Target volume (GTV and CTV) definition is
one of the most critical steps. Most variability, uncertainty and even mistakes
are happening in defining target volumes.
In NSCLC, especially in larger primary
tumor volumes, the GTV as depicted on CT scans generally overestimates the real
size of the pathological tumor. The FDG uptake on strictly standardized PET-CT
scans comes closer to pathological reality, but because at present no robust
(semi)-automated delineation software exists that considers pathological tumor
volumes, the tumor is delineated on the planning CT scan.
The GTV of the primary tumour and GTV of
the lymph node(s) should be drawn separately, if anatomically distinguishable.
The pre-set lung window setting (W = 1600 and L = _600) should be used to delineate
tumours surrounded by lung tissue while the mediastinum pre-set window setting
(W = 400 and L = 20) should be used to delineate lymph nodes and primary
tumours invading the mediastinum or chest wall. In selected cases, integration
with MRI may be useful.
The diagnostic CT or PET-CT information
should be recent and mostly it is recommended that it should not be older than
4 weeks. Regions of atelectasis visible on the CT image beyond the edge of the
increased FDG uptake may be excluded from the GTV. The GTV of the primary tumor
post induction chemotherapy should be based on current CT imaging, however prechemotherapy
imaging (including PET-CT) should be considered. The GTV of the lymph nodes
should include all involved lymph nodes or lymph node stations based on
pre-chemotherapy clinical, pathological and imaging information, even if a node
has completely disappeared in imaging. Lymph nodes which are proven malignant
by biopsy or considered pathological on PET (focal accumulation above blood
pool) are delineated as GTV. Because of the significant inter-observer
variation of reporting FDG-positive mediastinal nodes, in case of diagnostic uncertainty,
a node should rather be included than excluded in the GTV. Lymph nodes that are
FDG-avid and EBUS/EUS-negative should be included in the GTV as the false
negative rates of EBUS/EUS are high. FDG-avid nodes may only be omitted if
there is clear non-malignant biopsy explanation for the FDG positivity or if a
mediastinoscopy has been performed showing no malignant cells in the lymph
node.
The CTV of the primary tumor should be
created by expansion from the GTV by e.g. 5–8 mm and should be edited accounting
for surrounding anatomy, e.g. natural barriers such as
bones or heart. There are two options to
create the CTV around lymph nodes:
1 (lymph node stations): inclusion of the
whole pathologically affected lymph node station including at least a 5–8 mm
margin around the GTV.
2 (geometric expansion): geometric
expansion of nodal GTV to CTV in analogy to the primary tumor (5–8 mm). This margin
may be tailored according to the size of lymph nodes or
histology of the primary tumour.
In both scenarios, care should be taken
with respect to neighbouring normal organs (e.g. esophagus) in order to not
increase toxicity.
Beyond this, elective inclusion of the
hilum and/or neighbouring nodal lymph node stations can be considered.
Inclusion of uninvolved areas between involved stations (especially the hilum)
is optional. Further inclusion of elective
lymph nodes in the CTV is not recommended.
When post-operative RT (PORT) is
indicated, the CTV consists of the resected involved anatomical mediastinal lymph
node regions, the bronchial stump, the ipsilateral hilum and nodal stations 4
and 7.
Adaptive re-planning may be performed on
an individual patient basis. Adaptation of target volumes should not be applied
to the GTVn as discussed above in relation to systemic therapy prior to CRT. Treatment
should not be interrupted, as the risk of repopulation is of particular concern
in small cell lung cancer.
For stage III NSCLC, treated
with concurrent chemotherapy and radiotherapy, the preferred dose and
fractionation is 60 Gy in 30 once-daily fractions of 2 Gy, 5 days per week. No
other strategy has shown to result in better outcomes, including dose
escalation by adding 2 Gy fractions, accelerated radiotherapy or isotoxic dose
escalation. Two cycles of chemotherapy, administered during radiotherapy, are
sufficient.
In patients selected for
sequential chemotherapy and radiotherapy or for radiotherapy alone, there is
also no evidence that higher total doses than 60 Gy would be beneficial, although
acceleration is associated with better overall survival. The latter may be
accomplished with gentle hypofractionation such as fraction sizes of 2.4-2.75
Gy.
For stage III small cell lung
cancer, the first choice radiotherapy schedule remains 45 Gy BID, i.e.
twice-daily 1.5 Gy, 5 days per week, starting at the latest at the second cycle
of platinum-etoposide chemotherapy. A dose of 66 Gy in 33 once-daily fractions
of 2 Gy might be slightly less effective.