American Journal of Otolaryngology - Head and Neck Medicine and Surgery
Volume 24, Issue 1 , Pages 41-50, January 2003

Postoperative radiation therapy for squamous cell carcinoma of the head and neck

From the Departments of *Radiation Oncology and †Otolaryngology, University of Florida, College of Medicine, Gainesville, FL

Reprints not available from the authors. Please address correspondence to: William M. Mendenhall, MD, Department of Radiation Oncology, University of Florida Health Science Center, PO Box 100385, 2000 SW Archer Rd, Gainesville, FL 32610-0385.

Article Outline

Abstract 

Purpose: To discuss the role of postoperative radiation therapy (RT) for patients with squamous cell carcinoma of the head and neck. Results: Patients with adverse pathologic features have a high likelihood of local-regional recurrence and a decreased probability of survival after surgery alone. Postoperative RT reduces the risk of local-regional failure and probably improves survival. Patients who are at high risk for recurrence after surgery benefit from more aggressive dose-fractionation schedules that may include altered fractionation to decrease the overall time from surgery to the completion of RT. Adjuvant chemotherapy also appears to improve the probability of cure in high risk patients. Conclusion: Patients who have a high likelihood of local-regional recurrence after surgery have improved disease control and survival after postoperative RT. (Am J Otolaryngol 2003;24:41-50. Copyright 2003, Elsevier Science (USA). All rights reserved.)

 

The 2 major treatment modalities for patients with squamous cell carcinoma of the head and neck are surgery and radiation therapy (RT). Patients with stage I and II disease as defined by the American Joint Committee on Cancer (AJCC) are optimally treated with 1 modality.1 Unfortunately, a substantial proportion of patients present with stage III and IV disease and, although organ preservation treatment strategies using RT alone or with concomitant chemotherapy have proven to be successful for patients with favorable low volume malignancies, those with unfavorable cancer have a low chance of cure.2, 3, 4 Depending on primary site and location, patients with advanced stage III-IV lesions are optimally treated with primary surgery. The rationale for postoperative RT is that it is most likely to be effective against microscopic deposits of cancer cells, which, if they remain after resection, would progress and lead to a local-regional recurrence.5 Although many clinicians currently recommend postoperative adjuvant RT, some have suggested that although irradiation may reduce the likelihood of local-regional recurrence this may be offset by an increased risk of distant metastases so that survival is unchanged. If there is no survival benefit, one could argue to withhold RT and treat only those patients who relapse above the clavicles.6

The aim of this article is to review the pertinent literature and to define the role of postoperative RT in the management of patients with resected head and neck cancer. The discussion will be limited, for the most part, to patients who have undergone at least resection of all gross tumors. The bias of the authors is to treat patients who would best be treated surgically but are judged to have incompletely resectable cancers, with preoperative RT followed by reevaluation for an anticipated operation.7

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Adverse prognostic factors after surgery alone 

Pathologic factors predictive of local-regional recurrence after surgery may be related to the primary tumor and/or metastatic cervical nodes. Important parameters include close (<5 mm) or positive margins, extracapsular extension, invasion of the soft tissues and/or skin of the neck, more than 5 mm subglottic invasion, 2 or more positive lymph nodes, perineural invasion, and endothelial-lined space invasion.8, 9, 10, 11

Some of these factors are more ominous than others. For example, early bone erosion of the mandible is not likely to have the same negative prognostic influence as positive margins. One also might argue that for subglottic extension, 1 cm or more should be the threshold rather than 5 mm. Additional factors include an initially positive margin that is reresected until negative margins are achieved and/or the surgeon's uneasiness regarding final, apparently tumor-free margins. High risk of occult tumor in an undissected, clinically negative N0 neck is not an adequate reason to add adjuvant RT unless there are additional indications for treatment; the high-risk neck should be electively dissected.

Ang et al12 reported a prospective trial of 213 patients who were thought to be likely to require postoperative RT after surgery for squamous cell carcinoma of the oral cavity, oropharynx, and hypopharynx. Pathologic T stage was T3-T4 in 61% of patients, and 58% had N2-N3 neck disease. The majority of patients had stage III (48%) or IV (38%) cancers. After surgery, 31 (15%) had no adverse pathologic factors and received no additional treatment; these patients had a 5-year local-regional control rate of 83%. This finding suggests that a small subset of patients that originally presented with advanced head and neck cancer but after surgery was found to have no adverse pathologic factors would have an excellent prognosis with surgery alone.

In contrast, Olsen et al10 reported a series of 284 patients with pathologic stage N1 and N2 squamous cell carcinoma treated with surgery alone at the Mayo Clinic. The 5 year neck-recurrence-free survival rates were as follows: N1, 76%; N2, 60%; and overall, 69%. Multivariate analysis revealed the following parameters to be significantly associated with increased risk of neck recurrence: 4 or more positive nodes (P = .005), invasion of vascular or lymphatic spaces (P = .003), invasion of the soft tissues (P = .008), and desmoplastic stromal pattern (P = .0001). Huang et al13 reported 71 patients with positive margins and/or extracapsular extension who were treated with surgery alone at the Medical College of Virginia. The 3-year local control rates were positive margins, 41%; extracapsular extension, 31%; and both, 0%. Because the likelihood of salvage is low after a local-regional recurrence, factors that adversely impact the probability of disease control above the clavicles are also likely to have a negative influence on survival.

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Does postoperative RT improve local-regional control and survival? 

Although no randomized trials have addressed the efficacy of postoperative adjuvant RT in the treatment of head and neck cancer, an excellent data set that has bearing on this issue is available from the Medical College of Virginia. Two groups of surgeons operated on patients with head and neck cancer: general surgical oncologists who used surgery alone and reserved RT for treatment of recurrent disease and otolaryngologists who routinely sent patients with locally advanced disease for postoperative RT.13 One hundred twenty-five of 441 patients treated surgically between 1982 and 1988 had extracapsular extension and/or positive margins; 71 were treated with surgery alone, and 54 received postoperative RT. Patients were irradiated once daily at 1.8 to 2.0 Gy per fraction with cobalt 60 or 4 MV x-rays to doses of 50 to 50.99 Gy in 26 patients and to 60 Gy or more in the remainder. Local control rates at 3 years after surgery alone compared with surgery and RT were as follows: extracapsular extension, 31% and 66% (P = .03); positive margins, 41% and 49% (P = .04); and extracapsular extension and positive margins, 0% and 68% (P = .001). A multivariate analysis of local control was performed evaluating the impact of T stage, N stage, use of postoperative RT, the number of positive nodes, the number of nodes with extracapsular extension, primary site, microscopic and macroscopic extracapsular extension, and margin status. For the endpoint of local control, use of postoperative RT (P = .0001), macroscopic extracapsular extension (P = .0001), and margin status (P = .09) were of independent significance. Disease-free survival at 3 years was 25% after surgery alone and 45% after combined-modality treatment (P = .0001). Cause-specific survival rates at 3 years were 41% for surgery alone and 72% for surgery and postoperative RT (P = .0003). Multivariate analysis of cause-specific survival showed that postoperative RT (P = .0001) and the number of nodes with extracapsular extension (p = .0001) significantly influenced this endpoint. Two irradiated patients experienced mandibular necrosis; 1 was treated with hyperbaric oxygen treatments and the other with conservative management.

In another series, Lundahl et al14 reported on 95 patients with node-positive squamous cell carcinoma who were treated with a neck dissection and postoperative RT at the Mayo Clinic. A matched-pair analysis was performed using a series of patients treated with surgery alone; 56 matched pairs of patients were identified. The results showed that the rates of recurrence in the dissected neck (relative risk [RR] = 5.82, P = .0002), recurrence in either side of the neck (RR = 2.21, P = .0052), and death from any cause (RR = 1.67, P = .0182) were significantly higher for patients treated with neck dissection alone.

Thus, it would appear that for patients who are at high risk for local-regional failure after surgery, postoperative RT may significantly improve both disease control above the clavicles and survival.

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Postoperative RT technique 

At the University of Florida, patients are treated with 1.8 to 2.0 Gy per fraction, 1 fraction per day, 5 days per week in a continuous course. The total dose depends on the likelihood and density of occult residual disease and usually varies from 60 to 66 Gy. For patients who have undergone a partial laryngectomy, the dose is reduced to 55.8 Gy at 1.8 Gy per fraction because of an increased risk of complications.15 The primary site and upper neck are irradiated with parallel opposed fields and the low neck is irradiated with an en face anterior field with the dose specified at the maximum depth. The inferior border of the lateral fields is placed at the top of the stoma for patients who have undergone a total laryngectomy (Fig 1).

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  • Fig. 1. 

    Fields for postoperative irradiation of a patient with advanced cancer of the laryngopharynx. (A) Typical simulation film. The initial “off-cord” reduction (50 Gy) is indicated by the dashed line and the final reduction (60 Gy) by the dotted line. Wires mark the surgical scars and stoma. Slanting line used on lower border reduces the length of spinal cord treated by the primary field, allows better caudal coverage of the mucosal surfaces while simultaneously bypassing the shoulders, and facilitates matching the low neck field. (B) Schematic diagram of low-neck field. The rectangle (solid line) represents the light field. The dashed lines denote the central axis. The shaded areas represent the blocked portions of the field (stacked lead blocks). The superior border of the neck field is the inferior border of the primary field. The actual line is treated only in the primary field. The upper border of the low-neck field assumes a V shape. In the midline of the patient, the apex of the V generally is at or close to the central axis, so that the portion of the low-neck portal that treats the spinal cord is nondivergent in its upper portion and diverges away from the primary fields in its lower portion. At the junction of the three fields, a short (2–3 cm) segment of spinal cord remains untreated by any of the three fields. (Reprinted with permission.8)

Although no midline block is used in the low-neck field, the dose to the spinal cord is low because the central axis is placed at the superior border so that the beam is nondivergent and because the inferior border of the lateral fields slopes superiorly as it proceeds posteriorly (Fig 2).
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  • Fig. 2. 

    Averaged 6 MV dose distribution for larynx primary field with low-neck match and trachea block removed in an anthropomorphic head and neck phantom made of tissue-equivalent polyacrylamide gel with a 2-dimensional thermoluminescent dosimeter array in its sagittal midplane. The doses are normalized to the primary field's central axis dose. (Reprinted with permission.38)

The lower border of the lateral fields is placed at approximately the thyroid notch for patients with malignancies of the oral cavity and oropharynx (Figs 3 and 4).
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  • Fig. 3. 

    Typical portal after a hemimandibulectomy, partial maxillectomy, and radical neck dissection for a pathologic T4N0 retromolar trigone lesion. (A) Field reductions were made at 45 Gy (dashed line) and 60 Gy (dotted line). (B) The low neck received 50 Gy given dose (at Dmax) in 25 fractions. The larynx and a segment of the spinal cord were shielded by a tapered midline block. (Reprinted with permission.8)

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  • Fig. 4. 

    Averaged 60Co dose distribution for oropharynx field with low-neck match and larynx block. The dose distribution was obtained using an anthropomorphic head and neck phantom and a 2-dimensional thermoluminescent dosimeter array. The doses are shown as a percentage of the central axis dose. (Reprinted with permission.38)

A tapered midline block is placed in the anterior en face low-neck field with the inferior border of the block at approximately the bottom of the cricoid cartilage. Patients are optimally treated with either cobalt 60 or 4 MV x-rays; 6 MV x-rays may be used if these are unavailable. Vaseline gauze is used as bolus over the incisions if there is a high risk of failure in the neck. Recent technical advances in the RT of head and neck cancer patients include the use of 3-dimensional computed tomography treatment planning and intensity modulated radiation therapy. The latter technique may be used to reduce the dose delivered to one or more of the major salivary glands, thus reducing the likelihood of long-term xerostomia.

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Adverse prognostic factors after surgery and postoperative RT 

Vikram16 was among the first to report a decreased likelihood of cure secondary to delay in initiation of postoperative adjuvant RT in a series of 21 patients treated at the Memorial Sloan-Kettering Cancer Center. Schiff et al17 updated the Memorial Hospital experience and reported a series of 111 patients treated with surgery and postoperative irradiation. Patients who received less than 60 Gy had an increased risk of failure if the interval between surgery and RT exceeded 6 weeks (P < .05). There was no adverse impact of delay over 6 weeks if the irradiation dose was more than 60 Gy. In contrast, Amdur et al8 reported a series of 134 patients treated with continuous-course postoperative irradiation within 3 months of surgery. Despite stratification for dose, margin status, and number of indications for adjuvant RT, the interval was not prognostically significant. Bastit et al18 recently reported a series of 2,052 patients treated with surgery and postoperative irradiation for carcinoma of the oropharynx and hypopharynx at the Centre Henri Becquerel. They found that the interval between the 2 modalities had no significant impact on local-regional control or survival.

Altered fractionation has been used to reduce overall treatment time and improve the likelihood of cure for patients treated with RT alone.19 The overall treatment time is influenced by both the interval between surgery and postoperative RT as well as the dose-fractionation schedule. It can be shortened by treating on weekends or by using 2 or more fractions per day for all or part of the irradiation course. Parsons et al20 reported on 134 patients treated with surgery and continuous-course RT at the University of Florida for squamous cell carcinoma of the oral cavity. Patients were considered to be in a favorable category if they had less than 4 indications for postoperative RT and unfavorable if there were 4 or more indications. Patients in the unfavorable category had a 60% local-regional control rate when the overall treatment time was 100 days or less compared with 14% when the overall time was greater than 100 days (P = .04). Overall treatment time was not prognostically important for patients categorized as favorable. In a similar study, Rosenthal et al21 reported a series of 208 patients treated with surgery and once daily postoperative RT at the University of Pennsylvania between 1992 and 1997. Patients were stratified into intermediate and high-risk group, and overall treatment time was defined as short (100 days or less) and long (more than 100 days). Multivariate analysis revealed that both risk groups and overall treatment time significantly influenced local-regional control (P = .017 and P = .022; respectively) and overall survival (P < .001 and P = .035, respectively). In a recent study, Ang et al12 reported a prospective trial of 213 patients who were treated surgically and stratified as follows: low risk, no adverse pathologic factors; intermediate risk, 1 adverse pathologic factor other than extracapsular extension; and high risk, extracapsular extension and/or 2 or more adverse pathologic factors. Low-risk patients received no further treatment, intermediate-risk patients received 57.6 Gy in 6.5 weeks, and high-risk patients were randomized to receive conventionally fractionated treatment with 63 Gy in 7 weeks or 63 Gy in 5 weeks with altered fractionation. A prolonged interval between surgery and conventionally fractionated RT was associated with decreased local-regional control (P = .02) and survival (P = .01) for high-risk patients. High-risk patients treated with accelerated fractionation had no difference in local-regional control (P = .36) or survival (P = .50) as a function of the interval between the 2 modalities. Overall treatment time significantly influenced local-regional control (P =.005) and survival (P = .03) for high-risk patients. Taken together, these findings suggest that high-risk patients who experience a significant delay (>6 weeks) between surgery and postoperative irradiation benefit from altered fractionation to reduce the overall treatment time.

Another treatment-related issue that may influence the likelihood of cure is beam energy. In the past, patients were often treated with cobalt 60 or 4 MV x-rays, which deliver a high proportion of the dose to subcutaneous tissues. Currently, the lowest energy beam in most departments is 6 MV x-rays, and there is a possibility that tumor in the subcutaneous tissues may be underdosed. This is of particular concern in the low neck in which a single en face field is used. This is less of an issue in the upper neck in which parallel-opposed portals are used, and the exit dose from the contralateral side contributes to the dose in the ipsilateral subcutaneous tissues. Fortin et al22 reported a study of 471 patients treated with postoperative cobalt 60 (212 patients) or 6 MV x-rays (259 patients) at the L' Hôtel Dieu de Québec between 1989 and 1997. Whereas the overall local control rate was better for patients treated with 6 MV x-rays, the neck control rate was improved for high-risk patients (extracapsular extension, more than 2 positive nodes, and/or T4 primary) treated with cobalt 60 (P = .09). Multivariate analysis revealed that high-risk patients treated with cobalt 60 had a significantly higher likelihood of neck control (P = .03). Aref et al23 recently reported a secondary analysis of Intergroup Study 003424 where 392 patients with advanced squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx underwent surgery and were randomized to receive postoperative irradiation alone or combined with three cycles of induction cisplatin and fluorouracil. Patients were stratified into high risk (<5 mm margins, extracapsular extension, and/or carcinoma in situ at the margins) and low risk (all others) groups. Patients were treated once daily, 1.8 to 2.0 Gy per fraction, to 50 to 54 Gy for low-risk patients, and 60 Gy for high-risk patients. Patients were irradiated using the following: cobalt 60, 4 MV x-rays, or 6 MV x-rays (157,140, and 95 patients, respectively). Beam energy had no significant impact on acute or late toxicity. Also, there was a nonsignificant increased rate of failure in the ipsilateral neck as the first site of recurrence for patients treated with 6 MV x-rays (13%) compared with those treated with cobalt 60 or 4 MV x-rays (9%). However, there was no significant difference (P = .61) in local-regional control: cobalt 60 (75%), 4 MV x-rays (79%), and 6 MV x-rays (80%). This leads to the conclusion that most patients may be adequately irradiated with 6 MV x-rays. A beam spoiler can be added to increase the surface dose for patients thought to be at a particularly high risk for tumor in the subcutaneous tissues.

In addition to treatment-related parameters, a variety of clinical and pathologic factors have been correlated with prognosis after surgery and postoperative RT. Parsons et al20 reported a 71% local-regional control rate at 10 years in 134 patients treated for squamous cell carcinoma of the oral cavity, with 94% of local-regional recurrences arising in the parallel opposed fields that included the primary site and upper neck anterior to the plane of the spinal cord. The probability of local-regional control as it relates to resection margins and the number of indications for RT is shown in Figures 5 and 6, respectively.

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  • Fig. 5. 

    Local-regional control according to surgical margin. Other includes margins that were close, contained dysplasia, or carcinoma in situ or were initially positive but negative after re-resection. (Reprinted with permission.20)

Multivariate analysis of local-regional control showed that positive margins (P = .0255) and the number of indications for adjuvant RT (P = .002) significantly influenced this endpoint (Table 1).
Table 1. Local–regional control: Overall multivariate analysis of pathologic variables
VariableRankP
Number of indications for irradiation1.0020
Surgical margins2.0255
Multifocal tumor3.0797
Extracapsular extension4.3082
Pathologic AJCC stage5.4521
Neural invasion6.2393
Pathologic N stage7.5185
Soft tissue extension8.4150
Tongue primary site9.4635
Vascular invasion10.4841
Bone invasion11.4514

Reprinted with permission.20.

Peters et al9 reported a prospective trial including 240 patients treated with surgery and postoperative RT at the M.D. Anderson Cancer Center. Clusters of 2 or more of the following factors were associated with an increased risk of recurrence: oral cavity primary site, close or positive mucosal margins, nerve invasion, 2 or more positive nodes, largest node more than 3 cm, treatment delay more than 6 weeks, and Zubrod performance status more than or equal to 2. Analysis of variables predictive of local-regional control revealed that the only independent variable of note was extracapsular extension. Pfreundner et al25 reported on 257 patients treated with surgery and postoperative irradiation at the University of Wuerzburg between 1987 and 1997. Resection margins were defined as negative (>3 mm, 64 patients), close (<3 mm, 66 patients), R1 (microscopically positive, 101 patients), and R2 (gross residual, 26 patients). Five-year local-regional control and survival rates were as follows: negative margins, 100% and 67%; close margins, 92% and 59%; R1 resection, 87% and 26%; and R2 resection, 69% and 27%, respectively. Multivariate analysis of local-regional control revealed that only resection margins (P = .00031) and high RT dose (P = .0046) were significantly associated with this endpoint. T stage (P = .144), N stage (P = .166), extracapsular extension (P = .120), lymphangiosis carcinomatosa (P = .525), and adjuvant chemotherapy did not significantly influence local-regional control. Multivariate analysis of survival revealed that total dose (P < .00000), resection margins (P = .000015), T stage (P= .0057), and N stage (P = .024) significantly influenced this endpoint. Survival was marginally impacted by the presence of extracapsular extension (P = .055) and lymphangiosis carcinomatosa (P = .066).

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Salvage of patients with local-regional recurrence 

Fifty-eight (24%) of 240 patients treated with surgery and postoperative RT at the M.D. Anderson Hospital developed a local-regional recurrence.9 Thirty-six patients underwent salvage therapy with surgery alone or combined with chemotherapy (11), RT alone or combined with chemotherapy (3), or chemotherapy alone (22). Only 1 (2%) of 58 patients was a long-term survivor 22 months after salvage therapy. Thus, the probability of successful salvage is remote, and treatment must be designed to maximize the chance of cure with the initial operation and adjuvant RT.

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Prognostic influence of dose-fractionation parameters 

Zelefsky et al11 reported a study of 102 patients treated with surgery and postoperative RT at Memorial Sloan-Kettering Cancer Center for squamous cell carcinoma of the oral cavity and oropharynx. Margins were microscopically positive in 25 patients, close (≤5 mm) in 41 patients, and negative in 36 patients. The median postoperative dose was 60 Gy. Patients with close or positive margins and a non-oral-tongue primary site had a 7-year local control rate of 92% for doses of 60 Gy or more compared with 44% for those who received less than 60 Gy (P = .0007).

Pfreundner et al25 observed an improvement in the probability of local-regional control at 5 years when patients were stratified according to resection margins (Table 2).

Table 2. Five-year local-regional control rates versus resection margins and radiotherapy dose
MarginsNo. PatientsRadiotherapy Dose (Gy)5-Year Local-RegionalControl (%)P
Close (<3 mm)66≤6662.07
>6680
Gross total excision with positive margins101≤6828.0002
>6855
Gross residual disease26≤6650.15
>6684

Data from reference 25.

Patients were treated once daily at 2 Gy per fraction. Multivariate analysis revealed that increasing dose was associated with increased local-regional control and survival.

Peters et al9 reported on 240 patients who were included in a prospective study of surgery and postoperative RT at the M.D. Anderson Hospital. Patients were stratified into low- and high-risk groups based on clinical stage and pathologic parameters. Patients underwent resection of all gross tumors and were irradiated once daily at 1.8 Gy per fraction. Low-risk patients were initially randomized to receive either 52.2 to 54 Gy or 63 Gy; the lower dose arm was increased to 57.6 Gy after an interim analysis showed a higher risk of recurrence in patients who received 52.2 to 54 Gy. High-risk patients were randomized to receive either 63 Gy or 68.4 Gy. Low-risk patients who received 54 Gy or less had a significantly higher local failure rate than those who received 57.6 Gy or more. No significant dose response was observed at doses more than 57.6 Gy except for patients with extracapsular extension; such patients who received 63 Gy or more had a significantly (P = .03) higher control rate than those who received 57.6 Gy. Doses more than 63 Gy did not seem to be beneficial.

The overall time from surgery to the completion of RT has been shown to be inversely related to prognosis for some subsets of high-risk patients.12, 20 Therefore, it stands to reason that the overall time of the RT course might influence the effectiveness of the treatment. Amdur et al26 reported results of 161 patients treated with once daily continuous (134 patients) or planned split-course (27 patients) postoperative RT at the University of Florida. Patients treated with the planned split-course technique, which was routinely used between 1970 and 1974, had a significantly worse outcome (Table 3).

Table 3. Five-year outcome for continuous-course versus planned split-course postoperative radiotherapy
ParameterSplit Course (N = 27) (%)Continuous Course (N = 134) (%)P
Local-regional control4480.002
Survival1533.005
Cause specific survival3757<.001

Data from reference 26.

Multivariate analysis revealed that split-course RT was significant factor in the probability of local-regional control and death with cancer present. Patients treated with split-course RT had the same likelihood of acute and late complications as those treated with continuous-course RT. In another study at the University of Florida,20 134 patients with 135 oral cavity tumors were treated with continuous-course, once daily (111 lesions), or twice daily (24 lesions) postoperative RT. Patients treated twice daily usually had close or positive margins. They were irradiated at 1.2 Gy per fraction and tended to receive a somewhat higher dose over a shorter period of time. Local-regional control for patients with positive margins was 6 of 10 (60%) after twice daily RT compared with 9 of 22 (41%) after once daily RT (P = .27). Ang et al12 recently reported a prospective trial in which high-risk patients who had a significant delay between surgery and postoperative RT had an improved outcome with a more aggressive altered fractionation schedule compared with those irradiated once daily.

Therefore, it would appear that some subsets of high-risk patients may benefit from a more aggressive course of postoperative RT. Intensification of the treatment might be accomplished by increasing the total dose and reducing the overall treatment time. Achieving the latter may be done by treating on weekends or using an altered fractionation schedule.

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Adjuvant chemotherapy and future directions 

Although postoperative RT is associated with an improved prognosis for patients with advanced head and neck cancer, a substantial proportion of high-risk patients relapse and have only a remote probability of salvage.

Concomitant chemotherapy has been shown to be beneficial for patients with advanced stage III-IV disease treated with RT alone.27, 28, 29, 30, 31, 32 Bachaud et al33 reported a prospective trial in which 83 patients with stage III-IV head and neck cancer with extracapsular extension underwent surgery and were then randomized to postoperative RT alone or combined RT and weekly cisplatin (50 mg). Patients who received adjuvant cisplatin had improved local-regional control (P =.05), cause-specific survival (P < .05), and overall survival (P < .01). There was no difference in the rates of distant metastases or late complications. A recent multi-institution trial included 334 patients who were operated on for locally advanced squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx and were then randomized to postoperative RT alone or combined with concomitant cisplatin.34 Radiotherapy was given once daily in 2 Gy fractions up to a total dose of 66 Gy. Cisplatin was delivered 100 mg/m2 on days 1, 22, and 43 of RT. At a median 34 months of follow-up, patients treated with adjuvant chemotherapy had significantly improved 3-year disease-free survival rates (59% v 41%, P = .0096) and 3-year overall survival rates (65% v 49%, P = .0057). Similarly, local control and time to progression were significantly higher (P = .0014 and P = .0016, respectively) for patients randomized to receive cisplatin. There was no difference in late complications between the 2 arms. Ongoing trials continue to define the role of adjuvant chemotherapy combined with postoperative RT. Other, perhaps less toxic, adjuvant therapies that may prove to be beneficial include carbogen breathing alone or combined with nicotinamide to reduce tumor hypoxia.35, 36 In addition, the development of new experimental therapies used as adjuvant to radiotherapy, particularly those targeted to the tumor vasculature,37 may provide future opportunities in the management of head and neck cancer.

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References 

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PII: S0196-0709(02)32403-7

doi:10.1053/ajot.2003.1

American Journal of Otolaryngology - Head and Neck Medicine and Surgery
Volume 24, Issue 1 , Pages 41-50, January 2003

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