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Table of Contents
Year : 2020  |  Volume : 3  |  Issue : 2  |  Page : 390-393

Authors' reply to Kuriakose et al., Mallick et al., and Chaukar et al.

1 Department of Medical Oncology, HBCH, Sangrur, Punjab, India
2 Department of Head and Neck Surgical Oncology, HBCH, Sangrur, Punjab, India
3 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Submission28-Mar-2020
Date of Decision01-Apr-2020
Date of Acceptance11-Apr-2020
Date of Web Publication19-Jun-2020

Correspondence Address:
Kumar Prabhash
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/CRST.CRST_99_20

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How to cite this article:
Goel AK, Singla A, Prabhash K. Authors' reply to Kuriakose et al., Mallick et al., and Chaukar et al. Cancer Res Stat Treat 2020;3:390-3

How to cite this URL:
Goel AK, Singla A, Prabhash K. Authors' reply to Kuriakose et al., Mallick et al., and Chaukar et al. Cancer Res Stat Treat [serial online] 2020 [cited 2021 Dec 4];3:390-3. Available from: https://www.crstonline.com/text.asp?2020/3/2/390/287285

We read with interest the letter from Kuriakose et al.,[1] Mallick Mallick et al.,[2] and Chaukar et al.[3] for our article titled, “Neoadjuvant chemotherapy in oral cancer: Current status and future possibilities.”[4] Unfortunately, hardly any of their opinions were backed by evidence. For instance, Kuriakose et al. have stated that the concept of technically unresectable or borderline resectable oral cancers has not been validated by other groups. The authors perhaps have not done a literature search before making this comment. We found multiple articles on technically unresectable oral cancers from South India,[5],[6] Northern-Central India,[7],[8] Sub-Himalayan region,[9] Western India,[10],[11],[12] and Eastern India.[13],[14] Consequently, these cancers are included in the current treatment guidelines.[15] The outcomes reported in most of the studies are in line with those reported by Patil et al.[16] In addition, multiple studies have used this concept, even internationally with induction chemotherapy [17],[18],[19] and induction chemoradiation.[20] Hence, it is unimpeachable to say that this concept is accepted widely, both nationally and internationally.

We agree that there can be multiple ways of treating tumors, and our senior colleague from South India believes in performing upfront surgery for technically unresectable oral cancers. However, this strategy has very limited evidence. Kuriakose et al. have published a series on the outcomes of T4a and T4b oral cancers.[21] Although 282 patients were accrued in the study, only 51 had Type 2 or Type 3 masticator space involvement; these should have been considered as cases of technically unresectable tumors. Considering that the authors work in a specialized head-and-neck cancer unit with a high patient load, it is surprising that in a period of 8 years (2009–2016), the authors could operate on only 51 patients. It is highly likely that these 51 patients were supraselected, unlike the consecutively selected 721 patients reported by Patil et al. over a period of 5 years. The authors reported an inconceivably low rate (6.8%) of positive margins in T4b patients. In the best of centers, the rate of positive pathological margins for oral cancers is in the range of 11%–51%,[22] even for patients with T2–T4a tumors. Similarly, a clear margin status of only 71% in T4a patients was reported in an abstract presented at the Foundation for Head and Neck Oncology 2018 by a tertiary care cancer center from Kolkata.[23] At the same conference, outcomes of 50 patients with borderline resectable oral cancer were reported from Ahmedabad. The median disease-free survival (DFS) was 2–6 months.[24] This suggests that the authors' results need validation and are applicable in select few patients.

Performing a radical compartmental resection, as proposed by the authors, in T4b tumors is a major surgery, with considerable postoperative morbidity (40%–63%) and deterioration in the quality of life.[25],[26],[27] There is no evidence to suggest that this approach has been compared with current approach. The concept of futile surgery needs to be revisited here in view of these findings. Failure within 1 year of surgery is considered the definition of futile surgery.[28],[29] The authors have shown that for patients with T4b tumors with lateral pterygoid involvement, i.e., for cases with Type 2 masticator space involvement, the median DFS is in the range of 1 year [Figure 3]c in authors' study].[21] This suggests that surgery was a futile procedure in nearly 50% of the patients. Considering that the definition of DFS did not include death without recurrence as an event, there is a possibility of overestimation of DFS, thus suggesting that in >50% of the cases, such an effort is likely to be considered futile as per international definitions.

Further, the authors have commented that there is a widespread, irrational, and inappropriate use of chemotherapy; yet again, the comments have not been backed by published literature. These are the statements we should always avoid in public discourse by researchers. Considering the New England definition of futile surgery,[28],[29] performing unnecessary surgery and deforming the face and impairing the functions of the oral cavity of patients is irrational and inappropriate; this has been validated in an international survey.[30]

The authors have discredited the results of the mandibular preservation study. It was a well-planned Phase 2 study, and the long-term results will be presented at ASCO 2020, in the “poster highlight” session. The reporting of results must be reasonable and logical. The study, when presented in 2015, had a limited follow-up of 2 years, and hence, the publication was deferred until 5 years post recruitment of the last patient. We are surprised that Kuriakose et al. have discredited the subgroup analysis results of Licitra et al.[31] However, their opinion that surgery should be the preferred treatment for oral cancer is also based on a subgroup analysis from a randomized study from Singapore.[32] Overall, this randomized study on locally advanced, resectable head-and-neck cancers showed no difference between the outcomes of chemoradiation and surgery, followed by adjuvant therapy. The benefit of surgery in oral cancer was suggested based on an unplanned subgroup analysis without any multiplicity correction. Therefore, it appears that the authors are willing to accept subgroup analyses if they favor surgery but not if they favor other treatment modalities. The authors have used a breast cancer analogy to suggest that neoadjuvant chemotherapy (NACT) might leave behind microscopic disease. Again, it is surprising that the authors have discredited multiple randomized studies on breast cancer that have shown that despite the microscopic disease, there is no impact on the overall survival.[33] Hence, NACT is an established treatment modality for breast cancer.[34]

The authors have commented that the mortality with NACT in a community setting could be as high as 15.3%, and hence, NACT cannot be used. Again, the author has not provided a reference for this mortality rate. This figure is reported from the United States of America, in susceptible patients. Multiple community series from India have confirmed that the mortality with NACT is well below 5%. Selection of a patient is key for any treatment modality. Surgical complications in fragile patients can lead to a mortality of >8%–10%.[35],[36],[37] Therefore, by the authors' logic, performing surgery on fragile patients would be highly questionable. A Phase II trial from SGPGI, Lucknow, India, reported a mortality rate of >15% with chemoradiation in patients with head-and-neck cancer.[38] This suggests that regardless of the setting, appropriate patient selection is the key to treatment.

”[Table 1]” in Kuriakose et al.'s opinion piece has a factual error. The authors have commented that carboplatin +5-fluorouracil is not a standard concurrent chemotherapy schedule. We would like to refute this claim. The MACH-NC analysis had suggested two schedules with consistent and similar survival benefits as radiation;[39],[40] the first was cisplatin 100 mg/m 2 3 weekly, and the other was the carboplatin-5-FU schedule. These two schedules have never been compared with each other, but in an indirect comparison through meta-analysis, both have shown similar effectiveness and hence are considered category one recommendation by multiple international guidelines.[41],[42],[43]

We respect the opinion of our senior colleagues and appreciate their criticism. However, the best way to settle this discourse is through collaborative studies.[44] Multiple studies directed at answering these questions are either ongoing or will commence soon at the Tata Memorial Center, Mumbai. We would greatly appreciate the contribution of our colleagues toward these studies. Collectively, we could move toward the betterment of our patients.

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Conflicts of interest

There are no conflicts of interest.

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