(Chest. 2000;117:127S-132S.)
© 2000
American College of Chest Physicians
Combined Modality Therapy for Unresectable Stage III Non-Small Cell Lung Cancer*
New Chemotherapy Combinations
Chandra P. Belani, MD
*
From the Division of Medical Oncology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA.
Correspondence to: Chandra P. Belani, MD, University of Pittsburgh Cancer Institute, 200 Lothrop St, MUH N-725, Pittsburgh, PA 15213; e-mail: belanicp{at}msx.upmc.edu
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Abstract
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Over the last decade, we have witnessed improved outcome among
patients with non-small cell lung cancer (NSCLC), principally through
the use of new and novel treatment programs. A meta-analysis of
randomized clinical trials comparing combined chemotherapy and
radiation to radiation therapy alone clearly has shown a survival
benefit with platinum-based combination chemotherapy administered
sequentially or concurrently with thoracic radiation therapy over
radiation therapy alone. In addition, combining thoracic radiation
therapy with novel drugs or new drug combinations has yielded
improvements in median survival duration and long-term survival rates
in locally advanced unresectable NSCLC. Paclitaxel and carboplatin are
two novel agents that have undergone extensive clinical evaluation at
various doses and schedules in combination with thoracic radiation
therapy in patients with locally advanced disease. There remains a
need, however, for further improvement in metastatic control and
prevention of locoregional recurrences. This will likely be achieved
through the optimization of chemotherapy regimens to be used in
combined modality therapy with thoracic radiation therapy.
Key Words: combined modality esophagitis non-small cell lung cancer radiosensitization survival therapy thoracic radiation
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Introduction
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Thoracic
radiation therapy (TRT) by itself provides local control and effective
palliation of symptoms, but has minimal effect on survival for patients
with locally advanced unresectable stage III non-small cell lung cancer
(NSCLC).1
2
3
Novel schemes of radiation such as
hyperfractionated radiation (HRT)4
and continuous
hyperfractionated accelerated radiotherapy (CHART)5
6
appear promising. The recommended dose for HRT in unresectable NSCLC is
69.6 Gy as established by a Radiation Therapy Oncology Group
study.4
Saunders et al6
demonstrated that the
CHART regimen (54 Gy in 36 fractions over 12 continuous days) was
superior to conventional TRT in the treatment of patients with
NSCLC, but was associated with substantial esophagitis.
Addition of chemotherapy to TRT sequentially,7
8
9
10
or
concurrently11
12
13
has shown an impact on survival among
patients with unresectable NSCLC, especially those with good
performance status and < 5% weight loss,8
9
10
compared
to TRT alone (Table 1
). In the study by Dillman et al,8
9
comparing cisplatin,
100 mg/m2 (days 1 and 29), and vinblastine, 5
mg/m2 (days 1, 8, 15, 22, and 29), followed by
TRT beginning on day 50 (60 Gy) vs TRT alone, the median survival
duration of 13.7 months in the combined modality arm was significantly
better than the 9.6 months observed in the TRT alone arm (p = 0.01),
and there were more than twice the number of survivors at 3, 4, and 5
years. This study was duplicated by the Radiation Therapy
Oncology Group and the Eastern Cooperative Oncology Group with addition
of a third arm utilizing HRT 69.6 Gy.10
The 1-year
survival rate and median survival duration were significantly better in
the combined modality arm (60% and 13.8 months, respectively) than in
the arms that received HRT alone (51%, 12.3 months) or standard TRT
(46%, 11.4 months; p = 0.03). The difference between the 1-year
survival rate achieved with standard TRT and that achieved with HRT was
not significant. A French group also demonstrated a survival benefit
and improved systemic control, as marked by a reduction in distant
metastases, with chemotherapy plus sequential TRT compared with TRT
alone.7
 |
Concurrent Chemoradiation
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Administering radiosensitizing chemotherapy concurrently with TRT
may further improve locoregional control. A number of randomized
studies have examined radiosensitizing doses of platinum compounds
combined with concurrent TRT (Table 1)
.11
12
13
In a
three-arm study, Schaake-Koning et al11
used split-course
TRT in the treatment of 330 patients with inoperable NSCLC. The first
group received 30 Gy TRT over 2 weeks followed by a 3-week rest period,
plus an additional 25 Gy TRT administered over 2 weeks; the second
group received the same TRT dose and schedule, to which concurrent
cisplatin, 30 mg/m2, was added on the first day
of each treatment week; a third group received the same TRT with
cisplatin, 6 mg/m2, given daily before each
radiation fraction. The 3-year survival rate was 2% in the TRT arm,
compared with 13% in the group receiving TRT and weekly cisplatin
(p = 0.36). The daily cisplatin/TRT arm demonstrated significantly
improved survival compared with the TRT-only arm (p = 0.009). The
addition of chemotherapy to TRT did not increase the incidence of
esophagitis in this study; however, nausea and vomiting were a
significant problems, affecting approximately 70% of patients who
received cisplatin chemotherapy plus TRT, compared with only 24% who
received TRT alone.
Concurrent chemotherapy and HRT was evaluated by Jeremic et
al12
13
in two randomized studies. In the first
study,12
patients with stage III NSCLC received HRT 64.8
Gy either alone, with concurrent weekly carboplatin, 100 mg on days 1
and 2, and etoposide, 100 mg on days 1 to 3, added, or with concurrent
carboplatin, 200 mg on days 1 and 2, and etoposide, 100 mg on days 1 to
5, given in the first, third, and fifth weeks of TRT.
Median and 3-year survivals were highest in the group that received HRT
with the lower dose of weekly carboplatin and etoposide (18 months and
23%, respectively). The 3-year survival in this group approached
statistical significance, compared with the group that received HRT
alone (6.6%; p = 0.0027). In their second study,13
the
total dose of HRT was increased to 69.6 Gy (given as 1.2 Gy bid); in
one group, concurrent chemotherapy with carboplatin and etoposide (both
given at doses of 50 mg IV) was given prior to each radiation fraction.
Median and 4-year survivals were 22 months and 23%,
respectively, in the combined modality arm vs 14 months and 9% in the
HRT only arm (p = 0.021 for differences in 4-year survival). The two
groups showed similar rates of acute and late high-grade toxic
reactions. Thus, concurrent chemotherapy enhanced the effect of TRT and
significantly improved local control compared with HRT alone (4-year
local recurrence-free survival, 42% vs 19%, respectively;
p = 0.015).
A meta-analysis of randomized studies comparing the efficacy of TRT
alone to combined chemotherapy and TRT in patients with locally
advanced, unresectable NSCLC14
showed the relative risk
for death at 1, 2, and 3 years to be reduced by 12, 13, and 17%,
respectively, in the combined modality therapy group. The benefit of
chemotherapy appeared to increase with time, reaching a maximum at 31
to 36 months after start of treatment. The mean gain in life expectancy
was approximately 2 months at the end of 3 years, with median survival
improved by 1.7 months. Although chemotherapy did not impair delivery
of TRT, serious toxic effects, particularly febrile neutropenia and GI
disturbances, were more prevalent among patients receiving
cisplatin-based chemotherapy. Thus, the addition of chemotherapy to TRT
offers an advantage in patients with locally advanced, unresectable
stage III NSCLC, but the optimal and most effective chemotherapeutic
regimen is not known. The other controversy revolves around the ways of
integrating chemotherapy and radiotherapy.
 |
Concurrent Chemotherapy and TRT Using Carboplatin/Paclitaxel
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In an attempt to decrease the toxicity of cisplatin-based
chemoradiation, we conducted a pilot study using weekly carboplatin (a
less toxic analog of cisplatin) plus TRT to treat patients with locally
advanced NSCLC.15
In this study, 35 previously untreated
patients with stage III NSCLC were given weekly carboplatin, 100
mg/m2, with concurrent TRT (total dose, 60 Gy),
yielding a response rate of 34% and median survival duration of 13
months. The treatment was well tolerated, with only three patients
requiring treatment prolongations of > 1 week. This regimen was
active, with mild toxicities and suitable for combination with other
chemotherapeutic agents.
Paclitaxel is a known radiosensitizer,16
17
and a novel
agent with a wide spectrum of activity in advanced and metastatic
NSCLC.18
It has shown impressive single-agent
activity,19
20
as well as activity in combination therapy
with carboplatin.21
22
23
24
A phase I study by Choy et
al25
established that the maximum-tolerated dose of
paclitaxel in locally advanced NSCLC was 60
mg/m2, with concurrent TRT of 60 Gy. Although
there is evidence that p53 mutations herald a poor response to
chemotherapy in patients with NSCLC,26
one report
suggests that they do not predict response to a regimen of
concurrent TRT and paclitaxel, and that this combination may be
effective even in patients with locally advanced tumors with high rates
of p53 mutations.27
Based on these observations, we designed a phase II trial incorporating
weekly paclitaxel into our regimen of weekly carboplatin plus
concurrent TRT for patients with stage III NSCLC.28
The
paclitaxel dose was 45 mg/m2/wk based on its
potential to act as radiosensitizer at relatively low concentrations.
Thirty-eight patients received paclitaxel, 45
mg/m2 over 3 h, with standard premedication
followed by carboplatin, 100 mg/m2 over 30 min,
both given IV. Concurrent TRT was given to a total of 60 to 65 Gy over
6 to 7 weeks (Table 2 ).
Toxicity was monitored during weekly patient visits for chemotherapy.
Dose modifications were made in the event of neutropenia, mucositis, or
esophagitis. Radiographic response was evaluated 4 weeks after
completion of all treatment. Approximately two thirds of the patients
had stage IIIB disease, and the rest had macroscopic stage IIIA (N2)
disease (Table 3
). Adenocarcinoma and squamous cell carcinoma were the most common
histologies.
Overall, the regimen was well tolerated and toxicities have been
manageable; no grade 4 toxicities occurred in 38 evaluable patients.
Dose reduction was necessary in 12 instances, and treatment was delayed
> 1 week in five patients. Only two patients developed grade 3
mucositis and esophagitis; three patients died as a result of rapidly
progressive disease without any evidence of dose-limiting toxicities
(Table 4
).
The preliminary results from this study indicate that combination of
paclitaxel/carboplatin plus concurrent radiotherapy is feasible in
stage IIIA/IIIB unresectable, regionally advanced NSCLC. In general,
toxicity associated with this treatment regimen was acceptable. The
combined modality regimen using concurrent chemotherapy and
radiotherapy was active, with promising long-term survival (Table 5
).
Choy and colleagues29
30
reported results utilizing their
regimen of paclitaxel, 50 mg/m2 by 1-h infusion
weekly; carboplatin weekly, with a dose targeted to achieve an area
under the plasma concentration-vs-time curve (AUC) of 2, and concurrent
TRT to a total of 66 Gy. Patients then went on to receive two
additional cycles of chemotherapy (Table 6
). The overall response rate among 37 evaluable patients was 75%, and
the 1- and 2-year survival rates were 54% and 40%, respectively. The
incidence of esophagitis (grade 3 to 4) was 49% but was of short
duration. Other rare toxicities included nausea, vomiting, neuropathy,
weight loss, and pulmonary complications. Based on these encouraging
results, the same doses of weekly paclitaxel and carboplatin plus HRT
are being utilized in a current study being performed by Choy and
colleagues.31
Investigators at the Fox Chase Cancer Center32
designed a
study to test induction therapy with full-dose paclitaxel and
carboplatin (with growth factor support), followed by two cycles of
escalating doses of concurrent carboplatin and paclitaxel (day 43 and
64) with TRT. The response to induction therapy has been 38%, but the
overall response rate after both phases is 59%. Paclitaxel, 175
mg/m2, has been tolerated with carboplatin dose
targeted to achieve an AUC of 3.75 during the concurrent phase (Table 7 ). Inferences regarding toxicity, especially esophagitis, cannot be made
from this study because it is a dose-escalation trial. Nevertheless,
these investigators have shown that the length of esophagus exposed to
the radiation field is an important factor resulting in esophagitis,
especially with combined modality regimens.33
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Table 7.. Induction and Concurrent Paclitaxel and Carboplatin
With Thoracic Radiation in Stage III NSCLC: Fox Chase Cancer Center
Experience*
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Discussion
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Carboplatin and paclitaxel have been successfully integrated with
TRT for patients with locally advanced unresectable NSCLC, and early
results have shown improved outcome. Both sequential and concurrent
regimens are feasible and the toxicity profiles are acceptable.
Concurrent chemoradiotherapy incorporating low doses of weekly
paclitaxel and carboplatin is not only feasible but also effective in
prolonging survival of patients with locally advanced NSCLC. The dose
and schedule of paclitaxel administration in the combined modality
programs continues to be a subject of controversy. Based on preliminary
results, the doses of paclitaxel 45 to 50
mg/m2/wk (1- or 3-h infusion) and carboplatin,
100 mg/m2 or AUC 2, can be combined with
concurrent TRT for the treatment of locally advanced NSCLC. There
appears to be no advantage to administering paclitaxel on a prolonged
schedule, (eg, daily bolus during TRT).34
When
cisplatin, 75 mg/m2, and full-dose paclitaxel,
135 mg/m2, were combined with concurrent TRT 64.8
Gy (34 fractions over 7 weeks) for patients with unresectable stage
IIIA and IIIB NSCLC to assess treatment tolerability, efficacy, and
survival,35
the major toxicities encountered were
esophagitis and leukopenia. The investigators concluded that
administration of larger/full doses of paclitaxel every 4 weeks with
concurrent TRT could not be recommended for use because of prohibitive
toxicity.
Administration of a larger dose of paclitaxel on a 3- to 4-week
schedule in concurrent chemoradiotherapy programs provides the same
dose intensity, but is clearly associated with prohibitive toxicity.
The length of the esophagus included in the radiation field also should
be minimized so as to avoid excessive toxicity.33
The patterns of failure in patients treated with concurrent paclitaxel,
carboplatin, and thoracic radiation suggest the need for additional
chemotherapy either at the front end or after the completion of the
concurrent regimen. A large, multicenter, randomized study (Locally
Advanced Multimodality Protocol; Table 8 ) has been initiated to address these issues of improvement in distant
control and to further refine the combined modality approach for
patients with locally advanced NSCLC. The hope for the immediate future
is to define an effective and optimal regimen that can be given
simultaneously with TRT, and that can result in improved local and
systemic control in patients with regionally advanced NSCLC.
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Table 8.. Randomized Study of Combined Modality Treatment in
Locally Advanced NSCLC: Locally Advanced Multimodality Protocol*
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Footnotes
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Abbreviations: AUC = area under the plasma
concentration-vs-time curve; CHART = continuous hyperfractionated
accelerated radiotherapy; HRT = hyperfractionated radiation; NSCLC =
non-small cell lung cancer; TRT = thoracic radiation therapy
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References
|
|---|
-
Perez, CA, Bauer, M, Edelstein, S, et al (1986) Impact of tumor control on survival in carcinoma of the lung treated with irradiation. Int J Radiat Oncol Biol Phys 12,539-547[ISI][Medline]
-
Perez, CA, Stanley, K, Grundy, G, et al (1982) Impact of irradiation technique and tumor extent in tumor control and survival of patients with unresectable non-oat cell carcinoma of the lung: report by the Radiation Therapy Oncology Group. Cancer 50,1091-1099[CrossRef][ISI][Medline]
-
Johnson, DH, Einhorn, LH, Bartolucci, A, et al (1990) Thoracic radiotherapy does not prolong survival in patients with locally advanced, unresectable non-small cell lung cancer. Ann Intern Med 113,33-38
-
Cox, JD, Azarnia, N, Byhardt, RW, et al (1990) A randomized phase I/II trial of hyperfractionated radiation therapy with total doses of 60.0 Gy to 79.2 Gy: possible survival benefit with greater than or equal to 69.6 Gy in favorable patients with radiation therapy oncology group stage III non-small cell lung carcinoma; report of Radiation Therapy Oncology Group 8311 J Clin Oncol 8,1543-1555[Abstract]
-
Saunders, MI, Dische, S, Grosch, EJ, et al (1991) Experience with CHART. Int J Radiat Oncol Biol Phys 21,871-878[ISI][Medline]
-
Saunders, MI, Dische, S, Barrett, A, et al (1996) Randomized multicenter trials of CHART vs conventional radiotherapy in head and neck and non-small cell lung cancer: an interim report. CHART Steering Committee. Br J Cancer 73,1455-1462[ISI][Medline]
-
Le Chevalier, T, Arriagada, R, Tarayre, M, et al (1992) Significant effect of adjuvant chemotherapy on survival in locally advanced non-small-cell lung carcinoma [letter]. J Natl Cancer Inst 84,58[Free Full Text]
-
Dillman, RO, Seagren, SL, Herndon, J, et al (1993) Randomized trial of induction chemotherapy plus radiation therapy vs RT alone in stage III non-small cell lung cancer (NSCLC): five-year follow-up of CALGB 8433 [abstract 1092]. Proc Am Soc Clin Oncol 12,317
-
Dillman, RO, Seagren, SL, Propert, KJ, et al (1990) A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med 323,940-945[Abstract]
-
Sause, WT, Scott, C, Taylor, S, et al (1995) Radiation Therapy Oncology Group (RTOG) 8808 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer. J Natl Cancer Inst 87,198-205[Abstract/Free Full Text]
-
Schaake-Koning, C, van den Bogaert, W, Dalesio, O, et al (1992) Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med 326,524-530[Abstract]
-
Jeremic, B, Shibamoto, Y, Acimovic, L, et al (1996) Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-small-cell lung cancer: a randomized study. J Clin Oncol 14,1065-1070[Abstract/Free Full Text]
-
Jeremic, B, Shibamoto, Y, Acimovic, L, et al (1995) Randomized trial of hyperfractionated radiation therapy with or without concurrent chemotherapy for stage III non-small-cell lung cancer. J Clin Oncol 13,452-458[Abstract/Free Full Text]
-
Pritchard, RS, Anthony, SP (1996) Chemotherapy plus radiotherapy compared with radiotherapy alone in the treatment of locally advanced unresectable, non-small cell lung cancer: a meta-analysis. Ann Intern Med 125,723-728[Abstract/Free Full Text]
-
Belani, CP, Ramanathan, RK (1997) Combined modality treatment of locally advanced non-small cell lung cancer: incorporation of novel chemotherapeutic agents. Chest 113(suppl),53S-61S[ISI][Medline]
-
Choy, H, Browne, MJ (1995) Paclitaxel as a radiation sensitizer in non-small cell lung cancer. Semin Oncol 22,70-74
-
Tishler, RB, Geard, CR, Hall, EJ, et al (1992) Taxol sensitizes human astrocytoma cells to radiation. Cancer Res 52,3495-3497[Abstract/Free Full Text]
-
Rowinsky, EK, Donehower, RC (1995) Paclitaxel (taxol). N Engl J Med 332,1004-1014[Free Full Text]
-
Murphy, WK, Fossella, FV, Winn, RJ, et al (1993) Phase II study of taxol in patients with untreated advanced non-small cell lung cancer. J Natl Cancer Inst 85,384-388[Abstract/Free Full Text]
-
Chang, AY, Kim, K, Glick, J, et al (1993) Phase II study of taxol, merbarone, and piroxantrone in stage IV non-small cell lung cancer: the Eastern Cooperative Oncology Group Results. J Natl Cancer Inst 85,388-394[Abstract/Free Full Text]
-
Muggia, FM, Vafai, D, Natale, R, et al (1995) Paclitaxel 3-hour infusion given alone and combined with carboplatin: preliminary results of dose-escalation trials. Semin Oncol 22,63-66[ISI][Medline]
-
Belani, CP, Aisner, J, Hiponia, D, et al (1995) Paclitaxel and carboplatin with and without filgrastim support in patients with metastatic non-small cell lung cancer. Semin Oncol 22,7-12
-
Langer, CJ, Leighton, JC, Comis, RL, et al (1995) Paclitaxel and carboplatin in combination in the treatment of advanced non-small cell lung cancer: a phase II toxicity, response, and survival analysis. J Clin Oncol 16,1860-1870
-
Johnson, DH, Paul, DM, Hande, KR, et al (1995) Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial-LUN-46. Semin Oncol 22,30-33
-
Choy, H, Akerley, W, Safran, H, et al (1994) Phase I trial of outpatient weekly paclitaxel and concurrent radiation therapy for advanced non-small cell lung cancer. J Clin Oncol 12,2682-2686[Abstract/Free Full Text]
-
Kawasaki, M, Nakanisi, Y, Kuwano, K, et al (1996) The utility of p53 immunostaining for the transbronchial biopsy specimens of lung cancer: p53 overexpression may predict poor prognosis and chemoresistance in advanced non-small cell lung cancer [abstract 40]. Proc Am Soc Clin Oncol 15,94
-
Safran, H, King, T, Choy, H, et al (1996) p53 mutations do not predict response to paclitaxel/radiation for non-small cell lung carcinoma. Cancer 78,1203-1210[CrossRef][ISI][Medline]
-
Belani, CP, Aisner, J, Hiponia, D, et al (1996) Paclitaxel and carboplatin with concurrent thoracic radiotherapy for regionally advanced non-small cell lung cancer (NSCLC) [abstract 1201]. Proc Am Soc Clin Oncol 15,396
-
Choy, H (1997) Concurrent paclitaxel, carboplatin and radiation therapy for non-small cell lung cancer [abstract 269]. Lung Cancer 18(suppl 1),70
-
Choy, H, Akerley, W, Safran, H, et al (1997) Phase II trial of weekly paclitaxel, carboplatin and concurrent radiation therapy for locally advanced non-small cell lung cancer (NSCLC) [abstract 1637]. Proc Am Soc Clin Oncol 16,456A
-
Choy, H, DeVore, RD, Hande, KR, et al (1998) Phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small cell lung cancer: a Vanderbilt Cancer Center Affiliate Network (VCCAN) Trial [abstract 1794]. Proc Am Soc Clin Oncol 17,467A
-
Langer, CJ, Movsas, B, Hudes, R, et al (1997) Induction paclitaxel and carboplatin followed by concurrent chemoradiotherapy in patients with unresectable, locally advanced non-small cell lung carcinoma: report of Fox Chase Cancer Center Study 94001. Semin Oncol 24(suppl 12),S89-S95
-
Hudes, R, Langer, C, Movsas, B, et al (1997) Induction paclitaxel (Taxol) and carboplatin (CBDCA) followed by concurrent chemoradiotherapy (TRT-CT) in unresectable, locally advanced non-small cell lung carcinoma (NSCLC): report of FCCC 94001 [abstract 1609]. Proc Am Soc Clin Oncol 16,448A
-
Rathmann, J, Rigas, JR, Leopold, KA, et al (1997) Daily paclitaxel and thoracic radiation therapy for the treatment of stage II and III non-small cell lung cancer (NSCLC) [abstract 1722]. Proc Am Soc Clin Oncol 16,478A
-
Wagner, H, Antonia, SJ, Williams, CC, et al (1997) Concurrent paclitaxel/cisplatin (PC) with thoracic radiation (TR) in patients with stage IIIA/B non-small cell lung cancer (NSCLC) [abstract 1610]. Proc Am Soc Clin Oncol 16,448A
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