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Authors : Dr. Suraj Agarwal, Dr. Samta Goel Mittal .

Abstract

The choice of treatment for cancer depends upon many factors such as - The site and extent of the primary tumor, likelihood of complete surgical removal, possibility of preserving speech and swallowing mechanisms, bone and muscle involvement, metastasis, gross characteristic of a tumor, general health of the patient, experience and skill of the surgeon, physician and radiotherapist. As the real answer to a complete and successful cancer therapy still eludes us, the treatment modalities for cancers continue to evolve. The present paper is aimed at highlighting the rationale of radiotherapy including factors which affect decision making in treatment of head and neck cancers.

Introduction

Oral cancer is the sixth most common cancer in the world and is one of the ten most common causes of death. In India, the most common head and neck malignancy are those of oral cavity and pharynx. The majority of oral malignancies are squamous cell carcinoma. 1

Management for cancer has seen great strides in recent years. The aggressive and adamant nature of the cancerous disease demands a multidisciplinary approach to its management. The basic treatment modalities for cancer are surgery, chemotherapy and radiotherapy. Surgery was once upon a time the only cure available for treating cancers.

Surgery is indicated for tumors involving bone, when the side effects of surgery are expected to be less significant than those associated with radiation, for tumors that lack sensitivity for radiation and for recurrent tumors in areas that have previously received radiotherapy. Surgery also may be used in palliative cases to reduce the bulk of the tumor and to promote drainage from a blocked cavity. But it is not free from its many adverse side effects that results in a high rate of post operative morbidity. Surgery results in a sacrifice of structure, which may have important esthetic and functional considerations.1, 2, 3

With the modern advances extensive surgeries are on the verge of decline and the era of conservative surgery along with reconstruction has begun with promising results. The prospects of cure with surgery, radiation, combined chemotherapy, or a combination of any of these modalities are on the rise.4

Radiation was discovered more than a century ago and soon after its therapeutic benefits were identified. In its current state, radiation therapy plays an important role in the treatment of the cancers of the head and neck. More than 80% of cases diagnosed with head and neck cancer receive a course of radiation therapy as a component of therapy. For most early stage cancers, radiation therapy is as effective as surgery in curing the diseases but in general is better in preserving the structural integrity and function of organs.

For intermediate stage carcinomas, many oncologists prefer radiotherapy to surgery for better functional and esthetic outcomes. Many surgically treated patients need post-operative radiotherapy because of the presence of adverse surgical-pathologic features. For locally advanced cancers of the head and neck, radiotherapy is frequently given as an adjuvant to surgery to yield maximum loco-regional tumor control. Thus surgery and radiotherapy are complimentary to each other and radiotherapy has found a definite role for itself in the management of several forms of cancer, for almost all stages of the disease.4,5

TNM Staging system is practiced for effective treatment planning. T is determined by the size of the tumor, N indicates the presence of lymph node metastasis, and M indicates the presence of distant metastasis.

The TNM staging for the tumors of the oral cavity are as follows.1

T1S - Carcinoma in situ.
T1 - Tumor less than 2 cm.
T2 - Tumor greater than 2cm and less than 4cm.
T3 - Tumor greater than 4 cm.
T4 - Tumor greater than 4 cm. With invasion of adjacent structures.
NX - The regional nodal status cannot be assessed accurately.
NO - No clinically positive nodes.
N1 - Single, ipsilateral, bilateral positive lymph node less than or equal to 3cm in its maximum dimension.
N2 - Metastasis in ipsilateral, bilateral or contra lateral node.
N2a - single ipsilateral clinically positive node more than 3cm but not greater than 6 cm in the maximum dimension.
N2b - Multiple, ipsilateral, clinically positive nodes not greater than 6 cm in the maximum dimension.
N2c - Bilateral or Contralateral nodes of size not greater than 6 cm.
N3a - Ipsilateral node greater than 6 cm.
N3b - Bilateral nodes greater than 6 cm.
Mo - No known metastasis
M1- Metastasis present
 

Stagewise distribution is as follows:

Stage I   

T1 N0 M0

Stage II -      

T2 No M0

Stage III -           

T3 No M0 or T1 -T3 N1 M0

Stage IV - IV A

T4 No - M0. Any T N2 Mo

IV B -                               

Any T N3 M0

IVC-     

Any T Any N M1 1

Table 1


Cancers of head & neck are one of the most prevalent cancers and amongst the most common causes of death. Therefore, every effort should be made to find all primary sites before treatment of the index tumor is begun.

Investigations carried out for treatment may include:
 
  • Plain X-rays and panoramic views of the mandible.
  • CT Scan
  • MRI
  • Bone Scan (Tc 99)
  • PET Scan
  • Biopsy of primary tumor.

Radiotherapy doses are precisely divided to treat various types of carcinomas. Carcinomas of following sites of head and neck can be treated by radiotherapy as per required doses eliminating hazards of it, as possible.

Buccal Mucosa4,51

Radiation therapy will result in high cure rate for the localized T1 or T2 lesion. Interstitial implants are difficult in these regions, so radiotherapy is satisfactory choice for early tumors of buccal mucosa. The effective dose is between 60 Gy and 65 Gy. For the larger T3 lesions, where neck is not involved, external Radiotherapy dose of 45-50 Gy combined with interstitial post dose of 20-25 Gy. The external radiotherapy is delivered by 2 lateral fields covering the entire buccal mucosa up to the zygoma level and lower margin is up to the clavicle below. If preoperative radiotherapy is given then dose should be 40-45 Gy. The postoperative dose is delivered 4-6 weeks after surgery and a dose of 56-60 Gy can be administered over 51/2 to 6 weeks. Survival with radiotherapy and surgery is identical which ranges between 35% -45%.

1. Tongue 4,52

Radiation therapy is an alternative to surgery in early and intermediate size tumors of the anterior tongue.Early lesions (T1 and T2) are managed equally effectively by radiotherapy. Radiotherapy is an inferior choice to surgery for the larger tumors (T3 and T4) and radio therapeutic control in advanced tongue lesions are distinctly poor.

External radiotherapy or interstitial brachytherapy is used, but interstitial implantations are preferred choice. For interstitial brachytherapy alone a dose of 65 Gy to 70 Gy is preferable. Radium or Cesium needles were used in earlier years, but more recently, Iridium 192 wires or seeds are utilized.38 External radiotherapy dose of 45 Gy over 41/2 weeks to the primary plus mid-neck, followed by 20-25 Gy interstitial radiotherapy is the recommended schedule. Early exophytic T3 lesions with N0 status can also be treated selectively by the combinations of external irradiation and brachytherapy. The dose schedules as above, but a large dose of 30Gy is delivered by an implant.

The treatment for large T3 and T4 should be primary surgery followed by postoperative radiotherapy to the tumor and neck. Single modality treatment should be discouraged in stage III and IV diseases of the anterior tongue. In advanced inoperable disease, palliative radiotherapy to a dose of 20 Gy-30 Gy in 5-10 fractions is prescribed.

Both surgery and radiotherapy produce similar local control for TI and T2 Tumors approximately 80% for TI & 60%-65% for T2 lesions. The stage III and IV disease in oral tongue shows a poorer survival of 30% and 15 % respectively at 5 years. The combined surgery and radiotherapy can result in a 5-year survival of 35% or more for the stage II and IV tumors.

2. Floor of Mouth 4

Carcinoma of the floor of mouth is the second most common site of oral cancers next to anterior tongue. More cancer occurs in the anterior than the posterior half of U shaped region. As the lesion spreads peripherally, it can invade the gingiva and mandible and the deep infiltration causes indurations of the muscle, salivary gland and skin in the submandibular area. Early tumors (T1 and T2) which do not involve the mandible or deep muscles are suitable for radiotherapy as functional outcome of radiotherapy is superior to other treatment modalities.

External radiotherapy & Iridium 192 brachytherapy can give excellent results. The primary site plus entire cervical chain are treated by parallel opposed lateral fields to a dose of 50Gy in 25 fractions subsequent to that, after a 2-4 weeks gap, an implant boost dose of 20-25 Gy is delivered. More advanced lesions are treated by combined surgery and postoperative radiotherapy. The postoperative dose is 55-60 Gy over 1/2 - 6 weeks. Those tumors unsuitable for surgical resection are treated by palliative radiotherapy alone. Palliative dose is between 20-30 Gy in 5-10 fractions. Palliative chemotherapy is prescribed to the patients who have a good expectancy of life.

The treatment outcome for floor of mouth carcinoma is better, than that of carcinoma of anterior tongue. The local control with surgery or radiotherapy is around 90% for the TI and 70% for the T2 tumors. The overall 5-year survival rates with radiotherapy showed, 71%, 42% and 36% for TI and T2, T3 tumors respectively. The interstitial brachytherapy in combinations with external radiotherapy improves the local control, as compared to the external radiotherapy alone. The control of T4 disease is 20% or less. The overall 5 year survival of all stages of floor of mouth cancer is around 50% to 60%. Bone or soft tissue necrosis is seen in approximately 10% -15% of patients treated by definitive radiotherapy.

3. Alveolus and Hard Palate4,51

Lesions of lower alveolus require careful and accurate assessment of mandible involvement both by clinical and radiological means. The result of radiotherapy alone for carcinoma of the lower alveolus is inferior to those for other sites of oral cavity. The surgical modality is preferred over radiation therapy for all stages of alveolar tumors. In general, external radiotherapy is unsuitable when bone is involved and interstitial brachytherapy is technically impossible even when the lesions are small. The only patients who should be treated by radical radiotherapy are those who have small lesions but are unfit for surgery. The treatment is planned by the wedge pair technique, and a total dose of 60-65 Gy is delivered to the mandible.

With radiotherapy alone local control rates of 32% and 60% at 2 years were achieved for patients with or without bone involvement. The tumors of the hard palate and upper alveolus are grouped together for the clinical assessment and management. Radical radiotherapy is practiced very selectively for hard palate carcinomas. Lesions smaller than 2cm can be treated by radical dose of 60-65 Gy. Elective neck irradiation is not indicated since the incidence of occult node metastases is low (less than 15%). Neck dissection is always combined with primary surgery for the N+ status. The overall 5 year disease free survival rates, as achieved in various stages, are 75% for stage I, 46% for stage II, 36% for stage III, and 11% for stage IV hard palate tumors.

4. Retromolar Triangle 4

Retro molar trigone is the anterior mucosal surface of the ascending ramus, and roughly appears as a triangle with its base being behind the 3rd molar tooth and the apex extending up to the maxillary tubercle. It is important to appreciate that tumors arising in this location can spread to involve adjacent areas such as the pterygo- palatine fossa, the cheek, the tonsil, the floor of mouth and the tongue. Therefore, the radiotherapeutic approach for tumors of the retromolartrigone should be prescribed with fair amount of caution.

The primary tumor should be assessed carefully by clinical and radiological means, including CT scan if radical radiotherapy is contemplated. In small and superficial tumors the antero-lateral wedge pair technique is used. The treatment volume must include pterygo-mandibular space. Radical dose up to 65 Gy is advocated for the TI & Ti lesions. Radio- therapeutic control is around 70% for T1and 50% for T2 lesions. Approximately 30% of patients may present with nodal disease and the neck node management is included into primary surgery or radical irradiation. The stage III and IV disease are treated by surgery and postoperative radiotherapy, although the 5-yerar cure rate is less than 30%.

5. Carcinoma of the Lip 4

The tumors of the lip commonly arise from the vermillion border of the lower lip, less occasionally in 10-15% cases, tumor arises from the oral commissural area, and rarely in 5% of cases from the upper lip. Most of the lesions are squamous cell carcinoma. The lateral spread is the usual growth pattern, although deeper infiltration can invade the mandible and soft tissues. The lower lip has a large lymphatic network that drains into the submandibular and submental lymph nodes. The bone involvement and lymph nodes metastases are poor prognostic factors in lip cancer. Majority of the lesions are ulcerative squamous type, but occasionally a verrucous carcinoma may be present. The patient does not require too many investigations. A biopsy and X-ray of the mandible are the mandatory tests.

Surgery and radiotherapy are equally effective for early T1 and T2 tumors. The primary radiotherapy is possible for early T1 or T2 tumors, which includes interstitial brachytherapy alone in a dose of 60-65 Gy. Alternatively, electron beam therapy can deliver a similar dose over 6 week’s period. Care must be taken to protect the inner structures by lead cutout, inserted just behind the lip. The larger T3 and T4 lesions and N+ve disease are treated by primary surgery and postoperative radiotherapy. The recurrence following radiotherapy or surgery is very low for the early lesions, and the 5-year cure rate is around 90%. In large T3 and T4 tumors, the curability is below 60% and when histological positive nodes are present, the 5 year cure falls below 30%.

6. Cancer of Oropharynx 4

Primarily it includes, base of tongue, vallecula and lingual surface of epiglottis, tonsillar region, soft palate and uvula, and oropharyngeal walls. More than 90% of the neoplasms are of squamous cell origin. The primary management for majority of the oropharyngeal cancer patient is dependent upon radiation therapy.

7. Ca Tonsil 4

Early T1 and T2 lesions are generally treated by irradiations alone. Advantages of radiotherapy in early tumors include,
 
  1. Cosmetic as well as functional preservation.
  2. Irradiations can be applied to the ipsilateral and contra lateral aspects of neck.

Late T2, T3 and T4: curative Radiotherapy with or without neck dissection may be the treatment policy, and surgery for the primary tumor is reserved for failure cases. Local failure with radiotherapy is 20% for T2 lesions, 30-50% for T3 and more than 50% for T4 tumor. Cobalt-60 or 4 to 6 MV linear accelerator beam energy is considered suitable for the treatment.

Three field technique i.e. two lateral parallel opposed portals or two lateral portals opposed with one anterior portal for the lower neck can be used. In a very small localized lesion in the tonsil or tonsillar pillars (with NO neck), Cobalt-60 wedge pair oblique portals can be given up to the curative doses of 65 to 70 Gy. Tonsil is behind the mandible, therefore the dose calculations are to be done at 1 to 1.5cm depth. In this situation, the ipsilateral neck is treated by a separate field up to 50Gy. This can reduce the risk of Xerostomia. Stage wise dose recommendations are: TI 65 Gy, T2 65-70 Gy, T3 and T4 70 to 75Gy. For neck - N0 neck must receive 45-50 Gy, N1, N2- 60-65 Gy and N3 upto 70 Gy.

Interstitial radiotherapy -

It is used primarily as a boost procedure especially in T1, T2 and early T3 lesions. The advantages of this therapy are that higher doses up to 70-80 Gy when required can be delivered to the fossa and since the contribution from the external irradiation is lower, the incidence of Xerostomia and Osteoradionecrosis are reduced.

Radiation therapy provides excellent tumor control, of 90% or more in TI and in between 75% to 85% in T2. In the more advanced T3 and T4 lesions, the radiotherapeutic control rates are between 55% -70% for T3 approximately 40% for T4 tumors. The 5-year overall survivals are approximately 60% - 80% for T1 and T2, for T3 this ranges between 45% and 70% and T4 disease shows poor 5 year survival of 25 % or less.

8. Soft palate and Posterior pharyngeal wall 4

These cancers are less common than other oropharyngeal neoplasm. Due to the anatomic limitations of these tumors, surgery is not commonly practiced. On the other hand, radiation therapy has proven to be highly successful, especially where the lesions are small in volume. The radiotherapy is delivered with a curative intent in T1, T2 and T3 tumors. The palliative radiotherapy (20-30Gy) is applied to advanced T4 lesions.

9. Carcinoma Larynx 4

Irradiation technique schedule
 
  • For early glottis cancers - The radiation is delivered by either a cobalt 60 or 4-6 MV linear accelerator. The T1 lesion is treated to a dose of 5600 cGy in 28 fractions over 5 1/2 weeks. Larynx is irradiated to doses between 65-70 Gy in 6-7 weeks for the T1 and T2 lesions. The dose per fraction should be 200 cGy -225 cGy. Because the diameter of the larynx is less anteriorly than posteriorly, anterior commissure receives 15 to 20% greater dose than the posterior part of larynx. A homogeneous dose distribution is achieved by open fields in the beginning of treatment and wedge fields in the latter half of the treatment.

  • For T3 & T4 lesions- Subdigastric, midjugular, lower jugular lymph nodes and primary tumor have to be included into the treatment volume. Dose per fraction is 200 cGy. A total of 70 Gy is delivered. Lateral opposed fields are used for this definitive irradiation. The dose varies between 55 Gy to 60 Gy and the sites of positive margins and extracapsular spread may be boosted upto 63 Gy. The dose per fractions is between 180 cGy to 200 cGy. An altered fractionation regime in the form of hyperfractionation with twice a day dose of 120 cGy per fraction has also been attempted. The total dose in hyper fractionated regimen is between 70-76.8Gy.

11. CaHypopharynx4,

Hypo pharyngeal cancer is lower in incidence as compared to the laryngeal cancers. Approximately 70% of hypo pharyngeal lesions occur in the pyriform sinuses and the remaining 20% to 30% occur on the pharyngeal wall and in the postcricoid area. These tumors may spread submucosally and involve the recurrent laryngeal nerve, causing a unilateral vocal cord paralysis.

When the treatment is delivered by radiotherapy alone, a dose of 66Gy in 33 fractions over 61/2 weeks is necessary for T1 - T2 lesions. In T3 tumors treated radically, the required dose is 70Gy over 7 weeks. Postoperative radiotherapy is delivered by a fraction size of 1.8 Gy - 2 Gy. The elderly patients will tolerate the radiation course well if the dose per fraction is kept at 180 cGy. The entire treatment volume should receive a dose of 56 Gy in 28 fractions over 5 1/2 weeks.

The high risk sites are given a boost dose of 8-10 Gy in 4-5 fractions. Preoperative radiotherapy is less commonly practiced. A dose of 45 Gy – 50 Gy is delivered over 41/2 -5 week’s period. In the incurable advanced cancers of the hypo-pharynx, palliative radiotherapy is delivered for achieving growth restraint and relief from pain, dysphasia and fungation. The palliative dose commonly practiced is around 30-40Gy in 10-20 fractions over 2-4 weeks.

12. Ca Maxillary Sinus and other air sinuses 4

A wide variety of benign and malignant tumors affect the Para nasal sinuses. Approximately one-half of the para nasal sinus neoplasms are benign. The most common malignant tumor is squamous cell carcinoma. For maxillary sinus radiation therapy alone is used for a rare T1 and T2 tumors and a dose of 55 Gy-65 Gy is delivered over 5.5-6.5 week period. The routine radiotherapy practice involves preoperative irradiation since majority of the patients present with T3 or T4 lesions. Preoperative radiotherapy is practiced in cases showing anterior soft tissue and skin infiltration, pterygopalatine invasion and minimal invasion into the periorbital region. Preoperative doses are usually limited to 45 - 50 Gy over 5- week’s period since larger doses can increase the postoperative complications. The 5-year survival with combined treatment with the preoperative or postoperative dose of 50-65 Gy ranges from 35% to 65%.

13. Ca External auditory meatus 4

Carcinomas of external auditory meatus and middle ear are rare in occurrence and constitute less than 0.5% of all head & neck cancers. Radiation therapy is frequently used after local excision for the early and moderate size tumors. The radiotherapeutic aim is curative in nature. The value of postoperative radiotherapy is its ability to reduce the local recurrence rates following surgery. The unresectable advanced tumors which generally show a widespread local disease, with or without nodal metastases are treated by a short course of palliative radiotherapy.

14. Radiotherapy for thyroid and nasopharyngeal carcinomas 53,54,55

The ideal dose of radiation is that which reliably eradicates all tumor but does not result in normal tissue damage. Thyroid cancer is only moderately radio responsive but with high dose treatment, local control and survival can be improved. External beam therapy has a role in each histologic type of thyroid cancer. Intracavitary radiotherapy is conceptually attractive method of boosting dose to nasopharynx cancer while sparing sensitive normal tissue. Limitation of this method is restriction of its utilization to small volume primary disease. Treatment of nasopharyngeal and maxillary malignancies gave maximum doses to cornea. Radiotherapy is an effective modality of treatment for extramedullaryplasmacytoma like extensive tumor of nasopharynx which did not respond to chemotherapy.

Refrences
 
  1. Greenberg MS, Glick M. In: Burket’s Oral Medicine, Diagnosis and Treatment, 10th edition. Elsevier, 2006; pp194-234.
  2. Rhodus NL. Oral Cancer: leukoplakia and squamous cell carcinoma. Dent Clin N Am 2005;49:143-165.
  3. Zini A, Czerninski R, Harold D, Cohen S. Oral cancer over four decades:epidemiology, trends, histology, and survival by anatomical sites. J Oral Pathol Med 2010; 39:299-305.
  4. Mohanty BK, Bahadur S, Lal P, Garola M, Rath GK. In: Textbook of Radiation Oncology– Principles and Practice, 1st edition. BI Churchill Livingston, 2000; pp131- 187.
  5. Wong J, Breen D, Balogh J, Czarnota GJ, Kamra J, Barnes EA. Treating recurrent cases of squamous cell carcinoma with radiotherapy. CurrOncol 2008;15(5):229-233.
  6. R Yoshimura. Interstitial treatment for bilateral tongue cancer, Br Dent J, 1999:809-814.
  7. Harmer C, Bidmaed M, Shephard S. Radiotherapy planning techniques for thyroid cancer. Br J Radiol 1998;71:1069-1075.
  8. Slevein NJ, Wilkinson JM. Intracavitory Radiotherapy for nasopharynx cancer.Br J Radiol 1997;70:412-414.
  9. Jyotirmayl R, Gangadharan VP, Nair MK. Radiotherapy in the treatment of solitary plasmacytoma. Br J Radiol 1997;70:511-516.

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