Search

Simple Summary The conventional methods that seek to predict clinical treatment response are based on the number of circulating tumor cells (CTCs) present in liquid biopsies or genetic profiling of extracted CTCs. This paper presents a novel process by which CTCs can be extracted from blood samples taken from head and neck cancer patients and then expanded ex vivo to form organoids that can be tested with a panel of anti-cancer treatments. The resulting drug sensitivity profiles derived from cisplatin treatment of organoids were subsequently found to correlate with clinical treatment response to cisplatin in patients. CTCs extracted from liquid biopsies for ex vivo expansion negates the need for complicated and potentially risky biopsies of tumor material, thereby supporting the application of this procedure for checkups and treatment monitoring. Abstract The advanced-stage head and neck cancer (HNC) patients respond poorly to platinum-based treatments. Thus, a reliable pretreatment method for evaluating platinum treatment response would improve therapeutic efficiency and outcomes. This study describes a novel strategy to predict clinical drug responses in HNC patients by using eSelect, a lab-developed biomimetic cell culture system, which enables us to perform ex vivo expansion and drug sensitivity profiling of circulating tumor cells (CTCs). Forty liquid biopsies were collected from HNC patients, and the CTCs were expanded ex vivo using the eSelect system within four weeks. Immunofluorescence staining confirmed that the CTC-derived organoids were positive for EpCAM and negative for CD45. Two illustrative cases present the potential of this strategy for evaluating treatment response. The statistical analysis confirmed that drug sensitivity in CTC-derived organoids was associated with a clinical response. The multivariant logistic regression model predicted that the treatment accuracy of chemotherapy responses achieved 93.75%, and the area under the curves (AUCs) of prediction models was 0.8841 in the whole dataset and 0.9167 in cisplatin specific dataset. In summary, cisplatin sensitivity profiles of patient-derived CTCs expanded ex vivo correlate with a clinical response to cisplatin treatment, and this can potentially underpin predictive assays to guide HNC treatments.

Purpose: Although clinicians encounter patients aged &ge, 70 years with locally advanced oral cavity squamous cell carcinoma (LA-OCSCC), no evidence is available to facilitate decision making regarding treatment for this elderly population. Methods: We selected elderly (&ge, 70 years) patients from the Taiwan Cancer Registry database who had received a diagnosis of LA-OCSCC. Propensity score matching was performed. Cox proportional hazards model curves were used to analyze all-cause mortality in patients in different age groups receiving different treatments. Results: The matching process yielded a final cohort of 976 patients in concurrent chemoradiotherapy (CCRT), non-treatment, radiotherapy (RT) alone, and surgery cohorts who were eligible for further analysis. After stratified analysis, the adjusted hazard ratios (aHRs) (95% confidence intervals [CIs]) derived for surgery, RT alone, and non-treatment compared with CCRT were 0.66 (0.52 to 0.83), 1.02 (0.81 to 1.28), and 1.52 (1.21 to 1.91), respectively, in patients aged 70 to 80 years. In the oldest patients (aged &gt, 80 years), multivariate analysis indicated that the results of surgery or RT alone were nonsignificant compared with those of CCRT. The aHR (95% CI) derived for the highest mortality was 1.81 (1.11 to 2.40) for non-treatment compared with CCRT. Conclusions: Surgery for elderly patients with LA-OCSCC is associated with a significant survival benefit, but the association is nonsignificant in the oldest elderly patients. No survival differences were observed between RT alone and CCRT in these elderly patients. Non-treatment should not be an option for these patients.

Purpose: To propose a risk classification scheme for locoregionally advanced (Stages III and IV) head and neck squamous cell carcinoma (LA-HNSCC) by using the Wu comorbidity score (WCS) to quantify the risk of curative surgeries, including tumor resection and radical neck dissection. Methods: This study included 55,080 patients with LA-HNSCC receiving curative surgery between 2006 and 2015 who were identified from the Taiwan Cancer Registry database, the patients were classified into two groups, mortality (n = 1287, mortality rate = 2.34%) and survival (n = 53,793, survival rate = 97.66%), according to the event of mortality within 90 days of surgery. Significant risk factors for mortality were identified using a stepwise multivariate Cox proportional hazards model. The WCS was calculated using the relative risk of each risk factor. The accuracy of the WCS was assessed using mortality rates in different risk strata. Results: Fifteen comorbidities significantly increased mortality risk after curative surgery. The patients were divided into low-risk (WCS, 0&ndash, 6, 90-day mortality rate, 0&ndash, 1.57%), intermediate-risk (7&ndash, 11, 2.71&ndash, 9.99%), high-risk (12&ndash, 16, 17.30&ndash, 20.00%), and very-high-risk (17&ndash, 18 and &gt, 18, 46.15&ndash, 50.00%) strata. The 90-day survival rates were 98.97, 95.85, 81.20, and 53.13% in the low-, intermediate-, high-, and very-high-risk patients, respectively (log-rank p &lt, 0.0001). The five-year overall survival rates after surgery were 70.86, 48.62, 22.99, and 18.75% in the low-, intermediate-, high-, and very-high-risk patients, respectively (log-rank p &lt, 0.0001). Conclusion: The WCS is an accurate tool for assessing curative-surgery-related 90-day mortality risk and overall survival in patients with LA-HNSCC.