Carcinoma buccal mucosa treated with definitive hypofractionated accelerated radiotherapy: a retrospective analysis of treatment outcomes.

Introduction: Oral cancer is a major public health concern in India. Both conventional and altered fractionation radiotherapy schedules have been used in curative treatment of oral cancer. This study aimed to retrospectively evaluate the clinical profile and treatment outcomes of patients with carcinoma buccal mucosa who underwent treatment with definitive hypofractionated accelerated radiotherapy. Methods: A total of 517 patients treated from January 2011 to December 2016 were eligible for the analysis. All patients were treated with definitive hypofractionated accelerated radiotherapy schedule of 5,250 cGy in 15 fractions over 3 weeks. Survival estimates were generated using the Kaplan-Meier method. Results: At a median follow-up of 77.4 months, 473 (91.5%) patients attained complete remission with radiation therapy. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 69% and 80.5%, respectively. The 5-year OS for stage I, II, III and IVa tumours was 80.3%, 84.4%, 81.4% and 73.7%, respectively, and the DFS was 75.7%, 73.2%, 69.6% and 60.2%, respectively. Age >50 years was found to be a significant factor affecting DFS (P = 0.026) and OS (P = 0.048) in multivariate analysis. Fifty-three (10.3%) patients developed osteoradionecrosis of the mandible. Conclusion: Excellent outcome could be achieved in less-aggressive, low-volume carcinoma of the buccal mucosa with radical accelerated hypofractionated radiotherapy. A radiotherapy schedule over a 3-week period is useful in high-volume centres.

Treatment outcomes of squamous cell carcinoma of the lip: A retrospective study.

Oral and lip cancer is the most common type of cancer among males in India. Early stage tumours of the lip (stages I and II) are treated with single modality treatment, using either radiotherapy [external beam radiotherapy (EBRT) or brachytherapy] or surgery. Locally advanced tumours (stages III and IVa) are treated with surgery followed by adjuvant treatment. The aim of the present study was to retrospectively evaluate the clinical profile and treatment outcomes of patients with squamous cell carcinoma of the lip who were treated with radical intent at the Regional Cancer Centre (Thiruvananthapuram, India). For this purpose, a total of 120 patients treated with radical radiotherapy (brachytherapy or EBRT) or surgery with or without adjuvant treatment between January 2010 and December 2016 were eligible for the analysis. Kaplan-Meier analysis was used to generate the survival outcomes. Univariate and multivariate analyses were performed to determine the impact of various patient- and tumour-related factors and treatment modality on outcomes. At a median follow-up time of 67.6 months, the disease-free survival (DFS) and overall survival (OS) rates at 4 years for the entire cohort were 69.1 and 86.7%, respectively. The 4-year OS rates for patients with stage I, II, III and IV disease were 88.9, 95.2, 86.8 and 75.3%, respectively, and the DFS rates were 83.6, 69.5, 78.8 and 42.9%, respectively. Primary tumour (P=0.025), nodal (P=0.005) and composite clinical (P=0.006) stage were found to be significant factors affecting DFS rates in the univariate analysis. However, only the nodal stage (P=0.005) was found to be a significant factor affecting DFS rates in the multivariate analysis. On the whole, the present study demonstrates that the outcomes of patients with lip carcinoma are favourable when treated at the early stages, and the results from this series are in line with those already published.

Immune checkpoint inhibitors in head and neck squamous cell carcinoma: A systematic review of phase-3 clinical trials.

BACKGROUND: The outcomes of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal. A relatively new systemic therapy option that emerged in recent years in the treatment of advanced HNSCC is immunotherapy using immune checkpoint inhibitors (ICIs). The safety profile and anti-tumor activity of these agents demonstrated in early phase clinical trials paved the way to the initiation of several promising phase-3 trials in the field. AIM: To evaluate the evidence on the effectiveness of ICIs in HNSCC, based on published phase-3 clinical trials. METHODS: We searched PubMed, Cochrane Library, Embase, and Scopus to identify published literature evaluating immunotherapy using ICIs in recurrent or metastatic HNSCC (R/M HNSCC) and locally advanced head and neck squamous cell carcinoma (LAHNSCC). We used a combination of standardized search terms and keywords including head and neck squamous cell carcinoma, recurrent, metastatic, locally advanced, immunotherapy, immune checkpoint inhibitors, monoclonal antibodies, programmed cell death protein-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T- lymphocyte associated protein-4 (CTLA-4), and phase-3 clinical trial. A sensitive search filter was used to limit our results to randomized controlled trials. RESULTS: Five phase-3 clinical trials have reported the data on the effectiveness of immunotherapy in HNSCC so far: Four in R/M HNSCC and one in LAHNSCC. In patients with R/M HNSCC, anti-PD-1 agents nivolumab and pembrolizumab demonstrated improved survival benefits in the second-line treatment setting compared to the standard of care (standard single-agent systemic therapy). While the net gain in overall survival (OS) with nivolumab was 2.4 mo [hazard ratio (HR) = 0.69, P = 0.01], that with pembrolizumab was 1.5 mo (HR = 0.80 nominal P = 0.0161). The anti-PD-L1 agent durvalumab with or without the anti-cytotoxic T- lymphocyte associated protein-4 agent tremelimumab did not result in any beneficial outcomes. In the first-line setting, in R/M HNSCC, pembrolizumab plus platinum-based chemotherapy resulted in significant improvement in survival with a net gain in OS of 2.3 mo (HR = 0.77, P = 0.0034) in the overall population and a net gain in OS of 4.2 mo in the PD-L1 positive (combined positive score > 20) population compared to standard of care (EXTREME regime). In patients with PD-L1 positive R/M HNSCC, monotherapy with pembrolizumab also demonstrated statistically significant improvement in survival compared to EXTREME. In LAHNSCC, immunotherapy using avelumab (an anti-PD-L1 agent) along with standard chemoradiation therapy did not result in improved outcomes compared to placebo plus chemoradiation therapy. CONCLUSION: Anti-PD-1 agents provide survival benefits in R/M HNSCC in the first and second-line settings, with acceptable toxicity profiles compared to standard therapy. There is no proven efficacy in the curative setting to date.

Induction chemotherapy in nasopharyngeal carcinoma- A systematic review of phase III clinical trials.

BACKGROUND: Induction Chemotherapy (IC) has the potential advantage of resulting in early eradication of micro metastasis thereby reducing distant failure in Nasopharyngeal Carcinoma (NPC). This study is to evaluate the effectiveness of induction chemotherapy in NPC based on published phase III Randomized Controlled Trials (RCT) METHODS: : We searched PubMed, SCOPUS, EMBASE and COCHRANE databases for phase III trials evaluating the role of IC in NPC using the following key words: nasopharyngeal carcinoma, locally advanced, locoregionally advanced, induction chemotherapy, and concurrent chemoradiation. We included phase 3 RCTs of NPC in which intervention patients received induction chemotherapy plus concurrent chemoradiation (CCRT) and the control patients received CCRT alone. RESULTS: Six phase III RCTs have reported the data on effectiveness of IC in NPC so far. All except one study found statistically significant improvement in the primary outcome. One study demonstrated improved relapse free survival (RFS) with IC (stratified HR for recurrence or death 0.51; p=0.0001). Two studies reported improvement in disease free survival (DFS) with IC [adjusted HR 0.739 (p=0.0264) in one study; HR for 3-year and stratified HR for 5-year DFS 0.67 (p=0.028) and 0.66 (p=007) respectively in the other study]. One study demonstrated improvement in failure free survival (FFS) with IC [HR for 3-year and 5-year FFS 0.68 (p=0.034) and 0.67 (p=0.019) respectively] and another study reported improved progression free survival (PFS) [HR 0.44; p=0.042)]. Grade 3-4 acute adverse events were higher among patients who received IC. CONCLUSION: IC followed by CCRT showed superior clinical outcomes in NPC compared to CCRT alone. Conflicting results were found with regard to overall survival.

Update on the systemic management of radioactive iodine refractory differentiated thyroid cancer (Review).

The incidence of differentiated thyroid cancer (DTC) has increased over the last few decades, though it remains to be a rare disease. The prognosis of DTC is excellent; its treatment includes surgery (near-/total thyroidectomy), which is usually followed by remnant thyroid bed ablation using radio-iodine, as well as a risk-stratified follow-ups, including hormone replacement. Treatment of patients who are non-responsive to radioactive iodine (RAI) remains a challenge. Targeted therapies for RAI refractory DTC act primarily through inhibition of cell proliferation, survival and angiogenesis. Tyrosine kinase inhibitors (TKI) have achieved prolonged responses and improved progression-free survival, thereby representing a shift in the treatment of advanced thyroid cancer. There will be number of targeted treatment options for this patient population in the near future. Evidence regarding which drug should be used first and whether there is crossover drug resistance between these drugs is still lacking. Clinicians should be able to choose precisely which patients should be treated with novel targeted therapies after taking into account the following facts: i) TKIs have still not demonstrated a survival benefit. ii) The adverse effects of long-lasting treatment with TKIs could worsen quality of life, which is mostly excellent in these patients before starting treatment with these agents.

Current Role of Chemotherapy in Nonmetastatic Nasopharyngeal Cancer.

Nasopharyngeal carcinoma is highly radio- and chemosensitive tumor with its unique clinical and biological behavior. Treatment of stage I disease is radical radiotherapy alone. For stage II disease treatment is radiotherapy with or without chemotherapy. The standard of care for locally advanced nasopharyngeal cancer (stages III-IVB) is concurrent chemoradiation. Optimum timing and sequence of chemotherapy are not yet well-defined. The role of adjuvant and induction chemotherapy is debatable. Here we are going to highlight the role of chemotherapy in nasopharyngeal carcinoma, its benefit, and controversies regarding timing and sequences.

Current Status of Organ Preservation in Carcinoma Larynx.

Organ preservation in carcinoma larynx is a long debated topic. There are multiple organ preserving approaches in the management of carcinoma larynx depending on various factors. Radical radiotherapy (RT) and conservation laryngeal surgery have shown equivalent results in early laryngeal cancer. Concurrent chemoradiation (CTRT) is the standard treatment in stage III and IV laryngeal cancer with intact cartilage and functional larynx. Patients with cartilage destruction or dysfunctional larynx are not the candidates for organ preservation. This systematic review is aimed at discussing the evolution of different organ preserving approaches, their efficacy, impact on voice quality, their pitfalls and future directions.