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Oropharyngeal cancer


Table of Contents

GENERAL INFORMATION
CELLULAR CLASSIFICATION
STAGE INFORMATION
TNM definitions
AJCC stage groupings
Stage 0
Stage I
Stage II
Stage III
Stage IVA
Stage IVB
Stage IVC
TREATMENT OPTION OVERVIEW
STAGE I OROPHARYNGEAL CANCER
STAGE II OROPHARYNGEAL CANCER
STAGE III OROPHARYNGEAL CANCER
STAGE IV OROPHARYNGEAL CANCER
Resectable
Unresectable
RECURRENT OROPHARYNGEAL CANCER

GENERAL INFORMATION

Patients with carcinoma of the head and neck require a careful work-up and a multidisciplinary team approach to determine an optimal management. The multidisciplinary team includes a head and neck surgeon, radiation oncologist, medical oncologist, dentist, and social services.

Careful endoscopy under general anesthesia with mapping of the lesion using the written word and specific diagrams is indicated. Biopsy and histopathologic confirmation of the lesion as cancer is mandatory. Esophagoscopy is carried out together with laryngoscopy during evaluation of the oral cavity and pharynx. This is done because there is approximately a 10% to 15% incidence of synchronous primary tumors in the head and neck occurring at the same time as the presenting primary tumor. The esophagus is the most frequent site where subclinical second primary tumors are discovered. Bronchoscopy is not as productive as chest x-ray in defining a second primary tumor and thus is not mandatory. In the oral cavity, lesions are tattooed using India ink. This will facilitate later surgical procedures, particularly when cytoreduction occurs as a result of adjuvant radiation therapy or chemotherapy. Neither the liver/spleen scan nor the bone scan has been found to be of significant diagnostic value in the evaluation of patients with head and neck cancer. Magnetic resonance imaging is often more useful than computed tomographic (CT) scans in delineating the extent of the primary tumor and metastasis to lymph nodes. Other diagnostic evaluation besides the panendoscopy includes CT scan, angiography, Cine pharyngoesophagogram, and other modalities to be used as indicated.[1,2]

As a general rule for prognosis, as one proceeds anatomically from the lips posteriorly to the hypopharynx, the prognosis decreases. More important, however, is the relationship of cure rates to the size of the initial tumor burden. Tumor thickness correlates with lymph node metastases; increasing tumor thickness is associated with a decrease in survival.[3] Advanced cancers carry a very poor prognosis, with cure rates as low as 10% to 15% despite the modality or combination of modalities used.

Most treatment failures occur within the first years following definitive therapy. For this reason, patient follow-up must be frequent and careful during this period. Twenty percent to 30% of head and neck cancer patients develop second primary cancers in the upper aerodigestive tract. A study has shown that daily treatment of these patients with moderate doses of isotretinoin (13-cis-retinoic acid) for 1 year can significantly reduce the incidence of second tumors.[4] No survival advantage was demonstrated.[5,6]

There is a paucity of well designed and controlled prospective studies comparing treatment modalities in patients with head and neck cancer. Therefore, it is difficult to unequivocally state the ideal therapy for a specific site or stage of cancer originating in the head and neck. In general it can be said that stage I and stage II cancers respond equally well to radiation or surgery. The preferred treatment is based on the skills of the treating physician, the needs of the patient, and, most importantly, the treatment that causes the least functional disability. For stage I and II tumors of the base of the tongue, surgery plus radiation therapy or external radiation therapy plus implantation may give better control than external radiation therapy alone.[7] Stage III and operable stage IV cancers are most commonly managed with a combination of radiation therapy and surgery.

Most often the radiation therapy is used postoperatively. Advanced inoperable patients are frequently palliated with radiation therapy. Patients with stage III and advanced resectable stage IV cancer should be considered for chemotherapy clinical trials. Also, patients with advanced nonresectable stage IV cancers should be considered for ongoing clinical trials involving chemotherapy with radiation or radiosensitizers with radiation.[7]

Tumors of the head and neck have been clearly related to tobacco consumption, heavy ingestion of alcohol, and the use of chewing tobacco. Poor oral hygiene, mechanical irritation, and the Plummer-Vinson syndrome have been implicated in the etiology of head and neck cancer. A case-control study has found that use of mouthwash with high alcohol content is associated with a 40% to 60% increase in oropharyngeal malignancy after correction for known etiologic factors.[8] This topic has been reviewed.[9]

References:

  1. McGuirt WF: Panendoscopy as a screening examination for simultaneous primary tumors in head and neck cancer: a prospective sequential study and review of the literature. Laryngoscope 92(5): 569-576, 1982.

  2. National Institutes of Health: National Institutes of Health Consensus Development Conference: magnetic resonance imaging. Journal of the American Medical Association 259(14): 2132-2138, 1988.

  3. Baredes S, Leeman DJ, Chen TS, et al.: Significance of tumor thickness in soft palate carcinoma. Laryngoscope 103(4, Part 1): 389-393, 1993.

  4. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. New England Journal of Medicine 323(12): 795-801, 1990.

  5. Fitzpatrick PJ, Tepperman BS, Deboer G: Multiple primary squamous cell carcinomas in the upper digestive tract. International Journal of Radiation Oncology, Biology, Physics 10(12): 2273-2279, 1984.

  6. Black RJ, Gluckman JL, Shumrick DA: Multiple primary tumors of the upper aerodigestive tract. Clinical Otolaryngology and Allied Sciences 8(4): 277-281, 1983.

  7. Housset M, Baillet F, Dessard-Diana B, et al.: A retrospective study of three treatment techniques for T1-T2 base of tongue lesions: surgery plus postoperative radiation, external radiation plus interstitial implantation and external radiation alone. International Journal of Radiation Oncology, Biology, Physics 13(4): 511-516, 1987.

  8. Winn DM, Blot WJ, McLaughlin JK, et al.: Mouthwash use and oral conditions in the risk of oral and pharyngeal cancer. Cancer Research 51(11): 3044-3047, 1991.

  9. Spitz MR: Epidemiology and risk factors for head and neck cancer. Seminars in Oncology 21(3): 281-288, 1994.


CELLULAR CLASSIFICATION

Most head and neck cancers are of the squamous cell variety and may be preceded by various precancerous lesions. Minor salivary gland tumors are not uncommon in these sites. Specimens removed from the lesions may show the carcinomas to be noninvasive, in which case the term "carcinoma-in-situ" is applied. An invasive carcinoma will be either well-differentiated, poorly differentiated, or undifferentiated. Tumor grading is recommended using Broder's classification (Tumor Grade [G]):

G1: well-differentiated
G2: moderately well-differentiated
G3: poorly differentiated
G4: very poorly differentiated

Although the grade of the tumor does not enter into staging of the tumor, it should be recorded. However, vascular invasion is a poor prognostic factor.[1]

There is no statistically significant correlation between the degree of differentiation and the biologic behavior of the cancer.

Other tumors of glandular epithelium, odontogenic apparatus, lymphoid tissue, soft tissue, and bone and cartilage origin require special consideration and are not to be included. Reference to the World Health Organization (WHO) nomenclature is recommended.

The term "leukoplakia" should be used only as a clinically descriptive term meaning that the observer sees a white patch that does not rub off, the significance of which depends on the histologic findings. It can range from hyperkeratosis to an actual early invasive carcinoma or may represent only a fungal infection, lichen planus, or other benign oral disease.

References:

  1. Close LG, Brown PM, Vuitch MF, et al: Microvascular invasion and survival in cancer of the oral cavity and oropharynx. Archives of Otolaryngology, Head and Neck Surgery 115(11): 1304-1309, 1989.


STAGE INFORMATION

The staging systems are all clinical staging, based on the best possible estimate of the extent of disease before treatment. The assessment of the primary tumor is based on inspection and palpation when possible, and by both indirect mirror examination and direct endoscopy. The tumor must be confirmed histologically, and any other pathologic data obtained on biopsy may be included. The appropriate nodal drainage areas are examined by careful palpation. If a patient relapses, complete restaging must be done to select the appropriate additional therapy. Information from diagnostic imaging studies may be used in staging. Magnetic resonance imaging offers an advantage over computed tomographic scans in the detection and localization of head and neck tumors and the distinction of lymph nodes from blood vessels.[1]

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification.[2]


TNM definitions

Primary tumor (T)

TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor 2 cm or less in greatest dimension
T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension
T3: Tumor more than 4 cm in greatest dimension
T4: Tumor invades adjacent structures (e.g., pterygoid muscle[s], mandible,
hard palate, deep muscle of tongue, larynx)

Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest
dimension
N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not
more than 6 cm in greatest dimension, or in multiple ipsilateral lymph
nodes, none more than 6 cm in greatest dimension, or in bilateral or
contralateral lymph nodes, none more than 6 cm in greatest dimension
N2a: Metastasis in a single ipsilateral lymph node more than 3 cm but
not more than 6 cm in greatest dimension
N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6
cm in greatest dimension
N2c: Metastasis in bilateral or contralateral lymph nodes, none more
than 6 cm in greatest dimension
N3: Metastasis in a lymph node more than 6 cm in greatest dimension

In clinical evaluation, the actual size of the nodal mass should be measured, and allowance should be made for intervening soft tissues. Most masses larger than 3 centimeters in diameter are not single nodes but confluent nodes or tumors in soft tissues of the neck. There are three stages of clinically positive nodes: N1, N2, and N3. The use of subgroups a, b, and c is not required but recommended. Midline nodes are considered homolateral nodes.

Distant metastasis (M)

MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis


AJCC stage groupings


Stage 0

Tis, N0, M0


Stage I

T1, N0, M0


Stage II

T2, N0, M0


Stage III

T3, N0, M0
T1, N1, M0
T2, N1, M0
T3, N1, M0


Stage IVA

T4, N0, M0
T4, N1, M0
Any T, N2, M0


Stage IVB

Any T, N3, M0


Stage IVC

Any T, Any N, M1

References:

  1. National Institutes of Health: National Institutes of Health Consensus Development Conference: magnetic resonance imaging. Journal of the American Medical Association 259(14): 2132-2138, 1988.

  2. Pharynx (including base of tongue, soft palate, and uvula). In: American Joint Committee on Cancer: AJCC Cancer Staging Manual. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 31-40.


TREATMENT OPTION OVERVIEW

The oropharynx begins anteriorly where the oral cavity stops. It extends from the plane of the hard palate superiorly to the plane of the hyoid bone inferiorly. The lateral wall is comprised primarily of the tonsils and tonsillar fossa, the anterior and posterior tonsillar pillars, and the lateral pharyngeal wall. Posteriorly, it is bound by the pharyngeal wall mucosa, which extends from the superior to the inferior limits described above. Subdivisions of the oropharynx include the tongue base (including the pharyngoepiglottic and glossoepiglottic folds and the vallecula), the faucial arch (including the soft palate, uvula, and anterior tonsillar pillar), the tonsil and tonsillar fossa, and the pharyngeal wall (including the posterior tonsillar pillar, the lateral and posterior pharyngeal walls).

On attempting to define the optimal therapeutic approach to the oropharynx, it becomes clear that no single therapeutic regimen offers a clear-cut superior survival over other regimens. The literature is filled with reports highlighting various therapeutic options but does not contain reports presenting any valid comparative studies of therapeutic options. The ultimate therapeutic choice will depend on a careful review of each individual case, paying attention to the staging of the neoplasm, the general physical condition of the patient, the emotional status of the patient, the experience of the treating team, and the available treatment facilities.

A review of published clinical results of radical radiation therapy for head and neck cancer suggests a significant loss of local control when the administration of radiation therapy was prolonged; therefore, lengthening of standard treatment schedules should be avoided whenever possible.[1] Patients who smoke during treatment with radiation therapy appear to have lower response rates and shorter survival durations than those who do not;[2] therefore, patients should be counseled to stop smoking before beginning radiation therapy. The post-therapy performance status of patients with base of tongue primary tumors appears to be better following radiation therapy than following surgery. Local control and survival is similar in both, suggesting that radiation therapy may be superior.[3]

Accumulating evidence has demonstrated a high incidence (>30%-40%) of hypothyroidism in patients who have received external-beam irradiation to the entire thyroid gland or to the pituitary gland. Thyroid function testing of patients should be considered prior to therapy and as part of post-treatment follow-up.[4,5]

The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.

References:

  1. Fowler JF, Lindstrom MJ: Loss of local control with prolongation in radiotherapy. International Journal of Radiation Oncology, Biology, Physics 23(2): 457-467, 1992.

  2. Browman GP, Wong G, Hodson I, et al.: Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. New England Journal of Medicine 328(3): 159-163, 1993.

  3. Harrison LB, Zelefsky MJ, Armstrong JG, et al.: Performance status after treatment for squamous cell cancer of the base of tongue - a comparison of primary radiation therapy versus primary surgery. International Journal of Radiation Oncology, Biology, Physics 30(4): 953-957, 1994.

  4. Turner SL, Tiver KW, Boyages SC: Thyroid dysfunction following radiotherapy for head and neck cancer. International Journal of Radiation Oncology, Biology, Physics 31(2): 279-283, 1995.

  5. Constine LS: What else don't we know about the late effects of radiation in patients treated for head and neck cancer? International Journal of Radiation Oncology, Biology, Physics 31(2): 427-429, 1995.


STAGE I OROPHARYNGEAL CANCER

When radiation is given, careful choice of radiation technique by a radiation oncologist experienced in managing head and neck cancers is essential. The choice of treatment is dictated by the anticipated functional, cosmetic, and socioeconomic results of the treatment options as well as by the available expertise of the surgeon or radiotherapist. Treatment is individualized for each patient.

Treatment options:

Standard:

Surgery or radiation are equally successful in controlling this stage of
oropharyngeal cancer.
1. Surgery may be the preferred modality where the functional deficit will be minimal, such as tonsil pillar.

2. Radiation may be the preferred modality where the functional deficit will be great, such as the tongue base.

Under clinical evaluation:
Radiation clinical trials evaluating hyperfractionation schedules should be
considered. Mohs' micrographic surgery to determine free surgical margins
is under evaluation.[1] In nonrandomized studies, patients whose primary
tumors were treated with this technique in conjunction with postoperative
radiation therapy had higher disease-free interval rates compared with
historical controls.

References:

  1. Davidson TM, Haghighi P, Astarita R, et al: MOHS for head and neck mucosal cancer: report on 111 patients. Laryngoscope 98(10): 1078-1083, 1988.


STAGE II OROPHARYNGEAL CANCER

When radiation is given, careful choice of radiation technique by a radiation oncologist experienced in managing head and neck cancers is essential. Interstitial radiation techniques may be used when indicated. The choice of treatment is dictated by the anticipated functional, cosmetic, and socioeconomic results of the treatment options as well as by the available expertise of the surgeon or radiotherapist. Treatment is individualized for each patient.

Treatment options:

Standard:

Surgery or radiation are equally successful in controlling this stage of
oropharyngeal cancer.
1. Surgery may be the preferred modality where the functional deficit will be minimal, such as tonsil pillar.

2. Radiation may be the preferred modality where the functional deficit will be great, such as the tongue base.

Under clinical evaluation:
1. Radiation clinical trials evaluating hyperfractionation schedules and/or brachytherapy.

2. Mohs' micrographic surgery to determine free surgical margins.[1] In nonrandomized studies, patients whose primary tumors were treated with this technique in conjunction with postoperative radiation therapy had higher disease-free interval rates compared with historical controls.

3. Isotretinoin (13-cis-retinoic acid) daily for a year to prevent development of second upper aerodigestive tract primaries.[2]

References:

  1. Davidson TM, Haghighi P, Astarita R, et al: MOHS for head and neck mucosal cancer: report on 111 patients. Laryngoscope 98(10): 1078-1083, 1988.

  2. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. New England Journal of Medicine 323(12): 795-801, 1990.


STAGE III OROPHARYNGEAL CANCER

The management of stage III carcinomas of the oropharynx is complex and requires multidisciplinary input to establish the optimal treatment. New surgical techniques for resection and reconstruction that provide access and at least partial function restoration developed in the last 7 to 10 years have extended the surgical options. External-beam radiation therapy augmented with interstitial implantation and multiple daily treatment schemes have given new insights into the use of radiation for this group of tumors.[1] All of these patients may be considered for entry into neoadjuvant chemotherapy trials.

In general, the preferred treatment has been to combine surgery with postoperative radiation therapy where possible.[2] This approach has become the standard in this specific grouping whenever it can be applied.

It should be noted that specific surgical procedures and their modifications are not specifically designated here because there is a wide variety of surgical approaches to the area, the opinion as to the role of modified neck dissections varies from center to center, and there are multiple reconstructive techniques that may give the same results. This group of patients should be managed by surgeons skilled in the multiple procedures available and who are actively and frequently involved in the care of these patients.

Treatment options:

Standard:

A combination of surgery with postoperative radiation therapy.[2]

Under clinical evaluation:
1. Neoadjuvant chemotherapy as given in clinical trials has been used to shrink tumors and thereby render them more definitively treatable with either surgery or radiation. Chemotherapy is given prior to the other modalities, hence the designation neoadjuvant to distinguish it from standard adjuvant therapy, which is given after or during definitive therapy with radiation or after surgery. Many drug combinations have been used in neoadjuvant chemotherapy.[3-7]

2. Chemotherapy has been combined with radiation therapy in patients who have locally advanced disease that is surgically unresectable.[8-13] The best chemotherapy to use and the appropriate way to integrate the two modalities is still unresolved.[14]

Similar approaches in patients with resectable disease, where resection would lead to a major functional deficit, are also being explored in randomized trials but cannot be recommended at this time as standard.

3. Radiation clinical trials evaluating hyperfractionation schedules and/or brachytherapy should be considered.[15]

4. Isotretinoin (13-cis-retinoic acid) daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[16]

References:

  1. Puthawala AA, Syed AM, Eads DL, et al.: Limited external beam and interstitial 192 iridium irradiation in the treatment of carcinoma of the base of the tongue: a ten year experience. International Journal of Radiation Oncology, Biology, Physics 14(5): 839-848, 1988.

  2. Tupchong L, Phil D, Scott CB, et al.: Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03. International Journal of Radiation Oncology, Biology, Physics 20(1): 21-28, 1991.

  3. Al-Kourainy K, Kish J, Ensley J, et al.: Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer. Cancer 59(2): 233-238, 1987.

  4. Stupp R, Weichselbaum RR, Vokes EE: Combined modality therapy of head and neck cancer. Seminars in Oncology 21(3): 349-358, 1994.

  5. Ensley J, Crissman J, Kish J, et al.: The impact of conventional morphologic analysis on response rates and survival in patients with advanced head and neck cancers treated initially with cisplatin-containing combination chemotherapy. Cancer 57(4): 711-717, 1986.

  6. Pfister DG, Harrison LB, Strong EW, et al.: Organ-function preservation in advanced oropharynx cancer: results with induction chemotherapy and radiation. Journal of Clinical Oncology 13(3): 671-680, 1995.

  7. Dimery IW, Hong WK: Overview of combined modality therapies for head and neck cancer. Journal of the National Cancer Institute 85(2): 95-111, 1993.

  8. Al-Sarraf M, Pajak TF, Marcial VA, et al.: Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck: an RTOG study. Cancer 59(2): 259-265, 1987.

  9. Bachaud J, David J, Boussin G, et al.: Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. International Journal of Radiation Oncology, Biology, Physics 20(2): 243-246, 1991.

  10. Merlano M, Corvo R, Margarino G, et al.: Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck: the final report of a randomized trial. Cancer 67(4): 915-921, 1991.

  11. Browman GP, Cripps C, Hodson DI, et al.: Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer. Journal of Clinical Oncology 12(12): 2648-2653, 1994.

  12. Merlano M, Benasso M, Corvo R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. Journal of the National Cancer Institute 88(9): 583-589, 1996.

  13. Jeremic B, Shibamoto Y, Stanisavljevic B, et al.: Radiation therapy alone or with concurrent low-dose daily either cisplatin or carboplatin in locally advanced unresectable squamous cell carcinoma of the head and neck: a prospective randomized trial. Radiotherapy and Oncology 43(1): 29-37, 1997.

  14. Taylor SG, Murthy AK, Vannetzel JM, et al.: Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. Journal of Clinical Oncology 12(2): 385-395, 1994.

  15. Cox JD, Pajak TF, Marcial VA, et al.: Dose-response for local control with hyperfractionated radiation therapy in advanced carcinomas of the upper aerodigestive tracts: preliminary report of Radiation Therapy Oncology Group protocol 83-13. International Journal of Radiation Oncology, Biology, Physics 18(3): 515-521, 1990.

  16. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. New England Journal of Medicine 323(12): 795-801, 1990.


STAGE IV OROPHARYNGEAL CANCER


Resectable

The management of stage IV carcinomas of the oropharynx is complex and requires multidisciplinary input to establish the optimal treatment. New surgical techniques for resection and reconstruction which provide access and at least partial function restoration developed in the last 7 to 10 years have extended the surgical options. External-beam therapy augmented with interstitial implantation and multiple daily treatment schemes have given new insights into the use of radiation for this group of tumors.[1] All of these patients may be considered for entry into neoadjuvant chemotherapy trials.

In general, the preferred treatment has been to combine surgery with postoperative radiation therapy where possible.[2] This approach has become the standard in this specific grouping whenever it can be applied.

It should be noted that specific surgical procedures and their modifications are not specifically designated here as there is a wide variety of surgical approaches to the area, the opinion as to the role of modified neck dissections varies from center to center, and there are multiple reconstructive techniques that may give the same results. This group of patients, when surgically treated, should be managed by surgeons skilled in the multiple procedures available and who are actively and frequently involved in the care of these patients.

Treatment options:

Standard:

A combination of surgery with postoperative radiation therapy.[2]

Under clinical evaluation:
1. Chemotherapy has been combined with radiation therapy in patients who have locally advanced disease that is surgically unresectable.[3-8] The best chemotherapy to use and the appropriate way to integrate the two modalities are still unresolved.[9,10]

Similar approaches in patients with resectable disease, where resection would lead to a major functional deficit, are also being explored in randomized trials but cannot be recommended at this time as standard.

2. Radiation clinical trials evaluating hyperfractionation schedules and/or brachytherapy should be considered.[11]


Unresectable

Treatment options:

Standard:

These patients are candidates for radiation therapy.

Under clinical evaluation:
Neoadjuvant chemotherapy as given in clinical trials has been used to
shrink tumors and thereby render them more definitively treatable with
either surgery or radiation. Many drug combinations have been used in
neoadjuvant chemotherapy.[12-16]

1. Concomitant chemotherapy: chemotherapy with radiation clinical trials as well as with radiosensitizers.[5]

2. Radiation clinical trials evaluating hyperfractionation schedules and/or brachytherapy should be considered.[11]

3. Simultaneous chemotherapy and hyperfractionated radiation therapy.[17]

4. Particle-beam radiation therapy.

5. Hyperthermia combined with radiation therapy.

Post-treatment follow-up:
These patients should have a careful head and neck examination looking for
recurrence monthly for the first post-treatment year, every 2 months for
the second year, every 3 months for the third year, and every 6 months
thereafter. The use of isotretinoin (13-cis-retinoic acid) daily for
1 year to prevent development of second upper aerodigestive tract primary
tumors is under evaluation.[18]

References:

  1. Puthawala AA, Syed AM, Eads DL, et al.: Limited external beam and interstitial 192 iridium irradiation in the treatment of carcinoma of the base of the tongue: a ten year experience. International Journal of Radiation Oncology, Biology, Physics 14(5): 839-848, 1988.

  2. Tupchong L, Phil D, Scott CB, et al.: Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03. International Journal of Radiation Oncology, Biology, Physics 20(1): 21-28, 1991.

  3. Bachaud J, David J, Boussin G, et al.: Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. International Journal of Radiation Oncology, Biology, Physics 20(2): 243-246, 1991.

  4. Merlano M, Corvo R, Margarino G, et al.: Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck: the final report of a randomized trial. Cancer 67(4): 915-921, 1991.

  5. Al-Sarraf M, Pajak TF, Marcial VA, et al.: Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck: an RTOG study. Cancer 59(2): 259-265, 1987.

  6. Browman GP, Cripps C, Hodson DI, et al.: Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer. Journal of Clinical Oncology 12(12): 2648-2653, 1994.

  7. Merlano M, Benasso M, Corvo R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. Journal of the National Cancer Institute 88(9): 583-589, 1996.

  8. Jeremic B, Shibamoto Y, Stanisavljevic B, et al.: Radiation therapy alone or with concurrent low-dose daily either cisplatin or carboplatin in locally advanced unresectable squamous cell carcinoma of the head and neck: a prospective randomized trial. Radiotherapy and Oncology 43(1): 29-37, 1997.

  9. Taylor SG, Murthy AK, Vannetzel JM, et al.: Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. Journal of Clinical Oncology 12(2): 385-395, 1994.

  10. Zakotnik B, Smid L, Budihna M, et al.: Concomitant radiotherapy with mitomycin C and bleomycin compared with radiotherapy alone in inoperable head and neck cancer: final report. International Journal of Radiation Oncology, Biology, Physics 41(5): 1121-1127, 1998.

  11. Cox JD, Pajak TF, Marcial VA, et al.: Dose-response for local control with hyperfractionated radiation therapy in advanced carcinomas of the upper aerodigestive tracts: preliminary report of Radiation Therapy Oncology Group protocol 83-13. International Journal of Radiation Oncology, Biology, Physics 18(3): 515-521, 1990.

  12. Al-Kourainy K, Kish J, Ensley J, et al.: Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer. Cancer 59(2): 233-238, 1987.

  13. Stupp R, Weichselbaum RR, Vokes EE: Combined modality therapy of head and neck cancer. Seminars in Oncology 21(3): 349-358, 1994.

  14. Ensley J, Crissman J, Kish J, et al.: The impact of conventional morphologic analysis on response rates and survival in patients with advanced head and neck cancers treated initially with cisplatin-containing combination chemotherapy. Cancer 57(4): 711-717, 1986.

  15. Pfister DG, Harrison LB, Strong EW, et al.: Organ-function preservation in advanced oropharynx cancer: results with induction chemotherapy and radiation. Journal of Clinical Oncology 13(3): 671-680, 1995.

  16. Dimery IW, Hong WK: Overview of combined modality therapies for head and neck cancer. Journal of the National Cancer Institute 85(2): 95-111, 1993.

  17. Weissler MC, Melin S, Sailer SL, et al.: Simultaneous chemoradiation in the treatment of advanced head and neck cancer. Archives of Otolaryngology, Head and Neck Surgery 118(8): 806-810, 1992.

  18. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. New England Journal of Medicine 323(12): 795-801, 1990.


RECURRENT OROPHARYNGEAL CANCER

Treatment options:

Standard:

1. Surgical resection if radiation therapy fails and if technically feasible.

2. Radiation therapy when surgery fails if not previously given in curative doses that preclude further treatment.[1]

3. Surgical salvage when surgery fails and if technically feasible.

Under clinical evaluation:
1. Clinical trials evaluating the use of chemotherapy should be considered.[2-5]

2. Clinical trials evaluating the use of hyperthermia and radiation therapy.

Post-treatment follow-up:
These patients should have a careful head and neck examination looking for
recurrence monthly for the first post-treatment year, every 2 months for
the second year, every 3 months for the third year, and every 6 months
thereafter. If the patient has metastatic disease or local recurrence
that is no longer amenable to surgery or radiation, chemotherapy should
be considered.

References:

  1. Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in patients with recurrent head and neck cancer. American Journal of Surgery 150(4): 485-487, 1985.

  2. Hong WK, Bromer R: Chemotherapy in head and neck cancer. New England Journal of Medicine 308(2): 75-79, 1983.

  3. Kish JA, Ensley JF, Jacobs J, et al.: A randomized trial of cisplatin (CACP) + 5-fluorouracil (5-FU) infusion + CACP + 5-FU bolus for recurrent and advanced squamous cell carcinoma of the head and neck. Cancer 56(12): 2740-2744, 1985.

  4. Vogl SE, Schoenfeld DA, Kaplan BH, et al.: A randomized prospective comparison of methotrexate with a combination of methotrexate, bleomycin, and cisplatin in head and neck cancer. Cancer 56(3): 432-442, 1985.

  5. Jacobs C, Lyman G, Velez-Garcia E, et al.: A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. Journal of Clinical Oncology 10(2): 257-263, 1992.

Date Last Modified: 04/1999



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