Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
of localized bronchiectasis as reported by Churchill and Belsey (1939). In 1973,
Jensik reported their 15-year successful experience of segmentectomy for
lung cancer patients. However, the use of sublobar resection as definitive
management of NSCLC has been a controversial issue. Lung Cancer Study
Group (LCSG) (1995) conducted the only randomized trial comparing sublobar
resection with lobectomy for stage IA NSCLC patients. They observed a 75%
increase in recurrence and a 50% increase in cancer death in the patients
undergoing sublobar resection, compared to those in the patients undergoing
lobectomy. This is the reason why lobectomy has remained a standard lung
cancer surgery for a half century since Cahn’s successful report in 1960.
However, recently, we encounter many patients with the subsolid nodule,and
a certain percentage of those patients are multifocal lesion. The significance
and role of sublobar resection for subsolid tumor have become importanat so
far. Controversies in sublobar resection for patients with small-sized NSCLC:
Sublobar resection is a lung parenchyma-preserving surgery with limited
nodal dissection. However, even small-sized lung cancer less than 2 cm in
size shows hilar and mediastinal nodal disease with an incidence of more
than 20%. Although positron emission tomography (PET) is considered to
be the most sensitive and accurate investigation for screening of lymph
node involvement, with a sensitivity of 79 to 85% and specificity of 90 to
91% in a meta-analysis, the assessment of nodal status by PET is not reliable
in patients with microscopic nodal metastasis. Riquet (1989) reported that
lung cancer metastasizes so easily to the mediastinum that selection of the
patients for limited surgery should be discussed carefully. Furthermore,
lung cancer has a phenomenon termed “skip metastasis” consisting of N2
disease without N1 involvement with the incidence of 20-38% in N2 patients.
Therefore, lobectomy with hilar and mediastinal lymph node dissection is
considered to be a basic standard procedure for lung cancer. Differences
in survival between sublobar resection and lobectomy: However, with the
recent development of the CT scanner, the number of very early-stage lung
cancer showing ground-grass opacity (GGO) on CT is rising as well, and a
new therapeutic strategy for nodal dissection has been required. Proposals
of sublobar resection for small-size lung cancer less than 2 cm have been
undertaken in some previous reports. Many retrospective studies of sublobar
resection have already been undertaken for stage IA NSCLC patients.
Regarding surgery for compromised stage IA patients, Hoffmann (1980),
Landreneau (1997) and Campione (2004) showed no significant survival
difference between sublobar resection and lobectomy group. Okada (2001)
and Koike (2003) conducted the comparative study between intentional
sublobar resection and standard lobectomy in patients with tumors 20mm or
less in diameter. They showed no significant difference in survival between
two groups and suggested that sublobar resection was acceptable operation
for small-sized lung cancer. Nakamura (2005) reported the results of metaanalysis
of 14 comparative studies showing survival difference between
lobectomy and sublobar resection. He showed survival after lobectomy was
slightly better at 1, 3, and 5 years, but the differences were not significant.
Therefore, lobectomy with mediastinal dissection could be an excessive
resection for selected patients with early lesion. Lobectomy, however, still
remains to be a standard procedure for most patients with lung cancer, simply
because there has been no universally accepted guidelines for conducting
sublobar resection in the clinical settings. We should wait the final results of
clinical trials shown in the following chapter. Clinical trials regarding sublobar
resection vs. lobectomy and future perspective: Japan Clinical Oncology Group
(JCOG) has conducted a cohort study (JCOG0201) evaluating correlation
between radiological and pathological findings in stage I adenocarcinomas.
With pathologic non-invasive adenocarcinoma defined as those with no
lymph node metastasis or vessel invasion, radiological non-invasive lung
adenocarcinoma was defined as those with a consolidated maximum tumour
diameter to tumour diameter ratio (C/T ratio) of less than 0.5. Currently, a
prospective, randomized, multiinstitutional phase III trial for small-sized
( 80 years) patients and patients suffering from
severe comorbidities 1 . Simultaneously, the patient characteristics of
age, performance status and patients comorbidities are not suitable to
accurately predict a high risk of early non-cancer death such that these
patients could be offered best supportive care and they would not benefit
from SBRT as a curative treatment approach 2 . However, several studies
have identified interstitial lung disease as a highly significant factor for
severe post-SBRT radiation induced pneumonitis; these patients should be
treated only with caution 3 . On the other end of the patient spectrum, there
is an increasing amount of data comparing SBRT with surgical resection,
lobectomy and sublobar resection: despite a growing evidence suggests
equivalent outcome, lobectomy remains the standard of care for properly
selected patients 4,5 . SBRT planning and delivery: Multiple advanced
radiotherapy treatment planning and treatment delivery technologies as
well as dedicated SBRT delivery machines have been developed and have
become clinically available within the last years. Despite simulations studies
showed a benefit for most these technologies, it remains unclear whether
small improvements in accuracy and dosimetry will translate into a clinically
meaningful improvements of patient outcome. The upcoming ESTRO
ACROP practice guideline has therefore only identified few technologies
as mandatory components of up-to-date SBRT practice (e.g. type B dose
calculation algorithm, image guidance, 4D motion compensation strategy).
SBRT dose and fractionation has been one of the most controversially
discussed topics in lung SBRT and patterns-of-practice analyses reported a
large variability between institutions. Comparison of different fractionation
schedules requires radiobiological modelling and several recent studies
suggested that the traditional linear-quadratic model (LQ-model) describes
the observed outcome with sufficient accuracy 6 . Consequently, biological
effective doses (BED) or 2-Gy equivalent doses are used by most studies
for dose-effect modelling. Several studies consistently showed that a
threshold dose of minimum 100Gy BED (alpha/beta ratio 10Gy) is required
for a local tumor control probability of >90%. Furthermore, not only the
minimum dose at the PTV edge but also the maximum dose within the GTV
was shown as important predictor for local tumor control supporting the
traditional SBRT concept of inhomogeneous dose distributions within the
PTV. After central tumor location has been called a no-fly-zone for SBRT
based on studies with “excessive” toxicity of very high dose SBRT, recent
retrospective and prospective data suggest that lower total doses combined
with more fractionated SBRT protocols improve the therapeutic ratio.
Nevertheless, our understanding of the radiation tolerance of critical central
structures is still insufficient and further research is necessary. Follow-up:
The development of radiation induced fibrosis in the high dose region is well
documented following SBRT. Only recently, algorithms for differentiation
between local tumor recurrence and fibrosis have been developed and
validated 7,8 : CT features of bulging margin and cranio-caudal growth appear
to best differentiate between fibrosis and tumor recurrence. More advanced
studies evaluate the value of mathematical image analysis methods,
radiomics, but such studies strongly require external validation. 1. Takeda A,
Sanuki N, Eriguchi T, et al: Stereotactic ablative body radiation therapy for
octogenarians with non-small cell lung cancer. Int J Radiat Oncol Biol Phys
86:257-63, 2013 2. Klement RJ, Belderbos J, Grills I, et al: Prediction of Early
Death in Patients with Early-Stage NSCLC-Can We Select Patients without a
Potential Benefit of SBRT as a Curative Treatment Approach? J Thorac Oncol,
2016 3. Ueki N, Matsuo Y, Togashi Y, et al: Impact of pretreatment interstitial
lung disease on radiation pneumonitis and survival after stereotactic body
radiation therapy for lung cancer. J Thorac Oncol 10:116-25, 2015 4. Chang JY,
Senan S, Paul MA, et al: Stereotactic ablative radiotherapy versus lobectomy
for operable stage I non-small-cell lung cancer: a pooled analysis of two
randomised trials. Lancet Oncol 16:630-7, 2015 5. Nagata Y, Hiraoka M, Shibata
T, et al: Prospective Trial of Stereotactic Body Radiation Therapy for Both
Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical
S40 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017