|Year : 2021 | Volume
| Issue : 2 | Page : 58-65
Pattern of failure among HNSCC: An institution-based study
Afsana Shah1, Dinesh Kumar2, Govind Preet Singh1, Pragya Shukla1
1 Department of Clinical & Radiation Oncology, Delhi State Cancer Institute, Delhi, India
2 Department of Medical Physics & Radiation Oncology, Delhi State Cancer Institute, Delhi, India
|Date of Submission||01-Sep-2021|
|Date of Acceptance||17-Dec-2021|
|Date of Web Publication||24-Aug-2022|
Department of Clinical & Radiation Oncology, Delhi State Cancer Institute, Delhi 110095
Source of Support: None, Conflict of Interest: None
Aim: This retrospective study was conducted to evaluate the pattern of recurrence in head and neck squamous cell carcinoma (HNSCC) patients who received a definitive chemo-radiotherapy. Materials and Methods: In this retrospective study, the data of 308 head and neck patients from January 2015 to March 2015 were analyzed. Only patients who received definitive chemo-radiotherapy were included in the study. The pattern of recurrence was stratified based on age, gender, site involved, histopathological differentiation, stage, habitual risk factors, and treatments received. Results: The mean age of the patients was 51.6 years. No association in the pattern of recurrence based on age, gender, or histopathologic differentiation was found. Patients with habitual risk factors (smoking, tobacco chewing, and alcohol) showed the poorest response to chemo-radiotherapy and unresolved residual disease. Among the primary sites involved, oral cavity patients showed the poorest response with maximum cases of residual disease. In addition, patients with advanced stage remained with residual disease and have a maximum recurrence, and the difference was statistically significant. All the patients who received neoadjuvant chemo-radiation (NACT-RT) as compared to chemo-radiation (CT-RT) had residual disease. According to the pattern of recurrence, the local recurrence was the most common followed by regional and then local and regional, but the distance recurrence was the lowest. Conclusion: Of the patients who have received definitive chemo-radiotherapy, more than half of HNSCC had residual disease. Of the patients with no residual disease, about half of them had recurrence at follow-up. However, no association in the pattern of recurrence was found based on gender or histopathologic differentiation. Patients who have multiple habitual risk factors showed the worst outcome as compared to the patients who have a single habitual risk factor. Patients with multiple habitual risk factors have maximum cases of residual disease and maximum cases of recurrence. Among the habitual risk factors, tobacco chewing was the worst habitual risk factor for refractory residual disease and recurrence. Based on the sites, the patients with carcinoma of the oral cavity showed the worst outcome in terms of residual disease, which is followed by hypopharynx, oropharynx, and then larynx carcinoma, but the rate of recurrence does not depend on the site involved. Advanced-stage patients had a poor response and with maximum cases of recurrence. A combination of chemotherapy with radiation showed better results as compared to the radiation alone in terms of response and recurrence. As to the site of recurrence, the local recurrence was the most common, followed by regional and then distance recurrence. This study indicated that HNSCC is locally aggressive, and local failures are the most common.
Keywords: Chemotherapy, pattern of failure, radiotherapy
|How to cite this article:|
Shah A, Kumar D, Preet Singh G, Shukla P. Pattern of failure among HNSCC: An institution-based study. Bengal J Cancer 2021;1:58-65
| Introduction|| |
Head and neck cancer is common in several regions of the world including India. The primary risk factors associated with head and neck cancer include tobacco use, alcohol consumption, betel quid chewing, and human papillomavirus infection (for oropharyngeal cancer). The relative prevalence of these risk factors contributes to the variations in the observed distribution of head and neck cancer in different areas of the world. Worldwide, head and neck cancer accounts for more than 650,000 cases and 330,000 deaths annually. Head and neck cancers (HNCs) account for approximately 30%–40% of all cancer sites, in India. [2,3] The possible reasons for the higher incidence of HNCs in India include the extensive use of tobacco, pan masala (which include betel quid, areca nuts, and slaked lime), and gutkha. Males are affected significantly more than females, with a ratio ranging from 2:1 to 4:1. Mouth and tongue cancers are more common in the Indian subcontinent. In the past, the majority of patients with the advanced-stage disease were treated with a combination of surgery and radiotherapy, often with the costs of functional and cosmetic morbidity, inducing a diminished quality of life. Unresectable (technically inoperable) head and neck squamous cell carcinoma (HNSCC) was treated by radiotherapy with or without chemotherapy. It appeared that intensified radiotherapy schemes and combinations of chemotherapy and radiotherapy all contribute to an increased remission rate. In advanced HNSCC locoregional control rates, about 50% are reported. Historically, locoregional failure has been the predominant pattern of relapse following nonsurgical treatment. With the rapid advancement of nonsurgical treatment strategies, it is critical to document the pattern of treatment failure in relation to the radiotherapy dose distributions.
| Materials and Methods|| |
A retrospective study was conducted at Delhi State Cancer Institute from January 2015 to March 2015; 308 patients were included, who are suffering from HNSCC of stages 2, 3, and 4, mainly of the site of the oral cavity, oropharynx, hypopharynx, and larynx, which were confirmed by histopathological examination. The staging was done by clinical examination including in-direct laryngoscope, direct laryngoscope, and radiological examination based on AJCC 7th Ed Cancer Staging Manual.
Patient selection criteria
Patients of mainly sites oral cavity, oropharynx, hypopharynx, and larynx were included, which were confirmed by histopathological examination as squamous cell carcinoma (SCC). Patients who had undergone an initial therapeutic surgery to the primary tumor site were also included. Patients with nasopharynx carcinomas, or any other malignancy and Karnofsky performance scale (KPS) <70 were excluded from the study.
The treatment mainly received was NACT-CT + RT, CT + RT, neoadjuvant chemo-radiation (NACT-RT), and NACT only. For patients who were treated with induction chemotherapy, chemotherapy were administered as two to three cycles of docetaxel cisplatin and fluorouracil regimen, dose depending on the body surface area every 3 weeks.
In radiotherapy treatment planning, the patient was treated supine, immobilized with four-clamp thermoplastic cast, and planning computed tomography (CT) scan obtained from the vertex to below the carina with thickness 3–5 mm. Patients were treated using a parallel opposed pair. Planning target volume (PTV) was directly defined using virtual simulation. Patients were treated using conventionally fractionated treatment schedules (2 Gy per fraction): a maximum dose of 46 Gy to the spinal cord and 54 Gy to the brainstem was accepted, and 66–70 Gy in 33–35 fractions to the gross tumor volume. Treatment was commonly planned using a two-phase technique of laterally opposed pair of field-in-fields, with the posterior border moved anterior to the spinal cord before reaching spinal cord tolerance and matched posterior electron fields used to treat nodal areas overlying the cord. A 6 MV photon anterior neck field was matched geometrically to the lateral opposed photon fields. Planning was generated on the ECLIPSE planning system with version 8.9; the external beam radiation was delivered by Medical Accelerator (CLINAC 600C Varian with energy 6 MV).
For patients treated with concomitant chemotherapy, cisplatin 35 mg/m2 weekly was given depending on the KPS of the patient and grading of the reaction.
Tumor response was assessed at 6–8 weeks’ interval, by clinical examination and radiological examination (CT, magnetic resonance imaging [MRI]) based on World Health Organization [WHO] criteria as complete response (CR), partial response (PR), and no response (NR). PR and NR were categorized as a residual disease. Each local or regional treatment failure site was confirmed pathologically.
According to the degree of keratinization, cellular and nuclear pleomorphism, and mitotic activity, based on WHO criteria, the SCC is categorized into three categories: (A) well-differentiated, (B) moderately differentiated, and (C) poorly differentiated.
| Results|| |
A total of 308 primary HNC cases were registered during the period of study. All patients were having histopathology of SCC, except four patients; among them, three were verrucous, and one patient was of adenocarcinoma, who was excluded from the study.
Among all patients of SCC, only 133 (43.19%) patients received a definitive form of treatment and 175 (56.81%) patients received either no treatment or only a palliative form of treatment (chemotherapy only). Out of 133 patients, nine patients have no follow-up, so they were excluded from the study. Out of 124 patients on 2 years’ follow-up, 71 (57.3%) patients have residual disease, 26 (21%) patients were no abnormal disease (NAD), and 27 (21.8%) patients have a locoregional recurrence [Table 1].
The mean age of diagnosis was 51.76 ± 12.88 years, with the youngest patient diagnosed being of 26 years old and the oldest of 86 years of age at the time of registration. The mean age in patients of recurrence was 51.59 years [Table 2].
Of all the registered HNC cases, 85.06% (262) were diagnosed in males and 14.94% (46) in females, with a male to female ratio of 5.69:1. In patients who were having a recurrence, four were female and 23 were male, but that was not statistically significant [Table 3].
The distribution of patients according to the religion was 77.92% (240) among Hindus and 22.07% (68) among Muslims. Among 27 patients of recurrence, 20 were Hindus, and seven were Muslim, which was not statistically significant [Table 4].
|Table 4: Religion * Patient status (PT)-residual (1)/NAD (2)/recurrence (3)|
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HNSCC were further categorized into well-differentiated (34.09% (105)), moderately differentiated (48.37% (149)), and poorly differentiated (9.41% (29)). The pattern of recurrence about histopathologic differentiation was not statistically significant [Table 5].
According to the primary site of involvement, the most common site was oral cavity 55.84% (172), the oral cavity cases are further divided according to subsite buccal mucosa (BM) + gingiva buccal sulcus (GBS) 56.97% (98), floor of mouth (FOM) 3.48% (6), tongue 38.95% (67). Oropharynx 24.35% (75), larynx 14.28% (44), hypopharynx 5.19% (16), and one patient of secondary neck, unknown primary. In reference to the site, tongue shows the poorest outcome, having maximum cases of residual disease, which was statistically significant, and results show that the recurrence does not depend on the site of involvement [Table 6].
The most common predisposing factor was tobacco use, in 83.43% (257). Alcohol intake was not alone as a predisposing habitual factor, it was associated with the use of tobacco in 6.71% (21) patients, and 30 (9.74%) patients were having no habitual risk factor. Patient who were having all habitual risk patterns (smoking, tobacco chewing, and alcohol) show the poorest outcome; all patients were having a residual disease [Table 7].
|Table 7: Tobacco chew (1)/smoking (2)/alcohol (3) * patient status (PT)-residual (1)/NAD (2)/recurrence (3)|
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The most common stage at presentation was stage 4 (239, 77.58%), followed by stage 3 (56, 18.18%), stage 2 (10, 2.79%), and stage 1 (3, 0.8%). The advanced stage shows the worst outcome, having a maximum patient of residual disease, and maximum cases of recurrence that was statistically significant [Table 8].
|Table 8: Stage * patient status (PT)-residual (1)/NAD (2)/recurrence (3)|
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In patients who underwent surgery, patients have a low recurrence in comparison to those whose surgery was not done, which was statistically significant; this may be due to lower stages in a patient who underwent surgery [Table 9].
|Table 9: Surgery * patient status (PT)-residual (1)/NAD (2)/recurrence (3)|
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For the patients who received NACT-RT, all patients were having residual disease, as compared to patients who received CT + RT or NACT-CT + RT, which was also statistically significant. It shows that the best modality of treatment in HNSCC is CT + RT [Table 10].
|Table 10: TT-NACT (1)/NACT-RT (2)/NACT-RT + CT (3)/CT + RT (4) * patient status (PT)-residual (1)/NAD (2)/recurrence (3)|
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According to the distribution of the site of recurrence, the local recurrence was the most common, followed by regional and then local + regional. In spite of the maximum patient of the advanced stage, only four patients were having distance recurrence, three patients were having lung metastasis, one had liver metastasis, and two patients were of buccal mucosa (BM), one larynx, and one hypopharynx, and it was statistically significant [Table 11].
|Table 11: Type of recurrence (TOR)-local (1)/regional (2)/distance (3) * patient status (PT)-residual (1)/NAD (2)/recurrence (3)|
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In the follow-up time, the mean follow-up time of a patient who was NAD was 6 months, and a patient with recurrence was 1 year, which was statistically significant [Table 12].
The most common T (tumor) stage was T4 (59.09%, 182), followed by T3 (29.22%, 91), T2 (9.74%, 30), and T1 (0.97%, 3). The N (node) stage presentation was as follows: N2 was the most common (38.96%, 120), followed by N1 (27.59%, 85), N0 (21.10%, 65), and N3 (12.01%, 37).
| Discussion|| |
Our study aimed to evaluate the pattern of failure among head and neck carcinoma patients who have received definitive chemo-radiotherapy with or without surgery. In our study, most of the patients received incomplete treatment due to the financial burden or distance to the hospital, or issues not described. Among patients who received complete treatment, the most common pattern of recurrence was locoregional as found in other studies.[5-9] In our study, most of the patients were of stage 4, with advanced T stage. We report a significant association between advanced tumor stage (III–IV) and poor overall and disease-specific survival. The tumor size usually affects the choice and outcome of treatment. Increased tumor size has been linked to cervical involvement, [11,12] high recurrence rate, [11,13] and poor prognosis. [14,15] The tumor primary site, tumor thickness, and the degree of differentiation are the most important determents for lymphatic involvement. The site of the primary tumor is the most significant determinant, not only for survival but also for local and regional control. Patients with carcinomas of the larynx, oropharynx, and unknown origin had higher survival and local control rates than those with carcinoma of mobile tongue, the FOM, BM, and hypopharynx. It is now widely accepted that thickness is a more accurate predictor of subclinical nodal metastasis, local recurrence, and survival.
The influence of histological grading as a prognostic factor in oral squamous cell carcinoma was assessed in 215 patients by Kademani in 2006, and he found that the degree of differentiation is a significant predictor of locoregional failure and tumor recurrence, but we found no association in our study. The size of nodal involvement is a very important determent. Distance metastasis is usually reported in N2/N3. Extracapsular spread is also a very important determent as it significantly increases the risk of distance metastasis. It is well recognized that the presence of cervical metastasis is the most important prognostic factor in HNSCC, accounting for a 50% reduction in the 5-year survival rate for ipsilateral cervical lymph node metastasis[17-19] and a 75% reduction in the case of bilateral metastasis. [20,21] When the risk of metastasis exceeds 15%–20%, neck dissection or radiation therapy is indicated. [22,23] Advanced age and high comorbidity appeared to be the main clinical prognostic factors in this study, as also reported by many authors for various upper aero-digestive tract tumor sites.[24-27]
The majority of loco regional recurrence after a CR to treatment occurs within the PTV, and the isolated distant metastatic recurrence was uncommon. This may relate to intrinsic radio resistance or factors such as tumor hypoxia. These data provide a clear rationale for efforts aimed at improving locoregional tumor control. Useful approaches may include induction chemotherapy regimens, biological therapies, radio-sensitizers, altered fractionation, and dose escalation.
| Conclusion|| |
Our study at the institute is the first study showing a pattern of recurrence of head and neck cancer patients. HNC is most common in males compared with females; SCC is the most common histopathology, most common among <65 years of age. The oral cavity is the most common site with BM as the most common subsite; most commonly present as locally advanced, with the use of tobacco in most of the patients.
The mean age of diagnosis and mean age in patients of recurrence was 51 years. In patients who have received a definitive form of treatment, more than half of patients with head and neck carcinoma have residual disease, and on follow-up, patients who responded, around half of the patients have a recurrence. About sex and histopathologic differentiation, no association was found in the pattern of recurrence. Patients who have multiple habitual risk factors show worst outcome as compared to the single habitual risk factor; patients with multiple habitual risk factor have maximum cases of residual disease, and maximum cases of recurrence; if patients are further categorized, tobacco chewing is the worst habitual risk factor for head and neck carcinoma. In reference to the site, patients with carcinoma in the oral cavity show the worst outcome as a maximum patient of residual disease, followed by hypopharynx, oropharynx, and then larynx, but the rate of recurrence does not depend on the site of involvement. As the stage of the tumor increase, response and recurrence pattern shows the worst outcome. Combining chemotherapy with radiation shows better results as compared to radiation alone in response to the treatment and pattern of recurrence. In comparison to the site of recurrence, the local recurrence was the most common, followed by regional, and lowest distance recurrence. It concludes that in spite of maximum patient of the advanced stage, local failure is the most common, showing head and neck SCC is locally aggressive.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12]