Evaluating contralateral neck failure in patients with lateralized OPSCC treated with transoral robotic surgery and neck management based on pre-operative SPECT-CT lymphatic mapping

In the present study, we report early oncological outcomes of primary surgical treatment of lateralized early stage OPSCC. Our results demonstrate excellent overall survival outcomes, low rate of locoregional recurrence (7.7%), with no cases of contralateral neck failure. Many patients with lateralized tumors in the oropharynx treated with surgical resection undergo unilateral neck dissection in the absence of contralateral disease on axial imaging, notwithstanding the fact that occult nodal disease may occur in the contralateral neck with a low reported rate estimated to 7.4% of patients [6]. Here we demonstrate the feasibility of using lymphatic mapping with SPECT-CT to select patients for unilateral neck treatment. Our group has previously reported the feasibility of using this imaging modality to identify lymphatic drainage patterns, and now we demonstrate that treatment of the contralateral neck informed by lymphatic mapping provides acceptable early disease control in the contralateral neck and identifies patients at risk for contralateral nodal drainage [10].

In the present study, none of the patients subsequently failed in the contralateral neck. Several reports have consistently demonstrated low rates of contralateral neck failure for lateralized tumors [8, 9]. In a recent literature review, Al-Mamgani et al. [12] assessed regional recurrence for primary unilateral irradiation of oropharyngeal cancers. This review included 1116 patients treated for OPSCC and revealed an overall incidence of 2.4% for contralateral regional failure. In addition, the authors noted that midline tumor involvement was the most significant factor predictive for contralateral neck failure. Another recently published study in the surgical literature [13] showed in a cohort of 81 patients treated for T1-2 N0-2b squamous cell carcinomas of the tonsillar fossa, no cases of contralateral neck failure with an average follow-up of 5.7 years.

One patient in our study showed bilateral neck lymphatic drainage observed on pre-operative lymphoscintigraphy, with no concerning lymph nodes noted on CT and MRI imaging, and with a primary tumor involving the tonsillar fossa with soft palate invasion but not encroaching (> 1 cm) the midline. The patient was managed by primary site resection and unilateral neck dissection, given the absence of gross disease in the contralateral neck. Furthermore, the pre-operative imaging was suggestive of more than one ipsilateral lymph node and the initial plan was for planned adjuvant radiotherapy as the patient had declined upfront chemoradiotherapy due to concerns of toxicity related to systemic therapy. As such, the patient received adjuvant therapy to manage the potential for occult nodal metastases to the contralateral neck. Other potential treatment options exist for management of contralateral lymphatic drainage in the absence of gross disease. De Veij Mestdagh et al. are evaluating the use of sentinel lymph node biopsy for identification of occult contralateral neck disease in patients with lateralized oropharyngeal cancers [14]. The benefit of this approach is that pathologic disease can be identified and properly staged. Alternatively, one may consider contralateral neck dissection to identify pathologically occult nodal disease. However, the drawback of either of these approaches is the potential morbidity of further surgical intervention in the contralateral neck, despite the fact the patient was likely and did receive adjuvant radiotherapy to the undissected contralateral neck. Regardless of the approach, we would advocate for some management of the contralateral neck in patients with lymphatic drainage to that side because of the possibility of occult nodal disease.

A lymphatic mapping approach also identified unpredictable patterns of lymphatic drainage such as drainage to retropharyngeal lymph nodes. Drainage to the retropharyngeal lymph node basin may be relatively uncommon with reports describing a prevalence of less than 10% [15,16,17], and most commonly associated with pharyngeal wall primary tumors. In patients treated with a primary surgical modality, dissection of retropharyngeal nodal basin is not commonly performed although some centres have published techniques to dissect the retropharyngeal nodal basin [18, 19] with either a transcervical or transoral approach. Use of lymphatic mapping may help identify patients at risk for retropharyngeal nodal drainage. In the present series, we demonstrated one patient who had evidence of retropharyngeal lymphatic drainage. This same patient had an HPV negative primary tumor of the tongue base and glossotonsillar sulcus with a single metastatic lymph node with minor extranodal extension and with no evidence of pathologic disease in the dissected retropharyngeal basin. In this case, the lymphatic mapping study helped identify a potential route of spread requiring surgical management, albeit there was no evidence of pathologic disease in this basin. This finding may suggest that lymphatic mapping may further add value in directing treatment of patients with oropharyngeal cancers.

Our results also support a promising role for treatment deintensification among patients with lateralized oropharyngeal tumors. A cautious selection of patients and avoidance of unnecessary treatment to the contralateral neck, can significantly reduce short- and long-term treatment related toxicities [20]. A personalized management of patients can potentially reduce costs associated to treatment related toxicities, such as hospital admission (pneumonia, dysphagia, malnutrition, etc.) and additional interventions (gastrostomy feeding tube placement, tracheostomy, etc.) [21, 22]. Jensen et al. [23] has showed that incapacitating side effect of radiation therapy can be significantly reduced with ipsilateral treatment of the neck. Patients with unilateral treatment showed significantly lower levels of xerostomia, dysphagia, hoarseness, fibrosis and edema in comparison to patients that underwent bilateral irradiation. Other potential benefit includes improvement of quality of life and level of functioning [24]. Several ongoing prospective randomized trials are currently assessing the role of deintensification therapy for OPSCC [25].

Limitations of this study include a limited number of patients, the retrospective nature of the data, and a conservative long-term follow-up duration. Approximately three quarters of patients (76.6%) in our study showed positive staining for p16, demonstrating heterogenicity of the oropharyngeal tumors treated, however, previous studies did not show significant differences for nodal metastasis between HPV positive and negative OPSCC [26]. In addition, although SPECT-CT lymphoscintigraphy appears as an interesting tool for the assessment of oropharyngeal malignancies, it should be used with caution for tumors close to midline (soft palate, tongue base) which may not be amenable to ipsilateral treatment due to an increased risk of bilateral lymphatic drainage [12].

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