ABSTRACT
Aim:
The aim of the present study was to compare the treatment outcome in oral cancer cases treated with neoadjuvant chemotherapy (NACT) and upfront surgery in localized advance disease.
Materials and Methods:
A randomized, prospective study was conducted in 20 cases. Patients were divided into two groups. Group A was taken up for upfront surgery and group B was taken up for surgery after two to three cycles of NACT based on patients’ response, performance, and compliance.
Results:
Neither group showed statistically significant differences in clinical characteristics. In the present study, satisfactory outcomes were seen in nine patients belonging to NACT group and eight patients of non-NACT group had satisfactory outcomes after surgery, which were found to be statistically significant (P = 0.001).
Conclusion:
NACT may be considered as a treatment option for oral squamous cell carcinoma patients, particularly those with locally advanced tumors. Further prospective studies are needed to validate these findings in patients.
KEYWORDS: Neoadjuvant chemotherapy, oral cancer, oral squamous cell carcinoma, upfront surgery
INTRODUCTION
Around 300,000 new instances of oral squamous cell carcinoma (OSCC) are diagnosed every year throughout the globe. Surgery-based multi-modal therapy is the gold standard for treating OSCC.[1,2]
Neoadjuvant chemotherapy (NACT) refers to chemotherapy administered before surgery. The role of NACT is being explored with the premise of reducing extent of surgical resection, improving locoregional control, and decreasing distant metastasis, thereby improving treatment outcomes by decreasing mortality and morbidity.[3] Tumor shrinkage induced by NACT in resectable advanced oral cavity malignancies[4,5] may enhance locoregional control and overall survival and may aid in organ preservation. This research aims to evaluate the effectiveness of NACT versus primary surgical removal in the treatment of advanced oral cancer.
MATERIALS AND METHODS
The present study was conducted at the State Cancer Institute, Guwahati, after approval from the Institutional Ethical committee as well as the scientific committee of the State Cancer Institute. A randomized, prospective study was conducted on 20 patients of OSCC who were enrolled in the study. Inclusion criteria for this study included patients within the age group of 30 to 60 years of age, a tumor size within T3 to T4 and low ITF disease, and patients with good performance status. Exclusion criteria include high ITF disease, with medical co-morbidities, any known allergy to study drugs, patient refusal, and metastatic disease. Twenty OSCC patients were divided into two groups. Group A was taken up for upfront surgery and group B was taken up for surgery after two to three cycles of NACT based on the patient’s response, performance, and compliance.
Treatments
Two courses of pre-operative NACT were given to participants in the NACT group. Every 3 weeks, patients received the TPF regimen (docetaxel 60 mg/m2 IV on day 1, cisplatin 75 mg/m2 IV on day 1, and fluorouracil 750 mg/m2 IV daily, in a continuous infusion lasting 120 hours, on days 1 through 5). Dexamethasone, antiemetics, and hydration/diuretics were also given as supportive therapy.
The patients were followed for up to a year, with regular checkups occurring every 15 days, 1 month, 2 months, 3 months, and 6 months.
The Chi-square test was used to compare the two apostrophe baseline data to look for differences in clinical factors. The statistical study was performed using IBM’s SPSS statistics program, version 17.0. A significance level of 0.05 was used.
RESULTS
Twenty patients participated in the trial; ten in the non-NACT group had immediate access to radical surgery, and ten in the NACT group underwent NACT before undergoing surgery (NACT group).
One patient did not respond well, so the surgery was declined.
For remaining patients, there was a significant decrease in size, and they were operated as shown in Table 1.
Table 1.
Clinical data of the patients treated with conservative and radical surgery in the NACT subgroup
| Parameters | Conservative surgery (n=4) | Radical surgery (n=5) | Total (n=9) | P |
|---|---|---|---|---|
| Sex | ||||
| Male | 3 | 4 | 7 | 0.820 |
| Female | 1 | 1 | 2 | |
| Gender | ||||
| Range (median) | 30-55 | 31-60 | 30-60 | 0.785 |
| 30-40 | 1 | 1 | 2 | |
| 41-50 | 2 | 2 | 4 | |
| 51-60 | 1 | 2 | 3 | |
| Primary site | ||||
| Tongue | 1 | 2 | 3 | 0.385 |
| Gingiva | 1 | 2 | 3 | |
| Buccal | 1 | 1 | 2 | |
| Floor | 1 | 0 | 1 | |
| Palate | 0 | 0 | 0 | |
| Pathology differentiation | ||||
| Poor | 0 | 1 | 1 | 0.110 |
| Moderate | 2 | 2 | 4 | |
| Well | 2 | 2 | 4 | |
| T | ||||
| T3 | 1 | 1 | 2 | 0.719 |
| T4 | 3 | 4 | 7 | |
| N | ||||
| N0 | 2 | 3 | 5 | 0.024 |
| N1 | 1 | 1 | 2 | |
| N2 | 1 | 1 | 2 | |
| N3 | 0 | 0 | 0 | |
| Surgical margin | ||||
| + | 1 | 1 | 2 | 0.515 |
| – | 3 | 4 | 7 | |
| Response | ||||
| CR | 3 | 4 | 7 | 0.165 |
| PR | 1 | 1 | 2 | |
| MR | 0 | 0 | ||
| SD | 0 | 0 | ||
| Complications | Nact | Non Nact | ||
| Hair fall | 8 | 0 | ||
| Wound healing | 6 | 2 | ||
| Hospital stay | 10 days | 6 days | ||
| Recurrence | 1 patient | 2 patients |
These nine patients in NACT group are further divided into two subgroups, conservative surgery and radical surgery, as shown in Table 1. There was no significant difference between the two procedures, according to the Chi-square test (P = 0.515) [Table 2].
Table 2.
Comparison of treatment outcome in NACT group and Non-NACT group postoperative
| Treatment outcome | Non-NACT (n=10) | NACT (n=10) | P |
|---|---|---|---|
| Response | |||
| CR | 3 | 6 | 0.001 |
| PR | 4 | 3 | |
| MR | 2 | 0 | |
| SD | 1 | 0 |
DISCUSSION
Ten patients were treated with pre-operative NACT in an effort to reduce the disease’s severity to get a negative margin and prevent functional impairment after surgery, and ten patients were taken for upfront surgery. The clinical characteristics of the two groups were similar. Retrospective single-institution evaluation of NACT in patients with 141 operable oral cavity malignancies was reported in 1998 by Okura et al.[6] At least two well-designed, sufficiently powered randomized studies have been reported on the topic of NACT as a pre-operative treatment for resectable oral cavity tumors. The findings of a randomized, multi-center study including 195 patients with untreated, advanced resectable stage T2-T4 (>3 cm) squamous cell carcinoma (SCC) of the oral cavity were reported by Licitra et al.[7]
There is currently no consensus on the NACT’s role in the management of advanced OSCC.[8] Advanced OSCC patients’ survival rates increased when NACT was added to their treatment plans. With no recurrence rate during the 1-year follow-up period, the results of the present prospective analysis indicated that NACT would have higher survival than upfront surgery in the treatment of advanced OSCC, while the non-NACT group showed recurrence in three patients.
In patients who have a favorable response to NACT, the size of their tumors may actually decrease.
Post operations NACT patients were found to be having generalized weakness and took more time in skin healing which increased their hospital stay and few female patients had compliant about hair loss.
CONCLUSION
In conclusion, NACT can increase the rate of local disease control in OSCC patients without compromising surgical and oncological outcomes.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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