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Table of Contents
LETTER TO EDITOR
Year : 2020  |  Volume : 3  |  Issue : 2  |  Page : 385-387

Neoadjuvant chemotherapy in oral cancer: A Hydra that keeps coming back


1 Department of Surgical Oncology, Cochin Cancer Research Center, Kochi, Kerala, India
2 Head and Neck Institute, Amrita Institute of Medical Sciences, Kochi, Kerala, India
3 Department of Radiation Oncology, Cochin Cancer Research Center, Kochi, Kerala, India

Date of Submission08-Mar-2020
Date of Decision09-Mar-2020
Date of Acceptance19-Mar-2020
Date of Web Publication19-Jun-2020

Correspondence Address:
Moni Abraham Kuriakose
Cochin Cancer Research Center, Kochi, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_71_20

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How to cite this article:
Kuriakose MA, Thankappan K, Sood R, Abraham SL, George P. Neoadjuvant chemotherapy in oral cancer: A Hydra that keeps coming back. Cancer Res Stat Treat 2020;3:385-7

How to cite this URL:
Kuriakose MA, Thankappan K, Sood R, Abraham SL, George P. Neoadjuvant chemotherapy in oral cancer: A Hydra that keeps coming back. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Jul 9];3:385-7. Available from: http://www.crstonline.com/text.asp?2020/3/2/385/287262



The current standard of care for locally advanced oral squamous cell carcinoma (OSCC) is primary surgery and chemoradiotherapy for laryngopharyngeal carcinoma. Although neoadjuvant chemotherapy (NACT) has been tested since 2003; in all but one of the previous eight randomized trials in head-and-neck squamous cell carcinoma, it has categorically demonstrated no oncologic benefit. This includes three trials exclusively in OSCC [Table 1].[1] The current review by Goel et al.[2] is an attempt to rekindle its interest by demonstrating its potential effectiveness in a poorly defined entity called “technically unresectable” OSCC. This is based on the senior author's prior reports, which have not been validated by any other group. Although the data presented in the review are timely and accurate, the interpretation of the data is inaccurate. This can be misleading to your readership and further justify the widespread, inappropriate, and irrational use of chemotherapy in OSCC in India. This trend not only increases the cost of treatment but also can lead to higher mortality and morbidity.
Table 1: Induction chemotherapy trials in oral and head and neck squamous cell carcinomas

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In resectable tumors, although non-surgical treatment is currently practiced in laryngopharyngeal cancers for organ preservation, the use of NACT and mandible preservation surgery in OSCC is based on the flimsiest evidence. The speculation for organ preservation in OSCC is based on an unplanned subset analysis of a study by Licitra et al.[3] showing 21% better mandible preservation with NACT and from a presentation in 2015 from the authors' group showing 49% mandible preservation, which is yet to be published. This leads us to question the veracity of these results. Unlike laryngectomy, which though can be rehabilitated, it cannot be reconstructed; the functional reconstruction of the mandible including dental rehabilitation is now practical. Besides, the authors discredit the results of two randomized trials of NACT in OSCC suggesting the lack of power for not demonstrating oncological effectiveness, however, use the same studies to justify the use of NACT for mandible preservation! The organ preservation surgery following NACT is only feasible if the tumor shrinks concentrically following chemotherapy. Although there are no data available in OSCC, it is established in breast cancer that following NACT in 48% of the patients, tumor islands can be present beyond the main tumor mass.[4]

Of the five criteria listed as “technically unresectable,” the only two acceptable criteria are the inability to achieve negative margins and that the surgery could lead to unacceptable functional deficits. For buccal mucosal cancer with skin edema extending beyond the zygomatic bone or invasion of muscles above the zygomatic notch; although these entities have poor outcomes compared to less extensive tumors, Pillai et al.[5] have demonstrated 43% DFS in this sub-group with primary surgery. When appropriately reconstructed, extensive resection of buccal mucosal carcinoma will have little functional debility. For advanced oral tongue carcinoma, the need for additional laryngectomy along with glossectomy rather than an extension to vallecula or hyoid bone should be the criteria for technical unresectability. Total glossectomy defects can be adequately reconstructed and rehabilitated. The justification of recommending NACT in “technically unresectable” OSCC is based on two series from the senior author.[2] In this study, 43% of the patients had adequate response allowing surgical resection with an excellent OS of 19.6 months (95% confidence interval [CI], 9.59–22.21 months) in patients undergoing surgery versus 8.16 months (95% CI, 7.57–8.76 months) in patients receiving non-surgical treatment (P = 0.0001). This underscores the importance of surgery to achieve adequate oncologic results. Despite stable disease following NACT, 35% of patients in this series underwent surgery with a negative margin. Therefore, many patients who were deemed “technically unresectable” may have been resectable and denied the opportunity for cure.

The other question the current review attempted to answer was whether chemotherapy response could be used as a prognostic marker. Although the data reviewed demonstrated a good correlation between chemotherapy response and oncologic outcome, it is to be noted that it comes with a price. As the authors have pointed out, although docetaxel, platinum, and 5-fluorouracil (TPF), the most preferred NACT regimen is well-tolerated in the clinical trial setting that enrolls mostly young and fitter patients, it is associated with mortality as high as 15.3% when used in the community setting. It is highly questionable whether such a morbid regimen can be used as a prognostic tool to decide on definitive treatment. We do agree with the urgent need to identify clinical and biomarker profiles to triage the patients for appropriate treatment.

From the data presented in the review and others from the literature, it can be concluded that there is no role of NACT in OSCC either in resectable, “technically unresectable,” unresectable, recurrent or metastatic setting. There are also no data to suggest its use for organ preservation in OSCC. The use of NACT as a prognostic tool is highly questionable. There is, however, an immediate need to develop the molecular profile that can identify good responders to NACT.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ferrari D, Ghi MG, Franzese C, Codecà C, Gau M, Fayette J. The slippery role of induction chemotherapy in head and neck cancer: Myth and reality. Front Oncol 2020;10:7.  Back to cited text no. 1
    
2.
Goel A, Singla A, Prabhash K. Neoadjuvant chemotherapy in oral cancer: Current status and future possibilities. Cancer Res Stat Treat 2020;3:51-9.  Back to cited text no. 2
  [Full text]  
3.
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. 3
    
4.
Kim TH, Kang DK, Yim H, Jung YS, Kim KS, Kang SY. Magnetic resonance imaging patterns of tumor regression after neoadjuvant chemotherapy in breast cancer patients: correlation with pathological response grading system based on tumor cellularity. J Comput Assist Tomogr 2012;36:200-6.  Back to cited text no. 4
    
5.
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. 5
    



 
 
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