Demographics, Pattern of Care, and Outcome Analysis of Malignant Melanomas - Experience From a Tertiary Cancer Centre in India.

BACKGROUND: Treatment of malignant melanoma has undergone a paradigm shift with the advent of immune checkpoint inhibitors (ICI) and targeted therapies. However, access to ICI is limited in low-middle income countries (LMICs). PATIENTS AND METHODS: Histologically confirmed malignant melanoma cases registered from 2013 to 2019 were analysed for pattern of care, safety, and efficacy of systemic therapies (ST). RESULTS: There were 659 patients with a median age of 53 (range 44-63) years; 58.9% were males; 55.2% were mucosal melanomas. Most common primary sites were extremities (36.6%) and anorectum (31.4%). Nearly 10.8% of the metastatic cohort were BRAF mutated. Among 368 non-metastatic patients (172 prior treated, 185 de novo, and 11 unresectable), with a median follow-up of 26 months (0-83 months), median EFS and OS were 29.5 (95% CI: 22-40) and 33.3 (95% CI: 29.5-41.2) months, respectively. In the metastatic cohort, with a median follow up of 24 (0-85) months, the median EFS for BSC was 3.1 (95% CI 1.9-4.8) months versus 3.98 (95% CI 3.2-4.7) months with any ST (HR: 0.69, 95% CI: 0.52-0.92; P = 0.011). The median OS was 3.9 (95% CI 3.3-6.4) months for BSC alone versus 12.0 (95% CI 10.5-15.1) months in any ST (HR: 0.38, 95% CI: 0.28-0.50; P < 0.001). The disease control rate was 51.55%. Commonest grade 3-4 toxicity was anemia with chemotherapy (9.5%) and ICI (8.8%). In multivariate analysis, any ST received had a better prognostic impact in the metastatic cohort. CONCLUSIONS: Large real-world data reflects the treatment patterns adopted in LMIC for melanomas and poor access to expensive, standard of care therapies. Other systemic therapies provide meaningful clinical benefit and are worth exploring especially when the standard therapies are challenging to administer.

Chemotherapy-Induced Nausea and Vomiting (CINV) with GI Cancer Chemotherapy: Do We Need CINV Risk Score Over and Above Antiemetic Guidelines in Prescribing Antiemetic Regime?

Background Various predictive models have been developed which incorporates patient risk factors into the selection of optimal antiemetic therapy, one of which is chemotherapy-induced nausea and vomiting (CINV) risk scoring system developed by Multinational Association of Supportive Care in Cancer (MASCC). Patients and Methods Consecutive patients with gastrointestinal malignancy who had not received previous chemotherapy were eligible for enrollment in the study if they were scheduled to receive at least one cycle of chemotherapy. The CINV risk assessment tool was used to collect the study data and to assess CINV risk score. Results Ninety-eight patients fulfilling the eligibility criteria were included in this study, out of which 57% were males, median age was 48 years (range: 28-77). Colorectal cancer (32.7%) was the most common diagnosis followed by gastric cancer (27.6%). Gemcitabine/cisplatin and CAPOX regimen were the most common regimen being administered in 19.4% each. As per MASCC guidelines, 19.4% patients received highly emetogenic chemotherapy, 69.4% moderately emetogenic chemotherapy, while 11.2% received regimen with low emetogenicity. CINV risk module characterized 52% patients to have high risk for CINV, while 48% to have low risk of CINV, thus, 52% had the discrepancy in risk assigned by two methods, and this was statistically significant ( p = 0.025). In subgroup analysis, although patient cohort with acute nausea had no statistically significant discrepancy ( p = 0.123), but statistically significant discrepancy was found in patient cohort with delayed nausea ( p = 0.001), acute ( p = 0.038), and delayed ( p < 0.001) vomiting. Conclusion A significant percentage of patients who receive chemotherapy continue to experience nausea and vomiting despite receiving antiemetic treatment as per standard guidelines. The study generates a hypothesis for future large randomized studies looking at change in antiemetic prophylaxis based on CINV risk tool, leading to improvement in complete response rates of acute and delayed CINV.

Indian Antimicrobial Prescription Guidelines in Critically Ill Immunocompromised Patients.

How to cite this article: Kulkarni AP, Sengar M, Chinnaswamy G, Hegde A, Rodrigues C, Soman R, Khilnani GC, Ramasubban S, Desai M, Pandit R, Khasne R, Shetty A, Gilada T, Bhosale S, Kothekar A, Dixit S, Zirpe K, Mehta Y, Pulinilkunnathil JG, Bhagat V, Khan MS, Narkhede AM, Baliga N, Ammapalli S, Bamne S, Turkar S, Bhat KV, Choudhary J, Kumar R, Divatia JV. Indian Journal of Critical Care Medicine 2019;23(Suppl 1): S64-S96.

A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer.

BACKGROUND: Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings. METHODS: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed. RESULTS: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01). CONCLUSIONS: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT.

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.

Results of a phase II randomized controlled clinical trial comparing efficacy of Cabazitaxel versus Docetaxel as second line or above therapy in recurrent head and neck cancer.

BACKGROUND: Cabazitaxel has shown activity in squamous cancer cell lines and in taxane resistant cell lines. Hence we planned a phase 2 study to evaluate the efficacy of cabazitaxel against Docetaxel in recurrent head and neck cancer, post first line treatment. METHODS: This was a phase 2, investigator initiated, randomized controlled trial of Docetaxel (75 mg/m2) versus Cabazitaxel (20 mg/m2), in patients with head and neck cancer with ECOG performance status 0-2 who have been exposed to at least one line of chemotherapy, involving a sample size of 92 (46 per group)(CTRI/2015/06/005848). Disease control rate at 6 weeks was assessed and compared using the chi-square test. RESULTS: The disease control rate at 6 weeks was better in the Docetaxel arm over the cabazitaxel arm (52.3% versus 13.6%, p = 0.017). The median progression free survival was 21 days (95% CI 5.28 to 36.72 days) in the cabazitaxel arm versus 61 days (95% CI 21.39 to 100.60 days) in the Docetaxel arm (HR-1.455, 95% CI 0.919-2.304, p = 0.100). The median overall survival was 115 days (95% CI 74.04 to 155.95 days) in the cabazitaxel arm versus 155 days (95% CI 148.6 to 161.40 days) in the Docetaxel arm (HR-1.464, 95% CI 0.849-2.523, p = 0.170). CONCLUSION: Docetaxel had a superior disease control rate at 6 weeks compared to cabazitaxel.

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.