Nodal response after 46 Gy of intensity‐modulated radiotherapy is associated with human papillomavirus–related oropharyngeal carcinoma

Dronkers, Emilie A. C.; Koljenović, Senada; Verduijn, Gerda M.; Jong, Robert J. Baatenburg de; Hardillo, José A.

doi:10.1002/lary.27155

Cited by 3 publications

(6 citation statements)

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“…In a phase III study from the Trans-Tasman Radiation Oncology Group (TROG 02.02), 13.7% of 102 p16-positive patients were HPV negative [9]. Because the prognosis of HPV-mediated OPSCC is fair, it is possible that even if treatment intensity is lowered, the prognosis will not worsen [10, 11]. These de-escalation studies are fascinating in terms of a paradigm shift in OPSCC therapy, and we also consider that there might be a subgroup without HPV DNA in HPV-mediated OPSCC defined by p16 overexpression.…”

Section: Introductionmentioning

confidence: 99%

Staging and prognosis of oropharyngeal carcinoma according to the 8th Edition of the American Joint Committee on Cancer Staging Manual in human papillomavirus infection

Yamashita

Ikegami

Hirakawa

et al. 2018

Eur Arch Otorhinolaryngol

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PurposeThe aim of this study was to evaluate the 8th edition of the American Joint Committee on Cancer Staging Manual: Head and Neck Section on oropharyngeal squamous cell cancer (OPSCC) and to clarify the relationship between p16 overexpression and the presence of human papillomavirus (HPV) DNA using fresh frozen samples.MethodsSamples from 100 OPSCC patients were analyzed using polymerase chain reaction (PCR) and p16 immunohistochemistry.ResultsFive-year overall survival (OS) was 73.0%, 93.9%, and 62.2% in all, p16-positive (n = 34), and p16-negative (n = 66) cases, respectively. OS tended to be better aligned with stage in the 8th edition than in the 7th edition. The 5-year OS was 96.0% in never or light smokers (< 40 pack-years), and 87.5% in heavy smokers (≥ 40 pack-years) in the p16-positive group, respectively (p = 0.027). HPV infection was found in 100% of p16-positive and 21.2% of p16-negative cases. The p16-positive cases had higher viral load and integrated physical status than the p16-negative cases. Although 1 case with p16 overexpression showed no PCR amplification using consensus primers, PCR amplification was detected using HPV 16 E6-specific primers.ConclusionsThe 8th edition predicts OPSCC prognosis more accurately than the 7th edition and p16-overexpression is an excellent surrogate marker for detecting HPV infection. Although high-risk-type HPV infection was observed in p16-negative cases, it showed no significant effect in survival outcome.

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Section: Introductionmentioning

confidence: 99%

Staging and prognosis of oropharyngeal carcinoma according to the 8th Edition of the American Joint Committee on Cancer Staging Manual in human papillomavirus infection

Yamashita

Ikegami

Hirakawa

et al. 2018

Eur Arch Otorhinolaryngol

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“…Although a small number of previous studies have reported outcomes following an SBRT boost, these have been in the setting of more advanced and/or inoperable disease with a minority of patients with oropharynx cancer, precluding meaningful comparison . Of note, during the time frame of the study, p16 testing was selective and not on a routine basis; based on previous research in Dutch patients with OPSCC, the true incidence of human papilloma virus (HPV)‐associated OPSCC in the study population is approximately 40%‐50% …”

Section: Discussionmentioning

confidence: 99%

“…6,7 Of note, during the time frame of the study, p16 testing was selective and not on a routine basis; based on previous research in Dutch patients with OPSCC, the true incidence of human papilloma virus (HPV)-associated OPSCC in the study population is approximately 40%-50%. [17][18][19] Previous analyses of the location of recurrences with respect to RT fields have reported nearly all local recurrences to occur within the site of the previous GTV, suggesting radioresistance as the underlying mechanism. [1][2][3]8,9 Here, we observed a shift in this classic recurrence pattern: only 76% of local recurrences occurred with COM in-field (n = 12 within GTV and n = 1 within CTV), whereas 24% occurred out-of-field (n = 4 outside PTV).…”

Section: Discussionmentioning

confidence: 99%

“…The boost was delivered following the IMRT phase but such that the weekly dose never exceeded 16.5 Gy. Patients with node‐positive disease underwent a selective neck dissection 2 weeks after the SBRT boost, as previously described …”

Section: Methodsmentioning

confidence: 99%

“…Patients with nodepositive disease underwent a selective neck dissection 2 weeks after the SBRT boost, as previously described. 12…”

Section: Treatment Regimenmentioning

confidence: 99%

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Locoregional failures and their relation to radiation fields following stereotactic body radiotherapy boost for oropharyngeal squamous cell carcinoma

et al. 2019

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Background To investigate the location of recurrences with respect to the radiation fields in oropharynx cancer after intensity‐modulated radiotherapy and stereotactic body radiotherapy (SBRT) boost. Methods Local and regional recurrences were delineated on diagnostic scans which were rigidly coregistered with treatment planning scans, then classified based on the location of the center of mass (COM) as well as volumetrically. Results In 195 patients, the 5‐year local and regional control were 90% and 93%, respectively. By COM, 76% of local recurrences were in‐field; 24% were out‐of‐field, significantly higher than 0%‐5% in the literature for conventional regimens (P < 0.01). Regional recurrences (19 in 12 patients) were largely within unirradiated neck levels (47%) and electively irradiated regions (42%). Conclusions The regimen with biological equivalent dose intensification provides excellent overall and in‐field local control. The highly conformal boost technique was, however, associated with increased out‐of‐field local failure.

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Long-term outcomes following stereotactic body radiotherapy boost for oropharyngeal squamous cell carcinoma

et al. 2019

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Background/purpose: To determine the efficacy and toxicity profile of a stereotactic body radiotherapy (SBRT) boost as a first line treatment in patients with oropharyngeal squamous cell carcinoma (OPSCC). Materials and methods: We performed a retrospective cohort study in 195 consecutive OPSCC patients with T1-small T3 disease, treated at Erasmus MC between 2009 and 2016 with a SBRT (3 Â 5.5 Gy) boost after 46 Gy IMRT. Primary endpoints were disease-specific survival (DSS) and Grade !3 toxicity (Common Terminology Criteria). The Kaplan-Meier method and Cox regression model were applied to determine rates and risk factors. Results: The median follow-up was 4.3 years. Treatment compliance was high (100%). Rates of 5-year DSS and late grade !3 toxicity were 85% and 28%, respectively. Five-year overall survival was 67%. The most frequently observed toxicities were mucosal ulceration or soft tissue necrosis (n ¼ 30, 5 year 18%), dysphagia or weight loss (n ¼ 18, 5 year 12%) and osteoradionecrosis (n ¼ 11, 5 year 9%). Current smoker status (hazard ratio [HR] ¼ 2.9, p ¼ .001) and Charlson Comorbidity Index !2 (HR ¼ 1.9, p ¼ .03) were was associated with increased toxicity risk. Tooth extraction prior to RT was associated with increased osteoradionecrosis risk (HR ¼ 6.4, p ¼ .006). Conclusion: We reported on outcomes in the largest patient series to date treated with a hypofractionated boost for OPSCC. Efficacy was good with survival rates comparable to conventionally fractionated (chemo)radiotherapy. Grade !3 toxicity profiles showed high rates of soft tissue necrosis and osteoradionecrosis. Strategies to mitigate severe toxicity risks are under investigation to improve the tolerability of the SBRT boost.

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Nodal response after 46 Gy of intensity‐modulated radiotherapy is associated with human papillomavirus–related oropharyngeal carcinoma

Abstract: 4. Laryngoscope, 128:2333-2340, 2018.

Cited by 3 publications

References 30 publications

Staging and prognosis of oropharyngeal carcinoma according to the 8th Edition of the American Joint Committee on Cancer Staging Manual in human papillomavirus infection

Staging and prognosis of oropharyngeal carcinoma according to the 8th Edition of the American Joint Committee on Cancer Staging Manual in human papillomavirus infection

Locoregional failures and their relation to radiation fields following stereotactic body radiotherapy boost for oropharyngeal squamous cell carcinoma

Long-term outcomes following stereotactic body radiotherapy boost for oropharyngeal squamous cell carcinoma

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