Residual plasma Epstein-Barr virus DNA after intensity-modulated radiation therapy is associated with poor outcomes in nasopharyngeal carcinoma.

Aim: To investigate the effects of residual plasma Epstein-Barr virus (EBV) DNA levels after 3 months of intensity-modulated radiation therapy (IMRT) (postIMRT-EBV DNA) on prognosis in patients with nasopharyngeal carcinoma. Methods: Data from 300 patients were retrospectively collected for analysis. Results: Of these patients, 25 (8.3%) and 275 (91.7%) had positive and negative postIMRT-EBV DNA, respectively. Multivariate survival analysis showed that EBV DNA >688 IU/ml was independently associated with inferior distant metastasis-free survival (p = 0.003) and progression-free survival (p = 0.002). Moreover, postIMRT-EBV DNA was independently associated with inferior locoregional recurrence-free survival (hazard ratio: 4.325; p = 0.018), distant metastasis-free survival (hazard ratio: 10.226; p < 0.001) and progression-free survival (hazard ratio: 10.520; p < 0.001). Conclusion: Positive postIMRT-EBV DNA is a prognostic biomarker for nasopharyngeal carcinoma.

Risk factors of early thyroid dysfunction after definitive radiotherapy in nasopharyngeal carcinoma patients.

BACKGROUND: To explore the patterns and risk factors of early thyroid dysfunction in nasopharyngeal carcinoma (NPC) patients within 1 year after intensity-modulated radiation therapy (IMRT). METHODS: Patients with NPC who received definitive IMRT between April 2016 and April 2020 were included. All patients had normal thyroid function before definitive IMRT. The chi-square test, Student's T-test, Mann-Whitney U test, Kaplan-Meier method, receiver operating characteristics curve, and Cox proportional hazard analysis were used for statistical analysis. RESULTS: A total of 132 NPC patients were identified. Of these patients, 56 (42.4%) had hypothyroidism and 17 (12.9%) had hyperthyroidism. The median time to hypothyroidism and hyperthyroidism was 9 months (range, 1-12 months) and 1 month (range, 1-6 months) after definitive IMRT, respectively. In patients with hypothyroidism, 41 (73.2%) had subclinical hypothyroidism and 15 (26.8%) had clinical hypothyroidism. In those with hyperthyroidism, 12 patients (70.6%) had subclinical hyperthyroidism, and five patients (29.4%) had clinical hyperthyroidism. Age, clinical stage, thyroid volume, and V45 were independent risk factors for early radiation-induced hypothyroidism within 1 year after IMRT. Patients aged <47 years, stage III/IV disease, or pre-irradiation thyroid volume < 14 cm3 had higher risks of developing hypothyroidism. CONCLUSION: Primary subclinical hypothyroidism was the most common subtype of early thyroid dysfunction in NPC patients within 1 year after IMRT. Age, clinical stage, thyroid volume, and V45 were independent risk factors for early radiation-induced hypothyroidism in NPC patients.

Assessment of Response to Different Induction Chemotherapy Regimens in Locally Advanced Nasopharyngeal Carcinoma.

Purpose: To compare the short-term treatment response and survival of the three induction chemotherapy (IC) regimens, including gemcitabine and cisplatin (GP), docetaxel and cisplatin (TP), and docetaxel, cisplatin, and fluoropyrimidines (TPF) in locally advanced nasopharyngeal carcinoma (LANPC). Methods: We included stage III-IVA NPC patients who received ≥3 cycles of IC in this study. The chi-square test, multivariate logistic regression analysis, and Kaplan-Meier method were used for statistical analysis. Results: A total of 227 patients were included. The overall response rate (ORR) of the primary nasopharyngeal tumors after IC with GP, TP, and TPF was 91.9%, 83.8%, and 91.7%, respectively (P=0.729), and the ORR of the cervical lymph nodes was 94.6%, 72.3%, and 85.0%, respectively (P<0.001). For the primary nasopharyngeal tumor, there was no significant difference in the ORR among the three IC regimens. For cervical lymph nodes, patients treated with GP had significantly higher ORR compared to those treated with the TP regimen (P=0.014), and comparable ORR was found between TPF and GP regimens (P=0.161). Similar progression-free survival (PFS) (P=0.501) and overall survival (OS) (P=0.504) were found among three IC regimens. There were comparable PFS (P=0.123) and OS (P=0.478) among those with complete response (CR), partial response (PR), and stable disease (SD)/progressive disease (PD) in the primary nasopharyngeal tumors. However, patients who had CR in the primary nasopharyngeal tumor (P=0.014) and the cervical lymph nodes (P=0.022) had better PFS compared to those who had PR or SD/PD. Conclusion: GP and TPF regimens are equivalent to the TP regimen in the response to primary nasopharyngeal tumors after IC, but with better ORR in the cervical lymph nodes than the TP regimen. The response to IC may be a powerful indicator for predicting prognosis and developing individualized follow-up and treatment strategies for LANPC patients.

The addition of radiotherapy to breast-conserving surgery improves survival for elderly patients with early breast cancer.

Purpose: To evaluate whether adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) was associated with better survival among elderly (≥70 years) breast cancer patients with T1-2N0 and estrogen receptor (ER) positive disease. Methods: We included patients who met the inclusion criteria between 2010 and 2014 from the Surveillance, Epidemiology, and End Results program. Patients were subdivided into three groups based on surgery and RT: BCS alone, BCS plus RT, and refusal of RT. The primary outcomes were breast cancer-specific survival (BCSS) and overall survival (OS). Chi-squared tests, Kaplan-Meier method, and Multivariate Cox regression analysis were used for statistical analysis. Propensity score matching (PSM) was performed to minimize the potential selection bias. Results: A total of 26586 patients were included in this analysis. The median follow-up was 66 months. Of these patients, 15591 (58.6%) patients received RT, RT was recommended but not performed due to patient refusal for 1270 (4.8%) patients, and RT was not recommended for 9725 (36.6%) patients. The 5-year BCSS was 98.3% for patients receiving RT, 97.1% for patients refusal of RT, and 96.4% for patients not recommended RT (P<0.001). The 5-year OS was 88.6% for patients receiving RT, 77.6% for patients who refused RT, and 72.1% for patients not recommended RT (P<0.001). Multivariate Cox regression analyses showed that patients who received adjuvant RT after BCS had significantly better BCSS (hazard ratio [HR] 0.523, 95%confidence interval [CI] 0.447-0.612, P<0.001) and OS (HR 0.589, 95%CI 0.558-0.622, P<0.001) compared to those without RT. A total of 7721 pairs of patients were matched successfully between those with and without RT using PSM. The results also showed that patients who received RT after BCS had significantly better BCSS (HR 562, 95%CI 0.467-0.676, P<0.001) and OS (HR 0.612, 95%CI 0.0.575-0.652, P<0.001) compared to those without RT. Conclusions: These data suggest that individual counseling is important for treatment decision-making in elderly breast cancer patients with T1-2N0 and ER-positive disease. Given the relatively lower toxicity of modern RT techniques, adjuvant RT should be recommended in patients with high life expectancy.

The effect of human papillomavirus status on prognosis and local treatment strategies of T1-2N0 oropharyngeal squamous cell cancer.

Purpose: To explore the effect of human papillomavirus (HPV) status on prognosis and further investigate whether human papillomavirus (HPV) status has an impact on the local treatment strategies for T1-2N0 oropharyngeal squamous cell cancer (OPSCC) patients. Methods: Patients diagnosed with T1-2N0 OPSCC between 2010 and 2015 were included from the Surveillance, Epidemiology, and End Results database. Data were analyzed using propensity score matching (PSM), Chi-square test, Kaplan-Meier survival analysis, and Cox multivariable analyses. Results: A total of 1,004 patients were identified, of whom 595 (59.3%) had HPV-related tumors. Of all the patients, 386 (38.4%) and 618 (61.6%) received definitive radiotherapy and radical surgery, respectively. HPV status had no significant effect on local treatment strategies for early-stage OPSCC (P = 0.817). The 3-year cancer-specific survival (CSS) and overall survival (OS) were 89.6 and 80.1%, respectively. Compared to those with HPV-negative diseases, patients with HPV-positive diseases had better CSS and OS. A total of 222 pairs of patients were completely matched after PSM. The results of multivariate Cox regression analysis showed that patients with HPV-positive disease had significantly better CSS (P = 0.001) and OS (P < 0.001) compared to those with HPV-negative tumors. However, local treatment strategy was not associated with survival outcomes after PSM (CSS, P = 0.771; OS, P = 0.440). The subgroup analysis showed comparable CSS and OS between those treated with radical surgery and definitive radiotherapy regardless of HPV status. Conclusions: HPV status is an independent prognostic factor for the survival of stage T1-2N0 OPSCC patients. Local treatment strategies had no significant effect on the survival of early-stage OPSCC regardless of HPV status. Patients with early-stage OPSCC should be informed regarding the pros and cons of definitive radiotherapy or radical surgery.

Causes of Death in Long-Term Nasopharyngeal Carcinoma Survivors.

Purpose: To assess the causes of death (COD) and long-term survival after nasopharyngeal carcinoma (NPC) diagnosis. Methods: Using linked data from the Surveillance, Epidemiology, and End Results program, patients with NPC diagnosed from 1990 to 2010 and followed up >5 years were identified. Chi-squared test, the Kaplan-Meier method, and the Cox proportional hazard model were used for analyses. Results: Among the 3,036 long-term NPC survivors, 1,432 survived for >5-10 years and 1,604 survived for >10 years. The most common COD was primary NPC (36.9%), followed by other causes (28.7%), other cancers (15.3%), cardiac disease (12.9%), and non-malignant pulmonary disease (6.2%). With a median follow-up of 125 months, deaths from NPC decreased with increasing time from diagnosis, while death because of cardiac disease and other causes increased. In those aged <50 years, death due to NPC remained the main COD over time, while cardiopulmonary disease-related death was the leading COD in patients aged ≥50 years. In White patients, death due to NPC decreased, and death due to cardiac disease increased over time. Death from NPC remained significant in Black and Asian patients even 15 years after the diagnosis of NPC, while death due to cardiac disease significantly increased after 9 years of diagnosis in Black patients. Multivariate analyses showed that the independent factors associated with inferior NPC-specific survival were older age, Asians, American Indian/Alaska Native, regional stage, distant stage, and diagnosis in the early years. Conclusions: The probability of death from primary NPC remains significant even 15 years after the NPC diagnosis. Our study advocates continued surveillance for NPC survivors beyond the traditional 5 years. Individualized follow-up strategies are required for patients with NPC of different ages and races.

The Predictive Effect of the 8th AJCC Pathological Prognostic Staging on the Benefit of Postmastectomy Radiotherapy in N2/N3 Breast Cancer.

Background: The role of the 8th American Joint Committee on Cancer (AJCC) pathological prognostic staging (PPS) on treatment-decision making of breast cancer (BC) remains unclear. This study aimed to investigate the predictive effect of the 8th AJCC PPS on the benefit of postmastectomy radiotherapy (PMRT) in N2/N3 BC. Methods: We included women with stage N2/3 BC diagnosed between 2010 and 2018 from the Surveillance, Epidemiology, and End Results database. The effect of PMRT on breast cancer-specific survival (BCSS) was evaluated using the multivariate Cox proportional-hazards models. Results: A total of 13,445 patients were identified, including 10,547 (78.4%) patients treated with PMRT. All patients had reassigned stages based on the 8th AJCC PPS. There were 7102 patients (52.8%) that had stage changed, including 1160 patients (8.6%) were upstaged and 5942 patients (44.2%) were downstaged from the 7th AJCC anatomical staging (AS) to the 8th AJCC PPS. Regarding the 7th AJCC AS, 7603 (56.5%), 948 (7.1%), and 4895 (36.4%) were stage IIIA, IIIB, and IIIC diseases, respectively. Using the 8th AJCC PPS, 3525 (26.2%), 460 (3.4%), 1335 (9.9%), 3457 (25.7%), 2169 (19.1%), and 2100 (15.6%) patients were restaged as IB, IIA, IIB, IIIA, IIIB, and IIIC diseases, respectively. The PPS displayed increased prognostic accuracy and improved model fit with respect to BCSS compared to the 7th AS (C-index, 0.731 vs 0.605, P < 0.001; Akaike Information Criterion, 42141 vs 43118). Regarding the AS, the receipt of PMRT was associated with a better BCSS in those with stage IIIA (P = 0.004), IIIB (P = 0.003), and IIIC (P < 0.001) diseases. Using the PPS, the receipt of PMRT was not associated with a better BCSS among patients with stage IB (P = 0.446), IIA (P = 0.140), and IIB (P = 0.248) disease, while the receipt of PMRT was associated with a better BCSS for those with stage IIIA (P = 0.009), IIIB (P < 0.001), and IIIC (P < 0.001) disease. Conclusion: The 8th AJCC staging provides superior risk stratification and a better tool to predict the benefit of PMRT in N2/3 BC.

Impact of AJCC prognostic staging on prognosis and postmastectomy radiotherapy decision-making in hormone receptor-positive and HER2-positive breast cancer.

BACKGROUND: The role of postmastectomy radiotherapy (PMRT) in patients with node-positive hormone receptor-positive (HoR) and HER2-positive breast cancer (BC) regarding AJCC pathological prognostic staging (PPS) has not been fully determined. This study aimed to validate PPS in patients with node-positive HoR+/HER2+ BC after mastectomy and to investigate the role of PPS on PMRT decision-making in this patient subset. METHODS: Patients diagnosed with BC from the Surveillance, Epidemiology, and End Results database were included. Patients were classified based on the anatomical staging (AS) and PPS. Breast cancer-specific survival (BCSS) was calculated. RESULTS: In total, 6862 patients were included: 4306 (62.8 per cent) patients received PMRT and 2556 (37.2 per cent) patients had not. Compared to AS, PPS downstaged 5260 patients (76.7 per cent) and no patients were upstaged. The C-index was similar between PPS and AS (0.690 versus 0.682; P = 0.346). Regarding AS, patients who received PMRT had significantly better BCSS than those who had not in stage IIIA (P = 0.017) and stage IIIC (P < 0.001) disease, but not in stage IB (P = 0.675), IIA (P = 0.677), IIB (P = 0.100), and IIIB (P = 0.747) disease. Regarding PPS, patients who received PMRT had significantly better BCSS than those who had not in stage IIIA (P = 0.038) and stage IIIB (P = 0.017) disease, but not in stage IA (P = 0.336), IB (P = 0.893), IIA (P = 0.815), and IIB (P = 0.120) disease. PPS might allow approximately 1390 stage III patients (45.0 per cent) in the AS criterion to avoid PMRT. CONCLUSION: PPS does not provide better risk discriminatory ability in predicting prognosis than AS in patients with node-positive HoR+/HER2+ BC after mastectomy. However, PPS is valuable in providing prognostic counselling to patients and may also guide PMRT decision-making.

Distribution, Chemotherapy Use, and Outcome of the 21-Gene Recurrence Score Between Chinese and White breast Cancer in the United States.

PURPOSE: To compare the distribution, chemotherapy-decision making, and prognosis of the 21-gene recurrence score (RS) between Chinese breast cancer (BC) in the United States and White American (WA) BC. METHODS: We identified early-stage and estrogen receptor-positive BC patients diagnosed between 2004 and 2015. Multivariate logistic regression, Kaplan-Meier analysis, and multivariate Cox proportional hazards models were used for statistical analyses. RESULTS: A total of 67,486 patients were identified, including 66,215 (98.1%) WA patients and 1271 (1.9%) Chinese patients. Regarding the RS, 38,894 (57.6%) had low RS, 23,882 (35.4%) had intermediate RS, and 4710 (7.0%) had high RS. A similar distribution of RS was found between WA and Chinese BC (P = .280). The race was not the predictor associated with high RS. Similar trends of chemotherapy use were found in Chinese and WA BC. In WA BC, there were 4.1%, 31.5%, and 72.2% of patients receiving chemotherapy in low, intermediate, and high RS cohorts, respectively (P < .001). The proportion of chemotherapy use was 6.8%, 30.9%, and 74.0% in Chinese BC with low, intermediate, and high RS cohorts, respectively (P < 0.001). The multivariate prognostic analyses indicated that a higher RS was independently associated with an inferior breast cancer-specific survival. Similar trends were found among those with Chinese and WA BC. CONCLUSION: Our results demonstrate similar distribution, chemotherapy use, and outcome of the 21-gene RS between Chinese and WA BC in the United States.

Rare Metastasis to the Submandibular Gland in Oral Squamous Cell Carcinoma.

PURPOSE: In the current recommendation of neck dissection in oral squamous cell carcinoma (OSCC), the submandibular gland (SMG) should also be removed. This study aimed to investigate the incidence and the patterns of SMG involvement in OSCC patients. METHODS: Patients initially diagnosed with OSCC between January 2018 and October 2020 were included. The distribution of lymph nodes metastasis in level IB was analyzed. RESULTS: We included 145 patients who underwent primary surgery and neck dissection in this study. All patients had level IB lymph node dissection and simultaneous removal of the SMG. Of these patients, only one patient (0.7%) had involvement in SMG by directly infiltrating from the primary tumor. A total of 18 positive lymph nodes were found in level IB in 16 patients, and no positive lymph nodes were located in the SMG. There were 6 lymph nodes located in the lateral part of the SMG and 12 lymph nodes located in the anterior of the SMG. Patients with tumors located in the buccal mucosa and N3 stage were the independent predictive factors associated with level IB nodal metastasis. CONCLUSION: Involvement of SMG in OSCC is quite rare. Preservation of the SMG during neck dissection in selected patients with OSCC seems to be feasible and oncologically safe.

Increased risk of cerebrovascular mortality in head and neck cancer survivors aged ≥ 65 years treated with definitive radiotherapy: a population-based cohort study.

BACKGROUND: To investigate the relationship between radiotherapy (RT) and the risk of cerebrovascular mortality (CVM) in head and neck cancer (HNC) survivors aged ≥ 65 years. METHODS: Patients with HNC survivors aged ≥ 65 years diagnosed between 2000 and 2012 were included from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier analysis, Log-rank tests, and Cox proportional-hazards regression models were performed for statistical analyses. RESULTS: We included 16,923 patients in this study. Of these patients, 7110 (42.0%) patients received surgery alone, 5041 (29.8%) patients underwent RT alone, and 4772 (28.2%) patients were treated with surgery and RT. With a median follow-up time of 87 months, 1005 patients died with cerebrovascular disease. The 10-years CVM were 13.3%, 10.8%, and 11.2% in those treated with RT alone, surgery alone, and surgery plus RT, respectively (P < 0.001). The mean time for CVM was shorter in RT alone compared to surgery alone and surgery plus RT (52 months vs. 56-60 months). After adjusting for covariates, patients receiving RT alone had a significantly higher risk of developing CVM compared to those receiving surgery alone (hazard ratio [HR] 1.703, 95% confidence interval [CI] 1.398-2.075, P < 0.001), while a comparable risk of CVM was found between those treated with surgery alone and surgery plus RT (HR 1.106, 95% CI 0.923-1.325, P = 0.274). Similar trends were found after stratification age at diagnosis, gender, tumor location, and marital status. CONCLUSIONS: Definitive RT but not postoperative RT can increase the risk of CVM among older HNC survivors. Long-term follow-up and regular screening for CVD are required for HNC patients who received definitive RT to decrease the risk of CVM.

Biopsy of cervical lymph node does not impact the survival of nasopharyngeal carcinoma.

PURPOSE: The optimal practice regarding cervical lymph node biopsy (CLNB) remains to be defined to provide the best clinical management in nasopharyngeal carcinoma (NPC). This study aimed to investigate the effect of CLNB on the survival of NPC patients. METHODS: Patients diagnosed with NPC from 2004 to 2015 were identified using the Surveillance, Epidemiology, and End Results database. Multivariate logistic regression, Kaplan-Meier method, Cox proportional hazards regression analysis, and propensity score matching (PSM) were used to determine the factors associated with CLNB and prognostic effect of CLNB of NPC. RESULTS: We included 1903 patients in this study. There were 321 (16.9%) and 1582 (83.1%) patients with and without CLNB, respectively. The percentage of CLNB was 19.4% in 2004 and was decreased to 8.6% in 2015 (p = 0.044). Patients diagnosed in later years (p = 0.008), older age (p < 0.001), Chinese (p = 0.002), advanced tumor stage (p < 0.001), and early nodal stage (p = 0.003) were less likely to receive additional CLNB. In patients who received additional CLNB, the 5-years NPC-specific survival (NPCSS) was 83.6%, which was similar to patients without CLNB (80.1%, p = 0.159). In addition, a similar 5-years NPCSS was found between those receiving biopsy or aspiration of regional lymph node and those receiving lymph node resection (p = 0.584). There were 187 pairs of patients who were completely matched using PSM, the multivariate prognostic analyses indicated that the receipt of CLNB was not associated with an inferior outcome in the PSM cohort (p = 0.349). Similar results were found after stratification by the year of diagnosis, race/ethnicity, and histology. CONCLUSION: Additional CLNB is not associated with an inferior survival outcome in NPC. Our study provides a reference for the clinical practice of NPC.

The patterns of distant metastasis and prognostic factors in patients with primary metastatic Ewing sarcoma of the bone.

BACKGROUND: Ewing sarcoma (ES) of bone is accounting for the second most common type of primary bone cancer in children and adolescents. However, the patterns of distant metastasis (DM) and the effect of the sites of DM on survival outcomes were not investigated. AIMS: This study aimed to investigate the patterns of DM and the prognostic factors related to outcomes in primary metastatic ES of the bone. METHODS: Patients who were diagnosed with primary metastatic ES between 2010 and 2018 were identified from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier analysis, log-rank tests, and Cox proportional-hazards regression models were used for statistical analyses. RESULTS: We identified 277 patients in this study and 95.3% of them (n = 264) receiving chemotherapy. A total of 371 sites of DM were observed. Lung was the most common distant metastatic site (n = 182, 49.1%), followed by bone (n = 139, 37.5%), distant lymph node (n = 26, 7.0%), liver (n = 14, 3.8%), and brain (n = 10, 2.7%). Three-year cause-specific survival (CSS) was 56.1% in the entire cohort. Older age (hazard ratio [HR] 2.210, P < 0.001) and bone metastasis (HR 1.903, P = 0.002) were the independent prognostic factors associated with inferior CSS. Similar results were found in those with bone-only metastasis (n = 80) or lung-only metastasis (n = 117), which showed that patients with bone-only metastasis had an inferior CSS compared to those with metastases only to the lung (HR 1.926, P = 0.005). CONCLUSIONS: Lung and bone are the most frequently distant metastatic sites in patients with primary metastatic ES of bone. Bone metastasis is an independent risk factor for inferior survival.

Triple-negative breast cancer outcomes: Does AJCC 8th staging improve chemotherapy decision-making.

PURPOSE: To investigate the effect of the 8th American Joint Committee on Cancer (AJCC) pathological prognostic staging on chemotherapy decision-making for triple-negative breast cancer (TNBC) patients with T1-2N0M0 disease. METHODS: Patients diagnosed with T1-2N0M0 TNBC were retrieved from the Surveillance, Epidemiology, and End Results program. Statistical methods including Kaplan-Meier survival curve, receiver operating characteristics curve, and Cox proportional hazard model. RESULTS: We identified 12,156 patients, including 9371 (77.1%) patients who received chemotherapy. Overall, 57.4% of patients (n = 6975) were upstaged after being reassigned by the 8th AJCC staging. However, the 8th staging of AJCC did not have a greater prognostic value compared to the 7th staging (P = 0.064). The receipt of chemotherapy significantly improved the breast cancer-specific survival for stage T1c and T2 tumors (P < 0.001), but not for stage T1a (P = 0.188) and T1b (P = 0.376) tumors. Using AJCC 8th staging, chemotherapy benefit was only found in stage IIA patients (P = 0.002), but not for stage IA (P = 0.653) and IB (P = 0.492) patients. There were 9564 patients with stage T1c and T2 diseases and 4979 patients with 8th AJCC stage IIA disease. Therefore, approximately half of patients (47.9%, n = 4585) may be safe to omit chemotherapy using the AJCC 8th staging compared to the current chemotherapy recommendation for T1-2N0M0 TNBC. CONCLUSION: The 8th AJCC staging system did not demonstrate the superior discriminatory ability of prognostic stratification than the 7th AJCC staging system in T1-2N0M0 TNBC. However, this new AJCC staging could more accurately predict the chemotherapy benefit, thereby enabling more patients to avoid unnecessary chemotherapy.

Survival Outcomes and Treatment Decision by Human Papillomavirus Status Among Patients With Stage IVC Head and Neck Squamous Cell Carcinoma.

PURPOSE: To investigate the influence of human papillomavirus (HPV) status on survival outcomes and treatment decisions for patients with de novo stage IV head and neck squamous cell cancers (HNSCC). METHODS: Patients initially diagnosed with de novo stage IVC HNSCC between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Cox multivariable analyses were performed to determine prognostic factors associated with head and neck cancers specific survival (HNCSS) and overall survival (OS). RESULTS: We identified 303 patients who received chemotherapy in this study, including 52.5% of them had HPV-positive disease. HPV-positive HNSCC had better HNCSS (P < 0.001) and OS (P < 0.001) compared to those with HPV-negative disease. The results of Cox multivariable analyses showed that HPV-negative status (P = 0.007), N3 stage (P = 0.004), bone metastases (P < 0.001), and lung metastases (P = 0.003) were associated with worse HNCSS. Similar results were found regarding the OS. The sensitivity analyses indicated that HPV-positive HNSCC patients who were treated with radiotherapy had better survival outcomes. However, no survival benefits were found in those with HPV-positive disease receiving surgery. For HPV-negative patients, no survival benefit was observed among those treated with radiotherapy or surgery. CONCLUSIONS: Approximately half of the stage IVC HNSCC patients are HPV-related. The presence of HPV infection appears to be strongly associated with the survival outcome in patients with de novo stage IV HNSCC. Determination of HPV status may help guide clinicians in prognostic assessment and treatment decision-making in this population.

circ-PTK2 (hsa_circ_0008305) regulates the pathogenic processes of ovarian cancer via miR-639 and FOXC1 regulatory cascade.

BACKGROUND: Precise quantification of microRNA is challenging since circulating mRNA and rRNA in the blood are usually degraded. Therefore, it is necessary to identify specific biomarkers for ovarian cancer. This study aimed to investigate candidate circular RNAs (circRNAs) involved in the pathogenic process of ovarian cancer after inhibition of chromodomain helicase DNA binding protein 1-like (CHD1L) and the corresponding mechanism. METHODS: CHD1L mRNA-targeted siRNA was designed and induced a decreased level of CHD1L function in SK-OV-3 and OVCAR-3 cells observed via transwell and wound healing assays and assessment of epithelial-mesenchymal transition (EMT)-related protein expression by immunofluorescence (IF) and western blotting (WB). After decreasing the level of CHD1L, RNA-seq was conducted, and the circRNA expression profiles were obtained. cirRNAs were then selected and validated by PCR together with Sanger sequencing, fluorescent in situ hybridization (FISH), and reverse transcriptase-quantitative PCR (RT-qPCR). Selected circRNA function in vitro was adjusted via interference and overexpression and assessed via transwell assay, tube formation, and EMT-related protein assay by IF and WB; tumor formation in vivo was followed via hematoxylin and eosin (HE) staining and immunohistochemistry of EMT-related proteins. Based on the competing endogenous RNA prediction of circRNA targets, candidate miRNAs were found, and their downstream mRNAs targeted by the selected miRNA were identified and validated by luciferase assay. The functions of these selected miRNA and mRNA were then further investigated through transwell and WB assay of EMT-related proteins. RESULTS: CHD1L was significantly upregulated in ovarian cancer tissues and patients with higher expression of CHD1L had a shorter relapse-free survival (P < 0.001) and overall survival (P < 0.001). Inhibiting the level of CHD1L significantly decreased cell migration and invasion (P < 0.05), increased the expression of epithelial markers, and decreased the expression of mesenchymal markers. Following inhibition of CHD1L expression, RNA-seq was conducted and 82 circRNAs had significantly upregulated expression, while 247 had significantly downregulated expression. The circRNAs were validated by PCR, and hsa_circ_0008305 (circ-PTK2) was selected and further validated by Sanger sequencing, FISH, and RT-qPCR. Circ-PTK2 expression was significantly higher in the ovarian cancer tissues compared with normal ovary tissues (P < 0.001). By regulating the level of circ-PTK2 with siRNA and an overexpression vector, expression of circ-PTK2 was found to be positively correlated to cell migration and invasion. Overexpression of circ-PTK2 enhanced tumor formation and was correlated to expression of EMT pathway markers. Prediction of the target of circ-PTK2 was validated with dual luciferase assay and identified miR-639 and FOXC1 as the valid target of circ-PTK2 and miR-639, respectively. The RNA level of miR-639 was negatively correlated to cell proliferation and migration, whereas the mRNA level of FOXC1 was positively correlated to those processes. miR-639 mimics reversed the function of circ-PTK2 overexpression; however, interference of FOXC1 mRNA also reversed the function of circ-PTK2. CONCLUSIONS: circ-PTK2 is an important molecule in regulating the pathogenic processes of ovarian cancer via the miR-639 and FOXC1 regulatory cascade.

Evaluation of Subjective Sleep Disturbances in Cancer Patients: A Cross-Sectional Study in a Radiotherapy Department.

Background: The factors associated with sleep disturbances in cancer patients remains unclear. This study aimed to explore the prevalence of sleep disorders and predictors associated with sleep disturbance in cancer patients from a radiotherapy department. Methods: Patients with cancers were recruited before the start of radiotherapy from our institution between January 2019 and February 2020. Pittsburgh Sleep Quality Index (PSQI) scale was used to assess sleep quality. Descriptive statistics, Chi-square test, and multivariate logistic regression analysis were used to conduct statistical analysis. Results: A total of 330 eligible patients were included. Of them, 38.3% (n = 127) had the globe PSQI score >7, indicating that they suffered from sleep disorders. Patients with lung cancer (45.2%) were more likely to suffer from sleep disturbance, followed by cervical cancer (43.8%), nasopharyngeal carcinoma (41.7%), esophageal cancer (41.5%), breast cancer (37.7%), and colorectal cancer (30%). With regard to the PSQI components, the mean sleep duration was 8 h, 20.3% (n = 67) of them reported poor subjective sleep quality, 6.1% (n = 20) needed medication to improve sleep, and 53.6% (n = 177) suffered daytime dysfunction. Multivariate logistic regression models showed body mass index (BMI) ≥ 20 kg/m2 [odds ratio (OR) 0.599, 95% confidence interval (CI) 0.329-0.948, P = 0.031] and the receipt of surgery (OR 0.507, 95% CI 0.258-0.996, P = 0.048) were the significant favorable predictors for sleep disturbance, while age, gender, marital status, education level, comorbidity, metastasis status, diagnostic status, and cancer type were not significantly associated with sleep disturbance. Conclusions: Approximately 40% of the cancer patients suffer from sleep disturbance before the start of radiotherapy. Patients with BMI ≥ 20 kg/m2 and receiving surgery are less likely to develop sleep disturbance in comparison with others.

Identification of MEG8/miR-378d/SOBP axis as a novel regulatory network and associated with immune infiltrates in ovarian carcinoma by integrated bioinformatics analysis.

BACKGROUND: To investigate the potential molecular mechanism of ovarian cancer (OC) evolution and immunological correlation using the integrated bioinformatics analysis. METHODS: Data from the Gene Expression Omnibus was used to gain differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Gene and Genome pathway analysis were completed by utilizing the Database for Annotation, Visualization, and Integrated Discovery. After multiple validations via The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) projects, the Human Protein Atlas, Kaplan-Meier (KM) plotter, and immune logical relationships of the key gene SOBP were evaluated based on Tumor Immune Estimation Resource, and Gene Set Enrichment Analysis (GSEA) software. Finally, the lncRNAs-miRNAs-mRNAs subnetwork was predicted by starBase, TargetScan, miRBD, and LncBase, individually. Correlation of expression and prognosis for mRNAs, miRNAs, and lncRNAs were confirmed by TCGA, Gene Expression Profiling Interactive Analysis 2 (GEPIA 2), starBase, and KM. RESULTS: A total of 192 shared DEGs were discovered from the four data sets, including 125 upregulated and 67 downregulated genes. Functional enrichment analysis presented that they were mainly enriched in cartilage development, pathway in PI3 K-Akt signaling pathway. Lower expression of SOBP was the independent prognostic factor for inferior prognosis in OC patients. The downregulation of SOBP enhanced the infiltration levels of B cells, CD8+ T cells, Macrophage, Neutrophil, and Dendritic cells. GSEA also disclosed low SOBP showed a significantly associated with the activation of various immune-related pathways. Finally, we first reported that the MEG8/miR-378d/SOBP axis was linked to the development and prognosis of OC through regulating the cytokines pathway. CONCLUSIONS: Our study establishes a novel MEG8/miR-378d/SOBP axis in the development and prognosis of OC, and the triple subnetwork probably affects the progression of the OC by regulating the cytokines pathway.

The prognostic and predictive value of the 8th American Joint Committee on Cancer (AJCC) staging system among early breast cancer patients aged <50 years.

BACKGROUND: This study respectively analyzed the prognostic value and the role in treatment decision-making [breast-conserving surgery (BCS) + radiotherapy (RT) or mastectomy (MAST)] of the 8th American Joint Committee on Cancer (AJCC) pathological prognostic staging system compared with the 7th AJCC anatomical staging system among early breast cancer patients aged <50 years. METHODS: Patients with T1-2N0M0 breast cancer aged <50 years were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2014. Breast cancer-specific survival (BCSS) was used as the primary endpoint. Chi-squared test, receiver operating characteristics analysis, Kaplan-Meier method, and multivariate Cox proportional models were used to conduct statistical analysis. RESULTS: A total of 22,640 female patients were identified, and 24.4% of them reallocated to new stage groups from the 7th to the 8th AJCC staging. Among them, 46.2% (n=10,450) and 53.8% (n=12,190) of patients received BCS + RT and MAST, respectively. The 8th AJCC staging system was an independent prognostic factor for BCSS. Patients treated with BCS + RT had better BCSS compared to those treated with MAST (P<0.001). According to the 8th AJCC staging, BCS + RT could improve 5-year BCSS compared with MAST in patients with stage IA (P=0.006) and stage IB (P=0.001) diseases, while comparable BCSS was found between the two treatment arms in patients' stage IIA disease (P=0.366). Multivariate analyses replicated similar findings after stratification by the 8th AJCC stages. CONCLUSIONS: In patients with T1-2N0 breast cancer and aged <50 years, the 8th AJCC pathological staging system provides accurate prognostic information than the 7th anatomical staging. BCS + RT is the optimal local management for stage IA and IB diseases, while it is the optional management in stage IIA disease according to the 8th AJCC staging.

Additional radiotherapy to breast-conserving surgery is an optional treatment for de novo stage IV breast cancer: A population-based analysis.

BACKGROUND: We aim to assess the value of locoregional treatment (LRT) including breast-conserving surgery (BCS), mastectomy (MAST), and radiotherapy (RT) in patients with de novo stage IV breast cancer. METHODS: Patients with de novo stage IV breast cancer were retrospectively identified from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. Kaplan-Meier analysis, log-rank tests, propensity score matching (PSM), and the multivariate Cox proportional model were used for statistical analysis. RESULTS: A total of 5798 patients were identified including 849 (14.6%), 763 (13.2%), 2338 (40.3%), and 1848 (31.9%) who received BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively. The proportions of receiving BCS decreased from 35.9% in 2004 to 26.2% in 2014 (p = 0.002), and the probability of patients receiving MAST increased from 64.1% in 2004 to 74.8% in 2014 (p = 0.002). Before PSM, there was a significant difference in breast cancer-specific survival (BCSS) among the treatment arms. Patients who received RT had better BCSS, the 5-year BCSS was 40.5%, 52.3%, 41.5%, and 47.7% in patients treated with BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively (p < 0.001). In the PSM cohort, patients treated with BCS alone had lower 5-year BCSS compared to those treated with BCS+RT (43.9% and 52.1%, p = 0.002). However, there were comparable 5-year BCSS between BCS+RT and MAST alone groups (51.3% and 50.1%, p = 0.872), and BCS+RT and MAST+RT cohorts (51.5% and 55.7%, p = 0.333). Similar results were confirmed in multivariate analysis. CONCLUSIONS: Postoperative RT improves BCSS in patients with de novo stage IV breast cancer, and BCS+RT shows a non-inferior outcome compared to MAST+RT. BCS+RT may be the optimal local management of de novo stage IV breast cancer.