Oropharynx‐directed ipsilateral irradiation for p16‐positive squamous cell carcinoma involving the cervical lymph nodes of unknown primary origin

Chen, Allen M.; Meshman, Jessica; Hsu, Sophia; Yoshizaki, Taeko; Abemayor, Elliot; John, Maie St.

doi:10.1002/hed.24906

Cited by 15 publications

(21 citation statements)

References 24 publications

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“…EMI to the oropharynx will likely play an important role in optimizing locoregional control and alleviating acute and late toxicity by sparing the aerodigestive tract. [24][25][26] Regarding radiation dose, a dose of 60Gy were used in our study for the consideration that the high-risk mucosal regions were hiding small cancers. IMRT techniques could spare patients from extensive toxicity.…”

Section: Discussionmentioning

confidence: 99%

Long‐term results of elective mucosal irradiation for head and neck cancer of unknown primary in Chinese population: The EMICUP study

Dou

Zhang

et al. 2020

Cancer Medicine

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Objective Controversy still exists regarding the volume of radiation for head and neck cancer of unknown primary (HNCUP). Theoretically, elective mucosal irradiation (EMI) should achieve a balance between survival and toxicity. This prospective study was conducted to evaluate the long‐term benefit of EMI in Chinese HNCUP patients. Methods A phase II, single‐arm trial was performed at two centers in China. HNCUP patients with pathologically confirmed metastatic squamous cell carcinoma or poorly differentiated carcinoma were enrolled. Patients with metastatic lymph nodes limited to level IV and/or the supraclavicular fossa were excluded. The EMI approach was specifically customized to Chinese patients by differentiating HNCUP as putative nasopharyngeal carcinoma (NPC) or non‐putative NPC. The primary endpoint was 3‐year mucosal recurrence‐free survival (MRFS). Results A total of 48 patients were enrolled between 02/02/2010 and 08/01/2018; 46 patients were analyzed, including 24 putative NPC and 22 non‐putative NPC patients. No primary recurrence was observed during a median follow‐up period of 70 months, and only 1 patient experienced out of field recurrence in the contralateral neck. The 3‐year MRFS was 90.6% (95%CI: 76.4%‐96.4%). The 5‐year MRFS, regional‐recurrence free survival (RRFS) and overall survival (OS) were 90.6% (95%CI: 76.4%‐96.4%), 86.0% (95%CI: 71.1%‐93.7%), and 90.6% (95%CI: 76.4%‐96.4%), respectively. No grade 4 acute or late toxicities occurred, and the most frequent grade 3 acute toxicity was oral mucositis (45.7%). Conclusion To the best of our knowledge, this is the first prospective study to evaluate the long‐term outcomes of EMI in Chinese HNCUP patients. Excellent MRFS and OS rates were observed. Further randomized studies are warranted.

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Section: Discussionmentioning

confidence: 99%

Long‐term results of elective mucosal irradiation for head and neck cancer of unknown primary in Chinese population: The EMICUP study

Dou

Zhang

et al. 2020

Cancer Medicine

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“…79,80 Four studies using unilateral cervical neck radiation in a subset of patients with HPV/p16-positive SCCUP yielded different results in terms of treatment outcomes ranging from inferior to equal or superior to bilateral radiation. 81 The use of long-term gastrostomy tube is rare with very few stenosis and stricture complications. 81 The use of long-term gastrostomy tube is rare with very few stenosis and stricture complications.…”

Section: Radiation With or Without Concomitant Chemotherapymentioning

confidence: 99%

“…23,54,68,69 Ipsilateral radiotherapy seems well tolerated with acceptable toxicity, which includes dysgeusia, salivary alteration, and skin erythema that reversed after symptomatic treatment. 23,81 Ninety percent of patients rated their health-related quality of life as very good. 23,81 Ninety percent of patients rated their health-related quality of life as very good.…”

Section: Radiation With or Without Concomitant Chemotherapymentioning

confidence: 99%

Comprehensive management of HPV‐related squamous cell carcinoma of the head and neck of unknown primary

2019

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Background Human papillomavirus (HPV)‐related squamous cell carcinoma of unknown primary (SCCUP) is currently rising in incidence but lacks a validated management approach. Aims This paper reviews the clinical presentation, diagnosis, and treatment of HPV‐related SCCUP. Materials and Methods The Medline/Pubmed database was searched by using the following keywords “CUP”, “cancer of unknown primary”, “HPV”, “human papilloma virus”, and “head and neck”. The references of the publications of interest were also screened for relevant papers. Results The clinical assessment of HPV‐related SCCUP includes a complete clinical examination, an endoscopic evaluation with white‐light and narrow band imaging, and radiologic assessment using morphologic and metabolic imaging. If the diagnosis remains unconfirmed, endoscopic examination under anesthesia with tonsillectomy ± base of tongue mucosectomy is performed. The therapeutic rationale aims to eradicate the involved lymph nodes and potential primary tumor with a sequence of chemoradiotherapy and neck dissection. Discussion As a general approach, p16‐negative SCCUP are truly HPV negative, whereas p16‐positive specimens require confirmation with HPV in situ hybridization or polymerase chain reaction to confirm HPV infection. If a cervical metastasis is considered HPV positive, the primary lesion is likely in the oropharynx, and further diagnostic interventions such as tonsillectomy seems to be mandatory. Whether the optimal treatment is neck dissection followed by adjuvant radiotherapy or concomitant chemoradiotherapy (CRT) (in case of extranodal extension or advanced lymph node stages) or definitive CRT followed by neck dissection (in case of positive 18F‐FDG‐PET/CT) remains a matter of debate. Solid scientific evidence supporting treatment de‐escalation in HPV‐related SCCUP is lacking, and the results of ongoing trials are at the brink of reporting. Conclusion Currently, the treatment of patients with HPV‐related SCCUP should not differ from the standard treatment of other SCCUP patients and is similarly based on the staging of the disease and general condition of the patient.

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“…Efforts to de‐intensify therapy have resulted in studies of limited pharyngeal axis radiation. Chen et al reported 2‐year PFS of 87% in p16+ patients treated with oropharynx directed ipsilateral irradiation . Similarly, Hu et al showed a 5‐year regional control of 90% with an oropharynx‐directed radiation approach .…”

Section: Discussionmentioning

confidence: 95%

“…The decision to treat unilateral or bilateral necks in patients with HNCUP remains controversial; however, studies have shown decreased toxicity and improved patient‐reported outcomes for patients treated with unilateral neck treatment . Chen et al showed that a treatment approach targeting the unilateral neck can be used in well‐selected patients with p16‐positive disease . Tiong et al also found no contralateral neck recurrences in patients with p16‐positive HNCUP .…”

Section: Discussionmentioning

confidence: 99%

Pharyngeal‐sparing radiation for head and neck carcinoma of unknown primary following TORS assisted work‐up

Grewal

Rajasekaran²,

Cannady³

et al. 2019

The Laryngoscope

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Objective In patients with head and neck carcinoma of unknown primary (HNCUP;pT0) following TORS‐assisted workup, we have adopted a pharyngeal‐sparing radiation therapy (PSRT) approach targeting only the at‐risk neck and omitting treatment of the pharynx. We report outcomes following PSRT, and compare to institutional historical control subjects who received pharyngeal‐targeted RT (PRT). Methods Between 2009 and 2018, 172 patients underwent TORS‐assisted endoscopy as part of their workup for HNCUP. Following TORS, 54 patients had pT0 disease, of which 45 received RT. Forty‐nine percent received PSRT and 51% received PRT. Results No statistically significant differences existed between the PSRT and PRT groups with respect to overall nodal distribution, p16 positivity (55% vs. 43%, P = .12), neck dissection rates (77% vs. 65%, P = .51), and administration of chemotherapy (55% vs. 65%, P = .55). Median follow‐up for PSRT and PRT groups were 24 and 28 months, respectively (P = .04). Two‐year RFS was 86% and 74% for PSRT and PRT patients, respectively (log‐rank P = .30). Three and six patients recurred after PSRT and PRT, respectively. Two‐year OS for PSRT and PRT patients was 91% and 74%, respectively (log‐rank P = .31). Compared to PRT, PSRT was associated with statistically significantly less: grade 2+ mucositis (18% vs. 91%, P < .01), new opioid requirement (27% vs. 91%, P < .01), mean weight loss during RT (6.2 lbs vs. 17.4 lbs, P < .01), feeding tube placement during RT (5% vs. 43%, P < .01), and treatment‐related unplanned hospitalizations (9% vs. 39%, P = .04). Conclusion Following TORS‐assisted management of patients with pT0 HNCUP, we observed reduced toxicity following PSRT compared to PRT without apparent compromise of disease cure. Level of Evidence Level 3 evidence, retrospective review comparing cases and controls Laryngoscope, 130:691–697, 2020

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Oropharynx‐directed ipsilateral irradiation for p16‐positive squamous cell carcinoma involving the cervical lymph nodes of unknown primary origin

Abstract: Oropharynx-directed, ipsilateral radiation results in disease control that compares favorably with historical controls treated by comprehensive mucosal and bilateral neck radiation.

Cited by 15 publications

References 24 publications

Long‐term results of elective mucosal irradiation for head and neck cancer of unknown primary in Chinese population: The EMICUP study

Long‐term results of elective mucosal irradiation for head and neck cancer of unknown primary in Chinese population: The EMICUP study

Comprehensive management of HPV‐related squamous cell carcinoma of the head and neck of unknown primary

Pharyngeal‐sparing radiation for head and neck carcinoma of unknown primary following TORS assisted work‐up

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