Neoadjuvant Therapy for Organ Preservation in Head and Neck Cancer

Abstract

Objectives/Hypothesis: We designed two sequential trials of induction chemotherapy followed by definitive radiation in patients with potentially resectable head and neck cancer to determine whether organ preservation is feasible without apparent compromise of survival. Study Design: Both trials were Phase II studies. Methods: Two clinical trials were conducted sequentially at the University of Michigan. Fifty-two patients enrolled in the first study and were treated with a planned three cycles of carboplatin and 5-fluorouracil. Patients who achieved at least 50% reduction in the size of the primary tumor received definitive radiation therapy, to a dose of 6600 to 7380 cGy. Patients with minimal response or progression had immediate salvage surgery. Thirty-seven patients enrolled in the second trial, in which the chemotherapy consisted of carboplatin, 5-fluororuracil, and leukovorin. Responders were treated with accelerated radiation therapy, to a total dose of 7120 cGy delivered in 41 fractions over 5.5 weeks. Results: Toxicity and response were similar in both trials; therefore, the results are reported first separately and then combined for all 89 patients. Tumor sites included: oropharynx, 55 patients; hypopharynx, 34 patients. Eighty-three percent of patients tolerated all three cycles of chemotherapy and toxicity was mild. Response to chemotherapy was: 48% complete response at the primary tumor site, and 34% partial response at the primary tumor site. Initial organ preservation at individual tumor sites was: oropharynx, 58%; hypopharynx, 59%. Median survival was 28 months, and survival at 3 and 5 years was 40% and 24%, respectively. Conclusions: These two regimens were well tolerated, and survival did not appear to be compromised by organ preservation treatment compared with historical controls. This approach warrants further investigation, particularly in those patients for whom surgery could be functionally debilitating.

T1 and T2 hypopharyngeal cancer treatment with laser microsurgery

“…This is already the preferred treatment strategy for cases with advanced disease [12][13][14]. Results from the present study suggest that even cases with early local disease might benefit from this tactic.…”

“…Hypopharyngeal lesions in general have been traditionally characterized by poor survival outcomes [2]. The use of open surgery, radiation treatment followed by surgery as salvage, and combined nonsurgical conservation regimens have all produced 5-year DSS rates ranging between 17% and 59% [1,[8][9][10][11][12][13][14]. It is obvious that, although these studies did not specifically focus on early local lesions, they produced discouraging oncologic results.…”

“…It is obvious that, although these studies did not specifically focus on early local lesions, they produced discouraging oncologic results. Moreover, organ preservation rates have been similarly discouraging, even with modalities that actually aimed on function retention [8][9][10][11][12][13][14].…”

Different clinical outcomes between locally advanced hypopharyngeal and oropharyngeal cancer treated with definitive concurrent chemoradiotherapy: implication for subgroup selection for induction chemotherapy

“…Multidisciplinary treatment including surgery, radiotherapy and chemotherapy has been applied to treat this tumor, and has improved the prognosis of these patients (14,15).…”

IMRT in Hypopharyngeal Tumors

“…Locoregional disease control rates of approximately 40-70% [2,3,6,11,15,17,18,20,21,24,26,27,30] or even less [4,9,13] are reported for hypopharyngeal cancer (HC) patients receiving three-dimensional conventional radiation therapy (3DCRT) ± chemotherapy, while late-term dysphagia rates range between 40% and 75% in the majority of published articles [1,6,19,20,28]. The main challenge in conventional irradiation of HC is an appropriate dose coverage mainly to the dorsal aspect of the tumor and the boost planning target volume (PTV1), respectively, which is often close to or overlaps the spinal cord in the lateral-beam projection used for 3DCRT.…”