the general basis for the development of head and neck cancer along with recent advances in its treatment.

1. General Oncological
basis of
HEAD n NECK Cancer
Dr. Firoz Ansari
Pgr Ent-I
Mentor :- Prof. Dr. Khalid cheema

2. Incidence of various head and neck cancer
worldwide and local
• The most common type of head and neck carcinoma is squamous cell carcinoma(SCC) of the
mucosa of the upper aero digestive tract (UADT ). If a cancer is only found in the squamous
layer of cells, it is called carcinoma in situ. If the cancer has grown beyond this cell layer and
moved into the deeper tissue, then it is called invasive squamous cell carcinoma.
• The incidence and risk factor for UADT SCC differ by tumor sub site. The major 5 being the
naso,oro,hpo-pharynx,oral cavity and larynx. (others- nasal cavity and PNS, salivary gland)
Eg:- Nasopharyngeal carcinoma are typically related to Epstein barr virus and are a major
contributors to UADT in southeast Asia and southern china, however its relatively rare in other
populations.
North America, Europe and Australia there is an epidemic oropharyngeal SCC (OPSCC) caused
by human papilloma virus (HPV) and HPV positive SCC more common than that caused by
alcohol-tobacco. The major of the world SCC are due to alcohol and tobacco.
The rate of oral cavity SCC is more common in south Asian countries than any other countries
globally .

3. Staging
• Classification of the anatomical extent of head and neck cancer as determined
clinically and histopathologically is called the TNM system.It is a system designed
to express the relative severity, or extent, of the disease. It is meant to facilitate
an estimation of prognosis and provide useful information for treatment
decisions.
• Two classification should be documented for each site namely
clinical (pre-treatment) cTNM and
 pathological (post-surgical histopathological) pTNM.
• The clinical stage is essential to select and evaluate therapy, while the
pathological stage provide the most precise data to estimate prognosis and
calculate end results.

4. The response to t/t of cervical nodal metastases from the nasopharynx are
different in terms of their impact on prognosis and hence justifies a different N
classification.
Regional LN metastasis from well-diff. thyroid ca. do not significantly
affect the ultimate prognosis and therefore warrants a unique system.

5. Superficial erosion alone of bone/tooth socket by gingival primary is
not sufficient to classify a tumour as T4a
T4b has been removed –the survival curves proves
indistinguishable from T4a.

9. Drawbacks
Limitations of T staging:-
• T stage alone is of little prognostic significance in many head and neck carcinomas.
• Tumors of the larynx are classified according to the number of anatomical surfaces involved this has led to several confusion.
• For eg:- a large 3cm tumor of the supraglottic may remain T1, whereas in the glottis this will almost certainly be a T3.
• The size of the tumor in oral cavity or oropharynx is not always easily measured.
• The depth of invasion is not measured, but is of prognostic and therapeutic importance.
• For eg:- a superficial tumor of the vocal cord mucosa would be a T1a. The same tumor may be deep infiltrating into the vocalis muscle and yet remain
T1a.
• The depth of invasion of the lesions of the floor of the mouth has been shown to be of prognostic significance and this is difficult to assess by either
clinical or radiological means.
• The dual listing of the aryepiglottic fold in both the supraglottis and hypopharynx sites invoke a problem in trying to classify the site of origin in some
situation.
Limitations of N staging
• There is considerable inter- and intra-observer error in estimating the size of the node by palpation alone without a measuring device.
• Most masses over the size of 3 cm in diameter are not single nodes.
Limitations of stage grouping
• one of the main criticism is that the size of some groups defined by the combination of TNM classification is small, preventing accurate
prediction from previous experience.
• Stage grouping should meet the following (Groome et al) :- similar survival rates within the group, survival rates differ, prediction should be
high, distribution of patients across the group should be balanced.
EG:- TANIS SCORE (combining the integer of T and N) ( it does not hold true, eg:- T2N0 does not have the same survival as T1N1 ,which would be
categorized as TANIS-2)

10. Selection of patient for chemo, radio or both
• At the beginning of the 20th century, lack of early diagnosis, anesthetic limitations, the lack of
antibiotics with a high surgical mortality rate and laryngeal carcinoma occurring as hopeless
situation developed tendency towards the use of radiation therapy as the, primary treatment.
• In the middle 20th century, advancements in perioperative care, combined with the
recognized side effects and treatment failures of early RT techniques, led to the emergence of
surgery as primary treatment with or without adjuvant RT for most head and neck cancers.
• In the second half of the 20th century, a focus on functional outcomes and an increasing role
of chemotherapy led to both surgical and nonsurgical organ-preservation approaches.
Pathologic findings on END, including ECS and multiple positive lymph nodes, became
indications for postoperative RT and, eventually, chemotherapy.
• Subsequent advancements in RT improved cure rates and decreased toxicities ,Today, RT
remains an important single-modality option in early-stage cancers and plays an important role
in the adjuvant setting.
• Recently, combinations of chemotherapy and RT have been used increasingly for advanced-
stage cancers, both for primary and adjuvant treatment.
• Finally, the development of targeted molecular therapies offers new options in the
management of HNSCC, which may further improve survival and functional results.

11. Radiotherapy
• Before 1948, the administration of RT was limited to orthovoltage generators and radium
implants.Orthovoltage radiation was characterized by poor depth distribution with limited
efficacy against deeper tumors and a high degree of skin damage.
• In the 1950s, however, the era of modern RT began with the advent of the linear accelerator
and telecobalt units, which generated supervoltage radiation.Supervoltage radiation, with its
vastly improved depth distribution, allowed for the treatment of deeper tumors while sparing
the skin. This advancement allowed radiation to maintain a prominent role in the treatment of
HNSCC.
• The most common type of radiation treatment is called external-beam radiation therapy,
which is radiation given from a machine outside the body. A newer method of external-beam
radiation therapy, known as intensity modulated radiation therapy (IMRT), allows more
effective doses of radiation therapy to be delivered while reducing the damage to healthy cells.
• When radiation treatment is given using implants, it is called internal radiation therapy or
brachytherapy. Brachytherapy allows for an increase in the concentration of radiation at the
implant site while minimizing effects on normal surrounding tissue and has been shown to
provide benefit in patients with previously irradiated, unresectable, recurrent disease at the
primary site or in the neck.
• New clinical trials are researching the use of proton beam therapy to see if this can further
reduce the damage to healthy tissues during therapy. Proton beam therapy is a type of
external-beam radiation therapy that uses protons rather than x-rays (photons) to destroy
cancer cells.

12. Mechanism of action
• For radio therapy photons are used normally of energy 6 MV, which are produced in a
linear accelerator by acceleration of electrons into a target.
• Photons cause ionization in the tissues resulting in the formation of secondary
electrons which cause further ionization, in presence of oxygen a free radical is formed.
• Radiation causes cell death primarily through single or double stranded breaks in DNA.
• The single stranded breaks are due to this free radical formation and the double
stranded breaks are directly proportional to the radiation dose or secondary electrons.
• In general it is the double stranded breaks that is crucial for lethal effects of radiation.
Which is also known as CELL KILL which renders the tumor cell sterile (incapable of
proliferative capabilities).
• It is the difference in response between tumor cell and the normal tissues In their
ability to repair DNA lesions in response to the amount of radiotherapy delivered per
treatment. (fraction size)

13. • Acceleration :- is a reduction in the overall treatment time below the standard 46 days.
• Hyper-fractionation:- the use of less than 2 Gy per fraction.
• Hypo-fractionation:- the use of more than 2 Gy per fraction.
• Dose escalation:- increase in the total physical dose.
• Biologically effective dose :- allows comparison of dose fractions.
• Equivalent dose in 2Gy fraction:-
• one gray (Gy) is equivalent to 1 joule of energy deposited per kilogram of tissue.
• Prolonging the overall time reduces the efficacy of radiotherapy. This is thought to occur due to
increase rate of cell proliferation in surviving cells once radiotherapy has commenced.it has
been known to occur at around 21 days known as KICK OFF TIME Tk. The cell turn over time (Tp)
for squamous cell carcinoma is termed at 3 days.
• The addition of chemotherapy to radiotherapy is equivalent to the addition of three –four 2Gy
fractions in terms of local control

14. • Side effects:-
1. Acute :-
• Mucositis (often requiring use of strong opiod analgesics)
• Taste disturbance
• Hair loss
• Acute xerostomia
• Dysphagia (requiring use of temporary feeding tube)
2. Long term :-
• osteoradionecrosis
• Xerostomia
• Stricture formation
• Fibrosis
• necessitating the use of feeding tube for long duration
Before beginning radiation therapy for any head and neck cancer, people should receive a thorough
examination from an oncologic dentist. An oncologic dentist is a dentist with experience in caring for
the dental and oral health of people with cancer. Since radiation therapy can cause tooth decay,
damaged teeth may need to be removed before treatment begins.
Death during or within 8 weeks of completion of treatment, occurs in 0-7% of patients undergoing
radiotherapy alone and 0-14% with chemo-radiation .
Deaths definitely due to treatment are reported in 0-3% and 0-5% of patients respectively.

15. When the
gantry is fixed
the t/t is
known as fixed
beam step and
shoot
IMRT(intensity
modulated
radiotherapy)
If the
gantry is
rotating
while
delivering
the IMRT
it is
known as
dynamic
arc IMRT.
IMRT
IMPT

17. Chemotherapy
Chemotherapy alone cannot cure head and neck cancer.
Induction/neoadjuvant chemotherapy:- Treatment given before the principal treatment.
 Regimens:-
• the standard regimen formerly was cisplatin 100 mg/m2 and 5-fluorouracil, 1g/m2 per day for 4-5 days via a chemotherapy infusion bottle.
This was given 3 weekly for two to three cycles, before definitive treatment. The latter which is almost always chemoradiotherapy except in
few cases where it can be used in hope of converting inoperable loco-regional disease to more surgically manageable disease.
• Trials then revealed that adding TAXANE such as Docetaxel or Paclitaxel to above regimen improved survival but at cost of higher toxicity
both hematological (myelo-suppression and neutropenia) and non- hematological (esp. increasing mucositis)  offered to patients where
surgery is not appropriate.
• The most effective, optimal and least toxic sequential chemotherapy regimen is still debated.
 Rationale for use of induction chemotherapy:-
• If induction chemotherapy could shrink primary tumor volumes before the principal treatment of radio or chemo therapy, this might allow
better blood flow into the tumor allowing a greater tumoricidal dose of drugs to be delivered and decrease the radioresistance that hypoxic
cells show  two most common drugs in use are anti-helminthic NIMORAZOLE and an anticoagulant TIRAPAZIMINE which is activated in
hypoxic environment.
• Induction chemotherapy could theoretically treat distant subclinical metastatic disease. Reviews suggest that induction chemotherapy may
reduce distant metastasis, more effectively than concomitant chemotherapy.
• It can shrink and render fixed cervical nodes mobile, enabling technically easier surgery.
• The response to induction chemotherapy could give important prognostic information. Eg:- if there was a response pts went on to have chemo
and radio but if there was no response the pts can go directly for laryngectomies.
 Drawbacks of use of induction chemotherapy:-
• It fails to show overall survival benefit when compared to radiotherapy or surgery alone.
• There is still debate weather induction followed by concomitant is more beneficial than concomitant alone.
• There is a risk that patients undergoing induction chemotherapy may be more at risk of not completing or having breaks in the subsequent
definitive radiotherapy treatment because of the morbidity caused by induction chemo, resulting in poorer outcomes.

18. Concomitant/concurrent chemotherapy :- chemotherapy given with subsequent radiotherapy.
 Regimens:-
• the most common regimen are cisplatin 100mg/m2 at days 1, 22 and 43 of radiotherapy, either alone or with 5-flurouracil, 1g per day on days 1 and 4.
• Daily cisplatin at a dose of 6 mg/m2 is also an occasionally used regimen.
• If cisplatin is contraindicated due to RFT status then:-
 CARBOPLATIN can be considered as it causes less nephrotoxicity but is more myelosuppresive and not as tumoricidal as cisplatin.
 It now been over taken by epidermal growth factor receptor (EGFR) inhibitor CETUXIMAB, in clinical practice, when cisplatin is C/I.
• Other targeted biological agents such as EGFR monoclonal antibodies (PANITUMUMAB OR ZALUTUMUMAB OR ERLOTINIB) are under investigation.
• Cetuximab has also been tried with above cisplatin and 5-FU in extreme cases as it increases response rate and short term survival. In patients who have
become refractory to cisplatin and 5-FU, cetuximab as a single agent does have a low response rate of approximately 10-15%.
• It is more frequently used in compared to induction or adjuvant chemotherapy.
• Elderly patients benefit least in terms of survival advantage.
Adjuvent chemotherapy:- treatment given after the principal treatment.
• It is not used as a sole modality after radiotherapy, as it has not been shown to have benefit in this setting.
• However, when given with adjuvant radiation, it has been shown to improve local control and increase survival where, primary surgery has been the definitive
treatment. This benefit is seen in patients who have a higher risk of recurrence with positive surgical margins, nodal involvement, especially with multiple nodal
involved or extra capsular spread.
Mechanism of action:-
 Cisplatin is believed to kill cancer cells by binding to DNA and interfering with its repair mechanism, eventually leading to cell death. Carboplatin also has the same
m/e.
 The precise mechanism of action of 5-fluorouracil has not been fully determined, but the main mechanism of fluorouracil is thought to be inhibition of the
formation of thymidylate from uracil, which leads to the inhibition of DNA and RNA synthesis and cell death.
 Cetuximab binds to the epidermal growth factor receptor (EGFr) on both normal and tumor cells. Cetuximab competitively inhibits the binding of epidermal
growth factor (EGF) and TGF alpha, thereby reducing their effects on cell growth and metastatic spread.

20. Mutidisciplinary team (MDT)
• The oxford English dictionary defines MDT as :- “combining or involving several academic disciplines or professional
specialisations in an approach to a topic or problem”.
• The UK department of health defines it as :- “group of people of different health-care disciplines, which meet together at a
given time (whether physical in one place, or by video or teleconferencing) to discuss a given patient and who are each able to
contribute independently to the diagnostic and treatment decisions about the patients”.
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23. Irradiated or recurrent HNSCC
Patients who have been irradiated previously and have unresectable recurrent
disease pose a more difficult challenge; for these patients, palliative
chemotherapy is the standard treatment option.
Bleomycin, taxanes, carboplatin, methotrexate, and 5-FU are active in recurrent
HNSCC and produce response rates from 10% to 40%

24. Recent updates……
• New clinical trials are researching the use of proton beam therapy to see if this can
further reduce the damage to healthy tissues during therapy. Proton beam therapy is a
type of external-beam radiation therapy that uses protons rather than x-rays (photons)
to destroy cancer cells.
• Trials then revealed that adding TAXANE such as Docetaxel or Paclitaxel to above
regimen improved survival but at cost of higher toxicity both hematological (myelo-
suppression and neutropenia) and non- hematological (esp. increasing mucositis) 
offered to patients where surgery is not appropriate.
• Other targeted biological agents such as EGFR monoclonal antibodies
(PANITUMUMAB OR ZALUTUMUMAB OR ERLOTINIB) are under investigation.
• Cetuximab has also been tried with above cisplatin and 5-FU in extreme cases as it
increases response rate and short term survival. In patients who have become
refractory to cisplatin and 5-FU, cetuximab as a single agent does have a low
response rate of approximately 10-15%.

25. Thank you !!!