Dexamethasone-free antiemetic strategy for highly emetogenic chemotherapy: safety and efficacy-pilot study.

OBJECTIVES: Dexamethasone sparing strategies have shown success. The feasibility of a dexamethasone-free antiemetic strategy remains undetermined. A prospective, single-arm, pilot study was planned to determine the efficacy of an olanzapine-based, dexamethasone-free, three-drug antiemetic regimen. METHODS: Chemotherapy naïve, adult patients (≥18 years) who received ondansetron, aprepitant and olanzapine during the first cycle of highly emetogenic chemotherapy were enrolled. The primary endpoint was the rate of complete response (CR: no vomiting and no use of rescue medications) during the overall period (0-120 hours). RESULTS: Out of the total of 101 patients enrolled, most were women (82%) and received anthracycline cyclophosphamide (73%) combination therapy. The rate of CR for the overall period was 65% (95% CI 55.2% to 74.5%). The rate of CR for the acute and delayed period was 79% (95% CI 70% to 86.7%) and 76% (95% CI 66.7% to 84.1%). The rate of nausea control rates for the acute, delayed and overall periods were 34%, 29% and 24%, respectively. The grade I, II and III sedation rates over the 5 days were 8%, 5% and 1%, respectively. CONCLUSIONS: The dexamethasone-free antiemetic strategy showed modest efficacy with low incidence of clinically significant somnolence. There is a need to prospectively investigate the role of dexamethasone in the era of newer potent antiemetics in a randomised fashion. TRIAL REGISTRATION NUMBER: CTRI/2021/07/034813.

Role of circulating tumour cells (CTCs) in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

Background: Liquid biopsy is emerging as a non-invasive tool, providing a personalized snapshot of a primary and metastatic tumour. It aids in detecting early metastasis, recurrence or resistance to the disease. We aimed to assess the role of circulating tumour cells (CTCs) as a predictive biomarker in recurrent/metastatic head and neck cancer (head and neck squamous cell carcinoma (HNSCC)). Methodology: Thirty-five patients receiving palliative chemotherapy underwent blood sampling [2 mL in Ethylenediaminetetraacetic acid (EDTA) vial] at baseline and at 3 months intervals. The CTCs were isolated and evaluated using anti-epithelial cell adhesion molecule antibody-based enrichment using the OncoDiscover platform. Results: CTCs isolated from 80% of patients (n = 28) showed the sensitivity of cell detection at the baseline and 3 months intervals. The median CTC count was 1/1.5 mL of blood and the concordance with clinic-radiological outcomes was 51.4%. The median CTC count (1 (range:0-4) to 0 (range:0-1)) declined at 3 months in responders, while the non-responders had an increase in levels (0 (range :0-2) to 1 (range :0-3)). Although CTCs positively correlated with progression-free survival (PFS) and overall survival (OS), the association of CTCs did not show a significant difference with these parameters (PFS: 6 months versus 4 months; hazard ratio: 0.68; 95% confidence interval (CI): 0.29-1.58, p = 0.323; OS: 10 months versus 8 months; hazard ratio: 0.54; 95% (CI):0.18-1.57 p = 0.216) between CTC positive and CTC negative patients at 3 months. Conclusion: This study highlights the utility of CTC as a disease progression-monitoring tool in recurrent HNSCC patients. Our findings suggest the potential clinical utility of CTC and the need for exploration in upfront settings of the disease as well (NCT: CTRL/2020/02/023378).

Insights into the medical management of gastrointestinal stromal tumours: lessons learnt from a dedicated gastrointestinal stromal tumour clinic in North India.

Background: The advent of molecular driver alterations has brought in a revolutionary transformation in the treatment landscape of gastrointestinal stromal tumour (GIST). However, there is a paucity of data regarding mutational testing prevalence and associated outcomes from India. Methods: It was a retrospective study. We reviewed the case records of all patients diagnosed with GIST in a tertiary care centre from 2015 to 2021. The clinicopathological, mutational analysis and treatment plans were recorded. The study cohort was characterised by descriptive statistics. Results: Our study included 120 patients with a median age of 53 years (range: 28-77), with a male preponderance of 2:1. The most common site of the primary was the stomach (50%), followed by the small intestine (37%), with 55.8% of the patients having disseminated disease at presentation with a predominance of liver metastasis (67%). The prevalence of mutational analysis among patients prior to referral was 4%. 60.8% of the patients at our clinic had mutational analysis performed, and unavailability of analysis in the rest was due to financial constraints (12.5%), exhaustion of tissue (7.5%), reluctance to repeat biopsy (4.1%) and low-risk patients. We report c-kit in the majority (52%), platelet-derived growth factor receptor (PDGFR) in 19.2% and wild type in 16.4% along with the rarer subtypes: succinate dehydrogenase (SDH)-deficient GIST in 10.9% and Neurotrophic tyrosine receptor kinase (NTRK) fusion in 1.3%. Four of the eight SDH-deficient GIST patients had germline mutations (50%). The knowledge of driver mutations led to a change of treatment in 39.7% (29/73), i.e. stoppage of tyrosine kinase inhibitor (TKI) in 3, switch of TKI in 23, increase in TKI dose in 2 and upfront surgery in 1. The most common change was the use of sunitinib and regorafenib in patients with SDH-deficient GIST. Conclusion: Our study is one of the largest comprehensive series describing the clinical and mutational profile of GIST from India. The mutation testing rates at primary care centres continue to be low. Despite the hurdles, a large percentage of our patients underwent molecular testing, aiding in therapeutic decision-making.

Autologous stem cell transplant for multiple myeloma: Impact of melphalan dose on the transplant outcome.

We evaluated impact of melphalan dose on transplant outcomes for multiple myeloma. Between 1995 and 2019 459 consecutive patients received a transplant; 69(15%) received melphalan ≤150 mg/m2 (Mel 150 cohort) and 390 (85%) melphalan 200 mg/m2 (MEL 200 cohort). The primary outcome was overall survival (OS) from the date of transplant. Progression-free survival (PFS), engraftment, transplant response, and cumulative relapse at 2 years were secondary outcome measures. Patients in Mel 150 cohort had adverse clinical and laboratory parameters at base line. Transplant response was better for Mel 200 cohort (p < 0.024). Median OS at a median follow-up of 88 months was similar in the two cohorts; 100 Vs 102 months (Mel 200), p = 0.817. Median PFS (60.0 Vs 53 months, p = 0.746), relapse at two years (32.4% Vs 30.9%, p = 0.745) and grade 3-4 mucositis (p = 0.823) were similar. Initial treatment prepares patients better for subsequent similar transplant outcomes despite differences in baseline characteristics.

A single-arm feasibility phase II study of EMF (erlotinib + methotrexate + 5-fluorouracil) regimen in platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).

Background: Head and neck squamous cell carcinoma (HNSCC) is a huge burden in India with the majority of patients presenting in advanced unresectable stages. Innovative, low-cost but efficacious regimens that can be easily administered in the outpatient setting are the need of the hour. We envisaged assessing whether a readily available triplet therapy of erlotinib + methotrexate + 5-fluorouracil (EMF) is efficacious in terms of extending life and maintaining the quality of life in such patients. Patients and methods: This was a single-arm, phase II, investigator-initiated interventional study. Thirty-five platinum-resistant/refractory patients of HNSCC were treated with a combination of erlotinib 150 mg, methotrexate 40 mg/m2 (d1, d8) and 5-fluorouracil 500 mg/m2 (d1, d8) every 28 days till progression or unacceptable toxicities. The primary endpoint was overall response rates (ORRs) at 3 months; additional endpoints were disease control rate (DCR) at 3 months, overall survival (OS) and progression-free survival (PFS), safety and patient-reported quality of life. Results: The ORR and DCR at 3 months were 45.7% and 68.5%, respectively. The PFS was 5 months (95% confidence interval (95% CI): 3.9-6 months) and the OS was 9 months (95% CI: 7.4-10.5 months). The 3- and 6-month PFS rates were 86% ± 6% and 45% ± 9%, respectively, while the OS rates at 3 and 6 months were 91% ± 5% and 68% ± 8%, respectively. Rash, mucositis and fatigue were common adverse events occurring in 23 (65%), 14 (40%) and 9 (25.7%), respectively. The most common grade 3 events seen were rash in 5 (14.2%) and diarrhoea in 2 (5.7%). Clinically significant improvement from baseline was seen in many domains of Quality of Life Core Questionnaire and Quality of Life Head and Neck Module. Conclusions: The triplet regimen of EMF is a feasible and safe therapeutic option in patients with platinum-resistant/refractory HNSCC. It has demonstrated favourable response rates and improvement in quality of life; however, a randomised phase III study would add more robust value (NCT: CTRI/2020/02/023378).

Malignant Melanoma of Glans Penis: Findings on 18F FDG PET/CT.

ABSTRACT: Melanomas usually arise in the sun exposed parts of the skin. Mucosal melanoma is a rare condition. Melanoma of glans penis is even a rarer phenomenon with less than 250 cases reported in literature so far. Here we present a case of a 55-year-old man diagnosed with melanoma of glans penis with findings on 18F FDG PET/CT scan done for metastatic workup. 18F-FDG PET/CT showed primary in the glans penis with metastases in the right supraclavicular, mediastinal, and abdominal lymph nodes.

Unfolding the rarity of SMARCA4 deficient uterine sarcoma (SDUS): A case report.

BACKGROUND: SMARCA4 deficient uterine sarcoma (SDUS) is a relatively new entity added to the family of uterine sarcoma characterised by SMARCA4/BRG1 deficiency. CASE: A 62 years old lady presented with abdominal pain and vaginal discharge. On evaluation, found to have a pelvic mass with lymph nodal involvement. She underwent hysterectomy with bilateral salpingo-oophorectomy and lymphadenectomy. Preliminary diagnosis made outside was endometrial stromal sarcoma. On further review, had epithelioid and rhabdoid morphology with SMARCA4 loss documented on comprehensive gene profiling. Recurrence within few months of surgery was seen. She was started on gemcitabine and taxol based chemotherapy, showing significant clinical and radiological improvement. CONCLUSION: Diagnostic dilemma of this infrequent, aggressive subtype of uterine sarcoma adds to the hindrance in early recognition. Identifying histology surmounted with gene profiling is helpful in establishing diagnosis resulting in early treatment and improving outcomes.

Unusual Gastric Metastasis in Triple-Negative (Estrogen Receptor/Progesterone Receptor/HER2neu Negative) GATA-Binding Protein 3-Positive Breast Cancer.

Triple-negative breast cancer (TNBC) accounts for 20%-25% of breast cancer cases. Around 10%-15% of patients with breast cancer present with upfront metastasis. Lymph node, bone, and liver are common sites of metastasis in hormone-positive breast cancer while brain, lungs, and liver in TNBC. Although visceral metastasis is common in TNBC, metastasis to stomach is unusual. Morphological similarity of primary gastric carcinoma and lobular invasive breast carcinoma often leads to misdiagnosis. Meticulous review of histopathology and immunohistochemistry is essential for diagnosis. We present a case of carcinoma breast with unusual gastric nodular metastasis detected on 18F-fluorodeoxyglucose positron emission tomography-computed tomography.