Salivary Gland Hypofunction and/or Xerostomia Induced by Nonsurgical Cancer Therapies: ISOO/MASCC/ASCO Guideline.
Mercadante Valeria,Jensen Siri Beier,Smith Derek K,Bohlke Kari,Bauman Jessica,Brennan Michael T,Coppes Robert P,Jessen Niels,Malhotra Narinder K,Murphy Barbara,Rosenthal David I,Vissink Arjan,Wu Jonn,Saunders Deborah P,Peterson Douglas E
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE:To provide evidence-based recommendations for prevention and management of salivary gland hypofunction and xerostomia induced by nonsurgical cancer therapies. METHODS:Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials published between January 2009 and June 2020. The guideline also incorporated two previous systematic reviews conducted by MASCC/ISOO, which included studies published from 1990 through 2008. RESULTS:A total of 58 publications were identified: 46 addressed preventive interventions and 12 addressed therapeutic interventions. A majority of the evidence focused on the setting of radiation therapy for head and neck cancer. For the prevention of salivary gland hypofunction and/or xerostomia in patients with head and neck cancer, there is high-quality evidence for tissue-sparing radiation modalities. Evidence is weaker or insufficient for other interventions. For the management of salivary gland hypofunction and/or xerostomia, intermediate-quality evidence supports the use of topical mucosal lubricants, saliva substitutes, and agents that stimulate the salivary reflex. RECOMMENDATIONS:For patients who receive radiation therapy for head and neck cancer, tissue-sparing radiation modalities should be used when possible to reduce the risk of salivary gland hypofunction and xerostomia. Other risk-reducing interventions that may be offered during radiation therapy for head and neck cancer include bethanechol and acupuncture. For patients who develop salivary gland hypofunction and/or xerostomia, interventions include topical mucosal lubricants, saliva substitutes, and sugar-free lozenges or chewing gum. For patients with head and neck cancer, oral pilocarpine and oral cevimeline, acupuncture, or transcutaneous electrostimulation may be offered after radiation therapy.Additional information can be found at www.asco.org/supportive-care-guidelines.
10.1200/JCO.21.01208
Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study.
The Lancet. Oncology
BACKGROUND:Actinium-225 (Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC). We aimed to report the safety and antitumour activity of Ac-PSMA RLT of mCRPC in a large cohort of patients treated at multiple centres across the world. METHODS:This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa. We pooled data of consecutive patients of any age and Eastern Cooperative Oncology Group performance status with histopathologically confirmed adenocarcinoma of the prostate who were treated with one or more cycles of 8 MBq Ac-PSMA RLT administered intravenously for mCRPC. Previous lines of mCRPC treatment included taxane-based chemotherapy, androgen-receptor-axis inhibitors, lutetium-177 (Lu) PSMA RLT, and radium-223 dichloride. The primary outcomes were overall survival and progression-free survival. FINDINGS:Between Jan 1, 2016, and May 31, 2023, 488 men with mCRPC received 1174 cycles of Ac-PSMA RLT (median two cycles, IQR 2-4). The mean age of the patients was 68·1 years (SD 8·8), and the median baseline prostate-specific antigen was 169·5 ng/mL (IQR 34·6-519·8). Previous lines of treatment were docetaxel in 324 (66%) patients, cabazitaxel in 103 (21%) patients, abiraterone in 191 (39%) patients, enzalutamide in 188 (39%) patients, Lu-PSMA RLT in 154 (32%) patients, and radium-223 dichloride in 18 (4%) patients. The median follow-up duration was 9·0 months (IQR 5·0-17·5). The median overall survival was 15·5 months (95% CI 13·4-18·3) and median progression-free survival was 7·9 months (6·8-8·9). In 347 (71%) of 488 patients, information regarding treatment-induced xerostomia was available, and 236 (68%) of the 347 patients reported xerostomia after the first cycle of Ac-PSMA RLT. All patients who received more than seven cycles of Ac-PSMA RLT reported xerostomia. Grade 3 or higher anaemia occurred in 64 (13%) of 488 patients, leukopenia in 19 (4%), thrombocytopenia in 32 (7%), and renal toxicity in 22 (5%). No serious adverse events or treatment-related deaths were recorded. INTERPRETATION:Ac-PSMA RLT shows a substantial antitumour effect in mCRPC and represents a viable therapy option in patients treated with previous lines of approved agents. Xerostomia is a common side-effect. Severe bone marrow and renal toxicity are less common adverse events. FUNDING:None.
10.1016/S1470-2045(23)00638-1
Multi-omics reveals lactylation-driven regulatory mechanisms promoting tumor progression in oral squamous cell carcinoma.
Genome biology
BACKGROUND:Lactylation, a post-translational modification, is increasingly recognized for its role in cancer progression. This study investigates its prevalence and impact in oral squamous cell carcinoma (OSCC). RESULTS:Immunohistochemical staining of 81 OSCC cases shows lactylation levels correlate with malignancy grading. Proteomic analyses of six OSCC tissue pairs reveal 2765 lactylation sites on 1033 proteins, highlighting its extensive presence. These modifications influence metabolic processes, molecular synthesis, and transport. CAL27 cells are subjected to cleavage under targets and tagmentation assay for accessible-chromatin with high-throughput sequencing, and transcriptomic sequencing pre- and post-lactate treatment, with 217 genes upregulated due to lactylation. Chromatin immunoprecipitation-quantitative PCR and real-time fluorescence quantitative PCR confirm the regulatory role of lactylation at the K146 site of dexh-box helicase 9 (DHX9), a key factor in OSCC progression. CCK8, colony formation, scratch healing, and Transwell assays demonstrate that lactylation mitigates the inhibitory effect of DHX9 on OSCC, thereby promoting its occurrence and development. CONCLUSIONS:Lactylation actively modulates gene expression in OSCC, with significant effects on chromatin structure and cellular processes. This study provides a foundation for developing targeted therapies against OSCC, leveraging the role of lactylation in disease pathogenesis.
10.1186/s13059-024-03383-8
Cancer therapy-related salivary dysfunction.
The Journal of clinical investigation
Salivary gland dysfunction is a common side effect of cancer treatments. Salivary function plays key roles in critical daily activities. Consequently, changes in salivary function can profoundly impair quality of life for cancer patients. We discuss salivary gland anatomy and physiology to understand how anticancer therapies such as chemotherapy, bone marrow transplantation, immunotherapy, and radiation therapy impair salivary function. We discuss approaches to quantify xerostomia in the clinic, including the advantages and limitations of validated quality-of-life instruments and approaches to directly measuring salivary function. Current and emerging approaches to treat cancer therapy-induced dry mouth are presented using radiation-induced salivary dysfunction as a model. Limitations of current sialagogues and salivary analogues are presented. Emerging approaches, including cellular and gene therapy and novel pharmacologic approaches, are described.
10.1172/JCI182661
Impact of Postoperative Radiotherapy on the Prognosis of Early-Stage (pT1-2N0M0) Oral Tongue Squamous Cell Carcinoma.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE:To identify subgroups of patients with early-stage (pT1-2N0M0) oral tongue squamous cell carcinoma (OTSCC) who may benefit from postoperative radiotherapy (PORT). PATIENTS AND METHODS:This retrospective cohort study included 528 patients diagnosed between October 2009 and December 2021. Clinicopathological characteristics and treatments with or without PORT were analyzed for their impact on outcomes. RESULTS:Among 528 patients who underwent radical surgery (median age, 62 years [IQR, 52-69]), 145 (27.5%) also underwent PORT. Multivariate analyses revealed that PORT was associated with improved survival outcomes, whereas moderate-to-poor differentiation, perineural infiltration (PNI), lymphovascular invasion (LVI), and increasing depth of invasion (DOI) were associated with poorer survival outcomes. For patients with moderate-to-poor differentiation, the surgery + PORT group showed improved outcomes compared with the surgery-alone group. After propensity score matching, the results were as follows: overall survival (OS), 97% versus 69%, = .003; disease-free survival (DFS), 88% versus 50%, = .001. After excluding cases with PNI/LVI, the differences persisted: OS, 97% versus 82%, = .040; DFS, 87% versus 64%, = .012. Similar survival benefits were observed in 104 patients with PNI and/or LVI (OS, 81% 58%; = .022; DFS, 76% 47%; = .002). In subgroups with DOI >5 mm or close margins, PORT contributed to improved DFS (80% 64%; = .006; 92% 66%; = .049) but did not significantly affect OS. CONCLUSION:Patients with moderately-to-poorly differentiated pT1-2N0M0 OTSCC benefited from PORT. Our study provided evidence that patients with PNI and/or LVI who underwent PORT had improved survival. PORT also offered DFS benefit among patients with DOI >5 mm.
10.1200/JCO.23.01106
A novel saliva-based miRNA profile to diagnose and predict oral cancer.
International journal of oral science
Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD). The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n = 50), OPMD (n = 52), and controls (n = 60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p, miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was: area under curve (AUC): 0.954, sensitivity: 86%, specificity: 90%, positive predictive value (PPV): 87.8% and negative predictive value (NPV): 88.5% whereas between OC and OPMD was: AUC: 0.911, sensitivity: 90%, specificity: 82.7%, PPV: 74.2% and NPV: 89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC, revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.
10.1038/s41368-023-00273-w
Global burden of oral cancer in 2022 attributable to smokeless tobacco and areca nut consumption: a population attributable fraction analysis.
The Lancet. Oncology
BACKGROUND:Consuming products that contain smokeless tobacco or areca nut increases the risk of oral cancer. We aimed to estimate the burden of oral cancer attributable to smokeless tobacco or areca nut consumption globally and by type of smokeless tobacco or areca nut product in four major consuming countries. METHODS:We calculated population attributable fractions (PAFs) using prevalence of current use of smokeless tobacco or areca nut products from national surveys and corresponding risks of oral cancer from the literature. We applied PAFs to national estimates of oral cancer incidence in 2022 from the Global Cancer Observatory's Cancer Today database to obtain cases attributable to smokeless tobacco or areca nut consumption. We modelled 95% uncertainty intervals (UIs) using Monte Carlo simulations. FINDINGS:Globally, an estimated 120 200 (95% UI 115 300-124 300) cases of oral cancer diagnosed in 2022 were attributable to smokeless tobacco or areca nut consumption, accounting for 30·8% (95% UI 29·6-31·9) of all oral cancer cases (120 200 of 389 800). An estimated 77% of attributable cases were among male patients (92 600 cases, 95% UI 88 000-96 500) and 23% were among female patients (27 600 cases, 26 000-29 000). Regions with the highest PAFs were Melanesia, Micronesia, and Polynesia (78·6%, 95% UI 74·4-80·5), southcentral Asia (57·5%, 54·8-59·5), and southeastern Asia (19·8%, 19·0-20·6). Lower-middle-income countries represented 90·2% of the world total attributable cases (108 400 cases, 95% UI 103 400-112 200). INTERPRETATION:Our findings suggest that one in three cases of oral cancer globally are attributable to smokeless tobacco or areca nut consumption, and could be prevented through smokeless tobacco and areca nut control. Global cancer control efforts must incorporate further measures to reduce smokeless tobacco and areca nut consumption in populations with the largest attributable burden. FUNDING:French National Cancer Institute.
10.1016/S1470-2045(24)00458-3