Transcript Non-Small Cell Lung Cancer

Non-Small Cell Lung
Cancer
Signs and symptoms
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persistent cough
trouble breathing
chest discomfort
wheezing
streaks of blood in sputum
hoarseness
loss of appetite
weight loss for no known reason
feeling very tired
Diagnostic tests
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chest X-rays
CT, PET scan
sputum cytology
fine-needle aspiration biopsy
bronchoscopy
thoracoscopy
thoracotomy
thoracentesis
NSCLC
Non-small cell lung cancer (NSCLC)
is a heterogeneous aggregate of
histologies. The most common
histologies are epidermoid or
squamous carcinoma,
adenocarcinoma, and large cell
carcinoma. These histologies are
often classified together because
approaches to diagnosis, staging,
prognosis, and treatment are similar.
Cellular Classification
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Squamous cell carcinoma
Adenocarcinoma
Large cell carcinoma
Adenosquamous carcinoma.
Carcinomas with pleomorphic,
sarcomatoid or sarcomatous elements
Carcinoid tumor
Carcinomas of salivary-gland type
Unclassified carcinoma
NSCLC
At diagnosis, patients with NSCLC
can be divided into 3 groups that
reflect both the extent of the disease
and the treatment approach
NSCLC
The first group - tumors that are
surgically resectable (generally stage I,
stage II, and selected stage III patients).
Patients with resectable disease who have
medical contraindications to surgery are
candidates for curative radiation therapy.
Adjuvant cisplatin-based combination
chemotherapy may provide a survival
advantage to patients with resected stage
IB, stage II, or stage IIIA NSCLC.
NSCLC
The second group includes patients with
either locally (T3-T4) and/or regionally
(N2-N3) advanced lung cancer. This
group has a diverse natural history.
- unresectable or N2-N3 disease : radiation
therapy in combination with chemotherapy
- selected patients with T3 or N2 disease
can be treated effectively with surgical
resection and either preoperative or
postoperative chemotherapy or
chemoradiation therapy.
NSCLC
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final group: metastatic disease (M1) at the
time of diagnosis
radiation therapy or chemotherapy for palliation
of symptoms from the primary tumor.
platinum-based chemotherapy has been
associated with short-term palliation of
symptoms and with a survival advantage.
patients previously treated with platinum
combination chemotherapy may derive symptom
control and survival benefit from docetaxel,
pemetrexed, or epidermal growth factor receptor
inhibitor.
Prognostic determinants after
surgery
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Presence of pulmonary symptoms.
Large tumor size (>3 cm).
Nonsquamous histology.
Metastases to multiple lymph nodes
within a TNM-defined nodal station
Vascular invasion
Increased numbers of tumor blood
vessels in the tumor specimen.
NSCLC
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For patients with inoperable disease,
prognosis is adversely affected by
poor PS and weight loss of >10%.
Stage 0 Non-Small Cell Lung
Cancer
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Surgical resection using the least
extensive technique possible
(segmentectomy or wedge resection)
to preserve maximum normal
pulmonary tissue because these
patients are at high risk for second
lung cancers.
Endoscopic photodynamic therapy
Stage I : T1, N0, M0, T2, N0, M0
Surgery is the treatment of choice lobectomy or limited resection
Patients with inoperable stage I disease and
with sufficient pulmonary reserve may be
candidates for radiation therapy with
curative intent
Patients with stage IB disease may benefit
from adjuvant platinum-based
combination chemotherapy.
5 year OS 27-71%
Stage II: T1, N1, M0; T2, N1, M0; T3,
N0, M0
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Lobectomy; pneumonectomy; or segmental,
wedge, or sleeve resection as appropriate.
Radiation therapy with curative intent (for
potentially operable patients who have medical
contraindications to surgery).
Adjuvant chemotherapy with or without other
modalities after curative surgery
5 year OS 10-60%
Stage IIIA T1-2 N2; T3 N1-2
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Surgery alone in operable patients without bulky
lymphadenopathy.
Radiation therapy alone, for patients who are not
suitable for neoadjuvant chemotherapy plus
surgery.
Chemotherapy combined with other modalities.
5 year OS 2-28%
Stage IIIB Any T, N3, M0; T4, any N,
M0
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initial chemotherapy, chemotherapy plus
radiation therapy, or radiation therapy alone,
depending on the sites of tumor involvement and
their performance status (PS).
patients with malignant pleural effusion are
rarely candidates for radiation therapy and should
generally be treated similarly to stage IV
patients.
A meta-analysis of patient data from 11
randomized clinical trials showed that
neoadjuvant or concurrent cisplatin-based
combinations plus radiation therapy resulted in a
10% reduction in the risk of death compared with
radiation therapy alone.
Stage IV Any T, any N, M1
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External-beam radiation therapy,
primarily for palliative relief of local
symptomatic tumor growth.
Cisplatin- based chemotherapy.
SCLC
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Without treatment, small cell carcinoma
of the lung has the most aggressive
clinical course of any type of pulmonary
tumor, with median survival from
diagnosis of only 2 to 4 months.
Compared with other cell types of lung
cancer, small cell carcinoma has a greater
tendency to be widely disseminated by the
time of diagnosis but is much more
responsive to chemotherapy and
irradiation.
SCLC
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With incorporation of current
chemotherapy regimens into the
treatment program, survival is
prolonged, with at least a 4- to
5-fold improvement in median
survival compared with patients who
are given no therapy.
The overall survival at 5 years is 5%
to 10%.
Cellular Classification
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Small cell carcinoma.
Mixed small cell/large cell carcinoma.
Combined small cell carcinoma (i.e.,
small cell lung cancer combined with
neoplastic squamous and/or
glandular components).
Limited-stage disease
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tumor confined to the hemithorax of
origin, the mediastinum, and the
supraclavicular nodes, which can be
encompassed within a tolerable radiation
therapy port. No universally accepted
definition of this term is available, and
patients with pleural effusion, massive
pulmonary tumor, and contralateral
supraclavicular nodes have been both
included within and excluded from limited
stage by various groups.
Extensive-stage disease
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Extensive-stage small cell lung
cancer means tumor that is too
widespread to be included within the
definition of limited-stage disease
above. Patients with distant
metastases (M1) are always
considered to have extensive-stage
disease
Prognostic factors
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good performance status, female
gender, and limited-stage disease
patients with involvement of the
central nervous system or liver at the
time of diagnosis have a significantly
worse outcome
Limited-Stage Small Cell Lung
Cancer- treatment
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Combination chemotherapy with chest
irradiation:
EC: etoposide + cisplatin + 4,500 cGy chest
radiation therapy
Combination chemotherapy especially in
patients with impaired pulmonary function or poor
performance status.
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Surgical resection followed by chemotherapy
or chemotherapy plus chest radiation therapy
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PCI prophylactic cranial irradiation
Limited-Stage Small Cell Lung
Cancer
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combination chemotherapy is superior to
single-agent treatment,
current programs yield overall objective
response rates of 65% to 90% and
complete response rates of 45% to 75%
because of the frequent presence of occult
metastatic disease, chemotherapy is the
cornerstone of treatment for patients with
limited-stage small cell lung cancer.
Limited-Stage Small Cell Lung
Cancer
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combined modality therapy produces
significant improvement in survival
compared with chemotherapy alone
two meta-analyses showed an
improvement in 3-year survival rates of
about 5% for those receiving
chemotherapy and radiation therapy
compared with those receiving
chemotherapy alone. Most of the benefit
occurred in patients younger than 65
years.
Combined modality treatment
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Studies strongly suggest that
minimal tumor doses in the range of
4,000 cGy to 4,500 cGy or more
(standard fractionation) are
necessary to effectively control
tumors in the thorax.
Combined modality treatment
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median survivals: 18 to 24 months and
40% to 50% 2-year survival with <3%
treatment-related mortality
once-daily and twice-daily chest radiation
schedules have been used in regimens
with etoposide and cisplatin.
One randomized study showed a modest
survival advantage in favor of twice-daily
radiation therapy given over 3 weeks,
compared with once-daily radiation
therapy given over 5 weeks (26% vs. 16%
at 5 years, P = .04).
Limited-Stage Small Cell Lung
Cancer
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Combined modality treatment is
associated with increased morbidity
and, in some trials, increased
treatment-related mortality from
pulmonary and hematologic toxic
effects; proper administration
requires close collaboration between
medical and radiation oncologists
PCI prophylactic cranial irradiation
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Patients whose cancer can be
controlled outside the brain have a
60% actuarial risk of developing
central nervous system metastases
within 2 to 3 years after starting
treatment. The majority of these
patients relapse only in their brain,
and nearly all of those who relapse in
their central nervous system die of
their cranial metastases
PCI- prophylactic cranial irradiation
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Patients who have achieved a
complete remission can be
considered for prophylactic cranial
irradiation (PCI).
PCI prophylactic cranial irradiation
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The risk of developing central nervous
system metastases can be reduced by
>50% by the administration of PCI in
doses of 2,400 cGy
a meta-analysis of 7 randomized trials
evaluating the value of PCI reported
improvement in brain recurrence, diseasefree survival, and overall survival with the
addition of PCI. The 3-year overall survival
was improved from 15% to 21% with PCI.
PCI
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The majority of patients with small
cell lung cancer have
neuropsychological abnormalities
present before the start of cranial
irradiation and have no detectable
decline in their neurological status
for as long as 2 years after the start
of their cranial irradiation
Extensive-Stage Small Cell Lung
Cancer
Combination chemotherapy with one of the
following regimens with or without PCI given to
patients with complete responses:
-CAV: cyclophosphamide + doxorubicin +
vincristine.
-CAE: cyclophosphamide + doxorubicin +
etoposide.
-EP or EC: etoposide + cisplatin or carboplatin.
-ICE: ifosfamide + carboplatin + etoposide.
-Cisplatin + irinotecan
 irradiation reserved for nonresponding patients
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Skin cancer
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Basal cell carcinoma
squamous cell carcinoma
Although these 2 types of skin
cancer are the most common of all
malignancies, they account for
<0.1% of patient deaths due to
cancer.
Skin cancer
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Both of these types of skin cancer
are more likely to occur in individuals
of light complexion who have had
significant exposure to sunlight, and
both types of skin cancer are more
common in the southern latitudes of
the Northern hemisphere.
Basal Cell Carcinoma of the Skin
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Mohs micrographic surgery- the tumor is
microscopically delineated until it is completely
removed. Indications:
tumors with poorly defined clinical borders;
tumors with diameters >2 cm;
tumors with histopathologic features showing
morpheaform or sclerotic patterns;
tumors arising in regions where maximum
preservation of uninvolved tissue is desirable,
such as eyelid, nose, finger, and genitalia.
cure rates have been reported at 96%
Basal Cell Carcinoma of the Skin
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Simple excision- tumor recurrence is not
uncommon because only a small fraction
of the total tumor margin is examined
pathologically. Recurrence rate for primary
tumors >1.5 cm in diameter is at least
12% within 5 years; if the primary tumor
measures >3 cm, the 5-year recurrence
rate is 23.1%. Primary tumors of the ears,
eyes, scalp, and nose have recurrence
rates ranging from 12.9% to 25%.
Basal Cell Carcinoma of the Skin
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Electrodesiccation and curettage.
This method is the most widely
employed method for removing
primary basal cell carcinomas.
Although it is a quick method for
destroying the tumor, adequacy of
treatment cannot be assessed
immediately since the surgeon
cannot visually detect the depth of
microscopic tumor invasion.
Basal Cell Carcinoma of the Skin
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Cryosurgery- may be considered for
patients with small, clinically welldefined primary tumors. It is
especially useful for debilitated
patients with medical conditions that
preclude other types of surgery.
Basal Cell Carcinoma of the Skin
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Radiation therapy: for patients with
primary lesions requiring difficult or
extensive surgery (e.g., eyelids, nose, or
ears)
Cosmetic results are generally good to
excellent with a small amount of
hypopigmentation or telangiectasia in the
treatment port.
Radiation therapy can also be used for
lesions that recur after a primary surgical
approach.
Squamous Cell Carcinoma of the
Skin
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Localized squamous cell carcinoma of the
skin is a highly curable disease.The
traditional methods of treatment involve
the use of cryosurgery, radiation therapy,
electrodesiccation and curettage, and
simple excision.
Of all treatment methods available, Mohs
micrographic surgery has the highest 5year cure rate for both primary and
recurrent tumors.
Lymphadenectomy is indicated when
regional lymph nodes are involved.
Melanoma malignum
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most melanomas arise in the skin,
they may also arise from mucosal
surfaces or at other sites to which
neural crest cells migrate
Melanoma occurs predominantly in
adults, and more than 50% of the
cases arise in apparently normal
areas of the skin
Prognosis
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Thickness and/or level of invasion of the
melanoma, mitotic index, presence of
tumor infiltrating lymphocytes, number of
regional lymph nodes involved, and
ulceration or bleeding at the primary site
affect the prognosis.
Patients who are younger, female, and
who have melanomas on the extremities
generally have a better prognosis.
Prognosis
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For disease clinically confined to the
primary site, the greater the
thickness and depth of local invasion
of the melanoma, the higher the
chance of lymph node or systemic
metastases and the worse the
prognosis
Stage
Clark’s classification (level of
invasion)
TNM definitions
Clinical staging
AJCC stage groupings
Pathologic staging
AJCC stage groupings
Melanoma malignum
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localized melanoma: surgical excision
with margins proportional to the
microstage of the primary lesion
melanomas that have spread to
regional lymph nodes may be curable
with excision of the primary tumor
and removal of the involved lymph
nodes
Melanoma malignum
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adjuvant high-dose interferon was
shown to increase relapse-free and
overall survival when compared to
observation
adjuvant chemotherapy does not
improve survival
Patients with distant metastasis
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Treatment in clinical trials:
combination chemotherapy
biological response modifiers (such
as specific monoclonal antibodies,
interferons, IL-2, or tumor necrosis
factor-alfa), vaccine immunotherapy,
or chemoimmunotherapy.
Recurrent Melanoma
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Resection of isolated single or localized metastases from
skin, visceral, or brain sites in selected patients is
sometimes associated with prolonged survival.
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Palliative radiation therapy for bone, spinal cord, or brain
metastases.
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Palliative biologic therapy and/or chemotherapy in phase
I and II clinical trials.
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Palliative treatment with interleukin-2 or interferon can
occasionally result in prolonged survival.
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Isolated hyperthermic limb perfusion for extremity
recurrences.
Primary brain tumors
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Anaplastic astrocytoma and glioblastoma
account for approximately 38%
meningiomas and other mesenchymal
tumors account for approximately 27%.
pituitary tumors, schwannomas, CNS
lymphoma, oligodendrogliomas,
ependymomas, low-grade astrocytomas,
and medulloblastoma
Pirmary spinal tumors
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Schwannomas, meningiomas,
and ependymomas account for
as much as 79% of primary
spinal tumors
Signs and symptoms
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headache;
gastrointestinal symptoms such as
nausea, loss of appetite, and
vomiting;
changes in personality, mood, mental
capacity, and concentration.
focal cerebral syndromes such as
seizures
Signs and symptoms
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Of all patients with brain tumors,
70% with primary tumors and 40%
with metastatic brain tumors develop
seizures at some time during the
clinical course.
Treatment
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Surgical removal is recommended for
most types of brain tumors, in most
locations, removal should be as complete
as possible within the constraints of
preservation of neurologic function.
An exception to this role for surgery is
deep-seated tumors such as pontine
gliomas, which are diagnosed on clinical
evidence and treated without initial
surgery approximately 50% of the time.
Treatment
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Radiation therapy has a major role in
the treatment of patients with most
tumor types and can increase the
cure rate or prolong disease-free
survival.
may also be useful in the treatment
of recurrences in patients initially
treated with surgery alone.
Treatment
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Chemotherapy may prolong survival
in patients with some tumor types
and has been reported to lengthen
disease-free survival in patients with
gliomas, medulloblastoma, and some
germ cell tumors.
Treatment
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Dexamethasone, mannitol, and
furosemide are used to treat the
peritumoral edema associated with
brain tumors. Use of anticonvulsants
is mandatory for patients with
seizures.
Brain Stem Gliomas
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Brain stem gliomas have relatively
poor prognoses that correlate with
histology (when biopsies are
performed), location, and extent of
tumor. The overall median survival
time of patients in studies has been
44 to 74 weeks. The best results
have been attained with
hyperfractionated radiation therapy.
Pilocytic Astrocytomas- grade I
tumors (WHO)
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Surgery alone if the tumor is totally
resectable.
Surgery followed by radiation
therapy to known or suspected
residual tumor
Diffuse Astrocytomas- grade II
astrocytic tumor
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Surgery plus radiation therapy;
Or surgery alone if the patient is
younger than 35 years and if the
tumor does not contrast-enhance on
a computed tomographic scan.
Anaplastic Astrocytomas-grade
III tumors
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Surgery plus radiation therapy.
Surgery plus radiation therapy and
chemotherapy
clinical trials that evaluate
hyperfractionated irradiation, acceleratedfraction radiation, stereotactic
radiosurgery, radiosensitizers,
hyperthermia, interstitial brachytherapy,
or intraoperative radiation therapy used in
conjunction with external-beam radiation
therapy
Glioblastoma- grade IV tumors
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Surgery plus radiation therapy and
chemotherapy
Surgery plus radiation therapy
Patients with newly diagnosed
glioblastoma multiforme
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A randomized study of RT versus RT plus
temozolomide followed by 6 months of
adjuvant temozolomide: a statistically
significant increase in median survival of 3
months in the combination-treated group.
The 2-year survival rate was 26.5% in the
combination group compared with only
10.4% in the radiation-only group. The
treatment is relatively safe and well
tolerated.
Oligodendrogliomas
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Oligodendrogliomas behave much like
diffuse astrocytomas
Standard treatment options:
Surgery plus radiation therapy; however,
some controversy exists. Some physicians
treat these patients with surgery alone if
the patient is younger than 45 years and if
the tumor does not contrast-enhance on a
computed tomographic scan.
Ependymal Tumors
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Surgery plus radiation therapy (brain
irradiation with or without spinal
irradiation)
Embryonal Cell Tumors:
Medulloblastoma
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Surgery plus craniospinal irradiation