Plasma Circulating Tumor Epstein-Barr Virus for the Surveillance of Cancer Progression in Bone-Only Metastatic Nasopharyngeal Carcinoma.

Background: Plasma Epstein-Barr virus DNA (EBV-DNA) is a sensitive and specific biomarker for nasopharyngeal carcinoma (NPC). We investigated whether longitudinal monitoring of EBV-DNA could accurately detect clinical disease progression in NPC patients with bone-only metastases. Methods: In this retrospective study, a total of 105 patients with bone-only metastatic NPC who were treated with platinum-based first-line chemotherapy were enrolled. Undetectable EBV-DNA after first-line chemotherapy was defined as a biochemical complete response (BCR). The correlation of the EBV-DNA dynamic status with overall survival (OS) and progression-free survival (PFS) was determined by Cox regression. The correlation between non-normalized EBV-DNA period and PFS period was determined. Results: After a median follow-up time of 53.4 months [Interquartile range (IQR): 42.8-80.6], 64 patients had disease progression. Thirty-nine of 105 patients (37.1%) had a BCR at all follow-up time points, and none of these 39 patients had disease progression, corresponding to a negative predictive value (NPV) of 100%. Sixty-six patients had a detectable EBV-DNA during surveillance, with 64 diagnosed as disease progression at the last follow-up, for a positive predictive value (PPV) of 97.0%. Actuarial 3-year OS rates were 45.0% for patients with detectable EBV-DNA during posttreatment surveillance and 100% for patients with undetectable EBV-DNA. Lastly, median lead time between non-normalized EBV-DNA and clinically proven progression was 5.87 ± 0.67 months. Conclusions: Taken together, EBV-DNA provided predictive value for the bone-only metastatic NPC patients. The results should be validated in prospective randomized studies.

The Selection of Treatment Modality for Breast Ductal Carcinoma In Situ: Experience From a Single Institution.

PURPOSE: Although breast conservation surgery(BCS) followed by adjuvant radiotherapy is now the mainstream treatment method for breast ductal carcinoma in situ(DCIS), mastectomy is still performed in some patients who refuse to undergo radiation. However, the most effective treatment method for these patients is still unknown. In the current study, we aimed to compare the survival rates between mastectomy and BCS plus adjuvant radiotherapy in patients with DCIS. MATERIALS AND METHODS: We performed a retrospective study of 333 patients with DCIS from May 2004 to December 2016. There were 209 patents who were treated with BCS and adjuvant radiotherapy, while the remaining of 124 patients underwent mastectomy. The disease-free survival (DFS) and local recurrence-free survival(LRFS) rates were compared between the 2 treatment groups. Cox proportional hazards regression was performed to explore factors associated with DFS and LRFS. RESULTS: The 10-year local recurrence(LR) rates in the mastectomy and BCS plus adjuvant radiotherapy groups were 2.6% and 7.5%, respectively. There was no difference in the LR rate between the 2 groups. Furthermore the DFS rate was also similar between the mastectomy and BCS plus adjuvant radiotherapy groups. Based on the multivariable analysis, age and tumor grade were significantly correlated with the LRFS and DFS rates. In the subgroup analysis based on the factors of age and tumor grade, patients with a tumor grade of III who underwent mastectomy had better LRFS and DFS rates compared to those who received BCS plus radiotherapy. CONCLUSION: In patients with DCIS, the long-term efficacy was similar between mastectomy and BCS followed by adjuvant radiotherapy. However, in the subgroup of patients with grade III tumors, mastectomy seems to offer a better LRFS and DFS than BCS plus radiotherapy.

Large Tumor Size is an Indicator for the Timely Administration of Adjuvant Radiotherapy in Luminal Breast Cancer with Positive Lymph Node.

PURPOSE: The optimum timing of adjuvant radiotherapy for breast cancer patients who had undergone surgery remains unclear. The present study aimed to identify the clinical factors which could assist the selecting of time interval (TI) between surgery and adjuvant radiotherapy in luminal breast cancer with lymph node metastasis. PATIENTS AND METHODS: This retrospective study included 1054 luminal breast cancer patients with lymph node metastasis, diagnosed between May 2004 and December 2014, and treated with surgery followed by adjuvant therapy. Overall survival (OS) and disease-free survival (DFS) were compared between patients in the short and long TI groups. Multivariate analysis was performed to examine clinical factors associated with DFS. Subgroups analysis was further performed based on the significant predictors of DFS to explore the association of TI and tumor prognosis. RESULTS: For the whole group of patients, there was no difference in OS and DFS between patients with long and short TI. Multivariate analysis showed that age, N stage and tumor size were significant predictors of DFS. Subgroup analysis demonstrated that neither age nor N stage were informative in TI selection; in contrast, in patients with large tumors, a short TI was associated with better DFS than a long TI. In patients with small tumors, there was no significant association between TI and tumor prognosis. In the multivariable analysis, TI was independent predictor of DFS and local recurrence-free survival in patients with large tumors. CONCLUSION: Large tumor size is an indicator for the timely administration of adjuvant radiotherapy in luminal breast cancer with positive lymph node.

Sarcomatoid Carcinoma in the Head and Neck: A Population-Based Analysis of Outcome and Survival.

OBJECTIVES: To characterize sarcomatoid cell carcinoma (SaC) in head and neck, explore the value of radiotherapy (RT) and chemotherapy, and build a nomogram to predict the prognosis. STUDY DESIGN: Retrospective cohort study. METHODS: In total, 559 patients diagnosed with head and neck SaC from 2004 to 2015 were included from the Surveillance, Epidemiology, and End Results program. All the cases were divided into training (N = 313) and validation (N = 246) cohorts according to the year of diagnosis. The cases were analyzed on the age, site, sex, race, T stage, N stage, M stage, surgery, RT, and chemotherapy. Cancer-specific survival (CSS) and overall survival (OS) were compared among disease-related categories. The parameters significantly correlated with CSS were used to construct a nomogram. RESULTS: The multivariate analysis showed that age, T stage, N stage, and M stage were significantly correlated with CSS and OS. Overall, RT was correlated with improved CSS for Stage T3-4 and Stage N1-3. The subgroup analysis showed that RT was correlated with CSS in the Stage N1-3 patients after surgery while chemotherapy indicated an improved survival for Stage T3-4 and N1-3 patients without surgery. The prognostic nomogram was constructed and had a powerful discriminatory ability with the C-index of CSS: 0.711. CONCLUSION: Late-stage head and neck SaC patients unfit for surgery need comprehensive treatment based on chemotherapy, and patients with node metastasis require adjuvant RT after surgery. Generally, RT might improve the survival of late-stage patients. A reliable and powerful nomogram was established that can provide an individual prediction of CSS for head and neck SaC. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E489-E499, 2021.

Identifying Risk Factors for Regional Recurrence in Early-Stage Breast Cancer with pT1-2 and Negative Sentinel Lymph Node Biopsy.

BACKGROUND: Due to the low rate of regional recurrence (RR) in early-stage breast cancer with pT1-2 and negative sentinel lymph node biopsy (SLNB), no regional therapy is suggested for them. However, whether there is a subset of patients who were with high risk of regional failure and may benefit from regional treatment is still unknown. The current study was designed to identify the patients with high risk of RR, thereby providing clues for enhanced regional therapy. METHODS: We analyzed a total of 1124 breast cancer patients with pT1-2N0 from May 2004 to Dec 2014. All the patients were treated with breast-conservation surgery (BCS) and adjuvant whole-breast radiotherapy. The regional recurrence-free survival (RRFS), local regional recurrence-free survival (LRRFS), disease-free survival (DFS) and overall survival (OS) were assessed by using the Kaplan-Meier method. Cox proportional hazards regression was performed to detect factors in predicting the RRFS. RESULTS: In multivariable analysis, both T stage and molecular type were significant predictors of RRFS. Patients with T2 stage had a lower RRFS than those with T1stage. Triple-negative patients were more likely to suffer regional failure than the patients with other molecular types. The two predictors were then employed to divide all the patients into three groups based on the risk level of RR. Patients with both T2 and triple-negative molecular type had the lower RRFS, LRRFS, DFS and OS than the patients with one or no risk factor. CONCLUSION: For early-stage breast cancer patients with negative SLNB, those who were with both T2 stage and triple-negative molecular type had a high rate of RR and enhance regional therapy may be needed for them.

Selective use of concurrent chemotherapy in elderly cervical cancer patients treated with definitive radiotherapy: experience from two institutions.

Background: Whether concurrent chemotherapy could bring about better oncological outcomes in elderly patients receiving definitive radiotherapy is still unknown. So, the purpose of this study was to find out whether it is essential for elderly patients to undergo concurrent chemotherapy. Methods: We performed a retrospective study of 246 elderly cervical cancer patients who were treated with definitive radiotherapy or chemo-radiation between August 2004 and August 2015. All patients were divided into two groups according to whether they were receiving concurrent chemotherapy or not. Overall survival (OS) and disease-free survival (DFS) were compared between the two groups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival, and distant metastasis-free survival (DMFS). Results: The 5-year OS in the radiotherapy and chemo-radiation groups were 72.89% and 82.25%, respectively. A significant difference was found between the two groups (P=0.016). The 5-year DFS in the radiotherapy and chemo-radiaton groups were 58.19% and 75.52%, respectively, also with a significant difference between the two groups (P=0.028). Further subgroup analysis showed that in patients with negative lymph nodes, there were no differences in both OS and DFS between patients who did and did not receive concurrent chemotherapy. However, in patients with positive lymph nodes, patients who received concurrent chemotherapy acquired better OS and DFS than those who did not. Multivariable analysis showed that concurrent chemotherapy was an independent predictor of DFS and DMFS. Conclusion: Concurrent chemotherapy could improve oncological outcomes in elderly cervical cancer patients with positive lymph nodes, but not in those with negative lymph nodes.

Molecular detection of epithelial-mesenchymal transition markers in circulating tumor cells from pancreatic cancer patients: Potential role in clinical practice.

AIM: To evaluate the clinical properties of three subpopulations of circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: We identified CTCs for expression of the epithelial cell marker cytokeratin or epithelial cell adhesion molecule (EpCAM) (E-CTC), the mesenchymal cell markers vimentin and twist (M-CTC), or both (E/M-CTC) using the CanPatrol system. Between July 2014 and July 2016, 107 patients with PDAC were enrolled for CTC evaluation. CTC enumeration and classification were correlated with patient clinicopathological features and outcomes. RESULTS: CTCs were detected in 78.5% of PDAC patients. The number of total CTCs ranged from 0 to 26 across all 107 patients, with a median value of six. CTC status correlated with lymph node metastasis, TNM stage, distant metastasis, blood lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR). Kaplan-Meier survival analysis showed that patients with ≥ 6 total CTCs had significantly decreased overall survival and progression-free survival compared with patients with < 6 total CTCs. The presence of M-CTCs was positively correlated with TNM stage (P < 0.01) and distant metastasis (P < 0.01). Additionally, lymphocyte counts and NLR in patients without CTCs were significantly different from those in patients testing positive for each CTC subpopulation (P < 0.01). CONCLUSION: Classifying CTCs by EMT markers helps to identify the more aggressive CTC subpopulations and provides useful evidence for determining a suitable clinical approach.

ß-Elemene Inhibits Human Sperm Function by Affecting Sperm Vitality and Intracellular Calcium.

BACKGROUND/AIMS: ß-Elemene is a bioactive sesquiterpene compound that exhibits a potent anti-tumor effect and is used in various clinical applications. However, little is known about its effect on the male reproductive system. The objective of this study was to investigate the in vitro actions of ß-elemene on human sperm function and elucidate the underlying mechanism. METHODS: The cytotoxicity of ß-elemene toward MCF-10A, MDA-MD-231, and A549 cells was evaluated with cell proliferation and colony formation assays. Additionally, human sperm were treated with different concentrations (0, 10, 20, 40, 80, 160, and 320 µM) of ß-elemene in vitro. The characteristics in human sperm essential for fertilization, including vitality, motility, capacitation, acrosome reaction, responsiveness to progesterone, and intracellular calcium concentration ([Ca2+]i) were examined with a computer-assisted sperm analysis system, chlortetracycline staining, and a fluorescent Ca2+ indicator. RESULTS: A comprehensive evaluation of sperm motility, especially hyperactivated motility, revealed that treatments with 40-320 µM ß-elemene decreased human sperm vitality, motility (total motility, progressive motility, and curvilinear velocity), and penetrating ability in a dose-dependent manner, but were non-toxic or minimally toxic toward MCF-10A, MDA-MD-231, and A549 cells. Although 10 and 20 µM ß-elemene did not affect sperm vitality and motility, these concentrations increased the spontaneous acrosome reaction and inhibited progesterone-induced sperm functions by affecting sperm [Ca2+]i. CONCLUSION: These results suggest that ß-elemene inhibits human sperm function by affecting sperm vitality and [Ca2+]i. These observations must be considered when using ß-elemene to treat cancer patients who may wish to preserve their fertility.

The Selection of Time Interval Between Surgery and Adjuvant Therapy in Early Stage Cervical Cancer.

OBJECTIVES: The optimal interval between surgery and adjuvant treatment has not yet been found in cervical cancer. And whether patients with different FIGO stage should choose different interval is unknown. The purpose of this study was to evaluate whether interval has a different effect on oncologic outcome for patients with different tumor stages. METHODS: We performed a retrospective study of 226 cervical cancer patients who were treated by surgery and adjuvant therapy from May 2005 to August 2015. All patients were divided into 2 groups according to the interval of 5 weeks. Overall survival (OS) and disease-free survival (DFS) were compared between patients with interval shorter and longer than 5 weeks in the whole group and subgroups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival and distant metastasis-free survival for patients with stage IB2-IIA. RESULTS: For patients with stage IA2-IB1, the 5-year OS and DFS were similar between groups of short and long interval with also the comparable results of local and distant failure. For patients with IB2-IIA, both the OS and DFS in the short-interval group were higher than that in the long-interval group. Besides, the rates of local recurrence were found higher in the group of long interval compared with short interval. Multivariable analysis indicated that time interval was an independent predictor of DFS and local recurrence-free survival for patients with stage IB2-IIA. CONCLUSIONS: In cervical cancer patients, time interval between surgery and adjuvant therapy may have different effects on the prognosis in different FIGO stages.

Outcomes of Induction Chemotherapy Plus Intensity-Modulated Radiotherapy (IMRT) Versus IMRT Plus Concurrent Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma: A Propensity Matched Study.

PURPOSE: It deserves investigation whether induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) is inferior to the current standard of IMRT plus concurrent chemotherapy (CC) in locoregionally advanced nasopharyngeal carcinoma. METHODS: Patients who received IC (94 patients) or CC (302 patients) plus IMRT at our center between March 2003 and November 2012 were retrospectively analyzed. Propensity-score matching method was used to match patients in both arms at equal ratio. Failure-free survival (FFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: In the original cohort of 396 patients, IC plus IMRT resulted in similar FFS (P = .565), OS (P = .334), DMFS (P = .854), and LRFS (P = .999) to IMRT plus CC. In the propensity-matched cohort of 188 patients, no significant survival differences were observed between the two treatment approaches (3-year FFS 80.3% vs 81.0%, P = .590; OS 93.4% vs 92.1%, P = .808; DMFS 85.9% vs 87.7%, P = .275; and LRFS 93.1% vs 92.0%, P = .763). Adjusting for the known prognostic factors in multivariate analysis, IC plus IMRT did not cause higher risk of treatment failure, death, distant metastasis, or locoregional relapse. CONCLUSIONS: IC plus IMRT appeared to achieve comparable survival to IMRT plus CC in locoregionally advanced nasopharyngeal carcinoma. Further investigations were warranted.

[Whole brain radiation therapy plus temozolomide in the treatment of brain metastases from non small cell lung cancer: a meta-analysis].

OBJECTIVE: To explore the efficacy and safety of whole brain radiation therapy (WBRT) plus temozolomide (TMZ) versus WBRT alone in the treatment of brain metastases from non-small cell lung cancer (NSCLC) through a meta-analysis. METHODS: All previously published and some unpublished studies were comprehensively searched from the databases of MEDLINE, EMBASE, Cochrane Library and CBM, etc. The meta-analysis included all randomized controlled trials (RCTs) to compare WBRT plus TMZ with WBRT alone in treatment of brain metastases from NSCLC. The primary meta-analysis was based upon objective remission (OR) and toxicity and the second overall survival (OS). RESULTS: Four RCTs identified by two reviewers were included. There was significant improvement for the WBRT + TMZ group in OR rate (RR = 1.55, P = 0.003); but without significant improvement in OS (P = 0.69). Meanwhile, WHO grade III/IV hematologic toxicity of myelosuppression increased in the WBRT + TMZ group (RR = 2.47, P = 0.008), but without significant difference in gastrointestinal toxicity (P = 0.14). CONCLUSIONS: For the treatment of brain metastases from NSCLC, the combined therapy of WBRT plus TMZ improves OR, but without significant improvement in OS. And the incidence of myelosuppression is elevated. Future large-scale, high-quality and prospective phase III RCTs are needed to confirm the clinical efficacy and safety of WBRT plus TMZ.

Phase I clinical trial of nasopharyngeal radiotherapy and concurrent celecoxib for patients with locoregionally advanced nasopharyngeal carcinoma.

We evaluated the incidence of acute toxicity of concurrent cyclooxygenase-2 inhibitor (celecoxib) plus radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Thirty-four patients received an accumulated radiation dose of 72-76Gy in 36-38 fractions to the primary lesion and 60Gy in 30 fractions to cervical lymph-node lesions. Palpable residual nodes were boosted to 70Gy at the 90% isodose level with an electron field. Celecoxib was administered at escalating doses of 400, 600, and 800mg/day, starting 3days before the first fraction of radiotherapy and continuing throughout the course of radiotherapy. The majority of toxicities were grade 1, with mucositis and weight loss most frequently observed (28 of 34, 82.4%), followed by dermatitis (27 of 34, 79.4%) and otitis (14 of 34, 41.2%). The toxicities were not related to celecoxib dose (all P>0.05). Stomach pain was considered related to celecoxib, which developed in 2 patients at doses of 400mg and 800mg/day. No grade-3 or -4 toxicities or episodes of toxic death occurred. The tumors in 31 patients (31/34, 91.2%) showed a complete response, and 3 patients (3/34, 8.8%) had partial responses. The actuarial local progression-free survival was 96.6% at 1year, and the 2year overall survival rate was 84.6%. Celecoxib can be safely administered concurrently with nasopharyngeal radiotherapy at doses up to 800mg/day. The tumors responded well to treatment warranting further assessment in a phase II trial.

Efficacy and adverse effects of transdermal fentanyl and sustained-release oral morphine in treating moderate-severe cancer pain in Chinese population: a systematic review and meta-analysis.

BACKGROUND: Previous meta-analysis suggested that transdermal fentanyl was not inferior to sustained-release oral morphine in treating moderate-severe cancer pain with less adverse effects. Now, we updated the data and performed a systematic review. METHODS: Updated cohort studies on transdermal fentanyl and oral morphine in the treatment of cancer pain were searched in electronic databases including CBMdisc, CNKI, VIP, Medline, EMBASE and Cochrane Library. Primary end points assessed by meta-analysis were remission rate of pain and incidence of adverse effects. Quality of life was assessed by systematic review, which was the second end point. RESULTS: 32 cohort studies, which included 2651 patients, were included in present study. The remission rate in transdermal fentanyl group and sustained-release oral morphine group were 86.60% and 88.31% respectively, there was no significant difference [RR = 1.13, 95% CI (0.92, 1.38), P = 0.23]. Compared with oral morphine group, there were less adverse effects in terms of constipation [RR = 0.35, 95% CI (0.27, 0.45), P < 0.00001], nausea/vomiting [RR = 0.57, 95% CI (0.49, 0.67), P < 0.00001], and vertigo/somnolence [RR = 0.59, 95% CI (0.51, 0.68), P < 0.00001] in transdermal fentanyl group. Six of selected trials supported either transdermal fentanyl or sustained-release oral morphine improved QOL of cancer patients and one of them showed more patients got better QOL after sustained-release oral morphine transferred to transdermal fentanyl. CONCLUSIONS: Our study showed again that both transdermal fentanyl and oral morphine had the same efficacy in the treatment of moderate-severe cancer pain in Chinese population, but the former might have less adverse effects and better quality of life.

Gemcitabine-based cytotoxic doublets chemotherapy for advanced pancreatic cancer: updated subgroup meta-analyses of overall survival.

OBJECTIVE: Previous meta-analyses showed a survival advantage with gemcitabine (GEM)-based combinations over GEM in advanced pancreatic cancer. Therefore, it would be valuable to explore the specific active regimens based on a subgroup meta-analysis. METHODS: Updated data by comprehensive search of the literature from databases and conference proceedings. Subgroup meta-analysis compared GEM with GEM-based doublets chemotherapy in terms of 6-month overall survival (OS) and 1-year OS. RESULTS: Eighteen randomized controlled trials with 4237 patients were included, which were divided into five subgroups: GEM/capecitabine, GEM/cisplatin, GEM/5-fluorouracil, GEM/irinotecan and GEM/oxaliplatin. In each subgroup, risk ratios (RRs) for 6-month OS were 0.85 (P = 0.04), 0.99 (P = 0.88), 0.95 (P = 0.46), 1.03 (P = 0.77) and 0.80 (P = 0.001), respectively, and RRs for 1-year OS were 0.94 (P = 0.14), 0.99 (P = 0.75), 0.96 (P = 0.19), 1.00 (P = 0.97) and 0.93 (P = 0.05), respectively. A meta-analysis of the trials with adequate information on performance status (PS) was performed in four trials with 1325 patients. Patients with a good PS did not show a survival benefit when receiving combination chemotherapy. RRs for 6-month and 1-year OS were 0.82 (P = 0.18) and 0.93 (P = 0.08). In contrast, application of combination chemotherapy to patients with a poor PS appeared to be harmful. RRs were 1.17 (P = 0.04) for 6-month OS and 1.09 (P = 0.04) for 1-year OS. CONCLUSIONS: The meta-analysis indicated a significant survival benefit when GEM was either combined with capcitabine or oxaliplatin. On the basis of a preliminary subgroup analysis, pancreatic cancer patients with a poor PS appeared to have a worse survival benefit from GEM-based cytotoxic doublets.