Dr. Jack West highlights 5 key principles that guide optimal multidisciplinary management of stage III, locally advanced non-small cell lung cancer (NSCLC), which comprises about 40% of patients diagnosed with lung cancer in the US. Hyperlinks are to this prior sldieshare: http://www.slideshare.net/JackWestMD/treating-invisible-disease-grace

1. Core Principles of Managing Locally Advanced
Non-Small Cell Lung Cancer (NSCLC)
H. Jack West, MD

2. Locally Advanced, also known as Stage III
NSCLC, may be treated in any of several ways
• There is no single “best treatment” for patients
with locally advanced NSCLC. In general, it requires
a combination of treatment for “local disease” that
you can see, as well as potential “distant disease”
that you cannot.
• Higher T (tumor) stage tends to be associated with
greater risk of local disease. Higher N (nodal) stage
and greater number of nodes tends to be
associated with greater risk of distant disease.
Local treatment
(radiation or
surgery)
Systemic treatment
(generally chemo)

3. Multimodality Therapy: A Team Approach
• Because optimal treatment of
locally advanced NSCLC is
“multimodality” (requires a
combination of chemo with
radiation or surgery or both), it is
ideal to have treatment plans
developed by a team of
specialists in these fields prior to
staring therapy.
• Recommendations may vary from patient to patient
based on size of the cancer, its location, T stage, N
stage, health of the patient, and other factors.

4. Hot Light, Cold Steel: Is Surgery the Path
to Cure in Locally Advanced NSCLC?
• Surgery is sometimes recommended for patients with stage IIIA
disease and non-bulky “N2” nodes on the same side as the
main tumor in the mid-chest (mediastinum). This is typically
preceded by “induction” chemo or chemo and radiation.
• Chemo and radiation, without surgery, are considered more
appropriate when there are many areas of nodal
involvement, bulky lymph nodes, or “N3” nodes in the mid-
chest opposite the main tumor.
Not necessarily. Chemo and
radiation combined together
produces comparable survival
to surgery for stage IIIA and
IIIB NSCLC overall and is NOT a
consolation prize.

5. Chemo/Radiation without Surgery to
Cure Locally Advanced NSCLC
• Originally, only radiation or surgery were
used for locally advanced NSCLC.
Unfortunately, only a small minority of
patients with stage III NSCLC were cured
of their cancer (about 5%).
• Chemo was then added sequentially (preceding radiation),
improving survival at 3-5 years (to about 10%). It can help treat
“invisible”, distant disease in addition to the visible disease
treated with local therapy.
• Administering chemo concurrently with radiation can improve
cure rates (~15-25%). Chemo acts as a “radiosensitizer”,
increasing efficacy of the radiation. The most common chemo
regimens combined with radiation are cisplatin/etoposide or
carboplatin/Taxol (paclitaxel), but others can be used.

6. Balancing Efficacy with Safety
• Stage III NSCLC has a high risk of recurrence/progression
through treatment. Combining chemotherapy with radiation
and/or surgery to treat the cancer aggressively has the
potential to improve the cure rate against the cancer, but it
also increases the side effects of treatment.
• These can sometimes be life-threatening, or even fatal. Even
in carefully conducted studies, about 5-7% of patients can die
from treatment, and more or left with significantly
compromised lung function.
• Beyond a certain level (that varies with
the health of the patient), escalating
intensity of treatment may cause more
harm than good and worsen survival.

7. Too much of a good thing?
• A key clinical trial compared about 6.5-7 weeks of daily chest
radiation (Mon-Fri) to a longer course and higher dose with
concurrent chemotherapy. This showed that more radiation was
associated with WORSE survival than the standard dose.
• The best studied chemo is about 6-7 weeks, either two courses
of every 3-4 week cisplatin/etoposide or 7 low weekly doses of
carboplatin/Taxol. Giving additional chemo before or after this
has never been shown to be better (though we often give it,
hoping it could be). Taxotere (docetaxel) after chemo/radiation
increased side effects but not survival.
• There is no role established for targeted therapies in locally
advanced NSCLC. Iressa (gefitinib) was significantly harmful,
worsening survival, after chemo/radiation in an unselected
population (most didn’t have an EGFR mutation).

8. 1. Optimal treatment is individualized to the patient and their
cancer but almost always involves two or three modalities of
therapy (chemo, radiation, surgery).
2. A multimodality plan should be developed by a group of
specialists considering the range of combined therapy options.
3. Surgery may have a role in more limited, less bulky stage III
NSCLC (almost always stage IIIA). A nonsurgical approach with
chemo/radiation can lead to comparable survival.
4. Concurrent chemo and chest radiation (as an alternative to
surgery) leads to improved survival compared with sequential
treatment but isn’t for every patient.
5. Risk from treatment can counterbalance benefit as treatment
becomes more intensive.
Conclusions: 5 Key Points for Managing
Locally Advanced NSCLC

9. For questions, comments, and
further information, check out
CancerGRACE.org