Abstract

Introduction: The recurrence of any type of cancer can be a great physical, mental and financial burden for the patients, and can also negatively impact the overall health status of a country. Despite the availability of multiple treatment methods, patients with recurrence of cancer still show up. Which is why, the present study of 2 recurrent carcinoma patients, who after being treated with immunotherapy, did no see any recurrence and observed significant clinical and radiological improvement, is of great importance. Case Presentation: This study was conducted with 2 cases of recurrent head and neck cancer, both of whom were Bangladeshi female. The first patient was 70-year-old, while the second patient was 59 years old. Both had received multiple previous treatment, including surgical treatment and chemotherapy, but still had recurrence of cancer. Conclusion: The use of immunotherapy in recurring Head & Neck Cancer shows promising Clinical and Radiological response, with much fewer observable side-effects compared to previous treatment methods.

1. Introduction

Cancer, a disease characterized by uncontrolled growth and spread of abnormal cells, affects billions of individuals worldwide. ¹ Despite extensive research and clinical trials, it continues to be a significant source of morbidity and mortality. ² This complex disease can arise from various parts of the body, presenting in numerous forms such as breast cancer, lung cancer, colon cancer, bladder cancer, leukemia, kidney cancer, and more. ³ A particularly concerning form of cancer is found in the head and neck region. This type of cancer comprises various malignant tumors originating in the throat, larynx, nose, sinuses, and mouth. ⁴ Risk factors for developing these cancers include tobacco use, heavy alcohol consumption, and human papillomavirus (HPV) infection. ⁴ The majority of these cancers are squamous cell carcinomas. According to the Global Cancer Observatory 2020, this cancer type ranks as the most prevalent in Bangladesh, affecting both genders but showing a higher incidence in men. ⁵ Further research in Bangladesh suggests that the lower socio-demographic population experiences a higher incidence of these cases. ^{6, 7} Despite standard treatments involving surgery, chemotherapy, and radiotherapy, prognosis for head and neck cancers remains poor. However, new treatment modalities, such as immunotherapy, offer some hope for improved patient outcomes. This study presents two such cases of head and neck cancer in patients who saw no satisfactory results from primary treatment but experienced enhanced outcomes following immunotherapy.

2. Case 1

Our first patient was a 70-year-old woman from Mirpur, Dhaka, who had hypertension and hypothyroidism as comorbidities. She was diagnosed with squamous cell carcinoma of the tongue, specifically on its lateral border, as well as a metastatic neck node. Her diagnosis was confirmed through a submandibular lymph node biopsy. As part of her treatment, the patient underwent a right partial glossectomy with neck dissection. Following this, she also received concurrent chemo-radiotherapy. Initially, the treatment was successful in eradicating the cancer. However, several months later, a partial recurrence of the disease was observed. Unfortunately, the development of cardiomyopathy rendered her medically inoperable, which limited her treatment options. She received three cycles of standard chemotherapy with Cetuximab, but the cancer persisted, as evidenced by a recurrent right auxiliary lesion.

The next course of action proposed for the patient was pembrolizumab monotherapy, based on the FDA-approved indications from the KEYNOTE-040 study. ⁸ The patient, along with her relatives, agreed to proceed with this immunotherapy. She underwent three cycles of pembrolizumab, receiving the standard dose of 200mg every three weeks. This immunotherapy treatment with pembrolizumab resulted in mild and manageable side effects, specifically grade-1 anemia and constipation. After the third cycle, treatment was halted due to undisclosed reasons.

Post immunotherapy treatment with pembrolizumab, the patient demonstrated significant clinical stabilization. In comparison to her pre-treatment state, radiological examination revealed impressive improvement in the right auxiliary lesion. Furthermore, the patient's oral and lip ulceration, a notable symptom of her condition, ameliorated significantly following the immunotherapy regimen.

3. Case 2

Our second case involved a 59-year-old woman from Sylhet, who had a medical history of hypertension and right maxilla carcinoma. She was diagnosed with invasive squamous cell carcinoma of the left alveolar mucosa. As part of her initial treatment in 2013, she underwent surgery and received radiotherapy, with subsequent CT scans monitoring her progress. These scans, however, suggested a recurrence of the tumor. Despite this concerning finding, the patient opted against further surgical intervention. By March 10, 2021, she had completed five standard cycles of chemotherapy to address the recurrent carcinoma. Additionally, she had received 30% of the planned radiation therapy by June 10, 2021. Regrettably, despite these comprehensive treatments, her CT scans indicated ongoing disease progression.

The next proposed course of treatment was pembrolizumab monotherapy, guided by FDA-approved indications from the KEYNOTE-040 study. ⁸ She received the standard dose of 200mg of pembrolizumab in a three-week cycle. The treatment was discontinued after this period. During the immunotherapy treatment, she experienced no major side effects, although grade-2 fatigue and grade-1 pyrexia were observed.

Following the immunotherapy treatment with pembrolizumab, the patient displayed significant clinical and radiological improvement. Further, several months of follow-up revealed no disease progression post-immunotherapy treatment.

4. KEYNOTE-040 Comparison

The treatment approach for both cases was guided by the findings from the KEYNOTE-040 study. ^{8, 9} This global, open-label, phase 3 trial involved patients with recurrent or metastatic head and neck squamous cell carcinoma who had previously received platinum-based chemotherapy. In this study, patients were randomly assigned to receive either pembrolizumab or a standard care treatment chosen by the investigator—either methotrexate, docetaxel, or cetuximab. ⁸ This trial found pembrolizumab to be associated with dramatically improved patient outcomes and a marginally higher survival rate.

5. Final Thought

The results from our study corroborate the promise of immunotherapy for head and neck cancer, demonstrating notable clinical and radiological responses and fewer observable side effects compared to prior treatment methods. However, our conclusions are based on a small sample size of just two patients, which is insufficient to make definitive conclusions. Therefore, taking the lead from the KEYNOTE-040 study, we recommend further research with larger sample sizes across diverse regions to accurately assess survival rates, improvement rates, recurrence rates, side effects, and long-term effects of immunotherapy treatment for carcinoma.

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