|Year : 2014 | Volume
| Issue : 2 | Page : 100-103
Referral pattern for neoadjuvant chemotherapy in the head and neck cancers in a tertiary care center
VM Patil1, V Noronha1, A Joshi1, VM Krishna1, S Dhumal1, V Chaudhary1, S Juvekar2, PS Pai3, C Pankaj3, D Chaukar3, AK Dcruz3, K Prabhash1
1 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
3 Department of Head and Neck Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||7-Aug-2014|
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Use of any treatment modality in cancer depends not only on the effectiveness of the modality, but also on other factors such as local expertise, tolerance of the modality, cost and prevalence of the disease. Oropharyngeal and laryngeal cancer are the major subsites in which majority of neoadjuvant chemotherapy (NACT) literature in the head and neck cancers is available. However, oral cancers form a major subsite in India. Materials And Methods: This is an analysis of a prospectively maintained data on NACT in the head and neck cancers from 2008 to 2012. All these patients were referred for NACT for various indications from a multidisciplinary clinic. Descriptive analysis of indications for NACT in this data base is presented. Results: A total of 862 patients received NACT within the stipulated time period. The sites where oral cavity 721 patients (83.6%), maxilla 41 patients (4.8%), larynx 33 patients (3.8%), laryngopharynx 8 patients (0.9%) and hypopharynx 59 patients (8.2%). Out of oral cancers, the major indication for NACT was to make the cancer resectable in all (100%) patients. The indication in carcinoma of maxilla was to make the disease resectable in 29 patients (70.7% of maxillary cancers) and in 12 patients (29.3% of maxillary cancers) it was given as an attempt to preserve the eyeball. The indication for NACT in laryngeal cancers was organ preservation in 14 patients (42.4% of larnyngeal cancer) and to achieve resectability in 19 patients (57.6% of larnyngeal cancer). The group with laryngopharynx is a cohort of eight patients in whom NACT was given to prevent tracheostomy, these patients had presented with early stridor (common terminology criteria for adverse events Version 4.02). The reason for NACT in hypopharyngeal cancers was for organ preservation in 24 patients (40.7% of hypopharyngeal cancer) and for achievement of resectability in 35 patients (59.3% of hypopharyngeal cancer). Conclusion: The major indication for NACT is to make disease resectable at our center while cases for organ preservation are few.
Keywords: Borderline resectable, neoadjuvant chemotherapy, oral cancers, unresectable
|How to cite this article:|
Patil V M, Noronha V, Joshi A, Krishna V M, Dhumal S, Chaudhary V, Juvekar S, Pai P S, Pankaj C, Chaukar D, Dcruz A K, Prabhash K. Referral pattern for neoadjuvant chemotherapy in the head and neck cancers in a tertiary care center. Indian J Cancer 2014;51:100-3
|How to cite this URL:|
Patil V M, Noronha V, Joshi A, Krishna V M, Dhumal S, Chaudhary V, Juvekar S, Pai P S, Pankaj C, Chaukar D, Dcruz A K, Prabhash K. Referral pattern for neoadjuvant chemotherapy in the head and neck cancers in a tertiary care center. Indian J Cancer [serial online] 2014 [cited 2019 Aug 22];51:100-3. Available from: http://www.indianjcancer.com/text.asp?2014/51/2/100/137956
| » Introduction|| |
Treatment of cancer is determined by the standard guidelines laid down by professional bodies. The use of chemotherapeutic agents is further governed by regulatory organizations in each country. By and large, the treatment strategies are developed on the basis of large, well-designed randomized controlled trials. However, such guidelines may not adequately address local influences such as prevalent epidemiology, socio-economic conditions, resource availability and infrastructure. 
In India, head and neck cancer is the most common malignancy among males. , Due to the limited number of trained head and neck surgeons and delay in seeking treatment, patients often present with locally advanced disease. The standard treatment in such patients is radical chemoradiotherapy. , However, the outcomes are not optimal. One option is giving induction chemotherapy followed by definitive surgery or radiation. Though neoadjuvant chemotherapy (NACT) has been evaluated in multiple studies, there is no consensus regarding the actual benefit and optimal situations where it may be beneficial. ,,,,,,,,, In the majority of NACT trials, the indication of chemotherapy has been either organ preservation or its use has been followed by chemoradiation in unresectable cancer settings. ,,,,, NACT followed by surgery has been evaluated in a few studies, nearly always in operable cancers. ,
At our center, NACT is given to patients based on discussions in a multidisciplinary clinic. In the present paper, we have attempted to analyze the patterns of use of NACT in our center.
| » Materials and Methods|| |
We maintain a prospective database of all patients how are referred for NACT in our Head and Neck Cancer Medical Oncology Out-patient Department. This was a retrospective analysis of patients undergoing NACT from 2009 to 2012. At our center, every case of head and neck cancer is discussed in a multidisciplinary joint clinic and a decision regarding the treatment is taken. For this analysis, only patients with squamous cell carcinoma and primary in the oral cavity, maxilla, larynx and hypopharynx were selected. There were 862 patients, fitting within the above criteria who had been referred for NACT during this period. The site distribution, stage distribution and the indication for NACT were recorded. The database, the hospital electronic medical record and the case papers of each patient were sought for the exact reason why the patient was considered for NACT. Indication for NACT was divided in to two broad categories either organ preservation or to achieve resectability. In addition, objective reasons as far as possible were sought for NACT referral. These reasons were objective involvement of anatomical landmarks, important spaces, proximity to important vital structures or extensive involvement of soft-tissue or skin, which would have required a morbid surgery.
The statistical analysis was performed by SPSS version 16. Descriptive analysis has been presented.
| » Results|| |
During the above mentioned period, 862 patients received NACT. Out of the 862 patient, oral cavity primary was seen in 721 patients (83.64%), maxillary primary in 41 patients (4.75%), laryngeal primary in 33 patients (3.83%), laryngopharyngeal primary in 8 patients (0.93%) and hypopharyngeal primary in 59 patients (8.18%). The subsite distribution has been depicted in [Table 1].
The stage grouping was Stage III in one patient and rest all where Stage IV. The details of T staging N staging according to major site are depicted in [Table 2].
|Table 2: Stage wise distribution according to site of primary. N0 nodal status is not depicted|
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Referral pattern for NACT
Overall the referral for NACT was for organ preservation in 76 patients (8.82%) and for achievement of resectability in patients in 786 patients (91.18%). The detailed referral pattern for each site and the reasons for NACT are described below at each site in detail.
Oral cavity cancer
- The referral for NACT was to make the cancer resectable in 721 patients (100.0% of oral cancers). The reasons for referral for NACT [Figure 1] were: Extensive skin infiltration, which would have necessitate extensive skin resection: 255 (35.36% of oral cancers)
- Peritumoral edema reaching up to or above zygoma: 260 (36.06% of oral cancers)
- Peritumoral edema reaching up to hyoid bone or below it: 82 (11.37% of oral cancers)
- Infratemporal fossa (ITF) involvement: 76 (10.54% of oral cancers)
- Borderline resectability: 39 (5.27% of oral cancers)
- Extensive involvement of the floor of mouth: 9 (1.25% of oral cancers).
|Figure 1: Depiction of reasons in stage IV a tumors for neoadjuvant chemotherapy because of which these tumors were considered borderline resectable. In the buccal mucosa primary if the tumor or edema related to it extends above the level of zygoma. In case of floor of mouth or anterior two-third of tongue primary if the tumor extents up to the level of hyoid bone or if the tumor extends into the vallecula or base of tongue. In case of primaries in larynx or hypopharynx if the tumor is extending up to oropharynx|
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Carcinoma of maxillary sinus
The indication was to make the disease resectable in 29 patients (70.73%). Among these patients two patients had intracranial extension, six had involvement of pterygoid plates and 20 had ITF involvement. In 12 patients (29.27%), it was given so that eyeball could be attempted to be preserved.
Carcinoma of larynx
The indication for NACT was organ preservation in 14 patients (42.42% of laryngeal cancer) and to achieve resectability in 19 patients (57.58% of laryngeal cancer). Among those for organ preservation, the need was due to exolaryngeal spread in 6 patients (18.18% of laryngeal cancer) and superficial cartilage invasion in 8 patients (24.24% of larnyngeal cancer). In those with unresectable disease, the reasons were carotid encasement in 3 patients (9.09% of larnyngeal cancer), mucosal extension of disease until tonsil in 10 patients (30.30% of larnyngeal cancer), N3 lymph node in 4 patients (12.12% of larnyngeal cancer) while prevertebral muscle extension and extension to the esophagus in one patient each (3.03%).
Carcinoma of laryngopharynx
The group with laryngopharynx is a cohort of eight patients in whom NACT was given to prevent tracheostomy (included in organ preservation), these patients had presented with early stridor (common terminology criteria for adverse events version 4.02). This was done to avoid deleterious effects of tracheostomy.
Carcinoma of hypopharynx
The reason for NACT was for organ preservation in 24 patients (40.68% of hypopharyngeal cancer) and for achievement of resectability in 35 patients (59.32% of hypopharyngeal cancer). The need for NACT in organ preservation was exolaryngeal spread without cartilage erosion in 4 patients (6.78% of hypopharyngeal cancer) and minor thyroid cartilage invasion in 20 patients (33.90% of hypopharyngeal cancer). In group for achievement of resectability the reasons were N3 node in 8 patients (13.56% of hypopharyngeal cancer), oropharyngeal involvement in 24 patients (40.68% of hypopharyngeal cancer) or extensive disease with cartilage erosion in 3 patients (5.08% of hypopharyngeal cancer).
| » Discussion|| |
The aim of surgery in the head and neck cancers is R0 resection. ,, The factors determining achievement of R0 resection includes tumor stage, surgeon's experience and skill and rehabilitative facilities. As such, it may be difficult to define strict objective criteria for resectability of a particular tumor and the surgical outcome will depend on myriad factors. This is especially true in case of tumors that are borderline resectable or which require morbid surgeries. In India and the developing countries, a major proportion of patients present with locally advanced and very locally advanced head and neck cancers. In such patients, achievement of R0 resection remains a challenge. 
Down-staging of tumor by preoperative chemotherapy may help by down-staging tumors and allow R0 resections in such technically challenging tumors with acceptable morbidity.  As can be seen in our analysis, this forms the major indication of our patients referred for NACT. This in contrast to the trials reported mainly from the western countries where the indication for use of NACT been mainly for organ preservation strategies or for improvement in local control. ,,,,, The use of NACT for organ preservation has been typically described in the larynx and hypopharynx. ,,, Several trials (RTOG 91-11, DeCIDE and PARADIGM) showed that NACT prior to concurrent chemoradiation (CT-RT) did not result in any improvement in the measured endpoints. , Even at our center, few patients have received NACT for organ preservation. Licitra et al. have previously reported that NACT in operable oral cavity cancers can increase the rate of mandibular preservation. However, other studies have shown that NACT followed by surgery in operable oral cancers is not associated with any improvement in disease free survival or overall survival. ,
We have mainly utilized NACT in the setting of locally advanced tumors of the oral cavity, which were considered unresectable or borderline unresectable. The decision was made in a multidisciplinary clinic, which included radiologists, surgical oncologists, radiotherapists and medical oncologists. The anatomical landmarks used for specifying resectability have been highlighted earlier in publications by Pradhan  and Patil et al.  These landmarks have been explained in [Figure 1]. Mostly, these are anatomical landmarks, spaces or boundaries, which when involved hamper the ability of the surgeon to achieve R0 resection. We believe that our approach might help improve outcomes especially in patients with cancers of the oral cavity, maxillary sinus and hypopharynnx. ,, These sites have traditionally had poor outcomes with chemoradiation alone. Recent reports from major centers in India appear to show benefit with NACT. ,
Theoretically, NACT followed by surgery might have more favorable outcomes compared with CT-RT due to the excision of chemoresistant and radioresistant tumor tissues. [Figure 2] shows a hypothetical diagrammatic representation of a cross-sectional view of locally advanced head and neck cancers. The tumor tissue can be postulated to consist of three types of cell populations. The peripheral cells are well oxygenated; the intermediate zone cells are hypoxic while the center has necrotic cells and negligible oxygen supply. Since the oxygen enhancement ratio is high for low linear energy transfer radiation, the use of radiation or chemoradiation will be associated with suboptimal outcomes. ,,, However, when such patients receive NACT, even a minimal shrinkage in the areas depicted can make these technically unresectable tumors resectable. Consequently, the tumor with the resistant clones can be completely excised. This is a biologically plausible explanation, which has to be confirmed by experimental and laboratory work. The clinical relevance of this approach needs to be confirmed in a well-conducted randomized trial in technically unresectable tumors where one arm should consist of NACT followed by CT/RT and the other arm CT/RT alone.
|Figure 2: The saggital profile of locally advanced tumor showing the population of well- oxygenated, hypoxic and necrotic tumors|
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| » Conclusions|| |
To conclude, our data shows that NACT referral pattern is different from that seen in western trials.
The major indication for NACT in our setting is to achieve resectability. A detailed analysis in future would provide us with the results of this approach and A in the subsequent period would through further light on this approach.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]