Toxicities faced by patients who receive Oral/Neck Radiotherapy

1. Radiation induced
toxicities and their
management (Oral
Cavity/Neck)
Dr. Debarshi Lahiri

2. Radiotherapy Toxicities
Almost every patient impacted
Functionally important structures
Close proximity Collateral damage
Functional compromise
(Swallowing, speech, taste, dry mouth etc.)

3. Problems reported in clinic by patients receiving
Oral/Neck RT
During/shortly after RT: (Acute)
1. Acute Mucosal reactions (Mucositis)
2. Acute Skin reactions (Dermatitis)
3. Pain during swallowing (odynophagia)
4. Sticky saliva/feeling of dryness (xerostomia)
5. Altered or loss of taste sensation
6. Speech and swallowing issues
7. Dental care issues
8. Hematological issues (patients on CCRT)
During Follow-up (beyond 3-6 months onwards): (Late)
1. Increasing Xerostomia
2. Persisting speech and swallowing issues
3. Persisting taste issues
4. Rare persisting mucositis/skin reactions
5. Neck fibrosis & Lymphedema
6. Trismus
7. Persisting dental complications
8. Rare ORN

4. Acute Reactions start during RT (< 90 days)
 Tissues with high cell turnover rate (mucous membranes, skin, bone
marrow etc, Salivary glands-exception & shows both early and late
effects)
 Usually transient and self limiting, recovery 4-6 weeks
 Superficial epithelial inflammation early depopulation of rapidly-
growing epithelial cells loss of barrier function, recovery through
repopulation and migration of healthy cells

5. Chronic (> 90 days) (few months to years after tx)
 Tissues with slow turnover (subcutaneous, muscle, fatty tissue, bone etc.)
 Usually persistent and progressive
TGF beta overexpression excessive production of fibrocytes excess collagen deposition
Fibrosis thickening of basement membrane late vascular damage
Consequential Late Toxicities:
 Severe early toxicities may not recover completely lead to subsequent late effects
Persistent mucositis, Xerostomia, Dysphagia, Skin changes like hyper/hypo-pigmentation,
Subcutaneous edema etc.)
 Continuing dysregulation of the tissue environment from sequence of events initiated
immediately after injury

6. Toxicity Grading/Scoring
Physician Assessed Toxicity scales
(PATs):
● Grades toxicity according to severity,
Grade (1 through 4)
● Interpreted by physician or HP
● Useful in clinic as well as clinical trials
EORTC/RTOG (mucositis/dermatitis scales
commonly used in clinical setting & earlier
trials used RTOG)
WHO (easy to use in clinical settings)
NCI CTCAE (v 5) (commonly used by
modern clinical trials ), Grading available for
most of the common toxicities
LENT/SOMA—grades only late effects
Patient Reported Outcomes (PROs):
● Goal: Assessment of patient
function and quality of life (QoL)
outcomes
● Direct reports from patients about
their health status (e.g. swallowing
function during radiation therapy)
without interpretation by others
(through validated questionnaires-
PROMs)
● Used in research studies and
clinical trials
NOT EASY TO IMPLEMENT IN A
BUSY CENTRE
FACT-HN, MDADI, DHI, EORTC QLQ
H&N 35, RISRAS etc.

7. Acute Mucositis
● Affects nearly all patients with radiation targeted at oral
cavity/Oropharynx.
● Most common cause of Tx disruptions
● Severe cases progress to ulceration with pseudomembrane formation
and constant pain
● Resultant pain and dysphagia affects oral intake and nutrition.
● Infection risk rises due to disruption of the mucosal barrier
● Patient factors: Age, nutritional status, oral hygiene, smoking, alcohol
etc.
● Treatment related factors: The volume of mucosa included in the high-
dose areas of radiation (Total dose/ fractionation/ technique/ use of
Concurrent chemo/ targeted tx.)

8. Management of Acute Mucositis
Trauma to the mucosal surfaces should be avoided: :
● Soft bland diet that requires minimal chewing,
● Avoid spicy or acidic foods, avoid hot beverages, hard food, mucosal irritants, caffeine and
alcohol
● Extra-soft tooth brush minimizes trauma/or by fingers, Ice chips for pain relief
Topical short-acting pain control is important to maintain oral intake and relieve pain
● Benzydamine: NSAID given as an oral rinse and has topical anti-inflammatory, analgesic,
anaesthetic, and antimicrobial activity
● Viscous Lidocaine rinse, gargle, can be swallowed before feed
● Lidocaine & Triamcinolone oral gel application
● Oral Paracetamol 1gm. (up to TDS)
If pain is continuous and refractory, blocking pain responses centrally is important for patient
well-being:
● Opioid analgesics
● Gabapentin has shown to produce improved analgesia and reduce opioid requirements

9. Nutritional Status to be carefully maintained.
● Ryles tube feeding may be required .
● Weight loss should be monitored.
● Regular dietician referral
● Monitoring of CBC, electrolytes
Oral cavity should be kept very clean and free of residue Rinse thoroughly after meals and frequent oral
cleansing and disinfection with a weak solution of salt and baking soda
● Excellent oral hygiene promotes control over microbial flora. Frequent rinsing and gargling advocated.
● Special care to be taken for removing food debris and residue that adheres to mucosal surfaces.
Monitoring for fungal infections- Candidiasis (whitish, cottony appearance which may be easily confused with
early mucositis or pseudo-membrane formation)
● Treated either topically or systemically:
■ Nystatin rinse
■ Clotrimazole troche
■ Fluconazole tablets in refractory
cases, oropharyngeal candidiasis
Bacterial infections should be appropriately diagnosed and treated with suitable antibiotics

11. Dysgeusia
● Radiation may cause alterations in taste perception (dysgeusia), ranging from complete (ageusia) to
partial (hypogeusia) loss of the sense of taste
● Alteration of taste may occur in up to 75% of head and neck cancer patients
● Dysgeusia results in anorexia, weight loss, malnutrition, and poor QOL
Timing
● RT causes a dose-related cytotoxic effect on taste buds which reduces their density, ( linked to taste
perception and sensitivity
● Dysgeusia correlates with the extent of oral cavity radiated to high doses (50 Gy), with peak
incidence of symptoms at 1 month after RT followed by recovery in most patients by 12 months
Prevention
● Avoidance of a high mean dose to the oral cavity may be the best form of prevention.
● Studies of zinc supplementation to prevent radiation-induced taste effects have yielded highly
conflicting results
● Reducing effects of xerostomia may help to mitigate some taste alteration.

12. XEROSTOMIA (dry mouth):
• Associated with decreased function or loss of function of the salivary glands
• RT alters the volume, consistency, and pH of secreted saliva. Saliva changes from thin secretions with
a neutral pH to thick and tenacious with increased acidity.
• Acute Xerostomia typically shows effect in the last two weeks of a radiation treatment course.
• Persists into Late Xerostomia if Parotid/salivary glands receive high dose (conventional RT). May be
irreversible
• Patients report thick, ropey secretions that result in gagging and regurgitation and predispose to
aspiration
Consequences: Impairs QOL
Altered taste, reduced intraoral lubrication, halitosis, dental infections/caries, speech, eating, &
swallowing difficulties.

13. Xerostomia Management
Best option is PREVENTION (Spare Salivary glands as much as feasible)
● IMRT is Standard of Care (PARSPORT Trial, Nutting et al.)
● Standard known tolerance levels, if exceeded, will result in increased effects. Mean dose to
bilateral parotid composite contour to be less than 26 Gy, mean dose to contralateral
parotid to be less than 20 Gy
● Try to spare submandibular glands (if possible)
● Unnecessary radiation of areas of oral cavity (minor salivary glands) to be avoided
● Maintenance of excellent oral hygiene & frequent water intake
● Salivary substitutes that temporarily hydrate the mucosa: Ingredients such as
carboxymethylcellulose
● Pharmacologic stimulants are generally parasympathomimetic agents: Pilocarpine (5 mg
TDS) (Residual salivary function is required)
● Radioprotector Amifostine (not in routine clinical use any more)

14. SWALLOWING issues:
● Post-treatment dysphagia is a recognized complication of head and neck cancer
therapy (risk of micro-aspiration pneumonia)
● After chemoradiation to pharyngeal region, it is estimated that as many as 50% of
patients silently aspirate.
● Most patients will be swallowing worse than baseline at 3 months after head and neck
chemoradiation—regardless of eventual long-term swallowing function.
● Eisbruch et. al. (2004) hypothesized that the preferential sparing of the
“Dysphagia/Aspiration-related structures (DARS)” (Pharyngeal constrictors, and glottic
& supraglottic larynx) prevents major radiation induced long term toxicities
● Results from the recent Phase 3 DARS RCT (Nutting et al.) suggest that DOIMRT
improves patient reported swallowing function compared with SIMRT, and should
be considered standard in pharyngeal cancers.

15. Prevention & Management
● Avoid unnecessary irradiation to the uninvolved pharyngeal constrictors:
Mean dose to the uninvolved pharynx to be less than 40- 50 Gy based on
tumor location
● Avoid unnecessary irradiation to the uninvolved larynx: Mean larynx dose to
be less than 40-45 Gy
● All patients to be evaluated by a SLP for a formal swallowing evaluation
prior to & after the initiation of head and neck radiation
● “Pharyngocise” : A randomized controlled trial suggested that active
swallowing exercises during chemoradiation improved swallowing outcomes
when compared to both “usual care” and a sham intervention (Mann-
Carnaby et. al 2012).
● Swallowing rehabilitation successfully improves majority of patients who
aspirate on oral intake after radiotherapy

17. Voice & Speech problems
● Speech: complex process that involves not only the glottic larynx, but the
oral cavity and pharynx in combination with adequate lubrication from
functioning salivary glands.
● Direct radiation effects to the upper aerodigestive tract can cause speech
problems during a course of radiation
● Dose avoidance to the glottic larynx and supraglottic larynx: Mean dose of
less than 40 Gy (Practical <45 Gy) is ideally recommended
● All patients should see an SLP(Speech Language Pathologist) prior to the
initiation of head and neck cancer treatment for speech exercise training
● Patients who receive voice rehabilitation posttreatment report better self-
rated voice function

18. Fibrosis
-Late complication
● Tends to be worse in older patients,
larger tumors, higher radiation
doses, higher treatment volume, and
in patients who have undergone
other treatment modalities such as
surgery and chemotherapy
● Even in patients treated with modern
techniques, such as intensity-
modulated radiation therapy (IMRT),
the occurrence still remains as high as
30%
● dysregulation of the wound healing
processes and upregulation of TGF-β
and inflammatory cytokines.

19. Lymphedema
Lymphedema:
● Often coexists with neck fibrosis (fibrosis
increases severity)
● when the lymphatic load exceeds the
transport capacity of the lymphatic system
secondary to tumor and/or surgery and/or
radiation.
● It may result in swelling, tightness, and
decreased range of motion with associated
discomfort.
● Post operative radiotherapy leads to
increased incidence & severity can increase
with time
● Avoidance of bilateral neck dissections if an
oncologically safe alternative is available.

20. Management of Fibrosis & Lymphedema
Referral to Physical Therapist with experience in management
• Complete decongestive therapy (CDT) has four components:
-Manual lymph drainage (MLD)
-Use of compression garments and pads
-Skin care
-Basic face, neck, and oral cavity exercises
● CDT improves head and neck lymphedema in 2/3rd of patients
● Early physical therapy after neck dissection is associated with increased range of
motion of the shoulder.
Medical Management:
• Pentoxifylline + vitamin E can be effective in the management of radiation induced
fibrosis
-Pentoxifylline dose is 800 mg/day
-Vitamin E dose is 1000 IU/day
-Duration of therapy long (at least 6 months).

22. Trismus
● Normal mouth opening varies within a range of 40–50 mm
● Inability to fully open the mouth (Trismus) is a common morbidity associated with head and
neck cancer (HNC) radiotherapy. Preexisting SMF, muscle involvement, post surgical patients
(worse outcome)
● Studies have used a cutoff of ≤35 mm to define trismus
● The higher the radiation dose delivered to the masticatory structures, the worse is the restriction
in mouth opening. Levels in excess of 60 Gy are more likely to cause trismus
● Patients who were previously irradiated and are currently being treated for recurrence are at a
higher risk of trismus than patients receiving their first treatment.
● Abnormal proliferation of fibroblasts in the muscles and ligaments (radiation-induced fibrosis)
● CCRT may be associated with a higher prevalence of trismus
● The reduction of mouth opening usually begins to appear toward the end of the radiation course
and continues to deteriorate in the following year. Most of the reduction occurs in the first 1 to 2
years

23. Management of Trismus
Physical Therapy:
● Start exercise during or soon after finishing radiation treatment
● Active exercises aim to strengthen the jaw-opening muscles (depressors of the mandible), Passive
exercises stretch the jaw-closing muscles (elevators of the mandible)
● Delaying physical therapy for a year or so after oncologic treatment lowers the chance of achieving
satisfactory results
Trismus Appliances:
● Impart mechanical forces to forcibly stretch the jaw-closing muscles by depressing the mandible
● Patients may open the mouth actively (if possible) using their own jaw-opening muscles, the appliance is
then inserted, and the number of spatulas or coils is counted. This helps the patient to set goals and
record progress
Drug Therapy (mentioned with fibrosis)
Release Surgery:
● Resection of scar tissue and fibrotic bands along with reconstruction of surgical defects can alleviate
some of the restriction and improve trismus
● All release-reconstructive surgeries must be followed by strict physical therapy programs
● Patients selected for these types of surgeries have to be cooperative and well motivated.

24. ● Wooden spatulas are stacked up and
used as a wedge between upper and
lower teeth to increase mouth
opening passively
● The threaded-tapered screw may be
fabricated in different sizes with
varying pitch distance between the
threads
● Metallic jaw opener/retractor is often
used, care to be taken not to
damage the teeth
● Non metallic jaw openers with a
padding seem to be safer with lesser
risk of damage to teeth
Trismus Appliances

25. Dental Impact:
Dental status has a significant impact on the QOL of head and neck cancer survivors. Many patients have poor dentition at
diagnosis, and poor dentition post treatment increases the risk of ORN and infection.
Xerostomia is known to increase the incidence of dental caries. Patients should meet with a dentist prior the initiation of
RT
Prevention (risk of ORN):
• Every patient who has received radiation that delivers dose to either the oral cavity or a major salivary gland should be
considered a “high-risk” dental patient for the remainder of their life.
• Good oral hygiene, Regular rinses, brushing, and flossing.
• Pretreatment dental evaluation—all non-restorable teeth should be extracted prior to the start of radiation. Pre-radiation
extractions of healthy teeth do not seem to decrease the incidence of ORN.
• Postradiation fluoride prophylaxis— Long-term fluoride and diligent oral hygiene are a must after the completion of therapy.
Regular visit to the dentist (with experience in managing post RT H&N patients) every 2-3 months.
• Limiting high-dose regions to the mandible/maxilla with highly conformal radiation plans along strict dental hygiene
results in a low risk of ORN. The mandible is the most commonly affected bone, as larger part of the mandible is typically
exposed to higher doses of radiation than the maxilla and has a poorer blood supply than the maxilla.
• Reduced radiation dose to the parotid gland with IMRT results in both increased salivary output and better posttreatment
salivation and avoidance of posttreatment dental caries.

26. Acute Radiation Dermatitis
Management
● Injury to the rapidly dividing cells of the
dermis, epidermis, and feeding
vasculature.
● The condition is characterized by
erythema, edema, dry and wet
desquamation, blistering and bleeding,
and erosion and ulceration of the skin.
● Rarely, radiation needs to be withheld for
a period
Timing
● Prodromal changes to skin begin within
24 hours of radiation exposure.
● Visible reaction starts around 10 to 14
days after radiation course begins.
● Dry desquamation can be expected at
dosages over 30 Gy.
● Moist desquamation can be expected in
few patients at dosages over 40 Gy.
● Protecting the skin from trauma and recognizing
signs of infection
● Avoid rubbing and scratching
● Wear loose-fitting clothing, collarless shirts
● Topical emollients are considered to hydrate the
skin and ameliorate itching and soreness.
● Good hygiene and cleanliness should be
maintained.
● Avoid perfumes, aftershave
● Use an electric razor to avoid cuts to the skin
● Steroid creams can be used prophylactically on
individuals identified as high risk of developing a
RISR i.e. a grade 3 skin reaction
● Infection should be addressed promptly with
topically applied antibiotic medications or
dressings.

28. THANK
YOU