44_03
Treatment Selection and Technique: Vocal Cord Carcinoma
Selection of Treatment Modality
In treating vocal cord carcinoma, the goal is cure with the best functional result and the least risk of a serious complication. Patients may be considered to be in an early group if the chance of cure with larynx preservation is high, they are in a moderately advanced group if the likelihood of local control is 60% to 70% but the chance of cure is still good, and they are in an advanced group if the chance of cure is moderate and the likelihood of laryngeal preservation is relatively low. The early group may be treated initially by radiation therapy or, in selected cases, by partial laryngectomy. The moderately advanced group may be treated with either irradiation with laryngectomy reserved for relapse or by total laryngectomy with or without adjuvant postoperative irradiation. The obvious advantage of the former strategy, which we use at the University of Florida, is that there is a fairly good chance that the larynx will be preserved. Although some patients may be rehabilitated with a tracheoesophageal puncture after laryngectomy, only about 20% of patients use this device long term and the majority use an electric larynx (62). The advanced group is treated with total laryngectomy and neck dissection with or without adjuvant radiation therapy or by radiation therapy and adjuvant chemotherapy (68). Data suggest that if patients whose tumors show a partial or complete response to two to three cycles of neoadjuvant chemotherapy are then given high-dose radiation therapy, the cure rates are comparable with those obtained with initial total laryngectomy (16). Another less expensive and less toxic method to select patients likely to be cured by radiation therapy alone is to calculate the primary tumor volume on
P.982
pretreatment CT or MRI. Data indicate that primary tumor volume is inversely related to the probability of local control after irradiation (61,64). Recent data indicate that whereas induction chemotherapy probably does not improve the likelihood of locoregional control and survival, concomitant chemotherapy and irradiation results in an improved possibility of cure compared with irradiation alone (23,68,90). There is a subset of patients with high volume, unfavorable, advanced cancers who may be cured by chemoradiation but have a useless larynx and permanent tracheostomy and/or gastrostomy (61). These patients are best treated with a total laryngectomy, neck dissection, and postoperative irradiation.
Carcinoma in Situ
Lesions diagnosed as carcinoma in situ may sometimes be controlled by stripping the cord. However, it is difficult to exclude the possibility of microinvasion on these specimens. Recurrence is frequent, and the cord may become thickened and the voice hoarse with repeated stripping. Localized carcinoma in situ can also be excised using the CO2 laser.
Early radiation therapy for carcinoma in situ often means a better chance of preserving a good voice, especially as many patients with this diagnosis eventually receive this treatment (28).
Many patients with a diagnosis of carcinoma in situ have obvious lesions that probably contain invasive carcinoma. We have often proceeded with radiation therapy rather than put the patient through a repeated biopsy procedure.
Early Vocal Cord Carcinoma
In most centers, irradiation is the initial treatment prescribed for T1 and T2 lesions, with surgery reserved for salvage after radiation therapy failure (60,71). Although hemilaryngectomy or cordectomy produces comparable cure rates for selected T1 and T2 vocal cord lesions, irradiation is generally preferred (71,79). Supracricoid laryngectomy, as reported by Laccourreye et al. (47) is a procedure designed to remove moderate-sized cancers involving the supraglottic and glottic larynx. The larynx may be removed with preservation of the cricoid and the arytenoid with its neurovascular innervation, the defect is closed by approximating the base of the tongue to the remaining larynx. The oncologic and functional results of this procedure in selected patients are reported to be excellent. Transoral laser excision also may provide high cure rates for select patients with small, well-defined lesions limited to the midthird of one true cord (58,103). A small subset of transoral laser surgeons, notably Professor Steiner, use this technique successfully in moderately advanced cancers (71). The major advantage of irradiation compared with partial laryngectomy is better quality of the voice. Partial laryngectomy finds its major use as salvage surgery in suitable cases after irradiation failure. Even if the patient has a local recurrence after salvage partial laryngectomy, there is a third chance with total laryngectomy, which may still be successful.
Verrucous lesions have the reputation of being unresponsive to radiation therapy and, in some instances, converting into invasive, often anaplastic, metastasizing lesions. Partial laryngectomy is recommended for early verrucous carcinoma of the glottis, but irradiation is recommended if the alternative is total laryngectomy. We have observed typical verrucous lesions that have disappeared with radiation therapy and not recurred. O'Sullivan et al. (80) also have made this observation. Additionally, a variety of tumors that recur after unsuccessful treatment (with surgery, radiation therapy, and/or chemotherapy) are more likely to exhibit more aggressive behavior.
Moderately Advanced Vocal Cord Cancer
Fixed-cord lesions (T3) may be subdivided into relatively favorable or unfavorable lesions. Patients with unfavorable lesions usually have extensive bilateral disease with a compromised airway and are considered to be in the advanced group. Patients with favorable T3 lesions have disease confined mostly to one side of the larynx, have a good airway, and are reliable for follow-up. Some degree of supraglottic and subglottic extension usually exists. The extent of disease and tumor volume, in particular, are related to the likelihood of control after radiation therapy (61).
The patient with a favorable lesion is advised of the alternatives of irradiation with surgical salvage or immediate total laryngectomy. Recent data suggest that the likelihood of locoregional control is better after some altered fractionation schedules compared with conventional once-daily radiation therapy (24,68). Follow-up examinations are recommended every 4 to 6 weeks for the first year, every 6 to 8 weeks for the second year, every 3 months for the third year, every 6 months for the fourth and fifth years, and annually thereafter. The patient must understand that total laryngectomy may be recommended purely on clinical grounds without biopsy-proven recurrence and that the risk of laryngeal osteochondronecrosis is about 5%.
Evaluation of cord mobility after 50.4 Gy or at the end of radiation therapy has not been helpful in predicting local control (64). Some patients in whom the vocal cord remained fixed have had local tumor control of the disease for 2 years or longer after radiation therapy.
The major difficulty in using irradiation for the more advanced lesions is distinguishing radiation edema from local recurrence during follow-up examinations (87). Progressive laryngeal edema, persistent throat pain, or fixation of a previously mobile vocal cord frequently signifies recurrent disease in the larynx, although a few patients with these findings remain disease-free with long-term follow-up.
Extended hemilaryngectomy has been used by a few surgeons in the treatment of well-lateralized fixed-cord lesions. A permanent tracheostomy is usually required because a portion of the cricoid is resected, but a useful voice may be retained (88).
Advanced Vocal Cord Carcinoma
Advanced lesions usually show extensive subglottic and supraglottic extension, bilateral glottic involvement, and invasion of the thyroid, cricoid, or arytenoid cartilage, or frequently all three (5,6). The airway is compromised, necessitating a tracheostomy at the time of direct laryngoscopy in approximately 30% of patients. Clinically positive lymph nodes are found in about 25% to 30% of patients.
The mainstay of treatment is total laryngectomy, with or without adjuvant radiation therapy. The most frequent sites of local failure after total laryngectomy are around the tracheal stoma, in the base of tongue, and in the neck lymph nodes or soft tissues of the neck. If the neck has clinically negative findings before surgery and if postoperative irradiation is planned, neck dissection may be withheld, and radiation therapy may be used to treat both sides of the neck. However, in practice, most surgeons prefer to perform elective bilateral selective (levels II-IV) neck dissections in conjunction with a total laryngectomy for T3N0 or T4N0 laryngeal cancer, even if postoperative irradiation is planned. If the lymph nodes are clinically positive, a therapeutic neck dissection is performed at the time of laryngectomy.
The indications for postoperative radiation therapy include close or positive margins, significant subglottic extension (1 cm or more), cartilage invasion, perineural invasion,
P.983
endothelial-lined space invasion, extension of the primary tumor into the soft tissues of the neck, multiple positive neck nodes, extracapsular extension, and control of subclinical disease in the opposite neck (2,41). Preoperative irradiation is indicated for patients who have fixed neck nodes, have had an emergency tracheotomy through tumor, or have direct extension of tumor involving the skin.
Definitive irradiation is prescribed for the patient who refuses total laryngectomy or is medically unsuitable for major surgery.
As previously stated, there is evidence that two to three cycles of neoadjuvant chemotherapy followed by radiation therapy in patients obtaining at least a partial response may provide a moderate likelihood of larynx preservation without compromising cure (16). Recent data suggest that concomitant chemotherapy and irradiation is more efficacious than irradiation alone or induction chemotherapy followed by radiation therapy (23,90). The optimal combination of concomitant chemotherapy and irradiation is unclear (68).
A randomized intergroup trial (Radiation Therapy Oncology Group 91–11) compared three treatment arms: Arm A, three cycles of induction cisplatin and fluorouracil followed by irradiation in complete and partial responders; Arm B, radiation therapy and concomitant cisplatin (100 mg/m2 on days 1, 22, and 43 of radiation therapy); and Arm C, once-daily irradiation (70 Gy in 35 fractions during 7 weeks) alone (23). Five hundred forty-seven patients were randomized and followed for a median of 3.8 years; 518 patients were evaluable. The rates of larynx preservation were: Arm A, 72%; Arm B, 84%; and Arm C, 67%. The rates of larynx presentation were significantly improved for Arm B; there was no significant difference between Arm A and Arm C. The 5-year survival rates were similar for the three treatment groups: Arm A, 55%; Arm B, 54%; and Arm C, 56%. The likelihood of developing distant metastases was lower for the two groups of patients that received adjuvant chemotherapy.
Surgical Treatment
Cordectomy is an excision of the vocal cord and may be performed by the transoral approach usually with a laser or externally by a thyrotomy. Its use is usually confined to small lesions of the middle third of the cord. After cordectomy, a pseudocord is formed, and the patient has a useful, if somewhat harsh, voice.
Vertical partial laryngectomy (i.e., hemilaryngectomy) allows removal of limited cord lesions with preservation of voice. One entire cord with as much as a third of the opposite cord with the adjacent thyroid cartilage is the maximum cordal involvement suitable for surgery in men; women have a smaller larynx, and usually only one vocal cord may be removed without compromising the airway. Partial fixation of one cord is not a contraindication to hemilaryngectomy, but only a few surgeons have attempted hemilaryngectomy for selected fixed-cord lesions. The maximum subglottic extension suitable for hemilaryngectomy is 8 to 9 mm anteriorly and 5 mm posteriorly; this limit is necessary to preserve the integrity of the cricoid. Tumor extension to the epiglottis, false cord, or both arytenoids is a contraindication to hemilaryngectomy.
Supracricoid partial laryngectomy is used for selected T2 and T3 glottic carcinomas and entails removal of both true and false cords as well as the entire thyroid cartilage. The cricoid is sutured to the epiglottis and hyoid (cricohyoidopexy).
Total laryngectomy with or without neck dissection is the operation of choice for advanced lesions and as a salvage procedure for radiation therapy failures in lesions that are not suited for conservation surgery. The entire larynx is removed, and the pharynx is reconstructed. A permanent tracheostomy is required. Speech may be reconstituted with a prosthesis or with an electrolarynx. One hundred four (63%) of 166 patients entered into the surgery and postoperative irradiation arm of the Veterans Affairs Laryngeal Cancer Study Group randomized trial were evaluable for communication status at 2 years after treatment (38). Ninety-six patients had undergone a total laryngectomy and communicated as follows: Tracheoesophageal, 27 (28%); esophageal, 5 (5%); artificial larynx, 47 (50%); nonvocal, 7 (7%); and no data, 10 (10%) (38). One hundred seventy-three patients underwent total laryngectomy and postoperative radiotherapy at the University of Florida and 69 patients were evaluable for 5 years or longer (62). Voice rehabilitation was accomplished as follows: Tracheoesophageal, 19%; artificial larynx, 57%; esophageal, 3%; nonvocal, 14%; and no data, 7%.
Radiation Therapy Technique
Irradiation for T1 or T2 vocal cord cancer is delivered by small portals covering only the primary lesion. The cervical lymph node chain is not electively treated. For T1 lesions, radiation therapy portals extend from the thyroid notch superiorly to the inferior border of the cricoid and fall off anteriorly. The posterior border depends on the posterior extension of the tumor (73). For T2 tumors, the field is extended depending on the anatomic distribution of the tumor. The field size ranges from 4 × 4 cm to 5 × 5 cm (plus an additional 1 cm of “flash” anteriorly) and is occasionally 6 × 6 cm for a large T2 lesion. Portals larger than this increase the risk of edema without improving the cure rate.
A commonly used dose-fractionation schedule at many institutions is 66 Gy for T1 lesions and 70 Gy for T2 cancers given in 2-Gy fractions. Evidence suggests that increasing the dose per fraction may improve the likelihood of local control (4,19,36,37,45,69,97,119). Ample data suggest that 1.8 Gy once daily results in significantly lower local control rates compared with 2 Gy once daily (45). Yamakazi et al. (121) recently reported a prospective trial in which patients with T1N0 squamous cell carcinoma of the glottic larynx were randomized to definitive radiotherapy at 2 Gy per fraction or 2.25 Gy per fraction. The 5-year local control rates were 77% after 2 Gy per fraction and 92% after 2.25 Gy per fraction (p = .004); there was no difference in either acute or late toxicity. Patients with T1 or T2 vocal cord cancer who are treated with once-a-day fractionation at the University of Florida are irradiated with 2.25 Gy per fraction; the dose-fractionation schemes used are shown as follows: Tis–T2 A, 63 Gy in 28 fractions; and T2B, 65.25 Gy in 29 fractions.
At the University of Florida, patients are treated in the supine position; the field borders for a patient with a T1N0 cancer are depicted in Fig. 44.7 (73). The field is checked by the physician at the treatment machine according to palpable anatomic landmarks. This allows the treatment volume to be kept at a minimum and reduces the risk of geographic miss. A three-field technique, using 4-or 6-MV x-rays, is used to deliver approximately 95% of the dose through opposed lateral wedged fields weighted to the side of the lesion; the remaining dose is delivered by an anterior field shifted 0.5 cm toward the side of the lesion (Fig. 44.8) (73). The tumor dose is usually specified at the 95% normalized isodose line.
Irradiation of T3 and T4 lesions requires larger portals, which include the jugulodigastric and middle jugular lymph nodes (Fig. 44.9) (74,85). The inferior jugular lymph nodes are included in a separate low-neck portal. Patients treated at the University of Florida are irradiated in a continuous-course twice daily at 1.2 Gy per fraction to a total dose of 74.4 Gy. The portals are reduced after 45.6 Gy in 38 fractions; the reduced portals cover only the primary lesion.
P.984
Intensity-modulated radiation therapy (IMRT) is employed if there is a clear advantage associated with this technique. Disadvantages associated with IMRT include increased dose inhomogeneity, increased total body dose, and increased labor and expense. The most common indications for IMRT for laryngeal cancers are the occasional patients with a node-positive T3–T4 cancer in which the retropharyngeal nodes are electively irradiated and the dose to the contralateral parotid gland reduced and/or a difficult low match between the lateral fields used to treat the primary site and upper neck and the anterior low neck field in a patient with a short neck and large shoulders. In the latter instance, IMRT could be used to encompass the entire target volume and avoid the problem of field junctioning entirely. IMRT is especially useful for patients with extensive subglottic invasion where achieving an adequate inferior margin with conventional lateral portals may not be possible.
Evidence from both retrospective and randomized trials points to improved therapeutic ratios with altered fractionation schedules (68). Given that irradiation is effective treatment for head and neck primary squamous cell carcinoma, it should not be surprising that higher doses of irradiation given more intensively would be more effective at providing tumor control. Because most observers have noted no increase in late toxicity with the various regimens, it generally is concluded that these schedules yield an improved therapeutic ratio. A recently updated Radiation Therapy Oncology Group 90–03 trial (24,109) reported on 1,073 patients who were randomly selected to receive one of four fractionation schedules:
• Standard fractionation: 2 Gy per fraction, once a day, 5 days a week, to a total dose of 70 Gy in 35 fractions during 7 weeks;
• Hyperfractionation: 1.2 Gy per fraction, twice daily (≥6 hours apart), 5 days a week, to a total dose of 81.6 Gy in 68 fractions during 7 weeks;
• Accelerated fractionation with split: 1.6 Gy per fraction, twice daily (≥6 hours apart), 5 days a week, to a total dose of 67.2 Gy in 42 fractions during 6 weeks, including a 2-week rest after 38.4 Gy, or;
• Accelerated fractionation with concomitant boost: 1.8 Gy per fraction, once a day, 5 days a week to a large field, plus 1.5 Gy per fraction once a day to a boost field given 6 or more hours after treatment of the large field for the last 12 treatments days, to a total dose of 72 Gy in 42 fractions during 6 weeks.
The 5-year locoregional failure rates were standard fractionation, 59%; hyperfractionation, 51%; accelerated split course, 58%; and concomitant boost, 52%. Both the hyperfractionation and concomitant boost schedules yielded locoregional control rates that were significantly better than standard fractionation. There was a trend toward improved overall survival with hyperfractionation, but no difference in cause-specific survival. Acute toxicity was increased with all three altered fractionation schedules; there was a modest increase in late effects with the concomitant boost schedule.
The treatment technique used for postoperative irradiation after total laryngectomy is depicted in Figure 44.10 (2). The treatment technique for preoperative irradiation is essentially the same as that used for irradiation alone. Alternatively, IMRT may be employed for the indications discussed previously.
Treatment of Recurrence
Most recurrences appear within 18 months, but late recurrences may appear after 5 years. The latter are likely second primary malignancies. The risk of metastatic disease in lymph nodes increases with local recurrence (63).
Recurrence after Radiation Therapy
With careful follow-up, recurrence is sometimes detected before the patient notices a return of hoarseness. There is often minimal lymphedema for 1 to 2 months after irradiation, which usually subsides or stabilizes. An increase in edema, particularly if associated with hoarseness or pain, suggests recurrence, even if there is no obvious tumor. Fixation of a previously mobile
P.985
vocal cord usually implies local recurrence, but we have occasionally observed a patient who has experienced a fixed cord with an otherwise normal-appearing larynx and who has not shown evidence of recurrence.
It may be difficult to diagnose recurrence if the tumor is submucosal. Generous, deep biopsies are required. If recurrence is strongly suspected, laryngectomy may rarely be advised without biopsy-confirmed evidence of recurrence. Positron emission tomography may be useful to distinguish recurrent tumor from necrosis.
Radiation therapy failures may be salvaged by cordectomy, hemilaryngectomy, supracricoid partial laryngectomy, or total laryngectomy. Biller et al. (8) reported a 78% salvage rate by hemilaryngectomy for 18 selected patients in whom irradiation failed; total laryngectomy was eventually required in 2 patients. Only two patients died of cancer. These investigators offered guidelines for using hemilaryngectomy: Contralateral vocal cord is normal, arytenoid is not involved, subglottic extension does not exceed 5 mm, and vocal cord is not fixed. In our experience, 14 patients irradiated for T1 or T2 vocal cord cancers underwent a hemilaryngectomy after local recurrence and 8 were successfully salvaged (60).
Recurrence after Surgery
The rate of salvage by irradiation for recurrences or new tumors that appear after initial treatment by hemilaryngectomy is about 50%. Lee et al. (53) reported seven successes among 12 patients; one lesion was later controlled by total laryngectomy. Total laryngectomy can be used successfully to treat hemilaryngectomy failures not suitable for radiation therapy. Irradiation rarely cures patients with recurrence in the neck or stoma after total laryngectomy.
Selection of Treatment Modality
In treating vocal cord carcinoma, the goal is cure with the best functional result and the least risk of a serious complication. Patients may be considered to be in an early group if the chance of cure with larynx preservation is high, they are in a moderately advanced group if the likelihood of local control is 60% to 70% but the chance of cure is still good, and they are in an advanced group if the chance of cure is moderate and the likelihood of laryngeal preservation is relatively low. The early group may be treated initially by radiation therapy or, in selected cases, by partial laryngectomy. The moderately advanced group may be treated with either irradiation with laryngectomy reserved for relapse or by total laryngectomy with or without adjuvant postoperative irradiation. The obvious advantage of the former strategy, which we use at the University of Florida, is that there is a fairly good chance that the larynx will be preserved. Although some patients may be rehabilitated with a tracheoesophageal puncture after laryngectomy, only about 20% of patients use this device long term and the majority use an electric larynx (62). The advanced group is treated with total laryngectomy and neck dissection with or without adjuvant radiation therapy or by radiation therapy and adjuvant chemotherapy (68). Data suggest that if patients whose tumors show a partial or complete response to two to three cycles of neoadjuvant chemotherapy are then given high-dose radiation therapy, the cure rates are comparable with those obtained with initial total laryngectomy (16). Another less expensive and less toxic method to select patients likely to be cured by radiation therapy alone is to calculate the primary tumor volume on
P.982
pretreatment CT or MRI. Data indicate that primary tumor volume is inversely related to the probability of local control after irradiation (61,64). Recent data indicate that whereas induction chemotherapy probably does not improve the likelihood of locoregional control and survival, concomitant chemotherapy and irradiation results in an improved possibility of cure compared with irradiation alone (23,68,90). There is a subset of patients with high volume, unfavorable, advanced cancers who may be cured by chemoradiation but have a useless larynx and permanent tracheostomy and/or gastrostomy (61). These patients are best treated with a total laryngectomy, neck dissection, and postoperative irradiation.
Carcinoma in Situ
Lesions diagnosed as carcinoma in situ may sometimes be controlled by stripping the cord. However, it is difficult to exclude the possibility of microinvasion on these specimens. Recurrence is frequent, and the cord may become thickened and the voice hoarse with repeated stripping. Localized carcinoma in situ can also be excised using the CO2 laser.
Early radiation therapy for carcinoma in situ often means a better chance of preserving a good voice, especially as many patients with this diagnosis eventually receive this treatment (28).
Many patients with a diagnosis of carcinoma in situ have obvious lesions that probably contain invasive carcinoma. We have often proceeded with radiation therapy rather than put the patient through a repeated biopsy procedure.
Early Vocal Cord Carcinoma
In most centers, irradiation is the initial treatment prescribed for T1 and T2 lesions, with surgery reserved for salvage after radiation therapy failure (60,71). Although hemilaryngectomy or cordectomy produces comparable cure rates for selected T1 and T2 vocal cord lesions, irradiation is generally preferred (71,79). Supracricoid laryngectomy, as reported by Laccourreye et al. (47) is a procedure designed to remove moderate-sized cancers involving the supraglottic and glottic larynx. The larynx may be removed with preservation of the cricoid and the arytenoid with its neurovascular innervation, the defect is closed by approximating the base of the tongue to the remaining larynx. The oncologic and functional results of this procedure in selected patients are reported to be excellent. Transoral laser excision also may provide high cure rates for select patients with small, well-defined lesions limited to the midthird of one true cord (58,103). A small subset of transoral laser surgeons, notably Professor Steiner, use this technique successfully in moderately advanced cancers (71). The major advantage of irradiation compared with partial laryngectomy is better quality of the voice. Partial laryngectomy finds its major use as salvage surgery in suitable cases after irradiation failure. Even if the patient has a local recurrence after salvage partial laryngectomy, there is a third chance with total laryngectomy, which may still be successful.
Verrucous lesions have the reputation of being unresponsive to radiation therapy and, in some instances, converting into invasive, often anaplastic, metastasizing lesions. Partial laryngectomy is recommended for early verrucous carcinoma of the glottis, but irradiation is recommended if the alternative is total laryngectomy. We have observed typical verrucous lesions that have disappeared with radiation therapy and not recurred. O'Sullivan et al. (80) also have made this observation. Additionally, a variety of tumors that recur after unsuccessful treatment (with surgery, radiation therapy, and/or chemotherapy) are more likely to exhibit more aggressive behavior.
Moderately Advanced Vocal Cord Cancer
Fixed-cord lesions (T3) may be subdivided into relatively favorable or unfavorable lesions. Patients with unfavorable lesions usually have extensive bilateral disease with a compromised airway and are considered to be in the advanced group. Patients with favorable T3 lesions have disease confined mostly to one side of the larynx, have a good airway, and are reliable for follow-up. Some degree of supraglottic and subglottic extension usually exists. The extent of disease and tumor volume, in particular, are related to the likelihood of control after radiation therapy (61).
The patient with a favorable lesion is advised of the alternatives of irradiation with surgical salvage or immediate total laryngectomy. Recent data suggest that the likelihood of locoregional control is better after some altered fractionation schedules compared with conventional once-daily radiation therapy (24,68). Follow-up examinations are recommended every 4 to 6 weeks for the first year, every 6 to 8 weeks for the second year, every 3 months for the third year, every 6 months for the fourth and fifth years, and annually thereafter. The patient must understand that total laryngectomy may be recommended purely on clinical grounds without biopsy-proven recurrence and that the risk of laryngeal osteochondronecrosis is about 5%.
Evaluation of cord mobility after 50.4 Gy or at the end of radiation therapy has not been helpful in predicting local control (64). Some patients in whom the vocal cord remained fixed have had local tumor control of the disease for 2 years or longer after radiation therapy.
The major difficulty in using irradiation for the more advanced lesions is distinguishing radiation edema from local recurrence during follow-up examinations (87). Progressive laryngeal edema, persistent throat pain, or fixation of a previously mobile vocal cord frequently signifies recurrent disease in the larynx, although a few patients with these findings remain disease-free with long-term follow-up.
Extended hemilaryngectomy has been used by a few surgeons in the treatment of well-lateralized fixed-cord lesions. A permanent tracheostomy is usually required because a portion of the cricoid is resected, but a useful voice may be retained (88).
Advanced Vocal Cord Carcinoma
Advanced lesions usually show extensive subglottic and supraglottic extension, bilateral glottic involvement, and invasion of the thyroid, cricoid, or arytenoid cartilage, or frequently all three (5,6). The airway is compromised, necessitating a tracheostomy at the time of direct laryngoscopy in approximately 30% of patients. Clinically positive lymph nodes are found in about 25% to 30% of patients.
The mainstay of treatment is total laryngectomy, with or without adjuvant radiation therapy. The most frequent sites of local failure after total laryngectomy are around the tracheal stoma, in the base of tongue, and in the neck lymph nodes or soft tissues of the neck. If the neck has clinically negative findings before surgery and if postoperative irradiation is planned, neck dissection may be withheld, and radiation therapy may be used to treat both sides of the neck. However, in practice, most surgeons prefer to perform elective bilateral selective (levels II-IV) neck dissections in conjunction with a total laryngectomy for T3N0 or T4N0 laryngeal cancer, even if postoperative irradiation is planned. If the lymph nodes are clinically positive, a therapeutic neck dissection is performed at the time of laryngectomy.
The indications for postoperative radiation therapy include close or positive margins, significant subglottic extension (1 cm or more), cartilage invasion, perineural invasion,
P.983
endothelial-lined space invasion, extension of the primary tumor into the soft tissues of the neck, multiple positive neck nodes, extracapsular extension, and control of subclinical disease in the opposite neck (2,41). Preoperative irradiation is indicated for patients who have fixed neck nodes, have had an emergency tracheotomy through tumor, or have direct extension of tumor involving the skin.
Definitive irradiation is prescribed for the patient who refuses total laryngectomy or is medically unsuitable for major surgery.
As previously stated, there is evidence that two to three cycles of neoadjuvant chemotherapy followed by radiation therapy in patients obtaining at least a partial response may provide a moderate likelihood of larynx preservation without compromising cure (16). Recent data suggest that concomitant chemotherapy and irradiation is more efficacious than irradiation alone or induction chemotherapy followed by radiation therapy (23,90). The optimal combination of concomitant chemotherapy and irradiation is unclear (68).
A randomized intergroup trial (Radiation Therapy Oncology Group 91–11) compared three treatment arms: Arm A, three cycles of induction cisplatin and fluorouracil followed by irradiation in complete and partial responders; Arm B, radiation therapy and concomitant cisplatin (100 mg/m2 on days 1, 22, and 43 of radiation therapy); and Arm C, once-daily irradiation (70 Gy in 35 fractions during 7 weeks) alone (23). Five hundred forty-seven patients were randomized and followed for a median of 3.8 years; 518 patients were evaluable. The rates of larynx preservation were: Arm A, 72%; Arm B, 84%; and Arm C, 67%. The rates of larynx presentation were significantly improved for Arm B; there was no significant difference between Arm A and Arm C. The 5-year survival rates were similar for the three treatment groups: Arm A, 55%; Arm B, 54%; and Arm C, 56%. The likelihood of developing distant metastases was lower for the two groups of patients that received adjuvant chemotherapy.
Surgical Treatment
Cordectomy is an excision of the vocal cord and may be performed by the transoral approach usually with a laser or externally by a thyrotomy. Its use is usually confined to small lesions of the middle third of the cord. After cordectomy, a pseudocord is formed, and the patient has a useful, if somewhat harsh, voice.
Vertical partial laryngectomy (i.e., hemilaryngectomy) allows removal of limited cord lesions with preservation of voice. One entire cord with as much as a third of the opposite cord with the adjacent thyroid cartilage is the maximum cordal involvement suitable for surgery in men; women have a smaller larynx, and usually only one vocal cord may be removed without compromising the airway. Partial fixation of one cord is not a contraindication to hemilaryngectomy, but only a few surgeons have attempted hemilaryngectomy for selected fixed-cord lesions. The maximum subglottic extension suitable for hemilaryngectomy is 8 to 9 mm anteriorly and 5 mm posteriorly; this limit is necessary to preserve the integrity of the cricoid. Tumor extension to the epiglottis, false cord, or both arytenoids is a contraindication to hemilaryngectomy.
Supracricoid partial laryngectomy is used for selected T2 and T3 glottic carcinomas and entails removal of both true and false cords as well as the entire thyroid cartilage. The cricoid is sutured to the epiglottis and hyoid (cricohyoidopexy).
Total laryngectomy with or without neck dissection is the operation of choice for advanced lesions and as a salvage procedure for radiation therapy failures in lesions that are not suited for conservation surgery. The entire larynx is removed, and the pharynx is reconstructed. A permanent tracheostomy is required. Speech may be reconstituted with a prosthesis or with an electrolarynx. One hundred four (63%) of 166 patients entered into the surgery and postoperative irradiation arm of the Veterans Affairs Laryngeal Cancer Study Group randomized trial were evaluable for communication status at 2 years after treatment (38). Ninety-six patients had undergone a total laryngectomy and communicated as follows: Tracheoesophageal, 27 (28%); esophageal, 5 (5%); artificial larynx, 47 (50%); nonvocal, 7 (7%); and no data, 10 (10%) (38). One hundred seventy-three patients underwent total laryngectomy and postoperative radiotherapy at the University of Florida and 69 patients were evaluable for 5 years or longer (62). Voice rehabilitation was accomplished as follows: Tracheoesophageal, 19%; artificial larynx, 57%; esophageal, 3%; nonvocal, 14%; and no data, 7%.
Radiation Therapy Technique
Irradiation for T1 or T2 vocal cord cancer is delivered by small portals covering only the primary lesion. The cervical lymph node chain is not electively treated. For T1 lesions, radiation therapy portals extend from the thyroid notch superiorly to the inferior border of the cricoid and fall off anteriorly. The posterior border depends on the posterior extension of the tumor (73). For T2 tumors, the field is extended depending on the anatomic distribution of the tumor. The field size ranges from 4 × 4 cm to 5 × 5 cm (plus an additional 1 cm of “flash” anteriorly) and is occasionally 6 × 6 cm for a large T2 lesion. Portals larger than this increase the risk of edema without improving the cure rate.
A commonly used dose-fractionation schedule at many institutions is 66 Gy for T1 lesions and 70 Gy for T2 cancers given in 2-Gy fractions. Evidence suggests that increasing the dose per fraction may improve the likelihood of local control (4,19,36,37,45,69,97,119). Ample data suggest that 1.8 Gy once daily results in significantly lower local control rates compared with 2 Gy once daily (45). Yamakazi et al. (121) recently reported a prospective trial in which patients with T1N0 squamous cell carcinoma of the glottic larynx were randomized to definitive radiotherapy at 2 Gy per fraction or 2.25 Gy per fraction. The 5-year local control rates were 77% after 2 Gy per fraction and 92% after 2.25 Gy per fraction (p = .004); there was no difference in either acute or late toxicity. Patients with T1 or T2 vocal cord cancer who are treated with once-a-day fractionation at the University of Florida are irradiated with 2.25 Gy per fraction; the dose-fractionation schemes used are shown as follows: Tis–T2 A, 63 Gy in 28 fractions; and T2B, 65.25 Gy in 29 fractions.
At the University of Florida, patients are treated in the supine position; the field borders for a patient with a T1N0 cancer are depicted in Fig. 44.7 (73). The field is checked by the physician at the treatment machine according to palpable anatomic landmarks. This allows the treatment volume to be kept at a minimum and reduces the risk of geographic miss. A three-field technique, using 4-or 6-MV x-rays, is used to deliver approximately 95% of the dose through opposed lateral wedged fields weighted to the side of the lesion; the remaining dose is delivered by an anterior field shifted 0.5 cm toward the side of the lesion (Fig. 44.8) (73). The tumor dose is usually specified at the 95% normalized isodose line.
Irradiation of T3 and T4 lesions requires larger portals, which include the jugulodigastric and middle jugular lymph nodes (Fig. 44.9) (74,85). The inferior jugular lymph nodes are included in a separate low-neck portal. Patients treated at the University of Florida are irradiated in a continuous-course twice daily at 1.2 Gy per fraction to a total dose of 74.4 Gy. The portals are reduced after 45.6 Gy in 38 fractions; the reduced portals cover only the primary lesion.
P.984
Intensity-modulated radiation therapy (IMRT) is employed if there is a clear advantage associated with this technique. Disadvantages associated with IMRT include increased dose inhomogeneity, increased total body dose, and increased labor and expense. The most common indications for IMRT for laryngeal cancers are the occasional patients with a node-positive T3–T4 cancer in which the retropharyngeal nodes are electively irradiated and the dose to the contralateral parotid gland reduced and/or a difficult low match between the lateral fields used to treat the primary site and upper neck and the anterior low neck field in a patient with a short neck and large shoulders. In the latter instance, IMRT could be used to encompass the entire target volume and avoid the problem of field junctioning entirely. IMRT is especially useful for patients with extensive subglottic invasion where achieving an adequate inferior margin with conventional lateral portals may not be possible.
Evidence from both retrospective and randomized trials points to improved therapeutic ratios with altered fractionation schedules (68). Given that irradiation is effective treatment for head and neck primary squamous cell carcinoma, it should not be surprising that higher doses of irradiation given more intensively would be more effective at providing tumor control. Because most observers have noted no increase in late toxicity with the various regimens, it generally is concluded that these schedules yield an improved therapeutic ratio. A recently updated Radiation Therapy Oncology Group 90–03 trial (24,109) reported on 1,073 patients who were randomly selected to receive one of four fractionation schedules:
• Standard fractionation: 2 Gy per fraction, once a day, 5 days a week, to a total dose of 70 Gy in 35 fractions during 7 weeks;
• Hyperfractionation: 1.2 Gy per fraction, twice daily (≥6 hours apart), 5 days a week, to a total dose of 81.6 Gy in 68 fractions during 7 weeks;
• Accelerated fractionation with split: 1.6 Gy per fraction, twice daily (≥6 hours apart), 5 days a week, to a total dose of 67.2 Gy in 42 fractions during 6 weeks, including a 2-week rest after 38.4 Gy, or;
• Accelerated fractionation with concomitant boost: 1.8 Gy per fraction, once a day, 5 days a week to a large field, plus 1.5 Gy per fraction once a day to a boost field given 6 or more hours after treatment of the large field for the last 12 treatments days, to a total dose of 72 Gy in 42 fractions during 6 weeks.
The 5-year locoregional failure rates were standard fractionation, 59%; hyperfractionation, 51%; accelerated split course, 58%; and concomitant boost, 52%. Both the hyperfractionation and concomitant boost schedules yielded locoregional control rates that were significantly better than standard fractionation. There was a trend toward improved overall survival with hyperfractionation, but no difference in cause-specific survival. Acute toxicity was increased with all three altered fractionation schedules; there was a modest increase in late effects with the concomitant boost schedule.
The treatment technique used for postoperative irradiation after total laryngectomy is depicted in Figure 44.10 (2). The treatment technique for preoperative irradiation is essentially the same as that used for irradiation alone. Alternatively, IMRT may be employed for the indications discussed previously.
Treatment of Recurrence
Most recurrences appear within 18 months, but late recurrences may appear after 5 years. The latter are likely second primary malignancies. The risk of metastatic disease in lymph nodes increases with local recurrence (63).
Recurrence after Radiation Therapy
With careful follow-up, recurrence is sometimes detected before the patient notices a return of hoarseness. There is often minimal lymphedema for 1 to 2 months after irradiation, which usually subsides or stabilizes. An increase in edema, particularly if associated with hoarseness or pain, suggests recurrence, even if there is no obvious tumor. Fixation of a previously mobile
P.985
vocal cord usually implies local recurrence, but we have occasionally observed a patient who has experienced a fixed cord with an otherwise normal-appearing larynx and who has not shown evidence of recurrence.
It may be difficult to diagnose recurrence if the tumor is submucosal. Generous, deep biopsies are required. If recurrence is strongly suspected, laryngectomy may rarely be advised without biopsy-confirmed evidence of recurrence. Positron emission tomography may be useful to distinguish recurrent tumor from necrosis.
Radiation therapy failures may be salvaged by cordectomy, hemilaryngectomy, supracricoid partial laryngectomy, or total laryngectomy. Biller et al. (8) reported a 78% salvage rate by hemilaryngectomy for 18 selected patients in whom irradiation failed; total laryngectomy was eventually required in 2 patients. Only two patients died of cancer. These investigators offered guidelines for using hemilaryngectomy: Contralateral vocal cord is normal, arytenoid is not involved, subglottic extension does not exceed 5 mm, and vocal cord is not fixed. In our experience, 14 patients irradiated for T1 or T2 vocal cord cancers underwent a hemilaryngectomy after local recurrence and 8 were successfully salvaged (60).
Recurrence after Surgery
The rate of salvage by irradiation for recurrences or new tumors that appear after initial treatment by hemilaryngectomy is about 50%. Lee et al. (53) reported seven successes among 12 patients; one lesion was later controlled by total laryngectomy. Total laryngectomy can be used successfully to treat hemilaryngectomy failures not suitable for radiation therapy. Irradiation rarely cures patients with recurrence in the neck or stoma after total laryngectomy.
posted by stefanoxx at 6:41 AM
0 Comments:
Post a Comment
<< Home