European Journal of Cardiovascular Medicine

Brachial Head and neck cancer is a common health concern across several regions globally.  Several established risk factors are associated with head and neck cancer, including tobacco use, consumption of alcohol, infection with human papillomavirus (HPV) - particularly for oropharyngeal cancer, and infection with Epstein-Barr virus (EBV) - particularly for nasopharyngeal cancer.  On a global scale, head and neck cancer accounts for over 650,000 cases and 330,000 deaths annually [1]. In the United States, head and neck cancer represents approximately 3% of all malignancies, with an estimated 53,000 Americans diagnosed with head and neck cancer each year and roughly 10,800 succumbing to the disease [2].  In Europe, there were an estimated 250,000 cases (around 4% of all cancers diagnosed) and 63,500 deaths in 2012 [3]. Strikingly, head and neck cancers are a considerably more prominent issue in developing countries, accounting for roughly one-third of all cancer cases, in contrast to developed nations where it represents only 4-5% of cancers [4]. Squamous cell carcinoma is the most prevalent histological type of head and neck cancer, encompassing all subsites. Patients diagnosed with advanced head and neck squamous cell carcinoma (HNSCC) often experience a relatively poor prognosis [5, 6, 7].  More than half of these patients will develop distant metastases, significantly reducing their chances of survival [5].

Patients with HNSCC will be diagnosed with locoregionally advanced and technically unresectable disease, or a resection will lead to significant mutilation or a poor functional outcome. Randomized controlled trials have shown that cisplatin-containing chemotherapy (CT) administered concurrently with RT improves OS in HNSCC patients treated either by surgery and adjuvant RT-CT or definite treatment with RT-CT. Conversely, adjuvant CT after completion of adjuvant or definite RT does not improve clinical outcome. Induction CT with cisplatin and 5-FU before definite treatment with RT was associated with a small benefit in OS, mainly due to a reduced distant failure rate.

Neoadjuvant chemotherapy aims to reduce the initial bulk of disease with organ preservation, alleviate symptoms, and improve the quality of life. Additionally, NACT is beneficial in better control of distant metastases. This was the rationale for using NACT in the study. However, when it comes to definitive treatment, chemoradiation or only radiation still remains unclear for a subset of inoperable LAHNSCC patients presenting with bulky and fixed primary/nodal disease or complicated with comorbidities.

In our present study, we aimed to reevaluate the data that neoadjuvant chemotherapy before definitive CTRT did not have any statistically significant difference compared to CTRT alone. GORTEC 94-01 compares definitive Radiotherapy (70 Gray with 2 Gray fraction) versus Chemoradiotherapy with concomitant Carboplatin & 5FU. There is significant improvement in local control, DFS (disease-free survival) & OS (overall survival). In our study, the addition of Neoadjuvant chemotherapy does not cause any statistically significant advantage in terms of response rate as well as toxicity. Therefore, we usually prefer concomitant chemoradiotherapy without Neoadjuvant chemotherapy in the management of LAHNSCC (locally advanced head and neck squamous cell carcinoma).

We conducted a retrospective evaluation over the last five years from 2013-2018, involving all Histopathologic ally proven non-metastatic LAHNSCC patients who attended the Radiotherapy Outpatients Department of RGKAR Medical College and Hospital, Kolkata. Eligibility criteria included patients of either sex, aged between 18 and 70 years, with normal baseline complete blood count (Hb > 10 gm/dl, ANC > 1500/µl, platelets > 100,000/µl), and normal liver and renal function tests (total serum Bilirubin < 1.5 mg/dl and serum creatinine < 1.5 mg/dl). All patients had Histopathologic ally proven head and neck squamous cell carcinoma, ECOG performance status 0-2, and locally advanced disease (stage III & IVA, according to the AJCC 8th edition staging manual).

Patients were divided into two arms for data collection: one arm received anterior neoadjuvant chemotherapy with inj. Paclitaxel 175 mg/m2 and inj. Carboplatin AUC 6 iv q21 days, followed by concurrent chemoradiotherapy (66 Gy/33#/6 weeks, 3 days), while the other arm received upfront concurrent chemoradiotherapy (66 Gy/33#/6 weeks, 3 days). Only patients who received three weekly concurrent inj. Cisplatin 100 mg/m2 were included in the data evaluation. Data was collected using predesigned worksheets and analyzed using Microsoft Excel Office 2007 and SPSS v17 (IBM Corp, Chicago). The study received institutional ethical committee approval

There was total two hundred and fifty-two patients(n-252) patients in total selected for data analysis. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy received in 123 patients and 129 patients received upfront concurrent chemotherapy. During analysis we have found 170 male patients & 82 female patients

The location of the primary tumor was tabulated in table 2. Arm A received NACT followed by concurrent chemo radiotherapy & Arm B received upfront concurrent chemo radiotherapy

Table 2: Location and Stage of the Primary tumor at diagnosis

After completion of full treatment, we have found that in 65% in neoadjuvant chemotherapy followed by concurrent chemo radiotherapy achieved complete response whereas 60% in upfront concurrent chemo radiotherapy arm.

Table 3 : Response after complete treatment

Table 4 showing the RTOG late toxicity observed between 2 arms. There is no significant late toxicity observed between 2 arms

Data from the Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC) illustrate that the major therapeutic benefit of platinum-based chemotherapy results from an improvement in locoregional disease control when the drugs are given concurrently with radiotherapy. No significant improvement occurs with induction chemotherapy followed by radiotherapy. Randomized controlled trials have shown that cisplatin-containing chemotherapy (CT) administered concurrently with RT improves OS in HNSCC patients treated either by surgery and adjuvant RT-CT or definite treatment with RT-CT. Conversely, adjuvant CT after completion of adjuvant or definite RT does not improve clinical outcome. Induction CT with cisplatin and 5-FU before definite treatment with RT was associated with a small benefit in OS mainly due to a reduced distant failure rate.

Neoadjuvant chemotherapy aims to reduce the initial bulk of disease with organ preservation, alleviate symptoms, and improve the quality of life. In addition, NACT is beneficial in better control of distant metastases. This was the rationale for using NACT in the study. However, when it comes to definitive treatment, chemoradiation or only radiation still remains unclear for a subset of inoperable LAHNSCC patients presenting with bulky and fixed primary/nodal disease or complicated with comorbidities.

In our present study, we aimed to reevaluate the data that neoadjuvant chemotherapy before definitive CTRT did not have any statistically significant difference than CTRT alone. GORTEC 94-01 compares definitive Radiotherapy (70 Gray with 2 gray fraction) versus Chemoradiotherapy with concomitant Carboplatin & 5FU. There is significant improvement in local control, DFS (disease-free survival) & OS (overall survival). In our study, the addition of Neoadjuvant chemotherapy does not cause any statistically significant advantage in terms of response rate as well as toxicity. Therefore, we usually prefer concomitant chemoradiotherapy without Neoadjuvant chemotherapy in the management of LAHNSCC (locally advanced head neck squamous cell carcinoma).

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