Platycodon D reduces obesity and non-alcoholic fatty liver disease induced by a high-fat diet through inhibiting intestinal fat absorption.

Background: Platycodin D (PD) has been reported to treat metabolic diseases, including non-alcoholic fatty liver disease. In addition, platycodin D has been reported to activate intestinal 5'AMP-activated protein kinase (AMPK) phosphorylation levels, thereby reducing lipid absorption. Therefore, the aim of this study is to explore whether PD activation of intestinal AMPK and reduced lipid absorption can improve non-alcoholic fatty liver disease. Methods: Clean-grade male C57/BL mice were fed a high-fat diet (HFD) (containing 60% calories) for 16 weeks, and oral PD (10 mg/kg/day) was administered at the same time. The liver and intestines were the collected, and the intestines were tested. The expressions of lipid absorption genes (CD36, NPC1L1, and ApoB), the serum total triglyceride (TG) and total cholesterol (TC) levels in the intestines and livers, the fecal free fatty acid (FFA) levels, and the expression of AMPK phosphorylated proteins in the intestines were examined using Western blot analyses. The lipid distribution in the livers, intestines, and fat was detected using Oil Red O and hematoxylin and eosin (H&E) staining. A colon cancer cell line (Caco2) was used to confirm the effect of PD on the cellular lipid uptake in vitro. In addition, serum inflammatory factors and liver enzymes were measured to clarify the impact of PD on the circulation of metabolic syndrome. Leptin-deficient mice (OB) were then used to further explore the improvement of PD on body weight and blood lipids. Results: PD had a very significant therapeutic or preventive effect on metabolic syndrome and fatty liver induced by a high-fat diet. PD improved body weight, insulin sensitivity, and glucose tolerance in mice fed a high-fat diet and also prevented non-alcoholic fatty liver disease, reduced blood lipid levels, and increased fecal lipid excretion. In addition, PD reduced lipid absorption by activating the intestinal AMPK protein, which may have involved the inhibition of the gene expression levels of intestinal lipid absorption genes (CD36, NPC1L1, and ApoB). The combined effect of these factors improved hepatic lipid accumulation and lipid accumulation in adipose tissue. It was further found that PD also improved the body weights and blood lipid levels of leptin-deficient mice (OB) mice. Conclusion: PD had a very strong therapeutic effect on mice under a high-fat diet. PD reduced high-fat diet-induced obesity and non-alcoholic fatty liver disease by inhibiting intestinal fat absorption.

Penpulimab, an anti-PD-1 antibody, for heavily pretreated metastatic nasopharyngeal carcinoma: a single-arm phase II study.

Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR) per RECIST (version 1.1), as assessed by an independent radiological review committee. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). One hundred thirty patients were enrolled and 125 were efficacy evaluable. At the data cutoff date (September 28, 2022), 1 patient achieved complete response and 34 patients attained partial response. The ORR was 28.0% (95% CI 20.3-36.7%). The response was durable, with 66.8% still in response at 9 months. Thirty-three patients (26.4%) were still on treatment. The median PFS and OS were 3.6 months (95% CI = 1.9-7.3 months) and 22.8 months (95% CI = 17.1 months to not reached), respectively. Ten (7.6%) patients experienced grade 3 or higher irAEs. Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development as third-line treatment of metastatic NPC.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Long-term survival outcomes and immune checkpoint inhibitor retreatment in patients with advanced cervical cancer treated with camrelizumab plus apatinib in the phase II CLAP study.

BACKGROUND: Camrelizumab plus apatinib have demonstrated robust antitumor activity and safety in patients with advanced cervical cancer (CLAP study; NCT03816553). We herein present the updated long-term results of the CLAP study and explore potential biomarkers for survival. The outcomes of patients who underwent immune checkpoint inhibitor (ICI) retreatment were also reported. METHODS: In this phase II trial, eligible patients received camrelizumab 200 mg intravenously every two weeks and apatinib 250 mg orally once daily in 4-week cycles for up to two years. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. RESULTS: Between January 21 and August 1, 2019, a total of 45 patients were enrolled. Data were analyzed as of July 31, 2023, representing > 48 months since treatment initiation for all patients. Nine (20.0%) patients completed the 2-year study. The median duration of response (DOR) was 16.6 months, and 45.0% of patients achieved a DOR of ≥ 24 months. The 12-month progression-free survival (PFS) rate was 40.7% (95% confidence interval [CI], 25.2-55.6), with an 18-month PFS rate of 37.8% (95% CI, 22.7-52.8). The median overall survival (OS) was 20.3 months (95% CI, 9.3-36.9), and the 24-month OS rate was 47.8% (95% CI, 31.7-62.3). Age > 50 years, programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 (versus [vs.] < 1), CPS ≥ 10 (vs. < 1), high tumor mutational burden, and PIK3CA mutations were associated with improved PFS (hazard ratio [HR] < 1) and longer OS (HR < 1). Eight patients who initially responded in the CLAP trial but later experienced disease progression were retreated with ICIs. Among them, 2 (25.0%) achieved a partial response, while 5 (62.5%) had stable disease. Notably, four patients who received retreatment with ICIs survived for more than 45 months. No new safety signals were identified in the present study. CONCLUSION: Long-term survival follow-up data demonstrated that camrelizumab plus apatinib has robust, sustained, and durable efficacy in patients with advanced cervical cancer who progress after first-line platinum-based chemotherapy. No new safety signals were noted with long-term treatment.

Efficacy and safety of sintilimab plus albumin-bound-paclitaxel in recurrent or metastatic cervical cancer: a multicenter, open-label, single-arm, phase II trial.

Background: Sintilimab is an antibody against programmed cell death protein 1. We assessed the efficacy and safety of sintilimab plus albumin-bound (nab)-paclitaxel for the treatment of recurrent or metastatic cervical cancer. Methods: This multicenter, open-label, single-arm, phase II study (ClinicalTrials.gov identifier NCT04341883) enrolled patients with recurrent or metastatic cervical cancer who progressed after at least one line of systemic therapy. The patients received sintilimab 200 mg and nab-paclitaxel 260 mg/m2 body surface area every 3 weeks. The primary endpoint was objective response rate (ORR) assessed by investigators per Response Evaluation Criteria in Solid Tumors version 1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety. Findings: From January 13, 2020 to February 21, 2022, 27 patients were enrolled and received treatment. Median patient age was 50 years (range, 34-68 years). By data cut-off (May 22, 2022), in intention-to-treat population, ORR was 44.4% (95% CI, 24.4%-64.5%). The disease control rate was 88.9% (95% CI, 70.8%-97.6%). Median PFS was 5.2 months (95% CI, 2.7-7.7 months). Median DoR was 3.8 months (95% CI, 0.7-6.9 months), and median OS was 13.1 months (95% CI, 5.8-20.4 months). Treatment-related grade 3 or 4 adverse events (AEs) occurred in 44.4% of the patients, and the most common AEs were decreased neutrophil count (22.2%), decreased white blood cell count (14.8%), and anemia (7.4%). The most common potential immune-related AEs were grade 1-2 hypothyroidism (18.5%), neutropenia (11.1%), and rash (7.4%). Interpretation: Sintilimab plus nab-paclitaxel treatment shows promising antitumor activity and manageable toxicity in patients with advanced cervical cancer. Larger randomized controlled trials are required for validation. Funding: Innovent Biologics Co., Ltd.; Csps Holdings Co., Ltd.

Treating radiation­related nasopharyngeal necrosis with endostar in patient with nasopharyngeal carcinoma: A report of two cases and a literature review.

Radiation-related nasopharyngeal necrosis (RRNN) is a rare and often fatal complication in patients with nasopharyngeal carcinoma (NPC). Currently, no standard treatments are recommended for RRNN. The effects of traditional conservative treatments are suboptimal, and surgery for RRNN cannot be performed by inexperienced doctors. In the present study, the use of Endostar in two patients with RRNN was evaluated. Two patients with RRNN were treated at the Department of Oncology, Panyu Central Hospital (Guangzhou, China). Endostar was administrated (15 mg/day from day 1 to day 7, every three weeks) intravenously for four and seven cycles in a male and a female patient, respectively. The effects of Endostar were assessed using magnetic resonance imaging (MRI) and a nasopharyngoscope. The symptoms of RRNN in both patients were relieved after treatment with Endostar. MRI and nasopharyngoscope analysis revealed that necrosis of the nasopharynx was substantially decreased and nasopharyngeal ulcers were healed. Endostar has the potential to be a novel, effective therapy for the treatment of patients with RRNN. However, clinical trials are required to confirm the results of the present study.

Efficiency and toxicity of nab-paclitaxel and camrelizumab in the second or above line treatment of advanced non-small cell lung cancer: a retrospective cohort study.

Background: Paclitaxel-based chemotherapy represented by nanoparticle albumin-bound paclitaxel (nab-ptx) combined with programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has become the standard model for the 1st treatment of advanced non-small cell lung cancer (NSCLC) with negative driver genes (such as EGFR, ALK, etc.), indicating that nab-ptx and PD-1/PD-L1 inhibitors are synergistic. Considering PD-1/PD-L1 inhibitors alone or chemotherapy single has limited efficiency in the 2nd line or above of NSCLC, so it is of great significance to explore the combination of PD-1/PD-L1 inhibitors and nab-ptx to further improve the therapeutic efficiency in such field. Methods: We retrospectively collected the date of these advanced NSCLC patients who accept the combination treatment of PD-1/PD-L1 inhibitor and nab-ptx in the 2nd or above line. We further analysed baseline clinical characteristics, therapeutic efficacy, treatment-related adverse events (AEs) and followed up survival. The main parameters of the study were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and AEs. Results: A total of 53 patients were enrolled in this study. The preliminary results indicated that the ORR of the combination of camrelizumab and nab-ptx was about 36% in the 2nd or above line of NSCLC, with 19 cases of partial response (PR), 16 of stable disease (SD), and 18 cases of progressive disease (PD); the mean PFS and OS were 5 months and 10 months, respectively. Further subgroup analysis demonstrated that the expression of PD-L1 level and the decrease of regulatory T cell (Treg) correlated with the efficiency. the main adverse reactions were neuropathy, bone marrow suppression, fatigue, and hypothyroidism, most of which were mild and tolerable, indicating such regimen was higher efficiency and lower cytotoxicity for NSCLC. Conclusions: The combination of nab-ptx and camrelizumab shows promising efficiency and lower toxicities for advanced NSCLC in the 2nd or above line treatment. The mechanism of action may be related to depleting Treg ratio; such a regimen may have the potential to become an effective treatment approach for NSCLC. However, due to the limitation of sample size, the real value of this regimen needs to be further confirmed in the future.

Treatment options for recurrent platinum-resistant ovarian cancer: A systematic review and Bayesian network meta-analysis based on RCTs.

Background: There are a variety of treatment options for recurrent platinum-resistant ovarian cancer, and the optimal specific treatment still remains to be determined. Therefore, this Bayesian network meta-analysis was conducted to investigate the optimal treatment options for recurrent platinum-resistant ovarian cancer. Methods: Pubmed, Cochrane, Embase, and Web of Science were searched for articles published until 15 June 2022. The outcome measures for this meta-analysis were overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of Grade 3-4. The Cochrane assessment tool for risk of bias was used to evaluate the risk of bias of the included original studies. The Bayesian network meta-analysis was conducted. This study was registered on PROSPERO (CRD42022347273). Results: Our systematic review included 11 RCTs involving 1871 patients and 11 treatments other than chemotherapy. The results of meta-analysis showed that the overall survival (OS) was the highest in adavosertib + gemcitabine compared with conventional chemotherapy, (HR=0.56,95%CI:0.35-0.91), followed by sorafenib + topotecan (HR=0.65, 95%CI:0.45-0.93). In addition, Adavosertib + Gemcitabine regimen had the highest PFS (HR=0.55,95%CI:0.34-0.88), followed by Bevacizumab + Gemcitabine regimen (HR=0.48,95%CI:0.38-0.60) and the immunotherapy of nivolumab was the safest (HR=0.164,95%CI:0.312-0.871) with least adverse events of Grades 3-4. Conclusions: The results of this study indicated that Adavosertib (WEE1 kinase-inhibitor) + gemcitabine regimen and Bevacizumab + Gemcitabine regimen would be significantly beneficial to patients with recurrent platinum-resistant ovarian cancer, and could be preferred for recurrent platinum-resistant ovarian cancer. The immunotherapeutic agent, Nivolumab, is of considerable safety, with a low risk for grade-III or IV adverse events. Its safety is comparable to Adavosertib + gemcitabine regimen. Pazopanib + Paclitaxel (weekly regimen), Sorafenib + Topotecan/Nivolumab could be selected if there are contraindications of the above strategies. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022347273.

Weekly versus triweekly cisplatin-based concurrent chemoradiotherapy for nasopharyngeal carcinoma: a systematic review and pooled analysis.

Background: Weekly and triweekly cisplatin-based concurrent chemoradiotherapy (CCRT) have been used in the treatment of nasopharyngeal carcinoma (NPC). Objective: This study aimed to compare the benefits and risks between the two treatments. Methods: We systematically searched electronic databases for prospective and retrospective clinical studies of NPC patients who received weekly compared with triweekly cisplatin-based CCRT. The primary endpoints comprised overall, failure-free, distant metastasis-free, and locoregional recurrence-free survivals (OS, FFS, DMFS, and LRFS). Secondary endpoints were toxicities. Results: Six studies were included in the systematic review, of which four with 1515 NPC patients were eligible for further pooled analysis. There were no significant differences between weekly and triweekly groups in terms of 5-year OS (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.51-1.79), FFS (OR 1.09, 95% CI 0.67-1.76), DMFS (OR 1.25, 95% CI 0.54-2.92), and LRFS (OR 0.83, 95% CI 0.55-1.25). For grade ≥ 3 toxicities, the weekly group had higher risks of anemia (risk ratio [RR] 2.96, 95% CI 1.12-7.81) and thrombocytopenia (RR 2.75, 95% CI 1.54-4.90), but a lower incidence of vomiting (RR 0.34, 95% CI 0.18-0.63) versus the triweekly group. Conclusion and Relevance: Both weekly and triweekly schedules could be recommended to NPC patients during CCRT. Additionally, hematologic adverse events in weekly strategy and non-hematologic adverse events in triweekly strategy are of higher concern.

Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial.

PURPOSE: Camrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer. METHODS: This multicenter, open-label, single-arm, phase II study enrolled patients with advanced cervical cancer who progressed after at least one line of systemic therapy. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once per day. The primary end point was objective response rate (ORR) assessed by investigators per RECIST version 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response, and safety. RESULTS: Forty-five patients were enrolled and received treatment. Median age was 51.0 years (range, 33-67 years), and 57.8% of patients had previously received two or more lines of chemotherapy for recurrent or metastatic disease. Ten patients (22.2%) had received bevacizumab. Median follow-up was 11.3 months (range, 1.0-15.5 months). ORR was 55.6% (95% CI, 40.0% to 70.4%), with two complete and 23 partial responses. Median PFS was 8.8 months (95% CI, 5.6 months to not estimable). Median duration of response and median OS were not reached. Treatment-related grade 3 or 4 adverse events (AEs) occurred in 71.1% of patients, and the most common AEs were hypertension (24.4%), anemia (20.0%), and fatigue (15.6%). The most common potential immune-related AEs included grade 1-2 hypothyroidism (22.2%) and reactive cutaneous capillary endothelial proliferation (8.9%). CONCLUSION: Camrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with advanced cervical cancer. Larger randomized controlled trials are warranted to validate our findings.

Outcomes of Adding Induction Chemotherapy to Concurrent Chemotherapy for Nasopharyngeal Carcinoma Patients with Moderate-Risk in the Intensity-Modulated Radiotherapy Era.

BACKGROUND: The aim of this study was to evaluate the efficacy of induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) patients with moderate-risk treated with intensity-modulated radiotherapy (IMRT). METHODS: We retrospectively assessed 506 patients with T1-2N1M0 or T3-4N0-1M0 NPC (according to the 2010 UICC/AJCC staging system) who received concurrent chemoradiotherapy (CCRT) with or without IC at a single center in China between 2005 and 2010. Survival outcomes were compared between the IC + CCRT and CCRT groups using the Kaplan-Meier method, Log-rank test and a Cox regression model. RESULTS: Among the 506 patients, CCRT alone resulted in equivalent overall survival (86.8% vs 88.5%, p=0.661), progression-free survival (79.6% vs 79.6%, p=0.756), locoregional relapse-free survival (90.2% vs 87.0%, p=0.364) and distant metastasis-free survival (88.0% vs 89.8%, p=0.407) to IC plus CCRT. In multivariate analysis, IC did not lower the risk of death (HR 0.76, 95% CI 0.46-1.25, p=0.278), progression (HR 0.78, 95% CI 0.51-1.19, p=0.244), locoregional relapse (HR 1.06, 95% CI 0.81-1.42, p=0.651) or distant metastasis (HR 0.66, 95% CI 0.38-1.15, p=0.140) in the entire cohort; similar results were obtained in stratified analysis based on N category (N0 vs N1) and EBV DNA (< vs ≥4000 copies/mL). CONCLUSION: Addition of IC to CCRT does not improve survival outcomes in moderate-risk NPC; the use of IC should be carefully considered in these patients, though additional prospective trials are warranted to confirm the conclusions of this study.

Fully-Automated Segmentation of Nasopharyngeal Carcinoma on Dual-Sequence MRI Using Convolutional Neural Networks.

In this study, we proposed an automated method based on convolutional neural network (CNN) for nasopharyngeal carcinoma (NPC) segmentation on dual-sequence magnetic resonance imaging (MRI). T1-weighted (T1W) and T2-weighted (T2W) MRI images were collected from 44 NPC patients. We developed a dense connectivity embedding U-net (DEU) and trained the network based on the two-dimensional dual-sequence MRI images in the training dataset and applied post-processing to remove the false positive results. In order to justify the effectiveness of dual-sequence MRI images, we performed an experiment with different inputs in eight randomly selected patients. We evaluated DEU's performance by using a 10-fold cross-validation strategy and compared the results with the previous studies. The Dice similarity coefficient (DSC) of the method using only T1W, only T2W and dual-sequence of 10-fold cross-validation as different inputs were 0.620 ± 0.0642, 0.642 ± 0.118 and 0.721 ± 0.036, respectively. The median DSC in 10-fold cross-validation experiment with DEU was 0.735. The average DSC of seven external subjects was 0.87. To summarize, we successfully proposed and verified a fully automatic NPC segmentation method based on DEU and dual-sequence MRI images with accurate and stable performance. If further verified, our proposed method would be of use in clinical practice of NPC.

Brain and frontal-bone metastasis from nasopharyngeal carcinoma: Case report and literature review.

BACKGROUND: Metastases to the bones, lungs, and liver are common in patients with nasopharyngeal carcinoma (NPC) but not to the brain and frontal bone (B + FB). METHODS: We describe a patient with NPC with B + FB metastasis. He received two cycles of palliative chemotherapy (gemcitabine and cisplatin) and then radiotherapy (60 Gy) for B + FB metastasis. A literature review of previous cases was also undertaken. RESULTS: Follow-up 6 months after completion of chemotherapy and radiotherapy showed that our patient experienced a complete response without signs of NPC progression. CONCLUSIONS: B + FB metastases from NPC are uncommon. Our case highlights the diagnostic and treatment difficulties clinicians face when dealing with patients with uncommon sites of metastasis. Optimal adjuvant therapy followed by local radiotherapy might elicit long survival in patients with NPC with uncommon sites of metastasis.

Prognostic impact of cigarette smoking on the survival of patients with established esophageal squamous cell carcinoma receiving radiotherapy: A retrospective study from southern China.

Cigarette smoking is associated with the development of esophageal squamous cell carcinoma (ESCC); however, the influence of smoking on survival of patients with ESCC receiving radiotherapy, with or without chemotherapy, has remained elusive. The present study retrospectively analyzed 479 patients with ESCC from southern China who were categorized based on their smoking history (never, previous or current). To consider the cumulative effect of smoking, the number of pack years (PYs) was used as a representative variable. Associations between cigarette smoking and survival were evaluated using the Kaplan-Meier analysis and Cox proportional hazards model. Among the 497 patients, 308 (64.3%) had reported a history of cigarette smoking. The 5-year overall survival for patients void of a smoking history, former smokers and current smokers was 50.9, 27.0 and 34.3%, respectively. The adjusted hazard ratios (HRs) for previous and current smoking vs. no smoking history were 1.57 [95% confidence interval (CI), 1.06-2.32] and 3.01 (95% CI, 1.15-7.86), respectively. Heavy smokers with a high number of PYs had a HR for death of 1.75 (95% CI, 1.28-2.41) compared with light smokers. In the cohort of 407 patients treated with intensity-modulated radiotherapy/three-dimensional conformal radiotherapy, similarly significant results were obtained. In conclusion, cigarette smoking is an independent and poor prognostic factor for patients with ESCC treated with radiotherapy and/or chemotherapy. It is associated with an increased risk of death, and the risk increases with the increase in PYs. This result may help to manage tobacco use among patients with ESCC. The smoking status should be taken into consideration in prospective studies on ESCC. More frequent follow-ups are recommended for those patients with ESCC with a history of smoking.

Prognostic impact of family history of cancer in Southern Chinese patients with esophageal squamous cell cancer.

Background: First degree family history of cancer is associated with developing esophageal cancer and sparse data is about the impact on poor survival among established esophageal squamous cell cancer (ESCC) patients. In this study, we investigated the prognoses of patients with ESCC with a family history. Methods: A total of 479 ESCC patients were retrospectively enrolled from a Southern Chinese institution. A positive family history was defined as having malignant cancer among parents and siblings. Kaplan-Meier plots and Cox proportional hazards regressions were applied for overall survival (OS) and progression-free survival (PFS). Results: Among 479 patients, 119 (24.8%) and 68 (14.2%) reported a first-degree family history of cancer and digestive tract cancer, respectively. Compared with patients without a family history of cancer, the adjusted hazard ratios (HR) among those with it were 1.40 (95% CI, 1.08-1.82, p=0.011) for death, 1.36 (95% CI, 1.05-1.76, p=0.018) for progression. Similar results were observed in those with a family history of digestive tract cancer (HR=1.69, 95%CI, 1.24-1.98, p=0.001 for death and HR=1.77, 95%CI, 1.30-2.37, p<0.001 for progression, respectively). Furthermore, there was a trend for increasing risk of overall mortality (p=0.021, p=0.004, respectively), and progression (p=0.022, p=0.001, respectively) with an increasing number of affected family members. Conclusion: A first-degree family history of cancer, especially digestive tract cancer is associated with poor survival for established ESCC patients and plays an important role in prognosis. The patients with a family history of cancer might need a greater intensity of treatment and more frequent follow-up.

Current Smoking has a Detrimental Effect on Survival for Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) negative Advanced non-squamous Non-small Cell Lung Cancer (NSCLC) Patients Treated with Pemetrexed Continuation Maintenance.

Objectives: The aim of this study is to investigate the predictive value of smoking history on treatment outcomes of pemetrexed continuation maintenance therapy in advanced non-squamous NSCLC patients without EGFR mutations and ALK rearrangements. Methods: 71 consecutive EGFR and ALK negative advanced non-squamous NSCLC patients who had received pemetrexed continuation maintenance therapy at least two cycles were retrospectively analyzed in our single center. The enrolled patients were categorized into two groups as never-/former light smokers and current smokers according to their smoking history. Results: In the 71 non-squamous NSCLC patients, 30 (42.3%) were never-/former light smokers and 41 (57.7%) were current smokers. The objective response rate (ORR) of never-/former light smokers was significantly higher than that of current smokers (26.7% vs. 7.3%, p = 0.026). Never-/former light smokers showed significantly longer progression free survival (PFS) (6.6 [95% CI 5.3-7.9] months vs. 5.1 [95% CI 3.5-6.7] months; HR: 0.557, 95% CI 0.339-0.915, p = 0.021) and overall survival (OS) (17.3 [95% CI 14.4-20.2] months vs. 15.7 [95% CI 12.0-19.4] months; HR: 0.578, 95% CI 0.338-0.986, p = 0.044) than current smokers. Multivariate analysis identified smoking history was an independent predictive factor for PFS and OS. Conclusions: Current smoking is an independent negative predictive factor of outcomes for pemetrexed continuation maintenance therapy in advanced non-squamous NSCLC patients without EGFR mutations and ALK rearrangements.

Supraglottic squamous cell carcinomas have distinctive clinical features and prognosis based on subregion.

OBJECTIVE: To analyze the clinicopathologic characteristics and prognosis of patients with squamous cell carcinoma localized to different supraglottic subregions. METHODS: Clinicopathologic data were reviewed retrospectively for 111 patients with supraglottic squamous cell carcinoma who were diagnosed between January 1, 1995 and December 31, 2005 and were initially treated with surgery. DNA from human papillomavirus (HPV) 16 and (or /and) HPV 18 were detected in all the 111 supraglottic carcinoma specimens using in situ hybridization. Survival analysis was performed by Kaplan-Meier analysis, factors were compared using log-rank test, and prognostic factors were determined using Cox proportional hazards model. The relationship between subregions and clinicopathologic factors was analyzed using Chi-square tests. RESULTS: HPV prevalence differed between patients with aryepiglottic fold carcinoma and ventricle carcinoma (P < .05). The local-regional control rates, overall survival rates or cancer specific survival rates were significantly different between different subregions. Univariate analysis indicated that pTNM classification, pN spread, and subregion were associated with prognosis (P < .05). Multivariate analysis indicated that pTNM classification and subregion were associated with supraglottic carcinoma prognosis. The survival rate was better for patients with carcinoma of the epiglottis or ventricular bands compared to those with carcinoma in the aryepiglottic fold or ventricle (P = .012). CONCLUSIONS: Subregion may be a new prognostic factor for supraglottic squamous cell carcinoma. Different supraglottic carcinoma subregions have distinct clinical features such as HPV expression, lymph node metastasis rate, local-regional control and prognosis. Therefore, it is necessary to subdivide supraglottic squamous cell carcinomas into several subregion groups to individualize therapy.

[Association of serum transforming growth factor-ß1 with radiation injury and survival of patients with early-stage nasopharyngeal carcinoma].

OBJECTIVE: To observe the changes in serum transforming growth factor-ß1 (TGF-ß1) in patients with early-stage nasopharyngeal carcinoma (NPC) after radiotherapy and explore the correlation of serum TGF-ß1 with radiation injury and disease-free survival. METHODS: The average serum TGF-ß1 level (50.2∓3.2 ng/ml) determined from 32 healthy volunteers was used as the standard value for NPC patients in this trial. Fifty-seven patients with early-stage (T1-2N0-1M0) NPC without prior treatment were divided into two groups with serum TGF-ß1 level before treatment lower than or equal to the standard value (group A, 29 cases) and a level beyond the standard value (group B, 28 cases). Serum TGF-ß1 level was determined in all the patients before, during and after the radiotherapy to evaluate the radiation injury and therapeutic effect. RESULTS: The serum TGF-ß1 level before radiotherapy was significantly lower in group A than in group B (35.4∓1.4 vs 58.8∓1.0 ng/ml, P<0.05). After radiotherapy, acute radiation mucositis and skin reaction was significantly severer in group B (P<0.05). The serum TGF-ß1 level before radiotherapy was significantly higher in patients with grade 3 acute radiation mucositis and skin reaction than in those with injuries below grade 3 (54.0∓2.2 vs 42.0∓2.3 ng/ml and 54.3∓2.4 vs 43.4∓2.2 ng/ml, P<0.05). The two groups showed no significant differences in the locoregional failure rate (3.4% vs 7.1%), distant metastasis rate (3.4% vs 10.8%) or disease-free survival (P>0.05). CONCLUSIONS: Radiotherapy can significantly decrease serum TGF-ß1 level in early NPC patients. Serum TGF-ß1 level before radiotherapy can help predict the degree of acute radiation mucositis and skin reaction, but shows no correlation with disease-free survival of early-stage NPC patients.

[Induction chemotherapy with docetaxel plus cisplatin (TP regimen) followed by concurrent chemoradiotherapy with TP regimen versus cisplatin in treating locally advanced nasopharyngeal carcinoma].

BACKGROUND AND OBJECTIVE: Clinical trials on docetaxel plus cisplatin (DDP) (TP regimen) in treating nasopharyngeal carcinoma (NPC) are still uncertain due to limited samples. This study was to compare the short-term efficacy and toxicity of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen versus DDP in treating locally advanced NPC. METHODS: Fifty-seven patients with stage T3-4N2-3M0 NPC diagnosed pathologically from December 2005 to December 2006 were randomized into TP group (30 patients) and DDP group (27 patients). Both groups received TP regimen as induction chemotherapy with docetaxel (70 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2, repeating every 21 days for 2 cycles. For concurrent chemotherapy, TP group were administered docetaxel (60 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2; DDP group were administered DDP (80 mg/m(2)) on Day 1. Both schedules were repeated every 21 days for 2 cycles. Linear accelerator was used as radioactive source. Irradiation field was designed with CT-simulation and conventional fractions. RESULTS: The 57 patients received 111 cycles of induction chemotherapy, and 53 of them received 103 cycles of concurrent chemotherapy; four patients ceased induction chemotherapy and three ceased concurrent chemotherapy. All patients completed radiotherapy. The major toxicity of induction chemotherapy was hematologic toxicity; the main toxicities of concurrent chemoradiotherapy were hematologic toxicity and mucositis. The occurrence rates of Grade 3-4 leucopenia and Grade 3-4 neutropenia were significantly higher in TP group than in DDP groups (p <0.05). In concurrent chemoradiotherapy, the application rate of granulocyte colony stimulating factor (G-CSF) was significantly higher in TP group than in DDP group (100% vs. 72.0%, p<0.05). After concurrent chemoradiotherapy, the complete remission (CR) rates of the nasopharynx and regional lymph nodes were 93.3% and 92.9% in TP group, and were 96.3% and 91.3% in DDP group (p>0.05). CONCLUSIONS: The short-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen on locally advanced NPC is similar to that of TP regimen followed by concurrent chemoradiotherapy with DDP. The toxicity of the former schedule is severer than that of the latter, but it is tolerable with the use of G-CSF. The long-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen need to be further studied.

[Comparison of efficacy of docetaxel combined cisplatin (TP regimen) and cisplatin combined 5-fluorouracil (PF regimen) on locally advanced nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Docetaxel and cisplatin (DDP) are effective drugs for head and neck tumors. Stage II-III clinical trial of TP regimen (docetaxel combined DDP) for head and neck tumors has completed. This study was to compare the efficacy and toxicity of TP regimen and PF regimen [DDP combined 5-fluorouracil (5-FU)] in treating nasopharyngeal carcinoma (NPC), to provide a new chemotherapeutic regimen for NPC. METHODS: Twenty NPC patients treated in Cancer Center of Sun Yat-sen University between Oct. 1, 2005 and Mar. 1, 2006 were subjected to study group (TP group). Twenty patients were chosen randomly from the 45 NPC patients treated with PF regimen between May 1, 2004 and Sep. 30, 2005 as control group (PF group). Both groups received concurrent radiotherapy. The efficacy and adverse events of the 2 groups were compared. RESULTS: The mean number of chemotherapy cycles was significantly higher in TP group than in PF group (3.85 cycles vs. 2.75 cycles, P<0.001). After induction chemotherapy, in TP group, 18 achieved partial remission (PR) and 2 had stable disease (SD) for nasopharyngeal lesions, 7 achieved complete remission (CR), 11 achieved PR and 2 had SD for regional lymph nodes; in PF group, 17 achieved PR and 3 had SD for nasopharyngeal lesions, 2 achieved CR, 15 achieved PR and 1 had SD for regional lymph nodes. After concurrent chemoradiotherapy, all in TP group and 18 in PF group achieved CR for nasopharyngeal lesions, and 19 in TP group and 15 in PF group achieved CR for regional lymph nodes. There was no significant difference in efficacy between the 2 groups (P>0.05). The occurrence rates of grade 3-4 neutropenia were significantly higher in TP group than in PF group (40.5% vs. 0% after induction chemotherapy, 40.5% vs. 10.2% after concurrent radiochemotherapy, P<0.05). The occurrence rates of anemia and thrombocytopenia were significantly lower in TP group than in PF group (P<0.05). The uses of antibiotics and parenteral nutritional support in the 2 groups were similar. CONCLUSION: The efficacy of TP regimen on NPC is similar to that of PF regimen, and the adverse events are tolerable, but the long-term outcomes and toxicities need to be further investigated.