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SEOM clinical guidelines for the treatment of head and neck cancer (2020)

SEOM2021Full text
Full text · CC BYMesia R, Iglesias L, Lambea J, Martínez-Trufero J, Soria A, Taberna M et al.. SEOM clinical guidelines for the treatment of head and neck cancer (2020). Clin Transl Oncol, 2021. Licensed under CC BY. Changes: reformatted for the web. Original: https://doi.org/10.1007/s12094-020-02533-1

Summary

Head and neck cancers (HNC) are defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2017 publication, the Spanish Society of Medical Oncology (SEOM) presents an update of the squamous cell HNC diagnosis and treatment guideline. Most relevant diagnostic and therapeutic changes from the last guideline have been updated: introduction of sentinel node biopsy in early oral/oropharyngeal cancer treated with surgery, concomitant radiotherapy with weekly cisplatin 40 mg/m2 in the adjuvant setting, new approaches for HPV-related oropharyngeal cancer and new treatments with immune-checkpoint inhibitors in recurrent/metastatic disease.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12094-020-02533-1.

Introduction

Squamous cell carcinomas of the head and neck (SCCHN) are defined as malignant tumors arising from mucosal surfaces located in the upper aerodigestive tract (paranasal sinuses, nasopharynx, oropharynx, hypopharynx, larynx, oral cavity, nostrils). In Spain, SCCHN represents 5% of all new cancer diagnoses in adults, being the sixth neoplasm (fifth in men), similar to the European median, and a mortality rate of three points below compared to the European median [1]. The most important risk factor in our region continues to be tobacco and alcohol use, but human papillomavirus (HPV) infection is a key etiological factor in oropharyngeal cancer burden, which is rising worldwide [2]. Despite the majority patients with early-stage SCCHN can be cured with surgery or radiation, those with aggressive disease and those with locally advanced stages, that represents two-thirds of new diagnosis, are more likely to recur (50% 5-year overall survival) [2]. A multidisciplinary team, bringing together all professionals who specialize in the diagnosis and treatment of these patients, will make the decision to establish the best sequence of individualized treatment for each patient. Within what is known as SCCHN, each location has a clinical presentation, staging, prognosis and different therapeutic approach. As this is a general guide, the particularities of each subsite will not be dealt with in depth. Nasopharyngeal cancer with a different epidemiological, pathological and natural history will not be included in this guide.

Methodology

SEOM guidelines have been developed with the consensus of ten oncologists from the Spanish Group for the Treatment of Head and Neck Tumors (TTCC) and SEOM. To assign a level and quality of evidence and a grade of recommendation to the different statements of this treatment guideline, the Infectious Diseases Society of America-US Public Health Service Grading System for Ranking Recommendations in Clinical Guidelines was used (Table 1). The final text has been reviewed and approved by all authors.

Table 1

Strength of recommendation and quality of evidence score

Category, gradeDefinition
Strength of recommendation
 AGood evidence to support a recommendation for use
 BModerate evidence to support a recommendation for use
 CPoor evidence to support a recommendation
 DModerate evidence to support a recommendation against use
 EGood evidence to support a recommendation against use
Quality of evidence
 IEvidence from ≥ 1 properly randomized, controlled trial
 IIEvidence from ≥ 1 well-designed clinical trial, without randomization; from cohort or case controlled analytic studies (preferably from > 1 centr*e); from multiple time series; or from dramatic results from uncontrolled experiments
 IIIEvidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of experts committees

*Studies reported as abstracts in congresses pending journal publication at the time of writing this guide

Diagnosis and staging

It is essential to start the diagnostic process with a good clinical history, including toxic and sexual habits and a methodical physical examination, with special attention to the head and neck area (inspection, indirect mirror examination or direct endoscopy and palpation of primary sites and neck).

To explore tumor extension, diagnosis imaging is needed:

  • -Imaging diagnosis before a large biopsy avoids false diagnosis from anatomy distortion [2].
  • -Cervical computed tomography (CT) or magnetic resonance (MR). Imaging MRI is superior to CT for evaluation of tongue, perineural spread, skull base invasion and intracranial extension. Regarding lymphatic dissemination, defining extracapsular nodal extension is of prognostic value.
  • -CT of chest preferably, or X-ray in early stages.
  • -Positron emission tomography-CT (PET-CT) is very useful in diagnosis of node (N) and metastases (M) and synchronous primary tumors. It is recommended in patients with stage III–IV disease when definitive treatment is indicated or in those with equivocal findings on CT or MRI scan [3].
  • -Esophageal–gastric contrast study or esophagoscopy in case of dysphagia.
  • -Histological diagnosis is mandatory by primary tumor biopsy or fine needle aspiration (FNA) of lymph nodes (biopsy is always better than FNA). If a node biopsy is needed, complete nodal resection is preferable to prevent extracapsular metastatic spread [2].
  • -Functionalism evaluation: chewing, swallowing, phonation, breathing (stability of the airway mast be assessed), odontology and nutritional status.
  • -Special evaluations if needed: psychological and social situation, cessation of smoking or alcohol dependence.

Accurate staging is crucial for coordinating and tailoring therapy to each individual patient. The 8th edition of TNM classisfication was implemented from January, 2018: [4]

  • -The most important introduction is an independent classification for p16-positive oropharyngeal tumors: in the T category, T4a and T4b were pooled as T4, and N category was reclassified. As a consequence, there is a downstaging.
  • -T category (T1–T3) of lip and oral cavity includes the extent of depth invasion.
  • -N3 category for non-HPV related tumors has been subdivided into N3a and N3b according to extranodal extension (in N1 and N2 categories lack of extranodal extension is specified).
  • -Perineural invasion or deep invasion is included within squamous cell carcinomas of the skin.

Early disease (clinical stage I–II) treatment

Surgery, 3D conformal radiotherapy (RT) and brachytherapy provide similar locoregional control and survival outcomes, but they have not been compared in randomized trials [2]. A multidisciplinary team should choose according to the characteristics and wishes of the patient and the potential functional outcomes, a single modality to avoid morbidity.

Transoral resection is preferred over RT in oral cavity because of the decreased long-term morbidity (II, B) [5]. In oropharyngeal carcinoma, minimally invasive transoral surgery such as robot (TORS) or laser (TLM), in selected patients, should be prioritized over open surgery (II, B) [6]. Alternative RT seems to have less tendency to long-term dysphagia (II, B) [7].

In both locations, cervical lymph nodes should be treated with prophylactic radiation or elective neck dissection (bilaterally in tumors that arise in or near the midline and guided by location and depth in oral carcinoma) (II, B) [8].

Recent data recommend treatment based on sentinel node biopsy for oral cavity and oropharynx tumors (T1–2 N0), since it obtains the same neck-relapse-free survival at 2 years than the neck dissection, with less morbidity during first year post-surgery (I, A) [9]. When cervical dissection is indicated, we would recommend elective neck dissection over therapeutic neck dissection due to similar efficacy with less morbidity associated (I,A) [10]. In the choice of treatment for hypopharyx and larynx carcinomas, laryngeal functional results will be considered in addition to survival. Conservative laryngeal surgery (TLM or supraglottic or supracricoid laryngectomy) will be priorized over open surgery, and considerer RT treatment in case of requiring extensive surgical resection [11, 12]. Elective treatment of the neck in hypopahrynx and supraglottic cancer is recommended (II, B), but not in glottic neoplasm (III, C).

If the pathological staging is superior to the clinical staging or there are poor prognosis factors, complementary treatments should be used (I, A) including the re-resection.

Locally advanced disease (clinical stages III, IVA, IVB) treatment

In all cases there must be a multidisciplinary assessment to decide the best combined treatment option for each patient either based on surgery or RT as the key treatment (I-A) Given its special interest, we will introduce a special section for larynx preservation and HPV-related oropharyngeal cancer treatments.

Surgery-based treatment

There is no universally accepted definition of unresectability in SCCHN, but some anatomical criteria are considered unequivocal and classified as T4b tumors (involvement of skull base, cervical vertebrae, prevertebral muscles, brachial plexus, mediastinal spread, involvement of nasopharynx, fixed tumor to collarbone, vascular encasement) [13].

Multidisciplinary Tumor Boards can exclude patients for surgery: few chances of achieving adequate margins, unacceptable functional and/or esthetic sequelae, little expectation of cure or due to patients’ comorbidities.

For patients with T3-4aN0 tumors an ipsilateral or bilateral neck dissection is an option (except oral cavity where it is mandatory). When neck nodes are palpable, all nodal levels should be dissected [14].

Adjuvant treatment

  • -Preferred Radiation technique: Intensity Modulated Radiotherapy (IMRT) 60–66 Gy (I-A) [15].
  • -Radiotherapy alone: it could be considered when there are multiple positive neck nodes (without extranodal extension), perineural invasion, vascular invasion, lymphatic invasion, pT3 or pT4 primary, oral cavity or oropharyngeal primary cancers with positive level IV or V nodes (I-A).
  • -Concurrent chemorradiotherapy (CCRT): three-weekly intravenous cisplatin 100 mg/m2 at days 1, 22, 43) in high-risk pathological features: extracapsular lymph node extension and/or affected margins (I-A) [16, 17]. Weekly 40 mg/m2 cisplatin can be non-inferior alternative with better safety profile (IB) [18].

Specific recommendations in special circumstances

  • -Oral cavity: in clinically node-negative cases, elective ipsilateral node dissection is recommended more than watchful waiting approach (I-A) [10].
  • -Unfit patients not candidate for platinum: consider administration of RT alone (I-A). There is no evidence for using agents such as cetuximab or carboplatin in the adjuvant setting [14].

Radiotherapy-based treatment

CCRT is preferred for patients that are not candidates for or refuse radical surgery (IA) (Fig. 1).

  • RT technique: IMRT is preferred (IA) [19]: with similar overall survival compared with conventional RT, it has shown reduction in xerostomia (IA) [15] and probably shorter duration of feeding tube placement (V) [20].
  • RT dose: for primary tumor and involved lymph nodes a total of 66 Gy (2.2 Gy/fraction) to 70 Gy (2.0 Gy/fraction) (IA) For elective irradiation of risk sites 44–50 Gy (2.0 Gy/fraction) is proposed (IA) [21–23].
  • Chemotherapy regimen: The standard schedule is cisplatin (100 mg/m2 days 1, 22, 43) (IA). Weekly cisplatin and other drug combinations have not demonstrated to be equivalent to high-dose cisplatin (IIB) [24, 25]. Concomitant cetuximab is an alternative treatment (400 mg/m2 at initial dose day -8 followed by 250 mg/m2 weekly concurrent) for patients with some contraindication for cisplatin such as neuropathy, nephropathy, heart disease and hearing loss (IA) [24].

Fig. 1

Treatment options in locally advanced SCCHN

— figure not reproduced here; see the original article.

Sequential therapy with induction chemotherapy (ICT) followed by CCRT or RT alone is an option for locally advanced tumors (IIB) (Fig. 1). Factors such as patients' comorbidities, high tumor volume and rapid tumor growth will influence its indication by a multidisciplinary team. ICT has not demonstrated improvement in overall compared with concurrent CRT but increase the response rate. Its limitation is the potential toxicity that could compromise the posterior CRT compliance.

The most recommended induction regimen is TPF schedule (three-weekly Cisplatin 75 mg/m2, Docetaxel 75 mg/m2, 5-Fluorouracil 750 mg/m2/d continue infusion 96 h) (IA) [25].

After ICT, there is no consensus for locoregional treatment (RT, chemoradiotherapy or RT plus cetuximab) (IIB). Decision should be made according to the response and tolerance to previous ICT [26]. Salvage neck dissection should be considered in patients with residual lymph node disease and a complete response in the primary tumor.

Organ preservation (larynx and hypopharynx)

All patients should have a multidisciplinary evaluation regarding their suitably for a larynx-preservation approach. Organ-preservation surgery, CRT and ICT, all with further surgery reserved for salvage, offer the potential for larynx preservation without compromising overall survival. Selection of a treatment option will depend on patient factors, including age, comorbidities, preferences, socioeconomic factors, local expertise and the availability of appropriate support and rehabilitation services.

For selected patients with extensive T3 or large T4a lesions and/or poor pretreatment laryngeal function, better survival rates and quality of life may be achieved with total laryngectomy rather than with organ-preservation approaches and may be the preferred approach (IA).

CCRT offers a significantly higher chance of larynx preservation than RT alone or ICT followed by RT alone (IA). The best available evidence supports the use of high-dose cisplatin as the drug of choice in this setting [27].

There is insufficient evidence to indicate that survival or larynx-preservation outcomes are improved by the addition of ICT before concurrent treatment [28]. However, in the setting of operable cancer with the goal of larynx preservation, response to ICT serves as a surrogate predictive biomarker for successful organ preservation with subsequent RT plus cisplatin.

Three options could be considered: Three options could be considered:

  • 1.Surgical resection (total versus partial laryngectomy + neck dissection) followed by RT (IA)

    • •Specially in T4a (IA).

    • •For the most part of subglottic tumors (IA).

      Non-surgical organ preservation alternatives are showed in Fig. 2:

  • 2.CRT with three-weekly cisplatin is recommended if patient refuses surgery (IA). If cisplatin cannot be administered, consider cetuximab concurrent to RT (IA).
  • 3.ICT with TPF schedule:
    • •If complete response of the primary tumors (without lymph node progression) → RT(IA).
    • •If partial response (50% reduction of primary tumor without lymph nose progression) → RT (IA) or concomitant RT (with cisplatin or cetuximab) [29] (IIB).
    • •If stable disease (primary tumor) or progression → total laryngectomy (including neck dissection) followed by RT (IA) or CRT (IIB) based on histopathological results.

Fig. 2

Organ preservation: Larynx/hypopharynx tumors candidate to total laryngectomy

— figure not reproduced here; see the original article.

HPV-related oropharyngeal cancer: a new biological and clinical entity

HPV status has widely been described as an independent predictor of improved outcomes in squamous cell oropharyngeal cancer (OPSCC) patients, proving a 58% reduction in the risk of death for patients with HPV-related OPC as compared HPV-negative tumors [30].

Diagnosis and staging

p16INK4a over-expression is a surrogate marker of HPV involvement and it is the most widely implemented technique in the clinical setting. Nevertheless, a recent study highly recommends confirming HPV relatedness in p16-positive patients with an HPV specific biomarker such us HPV DNA (IIA) [31]. Double testing for oropharyngeal HPV-related patients is especially important in our geographical area [31, 32].

Importantly, HPV-related oropharyngeal cancer patients’ staging should be done following AJCC TNM 8th edition, whereas clinical decision-making should follow AJCC TNM 7th edition.

Early disease

Minimally invasive surgery (TORS or TLM) or IMRT monotherapies are both validate techniques for early stages (IA). Importantly patient characteristics and wishes, functional outcomes and expertise of the treating team should be considered.

Locally advanced (LA) disease

The good prognosis has led the scientific community to develop de-escalation clinical trials for LA HPV-related OPSCC patients [33]. Two phase III de-escalation clinical trials have maintained cisplatin (100 mg/m2 every 3 weeks) in combination with RT (70 Gy in 35 fractions) as the standard of care (IA) [34, 35]. Deintensification protocols should be undertaken only within the context of clinical trials.

Recurrent or metastatic (R/M) disease

Surgery or re-irradiation should always be assessed by the multidisciplinary team for oligometastasic patients. If a radical approach is not possible, the clinical management of R/M HPV-related oropharyngeal patients does not differ from R/M HPV-negative HNSCC, except for patients included on specific clinical trials (IA).

R/M disease treatment

The multidisciplinary team will assess the benefit of salvage surgery or re-irradiation. In the presence of oligometastatic disease, treatment with curative intent should also be discussed. Systemic treatment will be considered in all other patients. All subjects should be recommended including in clinical trials if available.

First-line treatment

Decisions will be made based on Eastern Cooperative Oncology Group (ECOG) performance status (PS) comorbidities, symptom burden and PD-L1 expression (in archival or newly tumor samples and characterized by the combined positive score (CPS)).

  1. Chemotherapy-naïve patients or patients with progressive disease more than 6 months after locoregional treatment with cisplatin (Fig. 3):
    1. Pembrolizumab alone is preferred in patients with PS 0/1, CPS ≥ 20 and low symptom load (IA) [36].
    2. The combination of Pembrolizumab plus chemotherapy might be preferred for patients whose symptom burden indicates a greater importance of objective response. (IA) [36].
    3. In patients with CPS 1–19 the combination of Pembrolizumab plus chemotherapy (platinum plus 5 FU) is the treatment of choice too (IA) [37].
    4. If CPS < 1 or the patient cannot be treated with an immunotherapy protocol EXTREME (combination based on platinum plus 5-FU plus cetuximab) (IA) [38] or TPEX (combination based on cisplatin plus docetaxel plus cetuximab if there is any contraindication to 5-FU) only in PS 0/1 patients able to receive cisplatin (IIB) [39]* are the best option.
    5. Best supportive care is the treatment of choice in patients with PS 2. In these patients and those with comorbidities that could not receive platinum the combination ERBITAX (paclitaxel plus cetuximab) should be considered (IIB) [40].
    6. The treatment of choice for patients with PS 3/4 is best supportive care.
  2. Patients who have received chemotherapy at least 200 mg/m2 of cisplatin for locoregional disease within 6 months after last cisplatin dose should not receive cisplatin or carboplatin. The first option will be Nivolumab (IA) [41] or Pembrolizumab in those patients with a tumor positive score (TPS) >/=50% (IIA) [42]. According to PS or symptom burden treatment with ERBITAX [40] could be an alternative (Fig. 3).

Fig. 3

Recurrent/metastatic disease treatment. All patients should be recommended including in clinical trials if available. LA Locoregionally advanced, ECOG Eastern Cooperative Oncology Group, CPS combined positive score, BSC best supportive care, CT chemotherapy, ERBITAX combination of paclitatel and cetuximab, EXTREME combination of platinum, 5-Fluorouracil and cetuximab, TPEX combination of cisplatin, docetaxel and cetuximab

— figure not reproduced here; see the original article.

Second and subsequent line treatment

With the paradigm switch at the frontline we can find new treatment settings:

  1. After platinum-based therapy: immunotherapy with Nivolumab (IA) [41] Pembrolizumab in those patients with tumor positive score (TPS) PDL1 ≥ 50% (IIA) [42]
  2. After pembrolizumab alone: combination EXTREME is preferred or ERBITAX according to PS (IIIC).
  3. After pembrolizumab plus platinum and 5-FU: combination ERBITAX (IIIC).
  4. Other cases: considered according to PS single-agent therapy with taxanes (docetaxel, paclitaxel) or anti-metabolite drugs (capecitabine or 5-FU, methotrexate) (IIC). Second and subsequent-line trials tested different drugs with small sample sizes and patient heterogeneity which makes the evaluation of the relative efficacy of each drug challenging. There is no evidence of higher efficacy among the different drugs in the meta-analyses performed [43].

Supplementary Information

Below is the link to the electronic supplementary material.

References

  1. Ferlay J Colombet M Soerjomataram I Mathers C Parkin DM Piñeros M Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods Int J Cancer 2019 144 8 1941 1953 10.1002/ijc.31937 30350310 DOI PubMed
  2. Chow L Head and neck cancer N Eng J Med 2020 382 26 60 72 10.1056/NEJMra1715715 31893516 DOI PubMed
  3. Mehanna H Wong WL McConkey CC Rahman JK Robinson M Hartley AG PET-CT surveillance versus neck dissection in advanced head and neck cancer N Engl J Med 2016 374 1444 10.1056/NEJMoa1514493 27007578 DOI PubMed
  4. Classification TNM American Joint Committee on Cancer: AJCC cancer staging manual 2017 8 New York Springer
  5. Ellis MA Graboyes EM Wahlquist AE Nesquey DM Kaczmar JM Schopper KH Primary surgery vs radiotherapy for early stage oral cavity cancer Otolaryngol Head Neck Surg 2018 158 4 649 659 10.1177/0194599817746909 29256326 DOI PubMed
  6. Moore EJ Hinni ML Critical review: transoral laser microsurgery and robotic-assisted surgery for oropharynx cancer including human papilomavirus-related cancer Int J Radiat Oncol Biol Phys 2013 85 5 1163 1167 10.1016/j.ijrobp.2012.08.033 23182390 DOI PubMed
  7. Nichols AC Theurer J Prisman E Read N Berthelet E Tran E Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial Lancet 2019 20 10 1349 1359 10.1016/S1470-2045(19)30410-3 31416685 DOI PubMed
  8. Pentenero M Gandolfo S Carruzzo M Importance of tumor thickness and depth of invasión in nodal involvement and prognosis of oral squamous cell carcinoma: a review of the literatura Head Neck 2005 27 12 1080 1091 10.1002/hed.20275 16240329 DOI PubMed
  9. Garrel R, Perriard F, Favier V, Richard F, Duares JP, De Boutray M. Equivalence randomized trial comparing treatment based on sentinel node biopsy versus neck dissection in operable T1-T2 N0 oral and oropharyngeal cancer. J Clin Oncol. 2020; 38 (suppl; abstr 6501). 10.1200/JCO.20.01661 33052754 DOI PubMed
  10. D´Cruz AK Vaish R Kapre N Dandekar M Gupta S Hawaldar R Elective versus therapeutic neck disection in nondegenerative oral cancer N Eng J Med. 2005 373 6 521 529 10.1056/NEJMoa1506007 26027881 DOI PubMed
  11. Taker RP Strojan P Silver CE Bradely PJ Haigentz M Jr Wolf GT Current trends in initial management of hypopharyngeal cancer: the declining use of open surgery Head Neck 2012 34 2 270 281 10.1002/hed.21613 22228621 DOI PubMed
  12. Warner L Chudasama J Kelly CG Loughran S McKenzie J Wight R Radiotherapy versus open surgery versus endolaryngeal surgery (with or without laser) for early laryngeal squamous cell cancer Cochrane Database Syst Rev 2014 12 CD002027 10.1002/14651858.CD002027.pub2 PMC6599864 25503538 DOI PubMed
  13. Yousem DM Gad K Tufano RP Resectability issues with head and neck cancer AJNR Am J Neuroradiol. 2006 27 10 2024 2036 17110661 PMC7977212 PubMed
  14. Robbins KT Shaha AR Medina JE Califano JA Wolf GT Ferlito A Consensus statement on the classification and terminology of neck dissection Arch Otolaryngol Head Neck Surg 2008 134 536 538 10.1001/archotol.134.5.536 18490577 DOI PubMed
  15. Nutting CM Morden JP Harrington KJ Urbano TG Bhide SA Clark C Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial Lancet Oncol 2011 12 2 127 136 10.1016/S1470-2045(10)70290-4 21236730 PMC3033533 DOI PubMed
  16. Cooper JS Pajak TF Forastiere AA Jacobs J Campbell BH Saxman SB Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck N Engl J Med 2004 350 1937 1944 10.1056/NEJMoa032646 15128893 DOI PubMed
  17. Bernier J Domenge C Ozsahin M Matuszewska K Lefebvre JL Greiner RH Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer N Engl J Med 2004 350 1945 1952 10.1056/NEJMoa032641 15128894 DOI PubMed
  18. Kiyota N, Tahara M, Fujii H, Yamazaki T, Mitani H, Iwae S et al. Phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of head and neck (JCOG1008). J Clin Oncol. 2020; 38 (suppl; abstr 6502)*. 10.1093/jjco/hyu067 24842866 DOI PubMed
  19. Gregoire V Mackie TR State of the art on dose prescription, reporting and recording in Intensity-Modulated Radiation Therapy (ICRU report No. 83) Cancer Radiother 2011 15 555 559 10.1016/j.canrad.2011.04.003 21802333 DOI PubMed
  20. Beadle BM Liao KP Giordano SH Garden AS Hutcheson KA Lai SY Reduced feeding tube duration with intensity-modulated radiation therapy for head and neck cancer: a surveillance, epidemiology, and end results-medicare analysis Cancer 2017 123 283 293 10.1002/cncr.30350 27662641 PMC5222734 DOI PubMed
  21. Refaat T Choi M Thomas TO Bacchus I Agulnik M Pelzer HJ Whole-field sequential intensity-modulated radiotherapy for local-regional advanced head and neck squamous cell carcinoma Am J Clin Oncol 2015 38 6 588 594 10.1097/COC.0000000000000001 24136140 PMC4713122 DOI PubMed
  22. Bourhis J Sire C Graff P Grégoire V Maingon P Calais G Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99–02): an open-label phase 3 randomised trial Lancet Oncol 2012 13 145 153 10.1016/S1470-2045(11)70346-1 22261362 DOI PubMed
  23. Noronha V Joshi A Patil VM Agarwal J Ghosh-Laskar S Budrukkar A Once-a-week versus once-every-3-weeks cisplatin chemoradiation for locally advanced head and neck cancer: a phase III randomized noninferiority trial J Clin Oncol 2018 36 1064 1172 10.1200/JCO.2017.74.9457 29220295 DOI PubMed
  24. Bonner JA Harari PM Giralt J Cohen RB Jones CU Sur RK Radio-therapy plus cetuximab for locoregionally advanced head and neck cancer: 5 year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival Lancet Oncol 2010 11 21 28 10.1016/S1470-2045(09)70311-0 19897418 DOI PubMed
  25. Hitt R Grau JJ López-Pousa A Berrocal A García-Girón C Irigoyen A A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer Ann Oncol 2014 25 216 225 10.1093/annonc/mdt461 24256848 DOI PubMed
  26. Kim R Hahn S Shin J Ock CY Kim M Keam B The effect of induction chemotherapy using docetaxel, cisplatin, and fluorouracil on survival in locally advanced head and neck squamous cell carcinoma: a meta-analysis Cancer Res Treat 2016 48 3 907 916 10.4143/crt.2015.359 26582394 PMC4946346 DOI PubMed
  27. Forastiere AA Goepfert H Maor M Pajak TF Weber R Morrison W Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer N Engl J Med 2003 349 2091 2098 10.1056/NEJMoa031317 14645636 DOI PubMed
  28. Lefebvre JL Chevalier D Luboinski B Kirkpatrick A Collette L Sahmoud T Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer Phase III trial EORTC head and neck cancer cooperative group J Natl Cancer Inst 1996 88 890 899 10.1093/jnci/88.13.890 8656441 DOI PubMed
  29. Lefebvre JL Pointreau Y Rolland F Alfonsi M Baudoux A Sire C Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study J Clin Oncol 2013 31 853 859 10.1200/JCO.2012.42.3988 23341517 DOI PubMed
  30. Ang KK Harris J Wheeler R Weber R Rosenthal DI Nguyen-Tân PF Human papillomavirus and survival of patients with oropharyngeal cancer N Enl J Med 2010 363 24 35 10.1056/NEJMoa0912217 PMC2943767 20530316 DOI PubMed
  31. Taberna M Mehanna H Tous S Performance of dual p16 and HPV testing for determining prognosis in cancer of the oropharynx, the EPIC-OPC Study Ann Oncol. 2020 31 suppl_4 S599 S628 10.1016/annonc/annonc277 DOI
  32. Lewis JS Beadle B Bishop JS Chernock RD Colasacco C Lacchetti C Human papillomavirus testing in head and neck carcinomas: guideline from the College of American Pathologists Arch Pathol Lab Med 2018 142 5 559 597 10.5858/arpa.2017-0286-CP 29251996 DOI PubMed
  33. Bigelow EO Seiwert TY Fakhry C Deintensification of treatment for human papillomavirus-related oropharyngeal cancer: current state and future directions Oral Oncol 2020 105 104652 10.1016/j.oraloncology.2020.104652 32247987 PMC8035753 DOI PubMed
  34. Mehanna H Robinson M Harley A Kong A Foran B Fulton-Lieuw T 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 51 60 10.1016/S0140-6736(18)32752-1 30449623 PMC6319250 DOI PubMed
  35. Gillison ML Trotti AM Harris J Eisbruch A Harari PM Adelstein DJ Radiotherapy plus Cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial Lancet 2019 393 40 50 10.1016/S0140-6736(18)32779-X 30449625 PMC6541928 DOI PubMed
  36. Burtness B Harrington K Greil R Soulières D Tahara M de Castro G Jr Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the Head and Neck (KEYNOTE-048): a randomized, open-label, phase-III study Lancet 2019 394 10212 1915 1928 10.1016/S0140-6736(19)32591-7 31679945 DOI PubMed
  37. Pembrolizumab European Assessment Report EMA/CHMP/591139/2019. https://www.ema.europa.eu/en/documents/variation-report/keytruda-h-c-3820-ii-0065-epar-assessment-report-variation_en.pdf .
  38. Vermorken JB Mesia R Rivera F Remenar E Kawecki A Rottey S Platinum-based chemotherapy plus cetuximab in head and neck cancer N Engl J Med 2008 359 11 1116 1127 10.1056/NEJMoa0802656 18784101 DOI PubMed
  39. Guigay J Fayette J Mesia R Lafond C Saada-Bouzid E Geoffrois L TPExtreme randomized trial: TPEx versus Extreme regimen in 1st line recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) J Clin Oncol 2019 37 A6002 10.1200/JCO.2019.37.15_suppl.6002 DOI
  40. Hitt R Irigoyen A Cortes Funes H Grau JJ García-Sáenz JA Cruz-Hernandez JJ Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck Ann Oncol 2012 23 1016 1022 10.1093/annonc/mdr367 21865152 DOI PubMed
  41. Ferris R Blumenschein G Fayette J Guigay J Colevas AD Licitra L Nivolumab for recurrent squamous-cell carcinoma of the head and neck N Engl J Med 2016 375 1856 1867 10.1056/NEJMoa1602252 27718784 PMC5564292 DOI PubMed
  42. Cohen EW Soulières D Le Tourneau C Dinis J Licitra L Ahn MJ Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study Lancet 2019 393 10167 156 167 10.1016/S0140-6736(18)31999-8 30509740 DOI PubMed
  43. El Rassy E Assi T Bakouny Z El Karak F Pavlidis N Ghosn M Comparison of second-line treatments of recurrent and/or metastatic squamous cell carcinoma of the head and neck Future Oncol 2019 15 8 909 923 10.2217/fon-2018-0663 30669875 DOI PubMed

Conditions covered

Head and neck cancerSquamous cell carcinoma

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