Author: Mindy Tanzola, PhD
An Education Session at the 2023 ASCO Annual Meeting will focus on the treatment of oral cavity cancer, one of the most common types of head and neck cancer worldwide. The session will feature experts from medical, radiation, and surgical oncology to address all 3 treatment modalities, said Session Chair Ali Hosni, MBBCh, MSc, PhD, of Princess Margaret Cancer Center in Canada. The session will take place on June 4.
Although oral cavity cancer is diagnosed in more than 300,000 individuals worldwide each year,1 it receives less attention than other subsets of head and neck cancer, Dr. Hosni said, highlighting a need for education. In addition, oral cavity cancer often involves all 3 treatment modalities, which means there is a need for collaborative multidisciplinary care that also integrates the patient into treatment planning.
Role of Sentinel Lymph Node Biopsy
In his update on surgical approaches for oral cavity cancer, Stephen Y. Lai, MD, PhD, FACS, a head and neck cancer surgeon at The University of Texas MD Anderson Cancer Center, will first discuss the role of sentinel lymph node biopsy (SLNB) for these patients. Dr. Lai explained that lymph node metastases are sometimes found in patients with early-stage oral cavity cancer (T1-2) who are thought to be node-negative based upon imaging studies and clinical examination. However, evidence has shown that active management through elective neck dissection is associated with higher rates of overall survival and disease-free survival versus “watchful waiting” and therapeutic neck dissection.2 These findings highlight the importance of identifying lymph node involvement.
“The question has now become, do you need to comprehensively remove neck nodes … or can we do something similar to what is being done in melanoma and breast [cancer], where you are taking out just the first echelon lymph nodes that have the highest likelihood of harboring disease?” Dr. Lai asked.
SLNB could have multiple benefits, he added. It could reduce morbidity and maintain quality of life by reducing the risks associated with lymph node dissection in the neck, account for contralateral spread, and allow pathologists to focus on a small number of lymph nodes.
Although SLNB has been more widely adopted in Europe and Asia for early-stage oral cavity cancer, this is not yet the case in the United States. The phase II/III NRG-HN006 trial (NCT04333537), for which Dr. Lai is the study chair, is currently comparing SLNB against elective neck dissection for patients with early-stage oral cavity cancer and aims to provide a definitive answer regarding which treatment option is the optimal approach.
The other key topic Dr. Lai will discuss is how to define surgical margins in oral cavity cancer. “Even as we consider more conservative surgical approaches, tumor margin remains an absolutely critical factor for determining success of surgery,” he explained, adding that the margin status is also important for assessing the need for radiation therapy and/or chemotherapy after surgery.
Updates on Radiation Therapy
During his presentation, Dr. Hosni will discuss the role of radiation therapy in the treatment of oral cavity cancer. In addition to its use as adjuvant therapy after surgery to reduce the risk of recurrence, radiation therapy may be used in patients who do not wish to pursue surgery or who have comorbidities that excessively raise the risk of adverse outcomes with surgery.
For patients who are planning for radiation therapy after surgery, multidisciplinary management is important to ensure treatment is started in a timely manner, Dr. Hosni explained. In approximately 15% of patients planned for postsurgical radiation therapy, disease recurs before radiation therapy begins.3
The optimal management of patients with early recurrence has been a focus of Dr. Hosni’s research. He noted that these patients are often considered for purely palliative treatment, and their expected prognosis is quite poor. However, with the use of higher-dose radiation treatment and chemotherapy, the 3-year recurrence-free rate was 36%.3 Efforts are also underway to better understand factors associated with risk of distant metastasis in patients with oral cavity cancer, with the goal of adopting strategies to reduce its risk.4
Exploring the ‘Black Hole’ of Oral Cavity Cancer Treatment
Vanita Noronha, MD, of Tata Memorial Hospital in India, will discuss 2 areas that she said have until recently been a “therapeutic black hole” in the treatment of oral cavity cancer. First is the role of induction chemotherapy for maximizing mandibular preservation.
“In spite of sophisticated reconstruction,” she said, “there is a lot of data that shows that the quality of life of the patient goes down incrementally the more bone you resect.”
Moreover, she noted that pathology specimens sometimes show no tumor in the bone, so perhaps resection could have been avoided but was done to ensure negative margins.
Several trials have investigated neoadjuvant chemotherapy to improve mandibular preservation in oral cavity cancer. For example, one trial showed that the addition of primary chemotherapy to surgery did not affect survival but was associated with a higher rate of mandible preservation in patients with resectable oral cavity cancer.5 Similarly, in a single-center, randomized phase 2 study in patients with locally advanced oral cavity cancers, neoadjuvant chemotherapy was associated with mandibular preservation in 47% of patients with no negative impact on survival.6
Dr. Noronha will also discuss alternative options to high-dose cisplatin, the current standard of care for adjuvant concurrent chemoradiotherapy in patients with locally advanced head and neck cancer.
“This is a huge area of need,” she said, as toxicity substantially limits the use of cisplatin.
Multiple alternative regimens have been evaluated in clinical trials. Lower-dose weekly cisplatin has demonstrated noninferiority to high-dose cisplatin in patients with postoperative head and neck cancer if a sufficient dose is given.7 In a randomized phase 2 trial, postoperative chemoradiotherapy with docetaxel and cetuximab appeared to have more favorable outcomes than historic controls in patients with cisplatin-intolerant high-risk head and neck cancer.8 However, Dr. Noronha noted that if we were to extrapolate data from the definitive setting, cetuximab may not be an effective alternative to cisplatin as chemoradiotherapy.9,10
Recently, Dr. Noronha and colleagues published results from a randomized phase 3 trial demonstrating that in patients with cisplatin-ineligible locally advanced head and neck cancer who require chemoradiation, the addition of docetaxel to radiation therapy is associated with significant improvements in disease-free survival and overall survival.11
“In the past, [this was an area] that did not have a standard of care at all,” she said.
However, there is now progress, as a randomized phase 3 trial has shown an overall survival benefit with the addition of docetaxel to radiation therapy in cisplatin-ineligible patients who require chemoradiotherapy. Dr. Noronha concluded that although supporting data would be welcome, these findings suggest a new standard of care for these patients.
1.Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249.
2.D’Cruz AK, Vaish R, Kapre N, et al. Elective versus therapeutic neck dissection in node-negative oral cancer. N Engl J Med. 2015;373(6):521-529. Epub 2015 May 31.
3.Hosni A, Huang SH, Chiu K, et al. Predictors of early recurrence prior to planned postoperative radiation therapy for oral cavity squamous cell carcinoma and outcomes following salvage intensified radiation therapy. Int J Radiat Oncol Biol Phys. 2019;103(2):363-373. Epub 2018 Sep 21.
4.Hosni A, Huang SH, Xu W, et al. Distant metastases following postoperative intensity-modulated radiotherapy for oral cavity squamous cell carcinoma. JAMA Otolaryngol Head Neck Surg. 2017;143(4):368-375.
5.Licitra L, Grandi C, Guzzo M, et al. Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized controlled trial. J Clin Oncol. 2003;21(2):327-333.
6.Chaukar D, Prabash K, Rane P, et al. Prospective phase II open-label randomized controlled trial to compare mandibular preservation in upfront surgery with neoadjuvant chemotherapy followed by surgery in operable oral cavity cancer. J Clin Oncol. 2022;40(3):272-281. Epub 2021 Dec 6.
7.Kiyota N, Tahara M, Mizusawa J, et al. Weekly cisplatin plus radiation for postoperative head and neck cancer (JCOG1008): a multicenter, noninferiority, phase II/III randomized controlled trial. J Clin Oncol. 2022;40(18):1980-1990. Epub 2022 Mar 1.
8.Harari PM, Harris J, Kies MS, et al. Postoperative chemoradiotherapy and cetuximab for high-risk squamous cell carcinoma of the head and neck: Radiation Therapy Oncology Group RTOG-0234. J Clin Oncol. 2014;32(23):2486-2495. Epub 2014 Jul 7.
9.Gebre-Medhin M, Brun E, Engström P, et al. ARTSCAN III: a randomized phase III study comparing chemoradiotherapy with cisplatin versus cetuximab in patients with locoregionally advanced head and neck squamous cell cancer. J Clin Oncol. 2021;39(1):38-47. Epub 2020 Oct 14.
10.Mehanna H, Robinson M, Hartley A, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet. 2019;393(10166):51-60. Epub 2018 Nov 15.
11.Patil VM, Noronha V, Menon N, et al. Results of phase III randomized trial for use of docetaxel as a radiosensitizer in patients with head and neck cancer, unsuitable for cisplatin-based chemoradiation. J Clin Oncol. 2023;JCO2200980. [Epub ahead of print]
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