Advanced salivary gland neoplasm have variable natural history. The goal of systemic treatment is palliation however no clear evidence regarding when and to whom it needs to be administered.The objective of this study was to determine the molecular profile of malignant salivary gland tumors and to evaluate the impact of systemic therapy.This was a retrospective cohort study.
Head and Neck Medical Oncology outpatient department maintains a prospective chemotherapy database of patients planned for any form of systemic therapy. Adult patients (Age > or = 18 years) with (ECOG PS) 0-3 histologically proven salivary gland malignancy treated between January 2010- September 2018 at the host institute.Data regarding demographics, baseline characteristics, tumor details, staging details, treatment details, outcome details expression of ER, PR, AR and HER-2 Neu status was extracted.The procedure for performing IHC, interpreting, and quality assurance is already published.Molecular profilingSnapshot profiling was performed using Multiplex polymerase chain reaction (PCR) followed by multiplex base extension assay utilizing the SNaPshot TM methodology. It consists of a combination of real time PCR looking for 21 hotspot mutation sites in nine cancer genes: (EGFR, HER2, KRAS, NRAS,PIK3CA, BRAF, MEK1, PTEN,AKT1-).
Out of the 69 evaluable patients, 55% (n = 38) had actionable target. Androgen Receptor (AR) expression was present in majority of patients (n = 23,34%), with it alone being expressed in 17% (n = 12) of patients, and along with other actionable targets in the other. 60 (87%) patients received systemic therapy either in form of chemotherapy (35,58.3%) or targeted therapy (25,41.7%). The strategy of observation in asymptomatic status lead to an median OS of 32.27 (3.03-NA) similar to patients receiving systemic therapy (p = 0.992). In patients with visceral crisis, the median OS was higher in patients receiving chemotherapy than targeted therapy (19.07 (14.20-23.8) versus 6.07 (2.23-NA), p < 0.001).The median follow up was 42.1(95% CI 36.5-51.7) months.
Actionable targets are seen in salivary gland tumors and treatment strategies should be based on these and symptomatic status.
Tata Memorial Hospital Mumbai.
Has not received any funding.
All authors have declared no conflicts of interest.
Parathyroid neoplasms are characterized with hypersecretion of parathyroid hormone and potentially exhibit disruption of metabolic pathways. Mitochondria are essential for energy homeostasis and mitochondrial DNA (mtDNA) abnormalities are related to multiple types of malignancies. However, the status of mtDNA mutation and copy number variations in parathyroid carcinoma (PC) is not well known.
Ultra-deep targeted sequencing of mitochondrial genome was performed using tissues of 12 PCs and 12 parathyroid adenomas (PAs). Germline variants and somatic mutations in the mitochondrial genome were scanned and analysed in comparison with clinical features. The relative copy number of mtDNA in PCs and PAs was determined via quantitative real-time polymerase chain reaction.
A total of 528 germline variants and 16 somatic mutations were identified in 24 samples of parathyroid neoplasms. All 62 non-synonymous germline variants in coding sequence (CDS) were predicted to be of low pathogenicity in PA and PC samples. Five somatic mutations with high pathogenicity in CDSs were identified in 4 (33.3%, 4/12) PC samples and 1 PA sample (8.3%, 1/12). A somatic mutation in a CDS was correlated with high mtDNA copy number in parathyroid neoplasm (p = 0.004), CDC73 gene mutation (p = 0.017) and PC recurrence (p = 0.024). More C-19 genotypes in the D310 region were found in PA than in the PC samples (3.5% vs 1.9%, p = 0.045).
More somatic CDS mutations with high pathogenicity were identified in PC than in PA. A high mtDNA copy number was found in parathyroid neoplasms with somatic CDS mutations and in PCs with CDC73 mutations and recurrence.
The authors.
This work was supported by the Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS-I2M) (2017-I2M-1-001), Peking Union Medical College Innovative Team Development Program, the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018PT32014) and the 2016 Peking Union Medical College Hospital Science Foundation for Junior Faculty (pumch-2016.2.7).
All authors have declared no conflicts of interest.
Intensity modulated radiation therapy (IMRT) is the standard of care for nasopharyngeal carcinoma (NPC). Part of the IMRT quality assurance process involves accurate target volume delineation, which is crucial for local control and survival. Current practice utilizes a uniform contouring method for clinical target volume (CTV) for all stages of NPC. Here, we conducted a single-arm phase 2 trial investigating the tumor control rates of reduced CTV margins and corresponding doses in low-risk, early-stage NPC.
Patients with biopsy-proven stage I-IIb (6th UICC/AJCC) NPC were enrolled. All patients were treated with IMRT alone. Two CTVs (CTV1 [high risk] and CTV2 [low risk]) were outlined; CTV1 was defined by grossly identified tumour (on MRI or CT) plus 5-mm margin (3-mm posteriorly); CTV2 was CTV1 plus 5-mm margin (3-mm posteriorly). 60 Gy and 50–54 Gy in 30 fractions were prescribed to CTV1 and CTV2, respectively. Primary end-point was locoregional recurrence free survival (LRRFS).
From May 2001 to August 2006, 103 patients were recruited; all patients completed IMRT as planned (time duration 39-61 days). At a median follow-up of 12.6 years, five patients developed locoregional failures; of which one was in-field, and four were regional recurrence (two in-field and two marginal). 10-year LRRFS, distant metastasis free survival (DMFS), disease specific survival (DSS) and overall survival (OS) were 95.0% and 94.1%, 94.0% and 91.1%, respectively. The most common grade 1-2 late toxicities included subcutaneous fibrosis (79.6%), hearing loss (53.4%) and skin dystrophy (43.2%); grade 3 included subcutaneous fibrosis (2.9%) and hearing loss (2.9%); and no grade 4 late toxicity.
Reduced CTV margins and corresponding doses results in optimal longterm tumour control, with minimal late adverse events.
NCT03839602.
Prof. Chong Zhao.
Has not received any funding.
M.L.K. Chua: Honoraria (self), Advisory / Consultancy: Janssen, Astellas, Varian, Ferring Singapore and AstraZeneca; Research grant / Funding (institution): Ferring Singapore, GenomeDx Biosciences, Varian, MedLever. All other authors have declared no conflicts of interest.
The survival of patients with nasopharyngeal cancer (NPC) have been reported in endemic and non-endemic regions. However, this has never been analyzed in Indonesian cases although this malignancy is endemic. This study aimed to perform survival analysis of the local cases and determine the prognostic factors.
A total of 767 patients with NPC diagnosed from January 2007 to December 2016 at Dr Sardjito General Hospital were included. Potential prognostic variables included sociodemographic parameters, clinicopathology features and treatment strategy. Kaplan-Meier method and the log-rank test estimated the rates of overall survival (OS). Multivariate analyses were done by a Cox proportional hazards model.
The median OS was 14.38 months for the whole cohort. Patients with education ≥9 years, government insurance for civil servants, advanced stage and combination of chemo-radiation treatment had a significantly better OS than their counterparts (p < 0.005, p < 0.005, p < 0.050 and p < 0.001). Multivariate analyses showed that age, clinical stage and treatment modality were independent prognostic factors for OS. For age, individuals over the median age had a reduced OS (time ratio/TR= 0.733, 95% confidence interval/CI 0.570-0.944). Individuals with advanced clinical stage (stage IVc) also had a reduced OS (TR = 0.123, 95% CI 0.21-0.737). In stratified analysis, compared with chemotherapy or radiation alone, chemo-radiation demonstrated a significant benefit of the patients’ OS (TR 4.87; 95% CI 3.01-7.87).
Median OS of our cohort was low compared to those reported in international publications, emphasizing the importance to improve the local cancer management. Age, clinical stage and treatment modality were independent favourable predictos for the patients’ OS.
Ethics committee, Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada/Dr Sardjito Hospital.
Indonesian Society for Hematology and Medical Oncology Yogyakarta Branch; Dutch Cancer Society.
All authors have declared no conflicts of interest.
To predict the 90-day mortality in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) after concurrent chemoradiotherapy (CCRT), we propose a predictive scoring system, the Taipei Medical University (TMU)-CCRT Mortality Predictor Scoring System, and validate its accuracy.
This study extracted data of 16 029 patients with head and neck cancer who completed CCRT from the Taiwan Cancer Registry database (TCRD). Based on the 90-day mortality data after CCRT completion, the patients were divided into 2 groups: 90-day mortality (n = 1 068) and 90-day survival (n = 14 961). Stepwise multivariate Cox proportional hazards model was used to select the significant risk factors.
Multivariate analysis revealed that age ≥ 50 or ≥ 70 years, pneumonia, sepsis, hemiplegia, moderate or severe renal disease, leukemia, and metastatic non-HNSCC solid cancers were significant risk factors affecting the 90-day mortality rate. Next, the risk scores of 0, 1 to 3, 4 to 6, and 7 to 9+ were categorized to indicated very low, low, moderate, and high risks (90-day mortality rate = 3.37%, 5.00%-10.98%, 16.15%-29.13%, and 33.93%-37.50%, respectively).
Our TMU-CCRT Mortality Predictor Scoring System can accurately predict the 90-day mortality in CCRT-treated patients with LAHNSCC.
“Szu-Yuan Wu” without further recourse to the authors.
Has not received any funding.
The author has declared no conflicts of interest.
The EXTREME trial demonstrated that patients with R/M-HNSCC benefit from the addition of cetuximab to first-line platinum-based CT in relation to overall survival (OS), progression-free survival (PFS) and response rate. The aims of the study are to evaluate the survival outcomes and identify predictors of survival among these patients (pts).
Data regarding R/M HNSCC consecutive pts treated with cetuximab and platinum from 2009 to 2018 were retrospectively collected. The analyses of response (R.), PFS and OS, each evaluated starting from first treatment, were performed. A Cox proportional hazard model was run and Survival curves were estimated with the Kaplan-Meier method and compared using the log-rank test.
One hundred and eight pts were identified with ECOG-PS 0-1. Primary tumor sites were oropharynx 28(25,9%), oral cavity 19 (17.6%), larynx/hypopharynx 57 (52,7%) and others 4 (3.7%). Median OS was 16,9 m. (95% confidence interval [CI] 12.9-20.9), whereas mean PFS was 7.4 m. (95% CI 4.1-8.9). Only 43 pts (39.8%) were able to complete 6 cycles of treatment. R. rate (partial R. and complete R.) was 19% with 24 (22.2%) showing stable disease as best R. ECOG PS = 1 (HR = 1.71,95% CI 1.1-2.97) and the location of the primary tumor in the larynx/hypopharynx (HR = 1.98, 95% CI 1.14-3.48) were significantly associated with an increased risk of disease progression. 48 (44%) pts with stable disease who received CT plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects with statistical significant differences between this sub-group and those who weren’t able to receive Cetuximab monotherapy (OS 10.9 m. (95% CI 8.7-13.1 vs 23.6m. (95% CI 16.1-31.1) p = 0.001). OS was higher in pts with grade 2-4 skin toxicity associated with cetuximab (OS 13.7 (95% CI 8.7-18.8) vs 18.4m. (95% CI 13.7-23.1) m. p = 0.05).
In non-selected R/M HNSCC pts, we obtained a median PFS and OS of 7,4 and 16,9 months, superior to 5,6 and 10,1 months reported in Extreme trial (Vermorken et al. 2008). At baseline, ECOG PS, larynx/hypopharynx location and skin toxicity related to Cetuximab could be used to define pt prognosis.
The authors.
Has not received any funding.
All authors have declared no conflicts of interest.