Malignant Tracheal Tumors: Current Management Strategies
Malignant Tracheal Tumors: Current Management Strategies
The best opportunity for achieving long-term cure is still complete surgical resection of the tumor supplemented by postoperative adjuvant therapy. However, Honings et al. reported epidemiological data indicated that significantly more patients could have received curative surgical therapy than were actually treated (about 2.3 times).
The goal of surgical resection with a curative intent is to achieve complete resection without cancer cells seen microscopically at the margins. Because of the indolent nature of ACC, incomplete resection margins are commonly seen. Surgical resection has been shown to improve survival in the patients with ACC who have distant metastases. The role of other bronchoscopic modalities for the treatment of ACC is under study. In centers that have expertise with tracheal tumors, resection rates of up to 70% and perioperative mortality rates as low as 3% have been reported.
Five-year survival rate has been reported to be greater than 50% for patients undergoing surgery, whereas it is only 10% for the patients who are determined to be nonsurgical candidates. For tumors extending greater than 50% of the tracheal length, surgical resection and tracheal reconstruction have been associated with high mortality. Therefore, surgery is not recommended in these patients. Surgery is also contraindicated in patients with involvement of heart or aorta, distant metastases, involvement of multiple lymph nodes on PET scan, and in those with prior mediastinal surgeries or irradiation with a dose greater than 60 Gy.
Radiotherapy is indicated as adjuvant therapy following surgical resection for almost all patients. Improved survival has been reported in SCC, even in cases with negative postsurgical resection margins. ACCs are typically less radiosensitive as compared with SCC. However, adjuvant radiotherapy has been known to reduce recurrence rates in the patients with ACC.
Radiation therapy is the first-line treatment for nonsurgical candidates and can also be used for palliation in advanced disease. Neoadjuvant radiotherapy prior to surgery in surgical candidates does not appear to improve survival. Intraluminal brachytherapy is an additive therapy following external-beam radiation therapy, which increases local tumor control.
In the absence of prospective randomized control trials, the role of systemic chemotherapy as a primary treatment or as an adjunctive therapy remains unclear. However, there have been recent case reports demonstrating successful outcomes with a combination of chemotherapy with radiation therapy in nonsurgical candidates. Combination therapy might be a suitable option for patients with unresectable tumors or who are not surgical candidates. Some of the commonly used chemotherapeutic regimens include Carboplatin and Paclitaxel containing regimens, Cisplatin, 5-fluorouracil, and Etoposide containing regimens, and Cisplatin and Vinorelbine containing regimens. However, the use and timing of various regimens remains under study.
There is a lack of sufficient data to recommend general use of combined high-precision radiotherapy techniques such as image-guided radiation therapy, intensity-modulated radiation therapy, or volumetric intensity-modulated arc therapy combined with platinum-based chemotherapy for the treatment of locally advanced tracheal tumors. These techniques might offer better disease control and constitute opportunities for potential research.
It has been shown that interventional techniques, when combined with adjuvant therapy, provide definitive treatment in selected cases. Additionally, these techniques serve as emergency therapy in patients presenting with complete or significant central airway obstruction prior to definitive treatment. However, studies have recommended against stent placement in patients who are surgical candidates. Interventional techniques have a greater role in palliation for patients in which surgery is not possible. When combined with radiation therapy, patients undergoing interventional techniques for palliation have a median survival of less than 12 months.
Available interventional options include the use of laser therapy, cryotherapy, electrocautery, photodynamic therapy, brachytherapy, and argon plasma coagulation, with or without stents. These techniques allow for intraluminal debulking of the tumor. Each technique has its unique advantages and disadvantages (Table 3).
Alternative strategies such as tracheal transplantation or those that aim at replacing the trachea with other viable or nonviable substitutes such as foreign materials, tissue engineering, and autogenous tissues have not yet developed sufficiently to enter routine clinical practice. Despite advances in surgical techniques, attempts at tracheal transplantation in such patients have been limited.
Advances in Management
Surgical Techniques
The best opportunity for achieving long-term cure is still complete surgical resection of the tumor supplemented by postoperative adjuvant therapy. However, Honings et al. reported epidemiological data indicated that significantly more patients could have received curative surgical therapy than were actually treated (about 2.3 times).
The goal of surgical resection with a curative intent is to achieve complete resection without cancer cells seen microscopically at the margins. Because of the indolent nature of ACC, incomplete resection margins are commonly seen. Surgical resection has been shown to improve survival in the patients with ACC who have distant metastases. The role of other bronchoscopic modalities for the treatment of ACC is under study. In centers that have expertise with tracheal tumors, resection rates of up to 70% and perioperative mortality rates as low as 3% have been reported.
Five-year survival rate has been reported to be greater than 50% for patients undergoing surgery, whereas it is only 10% for the patients who are determined to be nonsurgical candidates. For tumors extending greater than 50% of the tracheal length, surgical resection and tracheal reconstruction have been associated with high mortality. Therefore, surgery is not recommended in these patients. Surgery is also contraindicated in patients with involvement of heart or aorta, distant metastases, involvement of multiple lymph nodes on PET scan, and in those with prior mediastinal surgeries or irradiation with a dose greater than 60 Gy.
Radiotherapy
Radiotherapy is indicated as adjuvant therapy following surgical resection for almost all patients. Improved survival has been reported in SCC, even in cases with negative postsurgical resection margins. ACCs are typically less radiosensitive as compared with SCC. However, adjuvant radiotherapy has been known to reduce recurrence rates in the patients with ACC.
Radiation therapy is the first-line treatment for nonsurgical candidates and can also be used for palliation in advanced disease. Neoadjuvant radiotherapy prior to surgery in surgical candidates does not appear to improve survival. Intraluminal brachytherapy is an additive therapy following external-beam radiation therapy, which increases local tumor control.
Chemotherapy
In the absence of prospective randomized control trials, the role of systemic chemotherapy as a primary treatment or as an adjunctive therapy remains unclear. However, there have been recent case reports demonstrating successful outcomes with a combination of chemotherapy with radiation therapy in nonsurgical candidates. Combination therapy might be a suitable option for patients with unresectable tumors or who are not surgical candidates. Some of the commonly used chemotherapeutic regimens include Carboplatin and Paclitaxel containing regimens, Cisplatin, 5-fluorouracil, and Etoposide containing regimens, and Cisplatin and Vinorelbine containing regimens. However, the use and timing of various regimens remains under study.
There is a lack of sufficient data to recommend general use of combined high-precision radiotherapy techniques such as image-guided radiation therapy, intensity-modulated radiation therapy, or volumetric intensity-modulated arc therapy combined with platinum-based chemotherapy for the treatment of locally advanced tracheal tumors. These techniques might offer better disease control and constitute opportunities for potential research.
Interventional Pulmonology Techniques
It has been shown that interventional techniques, when combined with adjuvant therapy, provide definitive treatment in selected cases. Additionally, these techniques serve as emergency therapy in patients presenting with complete or significant central airway obstruction prior to definitive treatment. However, studies have recommended against stent placement in patients who are surgical candidates. Interventional techniques have a greater role in palliation for patients in which surgery is not possible. When combined with radiation therapy, patients undergoing interventional techniques for palliation have a median survival of less than 12 months.
Available interventional options include the use of laser therapy, cryotherapy, electrocautery, photodynamic therapy, brachytherapy, and argon plasma coagulation, with or without stents. These techniques allow for intraluminal debulking of the tumor. Each technique has its unique advantages and disadvantages (Table 3).
Alternative Strategies
Alternative strategies such as tracheal transplantation or those that aim at replacing the trachea with other viable or nonviable substitutes such as foreign materials, tissue engineering, and autogenous tissues have not yet developed sufficiently to enter routine clinical practice. Despite advances in surgical techniques, attempts at tracheal transplantation in such patients have been limited.