|Year : 2020 | Volume
| Issue : 5 | Page : 12-15
Indian clinical practice consensus guidelines for the management of oropharyngeal cancer
Kumar Prabhash1, Govind Babu2, Pankaj Chaturvedi3, Moni Kuriakose4, Praveen Birur5, Anil K Anand6, Ashish Kaushal7, Abhishek Mahajan8, Judita Syiemlieh9, Manish Singhal10, Munish Gairola11, Prakash Ramachandra12, Sumit Goyal13, Subashini John14, Rohit Nayyar15, Vijay M Patil1, Vishal Rao16, Vikas Roshan17, GK Rath18
1 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India
3 Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
4 Department of Surgical Oncology, Cochin Cancer Research Centre, Cochin, Kerala, India
5 Department of Oral Medicine and Radiology, KLE Society's Institute of Dental Sciences (KLESIDS), Bangalore, Karnataka, India
6 Department of Radiation Oncology, Max Super Speciality Hospital, Saket, New Delhi, India
7 Department of Medical Oncology, HCG Cancer Centre, Ahmedabad, Gujarat, India
8 Department of Radiodiagnosis and Imaging, Tata Memorial Hospital, Mumbai, Maharashtra, India
9 Department of Radiation Oncology, Civil Hospital, Shillong, Meghalaya, India
10 Department of Medical Oncology, Indraprastha Apollo Hospital, New Delhi, India
11 Department of Radiation Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
12 Department of Radiation Oncology, Sri Shankara Cancer Hospital and Research Centre, Bangalore, Karnataka, India
13 Department of Medical Oncology, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India
14 Department of Radiotherapy, Christian Medical College, Vellore, Tamil Nadu, India
15 Department of Surgical Oncology, Max Super Speciality Hospital, Saket, New Delhi, India
16 Department of Surgical Oncology, HCG Cancer Centre, Bangalore, Karnataka, India
17 Department of Radiation Oncology, Shri Mata Vaishno Devi Narayana Superspeciality Hospital, Jammu, Jammu and Kashmir, India
18 Department of Radiation Oncology, National Cancer Institute, All India Institute of Medical Sciences, Delhi, India
|Date of Submission||25-Jul-2019|
|Date of Decision||13-Nov-2019|
|Date of Acceptance||29-Dec-2019|
|Date of Web Publication||25-Feb-2020|
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Prabhash K, Babu G, Chaturvedi P, Kuriakose M, Birur P, Anand AK, Kaushal A, Mahajan A, Syiemlieh J, Singhal M, Gairola M, Ramachandra P, Goyal S, John S, Nayyar R, Patil VM, Rao V, Roshan V, Rath G K. Indian clinical practice consensus guidelines for the management of oropharyngeal cancer. Indian J Cancer 2020;57, Suppl S1:12-5
|How to cite this URL:|
Prabhash K, Babu G, Chaturvedi P, Kuriakose M, Birur P, Anand AK, Kaushal A, Mahajan A, Syiemlieh J, Singhal M, Gairola M, Ramachandra P, Goyal S, John S, Nayyar R, Patil VM, Rao V, Roshan V, Rath G K. Indian clinical practice consensus guidelines for the management of oropharyngeal cancer. Indian J Cancer [serial online] 2020 [cited 2022 Jul 6];57, Suppl S1:12-5. Available from: https://www.indianjcancer.com/text.asp?2020/57/5/12/278976
| » Diagnosis Workflow for Evaluation of Clinical Stages|| |
Human papillomavirus (HPV) is associated with oropharyngeal squamous cell carcinoma (SCC) and p16 staining is used to predict the HPV status and prognosis. It has been demonstrated that patients with p16 expression have a better outcome and longer disease-specific survival than p16-negative patients.,, However, with few exceptions, management of HPV-positive and HPV-negative oropharyngeal cancer remains similar. HPV testing by p16 immunohistochemistry (IHC) is mostly preferred; however, polymerase chain reaction-based assays or in-situ hybridization can also be used for diagnosis of p16 expression. HPV testing is recommended for testing (1) newly diagnosed oropharyngeal SCC, nontobacco users (males/females), patients with high-risk sexual behavior, early T-stage with advanced N-stage, cystic nodal metastasis on radiological imaging, nonkeratinizing or basaloid SCC, and carcinoma unknown primary with neck nodes. HPV testing is done either from the primary tumor or from cervical nodal metastases, using p16 IHC with a 70% nuclear and cytoplasmic staining cutoff, and (2) not to be routinely tested for nonsquamous oropharyngeal carcinomas or nonoropharyngeal carcinomas (evidence level [EL] 4; Grade A)., Routine examination includes history and physical examination (with complete head and neck exam, mirror and fiberoptic examination), biopsy of primary site or fine-needle aspiration of the neck, pre-anesthesia studies, and examination under anesthesia with endoscopy, if indicated. Computed tomography and/or magnetic resonance imaging (with contrast) of primary and neck, chest CT (with or without contrast) or fluorodeoxyglucose -positron emission tomography/computed tomography (FDG-PET/CT) for stage III–IV disease, if indicated, should be performed. Dental evaluation, including panorex and nutrition, speech and swallowing evaluation/therapy only for selected at-risk patients (if indicated) should be performed. Pure tone audiometry may be performed prior to administering cisplatin (EL 2 and EL 4; Grade A).
| » Treatment of Oropharyngeal Cancer|| |
The aim of the treatment of oropharyngeal cancer should be to treat the disease and also to preserve speech and swallowing functions. The choice of treatment should be decided by the multidisciplinary team.
Early stage oropharyngeal cancer (T1–2, N0–1)
Early stage disease is generally treated using single modality. The patients with p16-negative (T1–2, N0)/positive (T1–2, N0–1) HPV status should be treated with transoral or open resection of the primary—with or without ipsilateral/bilateral neck dissection. Postsurgery in the case of adverse features, adjuvant chemotherapy and radiotherapy (CT/RT) or radiotherapy (RT) is recommended. Particularly, in cases with positive margins, re-resection is the preferred choice; however, alternative options are CT/RT or RT.,,
Selected patients, who are medically inoperable or refuse surgery, should be given a definitive RT, an alternative option for surgery. High-risk patients (EL 1; Grade A) may be treated with three alternative options: (i) conventional fractionation (66 Gy [2.2 Gy/fraction] to 70 Gy [2.0 Gy/fraction]; daily, Monday–Friday in 6–7 weeks), (ii) concomitant boost accelerated RT (72 Gy/6 weeks [1.8 Gy/fraction, large field; 1.5 Gy boost as second daily fraction during last 12 treatment days] or 66–70 Gy [2.0 Gy/fraction]; 6 fractions/week accelerated), or (iii) hyperfractionation (81.6 Gy/7 weeks [1.2 Gy/fraction, twice daily]), while low-to-intermediate risk (IIB) patients can be given 44–50 Gy (2.0 Gy/fraction) to 54–63 Gy (1.6–1.8 Gy/fraction) of radiation.
Patients with p16-negative (T1–2, N1 only)/positive (T2 only) HPV status should be treated with concurrent CT/RT (EL 1; Grade A).
Locally advanced oropharyngeal cancer (T3–4a, N0–1; any T, N2–3)
For patients with locally advanced disease, chemoradiation should be considered instead of radiation alone., Several studies with different schedules of cisplatin have confirmed that the concurrent chemoradiation is superior to radiation alone., A recent study in locally advanced head and neck carcinomas showed that concurrent chemoradiotherapy (CTRT) was significantly better in locoregional control than RT and accelerated RT.
The concurrent CTRT regimens for patients with p16-negative/positive disease (T3–4a, N0–1; any T, N2–3) include three-weekly cisplatin (100 mg/m2), nimotuzumab + weekly cisplatin (30 or 40 mg/m2),,,, (EL 1; Grade A), HPV-negative oropharyngeal tumors nimouzumab + weekly cisplatin (30 mg/m2), (EL 1; Grade A), weekly cisplatin (30 or 40 mg/m2), cisplatin + paclitaxel, carboplatin + infusional 5-FU, or weekly cisplatin (30 or 40 mg/m2)., However, patients unsuitable for cisplatin should be treated with weekly cetuximab, weekly nimotuzumab, carboplatin + infusional 5-FU, 5-FU + hydroxyurea, or carboplatin + paclitaxel.
The RT schedule for high-risk patients includes treatment with 70 Gy (2.0 Gy/fraction) and for low-to-intermediate risk patients, 44–50 Gy (2.0 Gy/fraction) to 54–63 Gy (1.6–1.8 Gy/fraction) (EL 1; Grade A) of radiation doses.
Patients with locally advanced disease can be treated with the transoral or open resection of primary + ipsilateral/bilateral neck dissection ± adjuvant CTRT/adjuvant RT.
Adjuvant treatment: Choice of adjuvant treatment should be based on the presence of adverse features postsurgery/neck dissection. Among patients with extranodal extension and/or positive margin, CTRT is recommended, and in patients with other risk factors, RT or CTRT is recommended. Postoperative RT is recommended only for p16-negative T3–4a, N0–1 patients who do not have adverse features.
In unresectable locally advanced disease, use of sequential induction chemotherapy (TPF [docetaxel, cisplatin, fluorouracil]) followed by locoregional treatment with RT or CT/RT can be considered.,,,
Cisplatin-based induction CT regimen is as follows:
- Docetaxel 75 mg/m2 on day 1 + cisplatin 75 mg/m2 on day 1 + 5-FU 750 mg/m2/day for 5 days every 3 weeks for three cycles
- Paclitaxel 175 mg/m2 on day 1 + cisplatin 100 mg/m2 on day 2 + 5-FU 500–750 mg/m2/day from day 2 to day 6 every 3 weeks for three cycles
- Cisplatin 100 mg/m2 on day 1 + 5-FU 1000 mg/m2/day for 4 days every 3 weeks for three cycles.
Algorithm for management of oropharyngeal cancer is given in [Figure 1]. Appendix 1 gives the summary of clinical evidences in oropharyngeal cancer.
We acknowledge the significant contribution of J Balawardana, C Vithanage, S Resnayaka from Sri Lanka during the meeting and S Ghosh Laskar, S Ranjan, P Chavan, R Halkud and C Ramachandra for their involvement and insights. We also acknowledge the medical writing support provided by an independent medical writing agency, IQVIA. We are fully responsible for the content of this manuscript and the recommendations described in the review reflect the views and opinions of the authors only.
Financial Support and Sponsorship
Oral Cancer Task Force (OCTF) with a multidisciplinary expert panel, has a long standing commitment to work for early detection and management of oral cancer in underserved populations. The task force members have taken this educational initiative of developing India specific consensus guidelines for management of head and neck cancer under its ambit. The meeting and supplement were supported by an unrestricted grant by Biocon Foundation.
Conflicts of interest
Oral Cancer Task Force (OCTF) members and authors do not have any conflicts of interest.
| » References|| |
Sedghizadeh PP, Billington WD, Paxton D, Ebeed R, Mahabady S, Clark GT, et al.
Is p16-positive oropharyngeal squamous cell carcinoma associated with favorable prognosis? A systematic review and meta-analysis. Oral Oncol 2016;54:15-27.
Barasch S, Mohindra P, Hennrick K, Hartig GK, Harari PM, Yang DT. Assessing p16 status of oropharyngeal squamous cell carcinoma by combined assessment of the number of cells stained and the confluence of p16 staining: A validation by clinical outcomes. Am J Surg Pathol 2016;40:1261-9.
Murthy V, Calcuttawala A, Chadha K, d'Cruz A, Krishnamurthy A, Mallick I, et al.
Human papillomavirus in head and neck cancer in India: Current status and consensus recommendations. South Asian J Cancer 2017;6:93-8.
] [Full text]
Lewis JS Jr, Beadle B, Bishop JA, Chernock RD, Colasacco C, Lacchetti C, et al.
Human papillomavirus testing in head and neck carcinomas. Arch Pathol Lab Med 2018;142:559-97.
Adelstein DJ, Ridge JA, Brizel DM, olsinger FC, Haughey BH, O'Sullivan B, et al.
Transoral resection of pharyngeal cancer: Summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6-7, 2011, Arlington, Virginia. Head Neck 2012;34:1681-703.
Li RJ, Richmon JD. Transoral endoscopic surgery: New surgical techniques for oropharyngeal cancer. Otolaryngol Clin North Am 2012;45:823-44.
Cracchiolo JR, Baxi SS, Morris LG, Ganly I, Patel SG, Cohen MA, et al.
Increase in primary surgical treatment of T1 and T2 oropharyngeal squamous cell carcinoma and rates of adverse pathologic features: National Cancer Data Base. Cancer 2016;122:1523-32.
Eisbruch A, Harris J, Garden AS, Chao CK, Straube W, Harari PM, et al.
Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00-22). Int J Radiat Oncol Biol Phys 2010;76:1333-8.
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al.
Human papillomavirus and survival of patients with oropharyngeal cancer. N
Engl J Med 2010;363:24-35.
Blanchard P, Baujat B, Holostenco V, Bourredjem A, Baey C, Bourhis J, et al.
; MACH-CH Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): A comprehensive analysis by tumour site. Radiother Oncol 2011;100:33-40.
Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, et al.
Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 2004;22:69-76.
Medina JA, Rueda A, de Pasos AS, Contreras J, Cobo M, Moreno P, et al.
Aphase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas. Radiother Oncol 2006;79:34-8.
Beckmann GK, Hoppe F, Pfreundner L, Flentje MP. Hyperfractionated accelerated radiotherapy in combination with weekly cisplatin for locally advanced head and neck cancer. Head Neck 2005;27:36-43.
Ghosh-Laskar S, Kalyani N, Gupta T, Budrukkar A, Murthy V, Sengar M, et al.
Conventional radiotherapy versus concurrent chemoradiotherapy versus accelerated radiotherapy in locoregionally advanced carcinoma of head and neck: Results of a prospective randomized trial. Head Neck 2016;38:202-7.
Patil VM, Noronha V, Joshi A, Agarwal J, Ghosh-Laskar S, Budrukkar A, et al.
Arandomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer. Cancer 2019;125:3184-97.
Kumar A, Chakravarty N, Bhatnagar S, Chowdhary GS. Efficacy and safety of concurrent chemoradiotherapy with or without Nimotuzumab in unresectable locally advanced squamous cell carcinoma of head and neck: Prospective comparative study-ESCORT-N study. South Asian J Cancer 2019;8:108-11.
] [Full text]
Li Z, Li Y, Yan S, Fu J, Zhou Q, Huang X, et al
. Nimotuzumab combined with concurrent chemoradiotherapy benefits patients with advanced nasopharyngeal carcinoma. Onco Targets Ther 2017;10:5445-58.
Laskar SG, Chaukar D, Deshpande M, Chatterjee A, Hawaldar RW, Chakraborty S, et al.
Phase III randomized trial of surgery followed by conventional radiotherapy (5 fr/Wk) (Arm A) vs concurrent chemoradiotherapy (Arm B) vs accelerated radiotherapy (6fr/Wk) (Arm C) in locally advanced, stage III and IV, resectable, squamous cell carcinoma of oral cavity- oral cavity adjuvant therapy (OCAT): Final results (NCT00193843). J Clin Oncol 2016;34:6004.
Noronha V, Joshi A, Patil VM, Agarwal J, Ghosh-Laskar S, Budrukkar A, et al.
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;36:1064-72.
Prabhash K, Patil VM, Noronha V, Joshi AP, Bhattacharjee A, Mathrudev V, et al.
Nimotuzumab-cisplatin-radiation versus cisplatin radiation in HPV-negative oropharyngeal cancer. Ann Oncol 2019;30:1121 [Abstract]. Available from: https://doi.org/10.1093/annonc/mdz252.013
. [Last accessed on 2019 Dec 01].
Kim R, Hahn S, Shin J, Ock CY, Kim M, Keam B, et al.
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;48:907-16.
Fayette J, Fontaine-Delaruelle C, Ambrun A, Daveau C, Poupart M, Ramade A, et al.
Neoadjuvant modified TPF (docetaxel, cisplatin, fluorouracil) for patients unfit to standard TPF in locally advanced head and neck squamous cell carcinoma: A study of 48 patients. Oncotarget 2016;7:37297-304.
Lorch JH, Goloubeva O, Haddad RI, Cullen K, Sarlis N, Tishler R, et al.
Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous-cell cancer of the head and neck: Long-term results of the TAX 324 randomised phase 3 trial. Lancet Oncol 2011;12:153-9.
Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, et al.
EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N
Engl J Med 2007;357:1695-704.
|This article has been cited by|
||Making the Best of Limited Resources: Improving Outcomes in Head and Neck Cancer
| ||Johannes J. Fagan, Vanita Noronha, Evan Michael Graboyes |
| ||American Society of Clinical Oncology Educational Book. 2021; (41): 279 |
|[Pubmed] | [DOI]|
||Validation of a Novel ‘Supportive Oral Care Protocol’ (SOCP), a Model for Care in Head and Neck Cancer Patients at Tertiary Cancer Centre in India
| ||Abhishek Kandwal, Sunil Saini, Mustaq Ahmad, Vipul Nautiyal, Manisa Pattanayak, Divya Raj, Ueno Takao |
| ||Indian Journal of Surgical Oncology. 2020; 11(4): 769 |
|[Pubmed] | [DOI]|