METHODS
This retrospective study included 105 patients. Treatment involved concurrent carboplatin and paclitaxel
with RT administered weekly followed by two cycles of consolidation carboplatin and paclitaxel
administered triweekly.
RESULTS
Comorbid disease was present in 46 (48.6%) patients. At least four cycles of CHT in the concurrent
phase and both cycles of CHT in the consolidation phase were able to be administered to 92.3% and
45.4% of patients, respectively. The most common type of toxicity in the entire treatment protocol was
hematological toxicity (34.8%). The objective response rate was 71.4%. Overall, recurrence was found in
71 (67.6%) patients. The most common type of recurrence was distant metastasis, which occurred in 47
(66.2%) patients. The median progression-free survival was 14 months. The 1, 2, and 3-year progressionfree
survival rates were 59%, 30%, and 26%, respectively. The median overall survival was 27 months.
The 1, 2, and 3-year overall survival rates were 81%, 57%, and 34%, respectively.
CONCLUSION
The survival outcomes in this study closely match those reported in the literature. This is notable because
our study included a higher proportion of patients with additional health conditions and fewer concurrent
CHT cycles during RT compared to randomized studies. These findings prompt us to consider what
the ideal number of concurrent CHT cycles should be when using modern involved-field RT techniques
after accurate disease staging.
Keywords: Carboplatin; chemotherapy; concurrent radiochemotherapy; non-small-cell lung cancer; paclitaxel; radiotherapy
RT with concurrent platinum-based doublet CHT
is the standard treatment for patients with medically
or surgically inoperable LA-NSCLC.[
In this study, we examined the early and late toxicities,
failure patterns, and survival outcomes of patients
with inoperable LA-NSCLC treated with a CP-based
CHT regimen combined with RT.
Patient Evaluation
In total, 105 patients with inoperable biopsy-verified
LA-NSCLC who received RT with a CP-based CHT
regimen from January 2013 to August 2022 were
enrolled. The staging work-up was performed using
magnetic resonance imaging of the brain and positron
emission tomography-computed tomography
(PET-CT) scanning of the whole body. The staging of
all patients was updated according to the American
Joint Committee on Cancer Eighth Edition Cancer
Staging Manual. All patients had a Zubrod performance
status score ≤2 with normal hematological,
renal, and hepatic function.
Radiotherapy Planning
RT planning was performed either three-dimensionally
or by four-dimensional intensity-modulated radiotherapy
(IMRT) using a CT simulator. The gross tumor
volume included the primary tumor and involved
lymph nodes. The clinical target volume was defined as
additional 8 mm and 6 mm uniform margins in all directions around the gross tumor volume for adenocarcinoma
and non-adenocarcinoma histologies, respectively.
The planning target volume (PTV) was created
around the clinical target volume with additional 5 mm
uniform margins in all directions for four-dimensional
plans or 1.0 to 1.5 cm nonuniform margins for threedimensional
plans. The PTV-total included the PTVs
of the primary tumor and lymph nodes. The organs at
risk were the lungs, esophagus, heart, and spinal cord.
Treatment
The prescribed dose of RT to the PTV-total was
60?66 Gy at the discretion of the treating radiation
oncologist. Dose constraints were applied according
to the National Comprehensive Cancer Network
(NCCN) guidelines. In the concurrent radiochemotherapy
phase, RT was started on the first day of CHT.
Concurrent CHT included carboplatin (area under
the curve [AUC]=2) and paclitaxel (45 mg/m2/day)
per week. The administration of consolidation CHT
was at the discretion of the medical oncologist and
was planned to start 2 weeks after the end of RT. In
this phase, administration of two cycles of carboplatin
(AUC=6) and paclitaxel (200 mg/m2) triweekly
was planned. CHT was omitted if the white blood cell
and neutrophil counts were <3000/µL and <1500/µL,
respectively, or the platelet count was <100,000/µL.
In addition, RT was interrupted in patients with any
grade ≥3 treatment-related toxicity. In patients whose
RT was interrupted, whether additional fractionation
was required was determined by taking time-dose
and fractionation factors into account.
Follow-up
During treatment, patients were evaluated by physical
examination, a complete blood count, and kidney and
liver function tests before each CHT cycle. After treatment,
the patients were followed up at 3-month intervals
in the first year, 4-month intervals in the second
year, 6-month intervals in years 3-5, and 12-month
intervals thereafter. The follow-up evaluation for each
patient consisted of a physical examination, complete
blood count, kidney and liver function tests, wholebody
PET-CT (at the first 3-month evaluation, at 3
months after the end of the radiochemotherapy phase
or 1 month after the consolidation phase, or as needed),
and CT of the chest (excluding the first 3-month
evaluation). Early (≤90-day) and late (>90-day) toxicity
grading was performed according to the toxicity criteria
of the Common Terminology Criteria for Adverse
Events (version 5) and the Radiation Therapy Oncology Group (RTOG), respectively. The response was
evaluated in accordance with the Response Evaluation
Criteria in Solid Tumors.
End Points and Statistical Analysis
Local control, regional control, distant control, death
from any cause or from disease, progression-free survival
(PFS), and overall survival (OS) were calculated
and recorded. PFS was defined as the time between the
date of diagnosis and the date of the first failure at any
site. OS was defined as the time between the date of
diagnosis and the date of death from any cause. Patient
characteristics were described using descriptive statistics.
The Kaplan-Meier method was used to analyze
survival.
Treatment
The RT technique was IMRT in 87 (82.9%) patients. The
median prescribed RT dose was 62 (range, 60-66) Gy.
The median total duration of planned concurrent radiochemotherapy
was 44 (range, 40-50) days. The median
duration of interruption of the radiochemotherapy
phase because of treatment-related toxicity was 4
(range, 1-14) days (n=17, 16%). The mean concurrent
carboplatin and paclitaxel doses were 1185±423 and
386±114 mg, respectively. The median administered
number of concurrent CHT cycles was six (range, 1-7)
(Table
Toxicity
Toxicity of any degree occurred in 73.3% and 54.7%
of patients in the concurrent radiochemotherapy
and consolidation phases, respectively. Most of the
concurrent radiochemotherapy phase-related toxicities
were grade 1-2 (61.8%). In four patients who
received at least four cycles of concurrent CHT, concurrent
treatment was performed with carboplatin
alone because of grade 3 anaphylaxis that developed
after paclitaxel administration. Grade 3 pneumonitis,
which responded dramatically to steroid treatment,
developed in one patient 2 months after concurrent
radiochemotherapy. Most of the consolidation CHT- related toxicities were grade 3-4 (29.7%). In both the
concurrent radiochemotherapy and consolidation
phases, the most common grade 3-4 toxicities were
hematological toxicities (6.7% and 28.0%, respectively).
No treatment-related grade 3-4 late toxicity
or death occurred (Table
Response and Survival
The median follow-up time was 21 (range, 3-86)
months. Three months after treatment completion,
there was a complete response in 17 (16.2%) patients,
partial response in 58 (55.2%), stable disease in 7
(6.7%), and progressive disease in 23 (21.9%). Overall,
recurrence developed in 71 (67.6%) patients. Locoregional
recurrence was detected in 24 (33.8%) patients,
distant metastasis in 25 (35.2%), and both locoregional
recurrence and distant metastasis in 22 (31.0%) (Table
The specific CHT regimen that should be administered
concurrently with RT remains unclear. It is
recommended to administer platinum-based doublet
CHT regimens rather than single-agent regimens because
of the survival advantage.[
CP with concurrent RT in patients with LA-NSCLC
was first reported by Choy, et al.[18] Twenty-three patients
were treated with RT (66 Gy) and concurrent
CHT (carboplatin AUC=2 per week, paclitaxel=50
mg/m2 per week) followed by two cycles of consolidation
CHT (carboplatin AUC=6 every 3 weeks, paclitaxel=
200 mg/m2 every 3 weeks). The objective response
rate was 82%, and the major grade 3/4 toxicity was esophagitis (45%). The authors reported that this
protocol had a high response rate with an acceptable
and manageable toxicity profile.[
In our study, all patients were staged using brain
magnetic resonance imaging and PET-CT. Our treatment
protocol for inoperable LA-NSCLC was standard
as recommended in the literature[
Limitations of the present study include its retrospective
design, small number of patients, short followup
time, and single-institution design.
Ethics Committee Approval: The study was approved by the Ondokuz Mayıs University Clinical Research Ethics Committee (no: 2023/86, date: 16/03/2023).
Authorship contributions: Concept -A.S., N.Ö.O., R.E.Y., B.G., D.M.; Design - A.S., N.Ö.O., R.E.Y., B.G., D.M.; Supervision - A.S., N.Ö.O., R.E.Y., B.G., D.M.; Materials - A.S., N.Ö.O.; Data collection and/or processing - A.S., N.Ö.O., R.E.Y.; Data analysis and/or interpretation - A.S., N.Ö.O.; Literature search - A.S., N.Ö.O.; Writing - A.S., N.Ö.O.; Critical review - A.S., N.Ö.O., R.E.Y., B.G., D.M.
Conflict of Interest: All authors declared no conflict of interest. Use of AI for Writing Assistance: None declared.
Financial Support: None declared.
Peer-review: Externally peer-reviewed.