Role of Selective Neck Dissection in Clinically Single Node Positive Disease in Oral Cavity Cancers.

Management of the neck in oral cavity squamous carcinoma is debatable. There is controversy regarding role of SND in single node positive neck in oral SCC. The aim of this study was to determine the efficacy of selective neck dissection (SND) for cN1 neck in patients with oral cancer. A retrospective chart review of 266 oral cancer patients who were clinically single node positive from August 2013 to December 2019 was done. Patients having clinical or radiological cN1 disease undergoing SND were included. Two hundred sixty-six patients were analysed with 86% male predominance. Median age was 48 years. The commonest primary site was Bucco-alveolar complex (64%). Total of 319 SNDs were done in 266 patients. At median follow-up of 29 months, 29 patients (9%) had neck recurrence among which 4 patients had recurrence at level V, along with recurrence at other nodal levels. Three-year regional control was 86%, while DFS and OS were 66% and 68% respectively. For oral cancer with single clinically node positive neck (cN1), SND is an effective and oncological safe treatment. Outcomes are similar with modified neck dissection reported in the literature.

Quality of life and quality-adjusted time without toxicity in palliatively treated head-and-neck cancer patients.

BACKGROUND: Quality-adjusted time without toxicity (Q-TWiST) and quality of life (QOL) are indicators of benefit provided by different chemotherapy regimens. METHODS: This was a prospective study, in which adult head-and-neck (H and N) cancer patients, treated with metronomic chemotherapy were enrolled. The Functional Assessment of Cancer Therapy-General H and N (FACT-G and H and N) version 4 pro formas were self-administered before the start of chemotherapy and then at 2, 4, and 6 months. FACT QOL and Q-TWiST analysis were then performed. RESULTS: There was an improvement in the social well-being (P = 0.370), emotional well-being (P = 0.000), functional well-being (P = 0.000), H and N cancer subscale (P = 0.001), FACT H and N trial outcome index (P = 0.000), FACT G-total score (P = 0.000), and FACT H and N total score (P = 0.000) with palliative chemotherapy. The QTWiST value for a utility score of 0.25 for toxicity and relapse state was 145.93 days. CONCLUSION: Metronomic chemotherapy is associated with improvement in QOL and has a low duration of time spent in toxicity state.

Distress Management in Patients With Head and Neck Cancer Before Start of Palliative Chemotherapy: A Practical Approach.

PURPOSE: This study reports the incidence of distress, the factors associated with distress, and a practical strategy to resolve distress in patients with head and neck cancer who are starting palliative chemotherapy. METHODS: Adult patients with head and neck cancer planned for palliative chemotherapy underwent distress screening before the start of treatment as part of this single-arm prospective study. Patients who had a distress score > 3 on the National Comprehensive Cancer Network (NCCN) distress thermometer were counseled initially by the clinician. Those who continued to have high distress after the clinician-led counseling were referred to a clinical psychologist and were started on palliative chemotherapy. After counseling, distress was measured again. The relation between baseline distress and compliance was tested using Fisher's exact test. RESULTS: Two hundred patients were enrolled, and the number of patients with high distress was 89 (44.5% [95% CI, 37.8% to 51.4%]). The number of patients who had a decrease in distress after clinician-led counseling (n = 88) was 52 (59.1% [95% CI, 48.6% to 68.8%]) and after psychologist-led counseling (n = 32) was 24 (75.0% [95% CI, 57.6% to 72.2%]; P = .136). Compliance rates did not differ between the patients with or without a high level of distress at baseline (74.2% v 77.4%, P = .620). CONCLUSION: The incidence of baseline distress is high in patients awaiting the start of palliative chemotherapy. It can be resolved in a substantial number of patients using the strategy of clinician-led counseling, with additional referral to a clinical psychologist as required. Patients with a greater number of emotional problems usually require psychologist-led counseling.

Outcomes in Treatment-Naïve Patients With Metastatic Extremity Osteosarcoma Treated With OGS-12, a Novel Non-High-Dose Methotrexate-Based, Dose-Dense Combination Chemotherapy, in a Tertiary Care Cancer Center.

PURPOSE: Metastatic osteosarcoma is largely treated with high-dose methotrexate (HDMTX)-based therapy, especially in the pediatric population. This mandates complex pharmacokinetic monitoring in a costly inpatient setting to mitigate unpredictable serious toxicities. Hence, a non-HDMTX-based regimen is worth exploring, especially in India and low- and middle-income countries. MATERIALS AND METHODS: All consecutive treatment-naïve patients with metastatic osteosarcoma were prospectively treated on the novel OGS-12 protocol consisting of sequential doublets of doxorubicin, cisplatin, and ifosfamide. Four cycles were administered as neoadjuvant therapy followed by planned curative intent surgery and metastasectomy when feasible, followed by four cycles of adjuvant chemotherapy. Baseline characteristics, histologic response, event-free survival (EFS), overall survival (OS), and toxicity data were prospectively collected. RESULTS: Three hundred seventeen patients were enrolled onto the OGS-12 protocol from 2011 to 2014, of whom 80 (25%) had metastatic disease; median age was 17 years. The majority of patients were nutritionally challenged with high-risk features. At presentation, 83% of patients (66 patients) had lung metastases. After neoadjuvant chemotherapy, 57% of patients were histologically good responders. Four-year EFS and OS rates were 24% and 27%, respectively, in the intent-to-treat population and 27% and 29%, respectively, in the per-protocol analysis. Significant grade 3 or 4 toxicities were febrile neutropenia (51%), thrombocytopenia (36%), and anemia (54%). Histologic response was an independent predictor for EFS and OS in patients who underwent surgery. Surgical intervention was found to be significant for survival in univariable analysis. CONCLUSION: The novel, low-cost, non-HDMTX-based, dose-dense OGS-12 regimen has shown comparable outcomes to international standards in metastatic osteosarcomas and is worthy of wider clinical application. An aggressive multimodality approach may result in long-term survival in a select group of patients and, hence, is worth considering.

Efficacy of gefitinib in epidermal growth factor receptor-activating mutation-positive nonsmall cell lung cancer: Does exon 19 deletion differ from exon 21 mutation?

BACKGROUND: This study was designed to evaluate the differential effect of epidermal growth factor receptor (EGFR) mutation status (exon 19 vs. 21) on progression-free survival (PFS) and overall survival (OS) in treatment-naïve advanced EGFR mutation-positive nonsmall cell lung cancer (NSCLC) treated with gefitinib as first-line agent. METHODS: This was a post hoc analysis of EGFR-mutated (exon 19 and 21) advanced-stage (Stage IIIB or IV), chemotherapy-naive NSCLC patients treated with gefitinib as first line in a phase 3 randomized study. Patients were treated with gefitinib 250 mg daily. Patients underwent axial imaging for response assessment on D42, D84, D126, and subsequently every 2 months till progression. Responding or stable patients were treated until progression or unacceptable toxicity. SPSS was used for statistical analysis. Kaplan-Meier method was used for survival estimation and log-rank test for comparison. Cox proportion hazard model was used for multivariate analysis. RESULTS: One hundred and forty-one patients were eligible for analysis, of which 78 were males and 63 were females. A total of 127 patients (90.1%) were ECOG 0-1 while 14 patients (9.1%) were ECOG >1. Exon 21 mutation was present in 65 patients (46.1%) and exon 19 mutation in 76 patients (53.9%). One hundred and thirty-three of 141 patients were evaluable for response. Response rate of patients having exon 19 mutation was 72.9% (51 patients, n = 70) while it was 55.6% in patients having exon 21 mutation (35 patients, n = 63) (P = 0.046). Median PFS in exon 19-mutated patients was 9.3 months (95% confidence interval [CI] 6.832-11.768) compared to 7.8 months (95% CI 5.543-10.0) (P = 0.699) in exon 21-mutated patients. The median OS in exon 19-mutated patients was 19.8 months (95% CI 16.8-22.7), and it was 16.5 months (95% CI 10.9-22.1) in exon 21-mutated patients (P = 0.215). CONCLUSION: There were no differential outcomes in the Indian patients of advanced-stage NSCLC with exon 19 and 21 EGFR mutations treated with gefitinib.

Efficacy of Second-Line Pemetrexed-Carboplatin in EGFR-Activating Mutation-Positive NSCLC: Does Exon 19 Deletion Differ from Exon 21 Mutation?

BACKGROUND: It is unknown whether the outcomes of second-line pemetrexed-carboplatin chemotherapy administered after progression on gefitinib are dependent on type of EGFR mutation present at baseline. METHOD: Adult non-small-cell lung cancer patients, with exon 19 deletion or exon 21 L858R mutation, who progressed on gefitinib and received pemetrexed-carboplatin chemotherapy were selected for this analysis. RESULT: 55 patients received pemetrexed-carboplatin as second-line treatment. Response rates in evaluable patients were 39.3% in exon 19 patients (n = 28) and 33.3% in exon 21 patients (n = 15) (p = 0.752, Fisher's exact 2-sided p value). The median PFS in exon 19 and 21 cohorts was 5.900 months (95% CI: 4.274-7.526) and 4.767 months (95% CI: 1.374-8.159), respectively. The median overall survival in exon 19 patients was (11.8 months, 95% CI: 9.916-13.684 months) significantly better than that seen in exon 21 mutation patients (6.2 months, 95% CI: 4.215-8.118 months, p = 0.024) on univariate analysis; however, on multivariate analysis, this association was not confirmed (HR = 0.361, 95% CI: 0.090-1.439, p = 0.149). CONCLUSION: Exon 19 deletion has no impact on PFS and OS in EGFR-mutated patients treated with second-line pemetrexed-carboplatin.

Impact of exon 19 versus exon 21 EGFR-activating mutation on outcomes with upfront pemetrexed-carboplatin chemotherapy.

BACKGROUND: EGFR mutation subtype is a recognised factor impacting outcomes of patients receiving oral tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). Evidence for the effect of this factor on outcomes in patients receiving pemetrexed is limited. METHODS: We completed a study comparing pemetrexed-platinum combination versus oral TKI in EGFR mutation-positive patients in lung cancer. We analysed the impact of EGFR mutation subtype, specifically, exon 19 and 21 on the PFS and OS of patients treated with pemetrexed (500 mg/m2 on day 1) and carboplatin (AUC 5 on day 1) as first-line therapy. Patients underwent axial imaging for response assessment on D42, D84, D126 and subsequently every two months till progression. Patients post-progression were treated with gefitinib. RESULTS: Fifty-one patients (36%) had exon 21 mutation, while 92 patients (64%) had exon 19 mutation. Response rates in evaluable patients was 47.7% in exon 19 patients (41 patients, n = 86) and 42.9 % in exon 21 patients (18 patients, n = 42). There was a significant increase in median overall survival for patients with exon 19 mutations (24.5 months, 95% CI: 21.3-27.7 months ) over the exon 21-mutated patients (18.1 months, 95% Cl: 13.5-22.6 months, p = 0.002). This differential impact was due to second-line gefitinib having a differential outcome on these mutations. CONCLUSION: Pemetrexed-based chemotherapy does not have a differential impact on exon 19- or exon 21-mutated patients. However, second-line treatment with gefitinib has a favourable response and outcome in exon 19-mutated patients.

Phase III study of gefitinib or pemetrexed with carboplatin in EGFR-mutated advanced lung adenocarcinoma.

OBJECTIVE: Oral tyrosine kinase inhibitor has been shown to prolong progression-free survival (PFS) in estimated glomerular filtration rate (EGFR) mutation positive adenocarcinoma; however, the comparator arm has not included the current standard adenocarcinoma regimen (pemetrexed carboplatin induction followed by maintenance pemetrexed) and patients from Indian subcontinent. Hence, this study was carried out in Indian patients to compare gefitinib with the above-mentioned chemotherapy regimen. METHODS: This was an open-labelled, randomised, parallel group study comparing gefitinib (250 mg orally daily) with pemetrexed (500 mg/m2) and carboplatin (area under the curve 5) doublet intravenous induction chemotherapy regimen followed by maintenance pemetrexed (500 mg/m2) in patients with EGFR-activating mutation-positive stage IIIB or stage IV adenocarcinoma lung in the first-line setting. The primary endpoint for the study was PFS. 260 patients were required to demonstrate a 50% improvement in PFS of gefitinib over chemotherapy, with 80% power and 5% type 1 error. With an expected 5% dropout rate, the sample size was 290 patients. RESULTS: The median PFS in gefitinib arm was 8.4 months (95% CI 6.3 to 10.5 months) compared with 5.6 months (95% CI 4.2 to 7.0 months) in pemetrexed-carboplatin arm (HR: 95% CI 0.513 to 0.851; p -0.001). The impact of gefitinib on PFS was seen across all subgroups.There was no statistically significant difference in overall survival between the two arms. Haematologicalgrade3-4toxicities likeanaemia,neutropaenia and thrombocytopaenia were common in the pemetrexed-carboplatin arm while grade3-4 acneiform rash and diarrhoeawere common in the gefitinib arm. CONCLUSION: The study confirms the superiority of gefitinib in prolonging PFS against the most active chemotherapy regimen of pemetrexed-carboplatin followed by maintenance pemetrexed in EGFR-mutated lung adenocarcinoma. The median PFS in Indian patients in gefitinib arm is similar to that reported in east Asians and Caucasians.

Expectations and preferences for palliative chemotherapy in head and neck cancers patients.

BACKGROUND: Head and neck cancer patients undergoing palliative chemotherapy have a limited overall survival. Expectations and preferences of such patients towards palliative chemotherapy after explanation of disease prognosis and treatment options are unknown. METHODS: This was a single arm, prospective, observational study where newly diagnosed head and neck cancer patients warranting palliative chemotherapy underwent protocol defined counselling. Following counselling, they were administered chemotherapy expectation and preference proforma (CEP). The primary objective of this study was to estimate the percentage of patients opting for an increase in survival as the primary expectation from chemotherapy. RESULTS: We recruited two hundred patients all patients except one answered the CEP. Prolongation of life as the primary expectation from palliative chemotherapy was seen only in 82 patients (41.0%; 95% CI 34.4-47.9%). Symptom relief was the primary expectation or an equally important expectation amongst the remaining 117 patients (58.5%; 95% CI 51.6-65.1%). There was a statistically significant difference between the preferences of patients having a primary expectation of prolongation of life as opposed to symptom relief regarding the minimum expected number of patients need to treat to get prolongation of life (p value -0.00). The minimum expected increment in life expectancy for taking palliative chemotherapy was ">1year" in 190 patients (94.5%; 95% CI 91.5-97.7%). CONCLUSION: The primary expectation from palliative chemotherapy in head and neck cancer patients is not necessarily living longer in all patients. The magnitude of benefit preferred by the patients from chemotherapy far exceeded the current standards for drug approval.

Metronomic palliative chemotherapy in maxillary sinus tumor.

BACKGROUND: Metronomic chemotherapy consisting of methotrexate and celecoxib recently has shown promising results in multiple studies in head and neck cancers. However, these studies have not included patients with maxillary sinus primaries. Hence, the role of palliative metronomic chemotherapy in patients with maxillary sinus carcinoma that is not amenable to radical therapy is unknown. METHODS: This was a retrospective analysis of carcinoma maxillary sinus patients who received palliative metronomic chemotherapy between August 2011 and August 2014. The demographic details, symptomatology, previous treatment details, indication for palliative chemotherapy, response to therapy, and overall survival (OS) details were extracted. SPSS version 16 was used for analysis. Descriptive statistics have been performed. Survival analysis was done by Kaplan-Meier method. RESULTS: Five patients had received metronomic chemotherapy. The median age was 60 years (range 37-64 years). The proportion of patients surviving at 6 months, 12 months, and 18 months were 40%, 40%, and 20%, respectively. The estimated median OS was 126 days (95% confidence interval 0-299.9 days). The estimated median survival in patients with an event-free period after the last therapy of <6 months was 45 days, whereas it was 409 days in patients with an event-free period postlast therapy above 6 months (P = 0.063). CONCLUSION: Metronomic chemotherapy in carcinoma maxillary sinus holds promise. It has activity similar to that seen in head and neck cancers and needs to be evaluated further in a larger cohort of patients.