Diagnosis and staging:
To determine tumor extension, diagnostic imaging is needed:
-Imaging diagnosis before a biopsy avoids misinterpretation from
anatomical distortion.
-Computed tomography (CT scan) and Magnetic Resonance Imaging (MRI sacn)
are also used in diagnosis. MRI can be beneficial than CT for evaluating
tongue, perineural spread, invasion to skull base and intracranial
extension.
-CT of chest is preferred, or X-ray is done in early stages.
-Positron emission tomography-CT (PET-CT) is useful in diagnosis of node
and metastases and some primary tumors. It is recommended in patients
with stage III and IV disease when definitive treatment is indicated.
-Esophagoscopy is carried out in case of dysphagia.
-Histological evaluation is mandatory by primary tumor biopsy or fine
needle aspiration (FNA) of lymph nodes.
-Functional evaluation: actions like chewing, swallowing, breathing,
odontology and nutritional status are assessed.
-Special evaluations if needed: psychological and social situation
assessmet, cessation of smoking or alcohol
dependence10.
The diagnosis of HNSCC can be established by biopsy of the primary
tumour. The biopsy method depends upon the location of the tumor.
Primary tumours are approached incisional biopsy or excisional biopsy,
whereas the suspicious cervical neck mass should be diagnosed with the
help of fine needle aspiration (FNA).
A well-differentiated tumour would be similar to the stratified
epithelium, with mature-appearing cells organizing into layers with
irregular keratinization. A poorly differentiated tumour is
characterized by immature cells with nuclear pleomorphism and atypical
mitoses, with minimal to no organized keratinization. HPV-negative
HNSCCs are moderately or well differentiated, with preservation of
stratification and keratinization, whereas HPV-positive HNSCCs are
poorly differentiated and even display basaloid morphology on
histopathological examination. The histopathological diagnosis of HNSCC
can usually be made using haematoxylin and eosin staining. However, in
the case of poorly differentiated tumours, immunohistochemistry may be
necessary to confirm an epithelial origin11.
TUMOR RESPONSE EVALUATION (RECIST GUIDELINES)
Evaluation of target lesions:
- Complete Response (CR): Disappearance of all target lesions. Any
pathological lymph nodes (whether target or non-target) must have
reduction in short axis to <10mm.
- Partial Response (PR): At least a 30% decrease in the sum of
diameters of target lesions, taking as reference the baseline sum
diameters.
- Progressive Disease (PD): At least a 20% increase in the sum of
diameters of target lesions, taking as reference the smallest sum on
study (this includes the baseline sum if that is the smallest on
study). In addition to the relative increase of 20%, the sum must
also demonstrate an absolute increase of at least 5 mm. (Note: the
appearance of one or more new lesions is also considered progression).
- Stable Disease (SD): Neither sufficient shrinkage to qualify for PR
nor sufficient increase to qualify for PD, taking as reference the
smallest sum diameters while on study.
Evaluation of non-target lesions:
- Complete Response (CR): Disappearance of all non-target lesions and
normalisation of tumour marker level. All lymph nodes must be
non-pathological in size (<10mm).
- Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or
maintenance of tumour marker level above the normal limits.
- Progressive Disease (PD): Unequivocal progression (see comments below)
of existing non-target lesions.
Measurability of tumour:
Measurable Tumour lesions:
Must be accurately measured in at least one dimension (longest diameter
in the plane of measurement is to be recorded) with a minimum size of:
• 10 mm by CT scan (CT scan slice thickness no greater than 5 mm
• 10 mm caliper measurement by clinical exam
• 20 mm by chest X-ray.
Malignant lymph nodes:
To be considered pathologically enlarged and measurable, a lymph node
must be <15 mm in short axis when assessed by CT scan. At
baseline and in follow-up, only the short axis will be measured and
followed.
Non-measurable:
All other lesions, including small lesions and non-measurable lesions
and these non-measurable include: leptomeningeal disease, ascites,
pleural or pericardial effusion, lymphangitic involvement of skin or
lung, abdominal masses/abdominal organomegaly identified by physical
exam that is not measurable by reproducible imaging techniques.
Special considerations regarding lesion measurability:
Bone lesions.
• Bone scan, PET scan or plain films are not considered adequate imaging
techniques to measure bone lesions. However, these techniques can be
used to confirm the presence or disappearance of bone lesions.
• Lytic bone lesions or mixed lytic-blastic lesions, with identifiable
soft tissue components, that can be evaluated by cross sectional imaging
techniques such as CT or MRI can be considered as measurable lesions if
the soft tissue component meets the definition of measurability
described above.
• Blastic bone lesions are non-measurable.
Cystic lesions:
• Lesions that meet the criteria for radiographically defined simple
cysts should not be considered as malignant lesions since they are
simple cysts.
• Cystic lesions thought to represent cystic metastases can be
considered as measurable lesions. However, if non-cystic lesions are
present in the same patient, these are preferred for selection as target
lesions.
Lesions with prior local treatment:
• Tumour lesions situated in a previously irradiated area, or in an area
subjected to other loco-regional therapy, are usually not considered
measurable unless there has been demonstrated progression in the lesion.
Study protocols should detail the conditions under which such lesions
would be considered measurable.
STAGING OF TUMOR (TNM CLASSIFICATION)
In the TNM system:
- The T refers to the size and extent of the primary tumor
- The N refers to the number of surrounding lymph nodes that have
cancer.
- The M refers to whether the cancer
has metastasized.
When your cancer is described by the TNM system, there will be numbers
after each letter that give more details about the cancer, which
include:
Primary tumor (T)
- TX: Main tumor cannot be measured.
- T0: Main tumor cannot be found.
- T1, T2, T3, T4: Refers to the size and/or extent of the main tumor.
The higher the number after the T, the larger the tumor or the more it
has grown into nearby tissues. T’s may be further divided to provide
more detail, such as T3a and T3b.
Regional
lymph nodes (N)
- NX: Cancer in nearby lymph nodes cannot be measured.
- N0: There is no cancer in nearby lymph nodes.
- N1, N2, N3: Refers to the number and location of lymph nodes that
contain cancer. The higher the number after the N, the more lymph
nodes that contain cancer.
Distant
metastasis (M)
- MX: Metastasis cannot
be measured.
- M0: Cancer has not spread to other parts of the body.
- M1: Cancer has spread to other parts of the body.
TNM classification is grouped into following stages:
- Stage 0: Abnormal cells are present but did not spread to surrounding
tissue. Also
called carcinoma
in situ. CIS is not cancer, but it may become cancer in future.
- Stage I, Stage II, and Stage III: Presence of cancer. The higher the
number, the larger the tumor and the more the spread into surrounding
tissues.
- Stage IV: Spread of cancer to remaining parts of the body.
TREATMENT AND PHARMACOLOGY:
By the end of the 20th century, radiation had just
been discovered, and surgical outcomes were of great use due to the lack
of antibiotics and the limitations of anaesthesia. Because of these
reasons, radiation therapy (RT) had been used as a primary treatment for
the first half of
the century. After few decades, due to treatment failures of early RT
techniques, led to the
emergency development of primary surgical treatment for most head and
neck cancers. Subsequent advancements in RT improved cure rates and
decreased treatment failures.
Today, RT remains an important option in early-stage cancers and plays
an
important role in the adjuvant setting. Recently, combinations of
chemotherapy and
RT have been used majorly for advanced-stage cancers, both for primary
and adjuvant
treatment. Finally, targeted molecular therapies have been developed
that bring out new options in managing of HNSCC, which may further
improve survival rates12. Figure 2 represents the
treatment options involving chemotherapy for locally advanced squamous
cell carcinoma of the head and neck.