Therapy with neoadjuvant imatinib is under evaluation. It may be used for patients with very large primary gastrointestinal stromal tumors (GIST) or poorly positioned small GIST (considered unresectable without the risk of unacceptable morbidity or functional deficit) until surgical therapy is feasible, which can take as long as 6 to 12 months.[1,2] There are no controlled trials addressing the benefits of imatinib in this setting, so the impact of neoadjuvant imatinib on overall survival (OS) is...
A combination of surgery with postoperative radiation therapy plus chemotherapy in high-risk patients.
Radiation therapy alone for patients with stage IVA cancer of the tonsil that does not deeply invade the tongue base.[2,3]
New surgical techniques for resection and reconstruction developed in the last 7 to 10 years that provide access and at least partial function restoration 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. 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 when possible, as shown in RTOG-7303, for example. This approach has become the standard in this specific grouping whenever it can be applied. Patients with stage IVA cancer of the tonsil treated by aggressive radiation therapy alone have similar results to patients treated with combination therapy.[Level of evidence: 3iiiDiii]
Specific surgical procedures and their modifications are not designated here because of the wide variety of surgical approaches to the area, the variety of opinions about the role of modified neck dissections, and the multiple reconstructive techniques that may give the same results. This group of patients should be managed by surgeons who are skilled in the multiple procedures available and actively and frequently involved in the care of these patients.
Treatment options under clinical evaluation:
Chemotherapy has been combined with radiation therapy in patients who have locally advanced disease that is surgically unresectable.[5,6,7,8,9,10] The best chemotherapy to use and the appropriate way to integrate the two modalities are still unresolved.[11,12]
Similar approaches in patients with resectable disease, when resection would lead to a major functional deficit, are also being explored in randomized trials. A trial has shown that chemotherapy (i.e., carboplatin plus fluorouracil) with radiation therapy provides better local control and improved 3-year actuarial overall survival (OS) and disease-free survival than daily radiation therapy alone.[14,15]
A meta-analysis of 63 randomized, prospective trials published between 1965 and 1993 showed an 8% absolute survival advantage in the subset of patients receiving concomitant chemotherapy and radiation therapy.[Level of evidence: 2A] Patients receiving adjuvant or neoadjuvant chemotherapy had no survival advantage. Cost, quality of life, and morbidity data, however, were not available; no standard regimen existed; and, the trials were felt to be too heterogenous to provide definitive recommendations. The results of 18 ongoing trials may further clarify the role of concomitant chemotherapy and radiation therapy in the management of oropharyngeal cancer.
Radiation clinical trials, such as RTOG-8313, for example, have evaluated hyperfractionation schedules and/or brachytherapy and should be considered. One trial has shown a higher local control rate with very accelerated radiation therapy, but the OS was not improved with this approach.[Level of evidence: 1iiA]