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 Table of Contents  
REVIEW ARTICLE
Year : 2022  |  Volume : 10  |  Issue : 2  |  Page : 127-131

Approach to T4b oral cancers – A surgeon's perspective


1 Department of ENT and Head and Neck Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
2 Department of ENT and Head and Neck Surgery, Seven Hills Hospital, Visakhapatnam, Andhra Pradesh, India
3 Department of Surgical Oncology, Shri Guru Ram Rai Institute of Medical and Health Sciences, Dehradun, Uttarakhand, India

Date of Submission25-Jul-2022
Date of Decision24-Aug-2022
Date of Acceptance25-Aug-2022
Date of Web Publication15-Dec-2022

Correspondence Address:
Achyuth Panuganti
Department of ENT and Head and Neck Surgery, All India Institute of Medical Sciences, Rishikesh, Uttarakhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jhnps.jhnps_46_22

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  Abstract 


T4b oral cancers are considered unresectable tumors according to most of the standard treatment guidelines. However, from a head-and-neck surgeon's perspective number of factors has to be considered before labeling a T4b cancer as unresectable. This narrative review aims to emphasize various aspects of decision-making in treating a T4b oral cancer, in particular tumors involving infratemporal fossa (ITF). We conducted a literature search in PubMed for articles published between January 1990 and December 2021 using the following key terms: Oral cancer, advanced oral cancer, Head and Neck cancer, T4b oral cancer, ITF, and Compartment surgery. Then, some of these terms were used in combination for the search. Finally, a result was manually checked for relevant articles. A narrative review is presented from the surgeon's perspective in the management of T4b oral cancer.

Keywords: Compartmental resection, head-and-neck cancer, infratemporal fossa, oral cancer, T4b oral cancer


How to cite this article:
Thaduri A, Panuganti A, Maharaj DD, Kaul P, Majumdar KS, Usmani SA, Garg PK. Approach to T4b oral cancers – A surgeon's perspective. J Head Neck Physicians Surg 2022;10:127-31

How to cite this URL:
Thaduri A, Panuganti A, Maharaj DD, Kaul P, Majumdar KS, Usmani SA, Garg PK. Approach to T4b oral cancers – A surgeon's perspective. J Head Neck Physicians Surg [serial online] 2022 [cited 2023 Feb 1];10:127-31. Available from: https://www.jhnps.org/text.asp?2022/10/2/127/363926




  Introduction Top


Oral cancer is one of the most prevalent cancers and a leading cause of mortality in Southeast Asian countries. They account for nearly one-third of all cancers.[1] In developing countries, a significant number of patients with oral cancers present to the clinician in an advanced stage. Treatment delays are associated with worse overall survival (OS). A Taiwanese cancer registry-based study quoted >40% of patients diagnosed with treatment delay of >20 days.[2]

Locally advanced-stage oral cancer requires multimodality treatment. They are routinely treated with surgery, followed by adjuvant radiotherapy (RT). Surgery requires clearances of a tumor with an adequate three-dimensional clear margin. Adjuvant chemoradiotherapy is based on risk factors. However, a subset of patients with locally advanced nonmetastatic disease is not a candidate for upfront surgery. They are either inability to achieve a clear resection margin or constraints in functional reconstruction after extensive resection. The first indication is still a daunting task to the oncosurgeon. Recent advances in reconstructive techniques made the latter indication less critical. This article aims to highlight current evidence in the management of T4b oral cancers.


  Definition of T4B Oral Cancers Top


The American Joint Committee on Cancer 8th edition defines T4b oral cancers as lesions with extension to masticator space, pterygoid plates, skull base, and internal carotid.[3] Liao et al. classified lesions of T4b involving the masticator space into supranotch and infranotch disease, supranotch being the tumor extension is at or above both the coronoid process and condylar process in the transaxial section on chemotherapy (CT).[4] Trivedi et al. classified T4b lesions as Class-I: Involvement of any of the following structures below the sigmoid notch-masseter and medial pterygoid (lower masticatory space, infranotch), Class-II: Involvement of lateral pterygoid, temporalis above the sigmoid notch (intermediate masticatory space, and low supranotch), and Class III: Involvement of pterygomaxillary fissure, inferior orbital fissure, and intracranial space (high supranotch).[5] Treatment dilemma still exists in a subset of T4b oral cancer patients with masticatory space involvement. There is a diverse opinion among oncologists on the treatment of T4b oral cancer.


  Resectable and Borderline Resectable Tumours Top


The ability to achieve clear resection margins is called a resectable tumor. This is a technical term as it depends on the ability of the surgeon and the extent of the tumor. Patil et al., in their study, described tumors extending into the high infratemporal fossa (ITF), which is on CT, lesions above an imaginary line passing at the level of the sigmoid notch in the axial plane as borderline resectable tumors.[6] NCCN 2019 guidelines suggest that patients be enrolled in clinical trials, where achieving negative margins are an issue.[7]


  Management of T4B Oral Cancer Top


There is still a grey area in treating such tumors, so various treatment options are followed across different centers. Our discussion is elaborated under the following headings:

  1. Definitive CTRT
  2. Neoadjuvant chemotherapy (NACT), followed by surgery
  3. NACT/RT, followed by surgery.



  Role of NEO Adjuvant Chemotherapy Top


The rationale for proposing NACT in advanced oral cancer malignancies is to improve the overall oncological outcome by reducing the size of the tumor before definitive therapy or facilitating possible R0 resection following tumor shrinkage.

None of the well-structured controlled studies so far have addressed the role of NACT in locally very advanced resectable or borderline resectable oral cancers. In resectable mouth cancers, there are two randomized controlled trial addressing the role of NACT. Licitra et al. showed no benefit in the OS in the NACT arm administering the PF (cisplatin & fluorouracil) regimen; however, mandibular preservation rates were better in the chemotherapy cohort.[8] Zhong et al. studied the Taxane, cisplatin & fluorouracil (TPF) regimen in 256 patients with no benefit in OS in the NACT arm.[9]

Evidence on the role of NACT in borderline resectable tumors (T4b) or unresectable tumors comes from a few retrospective studies. Prabhash et al. in 110 unresectable patients with masticator space and pterygoid plates, involvement was considered for NACT with the three-drug regimen in 20% and the two-drug regimen in 80% of patients post NACT 30.9% of patients had become operable.[10] In a study by Fang et al., 35 patients (44.3%) who received NACT before concurrent chemoradiotherapy (CCRT) reported no change in complete or partial response rates.[11] None of the studies showed any oncological benefit of NACT in terms of OS in patients with oral cancer. Neoadjuvant therapy has no established role in oral cancer except for the increase in the resectability of borderline operable tumors.[6]

However, with the introduction of three-drug regimens for induction therapy in locally advanced head-and-neck cancer in TAX 323 and TAX 324 studies, improved OS with three-drug regimens was at the cost of increased Grade III and Grade IV toxicity. However, the oral cavity patients constituted only 17% and 13%, respectively, in both studies.[12],[13]


  Surgery Versus Ctrt as Primary Modality Top


Even though there are no studies with the head-on comparison between the treatment modalities, few retrospective studies reported poor outcomes in T4b patients undergoing CRT as the primary treatment modality. Mair et al. reported OS among surgical groups ranging from 19 to 29 months and a median OS of 8.14 months in CCRT.[14] The National cancer database study of 1515 presented that only 24% of T4b patients underwent curative treatment, of which 56.7% of patients underwent primary surgery, which had better 2-year survival compared with nonsurgical treatment modality.[15] Prabhash et al. reported that 27% of T4b patients who underwent CCRT as a primary treatment modality had a median survival of 6.5 months and 18 months in surgical patients.[10] All the studies had selection bias as the patients with CCRT as the treatment modality are either with more advanced diseases due to high notch involvement or poor performance status. Results of various studies are illustrated in [Table 1].
Table 1: Illustrates results of various studies assessing role of Neo adjuvant therapy in T4b Oral cancer

Click here to view



  Surgical Issues in the Management of Advanced Oral Cancer Top


Approach and Concern of R0 resection

One main concern with T4b is the inability to achieve clear resection margins; the involvement of structures above the mandibular notch makes the desirable clear margin of 1 cm difficult because the distance between the notch and skull base is only 2 cm. Furthermore, the distance from the lower one-third of pterygoid plates to the skull base is only 3 cm.[4] Achieving clear margins are the core principle of any oncological resection. Due to extensive soft tissue and neurovascular structures in the masticator space, achieving a clear margin may be difficult in a few cases. A compartment approach with removal of the entire anatomic unit of the masticator space is proposed by Trivedi et al. for resection of T4b tumors involving masticator space with better oncological outcomes.[5] Surgical expertise matters under challenging cases. About 12–38% had close-cut margins in cases of T4b tumors reported across various studies in the literature [Table 2].[10],[14],[16],[17] Select cases with prior information on imaging regarding specific structures such as a lateral pterygoid muscle, pterygoid plates, and pterygomaxillary fissure help the surgeon decide other treatment options, where resectability is the primary concern. For complete excision of the tumor in advanced oral cancer, compartmental resection is the preferred surgical technique. Trivedi et al., in the pathological assessment of postresection specimens, identified that the pterygoid muscles were pathologically involved in 75% of cases.[18]
Table 2: Illustrates cut margin status across various studies assessing T4b oral cancer

Click here to view


Role of frozen sections in intraoperative margin assessment

The role of frozen section in advanced oral cancers is not well established; however, the recent meta-analysis by Bulbul et al. showed the questionable role of the intraoperative frozen section, with initial margin positive resection converted to negative margin showed poor 5-year local recurrence-free survival compared to initial R0 resection. Questioning the available or practiced frozen section methods.[19]

Complications and morbidity

Resection at the skull base is done with caution due to the critical neurovascular structures, and sometimes, bleeding from the pterygoid venous plexus can be troublesome. The internal carotid artery is located in the poststyloid compartment, which is in close relation to the ITF. T4b lesions involve resection of large areas, resulting in massive postoperative defects, associated mainly with swallowing problems and cosmetic defects. The advancement in microvascular reconstructive techniques, bone flaps, and soft-tissue flaps help in the reconstruction of these vast defects.

Survival outcomes

Various retrospective studies have shown that select T4b cases treated with surgery and adjuvant therapy had similar outcomes as T4a tumors. In a study by Baddour et al. of operable T4b cases, 2 years of OS and recurrence-free survival were 44.0% and 52.6%, respectively.[20] Liao et al. showed 5 years disease-free survival (DFS) in infranotch pT4b and pT4a tumors as 63% and 55%, respectively (P = 0.2813), and OS as 62% and 44% (P = 0.2643), respectively.[4] Mair et al., on comparison between T4a and T4b cases, observed no statistically significant difference in 3-year locoregional control (71.1% vs. 61.8%: P = 0.107) and OS (49.6% vs. 41.1%: P = 0.518).[14] However, all the studies are single institutional retrospective. Risk factors like nodal staging, extra nodal extension and tumor stage are few factors that may determine oncological outcome of the treatment provided. [Table 3] illustrates results of various studies assessing survival outcomes of T4b oral cancer.
Table 3: Illustrates results of various studies assessing outcomes of T4b oral cancer

Click here to view
[21]


  Conclusion Top


T4b cases need to be evaluated carefully for the disease extent; surgery with adjuvant therapy should be offered in infranotch disease. Neoadjuvant therapy and response assessment for operability can be offered in supranotch disease involving the lateral pterygoid muscle, temporalis, and lower third of pterygoid plates. High supranotch disease can be considered in clinical trials. A well-structured randomized control trial with all the available treatment options arms is the need of the hour.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Disclosure

This material has never been published and is not currently under evaluation in any other peer reviewed publication.

Ethical approval

Not applicable.

Informed consent

Not applicable.



 
  References Top

1.
Gupta N, Gupta R, Acharya AK, Patthi B, Goud V, Reddy S, et al. Changing trends in oral cancer – A global scenario. Nepal J Epidemiol 2016;6:613-9.  Back to cited text no. 1
    
2.
Liao CT, Chen HN, Wen YW, Lee SR, Ng SH, Liu TW, et al. Association between the diagnosis-to-treatment interval and overall survival in Taiwanese patients with oral cavity squamous cell carcinoma. Eur J Cancer 2017;72:226-34.  Back to cited text no. 2
    
3.
Edge Stephen B. and American Joint Committee on Cancer. Ajcc Cancer Staging Manual. 8th ed. New York: Springer; 2017.  Back to cited text no. 3
    
4.
Liao CT, Ng SH, Chang JT, Wang HM, Hsueh C, Lee LY, et al. T4b oral cavity cancer below the mandibular notch is resectable with a favorable outcome. Oral Oncol 2007;43:570-9.  Back to cited text no. 4
    
5.
Trivedi NP. Oral cancer involving masticator space (T4b): Review of literature and future directions. Head Neck 2018;40:2288-94.  Back to cited text no. 5
    
6.
Patil VM, Prabhash K, Noronha V, Joshi A, Muddu V, Dhumal S, et al. Neoadjuvant chemotherapy followed by surgery in very locally advanced technically unresectable oral cavity cancers. Oral Oncol 2014;50:1000-4.  Back to cited text no. 6
    
7.
head-and-neck.pdf. Available from: https://Www.Nccn.Org/Professionals/Physician_Gls/Pdf/Head-And-Neck.Pdf. [Last accessed on 2021 Jan 11].  Back to cited text no. 7
    
8.
Licitra L, Grandi C, Guzzo M, Mariani L, Lo Vullo S, Valvo F, et al. Primary chemotherapy in resectable oral cavity squamous cell cancer: A randomized controlled trial. J Clin Oncol 2003;21:327-33.  Back to cited text no. 8
    
9.
Zhong LP, Zhang CP, Ren GX, Guo W, William WN Jr., Sun J, et al. Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous cell carcinoma. J Clin Oncol 2013;31:744-51.  Back to cited text no. 9
    
10.
Prabhash K, Joshi A, Patil V, Noronha V, Juvekar S, Deshmukh A, et al. Is there a role of induction chemotherapy followed by resection in T4b oral cavity cancers? Indian J Cancer 2013;50:349.  Back to cited text no. 10
    
11.
Fang FM, Chuang HC, Chou SY, Huang TL, Wang CJ, Lin YT, et al. The therapeutic benefit of radical resection for T4b oral cavity squamous cell carcinoma with partial or complete response after radical chemo-intensity-modulated radiotherapy (IMRT). Ann Surg Oncol 2016;23:866-73.  Back to cited text no. 11
    
12.
Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 2007;357:1695-704.  Back to cited text no. 12
    
13.
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.  Back to cited text no. 13
    
14.
Mair MD, Sawarkar N, Nikam S, Sarin R, Nair D, Gupta T, et al. Impact of radical treatments on survival in locally advanced T4a and T4b buccal mucosa cancers: Selected surgically treated T4b cancers have similar control rates as T4a. Oral Oncol 2018;82:17-22.  Back to cited text no. 14
    
15.
Patel EJ, Oliver JR, Vaezi A, Li Z, Persky M, Tam M, et al. Primary surgical treatment in very advanced (T4b) oral cavity squamous cell carcinomas. Otolaryngol Head Neck Surg 2021;165:431-7.  Back to cited text no. 15
    
16.
Mohiyuddin SM, Harsha P, Maruvala S, Sumanth KR, Suresh TN, Manjunath GN, et al. Outcome of compartment resection of locally advanced oral cancers extending to infratemporal fossa: A tertiary rural hospital experience. Eur Arch Otorhinolaryngol 2018;275:2843-50.  Back to cited text no. 16
    
17.
Liao CT, Lee LY, Hsueh C, Lin CY, Fan KH, Wang HM, et al. Comparative outcomes in oral cavity cancer with resected pT4a and pT4b. Oral Oncol 2013;49:230-6.  Back to cited text no. 17
    
18.
Trivedi NP, Kekatpure VD, Shetkar G, Gangoli A, Kuriakose MA. Pathology of advanced buccal mucosa cancer involving masticator space (T4b). Indian J Cancer 2015;52:611-5.  Back to cited text no. 18
[PUBMED]  [Full text]  
19.
Bulbul MG, Tarabichi O, Sethi RK, Parikh AS, Varvares MA. Does clearance of positive margins improve local control in oral cavity cancer? A meta-analysis. Otolaryngol Head Neck Surg 2019;161:235-44.  Back to cited text no. 19
    
20.
Baddour HM, Ochsner MC, Patel MR, Switchenko JM, Beitler JJ, Magliocca K, et al. Surgical resection is justifiable for oral T4b squamous cell cancers with masticator space invasion. Laryngoscope 2021;131:E466-72.  Back to cited text no. 20
    
21.
Pillai V, Yadav V, Kekatpure V, Trivedi N, Chandrashekar NH, Shetty V, et al. Prognostic determinants of locally advanced buccal mucosa cancer: Do we need to relook the current staging criteria? Oral Oncol 2019;95:43-51.  Back to cited text no. 21
    



 
 
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Abstract
Introduction
Definition of T4...
Resectable and B...
Management of T4...
Role of NEO Adju...
Surgery Versus C...
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Conclusion
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