very low frequency of PLK
transcripts was only found in bronchiolo-alveolar carcinomas. NSCLC
patients whose tumors showed moderate PLK expression survived
significantly longer (5 year survival rate=51.8%) than those with high
levels of PLK transcripts (24.2%, P=0.001). No statistically significant
correlation was found between PLK mRNA expression and age, sex, TNM
status, histological type or degree of differentiation. Interestingly,
the prognosis of patients in post-surgical stages I and II was
correlated with PLK expression (5 year survival rates in stage I: 69.1%
(moderate PLK) - 43.5% (high PLK), P=0.03 or in stage II: 51.9%
(moderate PLK) - 9.9% (high PLK), P=0.006). These results suggest that
PLK mRNA expression provides a new independent prognostic indicator for
patients with NSCLC.
30
UI - 11373887
AU - Quddus AM; Kerr GR; Price A; Gregor A
TI -
Long-term survival in patients with non-small cell lung cancer treated
with palliative radiotherapy.
SO - Clin Oncol (R Coll Radiol) 2001;13(2):95-8
AD - Western General Hospital, Edinburgh, UK.
The aim of palliative thoracic radiotherapy in patients with advanced
non-small cell lung cancer (NSCLC) is to alleviate symptoms. This study
was designed to determine whether any patients achieved long-term
survival after this treatment. In Edinburgh, between 1974 and 1993, 4531
patients were treated with palliative radiotherapy for NSCLC, receiving
ten fractions or fewer. We reviewed the case notes of the long-term
survivors. Sixty-one (1.3%; 95% confidence interval (CI) 1.0-1.6)
patients survived for more than 5 years; 43 (70%) had histological
confirmation of cancer; 28 (46%) had stage Stage I or II, 28 (46%) Stage
III and one Stage IV disease; 53 (87%) patients were treated with doses
of 30-35 Gy in ten daily fractions, seven (12%) received 20 Gy in five
daily fractions and one received a 10 Gy single fraction. Forty-two
(69%) patients had a radiological complete response, 16 (26%) a partial
response and the remainder stable disease. Clinically significant
radiation pneumonitis occurred in one (2%) patient, radiation myelopathy
in two (3%) and multiple rib fractures in one (2%). There did not appear
to be an association between long-term survival and a radiosensitive
phenotype. On univariate analysis, long-term survival was more frequent
in patients receiving ten-fraction regimens than in those who underwent
a shorter course of radiotherapy (chi 2 = 19.5, P < 0.001). Thirty-four
(0.8%; 95% CI 0.6-1.0) patients were disease free at death or at last
review (median 10 years; range 5-17). We conclude that palliative
thoracic radiotherapy produces long-term survival in 1.3% and personal
cure in up to 1% of patients with advanced NSCLC.
31
UI - 11911271
AU - Xing T; Brattstrom D; Bergqvist M; Isaksson U; Wagenius G; Brodin O
TI -
Radiation responsiveness of human lung cancer cell lines measured with a
short term semiautomatic assay.
SO - Anticancer Res 2001 Nov-Dec;21(6A):3925-8
AD - Department of Oncology, Radiology and Clinical Immunology, Uppsala
University Hospital, Sweden.
BACKGROUND: Fluorometric microculture cytotoxicity assay (FMCA) is a
short-term semi-automatic method, based on dye-inclusion of surviving
cells. The assay was developed for investigations of drug resistance on
tumour cells from biopsy material. In the present study, this short-term
assay was evaluated, regarding usefulness in determining
radio-sensitivity. MATERIALS AND METHODS: Eight human lung cancer cell
lines were used. There were five small cell lung cancer (SCLC and three
non-small cell lung cancer (NSCLC cell lines. Results were compared with
the corresponding data derived from the clonogenic assay and/or the
extrapolation method. RESULTS: The surviving fraction (SF) after 2, 5
and 10 Gy compared with data from the clonogenic assay were not in
accordance for 5 of the 8 cell lines. The FMCA assay overestimated SF-
values for the SCLC cell lines. CONCLUSION: The FMCA assay is not useful
as a quick screening method for the radioresponsiveness in vitro of
human tumour cell lines.
32
UI - 11911293
AU - Mattern J; Volm M
TI -
Clinical estimation of the growth rate of lung cancer.
SO - Anticancer Res 2001 Nov-Dec;21(6A):4067-70
AD - German Cancer Research Center, Heidelberg. j.mattern@dkfz.de
It is well known that the growth rate of lung tumors is closely related
to prognosis and is an important determinant of responsiveness to
therapy and curability. In this study, the velocity of tumor growth was
calculated by dividing the area of the lesion at presentation divided by
the time elapsed since symptoms were first noted. This parameter was
applied to a group of patients with lung cancer and the predictive value
of the velocity of tumor growth was assessed. Survival expectancy was
found to be closely related to the growth rate of the tumors. The median
survival time of patients with more slowly growing tumors was 102 weeks,
while that of patients with fast-growing tumors was 30 weeks (log-rank
test, p=0.00001). Linear regression analysis between velocity of tumor
growth and tumor cell proliferation as measured by the PCNA-labelling
index revealed a significant correlation between these two parameters.
In conclusion, the velocity of a tumor measured in this way is an
independent and significant prognostic factor for patients with lung
cancer and may be used to non-invasively assess lung cancer
proliferation in vivo, identifying rapidly growing tumors with poor
prognosis that could benefit from a more aggressive therapy.
33
UI - 11911315
AU - Gridelli C; Curcio C; Iaffaioli R V; Brancaccio L; D'Aprile M; Gebbia V;
TI -
Rossi A; Tortoriello A; Veltri E; Maione P; Barbarisi A; Gallo C; Guida
C; Perrone F
Carboplatin + epirubicin +VP-16 + lenograstim followed by radiotherapy +
carboplatin as radiosensitizer in limited small cell lung cancer. A
multicenter phase II study.
SO - Anticancer Res 2001 Nov-Dec;21(6A):4179-83
AD - Oncologia Medica B, Istituto Nazionale Tumori, Napoli, Italy.
cgridelli@sirio-oncology.it
A phase II trial was undertaken to test the activity and toxicity of
carboplatin (300 mg/m2, i.v. day 1) + epirubicin (75 mg/m2, i.v. day 1)
+ VP-16 (100 mg/m2, i.v. days 1 to 3) + lenograstim (5 mcg/kg, s.c. days
6 to 15) administered every 3 weeks for 4 cycles and subsequent chest
irradiation (50 Gy) + daily carboplatin (25 mg/m2) in the first-line
treatment of adults affected by limited small cel
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