A tool for precisely stratifying postoperative patients with advanced oral cancer is crucial for the treatment plan, such as intensifying or deintensifying the regimen to improve their quality of ...life and prognosis.
To develop and validate a machine learning-based algorithm that can provide survival risk stratification for patients with advanced oral cancer who have comprehensive clinicopathologic and genetic data.
In this prognostic cohort study, the elastic net penalized Cox proportional hazards regression-based risk stratification model was developed and validated using single-center data collected between January 1, 1996, and December 31, 2011. In total, comprehensive clinicopathologic and genetic data (including clinical, pathologic, and 44 cancer-related gene variant profiles) of 334 patients with stage III or IV oral squamous cell carcinoma were used to develop and validate the algorithm in this 15-year cohort study. Data analysis was conducted between February 1, 2018, and May 6, 2020.
The main outcomes were cancer-specific survival, distant metastasis-free survival, and locoregional recurrence-free survival. Model performance was compared in terms of the Akaike information criterion and the Harrell concordance index (C index).
Complete data were available for 334 patients (315 men; median age at onset, 48 years interquartile range, 42-56 years). The predictive models using comprehensive clinicopathologic and genetic data outperformed those using clinicopathologic data alone. In the groups of postoperative patients receiving adjuvant concurrent chemoradiotherapy, the models demonstrated higher classification performance than those using clinicopathologic data alone in cancer-specific survival (mean SD C index, 0.689 0.050 vs 0.673 0.051; P = .02) and locoregional recurrence-free survival (mean SD C index, 0.693 0.039 vs 0.678 0.035; P = .004). The classification performance in distant metastasis-free survival was not different (mean SD C index, 0.702 0.056 vs 0.688 0.048; P = .09).
A risk stratification model using comprehensive clinicopathologic and genetic data accurately differentiated the high-risk group from the low-risk group in cancer-specific survival and locoregional recurrence-free survival for postoperative patients with advanced oral cancer. This algorithm could be used through an online calculator to provide additional personalized information for postoperative management of patients with advanced oral squamous cell carcinoma.
Purpose
Concurrent chemoradiotherapy (CCRT) is one of the standard treatments for patients with advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT may lead to decreased quality of ...life (QoL) and treatment compliance. This study aimed to determine the effects of PG2 (Astragalus polysaccharides) injection on CCRT-associated adverse events (AEs) and patients’ compliance with the CCRT course.
Methods
In this phase II double-blind randomized placebo-controlled trial, PG2 injection (sterile powder form) or placebo was administrated three times per week in parallel with CCRT to patients with HNSCC. The chemotherapy regimen included 50 mg/m
2
cisplatin every 2 weeks with daily tegafur–uracil (300 mg/m
2
) and leucovorin (60 mg/day).
Results
The study was terminated prematurely due to the successful launch of a newly formulated PG2 injection (lyophilized form). A total of 17 patients were enrolled. The baseline demographics and therapeutic compliance were comparable between the CCRT/PG2 and CCRT/placebo groups. During CCRT, severe treatment-associated AEs were less frequent in the CCRT/PG2 group than in the CCRT/placebo group. Furthermore, less QoL fluctuations from the baseline during CCRT were noted in the CCRT/PG2 group than in the CCRT/placebo group, with a significant difference in the pain, appetite loss, and social eating behavior. The tumor response, disease-specific survival and overall survival did not differ between the two groups.
Conclusion
This preliminary study demonstrated PG2 injection exhibited an excellent safety profile, and has potential in ameliorating the deterioration in QoL and the AEs associated with active anticancer treatment among patients with advanced pharyngeal or laryngeal HNSCC under CCRT. Further research in patients with other cancer types or treatment modalities may widen PG2’s application in clinical settings.
Amplification of 11q13.3 is a frequent event in human cancers, including head and neck squamous cell carcinoma. This chromosome region contains several genes that are potentially cancer drivers, ...including FADD (Fas associated via death domain), an apoptotic effector that was previously identified as a novel oncogene in laryngeal/pharyngeal cancer. This study was designed to explore the role of FADD in oral squamous cell carcinomas (OSCCs) samples from Taiwanese patients, by assessing copy number variations (CNVs) and protein expression and the clinical implications of these factors in 339 male OSCCs. The intensity of FADD protein expression, as determined by immunohistochemistry, was strongly correlated with gene copy number amplification, as analyzed using a TaqMan CNV assay. Both FADD gene copy number amplification and high protein expression were significantly associated with lymph node metastasis (P < 0.001). Patients with both FADD copy number amplification and high protein expression had the shortest disease-free survival (DFS; P = 0.074 and P = 0.002) and overall survival (OS; P = 0.011 and P = 0.027). After adjusting for primary tumor status, tumor differentiation, lymph node metastasis and age at diagnosis, DFS was still significantly lower in patients with either copy number amplification or high protein expression (hazard ratio H.R. = 1.483; 95% confidence interval C.I., 1.044-2.106). In conclusion, our data reveal that FADD gene copy number and protein expression can be considered potential prognostic markers and are closely associated with lymph node metastasis in patients with OSCC in Taiwan.
Objectives/Hypothesis
To elucidate the associations among the immunohistochemical expression of tumor markers, clinicopathological variables, and disease‐free survival (DFS) in patients with ...early‐stage glottic squamous cell carcinoma (SCC) who underwent transoral laser microsurgery (TLM) as the primary treatment.
Study Design
Retrospective chart review.
Methods
The records of consecutive patients with Tis‒T2N0 glottic SCC who underwent TLM between August 1, 2012 and October 31, 2015 were reviewed. Expression of Bcl‐2, pRB, p16INK4A, p53, c‐Myc, E‐cadherin, and EGFR was examined using tissue microarrays containing tumor specimens through immunohistochemistry. Three‐year DFS rates were calculated.
Results
A total of 65 consecutive patients were identified, of which 28 were excluded due to insufficient tissue (n = 22) and low biomarker quality (n = 6). Therefore, 37 patients with complete records were included. The included patients were significantly older and had a more advanced type of cordectomy than did the excluded patients (P = .015 and .009, respectively). According to the findings of univariate analysis, age, betel quid chewing, type of cordectomy, BCL‐2 expression, and pRB expression significantly predicted 3‐year DFS. According to the findings of multivariate analysis, age (adjusted hazard ratio: 0.94, 95% CI: 0.88‐1.00), betel quid chewing (adjusted hazard ratio: 5.07, 95% CI: 1.32‐19.44), and pRB expression (adjusted hazard ratio: 0.02, 95% CI: 0.00‐0.28) were independent predictors of 3‐year DFS.
Conclusions
Low pRB expression is a potential biomarker for predicting disease relapse after primary TLM for early‐stage glottic SCC and may help to identify high‐risk patients who can subsequently undergo intensive management.
Level of Evidence
4
Laryngoscope, 129:E220–E226, 2019
•Adequate surgical margin for OSCC needs to be re-evaluated.•The study enrolled 15,654 patients with OSCC from the TCR database.•Advanced N stage and positive margin are major risk factors for poor ...CSS and OS.•Surgical margins <4 mm and <5 mm predict poor CSS and OS, respectively.
Margin status and lymph node metastasis are the most important prognostic factors for oral cancers. However, while adequate surgical resection is crucial for local control and prognosis, the definition of clear margins has long been a subject of debate. In this study, we analyzed data from a nationwide population-based cancer registry database and evaluated the impact of surgical margins on cancer-specific survival (CSS) and overall survival (OS) as well as the optimal cutoff of adequate surgical margins.
This analysis included all cases of oral cancer diagnosed from 2011 to 2017 that were reported to the Taiwan Cancer Registry database. The staging system was converted from American Joint Committee on Cancer (AJCC) version 7 to AJCC version 8. Kaplan–Meier analysis and Cox proportional-hazards regression were performed to identify covariates that were significantly associated with CSS and OS.
Between 2011 and 2017, 15,654 of a total of 36,091 cases diagnosed with oral cancers were included in the final analyses. Advanced N stage, positive margins, and advanced T stage are the leading risk factors for poor CSS and OS. When surgical margins were subdivided into 1-mm intervals from 5 mm to positive margin, we found that surgical margins <4 mm and <5 mm predict poor CSS and OS, respectively.
This is the first nationwide, population-based cohort to revisit the question of the adequate surgical margins for oral cancers. We conclude that surgical margins ≥4 mm and ≥5 mm are adequate for good CSS and OS, respectively.
We investigated the relationships of cystic nodal metastasis, human papillomavirus (HPV) status, and treatment failure patterns in patients with oropharyngeal squamous cell carcinoma (OPSCC) treated ...with chemoradiotherapy.
We retrospectively reviewed pretreatment MRI and clinical courses of patients with OPSCC whose tumors were tested for HPV-induced p16 expression via immunohistochemistry and who completed chemoradiotherapy. Cervical cystic nodal metastasis and necrotic nodal metastasis were classified on MRI.
Of 98 patients eligible for analysis, 33 were p16-positive. Cystic nodal metastasis was significantly more prevalent in p16-positive than in p16-negative patients (39.4% versus 18.5%, respectively; p = 0.025). Necrotic nodal metastasis was significantly more prevalent in p16-negative than in p16-positive patients (73.8% versus 51.5%, respectively; p = 0.027). On multivariate analysis, necrotic nodal metastasis (odds ratio OR = 7.310, p = 0.011) was an independent predictor of regional failure, while advanced nodal stage (OR = 4.119, p = 0.022) and cystic nodal metastases (OR = 0.087, p = 0.026) were independent positive and negative predictors of distant failure, respectively.
Cervical cystic and necrotic nodal metastases are associated with HPV-induced p16-positive and p16-negative OPSCC, respectively. Patients with necrotic nodal metastasis at presentation have an increased risk of regional failure. Distant failure is directly and inversely correlated with advanced nodal stage and cystic nodal metastasis, respectively.
Background
Survival in oral cavity squamous cell carcinoma (OSCC) depends heavily on locoregional control. In this study, we sought to determine the independent prognosticators for local tumor ...control, disease-specific survival (DSS), and overall survival (OS) rates in a series of OSCC patients undergoing radical surgery.
Methods
We retrospectively reviewed 827 consecutive OSCC patients undergoing radical surgery from January 1998 to March 2005. Postoperative radiotherapy was performed in patients with pT4 tumors, positive lymph node(s), or close margins (≤4 mm). Local control rates and survivals were plotted using the Kaplan–Meier method.
Results
On multivariate analysis (MVA), unfavorable prognostic factors for local control were pathological margins ≤7 mm (
P
< 0.001), pathological tumor depth ≥10 mm (
P
< 0.001), pathological positive lymph node(s) (
P
= 0.001), and the presence of betel quid chewing (
P
= 0.012). The same predictors, with the exception of betel quid chewing and pathological positive lymph node(s), were independently associated with DSS and OS in MVA. A prognostic scoring system was formulated by summing up the four significant local control covariates from MVA. Patients with scores of 3–4 had a significantly poorer local control rate compared to patients with scores of 0–2 (score 3 versus score 0–2:
P
< 0.001; score 4 versus score 0–2:
P
< 0.001)
Conclusions
Taken together, our data suggest that pathological margins and pathological tumor depth are major independent prognosticators not only for local tumor control, but also for DSS and OS.
Purpose
The aims of this study were to identify the factors and reasons impacting discordance with the treatment plan in head and neck cancer (HNC) patients and compare the differences between the ...concordance group and the discordance group.
Methods
This secondary analysis was conducted from population-based data from Taiwan collected from January 1, 2016, to June 30, 2018. Logistic regression analysis was used to identify the factors related to discordance with the treatment plan.
Results
We examined 1095 HNC patients, 12.1% of whom were discordant with treatment. Patients with advanced cancer stage, old age, and treatment plans of best supportive care (BSC) or surgery combined with radiation (RT), chemotherapy (CT), or chemoradiation (CCRT) were more likely to have discordance with their treatment plan. Of the 133 patients who were discordant with their treatment plan, the top reasons were as follows: “patients or their family considered patients’ poor physical condition (chronic disease or unstable systemic disease), difficulty in enduring any condition likely to cause physical discomfort from disease treatment,” “inconvenient transportation,” and “disease progression.”
Conclusions
Patients’ cancer stage, age, and types of treatment plans recommended significantly influenced discordance with treatment plan. Poor physical condition was the major reason for discordance with the treatment plan. Patients in the concordance group were significantly more likely than those in the discordance group to be younger than 65 years, have less advanced cancer stage, and be recommended to receive surgery rather than any other regimen. Multidisciplinary team care can help patients make positive decisions about treatment.
ABSTRACT
Objectives
This study investigates the relationship between multidisciplinary team care (MDTC) and patient completion of their treatment regimen for oral squamous cell carcinoma (OSCC).
...Methods
We conducted a retrospective cohort study in patients diagnosed with OSCC in Taiwan from 1 January 2016 to 30 June 2018 using a linked cancer registry database.
Results
Of the 969 OSCC MDTC patients in the study cohort, 6.3% reported incomplete treatment, with 1.3% interrupting ongoing treatment and 5.0% terminating definitive treatment. Patients who had advanced‐stage disease, experienced primary cancer recurrence or a secondary cancer, or were treated with surgery combined with chemotherapy, radiotherapy or chemoradiotherapy were more likely to terminate treatment before completion. The major reasons for interruption of ongoing treatment included ‘patient or their family considered the patient to be in poor physical condition’ and ‘difficulty enduring physical discomfort caused by treatment’. The major reason for termination of definitive treatment was ‘patient or their families or friends experienced negative treatment effects and worried about the side‐effects of treatment’.
Conclusion
Advanced‐stage cancer, recurrence or secondary cancer, and surgery combined with chemotherapy, radiotherapy or chemoradiotherapy negatively affected treatment completion. MDTC allows for shared decision‐making to determine the optimal treatment.
MicroRNAs (miRNAs) have a major impact on regulatory networks in human carcinogenesis. In this study, we sought to investigate the prognostic significance of miRNAs in patients with oral cavity ...squamous cell carcinoma (OSCC). In a discovery phase, RNA was extracted from 58 OSCC tumor samples and paired normal tissues. MiRNAs expression was evaluated with TaqMan Array Card and TaqMan MicroRNA assays. The prognostic significance of the miRNA signature identified in the discovery phase was validated by qRT-PCR in a replication set consisting of 141 formalin-fixed, paraffin-embedded (FFPE) samples. We identified a miRNA regulatory network centered on the three hub genes (SP1, MYC, and TP53) that predicted distinct clinical endpoints. Three miRNAs (miR-218, miR-125b, and let-7g) and their downstream response genes had a concordant prognostic significance on disease-free survival and disease-specific survival rates. In addition, patients with a reduced expression of miR-218, miR-125b, and let-7g have a higher risk of poor outcomes in presence of specific risk factors (p-stage III-IV, pT3-4, or pN+). Our findings indicate that specific miRNAs have prognostic significance in OSCC patients and may improve prognostic stratification over traditional risk factors.
PDF
